Malaria Centre Report 2012-14

Malaria CentreLondon School of Hygiene & Tropical MedicineKeppel Street, London, WC1E 7HT, UKhttp://malaria.lshtm.ac.uk/[email protected]

Copies of this report may be obtained at http://malaria.lshtm.ac.uk/ or by writing to the address above.Cover image: Mala (Matt Murphy/Handsome Frank)

Malaria Centre Report

2012-14

The authoritative academic voice on malaria research

Improving health worldwide October 2014

Malaria C

entre Report 2012-14

London School of H

ygiene & Tropical M

edicine

Contents

Director’s message 2Executive summary 3

Capacity strengthening 4

Malaria biology 10 Parasite biology 12 Immunology and host resistance 24 Vector biology 31

Malaria prevention 38 Vector control 40 Insecticide resistance 51 Chemoprevention 57 Vaccine development 65

Treatment of malaria 66 Drug studies 69 Community-based case management 73 Facility-based case management 84

Malaria moving forward 94 Surveillance, monitoring and evaluation 96 Malaria control and development 110 Future priorities 112 Publications 114 Members 132

Executive summary 3

Malaria Centre Report 2012-14

2 Director’s message

London School of Hygiene & Tropical Medicine

Despite being preventable and treatable,

malaria continues to devastate populations

across the globe. Progress has been made on

many fronts but the Plasmodium parasite remains

a formidable foe, and one that is constantly

evolving. We continue to face many challenges,

from anti-malarial drug and insecticide resistance

to the genetic evolution of mosquitoes. However,

thanks to a combined effort of governments,

researchers, industry, and philanthropic funders,

deaths from malaria have been reduced by one

third in the last decade but in order to maintain

this progress, sustained investment is needed at

all levels.

The London School of Hygiene & Tropical

Medicine has, for over a century, had a

pioneering role in improving prevention,

diagnosis, and treatment of malaria. Established

in 1998, the School’s Malaria Centre has evolved

and grown to include over 300 researchers,

the largest such group under one roof in the

world. It leads and facilitates interdisciplinary

research and crucially, supports collaboration

Peter Piot

London School of Hygiene & Tropical Medicine Director and Professor of Global Health

with external groups, particularly in malaria

endemic countries, where the shortage of trained

personnel and adequate infrastructure continues

to be a major issue for malaria control. This

role in strengthening capacity for research, but

also education and knowledge transfer, is an

increasing focus of our work.

and the Centre works in a variety of malaria

research areas ranging from basic laboratory

science to social and economic studies. The

Centre also has access to our world-class

facilities that contribute to the diagnosis,

treatment and research of malaria, including the

insectaries at Keppel Street, which house the

world’s longest-established colonies of breeding

mosquitoes, the Malaria Reference Laboratory,

Centre.

I hope you will take time to read this report.

It highlights some of the achievements of

the Centre over the past two years and it is

heartening to see the many breakthroughs that

are being made. It is vital we don’t stand still, but

continue to work on improving existing solutions

and developing new ones, so that one day we

may hope to see the end of malaria.

Continued effective malaria control and

progress toward malaria elimination require

a comprehensive range of approaches to develop

and deliver the right tools. These approaches

need to be based on thorough understanding

of parasite and vector biology and interactions

with the human host. This annual report

work conducted by the Malaria Centre at the

London School of Hygiene & Tropical Medicine in

addressing these issues.

The report is structured broadly from the

nature of the Centre’s research. Examples

of excellence are evident at both ends of the

spectrum with parasite genomics outputs

including the barcode for Plasmodium falciparum

at one end and the multifaceted outputs from

also continue to build and evaluate vital research

resources. New parasite isolates are being

collected and established with our partners at the

Hospital for Tropical Diseases which are essential

insecticides and vector control strategies are

routinely being tested with our partners based in

of the Centre continue to be at the forefront of

evaluating both novel control approaches such

as Seasonal Malaria Chemoprophylaxis and

optimal combinations of existing approaches

with multicentre trials of interventions like indoor

residual spraying and long-lasting insecticidal-

programmes investigating the molecular and

spatial epidemiology of a newly emerging threat -

the zoonotic malaria, Plasmodium knowlesi.

Having

address new and emerging challenges such

as Plasmodium knowlesi is testament to core

attributes of the Malaria Centre: world-leading

researchers, strong overseas partnerships,

motivated students, and the prescience of those

that fund them. The ability to integrate new

techniques with established skills in parasitology,

entomology and epidemiology allows the Malaria

Centre to continue, and build on, the work of the

the world’s major public health issues.

Chris Drakeley

Malaria Centre Director and Professor of Infection and Immunity

Executive summary 3


2 Director’s message


Despite being preventable and treatable,

malaria continues to devastate populations

across the globe. Progress has been made on

many fronts but the Plasmodium parasite remains

a formidable foe, and one that is constantly

evolving. We continue to face many challenges,

from anti-malarial drug and insecticide resistance

to the genetic evolution of mosquitoes. However,

thanks to a combined effort of governments,

researchers, industry, and philanthropic funders,

deaths from malaria have been reduced by one

third in the last decade but in order to maintain

this progress, sustained investment is needed at

all levels.

The London School of Hygiene & Tropical

Medicine has, for over a century, had a

pioneering role in improving prevention,

diagnosis, and treatment of malaria. Established

in 1998, the School’s Malaria Centre has evolved

and grown to include over 300 researchers,

the largest such group under one roof in the

world. It leads and facilitates interdisciplinary

research and crucially, supports collaboration

Peter Piot

London School of Hygiene & Tropical Medicine Director and Professor of Global Health

with external groups, particularly in malaria

endemic countries, where the shortage of trained

personnel and adequate infrastructure continues

to be a major issue for malaria control. This

role in strengthening capacity for research, but

also education and knowledge transfer, is an

increasing focus of our work.

and the Centre works in a variety of malaria

research areas ranging from basic laboratory

science to social and economic studies. The

Centre also has access to our world-class

facilities that contribute to the diagnosis,

treatment and research of malaria, including the

insectaries at Keppel Street, which house the

world’s longest-established colonies of breeding

mosquitoes, the Malaria Reference Laboratory,

Centre.

I hope you will take time to read this report.

It highlights some of the achievements of

the Centre over the past two years and it is

heartening to see the many breakthroughs that

are being made. It is vital we don’t stand still, but

continue to work on improving existing solutions

and developing new ones, so that one day we

may hope to see the end of malaria.

Continued effective malaria control and

progress toward malaria elimination require

a comprehensive range of approaches to develop

and deliver the right tools. These approaches

need to be based on thorough understanding

of parasite and vector biology and interactions

with the human host. This annual report

work conducted by the Malaria Centre at the

London School of Hygiene & Tropical Medicine in

addressing these issues.

The report is structured broadly from the

nature of the Centre’s research. Examples

of excellence are evident at both ends of the

spectrum with parasite genomics outputs

including the barcode for Plasmodium falciparum

at one end and the multifaceted outputs from

also continue to build and evaluate vital research

resources. New parasite isolates are being

collected and established with our partners at the

Hospital for Tropical Diseases which are essential

insecticides and vector control strategies are

routinely being tested with our partners based in

of the Centre continue to be at the forefront of

evaluating both novel control approaches such

as Seasonal Malaria Chemoprophylaxis and

optimal combinations of existing approaches

with multicentre trials of interventions like indoor

residual spraying and long-lasting insecticidal-

programmes investigating the molecular and

spatial epidemiology of a newly emerging threat -

the zoonotic malaria, Plasmodium knowlesi.

Having

address new and emerging challenges such

as Plasmodium knowlesi is testament to core

attributes of the Malaria Centre: world-leading

researchers, strong overseas partnerships,

motivated students, and the prescience of those

that fund them. The ability to integrate new

techniques with established skills in parasitology,

entomology and epidemiology allows the Malaria

Centre to continue, and build on, the work of the

the world’s major public health issues.

Chris Drakeley

Malaria Centre Director and Professor of Infection and Immunity

4 Capacity strengthening Capacity strengthening 5

London School of Hygiene & Tropical Medicine Malaria Centre Report 2012-14

Summary

Members of the Malaria Centre have continued to

play an important role in strengthening research

capacity in the United Kingdom and malaria

endemic countries, particularly in sub-Saharan

Formal teaching and training programmes with

School of Hygiene & Tropical Medicine. There

has been increased interest from post graduate

students and researchers from disease endemic

countries mirroring global investment in control-

increase of registrations for the Distance Learning

from this training between 2011/2 and 2013/4.

The Centre currently supports two PhD students

Thorpe Legacy Studentship Fund but members

The guiding principle of the Malaria Centre’s capacity strengthening activities is to work

within interdisciplinary partnerships that respond to local, national and international

priorities to improve malaria control.

continue to supervise and/or co-supervise many

more students in all three faculties at the School.

The total number of PhD students graduating with

degrees focusing on malaria has continued to

increase, with 22 students successfully defend-

ing their PhDs between 2011/2 and 2013/4. The

geographic spread of our students continues

graduates coming from, and working in, disease

endemic countries.

Every year, Malaria Centre members also con-

tribute to capacity strengthening amongst MSc

students, with specialist malaria teaching forming

an integral part of both London-based and dis-

tance-learning MSc courses. Lectures and labo-

ratory practicals, designed to foster a detailed un-

derstanding of the life history of malaria parasites

and mosquito vectors, form a core component of

In addition, all London-based MSc students

have the option to take a 5-week module on the

Epidemiology and Control of Malaria which aims

to give students a deeper view of malaria as a

public health problem, and generate a compre-

hensive understanding of the environmental,

biological, political and social roots of malaria,

by building connections between a wide variety

of aspects and viewpoints. Strong emphasis is

placed on providing up-to-date knowledge of the

interventions that can be used to control malaria,

as well as a critical understanding of current and

future challenges to their effective use and appli-

cation.

Students apply this knowledge to inform the

design of either a control programme, intervention

trial or elimination strategy according to the

malaria epidemiology of a given setting (selected

from a choice of representative settings in sub-

module, attracting over 40 students each year,

many of whom have gone on to play an active

role either in malaria research and/or control in

academia, non-governmental agencies, national

control programmes and international agencies.



Summary

Members of the Malaria Centre have continued to

play an important role in strengthening research

capacity in the United Kingdom and malaria

endemic countries, particularly in sub-Saharan

Formal teaching and training programmes with

School of Hygiene & Tropical Medicine. There

has been increased interest from post graduate

students and researchers from disease endemic

countries mirroring global investment in control-

increase of registrations for the Distance Learning

from this training between 2011/2 and 2013/4.

The Centre currently supports two PhD students

Thorpe Legacy Studentship Fund but members

The guiding principle of the Malaria Centre’s capacity strengthening activities is to work

within interdisciplinary partnerships that respond to local, national and international

priorities to improve malaria control.

continue to supervise and/or co-supervise many

more students in all three faculties at the School.

The total number of PhD students graduating with

degrees focusing on malaria has continued to

increase, with 22 students successfully defend-

ing their PhDs between 2011/2 and 2013/4. The

geographic spread of our students continues

graduates coming from, and working in, disease

endemic countries.

Every year, Malaria Centre members also con-

tribute to capacity strengthening amongst MSc

students, with specialist malaria teaching forming

an integral part of both London-based and dis-

tance-learning MSc courses. Lectures and labo-

ratory practicals, designed to foster a detailed un-

derstanding of the life history of malaria parasites

and mosquito vectors, form a core component of

In addition, all London-based MSc students

have the option to take a 5-week module on the

Epidemiology and Control of Malaria which aims

to give students a deeper view of malaria as a

public health problem, and generate a compre-

hensive understanding of the environmental,

biological, political and social roots of malaria,

by building connections between a wide variety

of aspects and viewpoints. Strong emphasis is

placed on providing up-to-date knowledge of the

interventions that can be used to control malaria,

as well as a critical understanding of current and

future challenges to their effective use and appli-

cation.

Students apply this knowledge to inform the

design of either a control programme, intervention

trial or elimination strategy according to the

malaria epidemiology of a given setting (selected

from a choice of representative settings in sub-

module, attracting over 40 students each year,

many of whom have gone on to play an active

role either in malaria research and/or control in

academia, non-governmental agencies, national

control programmes and international agencies.



Palafox

Less than half

of malaria cases

receive the

recommended

treatment, called

artemisinin-based

combination therapy

This is partly due to problems

of drug availability and accessibility in

often turn to the private sector to obtain

treatment where they are more likely to

receive older or less effective medicines.

Using supply- and demand-side data

from four countries, my PhD work aims

to understand why malaria patients who

turn to the private sector are less likely

as facilitators and barriers to receiving

In particular, I focus on the

changes in price. I hope that this new

knowledge will help to design more

effective market interventions and ensure

that malaria infections are optimally

treated.

I was awarded a

Malaria Capacity

Development

studentship in 2009

and successfully

defended my PhD

from the University

of Liverpool/University of Malawi in 2013.

I am currently back in Kenya working as

a visiting Research Fellow at the Centre

for Biotechnology and Bioinformatics.

Here, I am working on an MCDC funded

post-doctoral fellowship and will use this

opportunity to undertake further laboratory

training in Plasmodium falciparum

genotyping, array design and analysis.

I am also supervising an MSc student

and am involved in MCDC’s career

development group.

The Malaria Centre couldn’t be a better

place to train – the excellent assembly

of world experts in malaria can only help

you get better and the interactions with

these researchers are so intense and

elaborate. I particularly want to extend my

gratitude to Dr Taane Clark who was very

supportive during my PhD. I hope our

collaboration will last for years to come.

The Malaria Capacity Development Consortium

to conduct high quality research on malaria.

highlight different aspects of the work being

activities of the MCDC programme for the 6th

Multilateral Initiative on Malaria meeting held

013 where

it was shown to over 1,000 guests at the gala

dinner. It will also be shown to members of the UK

parliament in late 2014.

Examples of work undertaken by the consortium

during the past two years include:

A PhD programme

Five of the 18 MCDC supported PhD students

had obtained their PhDs by the end of 2013, with

the remaining 13 due to graduate by the end

which provides opportunities to further enhance

their skills in this important early stage of their

career. Three such awards had been made by the

end of 2013.



Palafox

Less than half

of malaria cases

receive the

recommended

treatment, called

artemisinin-based

combination therapy

This is partly due to problems

of drug availability and accessibility in

often turn to the private sector to obtain

treatment where they are more likely to

receive older or less effective medicines.

Using supply- and demand-side data

from four countries, my PhD work aims

to understand why malaria patients who

turn to the private sector are less likely

as facilitators and barriers to receiving

In particular, I focus on the

changes in price. I hope that this new

knowledge will help to design more

effective market interventions and ensure

that malaria infections are optimally

treated.

I was awarded a

Malaria Capacity

Development

studentship in 2009

and successfully

defended my PhD

from the University

of Liverpool/University of Malawi in 2013.

I am currently back in Kenya working as

a visiting Research Fellow at the Centre

for Biotechnology and Bioinformatics.

Here, I am working on an MCDC funded

post-doctoral fellowship and will use this

opportunity to undertake further laboratory

training in Plasmodium falciparum

genotyping, array design and analysis.

I am also supervising an MSc student

and am involved in MCDC’s career

development group.

The Malaria Centre couldn’t be a better

place to train – the excellent assembly

of world experts in malaria can only help

you get better and the interactions with

these researchers are so intense and

elaborate. I particularly want to extend my

gratitude to Dr Taane Clark who was very

supportive during my PhD. I hope our

collaboration will last for years to come.

The Malaria Capacity Development Consortium

to conduct high quality research on malaria.

highlight different aspects of the work being

activities of the MCDC programme for the 6th

Multilateral Initiative on Malaria meeting held

013 where

it was shown to over 1,000 guests at the gala

dinner. It will also be shown to members of the UK

parliament in late 2014.

Examples of work undertaken by the consortium

during the past two years include:

A PhD programme

Five of the 18 MCDC supported PhD students

had obtained their PhDs by the end of 2013, with

the remaining 13 due to graduate by the end

which provides opportunities to further enhance

their skills in this important early stage of their

career. Three such awards had been made by the

end of 2013.



Establishment of a new molecular laboratory for malaria research in Moshi, Tanzania.

A post-doctoral programme

MCDC continues to support a cohort of 29 well

its ‘Investigator’ programme. Career development

support is provided through innovative mentoring,

Personal Development Planning and small grants

programmes.

A leadership programme

In late 2014, MCDC will launch a leadership

training programme which aims to strengthen the

skills of MCDC scientists to lead and manage

internationally competitive research groups.

The programme will use a series of facilitated

interactions (individual support, peer group

strengthen the leadership skills of investigators

over a 10-month period.

Institutional capacity strengthening

Following on from successes in strengthening

partner PhD programmes in Phase 1 of the

programme, MCDC is now using a similar

partner universities to attract and manage

research funding.

Management Support Systems will be completed

in 2104 and MCDC will provide support to

MCDC has now established working groups at

each partner institution (Career Development

development activities, such as mentoring and

PDP, within institutional structures, thereby

ensuring that career development support is

sustained beyond the lifespan of MCDC.

mcdconsortium.org

LSHTM Investigators: Mark Rowland, Natacha Protopopoff &

Alex Wright.

External Investigators/Collaborators: Franklin Mosha &

Reginald Kavishe (Kilimanjaro Christian Medical Centre,

Tanzania).

Funding: The United States Agency for International Develop-

ment.

The malaria research laboratory in Moshi, Tanzania was established to test human blood and mosquito samples for malaria parasites. The main aim of the

for malaria control trials and to increase capacity

these specialised techniques.The laboratory was originally established to

test samples for a large-scale malaria control study on Lake Victoria from 2011-2013. The techniques were established to run samples with PCR and

detecting mosquito resistance to insecticide. Testing to determine whether mosquitoes contained malaria parasite was also conducted, along with

activities include malaria parasite slide reading, mosquito dissections and trialing new PCR laboratory techniques to detect and speciate the Plasmodium parasite in the blood samples.

The laboratory is now strengthening through collaborations with other institutions from around the world. For the past 9 months, the lab has expanded availability to test samples for projects run by the following organisations: The London School of Hygiene & Tropical Medicine, The Malaria Capacity Development Consortium, THRiVE, Duke University-Medical Education Partnership Initiative, The Liverpool School of Tropical Medicine, The National Institute for Medical Research (Mwanza/Muheza/

Vector Control Consortium. The laboratory hopes to expand opportunities

for collaboration in the upcoming years, and is using

laboratory scientists.



Establishment of a new molecular laboratory for malaria research in Moshi, Tanzania.

A post-doctoral programme

MCDC continues to support a cohort of 29 well

its ‘Investigator’ programme. Career development

support is provided through innovative mentoring,

Personal Development Planning and small grants

programmes.

A leadership programme

In late 2014, MCDC will launch a leadership

training programme which aims to strengthen the

skills of MCDC scientists to lead and manage

internationally competitive research groups.

The programme will use a series of facilitated

interactions (individual support, peer group

strengthen the leadership skills of investigators

over a 10-month period.

Institutional capacity strengthening

Following on from successes in strengthening

partner PhD programmes in Phase 1 of the

programme, MCDC is now using a similar

partner universities to attract and manage

research funding.

Management Support Systems will be completed

in 2104 and MCDC will provide support to

MCDC has now established working groups at

each partner institution (Career Development

development activities, such as mentoring and

PDP, within institutional structures, thereby

ensuring that career development support is

sustained beyond the lifespan of MCDC.

mcdconsortium.org

LSHTM Investigators: Mark Rowland, Natacha Protopopoff &

Alex Wright.

External Investigators/Collaborators: Franklin Mosha &

Reginald Kavishe (Kilimanjaro Christian Medical Centre,

Tanzania).

Funding: The United States Agency for International Develop-

ment.

The malaria research laboratory in Moshi, Tanzania was established to test human blood and mosquito samples for malaria parasites. The main aim of the

for malaria control trials and to increase capacity

these specialised techniques.The laboratory was originally established to

test samples for a large-scale malaria control study on Lake Victoria from 2011-2013. The techniques were established to run samples with PCR and

detecting mosquito resistance to insecticide. Testing to determine whether mosquitoes contained malaria parasite was also conducted, along with

activities include malaria parasite slide reading, mosquito dissections and trialing new PCR laboratory techniques to detect and speciate the Plasmodium parasite in the blood samples.

The laboratory is now strengthening through collaborations with other institutions from around the world. For the past 9 months, the lab has expanded availability to test samples for projects run by the following organisations: The London School of Hygiene & Tropical Medicine, The Malaria Capacity Development Consortium, THRiVE, Duke University-Medical Education Partnership Initiative, The Liverpool School of Tropical Medicine, The National Institute for Medical Research (Mwanza/Muheza/

Vector Control Consortium. The laboratory hopes to expand opportunities

for collaboration in the upcoming years, and is using

laboratory scientists.

10 Malaria biology Malaria biology 11


whether for reducing the intensity of infections

or blocking transmission, is an underlying goal

of several projects on parasite development and

on characterization of antigens to which immune

responses may be most effective.

Immunology studies have focused on the

dynamic responses that are highly dependent

on the varying experiences of natural

infection or the precise vaccination regimens

in experimental trials. There has been an

increased focus on determining how long

protective immune responses last and how this

is determined by memory T and B lymphocyte

populations. Recognition of the importance of

immunopathology in malaria has also continued

to stimulate research on the regulation of

but a murine malaria model has been effective in

identifying targets of cytotoxic CD8+ T cells that

contribute to protection. Trials of the partially-

protective RTS,S vaccine has also provided an

important opportunity to study immune correlates

of protection, with a more controlled framework

than is possible for studies of naturally acquired

immunity.

Vector biology also incorporates a range of

innovative research, from discovery to application.

Many processes in mosquito behaviour, relating

to human-feeding or egg laying for example,

intervention.

Summary

Diverse biological disciplines are applied to understand malaria and the tools available for this have continued to develop. Malaria Centre members work across the spectrum of malaria biology in studies that range from molecular and cellular processes through to whole-organism behavioural assays and population analyses.

The studies presented in this section are ordered

in a manner that allows focus respectively on

parasites, human hosts, and mosquito vectors.

Novel prospects have arisen from the ever

expanding application of genomics, combined

with detailed analyses in clinical and community

settings as well as in experimental laboratories.

Each of these subjects, and the interactions

between them, have always been interesting and

complex, but the period covered by this report

worldwide that affect research priorities. Progress

in malaria control in particular areas is being

countered by the evolution of new mechanisms

of drug and insecticide resistance. Where

reduction of malaria incidence has been achieved

and sustained, this has led to decreasing

levels of acquired immunity and an increase in

average age at which people are infected. Novel

mechanisms and targets for future drugs and

vaccines are sought against this background.

Parasite biology here focuses on both the

sexual stage gametocytes that need to be

transmitted from humans to mosquitoes in a blood

meal, and also on the asexual parasites that

cyclically invade and replicate within red blood

cells. Common to these sexually or asexually

differentiated parasites is the need to escape

from red blood cells to continue the life cycle, with

biochemical processes of egress being studied

as potential steps that could be targeted by new



whether for reducing the intensity of infections

or blocking transmission, is an underlying goal

of several projects on parasite development and

on characterization of antigens to which immune

responses may be most effective.

Immunology studies have focused on the

dynamic responses that are highly dependent

on the varying experiences of natural

infection or the precise vaccination regimens

in experimental trials. There has been an

increased focus on determining how long

protective immune responses last and how this

is determined by memory T and B lymphocyte

populations. Recognition of the importance of

immunopathology in malaria has also continued

to stimulate research on the regulation of

but a murine malaria model has been effective in

identifying targets of cytotoxic CD8+ T cells that

contribute to protection. Trials of the partially-

protective RTS,S vaccine has also provided an

important opportunity to study immune correlates

of protection, with a more controlled framework

than is possible for studies of naturally acquired

immunity.

Vector biology also incorporates a range of

innovative research, from discovery to application.

Many processes in mosquito behaviour, relating

to human-feeding or egg laying for example,

intervention.

Summary

Diverse biological disciplines are applied to understand malaria and the tools available for this have continued to develop. Malaria Centre members work across the spectrum of malaria biology in studies that range from molecular and cellular processes through to whole-organism behavioural assays and population analyses.

The studies presented in this section are ordered

in a manner that allows focus respectively on

parasites, human hosts, and mosquito vectors.

Novel prospects have arisen from the ever

expanding application of genomics, combined

with detailed analyses in clinical and community

settings as well as in experimental laboratories.

Each of these subjects, and the interactions

between them, have always been interesting and

complex, but the period covered by this report

worldwide that affect research priorities. Progress

in malaria control in particular areas is being

countered by the evolution of new mechanisms

of drug and insecticide resistance. Where

reduction of malaria incidence has been achieved

and sustained, this has led to decreasing

levels of acquired immunity and an increase in

average age at which people are infected. Novel

mechanisms and targets for future drugs and

vaccines are sought against this background.

Parasite biology here focuses on both the

sexual stage gametocytes that need to be

transmitted from humans to mosquitoes in a blood

meal, and also on the asexual parasites that

cyclically invade and replicate within red blood

cells. Common to these sexually or asexually

differentiated parasites is the need to escape

from red blood cells to continue the life cycle, with

biochemical processes of egress being studied

as potential steps that could be targeted by new



The role of the subpellicular network in malaria parasite development and infectivity.

LSHTM Investigators: Annie Tremp, Sadia Saeed & Johannes

Dessens.

Funding: The Wellcome Trust.

parasites is a cortical cytoskeletal structure termed

maintain cell shape. Plasmodium alveolins comprise

Species barriers in ovale malaria parasites.

LSHTM Investigators: Mary Oguike & Colin Sutherland.

External Investigators/Collaborators: Abdoulaye Djimde (Malaria

Research and Training Center, Mali); Alyssa Barry (Walter and Eliza

Hall Institute of Medical Research, Australia).


In this Wellcome Trust funded project, we studied various aspects of parasite biology that may contribute to mainte-nance of the species barrier.

the UK for which we had a blood sample for analysis, the 74 Plasmodium ovale curtisi-infected malaria patients presented on average 85.7 days after arrival in the UK. By contrast, the 60 Plasmodium ovale wallikeri, cases

Both species showed an ability to occur in patients who took chemoprophylaxis, due to the ability to relapse from

biological difference found between these two related parasite species.

We then proceeded with genetic analysis of sexual-stage and fertilisation-related loci in both species, and

provides further evidence to support our favourite hypoth-esis: the species barrier between the two parasites is due to genetic distance that accrued while the two lineages

Parasite biology

A newly ruptured Plasmodium ovale curtisi schizont and gametocyte following in vitro maturation of parasites from patient blood.

were in different primate hosts, before modern Homo sapiens arose. When these two hypothetical proto-ovale lineages separately entered the new host Homo, crucial genetic changes had occurred which prevented cross-mating, and thus genetic isolation has continued.

The role of Plasmodium LCCL proteins in malaria transmission.

LSHTM Investigators: Sadia Saeed, Annie Tremp & Johannes

Dessens.


Plasmodium LCCL proteins comprise a family of six proteins that function as a protein complex and have essential roles in sporozoite transmission. In Plasmodium berghei, family members Pb Pb Pbhave been shown to be expressed in gametocytes and, following gametogenesis and fertilization, to be targeted to distinctive multivesicular organelles termed crystalloids

Schematic diagram of the Plasmodium LAP family. The names given are the most commonly used for these proteins in P. berghei (Pb) and P. falciparum (Pf). All proteins possess a predicted

that form in the ookinete. We have shown, by GFP-tagging, that Pb

Pb Pbassociated with the crystalloids. However, in contrast to their family members, protein expression of PbPb Pbeven though transcription of the corresponding genes is most prominent in the sexual blood stage parasites. These results suggest that translational repression controls expression of the LCCL protein repertoire and, consequently, the temporal function of the protein complex during Plasmodium berghei development in the mosquito.

structural components of the SPN, and alveolin gene knockout causes morphological abnormalities that coincide with markedly reduced tensile strength of the affected zoites, indicating the alveolins are prime cellshape determinants.

We have characterized a novel SPN protein of Plas-modium berghei ookinetes and sporozoites named G2

-veolins. G2 knockout abolishes parasite transmission and causes zoite malformations and motility defects similar to

those observed in alveolin null mutants. Unlike alveolins, however, G2 contributes little to tensile strength, argu-ing against a cause-effect relationship between tensile strength and cell shape. We also show that G2 null mu-tant sporozoites display an abnormal arrangement of their subpellicular microtubules.

These results provide important new understanding of the factors that determine zoite morphogenesis, as well as the potential roles of the cortical cytoskeleton in gliding motility.

Research with a genomic perspective focuses on discovery of parasite mechanisms that can be targeted for future development of drugs and vaccines, and on parasite susceptibility to existing drugs and immune responses in endemic populations.



The role of the subpellicular network in malaria parasite development and infectivity.

LSHTM Investigators: Annie Tremp, Sadia Saeed & Johannes

Dessens.


parasites is a cortical cytoskeletal structure termed

maintain cell shape. Plasmodium alveolins comprise

Species barriers in ovale malaria parasites.

LSHTM Investigators: Mary Oguike & Colin Sutherland.

External Investigators/Collaborators: Abdoulaye Djimde (Malaria

Research and Training Center, Mali); Alyssa Barry (Walter and Eliza

Hall Institute of Medical Research, Australia).


In this Wellcome Trust funded project, we studied various aspects of parasite biology that may contribute to mainte-nance of the species barrier.

the UK for which we had a blood sample for analysis, the 74 Plasmodium ovale curtisi-infected malaria patients presented on average 85.7 days after arrival in the UK. By contrast, the 60 Plasmodium ovale wallikeri, cases

Both species showed an ability to occur in patients who took chemoprophylaxis, due to the ability to relapse from

biological difference found between these two related parasite species.

We then proceeded with genetic analysis of sexual-stage and fertilisation-related loci in both species, and

provides further evidence to support our favourite hypoth-esis: the species barrier between the two parasites is due to genetic distance that accrued while the two lineages

Parasite biology

A newly ruptured Plasmodium ovale curtisi schizont and gametocyte following in vitro maturation of parasites from patient blood.

were in different primate hosts, before modern Homo sapiens arose. When these two hypothetical proto-ovale lineages separately entered the new host Homo, crucial genetic changes had occurred which prevented cross-mating, and thus genetic isolation has continued.

The role of Plasmodium LCCL proteins in malaria transmission.

LSHTM Investigators: Sadia Saeed, Annie Tremp & Johannes

Dessens.


Plasmodium LCCL proteins comprise a family of six proteins that function as a protein complex and have essential roles in sporozoite transmission. In Plasmodium berghei, family members Pb Pb Pbhave been shown to be expressed in gametocytes and, following gametogenesis and fertilization, to be targeted to distinctive multivesicular organelles termed crystalloids

Schematic diagram of the Plasmodium LAP family. The names given are the most commonly used for these proteins in P. berghei (Pb) and P. falciparum (Pf). All proteins possess a predicted

that form in the ookinete. We have shown, by GFP-tagging, that Pb

Pb Pbassociated with the crystalloids. However, in contrast to their family members, protein expression of PbPb Pbeven though transcription of the corresponding genes is most prominent in the sexual blood stage parasites. These results suggest that translational repression controls expression of the LCCL protein repertoire and, consequently, the temporal function of the protein complex during Plasmodium berghei development in the mosquito.

structural components of the SPN, and alveolin gene knockout causes morphological abnormalities that coincide with markedly reduced tensile strength of the affected zoites, indicating the alveolins are prime cellshape determinants.

We have characterized a novel SPN protein of Plas-modium berghei ookinetes and sporozoites named G2

-veolins. G2 knockout abolishes parasite transmission and causes zoite malformations and motility defects similar to

those observed in alveolin null mutants. Unlike alveolins, however, G2 contributes little to tensile strength, argu-ing against a cause-effect relationship between tensile strength and cell shape. We also show that G2 null mu-tant sporozoites display an abnormal arrangement of their subpellicular microtubules.

These results provide important new understanding of the factors that determine zoite morphogenesis, as well as the potential roles of the cortical cytoskeleton in gliding motility.

Research with a genomic perspective focuses on discovery of parasite mechanisms that can be targeted for future development of drugs and vaccines, and on parasite susceptibility to existing drugs and immune responses in endemic populations.



A scalable assessment of malaria transmission in the standard membrane feeding assay using transgenic GFP-luciferase Plasmodium falciparum gametocytes.

LSHTM Investigators: Teun Bousema.

External Investigators/Collaborators: Will Stone, Wouter

Dechering & Robert Sauerwein (Radboud University Medical Center,

Netherlands); Thomas Churcher (Imperial College, UK); Ashley

Research Institute, USA).

Funding:

Foundation.

The development of drugs and vaccines to reduce malaria transmission is an important part of eradication

these agents is currently determined in the standard

microscopical read-outs and with limitations in up-scaling

and throughput. To improve scalability and objectivity, we utilised

a Plasmodium falciparum

dissections in favour of a simple approach where whole mosquitoes are homogenised and examined directly for luciferase activity.

Anopheles stephensi mosquitoes across 68 experimental feeds, showed that the luminescence assay was as sensitive as microscopy for infection detection. The mean luminescence intensity of

mean oocyst intensity and generated comparable

The advantage of the luminescence based assay is a considerable increase in throughput so that 10-30 experimental feeds can be evaluated in a single 96-well plate. This new method of assessing Plasmodium infection and transmission intensity could expedite the screening of novel drug compounds, vaccine candidates

Microscopical and lumines-cence based assessments of the Transmission reducing activity (TRA) of transmission effective mAb

A shows TRA calculated sepa-rately using mean oocyst intensity by microscopy and mean luminescence intensity from individual mosquitoes

-mission reducing agent was applied. Panel B shows the same for pools of

show serial dilutions of a transmission blocking monoclonal antibody (C) and

by microscopical examination of indi-vidual mosquitoes and luminescence assessment of individual mosquitoes

Functional analysis of the Plasmodium falciparum cGMP-dependent protein kinase (PfPKG); a key regulator of parasite egress from red blood cells.

LSHTM Investigators: David Baker, Eloise Thompson & Christian

Flueck.

External Investigators/Collaborators: Michael Blackman (National

Institute for Medical Research, UK); Andrew Tobin (University of

Leicester, UK); Manoj Duraisingh (Harvard School of Public Health,

USA).


We and others have shown that cGMP signalling

plays important roles in several distinct stages of the malaria parasite life cycle.

PKG inhibitors in conjunction with an inhibitor-insensitive Plasmodium falciparum generated by mutation of a key inhibitor-binding amino acid. For example, PKG inhibitors block the rupture of asexual blood stage schizonts and prevent merozoite

of this project, in collaboration with co-investigator Mike Blackman, we recently showed that cGMP and PKG stimulate release of proteins from the apical organelles of merozoites within a schizont that allow them to egress from the surrounding erythrocyte prior to invasion of a new host cell. In collaboration with co-investigator

mass spectrometry-based approach, utilizing the T618Q inhibitor resistant line, to identify proteins which are phosphorylated by PKG.

Investigating the potential of phosphodiesterases as a target for anti-malarial drug discovery.

LSHTM Investigators: Laura Drought & David Baker.

External Investigators/Collaborators: Tanya Parkinson (Medicines

Medical Research, UK).

Funding: The Biotechnology and Biological Sciences Research

Council.

Cellular signalling plays a key role in the growth and development of Plasmodiumprogresses parasites sense changes in their environment and respond accordingly.

Cyclic nucleotides are important mediators of signalling, as secondary messengers they affect many downstream targets which have a variety of functions in the cell. Their levels must be tightly controlled for the parasites to complete their life cycle. The balance in a cell is determined by two groups of enzymes, cyclases and phosphodiesterases

respectively. These enzymes have proved to be important targets for drugs that treat a range of disorders in humans. Little is known about the malaria parasite PDEs. There are four Plasmodium

stages of the parasite life cycle. We have used a number of transgenic approaches to study the function of this enzyme at this stage of the Plasmodium falciparum life cycle.



A scalable assessment of malaria transmission in the standard membrane feeding assay using transgenic GFP-luciferase Plasmodium falciparum gametocytes.

LSHTM Investigators: Teun Bousema.

External Investigators/Collaborators: Will Stone, Wouter

Dechering & Robert Sauerwein (Radboud University Medical Center,

Netherlands); Thomas Churcher (Imperial College, UK); Ashley

Research Institute, USA).

Funding:

Foundation.

The development of drugs and vaccines to reduce malaria transmission is an important part of eradication

these agents is currently determined in the standard

microscopical read-outs and with limitations in up-scaling

and throughput. To improve scalability and objectivity, we utilised

a Plasmodium falciparum

dissections in favour of a simple approach where whole mosquitoes are homogenised and examined directly for luciferase activity.

Anopheles stephensi mosquitoes across 68 experimental feeds, showed that the luminescence assay was as sensitive as microscopy for infection detection. The mean luminescence intensity of

mean oocyst intensity and generated comparable

The advantage of the luminescence based assay is a considerable increase in throughput so that 10-30 experimental feeds can be evaluated in a single 96-well plate. This new method of assessing Plasmodium infection and transmission intensity could expedite the screening of novel drug compounds, vaccine candidates

Microscopical and lumines-cence based assessments of the Transmission reducing activity (TRA) of transmission effective mAb

A shows TRA calculated sepa-rately using mean oocyst intensity by microscopy and mean luminescence intensity from individual mosquitoes

-mission reducing agent was applied. Panel B shows the same for pools of

show serial dilutions of a transmission blocking monoclonal antibody (C) and

by microscopical examination of indi-vidual mosquitoes and luminescence assessment of individual mosquitoes

Functional analysis of the Plasmodium falciparum cGMP-dependent protein kinase (PfPKG); a key regulator of parasite egress from red blood cells.

LSHTM Investigators: David Baker, Eloise Thompson & Christian

Flueck.

External Investigators/Collaborators: Michael Blackman (National

Institute for Medical Research, UK); Andrew Tobin (University of

Leicester, UK); Manoj Duraisingh (Harvard School of Public Health,

USA).


We and others have shown that cGMP signalling

plays important roles in several distinct stages of the malaria parasite life cycle.

PKG inhibitors in conjunction with an inhibitor-insensitive Plasmodium falciparum generated by mutation of a key inhibitor-binding amino acid. For example, PKG inhibitors block the rupture of asexual blood stage schizonts and prevent merozoite

of this project, in collaboration with co-investigator Mike Blackman, we recently showed that cGMP and PKG stimulate release of proteins from the apical organelles of merozoites within a schizont that allow them to egress from the surrounding erythrocyte prior to invasion of a new host cell. In collaboration with co-investigator

mass spectrometry-based approach, utilizing the T618Q inhibitor resistant line, to identify proteins which are phosphorylated by PKG.

Investigating the potential of phosphodiesterases as a target for anti-malarial drug discovery.

LSHTM Investigators: Laura Drought & David Baker.

External Investigators/Collaborators: Tanya Parkinson (Medicines

Medical Research, UK).


Council.

Cellular signalling plays a key role in the growth and development of Plasmodiumprogresses parasites sense changes in their environment and respond accordingly.

Cyclic nucleotides are important mediators of signalling, as secondary messengers they affect many downstream targets which have a variety of functions in the cell. Their levels must be tightly controlled for the parasites to complete their life cycle. The balance in a cell is determined by two groups of enzymes, cyclases and phosphodiesterases

respectively. These enzymes have proved to be important targets for drugs that treat a range of disorders in humans. Little is known about the malaria parasite PDEs. There are four Plasmodium

stages of the parasite life cycle. We have used a number of transgenic approaches to study the function of this enzyme at this stage of the Plasmodium falciparum life cycle.



Directional selection at the pfmdr1, pfcrt, pfubp1 and pfap2mu loci of Plasmodium falciparum in Kenyan children treated with artemisinin-based combination therapy.

LSHTM Investigators

Beshir, Don van Schalkwyk, Teun Bousema & Colin Sutherland.

External Investigators/Collaborators: Patrick Sawa (International

Centre of Insect Physiology and Ecology, Kenya).

Funding: The European Union through the MALACTRES

Consortium.

Plasmodium falciparum may be threatened by the spread of parasite genotypes with reduced responsiveness to artemisinins.

sub-microscopic persistence of Plasmodium falciparum on day 3 post-treatment was shown to be associated with microscopically detected parasitaemia at day 28 or day 42.

and were determined in the Mbita cohort before treatment, on days 2 and 3 after initiation of treatment and on the day of treatment failure.

population to carry the wildtype haplotypes of pfcrt (NFD

alleles of the novel candidate resistance genes

genetic similarities were found to artemisinin-tolerant parasites recently described in Cambodia.

multi-locus Plasmodium falciparum genotypes are

and contribute to onward transmission and subsequent patent recrudescence. Detection and monitoring of these

determine whether the genotypes we describe pose a public health threat to malaria endemic countries in sub-

In vitro sensitivity of imported malaria parasites.

LSHTM Investigators: Colin Sutherland, Donelly van Schalkwyk &

Rebekah Burrow.

External Investigators/Collaborators: Xavier Ding (Medicines

(Hospital for Tropical Diseases, UK); Christian Hasford (University

College London Hospitals, UK).

Funding:

Many of the parasites used currently to study drug resistance and parasite biology were isolated from patient samples some 20-30 years ago.

However, it is only since 2000 that the World

for Plasmodium falciparum

European travellers presenting to the UK Hospital for Tropical Diseases with malaria to use their parasites for our research. We also noted their travel history. These

to grow in vitro. Thereafter, the isolates were tested for clonality and screened for drug sensitivity against a panel of antimalarial agents supplied by the Medicines for Malaria Venture.

reporting on the clonal diversity, drug sensitivity and mutations in known drug-resistance markers for our “HL” series of isolates. In addition, we have made the adapted isolates available to the wider malaria community. We plan to continue adapting isolates as a platform for measuring differences in drug sensitivity and investigating other aspects of parasite biology related to the genotypes currently circulating in endemic areas.

Alternative molecular mechanisms for erythrocyte invasion by Plasmodium falciparum in Ghana.

LSHTM Investigators: David Conway, Lindsay Stewart, Paul

Bowyer, Craig Duffy & Samuel Assefa.

External Investigators/Collaborators:

Mensah-Brown, James Abugri, Nicholas Amoako & Michael Ofori

Funding: The Leverhulme Trust; The Royal Society.

Development of a blood stage vaccine is hampered by inadequate understanding of the mechanisms by which parasites invade erythrocytes and evade immune responses. The invasive merozoite stage of Plasmodium falciparum has an array of ligands, each interacting with different receptors on the erythrocyte surface, as studied in clinical isolates here.

The aims of this study are to determine the ex vivo erythrocyte invasion phenotypes of Ghanaian Plasmodium falciparum isolates and their dependence on alternative receptors, as well as characterise gene

Plasmodium falciparum ligands involved in alternative invasion pathways. Finally, we aim to identify if parasite gene polymorphisms are under

selection from immune responses blocking particular invasion pathways.

Results so far indicate that a large proportion of parasites in Ghana use sialic acid-independent receptors, suggesting that in highly endemic areas immune selection operates against parasites using sialic acid-bearing

demonstrated by inhibition of invasion using anti-CR1 antibodies. Gene expression assays are testing the prediction that the CR1-cognate parasite ligand Rh4 is

receptor expression knockdown will further characterise selected cultured lines. Initial analyses of almost 100 parasite genome sequences from these populations reveals genes with exceptional allele frequency distributions consistent with balancing selection as expected on targets of acquired immunity. These include

encode proteins under immune selection, as well as other genes that are likely to include relatively uncharacterised targets of immune selection.

-



Directional selection at the pfmdr1, pfcrt, pfubp1 and pfap2mu loci of Plasmodium falciparum in Kenyan children treated with artemisinin-based combination therapy.

LSHTM Investigators

Beshir, Don van Schalkwyk, Teun Bousema & Colin Sutherland.

External Investigators/Collaborators: Patrick Sawa (International

Centre of Insect Physiology and Ecology, Kenya).

Funding: The European Union through the MALACTRES

Consortium.

Plasmodium falciparum may be threatened by the spread of parasite genotypes with reduced responsiveness to artemisinins.

sub-microscopic persistence of Plasmodium falciparum on day 3 post-treatment was shown to be associated with microscopically detected parasitaemia at day 28 or day 42.

and were determined in the Mbita cohort before treatment, on days 2 and 3 after initiation of treatment and on the day of treatment failure.

population to carry the wildtype haplotypes of pfcrt (NFD

alleles of the novel candidate resistance genes

genetic similarities were found to artemisinin-tolerant parasites recently described in Cambodia.

multi-locus Plasmodium falciparum genotypes are

and contribute to onward transmission and subsequent patent recrudescence. Detection and monitoring of these

determine whether the genotypes we describe pose a public health threat to malaria endemic countries in sub-

In vitro sensitivity of imported malaria parasites.

LSHTM Investigators: Colin Sutherland, Donelly van Schalkwyk &

Rebekah Burrow.

External Investigators/Collaborators: Xavier Ding (Medicines

(Hospital for Tropical Diseases, UK); Christian Hasford (University

College London Hospitals, UK).

Funding:

Many of the parasites used currently to study drug resistance and parasite biology were isolated from patient samples some 20-30 years ago.

However, it is only since 2000 that the World

for Plasmodium falciparum

European travellers presenting to the UK Hospital for Tropical Diseases with malaria to use their parasites for our research. We also noted their travel history. These

to grow in vitro. Thereafter, the isolates were tested for clonality and screened for drug sensitivity against a panel of antimalarial agents supplied by the Medicines for Malaria Venture.

reporting on the clonal diversity, drug sensitivity and mutations in known drug-resistance markers for our “HL” series of isolates. In addition, we have made the adapted isolates available to the wider malaria community. We plan to continue adapting isolates as a platform for measuring differences in drug sensitivity and investigating other aspects of parasite biology related to the genotypes currently circulating in endemic areas.

Alternative molecular mechanisms for erythrocyte invasion by Plasmodium falciparum in Ghana.

LSHTM Investigators: David Conway, Lindsay Stewart, Paul

Bowyer, Craig Duffy & Samuel Assefa.


Mensah-Brown, James Abugri, Nicholas Amoako & Michael Ofori

Funding: The Leverhulme Trust; The Royal Society.

Development of a blood stage vaccine is hampered by inadequate understanding of the mechanisms by which parasites invade erythrocytes and evade immune responses. The invasive merozoite stage of Plasmodium falciparum has an array of ligands, each interacting with different receptors on the erythrocyte surface, as studied in clinical isolates here.

The aims of this study are to determine the ex vivo erythrocyte invasion phenotypes of Ghanaian Plasmodium falciparum isolates and their dependence on alternative receptors, as well as characterise gene

Plasmodium falciparum ligands involved in alternative invasion pathways. Finally, we aim to identify if parasite gene polymorphisms are under

selection from immune responses blocking particular invasion pathways.

Results so far indicate that a large proportion of parasites in Ghana use sialic acid-independent receptors, suggesting that in highly endemic areas immune selection operates against parasites using sialic acid-bearing

demonstrated by inhibition of invasion using anti-CR1 antibodies. Gene expression assays are testing the prediction that the CR1-cognate parasite ligand Rh4 is

receptor expression knockdown will further characterise selected cultured lines. Initial analyses of almost 100 parasite genome sequences from these populations reveals genes with exceptional allele frequency distributions consistent with balancing selection as expected on targets of acquired immunity. These include

encode proteins under immune selection, as well as other genes that are likely to include relatively uncharacterised targets of immune selection.

-



Evaluating evidence of positive directional selection in a genome-wide scan of a malaria parasite population with long term retrospective data on drug resistance emergence.

LSHTM Investigators: Craig Duffy, Chris Drakeley, Colin

Conway.

External Investigators/Collaborators: Davis Nwakanma, Alfred

Amambua-Ngwa, Eniyou Oriero, Margaret Pinder & Kalifa Bojang

Bronwyn MacInnis (Wellcome Trust Sanger Institute, UK).

Funding: The Medical Research Council; The European Research

Council.

organisms has potential to identify genes under recent selection, but data on historical allele frequency changes

in four Plasmodium falciparum drug resistance genes

in 668 archived parasite-positive blood samples of a Gambian population, from eight different years between 1984 and 2008. This covered a period before antimalarial resistance was detected locally, through subsequent failure of multiple drugs until introduction of artemisinin-based combination therapy. We then performed genome-wide sequence analysis of 52 clinical isolates from 2008, to prospect for loci under recent directional selection.

Resistance alleles increased from very low frequencies, peaking in 2000 for chloroquine resistance-associated crt and genes and at the end of the survey period for dhfr and dhps genes respectively associated with pyrimethamine and sulphadoxine

drug resistance loci were in the top four regions under strong selection implicated by the genome-wide analysis.

Genome-wide polymorphism analysis of this endemic

documentation of recent selection, demonstrating power to prospectively detect emerging alleles using such a scan.

allele was of lower frequency).

PlasmoView: the visualisation of Plasmodium falciparum genomic variation.LSHTM Investigators: Mark Preston, Samuel Assefa, Teun Bousema, David Conway, Chris Drakeley, Cally Roper, Colin Sutherland

& Taane Clark.

External Investigators/Collaborators: Harold Ocholla (University of Malawi, Malawi); Steffen Borrmann (Kenya Medical Research

& Ogobara Doumbo (Malaria Research and Training Centre, Mali); Francois Nosten (Mahidol University, Thailand); Rick Fairhurst

(National Institute of Allergy & Infectious Diseases, USA).

Funding: The Medical Research Council.

This project is designed to identify, summarise and visualise all genomic variation in malaria parasite genomes from raw sequences in publicly available archives.

The PlasmoView tool displays over 600k polymorphisms across more than 600 samples sourced from 4 continents. The patterns of variation across genomic regions are displayed, including insights into their frequency and geographical informativeness (e.g. levels of

evolutionary processes, including the spread of drug resistance. The website can be accessed from http://pathogenseq.lshtm.ac.uk/plasmoview.

Mutations in the Plasmodium falciparum chloroquine resistance transporter gene.



Evaluating evidence of positive directional selection in a genome-wide scan of a malaria parasite population with long term retrospective data on drug resistance emergence.

LSHTM Investigators: Craig Duffy, Chris Drakeley, Colin

Conway.

External Investigators/Collaborators: Davis Nwakanma, Alfred

Amambua-Ngwa, Eniyou Oriero, Margaret Pinder & Kalifa Bojang

Bronwyn MacInnis (Wellcome Trust Sanger Institute, UK).


Council.

organisms has potential to identify genes under recent selection, but data on historical allele frequency changes

in four Plasmodium falciparum drug resistance genes

in 668 archived parasite-positive blood samples of a Gambian population, from eight different years between 1984 and 2008. This covered a period before antimalarial resistance was detected locally, through subsequent failure of multiple drugs until introduction of artemisinin-based combination therapy. We then performed genome-wide sequence analysis of 52 clinical isolates from 2008, to prospect for loci under recent directional selection.

Resistance alleles increased from very low frequencies, peaking in 2000 for chloroquine resistance-associated crt and genes and at the end of the survey period for dhfr and dhps genes respectively associated with pyrimethamine and sulphadoxine

drug resistance loci were in the top four regions under strong selection implicated by the genome-wide analysis.

Genome-wide polymorphism analysis of this endemic

documentation of recent selection, demonstrating power to prospectively detect emerging alleles using such a scan.

allele was of lower frequency).

PlasmoView: the visualisation of Plasmodium falciparum genomic variation.LSHTM Investigators: Mark Preston, Samuel Assefa, Teun Bousema, David Conway, Chris Drakeley, Cally Roper, Colin Sutherland

& Taane Clark.

External Investigators/Collaborators: Harold Ocholla (University of Malawi, Malawi); Steffen Borrmann (Kenya Medical Research

& Ogobara Doumbo (Malaria Research and Training Centre, Mali); Francois Nosten (Mahidol University, Thailand); Rick Fairhurst

(National Institute of Allergy & Infectious Diseases, USA).


This project is designed to identify, summarise and visualise all genomic variation in malaria parasite genomes from raw sequences in publicly available archives.

The PlasmoView tool displays over 600k polymorphisms across more than 600 samples sourced from 4 continents. The patterns of variation across genomic regions are displayed, including insights into their frequency and geographical informativeness (e.g. levels of

evolutionary processes, including the spread of drug resistance. The website can be accessed from http://pathogenseq.lshtm.ac.uk/plasmoview.

Mutations in the Plasmodium falciparum chloroquine resistance transporter gene.



Genomic epidemiology and population genetic analysis of Plasmodium falciparum malaria.

LSHTM Investigators: Mark Preston, Samuel Assefa, Francesc

Coll, Harold Ocholla, Hanif Samad, Cally Roper, Nuno Sepulveda &

Taane Clark.

External Investigators/Collaborators: Steffen Borrmann (Kenya

Medical Research Institute, Kenya), Rick Fairhurst (National Institute

of Health, USA), Chris Plowe (University of Maryland, USA).


We are attempting to mine large public repositories of Plasmodium falciparum sequence data to perform population genetic analyses and develop methods to identify important genomic variations. This work includes:

nuclear and non-nuclear Plasmodium falciparum

geographic origin

positive and balancing selection to inform drug resistance and vaccine candidate studies

performing genome-wide association studies

structural variants, and integrating them into web-based (

and population genetic signatures by accurately imputing missing genotype data using inferred recombination maps

includes investigations into highly variable gene families (e.g. Plasmodium species (e.g. Plasmodium vivax

Genome-wide analysis of selection on the malaria parasite Plasmodium falciparum in a highly endemic population in Guinea compared with a Gambian population of lower endemicity.

LSHTM Investigators

Jones, Lee Murray, Taane Clark & David Conway.

External Investigators/Collaborators: Kovana Marcel Loua &

Eugene Laman (National Institute of Public Health, Republic of

MacInnis (Wellcome Trust Sanger Institute, UK).


Council.

Genome-wide analysis of Plasmodium falciparum sequence variation was undertaken on 100 clinical isolates sampled from a highly endemic region of the Republic of Guinea where transmission occurs for most of each year, and compared with data from 52 clinical isolates from a previously sampled population from The Gambia where there is relatively limited seasonal malaria transmission.

evidence of recent positive directional selection and

and host immunity have been major selective agents. Many of the signatures of recent directional selection

resistance loci due to historically different antimalarial use between the countries. In contrast, both populations showed a similar set of loci likely to be under balancing

genes expressed at the merozoite stage that invades

exceptional differentiation of allele frequencies at a small

polymorphisms covering a 15kb region within and gene that regulates the early stages

of gametocyte development, which is likely related to the extreme differences in mosquito vector abundance and seasonality which determine the transmission opportunities for the sexual stage of the parasite.

ST) between the Plasmodium falciparum

STsingle nucleotide polymorphisms (SNPs) across the genome, with each chromosome identi-

ST

Population genetic structure of Plasmodium knowlesi.

LSHTM Investigators: Paul Divis, David Conway, Samuel Assefa &

Craig Duffy.

External Investigators/Collaborators: Balbir Singh (University of

Malaysia, Malaysia).

Funding: The European Research Council; Ministry of Education,

Malaysia.

Human knowlesi malaria cases have been recently

to be the reservoir hosts in Malaysian Borneo, but no systematic analysis has been performed to study the population structure of Plasmodium knowlesi.

In this study, we develop microsatellite genotyping assays, and apply these on Plasmodium knowlesi isolates to examine the population genetic structure throughout its geographical distribution. In the initial phase, genotyping

of Plasmodium knowlesi was performed on 238 blood samples from human clinical cases in six different areas of mainland Peninsular Malaysia and Malaysian

loci widely distributed in the genome. Most human Plasmodium knowlesi infections contained a single

between the different areas. Linkage disequilibrium was low in all areas, suggesting random assortment of alleles during cross-mating between different parasites. Pairwise genetic differentiation indicated that the Sarawak and Sabah subpopulations were relatively similar, but had marked differentiation from a population in mainland Peninsular Malaysia. Samples from other geographical areas and macaque hosts are being analysed in ongoing work, as well as whole genome sequence data from selected sites.



Genomic epidemiology and population genetic analysis of Plasmodium falciparum malaria.

LSHTM Investigators: Mark Preston, Samuel Assefa, Francesc

Coll, Harold Ocholla, Hanif Samad, Cally Roper, Nuno Sepulveda &

Taane Clark.

External Investigators/Collaborators: Steffen Borrmann (Kenya

Medical Research Institute, Kenya), Rick Fairhurst (National Institute

of Health, USA), Chris Plowe (University of Maryland, USA).


We are attempting to mine large public repositories of Plasmodium falciparum sequence data to perform population genetic analyses and develop methods to identify important genomic variations. This work includes:

nuclear and non-nuclear Plasmodium falciparum

geographic origin

positive and balancing selection to inform drug resistance and vaccine candidate studies

performing genome-wide association studies

structural variants, and integrating them into web-based (

and population genetic signatures by accurately imputing missing genotype data using inferred recombination maps

includes investigations into highly variable gene families (e.g. Plasmodium species (e.g. Plasmodium vivax

Genome-wide analysis of selection on the malaria parasite Plasmodium falciparum in a highly endemic population in Guinea compared with a Gambian population of lower endemicity.

LSHTM Investigators

Jones, Lee Murray, Taane Clark & David Conway.

External Investigators/Collaborators: Kovana Marcel Loua &

Eugene Laman (National Institute of Public Health, Republic of

MacInnis (Wellcome Trust Sanger Institute, UK).


Council.

Genome-wide analysis of Plasmodium falciparum sequence variation was undertaken on 100 clinical isolates sampled from a highly endemic region of the Republic of Guinea where transmission occurs for most of each year, and compared with data from 52 clinical isolates from a previously sampled population from The Gambia where there is relatively limited seasonal malaria transmission.

evidence of recent positive directional selection and

and host immunity have been major selective agents. Many of the signatures of recent directional selection

resistance loci due to historically different antimalarial use between the countries. In contrast, both populations showed a similar set of loci likely to be under balancing

genes expressed at the merozoite stage that invades

exceptional differentiation of allele frequencies at a small

polymorphisms covering a 15kb region within and gene that regulates the early stages

of gametocyte development, which is likely related to the extreme differences in mosquito vector abundance and seasonality which determine the transmission opportunities for the sexual stage of the parasite.

ST) between the Plasmodium falciparum

STsingle nucleotide polymorphisms (SNPs) across the genome, with each chromosome identi-

ST

Population genetic structure of Plasmodium knowlesi.

LSHTM Investigators: Paul Divis, David Conway, Samuel Assefa &

Craig Duffy.

External Investigators/Collaborators: Balbir Singh (University of

Malaysia, Malaysia).

Funding: The European Research Council; Ministry of Education,

Malaysia.

Human knowlesi malaria cases have been recently

to be the reservoir hosts in Malaysian Borneo, but no systematic analysis has been performed to study the population structure of Plasmodium knowlesi.

In this study, we develop microsatellite genotyping assays, and apply these on Plasmodium knowlesi isolates to examine the population genetic structure throughout its geographical distribution. In the initial phase, genotyping

of Plasmodium knowlesi was performed on 238 blood samples from human clinical cases in six different areas of mainland Peninsular Malaysia and Malaysian

loci widely distributed in the genome. Most human Plasmodium knowlesi infections contained a single

between the different areas. Linkage disequilibrium was low in all areas, suggesting random assortment of alleles during cross-mating between different parasites. Pairwise genetic differentiation indicated that the Sarawak and Sabah subpopulations were relatively similar, but had marked differentiation from a population in mainland Peninsular Malaysia. Samples from other geographical areas and macaque hosts are being analysed in ongoing work, as well as whole genome sequence data from selected sites.



Determinants of Plasmodium falciparum drug response in vitro.

LSHTM Investigators: Ifeyinwa Aniebo, Colin Sutherland & Taane

Clarke.

This study investigates alternative methods of assaying artemisinin resistance by in vitro exposure to

in vivo and so short drug pulses were applied to parasites in an effort to better mimic in vivo conditions.

were used to observe any differences that may exist in

project hypothesizes that differences in mean IC50 values exist between isolates using both the 6hr pulse assay and standard 48 hour assay methods in determining artemisinin drug sensitivity. These differences could be used to identify a phenotype which could form the basis to which artemisinin resistance can be explored.

values for the 6hr pulse assays were higher than that of the standard 48hr assays. This trend was seen as a shift to the right in the dose response curve. This

experiment had variations which could be explained by the polyclonal nature of the isolates used in this study.

out any differences that may be present and statistical analysis will also be done. Clones of each isolate will be separated using limiting dilution method and each clone would be studied genetically using whole genome sequencing technology. There is an urgent need to develop an in vitro assay that correlate with parasite clearance half life as this will be useful in elucidating the molecular basis of artemisinin resistance.

Development of an anti-malarial drug that targets the Plasmodium falciparum cGMP-dependent protein kinase.

LSHTM Investigators: David Baker, Paul Bowyer, Simon Croft &

Lindsay Stewart.

External Investigators/Collaborators: Katy Kettleborough &

Andrew Merritt (MRC Technology, UK).

Funding: The Medical Research Council .

We are aiming to develop a new antimalarial drug that cures malaria by killing the asexual erythrocytic parasites but also attacks additional life-cycle stages.

Plasmdoium falciparum protein kinase (cGMP-dependent protein kinase, Pf

essential in multiple life-cycle stages. PfPKG is a novel

with antimalarials that hit alternative targets. Selective inhibitors of PKG block Plasmodium blood-stage schizont, gamete and ookinete development. Recent data by others indicate an essential role for PKG in liver stages. Medicinal chemists at MRC Technology have synthesised more than 500 new inhibitors which have being tested at LSHTM for their ability to block the growth of malaria parasites at various life cycle stages. New potent, highly selective compounds have been generated in the low nM range against Plasmodium falciparum growth in vitro.

GENINVADE: parasite population genomics and functional studies towards development of a blood stage malaria vaccine.

LSHTM Investigators: David Conway, Craig Duffy, Paul Bowyer,

Lindsay Stewart & Samuel Assefa.

External Investigators/Collaborators: Alfred Amambua-Ngwa

Hospital, Senegal); Mahamadou Diakite (University of Bamako,

Mali); Dominic Kwiatkowski (Wellcome Trust Sanger Institute, UK);

Manoj Duraisingh (Harvard University, USA).

Funding: The European Research Council.

Understanding of natural selection operating on parasites in local endemic populations can enable understanding of molecular mechanisms of parasite invasion and immune evasion.

Powerful methods are now being developed for population genomic analyses and selection experiments on parasites in culture, including single-cell analysis, and this programme uses these together in an aim to identify optimal candidate components for a vaccine, taking the following approaches:

Plasmodium falciparum in sites of contrasting endemicity in West

hypotheses on mechanisms used by merozoites to invade erythrocytes and evade acquired immune responses

invasion into erythrocytes to identify the receptor-ligand interactions used by different parasite populations ex vivo. Novel receptor knockdown assays on cultured erythrocytes will be employed, and parasite adaptation experiments conducted to identify constraints on the use of alternative invasion pathways

and genome sequences. This is aimed to validate

to genetics and phenotyping of parasites in the future. Candidate molecule discoveries will be taken forwards to receptor-ligand interaction assays, antibody inhibition and immuno-epidemiological studies.

on the erythrocyte surface by neuraminidase).



Determinants of Plasmodium falciparum drug response in vitro.

LSHTM Investigators: Ifeyinwa Aniebo, Colin Sutherland & Taane

Clarke.

This study investigates alternative methods of assaying artemisinin resistance by in vitro exposure to

in vivo and so short drug pulses were applied to parasites in an effort to better mimic in vivo conditions.

were used to observe any differences that may exist in

project hypothesizes that differences in mean IC50 values exist between isolates using both the 6hr pulse assay and standard 48 hour assay methods in determining artemisinin drug sensitivity. These differences could be used to identify a phenotype which could form the basis to which artemisinin resistance can be explored.

values for the 6hr pulse assays were higher than that of the standard 48hr assays. This trend was seen as a shift to the right in the dose response curve. This

experiment had variations which could be explained by the polyclonal nature of the isolates used in this study.

out any differences that may be present and statistical analysis will also be done. Clones of each isolate will be separated using limiting dilution method and each clone would be studied genetically using whole genome sequencing technology. There is an urgent need to develop an in vitro assay that correlate with parasite clearance half life as this will be useful in elucidating the molecular basis of artemisinin resistance.

Development of an anti-malarial drug that targets the Plasmodium falciparum cGMP-dependent protein kinase.

LSHTM Investigators: David Baker, Paul Bowyer, Simon Croft &

Lindsay Stewart.

External Investigators/Collaborators: Katy Kettleborough &

Andrew Merritt (MRC Technology, UK).

Funding: The Medical Research Council .

We are aiming to develop a new antimalarial drug that cures malaria by killing the asexual erythrocytic parasites but also attacks additional life-cycle stages.

Plasmdoium falciparum protein kinase (cGMP-dependent protein kinase, Pf

essential in multiple life-cycle stages. PfPKG is a novel

with antimalarials that hit alternative targets. Selective inhibitors of PKG block Plasmodium blood-stage schizont, gamete and ookinete development. Recent data by others indicate an essential role for PKG in liver stages. Medicinal chemists at MRC Technology have synthesised more than 500 new inhibitors which have being tested at LSHTM for their ability to block the growth of malaria parasites at various life cycle stages. New potent, highly selective compounds have been generated in the low nM range against Plasmodium falciparum growth in vitro.

GENINVADE: parasite population genomics and functional studies towards development of a blood stage malaria vaccine.

LSHTM Investigators: David Conway, Craig Duffy, Paul Bowyer,

Lindsay Stewart & Samuel Assefa.

External Investigators/Collaborators: Alfred Amambua-Ngwa

Hospital, Senegal); Mahamadou Diakite (University of Bamako,

Mali); Dominic Kwiatkowski (Wellcome Trust Sanger Institute, UK);

Manoj Duraisingh (Harvard University, USA).

Funding: The European Research Council.

Understanding of natural selection operating on parasites in local endemic populations can enable understanding of molecular mechanisms of parasite invasion and immune evasion.

Powerful methods are now being developed for population genomic analyses and selection experiments on parasites in culture, including single-cell analysis, and this programme uses these together in an aim to identify optimal candidate components for a vaccine, taking the following approaches:

Plasmodium falciparum in sites of contrasting endemicity in West

hypotheses on mechanisms used by merozoites to invade erythrocytes and evade acquired immune responses

invasion into erythrocytes to identify the receptor-ligand interactions used by different parasite populations ex vivo. Novel receptor knockdown assays on cultured erythrocytes will be employed, and parasite adaptation experiments conducted to identify constraints on the use of alternative invasion pathways

and genome sequences. This is aimed to validate

to genetics and phenotyping of parasites in the future. Candidate molecule discoveries will be taken forwards to receptor-ligand interaction assays, antibody inhibition and immuno-epidemiological studies.

on the erythrocyte surface by neuraminidase).



Immunology and host resistance

Molecular mechanisms of malaria associated lung damage.

LSHTM Investigators: Brian de Souza, Eleanor Riley & Colin

Sutherland.

External Investigators/Collaborators: Alister Craig (Liverpool

School of Tropical Medicine, UK); Dan Milner (Harvard University

& Brigham Women’s Hospital, USA); Kevin Couper (University of

Manchester, UK).

It is clear that a good understanding of the underlying disease processes of malaria-induced lung damage (M-

Post-mortem examination of lung tissue from M-LD individuals shows parasites sequestering to the alveolar microvascular endothelium with vessel damage and

sequestration during infection is thus very important, but not possible to perform in humans.

We believe that studies to determine the fundamental host endothelium/parasite surface receptor interactions responsible for parasite sequestration in the lung, leading to endothelial cell dysfunction and development of M-LD,

can adequately be performed in vitro. Therefore, the primary aim of this proposal is to develop and utilise an in vitro assay system to dissect the pathogenesis of M-LD

host-parasite interactions leading up to endothelial cell damage. This in vitro study is ideal for determining the basic mechanisms of M-LD; the study will serve as a precursor for the development of an in vivo model for

objectives of the project are to:

enable parasite and leukocyte cytoadhesion to human lung endothelium in static in vitro assays then under

samples to verify the above in vitro

lung MVEC and that cytoadhesion of Plasmodium falciparum

Cytoadhesion of infected human RBC (A, B) and Pf PRBC (C, D) to non-activated (A, C) and TNF-activated hu lung

indicate PRBC in contact with endothelium.

Experimental cerebral malaria develops independently of caspase recruitment domain-containing protein 9 signaling.

LSHTM Investigators: Julius Hafalla.

External Investigators/Collaborators: Jan Burgold, Anca Dorhoi,

Stefan Kaufmann & Kai Matuschewski (Max Planck Institute for

Funding: The Royal Society; The European Federation of

Immunological Societies; The Wellcome Trust; The Max Planck

Biology Organisation.

The outcome of infection depends on multiple layers of immune regulation, with innate immunity playing a decisive role in shaping protection or pathogenic sequelae of acquired immunity.

The contribution of pattern recognition receptors and adaptor molecules in immunity to malaria remains poorly understood. Here, we interrogate the role of the caspase recruitment domain-containing protein

Plasmodium bergheiexpression was upregulated in the brains of infected

pathway in ECM pathogenesis. However, Plasmodium bergheineurological signs and presented with disrupted blood-brain barriers similar to WT mice. Furthermore, consistent with the immunological features associated with ECM

cerebral microvasculature. We conclude that ECM

Host candidate genes and malaria susceptibility in African populations.

LSHTM Investigators: Nuno Sepúlveda, Patrick Corran, Hugh

Reyburn, Eleanor Riley, Taane Clark & Chris Drakeley.

External Investigators/Collaborators: Alphaxard Manjurano

Mangano & David Modiamo (Sapienza University of Rome,

Italy); Bakary Maiga, Amagana Dolo, Mahamadou Thera &

Ogobara Doumbo (Malaria Research and Training Centre, Mali);

Consortium (University of Oxford, UK).

Funding:

Trust.

Malaria is a complex disease with many genetic and

variation in response to infection, progression and severity.

Several factors have a role, including parasite genetic make-up, host age, state of immunity and genetic background. Host genetic factors, including

risk. MalariaGEN has genotyped 150 candidate malaria polymorphisms across thousands of individuals from

sectional studies in Burkina Faso, Mali and Tanzania. Immunological titre data, including for IgE and MSP1, is also available. We have found strong protective effects

sectional study in Mali pinpointed the genetic (e.g. G6PD

the Fulani and Dogon, two sympatric populations differing

two association studies using data of asymptomatic individuals from Burkina Faso and Tanzania.

Malaria Centre members focus on identifying protective rather than immunopathological responses and on understanding the nature of immune memory in order to better design effective vaccines.



Immunology and host resistance

Molecular mechanisms of malaria associated lung damage.

LSHTM Investigators: Brian de Souza, Eleanor Riley & Colin

Sutherland.

External Investigators/Collaborators: Alister Craig (Liverpool

School of Tropical Medicine, UK); Dan Milner (Harvard University

& Brigham Women’s Hospital, USA); Kevin Couper (University of

Manchester, UK).

It is clear that a good understanding of the underlying disease processes of malaria-induced lung damage (M-

Post-mortem examination of lung tissue from M-LD individuals shows parasites sequestering to the alveolar microvascular endothelium with vessel damage and

sequestration during infection is thus very important, but not possible to perform in humans.

We believe that studies to determine the fundamental host endothelium/parasite surface receptor interactions responsible for parasite sequestration in the lung, leading to endothelial cell dysfunction and development of M-LD,

can adequately be performed in vitro. Therefore, the primary aim of this proposal is to develop and utilise an in vitro assay system to dissect the pathogenesis of M-LD

host-parasite interactions leading up to endothelial cell damage. This in vitro study is ideal for determining the basic mechanisms of M-LD; the study will serve as a precursor for the development of an in vivo model for

objectives of the project are to:

enable parasite and leukocyte cytoadhesion to human lung endothelium in static in vitro assays then under

samples to verify the above in vitro

lung MVEC and that cytoadhesion of Plasmodium falciparum

Cytoadhesion of infected human RBC (A, B) and Pf PRBC (C, D) to non-activated (A, C) and TNF-activated hu lung

indicate PRBC in contact with endothelium.

Experimental cerebral malaria develops independently of caspase recruitment domain-containing protein 9 signaling.


External Investigators/Collaborators: Jan Burgold, Anca Dorhoi,

Stefan Kaufmann & Kai Matuschewski (Max Planck Institute for



Biology Organisation.

The outcome of infection depends on multiple layers of immune regulation, with innate immunity playing a decisive role in shaping protection or pathogenic sequelae of acquired immunity.

The contribution of pattern recognition receptors and adaptor molecules in immunity to malaria remains poorly understood. Here, we interrogate the role of the caspase recruitment domain-containing protein

Plasmodium bergheiexpression was upregulated in the brains of infected

pathway in ECM pathogenesis. However, Plasmodium bergheineurological signs and presented with disrupted blood-brain barriers similar to WT mice. Furthermore, consistent with the immunological features associated with ECM

cerebral microvasculature. We conclude that ECM

Host candidate genes and malaria susceptibility in African populations.

LSHTM Investigators: Nuno Sepúlveda, Patrick Corran, Hugh

Reyburn, Eleanor Riley, Taane Clark & Chris Drakeley.

External Investigators/Collaborators: Alphaxard Manjurano

Mangano & David Modiamo (Sapienza University of Rome,

Italy); Bakary Maiga, Amagana Dolo, Mahamadou Thera &

Ogobara Doumbo (Malaria Research and Training Centre, Mali);

Consortium (University of Oxford, UK).

Funding:

Trust.

Malaria is a complex disease with many genetic and

variation in response to infection, progression and severity.

Several factors have a role, including parasite genetic make-up, host age, state of immunity and genetic background. Host genetic factors, including

risk. MalariaGEN has genotyped 150 candidate malaria polymorphisms across thousands of individuals from

sectional studies in Burkina Faso, Mali and Tanzania. Immunological titre data, including for IgE and MSP1, is also available. We have found strong protective effects

sectional study in Mali pinpointed the genetic (e.g. G6PD

the Fulani and Dogon, two sympatric populations differing

two association studies using data of asymptomatic individuals from Burkina Faso and Tanzania.

Malaria Centre members focus on identifying protective rather than immunopathological responses and on understanding the nature of immune memory in order to better design effective vaccines.



Parasite sequestration in uncomplicated and severe childhood Plasmodium falciparum malaria.

LSHTM Investigators: Aubrey Cunnington, Michael Bretscher,

Sarah Nogaro & Eleanor Riley.

External Investigators/Collaborators: Michael Walther (Medical


Mature red blood cell stages of Plasmodium falciparum sequester in peripheral tissues by adhering to vascular endothelium and this process is implicated in the pathogenesis of severe malaria but direct evidence is lacking.

The objective of this study was to determine whether sequestration of parasitized red blood cells differs between children with uncomplicated and severe Plasmodium falciparumcirculating-, total- and sequestered- parasite biomass, using a mathematical model based on plasma concentration of Plasmodium falciparum histidine rich protein 2. Circulating- and total-, but not sequestered-,

Gambian children with severe malaria than in those with uncomplicated malaria. Sequestered biomass estimates in children with hyperlactataemia or prostration were similar to those in uncomplicated malaria, whereas sequestered biomass was higher in patients with severe anaemia, and showed a trend to higher values in cerebral malaria and fatal cases. Blood lactate concentration correlated with circulating- and total-, but not sequestered parasite biomass.

We conclude that extensive sequestration is not a uniform requirement for severe paediatric malaria. In particular, the pathophysiology of hyperlactataemia and prostration appears to be unrelated to sequestered

mechanisms may underlie different severe malaria syndromes, and different therapeutic strategies may be required to improve survival.

The distribution of parasites in different malaria syndromes. The size of the hippopotamus represents the total parasite biomass in the human body. The proportion of the hippopotamus above or below the water-line indicates the relative proportion of circulating and sequestered parasites.

responses to malaria liver stages by genome-


External Investigators/Collaborators: Karolis Bauza & Adrian Hill

(University of Oxford, UK); Johannes Friesen & Kai Matuschewski



Foundation.

CD8+ T cells mediate immunity against Plasmodium liver

of CD8+ T cells has limited our current understanding of

To identify antigenic epitopes in a stringent murine malaria immunisation model, we performed a systematic

of Plasmodium berghei

PbS20318 and PbC57BL/6 mice vaccinated by whole parasite strategies known to protect against sporozoite challenge. While both PbS20318 and Pbeffector memory phenotypes in both the spleens and livers of immunised mice, only PbCD8+ T cells exhibit in vivo cytotoxicity. Moreover, Pb Pb

development. Prime/boost vaccination with Pb

sporozoite challenge. We conclude that Pb

antigen during liver-stage infection. Together, our results underscore the presence of CD8+ T cells with divergent potencies against distinct Plasmodium liver-stage

T cells will allow interrogation of the development of immune responses against malaria liver stages.

The role of IL-27 in the immunology and immunopathology of malaria.

LSHTM Investigators

Brian de Souza, Seen-Wai Lavelle, Tovah Shaw, Kevin Couper &

Eleanor Riley.


USA); Chris Hunter (University of Pennsylvania, USA).


Council;The Medical Research Council .

Successful resolution of infection requires the generation

simultaneously avoiding damage to host tissues.This balance is crucial for clinical immunity to malaria,

allowing parasitised red blood cells to be cleared whilst

to severe malaria and malaria deaths. This balance is

maintained by a suite of immunoregulatory cytokines

series of studies to investigate the role of IL-27 in malaria infection, making use of a model of malaria in mice lacking the essential IL-27 receptor molecule, WSX-1.

We have shown that IL-27/WSX-1 signalling restrains the development of pathogenic, terminally differentiated Th1 cells during infection by regulating their intrinsic responsiveness to IL-12. This process is independent of any effects of IL-10 or Foxp3. Furthermore, we have shown that IL-27 receptor signalling regulates CD4+ T cell chemotactic responses during infection and inhibits CD4+ T cell migration to the liver; and regulates memory CD4+

secondary and subsequent malaria infections. Taken together these studies have revealed a novel pathway of immunoregulation during malaria infection that may be amenable to therapeutic intervention to prevent severe disease.



Parasite sequestration in uncomplicated and severe childhood Plasmodium falciparum malaria.

LSHTM Investigators: Aubrey Cunnington, Michael Bretscher,

Sarah Nogaro & Eleanor Riley.

External Investigators/Collaborators: Michael Walther (Medical


Mature red blood cell stages of Plasmodium falciparum sequester in peripheral tissues by adhering to vascular endothelium and this process is implicated in the pathogenesis of severe malaria but direct evidence is lacking.

The objective of this study was to determine whether sequestration of parasitized red blood cells differs between children with uncomplicated and severe Plasmodium falciparumcirculating-, total- and sequestered- parasite biomass, using a mathematical model based on plasma concentration of Plasmodium falciparum histidine rich protein 2. Circulating- and total-, but not sequestered-,

Gambian children with severe malaria than in those with uncomplicated malaria. Sequestered biomass estimates in children with hyperlactataemia or prostration were similar to those in uncomplicated malaria, whereas sequestered biomass was higher in patients with severe anaemia, and showed a trend to higher values in cerebral malaria and fatal cases. Blood lactate concentration correlated with circulating- and total-, but not sequestered parasite biomass.

We conclude that extensive sequestration is not a uniform requirement for severe paediatric malaria. In particular, the pathophysiology of hyperlactataemia and prostration appears to be unrelated to sequestered

mechanisms may underlie different severe malaria syndromes, and different therapeutic strategies may be required to improve survival.

The distribution of parasites in different malaria syndromes. The size of the hippopotamus represents the total parasite biomass in the human body. The proportion of the hippopotamus above or below the water-line indicates the relative proportion of circulating and sequestered parasites.

responses to malaria liver stages by genome-


External Investigators/Collaborators: Karolis Bauza & Adrian Hill

(University of Oxford, UK); Johannes Friesen & Kai Matuschewski



Foundation.

CD8+ T cells mediate immunity against Plasmodium liver

of CD8+ T cells has limited our current understanding of

To identify antigenic epitopes in a stringent murine malaria immunisation model, we performed a systematic

of Plasmodium berghei

PbS20318 and PbC57BL/6 mice vaccinated by whole parasite strategies known to protect against sporozoite challenge. While both PbS20318 and Pbeffector memory phenotypes in both the spleens and livers of immunised mice, only PbCD8+ T cells exhibit in vivo cytotoxicity. Moreover, Pb Pb

development. Prime/boost vaccination with Pb

sporozoite challenge. We conclude that Pb

antigen during liver-stage infection. Together, our results underscore the presence of CD8+ T cells with divergent potencies against distinct Plasmodium liver-stage

T cells will allow interrogation of the development of immune responses against malaria liver stages.

The role of IL-27 in the immunology and immunopathology of malaria.

LSHTM Investigators

Brian de Souza, Seen-Wai Lavelle, Tovah Shaw, Kevin Couper &

Eleanor Riley.


USA); Chris Hunter (University of Pennsylvania, USA).


Council;The Medical Research Council .

Successful resolution of infection requires the generation

simultaneously avoiding damage to host tissues.This balance is crucial for clinical immunity to malaria,

allowing parasitised red blood cells to be cleared whilst

to severe malaria and malaria deaths. This balance is

maintained by a suite of immunoregulatory cytokines

series of studies to investigate the role of IL-27 in malaria infection, making use of a model of malaria in mice lacking the essential IL-27 receptor molecule, WSX-1.

We have shown that IL-27/WSX-1 signalling restrains the development of pathogenic, terminally differentiated Th1 cells during infection by regulating their intrinsic responsiveness to IL-12. This process is independent of any effects of IL-10 or Foxp3. Furthermore, we have shown that IL-27 receptor signalling regulates CD4+ T cell chemotactic responses during infection and inhibits CD4+ T cell migration to the liver; and regulates memory CD4+

secondary and subsequent malaria infections. Taken together these studies have revealed a novel pathway of immunoregulation during malaria infection that may be amenable to therapeutic intervention to prevent severe disease.



Analysis of antibodies to newly described Plasmodium falciparum merozoite antigens supports MSPDBL2 as a predicted target of naturally acquired immunity.

LSHTM Investigators: Kevin Tetteh,

Laura Drought & David Conway.


Kamuyu & Kevin Marsh (Kenya

Medical Research Institute, Kenya);

Marilyne Failly & Christoph Martin (PX

Therapeutics, France).


Prospective studies continue to identify malaria parasite genes showing patterns of polymorphism indicative of immune selection pressure, and such proteins require investigation.

Sixteen new recombinant protein reagents were designed to characterize three such polymorphic proteins expressed in Plasmodium falciparum schizonts and merozoites: MSPDBL1 (also

and SURFIN4.2, encoded by a member of the surface-associated interspersed (surftesting the antigenicities of these reagents by murine

analyzed naturally acquired antibody responses to the antigens in two cohorts in coastal Kenya in which the parasite was endemic (Chonyi [ ] and Ngerenya [n

antibodies increased with age. We then investigated correlations with subsequent risk of clinical malaria among children <11 years of age during 6 months follow-

region of MSPDBL2 were associated with reduced risk

remaining for the 3D7 allelic type after adjustment for individuals’ ages in years and antibody reactivity to whole-schizont extract (Chonyi, risk ratio, 0.51, and 95%

association in one cohort (Ngerenya, risk ratio, 0.53,

showed no protective associations after adjustment.

to the polymorphic region of MSPDBL2 contribute to protective immunity.

Searching for correlates of protection of the RTS,S malaria vaccine.

LSHTM Investigators: Eleanor Riley.

External Investigators/Collaborators: Michael White, Jamie

Olotu (Wellcome Trust-Kenya Medical Research Institute, Kenya);

Kent Kester & Christian Ockenhouse (Walter Reed National Military

Medical Center, USA).

Funding: The Medical Research Council; The Wellcome Trust;

Initiative.

Vaccination with the pre-erythrocytic malaria vaccine RTS,S induces high levels of antibodies and CD4+ T cells

Using a biologically-motivated mathematical model

naive adults vaccinated with RTS,S and subjected to experimental Plasmodium falciparum challenge, we

characterised the relationship between antibodies, T cell responses and protection from infection. Both anti-CSP

as immunological surrogates of protection, with RTS,S induced anti-CSP antibodies estimated to prevent 32%

is estimated to result from a 96.1% (95% CI, 93.4% –

indicating that in volunteers who developed Plasmodium falciparum infection, a small number of parasites

responsible for breakthrough blood-stage infections. These data indicate that it may not be biologically

plausible to achieve sterilising protection with this vaccine

on achieving and maintaining higher concentrations of antibodies with higher avidity.

Comparison of antibody -

sporozoite. Estimated

sporozoite (blue) with

as a function of anti-CSP antibody titres obtained using the sporozoite model. A histogram of the distribution of anti-CSP antibody titres is shown in grey.



Analysis of antibodies to newly described Plasmodium falciparum merozoite antigens supports MSPDBL2 as a predicted target of naturally acquired immunity.

LSHTM Investigators: Kevin Tetteh,

Laura Drought & David Conway.


Kamuyu & Kevin Marsh (Kenya

Medical Research Institute, Kenya);

Marilyne Failly & Christoph Martin (PX

Therapeutics, France).


Prospective studies continue to identify malaria parasite genes showing patterns of polymorphism indicative of immune selection pressure, and such proteins require investigation.

Sixteen new recombinant protein reagents were designed to characterize three such polymorphic proteins expressed in Plasmodium falciparum schizonts and merozoites: MSPDBL1 (also

and SURFIN4.2, encoded by a member of the surface-associated interspersed (surftesting the antigenicities of these reagents by murine

analyzed naturally acquired antibody responses to the antigens in two cohorts in coastal Kenya in which the parasite was endemic (Chonyi [ ] and Ngerenya [n

antibodies increased with age. We then investigated correlations with subsequent risk of clinical malaria among children <11 years of age during 6 months follow-

region of MSPDBL2 were associated with reduced risk

remaining for the 3D7 allelic type after adjustment for individuals’ ages in years and antibody reactivity to whole-schizont extract (Chonyi, risk ratio, 0.51, and 95%

association in one cohort (Ngerenya, risk ratio, 0.53,

showed no protective associations after adjustment.

to the polymorphic region of MSPDBL2 contribute to protective immunity.

Searching for correlates of protection of the RTS,S malaria vaccine.

LSHTM Investigators: Eleanor Riley.

External Investigators/Collaborators: Michael White, Jamie

Olotu (Wellcome Trust-Kenya Medical Research Institute, Kenya);

Kent Kester & Christian Ockenhouse (Walter Reed National Military

Medical Center, USA).

Funding: The Medical Research Council; The Wellcome Trust;

Initiative.

Vaccination with the pre-erythrocytic malaria vaccine RTS,S induces high levels of antibodies and CD4+ T cells

Using a biologically-motivated mathematical model

naive adults vaccinated with RTS,S and subjected to experimental Plasmodium falciparum challenge, we

characterised the relationship between antibodies, T cell responses and protection from infection. Both anti-CSP

as immunological surrogates of protection, with RTS,S induced anti-CSP antibodies estimated to prevent 32%

is estimated to result from a 96.1% (95% CI, 93.4% –

indicating that in volunteers who developed Plasmodium falciparum infection, a small number of parasites

responsible for breakthrough blood-stage infections. These data indicate that it may not be biologically

plausible to achieve sterilising protection with this vaccine

on achieving and maintaining higher concentrations of antibodies with higher avidity.

Comparison of antibody -

sporozoite. Estimated

sporozoite (blue) with

as a function of anti-CSP antibody titres obtained using the sporozoite model. A histogram of the distribution of anti-CSP antibody titres is shown in grey.



of a malaria transmission blocking vaccine (REDMAL).

LSHTM Investigators: Sophie Jones, Teun Bousema & Chris

Drakeley.

External Investigators/Collaborators: Robert Sauerwein &

Will Roeffen (Radboud University Nijmegen Medical Centre,

Netherlands); Michael Theisen (Statens Serum Institute, Denmark);

(Kilimanjaro Christian Medical Centre, Tanzania); Daniel Dodoo

Formation sur le Paludisme, Burkina Faso).

Funding:

Malaria transmission blocking vaccine targets are sexual stage antigens which are exposed to host immunity during parasite clearance from the blood.

It is therefore anticipated that individuals living in

endemic regions will already have antibodies against the vaccine candidates, which may provide boosting to the vaccine induced immunity. The aim of this work package was to explore recognition and functionality

we have demonstrated that school aged children in 3 endemic settings have antibodies against two new recombinant transmission blocking vaccine candidates, 10C (pf pfthe majority of previous research, we found evidence of an age dependant acquisition pattern, in the site of

prevalence and transmission reducing activity at the 90%

activity of serum from vaccinated rodents to block

-

Vector biology

Malaria Transmission Consortium: molecular characterisation reveals novel malaria vectors in the western Kenyan Highlands.

LSHTM Investigators: Jennifer Stevenson, Mary Cooke, Chris

Drakeley & Jon Cox.

External Investigators/Collaborators: Brandy St. Laurent, Neil

Lobo, Puji Asih, J.D Mueller & Frank Collins (University of Notre

Dame, USA); Sam Kahindi, Elizabeth Ayoma & Robin Oriango

Prevention, Kenya); Ralph Harbach (Natural History Museum, UK).

Funding:

Transmission Consortium.

The success of mosquito-based malaria control is dependent upon susceptible bionomic traits in local malaria vectors. It is therefore crucial to have accurate and reliable methods to determine mosquito species composition.

Anopheles species was collected in the western Kenyan highlands, including mosquitoes

anopheline specimens to determine species composition. Sixteen distinct sequence

to carry Plasmodium falciparum circumsporozoite

mosquitoes not previously described as vectors in the area and demonstrated the value of using molecular

This highlights the need for accurate characterization of mosquito species and their associated behaviours for effective malaria control. Further work continues to describe the foraging behaviour of these potentially novel vectors.

Research to identify innovative new anti-mosquito vector interventions involves



of a malaria transmission blocking vaccine (REDMAL).

LSHTM Investigators: Sophie Jones, Teun Bousema & Chris

Drakeley.

External Investigators/Collaborators: Robert Sauerwein &

Will Roeffen (Radboud University Nijmegen Medical Centre,

Netherlands); Michael Theisen (Statens Serum Institute, Denmark);

(Kilimanjaro Christian Medical Centre, Tanzania); Daniel Dodoo

Formation sur le Paludisme, Burkina Faso).

Funding:

Malaria transmission blocking vaccine targets are sexual stage antigens which are exposed to host immunity during parasite clearance from the blood.

It is therefore anticipated that individuals living in

endemic regions will already have antibodies against the vaccine candidates, which may provide boosting to the vaccine induced immunity. The aim of this work package was to explore recognition and functionality

we have demonstrated that school aged children in 3 endemic settings have antibodies against two new recombinant transmission blocking vaccine candidates, 10C (pf pfthe majority of previous research, we found evidence of an age dependant acquisition pattern, in the site of

prevalence and transmission reducing activity at the 90%

activity of serum from vaccinated rodents to block

-

Vector biology

Malaria Transmission Consortium: molecular characterisation reveals novel malaria vectors in the western Kenyan Highlands.

LSHTM Investigators: Jennifer Stevenson, Mary Cooke, Chris

Drakeley & Jon Cox.





Funding:


The success of mosquito-based malaria control is dependent upon susceptible bionomic traits in local malaria vectors. It is therefore crucial to have accurate and reliable methods to determine mosquito species composition.

Anopheles species was collected in the western Kenyan highlands, including mosquitoes

anopheline specimens to determine species composition. Sixteen distinct sequence

to carry Plasmodium falciparum circumsporozoite

mosquitoes not previously described as vectors in the area and demonstrated the value of using molecular

This highlights the need for accurate characterization of mosquito species and their associated behaviours for effective malaria control. Further work continues to describe the foraging behaviour of these potentially novel vectors.

Research to identify innovative new anti-mosquito vector interventions involves



Malaria Transmission Consortium: Estimating

highlands: integrating sleeping patterns and vector biting times.

LSHTM Investigators: Mary Cooke, Jennifer Stevenson, Chris

Drakeley & Jon Cox.





Funding:


This study was designed to estimate the protective

both malaria vector and human activity.Indoor and outdoor light trap collections were carried

out in a village in the highlands of western Kenya, to

calculate vector man biting rates per hour. Times of house-entry and exit and net usage of residents were captured using questionnaires to give individual hourly vector exposure indoors and outdoors. The reduction in exposure was calculated for net users and the true

Catches of Anopheles funestus and Anopheles arabiensis

peaks of activity were recorded as early as 19:30 outdoors and 18:30 indoors. Net use was calculated to reduce exposure from 1.3 bites per night to 0.63.

to bites occurs early and indoors in this area, additional control measures are needed to compliment the current protection provided by bednets and reduce the selection pressure for physiological or behavioural resistance to insecticides in the vector population.

MBR of vectors outdoors per hour, overlaid on human activity by age group.

Pan-African Malaria Vector Research Consortium (PAMVERC).

LSHTM Investigators: Mark Rowland, Richard Oxborough,

Kirby & Alex Wright.

External Investigators/Collaborators: Franklin Mosha,

Jovin Kitau, Johnson Matowo (Kilimanjaro Christian

Medical University College, Tanzania); William Kisinza,

Patrick Tungu, Robert Malima (National Institute for Medical

Research, Tanzania); Martin Akogbeto (Centre de recherche

entomologique de Cotonou, Benin).

Funding:

There is still a major lack of public health insecticides and in future we will continue evaluating promising new products at all stages from laboratory to community testing, as well as investigating resistance management strategies.

several major chemical manufacturers including

have focused on Phase 1 laboratory and Phase 2 experimental hut evaluation of novel products for the control of pyrethroid resistant mosquito populations.

Recent success stories have been the recommendation by of the indoor residual spraying insecticides pirimiphos-methyl CS, deltamethrin SC-PE. Results from

insecticides controlled malaria vectors for >6 months

formulations. We expect that some of the products we have evaluated will be used for widespread

years.

of new bi-treated mosquito nets in order to control pyrethroid-resistant malaria vectors.



Malaria Transmission Consortium: Estimating

highlands: integrating sleeping patterns and vector biting times.

LSHTM Investigators: Mary Cooke, Jennifer Stevenson, Chris

Drakeley & Jon Cox.





Funding:


This study was designed to estimate the protective

both malaria vector and human activity.Indoor and outdoor light trap collections were carried

out in a village in the highlands of western Kenya, to

calculate vector man biting rates per hour. Times of house-entry and exit and net usage of residents were captured using questionnaires to give individual hourly vector exposure indoors and outdoors. The reduction in exposure was calculated for net users and the true

Catches of Anopheles funestus and Anopheles arabiensis

peaks of activity were recorded as early as 19:30 outdoors and 18:30 indoors. Net use was calculated to reduce exposure from 1.3 bites per night to 0.63.

to bites occurs early and indoors in this area, additional control measures are needed to compliment the current protection provided by bednets and reduce the selection pressure for physiological or behavioural resistance to insecticides in the vector population.

MBR of vectors outdoors per hour, overlaid on human activity by age group.

Pan-African Malaria Vector Research Consortium (PAMVERC).

LSHTM Investigators: Mark Rowland, Richard Oxborough,

Kirby & Alex Wright.

External Investigators/Collaborators: Franklin Mosha,

Jovin Kitau, Johnson Matowo (Kilimanjaro Christian

Medical University College, Tanzania); William Kisinza,

Patrick Tungu, Robert Malima (National Institute for Medical

Research, Tanzania); Martin Akogbeto (Centre de recherche

entomologique de Cotonou, Benin).

Funding:

There is still a major lack of public health insecticides and in future we will continue evaluating promising new products at all stages from laboratory to community testing, as well as investigating resistance management strategies.

several major chemical manufacturers including

have focused on Phase 1 laboratory and Phase 2 experimental hut evaluation of novel products for the control of pyrethroid resistant mosquito populations.

Recent success stories have been the recommendation by of the indoor residual spraying insecticides pirimiphos-methyl CS, deltamethrin SC-PE. Results from

insecticides controlled malaria vectors for >6 months

formulations. We expect that some of the products we have evaluated will be used for widespread

years.

of new bi-treated mosquito nets in order to control pyrethroid-resistant malaria vectors.



Use of indoor attractive toxic sugar baits for control of pyrethroid resistant mosquitoes.

LSHTM Investigators

Patrick Tungu, Matt Kirby, Mark Rowland & Seth Irish.

External Investigators/Collaborators: National Institute for Medical

Research (Amani Research Centre), Tanzania; Kilimanjaro Christian

Medical University College, Tanzania.

Funding:

technology taking advantage of mosquito sugar feeding behaviour, by mixing insecticide with sugar solutions.

Many agricultural insecticides are designed to kill insects that consume them, and have not been

exposure of pyrethroid-susceptible and resistant Anopheles gambiae: implications for malaria transmission control.

LSHTM Investigators

Moore.

External Investigators/Collaborators: Achille Oumbouke, Augustin

Fongnikin & Martin Akogbeto (Centre de Recherche Entomologique

de Cotonou, Benin).

Funding:

Tackling malaria vectors indoor with insecticide treated

to behavior change of vectors and build up of residual outdoor malaria.

they would not be approved for malaria control until measurable entomological end points are established to show their potential to control malaria transmission in diverse epidemiological settings including areas with high pyrethroid resistance.

used by manwould confer against pyrethroid-susceptible and resistant Anopheles gambiae bearing the knock down resistance (kdr) gene. The ability of mosquitoes

to take a subsequentblood meal after surviving the SFT space containing vapours of the SRs was evaluated using a bioassay cage containing a shaved animal.

of both pyrethroid-susceptible and resistant Anopheles gambiae

>40% protection at 65m compared to only 10% with

With either product, repellence rates of pyrethroid-susceptible Anopheles gambiae were similar to that of the resistant strain and the trends at all distance range were notdistinguishable. Pyrethroid-resistant individuals recovered from SR exposure and bloodfed sooner than their susceptible counterpart. Forty hours after exposure, between 40-60% of susceptible Anopheles gambiae were unable to bloodfeed compared to nearly 100% feeding success with resistant Anopheles gambiae.

killing no greater than 25% of both pyrethroid susceptible and resistant Anopheles gambiae at all range.

control and suggest that they would do so by creating a vector-free space, even in areas with pyrethroid

was faster in Anopheles gambiae carrying the kdr mechanism suggests possible association/interaction between the target site of pyrethroids (the sodium

antennae where SRs bind to trigger repellence.

available for mosquito to use these insecticides against pyrethroid-resistant mosquitoes. Laboratory tests showed three insecticides

effective in killing mosquitoes. These insecticidal baits were then placed in experimental huts to see if wild, pyrethroid-resistant Anopheles arabiensis and Culex quinquefasciatus

mortality was found in mosquitoes entering experimental

optimize stations in a way that might be scalable, but the

similar control to long-lasting insecticidal nets in this area.

and assessment of putative semiochemicals and blends associated with the oviposition of Anopheles gambiae sensu stricto and Anopheles arabiensis.

LSHTM Investigators: Ulrike Fillinger, Mike Okal, Manuela Herrera-

External Investigators/Collaborators: Jenny Lindh, (KTH Royal

Institute of Technology, Sweden); Steve Torr (Liverpool School of

Tropical Medicine, UK); Baldwyn Torto (International Centre of Insect

Physiology and Ecology, Kenya).

Funding: National Institute of Health.

We study the oviposition behaviour of Anopheles gambiae and Anopheles arabiensis with the aims to

for controlling and monitoring Anopheles gambiae populations.

Whilst considerable research effort continues to

its host, almost nothing is known about how gravid females locate a breeding site. We investigate oviposition behaviour in Anopheles gambiae so that

we can ‘attract and kill’ or ‘push and pull’ egg-laying vectors and their offspring.

This approach is underpinned by multi-disciplinary research to identify the visual and olfactory stimuli that cause female Anopheles gambiae to oviposit at certain sites. Such knowledge will not only allow us to identify important breeding sites and selectively treat preferred sites with novel, long-lasting and environmentally friendly larvicides but also provide a rational basis for developing oviposition traps to monitor and kill adult mosquitoes. The aim is to optimise standard methods for preparing test insects from caged colonies in order to have a large production of gravid mosquitoes for mass screening of semiochemicals. Moreover, the aim is to develop new tools and methods for implementing and analyzing oviposition bioassays designed to show substrate preferences of gravid Anopheles gambiae. and characterise putative compounds as volatile attractants and repellents or non-volatile stimulants

using electroantennogram detections coupled with gas-chromatography and putative semiochemicals tested in the developed tool box.



Use of indoor attractive toxic sugar baits for control of pyrethroid resistant mosquitoes.

LSHTM Investigators

Patrick Tungu, Matt Kirby, Mark Rowland & Seth Irish.

External Investigators/Collaborators: National Institute for Medical

Research (Amani Research Centre), Tanzania; Kilimanjaro Christian

Medical University College, Tanzania.

Funding:

technology taking advantage of mosquito sugar feeding behaviour, by mixing insecticide with sugar solutions.

Many agricultural insecticides are designed to kill insects that consume them, and have not been

exposure of pyrethroid-susceptible and resistant Anopheles gambiae: implications for malaria transmission control.

LSHTM Investigators

Moore.

External Investigators/Collaborators: Achille Oumbouke, Augustin

Fongnikin & Martin Akogbeto (Centre de Recherche Entomologique

de Cotonou, Benin).

Funding:

Tackling malaria vectors indoor with insecticide treated

to behavior change of vectors and build up of residual outdoor malaria.

they would not be approved for malaria control until measurable entomological end points are established to show their potential to control malaria transmission in diverse epidemiological settings including areas with high pyrethroid resistance.

used by manwould confer against pyrethroid-susceptible and resistant Anopheles gambiae bearing the knock down resistance (kdr) gene. The ability of mosquitoes

to take a subsequentblood meal after surviving the SFT space containing vapours of the SRs was evaluated using a bioassay cage containing a shaved animal.

of both pyrethroid-susceptible and resistant Anopheles gambiae

>40% protection at 65m compared to only 10% with

With either product, repellence rates of pyrethroid-susceptible Anopheles gambiae were similar to that of the resistant strain and the trends at all distance range were notdistinguishable. Pyrethroid-resistant individuals recovered from SR exposure and bloodfed sooner than their susceptible counterpart. Forty hours after exposure, between 40-60% of susceptible Anopheles gambiae were unable to bloodfeed compared to nearly 100% feeding success with resistant Anopheles gambiae.

killing no greater than 25% of both pyrethroid susceptible and resistant Anopheles gambiae at all range.

control and suggest that they would do so by creating a vector-free space, even in areas with pyrethroid

was faster in Anopheles gambiae carrying the kdr mechanism suggests possible association/interaction between the target site of pyrethroids (the sodium

antennae where SRs bind to trigger repellence.

available for mosquito to use these insecticides against pyrethroid-resistant mosquitoes. Laboratory tests showed three insecticides

effective in killing mosquitoes. These insecticidal baits were then placed in experimental huts to see if wild, pyrethroid-resistant Anopheles arabiensis and Culex quinquefasciatus

mortality was found in mosquitoes entering experimental

optimize stations in a way that might be scalable, but the

similar control to long-lasting insecticidal nets in this area.

and assessment of putative semiochemicals and blends associated with the oviposition of Anopheles gambiae sensu stricto and Anopheles arabiensis.

LSHTM Investigators: Ulrike Fillinger, Mike Okal, Manuela Herrera-

External Investigators/Collaborators: Jenny Lindh, (KTH Royal

Institute of Technology, Sweden); Steve Torr (Liverpool School of

Tropical Medicine, UK); Baldwyn Torto (International Centre of Insect

Physiology and Ecology, Kenya).

Funding: National Institute of Health.

We study the oviposition behaviour of Anopheles gambiae and Anopheles arabiensis with the aims to

for controlling and monitoring Anopheles gambiae populations.

Whilst considerable research effort continues to

its host, almost nothing is known about how gravid females locate a breeding site. We investigate oviposition behaviour in Anopheles gambiae so that

we can ‘attract and kill’ or ‘push and pull’ egg-laying vectors and their offspring.

This approach is underpinned by multi-disciplinary research to identify the visual and olfactory stimuli that cause female Anopheles gambiae to oviposit at certain sites. Such knowledge will not only allow us to identify important breeding sites and selectively treat preferred sites with novel, long-lasting and environmentally friendly larvicides but also provide a rational basis for developing oviposition traps to monitor and kill adult mosquitoes. The aim is to optimise standard methods for preparing test insects from caged colonies in order to have a large production of gravid mosquitoes for mass screening of semiochemicals. Moreover, the aim is to develop new tools and methods for implementing and analyzing oviposition bioassays designed to show substrate preferences of gravid Anopheles gambiae. and characterise putative compounds as volatile attractants and repellents or non-volatile stimulants

using electroantennogram detections coupled with gas-chromatography and putative semiochemicals tested in the developed tool box.



Estimating the annual entomological inoculation rate for Plasmodium falciparum transmitted by Anopheles gambiae using three sampling methods in three sites in Uganda.

LSHTM Investigators: Robert Hutchinson, Sarah

Staedke & Chris Drakeley.

External Investigators/Collaborators: Maxwell

Surveillance Project, Uganda); David Smith (Johns

Hopkins University, USA); Moses Kamya (Makerere

University,Uganda); Martin Donnelly (Liverpool School

California, USA) & Steve Lindsay (Durham University,

UK).

The Plasmodium falciparum entomological

exposure to infectious mosquitoes. It is usually interpreted as the number of Plasmodium falciparum infective bites received by an individual during a season or annually (aPfaccuracy, precision, and seasonal distribution

PfEIR in three sites in Uganda with differing levels of transmission. We compared aPfEIR estimates derived from human landing catches – the classic method for estimating biting rates – with data from CDC light traps, and with the combined catches of knock down and exit traps.

Entomological surveillance was carried out over 1 year in 2011/12 in three settings: Nagongera, Tororo District, a rural area with exceptionally high malaria transmission; Kanungu, a rural area with moderate transmission; and Jinja, a peri-urban area with low transmission. Three sampling approaches were used from randomly selected houses in each setting with monthly collections: human-landing collections, CDC light traps and paired knock down and exit traps each

with Plasmodium falciparumThe estimated aPf

PfEIR values showed strong

between sites. Estimated HBRs using human landing catches were strongly correlated with those made using CDC

patterns in the SR were discernible because either the number of sporozoite positive mosquitoes or the total number of mosquitoes caught was too low.

We found that in these settings light traps provide an alternative method for sampling indoor-resting mosquitoes to human landing catches and have the advantage that they protect individuals from being bitten during collection, are easy to use, and are not subject to collector bias.

Olfactory mechanisms underlying behavioural manipulation of mosquitoes by malaria parasites.

LSHTM Investigators

External Investigators/Collaborators: Willem Takken & Renate

Smallegange (Wageningen Uninversity, Netherlands).


Council.

This project aims to determine if there are differences in the behaviour and olfactory responses of Anopheles gambiae Plasmodium falciparum malaria.

If mosquitoes with the transmissible stage of malaria are more likely to seek out a host, this would affect transmission dynamics, and also possibly involve a mechanism that we could take advantage of in vector control.

Infected and uninfected mosquitoe responses to human odour will be compared in behavioural choice tests, and compared using gas-chromatogram linked

compounds which the mosquitoes respond differentially to will be investigated as possible attractants/repellents.

vectors has been accomplished, and experiments with infected mosquitoes are currently ongoing.

Oocyst infection of Anopheles gambiae with Plasmodium faliparum malaria.

-vals (solid and dashed lines respectively).



Estimating the annual entomological inoculation rate for Plasmodium falciparum transmitted by Anopheles gambiae using three sampling methods in three sites in Uganda.

LSHTM Investigators: Robert Hutchinson, Sarah

Staedke & Chris Drakeley.

External Investigators/Collaborators: Maxwell

Surveillance Project, Uganda); David Smith (Johns

Hopkins University, USA); Moses Kamya (Makerere

University,Uganda); Martin Donnelly (Liverpool School

California, USA) & Steve Lindsay (Durham University,

UK).

The Plasmodium falciparum entomological

exposure to infectious mosquitoes. It is usually interpreted as the number of Plasmodium falciparum infective bites received by an individual during a season or annually (aPfaccuracy, precision, and seasonal distribution

PfEIR in three sites in Uganda with differing levels of transmission. We compared aPfEIR estimates derived from human landing catches – the classic method for estimating biting rates – with data from CDC light traps, and with the combined catches of knock down and exit traps.

Entomological surveillance was carried out over 1 year in 2011/12 in three settings: Nagongera, Tororo District, a rural area with exceptionally high malaria transmission; Kanungu, a rural area with moderate transmission; and Jinja, a peri-urban area with low transmission. Three sampling approaches were used from randomly selected houses in each setting with monthly collections: human-landing collections, CDC light traps and paired knock down and exit traps each

with Plasmodium falciparumThe estimated aPf

PfEIR values showed strong

between sites. Estimated HBRs using human landing catches were strongly correlated with those made using CDC

patterns in the SR were discernible because either the number of sporozoite positive mosquitoes or the total number of mosquitoes caught was too low.

We found that in these settings light traps provide an alternative method for sampling indoor-resting mosquitoes to human landing catches and have the advantage that they protect individuals from being bitten during collection, are easy to use, and are not subject to collector bias.

Olfactory mechanisms underlying behavioural manipulation of mosquitoes by malaria parasites.

LSHTM Investigators

External Investigators/Collaborators: Willem Takken & Renate

Smallegange (Wageningen Uninversity, Netherlands).


Council.

This project aims to determine if there are differences in the behaviour and olfactory responses of Anopheles gambiae Plasmodium falciparum malaria.

If mosquitoes with the transmissible stage of malaria are more likely to seek out a host, this would affect transmission dynamics, and also possibly involve a mechanism that we could take advantage of in vector control.

Infected and uninfected mosquitoe responses to human odour will be compared in behavioural choice tests, and compared using gas-chromatogram linked

compounds which the mosquitoes respond differentially to will be investigated as possible attractants/repellents.

vectors has been accomplished, and experiments with infected mosquitoes are currently ongoing.

Oocyst infection of Anopheles gambiae with Plasmodium faliparum malaria.

-vals (solid and dashed lines respectively).

38 Malaria prevention Malaria prevention 39


Summary

Malaria prevention is attainable

by protecting against the mosquito through vector control, by protect-ing against the parasite through chemoprevention, and by vaccina-tion. Malaria Centre members are active in each of these areas.

In our research on vector control, evaluation

of the impact of full versus partial intervention

coverage has been a recurrent theme. The last

few years has seen unprecedented intervention

coverage of long-lasting insecticidal-treated nets

national governments, and this is without question

the most widely accessed current form of malaria

prevention. We are involved in identifying the

cost as well as developing guidelines for deter-

mining and evaluating LLIN durability and insecti-

cide content over time by biological and chemical

tackling the vector by combined use of LLINs and

-

munity randomised trial, we have demonstrated

-

is now switching to long-lasting indoor residual

spraying formulation, pirimiphos methyl CS. We

have been determining the effectiveness of this

strategy in Tanzania, Burkina Faso and Ivory

Coast. Insecticide treated durable wall lining is

the latest in a trend to improve the residual life

of insecticide treatments on walls of houses, and

showed great potential in a multi-country trial.

-

dence to justify scaling up include larval source

-

lents. Studies on these important areas are also

presented here. For example, fundamental re-

search has emphasised the importance of maxi-

helping to settle the long-term debate over wheth-

er DDT and volatile pyrethroids work by toxicity,

repellency or a combination of actions.

The one-time spectre on the horizon, insec-

ticide resistance, is now a real presence. While

the evidence for a negative impact on malaria

control is yet to be demonstrated unequivocally,

various studies reported by our researchers are

all pointing in that direction. While LLIN remain

the primary preventive intervention it is impossible

to reverse the selection of pyrethroid resistance.

insecticide delivery a part of everyday life. The

best way to ensure this is to maintain the pipeline

of effective insecticides for nets - products we are

working in partnership with researchers and in-

dustry to develop.

In the area of chemoprevention, a number

of strategies of are being developed for different

-

ment to clear malaria parasites in school children

in Mali demonstrated success while a Kenyan

trial of school-based Intermittent Screening and

to be an ineffective intervention in low-moderate

transmission settings. In countries of seasonal

transmission such as the Sahel, seasonal malaria

SP-amodiaquine has been successfully taken to

scale in Senegal by community health workers.

comparing whether a strategy of IST in pregnancy

is non-inferior to a strategy which involves the use

IST as a potential alternative where falciparum is

highly resistant to SP. To improve the quality of

strategies for controlling malaria in pregnancy, en-

hanced district and health facility data collection

and monitoring tools are being developed and

integrated into current systems and will contribute

to a toolkit for assessing intervention coverage

and decision making in different contexts. Imple-

mentation research on the barriers to effective ac-

cess, delivery and use of interventions have high-

lighted blockages to delivery and to weaknesses

and problems in current survey techniques for

assessing coverage.

In terms of vaccines, many of our staff have

participated in the design, execution and evalua-

tion of the trials of the RTS,S candidate vaccine in

candidate vaccine (eg the prime boost vaccine



Summary

Malaria prevention is attainable

by protecting against the mosquito through vector control, by protect-ing against the parasite through chemoprevention, and by vaccina-tion. Malaria Centre members are active in each of these areas.

In our research on vector control, evaluation

of the impact of full versus partial intervention

coverage has been a recurrent theme. The last

few years has seen unprecedented intervention

coverage of long-lasting insecticidal-treated nets

national governments, and this is without question

the most widely accessed current form of malaria

prevention. We are involved in identifying the

cost as well as developing guidelines for deter-

mining and evaluating LLIN durability and insecti-

cide content over time by biological and chemical

tackling the vector by combined use of LLINs and

-

munity randomised trial, we have demonstrated

-

is now switching to long-lasting indoor residual

spraying formulation, pirimiphos methyl CS. We

have been determining the effectiveness of this

strategy in Tanzania, Burkina Faso and Ivory

Coast. Insecticide treated durable wall lining is

the latest in a trend to improve the residual life

of insecticide treatments on walls of houses, and

showed great potential in a multi-country trial.

-

dence to justify scaling up include larval source

-

lents. Studies on these important areas are also

presented here. For example, fundamental re-

search has emphasised the importance of maxi-

helping to settle the long-term debate over wheth-

er DDT and volatile pyrethroids work by toxicity,

repellency or a combination of actions.

The one-time spectre on the horizon, insec-

ticide resistance, is now a real presence. While

the evidence for a negative impact on malaria

control is yet to be demonstrated unequivocally,

various studies reported by our researchers are

all pointing in that direction. While LLIN remain

the primary preventive intervention it is impossible

to reverse the selection of pyrethroid resistance.

insecticide delivery a part of everyday life. The

best way to ensure this is to maintain the pipeline

of effective insecticides for nets - products we are

working in partnership with researchers and in-

dustry to develop.

In the area of chemoprevention, a number

of strategies of are being developed for different

-

ment to clear malaria parasites in school children

in Mali demonstrated success while a Kenyan

trial of school-based Intermittent Screening and

to be an ineffective intervention in low-moderate

transmission settings. In countries of seasonal

transmission such as the Sahel, seasonal malaria

SP-amodiaquine has been successfully taken to

scale in Senegal by community health workers.

comparing whether a strategy of IST in pregnancy

is non-inferior to a strategy which involves the use

IST as a potential alternative where falciparum is

highly resistant to SP. To improve the quality of

strategies for controlling malaria in pregnancy, en-

hanced district and health facility data collection

and monitoring tools are being developed and

integrated into current systems and will contribute

to a toolkit for assessing intervention coverage

and decision making in different contexts. Imple-

mentation research on the barriers to effective ac-

cess, delivery and use of interventions have high-

lighted blockages to delivery and to weaknesses

and problems in current survey techniques for

assessing coverage.

In terms of vaccines, many of our staff have

participated in the design, execution and evalua-

tion of the trials of the RTS,S candidate vaccine in

candidate vaccine (eg the prime boost vaccine



Vector control

long-lasting insecticidal nets.

LSHTM Investigators: Mark Rowland.


Health Organisation, Switzerland); K Raghavendra & R Bhatt (World

Health Organisation, India).

Funding: World Health Organisation.

in 2005. Considerable experience in testing LNs has since been gained, and on monitoring the durability of LNs under operational conditions.

pyrethroid-treated LNs, LNs containing new insecticides and/or synergists are

become available for use in the near future. The revised

procedures and guidelines for testing LNs for personal protection and malaria vector control. It is intended to harmonise testing procedures in order to generate data for registration and labelling of such products by national authorities and provide a framework for industry in developing novel LN products. Currently, an LN would be expected to retain its biological activity for at least 20 standard washes under laboratory conditions and 3 years

The document describes laboratory and small- and

Evaluation of the coverage and effective use rate of long-lasting insecticidal nets after nation-wide scale up of their distribution in Benin.

LSHTM Investigators


Control Programme, Benin).

Funding:

Agency for International Development through the President’s

In Benin, about four million long-lasting insecticide-

to prevent malaria in 2011. In contrast to a previous campaign that targeted only children under 5 years and pregnant women, this distribution campaign was conducted in order to achieve universal coverage.

This study presents the results of LLIN coverage and utilisation after the distribution campaign.

The study was a cross-sectional household survey

design. The strata represented the twelve districts covered by the national distribution campaign in 2011 and included a total of 4,800 households randomly selected

Malaria Indicator Survey Household Questionnaire was used. Data were entered using QPS software and analyzed with R 2.14.1.

Strategies for delivering insecticide-treated nets at scale for malaria control in endemic countries: a systematic review.

LSHTM Investigators: Joanna Schellenberg, Barbara Willey,

Lindsay Mangham-Jeffries & Lucy Paintain.

External Investigators/Collaborators: Josip Car (Imperial College

London, UK) .

Funding:

sectors and retail outlets, antenatal care clinics and

campaigns. Strategies that delivered insecticide-treated nets free through campaigns achieved highest usage.

Costs were comparable across strategies, with the nets being the main cost. Cost-effectiveness estimates were most sensitive to the assumed net lifespan and leakage. Common barriers to delivery included cost, stockouts of nets at distribution points, and poor logistics. Common facilitators were staff training and supervision, cooperation across departments or ministries and stakeholder involvement.

households that met the ratio one net for two persons was 77%.The proportions of individuals sleeping under LLINs

was 10% lower than in effective users from rural areas

The universal distribution campaign conducted in Benin has increased LLIN ownership and use in the community. But additional efforts are needed to improve and maintain LLIN coverage.

Malaria Centre members are conducting vector control research mainly in East and West Africa. We are working with multilateral agencies to evaluate the reach and usage of long-lasting insecticidal treated nets (LLINs) in universal coverage campaigns, the potential impact of combining indoor residual spraying campaigns with LLINs, and the potential of and constraints to less established form of vector control such as insecticide treated durable wall lining, larval source management, and topical and spatial repellent.



Vector control

long-lasting insecticidal nets.

LSHTM Investigators: Mark Rowland.


Health Organisation, Switzerland); K Raghavendra & R Bhatt (World

Health Organisation, India).

Funding: World Health Organisation.

in 2005. Considerable experience in testing LNs has since been gained, and on monitoring the durability of LNs under operational conditions.

pyrethroid-treated LNs, LNs containing new insecticides and/or synergists are

become available for use in the near future. The revised

procedures and guidelines for testing LNs for personal protection and malaria vector control. It is intended to harmonise testing procedures in order to generate data for registration and labelling of such products by national authorities and provide a framework for industry in developing novel LN products. Currently, an LN would be expected to retain its biological activity for at least 20 standard washes under laboratory conditions and 3 years

The document describes laboratory and small- and

Evaluation of the coverage and effective use rate of long-lasting insecticidal nets after nation-wide scale up of their distribution in Benin.

LSHTM Investigators


Control Programme, Benin).

Funding:

Agency for International Development through the President’s

In Benin, about four million long-lasting insecticide-

to prevent malaria in 2011. In contrast to a previous campaign that targeted only children under 5 years and pregnant women, this distribution campaign was conducted in order to achieve universal coverage.

This study presents the results of LLIN coverage and utilisation after the distribution campaign.

The study was a cross-sectional household survey

design. The strata represented the twelve districts covered by the national distribution campaign in 2011 and included a total of 4,800 households randomly selected

Malaria Indicator Survey Household Questionnaire was used. Data were entered using QPS software and analyzed with R 2.14.1.

Strategies for delivering insecticide-treated nets at scale for malaria control in endemic countries: a systematic review.

LSHTM Investigators: Joanna Schellenberg, Barbara Willey,



London, UK) .

Funding:

sectors and retail outlets, antenatal care clinics and

campaigns. Strategies that delivered insecticide-treated nets free through campaigns achieved highest usage.

Costs were comparable across strategies, with the nets being the main cost. Cost-effectiveness estimates were most sensitive to the assumed net lifespan and leakage. Common barriers to delivery included cost, stockouts of nets at distribution points, and poor logistics. Common facilitators were staff training and supervision, cooperation across departments or ministries and stakeholder involvement.

households that met the ratio one net for two persons was 77%.The proportions of individuals sleeping under LLINs

was 10% lower than in effective users from rural areas

The universal distribution campaign conducted in Benin has increased LLIN ownership and use in the community. But additional efforts are needed to improve and maintain LLIN coverage.

Malaria Centre members are conducting vector control research mainly in East and West Africa. We are working with multilateral agencies to evaluate the reach and usage of long-lasting insecticidal treated nets (LLINs) in universal coverage campaigns, the potential impact of combining indoor residual spraying campaigns with LLINs, and the potential of and constraints to less established form of vector control such as insecticide treated durable wall lining, larval source management, and topical and spatial repellent.



The useful life of bednets for malaria control in Tanzania:

Durability and insecticide resistance (ABCDR).

LSHTM Investigators: Lena Lorenz, Jason Moore

& John Bradley.

External Investigators/Collaborators: Hans

Overgaard (Norwegian University of Life Sciences,

Norway); Sarah Moore (Ifakara Health Institute,

Tanzania & Swiss Tropical and Public Health

Institute, Switzerland); William Kisinza (National

Institute for Medical Research, Tanzania).

Funding: The Research Council of Norway –

Long-lasting insecticide-treated nets

in malaria vector control in sub-Saharan

universal coverage campaigns with free or subsidised nets. However, there is only limited knowledge from a few countries of the effective life of LLINs under user conditions, an essential parameter for determining the operational and cost-effectiveness of this strategy.

Durability and insecticide resistance

prospective design to investigate LLIN durability by measuring attrition,

degradation in Tanzania following World

methodologies. LLINs from national net campaigns between 2009 and 2011 were evaluated retrospectively and data on net use, net loss and net disposal is being analysed and shared with the national malaria control programme.

approved LLIN products and are being followed up after 12, 24, 30 and 36 months to compare the performance of the LLIN brands in vivo.

We are also developing a GIS-based network to understand potential spatial reasons for net loss and deterioration and to monitor insecticide resistance.

The data collected will be of importance to policy makers and vector control specialists both in Tanzania and the

malaria control.

Walking or waiting? Topologies of the breeding ground in malaria control.LSHTM Investigators: Ann Kelly.

External Investigators/Collaborators: Javier Lezaun

(University of Oxford, UK).

accumulation of stagnant water where disease-carrying insects lay their eggs. Since the turn of the

transmission, these aquatic habitats have been a key object of epidemiological research and public health intervention against the disease. Yet the breeding ground can be incorporated into a number of different topologies, each implying a different spatialization of malaria and a distinct imagination of what kind of

of malaria control in Dar es Salaam, Tanzania, illuminates an essential tension between what we characterise as territorial and bionomic approaches to the breeding ground—that is, between control strategies premised on treating all mosquito habitats within a given region, and those that prioritise certain sites on the basis of their position within ecological networks. Each topology localises the breeding ground by reference to a distinct set of relations, and thus advances an idiosyncratic understanding of what sort of research is worthwhile conducting and what kinds of intervention are sustainable. The multiple ways in which the breeding ground can become an

topology as an infra-logic of public health, and makes explicit the politics implicit in efforts to bring different orders of the local to scale.



The useful life of bednets for malaria control in Tanzania:

Durability and insecticide resistance (ABCDR).

LSHTM Investigators: Lena Lorenz, Jason Moore

& John Bradley.

External Investigators/Collaborators: Hans

Overgaard (Norwegian University of Life Sciences,

Norway); Sarah Moore (Ifakara Health Institute,

Tanzania & Swiss Tropical and Public Health

Institute, Switzerland); William Kisinza (National

Institute for Medical Research, Tanzania).

Funding: The Research Council of Norway –

Long-lasting insecticide-treated nets

in malaria vector control in sub-Saharan

universal coverage campaigns with free or subsidised nets. However, there is only limited knowledge from a few countries of the effective life of LLINs under user conditions, an essential parameter for determining the operational and cost-effectiveness of this strategy.

Durability and insecticide resistance

prospective design to investigate LLIN durability by measuring attrition,

degradation in Tanzania following World

methodologies. LLINs from national net campaigns between 2009 and 2011 were evaluated retrospectively and data on net use, net loss and net disposal is being analysed and shared with the national malaria control programme.

approved LLIN products and are being followed up after 12, 24, 30 and 36 months to compare the performance of the LLIN brands in vivo.

We are also developing a GIS-based network to understand potential spatial reasons for net loss and deterioration and to monitor insecticide resistance.

The data collected will be of importance to policy makers and vector control specialists both in Tanzania and the

malaria control.

Walking or waiting? Topologies of the breeding ground in malaria control.LSHTM Investigators: Ann Kelly.

External Investigators/Collaborators: Javier Lezaun

(University of Oxford, UK).

accumulation of stagnant water where disease-carrying insects lay their eggs. Since the turn of the

transmission, these aquatic habitats have been a key object of epidemiological research and public health intervention against the disease. Yet the breeding ground can be incorporated into a number of different topologies, each implying a different spatialization of malaria and a distinct imagination of what kind of

of malaria control in Dar es Salaam, Tanzania, illuminates an essential tension between what we characterise as territorial and bionomic approaches to the breeding ground—that is, between control strategies premised on treating all mosquito habitats within a given region, and those that prioritise certain sites on the basis of their position within ecological networks. Each topology localises the breeding ground by reference to a distinct set of relations, and thus advances an idiosyncratic understanding of what sort of research is worthwhile conducting and what kinds of intervention are sustainable. The multiple ways in which the breeding ground can become an

topology as an infra-logic of public health, and makes explicit the politics implicit in efforts to bring different orders of the local to scale.



A simple colorimetric test for the rapid detection of type 2-pyrethroids on bed nets.

LSHTM Investigators: Harparkash Kaur.

External Investigators/Collaborators: Tunis Eggelte (University of

Amsterdam, Amsterdam, Netherlands).

Funding: The London School of Hygiene & Tropical Medicine

Insecticide treated nets are major modes of intervention,

amount of insecticide deposit on bed nets is essential for quality control.

Currently such information can only be provided by laboratory based high tech methods such as gas chromatography and high performance liquid

bioassays where insecticide susceptible strains of mosquitoes are exposed to the bed nets. They are technically demanding to perform and require skilled staff with access to laboratory and insectary facilities.

test part of the net is placed over the tube and the cap is pushed tightly to seal the net. The test tube is turned upside down so that the solution is in contact with the net for 10 minutes. Solution D is then added to stop the reaction and the pink/red colour formed estimates the amount of deltamethrin. The test is performed in situ and does not damage the net. Field evaluations of the prototype are underway in Bioko – Equatorial Guinea.

Indoor residual spraying in combination with insecticide treated nets compared to insecticide treated nets alone for protection against malaria: a cluster randomised trial in Tanzania.

LSHTM Investigators: Philippa West, Natacha Protopopoff

Alexandra Wright, Mark Rowland & Immo Kleinschmidt.

External Investigators/Collaborators: Franklin Mosha (Kilimanjaro

Christian Medical College, Moshi, Tanzania); William Kisinza &

Tanzania); Robinson Tigererwa (Department of Health, Tanzania).

Funding: United States Agency for International Development.

This cluster randomised trial showed that deploying

compared to using ITNs alone. The size of the added protection may depend on ITN use and on local vector ecology.

Fifty clusters were randomly allocated to ITNs only or ITNs and IRS. Dwellings in the ITN+IRS arm were sprayed with two rounds of bendiocarb in 2012. Plasmodium falciparum infection prevalence (Pf

Combined use of indoor residual spraying and long-lasting insecticidal nets for malaria reduction in endemic rural Tanzania.

LSHTM Investigators: Natacha Protopopoff, Philippa West,

Alexandra Wright, Immo Kleinschmidt & Mark Rowland.

External Investigators/Collaborators: Frank Mosha & Reginald

Kavishe (Kilimanjaro Christian Medical Colleges, Tanzania); Robert

Malima & William Kisinza (National Institute for Medical Research,

Tanzania).

Funding: President’s Malaria Initiative.

Numerous studies have shown that llong-lasting

is less certain is the added value of combining both or whether LLIN can substitute for IRS.

This study aims to evaluate the impact of combining IRS and LLINs compared to LLINs alone on malaria prevalence through a two-arm cluster randomised trial. The study is being carried out in Muleba district to the

in children 0.5-14, determined in three cross-sectional household surveys, and Entomological inoculation rate were compared between study arms.

IRS coverage was approximately 90%. ITN use ranged from 36-50%. Mean PfPR was 13% in the ITN+IRS arm and 26% in the ITN only arm, odds

effect was observed in the peak transmission season, six

ITN users were additionally protected if their houses were sprayed. Mean monthly entomological inoculation rate

added protection from combining IRS and ITNs compared to ITNs alone. The effect is likely to be attributable to IRS providing added protection to ITN users as well as compensating for inadequate ITN use. Policy makers should consider deploying IRS in combination with ITNs to control transmission if local ITN strategies on their own

for malaria control programmes to evaluate the cost effectiveness of deploying the combination.

west of Lake Victoria in Tanzania. The control villages

and the intervention villages LLIN and indoor residual spraying. Three household and prevalence cross-sectional surveys have been undertaken in children aged 6 months to 14 years and monthly entomology collection completed. IRS coverage in the intervention arm was 90%. 85% of households owned at least one insecticide

from 36 to 50%. Malaria prevalence was 13% in the

Anopheles gambiae

randomised trial that provides evidence that IRS, when

protection against malarial infection compared to ITN use alone.



A simple colorimetric test for the rapid detection of type 2-pyrethroids on bed nets.


External Investigators/Collaborators: Tunis Eggelte (University of

Amsterdam, Amsterdam, Netherlands).

Funding: The London School of Hygiene & Tropical Medicine

Insecticide treated nets are major modes of intervention,

amount of insecticide deposit on bed nets is essential for quality control.

Currently such information can only be provided by laboratory based high tech methods such as gas chromatography and high performance liquid

bioassays where insecticide susceptible strains of mosquitoes are exposed to the bed nets. They are technically demanding to perform and require skilled staff with access to laboratory and insectary facilities.

test part of the net is placed over the tube and the cap is pushed tightly to seal the net. The test tube is turned upside down so that the solution is in contact with the net for 10 minutes. Solution D is then added to stop the reaction and the pink/red colour formed estimates the amount of deltamethrin. The test is performed in situ and does not damage the net. Field evaluations of the prototype are underway in Bioko – Equatorial Guinea.

Indoor residual spraying in combination with insecticide treated nets compared to insecticide treated nets alone for protection against malaria: a cluster randomised trial in Tanzania.

LSHTM Investigators: Philippa West, Natacha Protopopoff

Alexandra Wright, Mark Rowland & Immo Kleinschmidt.

External Investigators/Collaborators: Franklin Mosha (Kilimanjaro

Christian Medical College, Moshi, Tanzania); William Kisinza &

Tanzania); Robinson Tigererwa (Department of Health, Tanzania).

Funding: United States Agency for International Development.

This cluster randomised trial showed that deploying

compared to using ITNs alone. The size of the added protection may depend on ITN use and on local vector ecology.

Fifty clusters were randomly allocated to ITNs only or ITNs and IRS. Dwellings in the ITN+IRS arm were sprayed with two rounds of bendiocarb in 2012. Plasmodium falciparum infection prevalence (Pf

Combined use of indoor residual spraying and long-lasting insecticidal nets for malaria reduction in endemic rural Tanzania.

LSHTM Investigators: Natacha Protopopoff, Philippa West,

Alexandra Wright, Immo Kleinschmidt & Mark Rowland.




Tanzania).

Funding: President’s Malaria Initiative.

Numerous studies have shown that llong-lasting

is less certain is the added value of combining both or whether LLIN can substitute for IRS.

This study aims to evaluate the impact of combining IRS and LLINs compared to LLINs alone on malaria prevalence through a two-arm cluster randomised trial. The study is being carried out in Muleba district to the

in children 0.5-14, determined in three cross-sectional household surveys, and Entomological inoculation rate were compared between study arms.

IRS coverage was approximately 90%. ITN use ranged from 36-50%. Mean PfPR was 13% in the ITN+IRS arm and 26% in the ITN only arm, odds

effect was observed in the peak transmission season, six

ITN users were additionally protected if their houses were sprayed. Mean monthly entomological inoculation rate

added protection from combining IRS and ITNs compared to ITNs alone. The effect is likely to be attributable to IRS providing added protection to ITN users as well as compensating for inadequate ITN use. Policy makers should consider deploying IRS in combination with ITNs to control transmission if local ITN strategies on their own

for malaria control programmes to evaluate the cost effectiveness of deploying the combination.

west of Lake Victoria in Tanzania. The control villages

and the intervention villages LLIN and indoor residual spraying. Three household and prevalence cross-sectional surveys have been undertaken in children aged 6 months to 14 years and monthly entomology collection completed. IRS coverage in the intervention arm was 90%. 85% of households owned at least one insecticide

from 36 to 50%. Malaria prevalence was 13% in the

Anopheles gambiae

randomised trial that provides evidence that IRS, when

protection against malarial infection compared to ITN use alone.



Combining organophosphate treated wall linings and long-lasting insecticidal nets for improved control of pyrethroid resistant Anopheles gambiae.

LSHTM Investigators: Corine Ngufor & Mark Rowland.

External Investigators/Collaborators: Emile Tchicaya & Benjamin

Sagnon N’Fale (Centre National de Recherche et de Formation sur

le Paludisme, Burkina Faso); Roch Dabire (Centre Muraz, Burkina

(Liverpool School of Tropical Medicine, UK).

Funding: European Union through the AvecNet project.

which can be produced in a long-lasting format. Non-pyrethroid versions could be used in combination with long-lasting insecticidal nets for improved control and management of insecticide resistant vector populations.

Experimental hut trials were carried out in Valley

pirimiphos methyl treated DL and NWH either alone or in combination with long-lasting insecticide-treated nets

Anopheles gambiae. Comparison was made with pyrethroid DL. Mosquitoes were genotyped for kdr and ace-1R resistant genes

to investigate the insecticide resistance management potential of the combination.

The overall kdr and ace-1R allele frequencies were 0.95 and 0.01 respectively. Mortality with p-methyl DL and NWH alone was higher than with pyrethroid DL alone

p-methyl DL or NWH with LLINs reduced biting rates

huts. Mosquitoes bearing the ace-1R gene were more

whereas all resistant and susceptible genotypes were killed by the combination.

P-methyl DL and NWH outperformed pyrethroid DL. Combining p-methyl DL and NWH with LLINs could

a vector population which is resistant to pyrethroids but susceptible to organophosphates. There was evidence that the single intervention would select kdr and ace-1R resistance genes and the combination intervention might select less strongly. Technology to bind organophosphates to plastic wall lining would be worth developing.

Multicentre studies of insecticide-treated durable wall lining in Africa and Southeast

LSHTM Investigators: Louisa Messenger, Mark Rowland & Immo

Kleinschmidt.

External Investigators/Collaborators: Abrahan Arnez (Medical

Louise Larsen (Technical Institute of Denmark, Denmark); Nathan P

Miller, The MENTOR Initiative, Angola); Adedapo Adeogun (Nigerian

Institute of Medical Research, Nigeria).

Funding:

insecticide is gradually released from an aesthetically attractive wall lining material to provide vector control for several years.

and household acceptability of DL, compared to conventional IRS in a variety of operational settings.

This study was conducted in 220 households over

was assessed using were gathered from focus group

containing questions relating to installation, exposure reactions, entomology, indoor environment, aesthetics

using bioassay tests.

The deltamethrin DL demonstrated little to no

study, supported by minimal loss of insecticide content.

bioactivity by 6 months and full loss after 12 months. The majority of participants in DL households perceived reductions in mosquito density and biting, but no changes

wanted to retain the DL, 73% cited protective reasons, 20% expressed a desire to keep theirs for decoration and 7% valued both assets equally. In Nigeria, a dichotomy between rural and urban respondents emerged. Rural participants favoured wall adornments and accepted DL because of its perceived decorative value and

preferred minimal wall decoration and rejected the DL based upon objections to its aesthetics and installation feasibility.

Just as long-lasting insecticidal nets overcame several of the technical and operational constraints associated with conventionally treated nets, this study demonstrated the potential of DL to sustain user compliance and overcome the operational challenges associated with IRS. The high level of acceptability

communities as the ideal target consumer group for DL. The poorer compliance among urban households suggests that DL would not be readily adopted or sustained in these areas. If DL is as well received in other rural areas it could overcome some of the logistical constraints associated with spray campaigns and has the potential to become a long-lasting alternative to IRS in malaria endemic areas.



Combining organophosphate treated wall linings and long-lasting insecticidal nets for improved control of pyrethroid resistant Anopheles gambiae.

LSHTM Investigators: Corine Ngufor & Mark Rowland.

External Investigators/Collaborators: Emile Tchicaya & Benjamin

Sagnon N’Fale (Centre National de Recherche et de Formation sur

le Paludisme, Burkina Faso); Roch Dabire (Centre Muraz, Burkina

(Liverpool School of Tropical Medicine, UK).

Funding: European Union through the AvecNet project.

which can be produced in a long-lasting format. Non-pyrethroid versions could be used in combination with long-lasting insecticidal nets for improved control and management of insecticide resistant vector populations.

Experimental hut trials were carried out in Valley

pirimiphos methyl treated DL and NWH either alone or in combination with long-lasting insecticide-treated nets

Anopheles gambiae. Comparison was made with pyrethroid DL. Mosquitoes were genotyped for kdr and ace-1R resistant genes

to investigate the insecticide resistance management potential of the combination.

The overall kdr and ace-1R allele frequencies were 0.95 and 0.01 respectively. Mortality with p-methyl DL and NWH alone was higher than with pyrethroid DL alone

p-methyl DL or NWH with LLINs reduced biting rates

huts. Mosquitoes bearing the ace-1R gene were more

whereas all resistant and susceptible genotypes were killed by the combination.

P-methyl DL and NWH outperformed pyrethroid DL. Combining p-methyl DL and NWH with LLINs could

a vector population which is resistant to pyrethroids but susceptible to organophosphates. There was evidence that the single intervention would select kdr and ace-1R resistance genes and the combination intervention might select less strongly. Technology to bind organophosphates to plastic wall lining would be worth developing.

Multicentre studies of insecticide-treated durable wall lining in Africa and Southeast

LSHTM Investigators: Louisa Messenger, Mark Rowland & Immo

Kleinschmidt.

External Investigators/Collaborators: Abrahan Arnez (Medical

Louise Larsen (Technical Institute of Denmark, Denmark); Nathan P

Miller, The MENTOR Initiative, Angola); Adedapo Adeogun (Nigerian

Institute of Medical Research, Nigeria).

Funding:

insecticide is gradually released from an aesthetically attractive wall lining material to provide vector control for several years.

and household acceptability of DL, compared to conventional IRS in a variety of operational settings.

This study was conducted in 220 households over

was assessed using were gathered from focus group

containing questions relating to installation, exposure reactions, entomology, indoor environment, aesthetics

using bioassay tests.

The deltamethrin DL demonstrated little to no

study, supported by minimal loss of insecticide content.

bioactivity by 6 months and full loss after 12 months. The majority of participants in DL households perceived reductions in mosquito density and biting, but no changes

wanted to retain the DL, 73% cited protective reasons, 20% expressed a desire to keep theirs for decoration and 7% valued both assets equally. In Nigeria, a dichotomy between rural and urban respondents emerged. Rural participants favoured wall adornments and accepted DL because of its perceived decorative value and

preferred minimal wall decoration and rejected the DL based upon objections to its aesthetics and installation feasibility.

Just as long-lasting insecticidal nets overcame several of the technical and operational constraints associated with conventionally treated nets, this study demonstrated the potential of DL to sustain user compliance and overcome the operational challenges associated with IRS. The high level of acceptability

communities as the ideal target consumer group for DL. The poorer compliance among urban households suggests that DL would not be readily adopted or sustained in these areas. If DL is as well received in other rural areas it could overcome some of the logistical constraints associated with spray campaigns and has the potential to become a long-lasting alternative to IRS in malaria endemic areas.



(Aquatain) and the insect growth regulator pyriproxifen (Sumilarv) for the control of immature Anopheles gambiae and Anopheles arabiensis.

LSHTM Investigators: Ulrike Fillinger, Oscar Mbare & Steve

Lindsay.

External Investigators/Collaborators: Bryson Ndenga (Kenya

Medical Research Institute, Kenya).

Funding: National Institute of Health; Sumitomo Chemical Ltd.

mosquito life cycle, but for the past 50 years efforts have focused almost exclusively on the control of host-seeking adults.

The opportunity provided by integrated vector

on a single intervention through sound integration of complimentary alternatives such as larval source

sustainability of available insecticides and country

are typically built around treatment of all aquatic habitats, irrespective of their productivity, and larvicides need to be applied weekly. For improving the cost-effectiveness of LSM it is important to:

space and time

to reduce the number of applications made

be incorporated into resistance management schemes

that are both potentially effective and long-lasting:

the possibility of auto-dissemination of pyriproxifen by gravid mosquitoes and a number of cage bioassays to test physiological impact of insecticides on fertility and fecundity.

Rationalising mosquito larval source management to develop a cost-effective tool for integrated vector management against malaria vectors in the western Kenya highlands.

LSHTM Investigators: Ulrike Fillinger & Oscar Mbare.


Medical Research Institute, Kenya); Stefan Dongus (Ifakara Health

Institute, Tanzania); Hilary Ranson (Liverpool School of Tropical

Medicine, UK).

Funding: European Union Seventh Framework Programme;

Sumitomo Chemical.

source management highlights the potential of this method in reducing malaria transmission especially in areas where larval habitats are focal and accessible, i.e. in highland areas.

Costs per person protected for implementing larval control programs at scale are estimated in the same range as indoor residual spraying programmes

and higher cost-effectiveness is likely for areas where targeting the intervention in time would be feasible and where high population density could be protected by the intervention; however there is a lack of empirical evidence to support this suggestion. Rationalising of this strategy

to date, is that the intervention is typically built around treatment of all aquatic habitats all year round in short re-application cycles. This pilot study was designed to investigate the insect growth regulator, pyriproxyfen, for its potential residual control of immature malaria vectors and to compare the technical feasibility and potential impact on malaria transmission of time-targeted (March-

of this insecticide in the western Kenya Highlands, the most highly populated area in Kenya with localised larval habitats. Data from this pilot trial will provide the necessary information to design a large scale randomised controlled trial.

Mosquito larval source management for controlling malaria.

LSHTM Investigators: Lucy Tusting, Ulrike Fillinger, Christian

Bottomley & Steve Lindsay.

External Investigators/Collaborators: Julie Thwing (Centers for

Disease Control and Prevention, USA); David Sinclair (Liverpool

and Prevention, USA); Kimberley Bonner (Princeton University,

Princeton, USA).

Funding:

of malaria vector control that targets mosquito larvae as they mature in aquatic habitats, for example by larviciding or draining land.

We carried out a Cochrane Review to evaluate the effectiveness of LSM for controlling malaria. We screened

eligible for inclusion. In two cluster-randomised controlled

and rural India and rural Kenya, results were inconsistent.

the Gambia River, larviciding by ground teams did not

larviciding reduced parasite prevalence by almost 90%

and-after trials in Greece, India, the Philippines, and Tanzania, LSM reduced parasite prevalence by two-thirds

another policy option, alongside long-lasting insecticide-treated nets and indoor residual spraying for malaria

proportion of larval habitats can be targeted. Further research is needed to evaluate whether larval source

larval habitats are more extensive.

Do topical repellents divert mosquitoes within a community? Health equity implications of topical repellents as a mosquito bite prevention tool.

LSHTM Investigators: Onyango Sangoro.

External Investigators/Collaborators: Marta Maia, Max Thele,

Emmanuel Simfukwe & Sarah Moore (Ifakara Health Institute,

Tanzania); Elizabeth Turner (Duke University, USA).

Repellents do not kill mosquitoes-they simply reduce human-vector contact. Thus it is possible that individuals who do not use repellents but dwell close to repellent users experience more bites than otherwise. The objective of this study was to measure if diversion occurs from households that use repellents to those that do not use repellents.

The study was performed in three Tanzanian villages

insecticide-treated nets. Three coverage scenarios were investigated: complete coverage (all households

crossover study design was used and coverage scenarios

were rotated weekly over a period of ten weeks. The placebo lotion was randomly allocated to households in the incomplete coverage scenario. The level of compliance was reported to be close to 100%. Mosquito densities were measured through aspiration of resting mosquitoes. Data were analysed using negative binomial regression models.

Repellent-users had consistently fewer mosquitoes in their dwellings. In villages where everybody had been given 15%-DEET, resting mosquito densities were fewer than half that of households in the no coverage scenario

a village where 80% of the households used 15%-DEET were likely to have over four-times more mosquitoes

dwellings in comparison to households in a village where nobody uses repellent.

There is evidence that high coverage of repellent use

incomplete coverage evidence suggests that mosquitoes are diverted from households that use repellent to those that do not. Therefore, if repellents are to be considered for vector control, strategies to maximise coverage are required.



(Aquatain) and the insect growth regulator pyriproxifen (Sumilarv) for the control of immature Anopheles gambiae and Anopheles arabiensis.

LSHTM Investigators: Ulrike Fillinger, Oscar Mbare & Steve

Lindsay.


Medical Research Institute, Kenya).

Funding: National Institute of Health; Sumitomo Chemical Ltd.

mosquito life cycle, but for the past 50 years efforts have focused almost exclusively on the control of host-seeking adults.

The opportunity provided by integrated vector

on a single intervention through sound integration of complimentary alternatives such as larval source

sustainability of available insecticides and country

are typically built around treatment of all aquatic habitats, irrespective of their productivity, and larvicides need to be applied weekly. For improving the cost-effectiveness of LSM it is important to:

space and time

to reduce the number of applications made

be incorporated into resistance management schemes

that are both potentially effective and long-lasting:

the possibility of auto-dissemination of pyriproxifen by gravid mosquitoes and a number of cage bioassays to test physiological impact of insecticides on fertility and fecundity.

Rationalising mosquito larval source management to develop a cost-effective tool for integrated vector management against malaria vectors in the western Kenya highlands.

LSHTM Investigators: Ulrike Fillinger & Oscar Mbare.


Medical Research Institute, Kenya); Stefan Dongus (Ifakara Health

Institute, Tanzania); Hilary Ranson (Liverpool School of Tropical

Medicine, UK).

Funding: European Union Seventh Framework Programme;

Sumitomo Chemical.

source management highlights the potential of this method in reducing malaria transmission especially in areas where larval habitats are focal and accessible, i.e. in highland areas.

Costs per person protected for implementing larval control programs at scale are estimated in the same range as indoor residual spraying programmes

and higher cost-effectiveness is likely for areas where targeting the intervention in time would be feasible and where high population density could be protected by the intervention; however there is a lack of empirical evidence to support this suggestion. Rationalising of this strategy

to date, is that the intervention is typically built around treatment of all aquatic habitats all year round in short re-application cycles. This pilot study was designed to investigate the insect growth regulator, pyriproxyfen, for its potential residual control of immature malaria vectors and to compare the technical feasibility and potential impact on malaria transmission of time-targeted (March-

of this insecticide in the western Kenya Highlands, the most highly populated area in Kenya with localised larval habitats. Data from this pilot trial will provide the necessary information to design a large scale randomised controlled trial.

Mosquito larval source management for controlling malaria.

LSHTM Investigators: Lucy Tusting, Ulrike Fillinger, Christian

Bottomley & Steve Lindsay.

External Investigators/Collaborators: Julie Thwing (Centers for

Disease Control and Prevention, USA); David Sinclair (Liverpool

and Prevention, USA); Kimberley Bonner (Princeton University,

Princeton, USA).

Funding:

of malaria vector control that targets mosquito larvae as they mature in aquatic habitats, for example by larviciding or draining land.

We carried out a Cochrane Review to evaluate the effectiveness of LSM for controlling malaria. We screened

eligible for inclusion. In two cluster-randomised controlled

and rural India and rural Kenya, results were inconsistent.

the Gambia River, larviciding by ground teams did not

larviciding reduced parasite prevalence by almost 90%

and-after trials in Greece, India, the Philippines, and Tanzania, LSM reduced parasite prevalence by two-thirds

another policy option, alongside long-lasting insecticide-treated nets and indoor residual spraying for malaria

proportion of larval habitats can be targeted. Further research is needed to evaluate whether larval source

larval habitats are more extensive.

Do topical repellents divert mosquitoes within a community? Health equity implications of topical repellents as a mosquito bite prevention tool.


External Investigators/Collaborators: Marta Maia, Max Thele,

Emmanuel Simfukwe & Sarah Moore (Ifakara Health Institute,

Tanzania); Elizabeth Turner (Duke University, USA).

Repellents do not kill mosquitoes-they simply reduce human-vector contact. Thus it is possible that individuals who do not use repellents but dwell close to repellent users experience more bites than otherwise. The objective of this study was to measure if diversion occurs from households that use repellents to those that do not use repellents.

The study was performed in three Tanzanian villages

insecticide-treated nets. Three coverage scenarios were investigated: complete coverage (all households

crossover study design was used and coverage scenarios

were rotated weekly over a period of ten weeks. The placebo lotion was randomly allocated to households in the incomplete coverage scenario. The level of compliance was reported to be close to 100%. Mosquito densities were measured through aspiration of resting mosquitoes. Data were analysed using negative binomial regression models.

Repellent-users had consistently fewer mosquitoes in their dwellings. In villages where everybody had been given 15%-DEET, resting mosquito densities were fewer than half that of households in the no coverage scenario

a village where 80% of the households used 15%-DEET were likely to have over four-times more mosquitoes

dwellings in comparison to households in a village where nobody uses repellent.

There is evidence that high coverage of repellent use

incomplete coverage evidence suggests that mosquitoes are diverted from households that use repellent to those that do not. Therefore, if repellents are to be considered for vector control, strategies to maximise coverage are required.



--

tions provides a disease exposure free tech-


External Investigators/Collaborators: Dickson Lweitojera, Emma-

nuel Simfukwe, Hassan Ngonyani, Edgar Mbeyela, Daniel Lugiko,

Japhet Kihonda, Marta Maia & Sarah Moore (Ifakara Health Institute,

Tanzania).

Before topical repellents can be employed as interven--

volunteers, are the main methods used for assessing the

However, laboratory tests are not representative of real life conditions under which repellents are used and

-ease. There is, therefore, a need to develop methods to

minimizing volunteer exposure to disease. -

compared to a placebo lotion in a 200 sq m (10 m x 20

Anopheles arabiensisagainst wild malaria vectors and nuisance-biting mosqui-toes. The average percentage protection against biting

used to determine relative risk of being bitten when wear-ing either of these repellents compared to the placebo.

15% DEET repellent after four hours of mosquito collec-

DEET in ethanol after four hours was 71.29% (CI 61.77-

applied mosquito repellents, thereby avoiding risks of exposure to mosquito-borne pathogens, associated with

An experimental hut study to quantify the ef-fect of DichloroDiphenylTrichloroethane (DDT) and airborne pyrethroids on entomological parameters of malaria transmission.

LSHTM Investigators: Sheila Ogoma & Lena Lorenz.

External Investigators/Collaborators: Hassan Ngonyani, Robert

Sangusangu, Mohammed Kitumbukile, Masoudi Kilalangongono,

Emmanuel Simfukwe, Anton Mseka, Edgar Mbeyela, Deogratius

Roman, Jason Moore, Katharina Kreppel Marta Maia & Sarah Moore

(Ifakara Health Institute, Tanzania).

Current malaria vector control programmes rely on insec-ticides with rapid contact toxicity. However, spatial repel-lents can also be applied to reduce man-vector contact, which might ultimately impact malaria transmission. The aim of this study was to quantify effects of airborne pyre-throids from coils and DDT used an indoor residual spray

transmission. -

pared to DDT on house entry, exit and indoor feeding be-haviour of Anopheles gambiae sensu lato were measured

-comes were deterrence - reduction in house entry of mos-

quitoes; irritancy or excito-repellency - induced premature exit of mosquitoes; blood feeding inhibition and effect on

and DDT reduced human vector contact through deter-rence by 38%, 30% and 8%, respectively and induced half of the mosquitoes to leave huts before feeding (56%,

than three quarters of mosquitoes in the DDT hut did not feed, almost none laid eggs and 67%, 72% and 70% of all

DDT huts, respectively had died after 24¬†hours.This study highlights that airborne pyrethroids and

DDT affect a range of anopheline mosquito behaviours that are important parameters in malaria transmission, namely deterrence, irritancy/excito-repellency and blood-

-cant toxicity and reduced mosquito fecundity that affect mosquito densities and, therefore, provide community protection against diseases for both users and non-users.

-lar effects on deterrence, irritancy and feeding inhibition. Therefore, it is suggested that airborne pyrethroids, if delivered in suitable formats, may complement existing mainstream vector control tools.

Insecticide resistance

Loss of household protection with insecticide treated nets against pyrethroid-resistant Anopheles gambiae.

LSHTM Investigators

& Mark Rowland.

External Investigators/Collaborators: Martin Akogbeto (The

Entomological Research Center of Cotonou, Benin).

Funding: London School of Hygiene & Tropical Medicine, Curtis

Foundation.

Pyrethroid resistance is becoming widespread in nopheles gambiae, coinciding with expansion of

To investigate whether nets in-use are still protective, household trials were undertaken in northern and Southern Benin where Anopheles gambiae is susceptible and resistant to pyrethroids respectively. Rooms were

blood-feeding and survival rates before and after the nets were treated with pyrethroid.

Sleeping under an ITN at the resistant location was no more protective than sleeping under an untreated net

Distribution and Spread of Pyrethroid and DichloroDiphenylTrichloroethane (DDT) Resistance among the Anopheles gambiae complex in Tanzania.

LSHTM Investigators: Mark Rowland & Natacha Protopopoff.

External Investigators/Collaborators: Bilali Kabula, Patrick

Tungu, Robert Malima, Stephen Magesa & William Kisinza (The

National Institute for Medical Research, Tanzania); Franklin Mosha

(Kilimanjaro Christian Medical Centre, Tanzania).

Funding: The United States Agency for International Development.

The development of insecticide resistance is a threat

annual surveys of resistance in 14 sentinel site. The report the 2011 National Survey is compared

to the situations in 2004 and 2010. Anopheles gambiae was resistant to pyrethroids in Muleba, Muheza, Moshi

Anopheles gambiae is becoming resistant to pyrethoids and DDT in several parts of Tanzania. This coincided with scaling up of vector control measures. Resistance may impair the effectiveness of these interventions and therefore demands close monitoring and adoption of a resistance management strategy.

at the susceptible location decreased by 66% the odds

ITNs provide little or no protection once the mosquitoes become resistant and the netting holed. Resistance presents a grave threat to malaria control strategy based on ITN.

With universal coverage of vector control interventions, selection of resistance to insecticide in the mosquito vector is following close behind. Strategies of combining insecticides are being evaluated for their potential to control malaria transmitted by insecticide resistant populations.



--

tions provides a disease exposure free tech-


External Investigators/Collaborators: Dickson Lweitojera, Emma-

nuel Simfukwe, Hassan Ngonyani, Edgar Mbeyela, Daniel Lugiko,

Japhet Kihonda, Marta Maia & Sarah Moore (Ifakara Health Institute,

Tanzania).

Before topical repellents can be employed as interven--

volunteers, are the main methods used for assessing the

However, laboratory tests are not representative of real life conditions under which repellents are used and

-ease. There is, therefore, a need to develop methods to

minimizing volunteer exposure to disease. -

compared to a placebo lotion in a 200 sq m (10 m x 20

Anopheles arabiensisagainst wild malaria vectors and nuisance-biting mosqui-toes. The average percentage protection against biting

used to determine relative risk of being bitten when wear-ing either of these repellents compared to the placebo.

15% DEET repellent after four hours of mosquito collec-

DEET in ethanol after four hours was 71.29% (CI 61.77-

applied mosquito repellents, thereby avoiding risks of exposure to mosquito-borne pathogens, associated with

An experimental hut study to quantify the ef-fect of DichloroDiphenylTrichloroethane (DDT) and airborne pyrethroids on entomological parameters of malaria transmission.

LSHTM Investigators: Sheila Ogoma & Lena Lorenz.

External Investigators/Collaborators: Hassan Ngonyani, Robert

Sangusangu, Mohammed Kitumbukile, Masoudi Kilalangongono,

Emmanuel Simfukwe, Anton Mseka, Edgar Mbeyela, Deogratius

Roman, Jason Moore, Katharina Kreppel Marta Maia & Sarah Moore


Current malaria vector control programmes rely on insec-ticides with rapid contact toxicity. However, spatial repel-lents can also be applied to reduce man-vector contact, which might ultimately impact malaria transmission. The aim of this study was to quantify effects of airborne pyre-throids from coils and DDT used an indoor residual spray

transmission. -

pared to DDT on house entry, exit and indoor feeding be-haviour of Anopheles gambiae sensu lato were measured

-comes were deterrence - reduction in house entry of mos-

quitoes; irritancy or excito-repellency - induced premature exit of mosquitoes; blood feeding inhibition and effect on

and DDT reduced human vector contact through deter-rence by 38%, 30% and 8%, respectively and induced half of the mosquitoes to leave huts before feeding (56%,

than three quarters of mosquitoes in the DDT hut did not feed, almost none laid eggs and 67%, 72% and 70% of all

DDT huts, respectively had died after 24¬†hours.This study highlights that airborne pyrethroids and

DDT affect a range of anopheline mosquito behaviours that are important parameters in malaria transmission, namely deterrence, irritancy/excito-repellency and blood-

-cant toxicity and reduced mosquito fecundity that affect mosquito densities and, therefore, provide community protection against diseases for both users and non-users.

-lar effects on deterrence, irritancy and feeding inhibition. Therefore, it is suggested that airborne pyrethroids, if delivered in suitable formats, may complement existing mainstream vector control tools.

Insecticide resistance

Loss of household protection with insecticide treated nets against pyrethroid-resistant Anopheles gambiae.

LSHTM Investigators

& Mark Rowland.

External Investigators/Collaborators: Martin Akogbeto (The

Entomological Research Center of Cotonou, Benin).

Funding: London School of Hygiene & Tropical Medicine, Curtis

Foundation.

Pyrethroid resistance is becoming widespread in nopheles gambiae, coinciding with expansion of

To investigate whether nets in-use are still protective, household trials were undertaken in northern and Southern Benin where Anopheles gambiae is susceptible and resistant to pyrethroids respectively. Rooms were

blood-feeding and survival rates before and after the nets were treated with pyrethroid.

Sleeping under an ITN at the resistant location was no more protective than sleeping under an untreated net

Distribution and Spread of Pyrethroid and DichloroDiphenylTrichloroethane (DDT) Resistance among the Anopheles gambiae complex in Tanzania.

LSHTM Investigators: Mark Rowland & Natacha Protopopoff.

External Investigators/Collaborators: Bilali Kabula, Patrick

Tungu, Robert Malima, Stephen Magesa & William Kisinza (The

National Institute for Medical Research, Tanzania); Franklin Mosha

(Kilimanjaro Christian Medical Centre, Tanzania).

Funding: The United States Agency for International Development.

The development of insecticide resistance is a threat

annual surveys of resistance in 14 sentinel site. The report the 2011 National Survey is compared

to the situations in 2004 and 2010. Anopheles gambiae was resistant to pyrethroids in Muleba, Muheza, Moshi

Anopheles gambiae is becoming resistant to pyrethoids and DDT in several parts of Tanzania. This coincided with scaling up of vector control measures. Resistance may impair the effectiveness of these interventions and therefore demands close monitoring and adoption of a resistance management strategy.

at the susceptible location decreased by 66% the odds

ITNs provide little or no protection once the mosquitoes become resistant and the netting holed. Resistance presents a grave threat to malaria control strategy based on ITN.

With universal coverage of vector control interventions, selection of resistance to insecticide in the mosquito vector is following close behind. Strategies of combining insecticides are being evaluated for their potential to control malaria transmitted by insecticide resistant populations.



Global project on the implications of insecticide resistance.

Testing local mosquitos for insecticide resistance, Chhattisgarh, India.

An online tool for mapping insecticide resistance in major Anopheles vectors of human malaria parasites and review of resistance status for the Afrotropical region.

LSHTM Investigators


Control and Prevention, Kenya & Maseno University, Maseno,

Ndungo & Patrick Chege (Esri Eastern Africa, Kenya); Richard Hunt

(University of the Witwatersrand, South Africa); Nabie M Bayoh

Prevention, Kenya); Riann Christian & Maureen Coetzee (University

of the Witwatersrand, South Africa; The National Health Laboratory

Service, South Africa).

Funding: President’s Malaria Initiative; The United States Agency

for International Development.

are facing increasing insecticide resistance in the major anopheline vectors.

In order to preserve or prolong the effectiveness of the main malaria vector interventions, up-to-date and easily accessible insecticide resistance data that are interpretable at operationally-relevant scales are critical. Here in we introduce and demonstrate the usefulness of an online mapping tool, IR Mapper.

literature was performed and Anopheles insecticide

susceptibility and resistance mechanisms data were extracted and added to a database after a two-level

exploration and projection of these data.Literature searches yielded a total of 4,084

susceptibility data points for 1,505 populations, and 2,097 resistance mechanisms data points for 1,000 populations of Anopheles collected via recommended World Health

abundant for populations of Anopheles gambiae, and

were more commonly used in susceptibility assays (51.1

and organophosphates. Between 2001 and 2012, there was a clear increase in prevalence and distribution

Anopheles gambiae to pyrethroids (from 41 to 87% of the mosquito populations

were widespread. For Anopheles funestus, relatively few populations were tested, although in 2010–2012 resistance was reported in 50% of 10 populations tested. Maps are provided to illustrate the use of IR Mapper and the distribution of insecticide resistance in malaria vectors

LSHTM Investigators: Immo Kleinschmidt & John Bradley.

External Investigators/Collaborators: World Health

Organization

Liverpool School of Tropical Medicine, UK;

Federal Ministry of Health, Sudan; Malaria Control

Kenya Medical Research Institute, Kenya; National Malaria

Control Programme, Kenya; National Malaria Control

Programme, Benin; The Entomological Research Center of

Benin; National University of Benin, Benin; National

Malaria Control Programme, Cameroon; , Organisation de

Centrale, Benin; India: Organisation de Coordination pour la

Institute for Medical Research, India; Ministry of Health, India;

Family Welfare, Chhattisgarh Directorate of Health Services,

India.

Funding: World

Health Organization

This study assesses the impact that insecticide resistance has on the effectiveness of malaria vector control tools long-lasting insecticide-treated nets

In two countries this is done by cluster randomised trials of universal coverage LLINs versus universal coverage LLINs in combination with IRS, with levels of insecticide resistance of the main vector balanced between the two study arms. In each cluster resistance to the insecticide used on LLINs is monitored, and malaria incidence is estimated from

the duration of the study. In three countries, clusters are established and malaria vector mosquitoes in each cluster assessed for resistance to the insecticide used. Cohorts of children recruited for follow-up and estimation of malaria incidence. Resistance impact will be assessed from the ratio of incidence rates in clusters with high compared to those with low resistance. Resistance mechanisms will be determined in subsets of study clusters.



Global project on the implications of insecticide resistance.

Testing local mosquitos for insecticide resistance, Chhattisgarh, India.

An online tool for mapping insecticide resistance in major Anopheles vectors of human malaria parasites and review of resistance status for the Afrotropical region.

LSHTM Investigators


Control and Prevention, Kenya & Maseno University, Maseno,

Ndungo & Patrick Chege (Esri Eastern Africa, Kenya); Richard Hunt

(University of the Witwatersrand, South Africa); Nabie M Bayoh

Prevention, Kenya); Riann Christian & Maureen Coetzee (University

of the Witwatersrand, South Africa; The National Health Laboratory

Service, South Africa).

Funding: President’s Malaria Initiative; The United States Agency

for International Development.

are facing increasing insecticide resistance in the major anopheline vectors.

In order to preserve or prolong the effectiveness of the main malaria vector interventions, up-to-date and easily accessible insecticide resistance data that are interpretable at operationally-relevant scales are critical. Here in we introduce and demonstrate the usefulness of an online mapping tool, IR Mapper.

literature was performed and Anopheles insecticide

susceptibility and resistance mechanisms data were extracted and added to a database after a two-level

exploration and projection of these data.Literature searches yielded a total of 4,084

susceptibility data points for 1,505 populations, and 2,097 resistance mechanisms data points for 1,000 populations of Anopheles collected via recommended World Health

abundant for populations of Anopheles gambiae, and

were more commonly used in susceptibility assays (51.1

and organophosphates. Between 2001 and 2012, there was a clear increase in prevalence and distribution

Anopheles gambiae to pyrethroids (from 41 to 87% of the mosquito populations

were widespread. For Anopheles funestus, relatively few populations were tested, although in 2010–2012 resistance was reported in 50% of 10 populations tested. Maps are provided to illustrate the use of IR Mapper and the distribution of insecticide resistance in malaria vectors

LSHTM Investigators: Immo Kleinschmidt & John Bradley.

External Investigators/Collaborators: World Health

Organization

Liverpool School of Tropical Medicine, UK;

Federal Ministry of Health, Sudan; Malaria Control

Kenya Medical Research Institute, Kenya; National Malaria

Control Programme, Kenya; National Malaria Control

Programme, Benin; The Entomological Research Center of

Benin; National University of Benin, Benin; National

Malaria Control Programme, Cameroon; , Organisation de

Centrale, Benin; India: Organisation de Coordination pour la

Institute for Medical Research, India; Ministry of Health, India;

Family Welfare, Chhattisgarh Directorate of Health Services,

India.

Funding: World

Health Organization

This study assesses the impact that insecticide resistance has on the effectiveness of malaria vector control tools long-lasting insecticide-treated nets

In two countries this is done by cluster randomised trials of universal coverage LLINs versus universal coverage LLINs in combination with IRS, with levels of insecticide resistance of the main vector balanced between the two study arms. In each cluster resistance to the insecticide used on LLINs is monitored, and malaria incidence is estimated from

the duration of the study. In three countries, clusters are established and malaria vector mosquitoes in each cluster assessed for resistance to the insecticide used. Cohorts of children recruited for follow-up and estimation of malaria incidence. Resistance impact will be assessed from the ratio of incidence rates in clusters with high compared to those with low resistance. Resistance mechanisms will be determined in subsets of study clusters.



High level resistance in Anopheles gambiae to pyrethroid insecticides and reduced susceptibility to bendiocarb in North-Western Tanzania.

LSHTM Investigators

Wright, Philippa West, Immo Kleinschmidt & Mark

Rowland.

External Investigators/Collaborators: Johnson

Matowo, Reginald Kavishe, Robert Kaaya & Franklin

Mosha (Kilimanjaro Christian Medical Centre, Tanzania);

Robert Malima & William Kisinza, (The National Institute

for Medical Research, Tanzania).

Funding: President’s Malaria Initiative; The United

States Agency for International Development.

To control malaria, long lasting insecticide-

Tanzania. The main threat to these measures is the selection of insecticide resistance.

To monitor the rapidly evolving situation, the resistance status of Anopheles gambiae to different insecticides were investigated in North West Tanzania, an area that has been subject to several rounds of pyrethroid IRS since 2006.

Collections of mosquitoes were exposed to diagnostic dosages of pyrethroid and

resistance test kits and samples analysed for resistance mechanisms using real time PCR.

80% were Anopheles gambiae and 20% Anopheles arabiensis. No fewer than 60% were resistant in any survey. The kdr-eastern variant was present in 97% of Anopheles gambiae but was absent in Anopheles arabiensis. Anopheles gambiae also showed reduced susceptibility to the carbamate insecticide, bendiocarb.

Anopheles gambiae has developed a high frequency of resistance to pyrethroids

Unlike in coastal Tanzania, where the ratio of Anopheles gambiae to Anopheles arabiensis has decreased in response to vector control, Anopheles gambiae persists at high frequency in north-western Tanzania, probably due to selection of pyrethroid resistance, and this trend is likely to arise in other areas as resistance spreads or is subject to local selection from IRS or LLINs.

Use of indoor residual spraying and long-lasting insecticidal nets with synergist for control of malaria transmitted by pyrethroid resistant vectors in endemic Tanzania.

LSHTM Investigators: Natacha Protopopoff, Alexandra Wright,

Immo Kleinschmidt & Mark Rowland.




Tanzania).

Funding: The Medical Research Council; The Wellcome Trust; The

UK Department for International Development.

The massive scale-up of vector control measures has

prevention and vector control tools are long-lasting

Both rely on pyrethroid insecticides either to provide a repellent barrier between humans and mosquitoes

or to kill mosquitoes before they can transmit malaria. With the huge efforts being taken to provide universal coverage of LLINs to those at risk there is, unfortunately, enormous selection pressure on mosquitoes to develop resistance to pyrethroids. Resistance is now occurring in most countries and some forms appear to be so strong that vector mosquitoes survive contact and continue to transmit malaria. In the present trial we will evaluate a new types of LLIN that incorporate a chemical synergist that knocks out the resistance mechanism so the LLIN continues to protect and long-lasting non-pyrethroid insecticides that can be sprayed on walls and provide control for almost a year compared to standard LLIN

will be randomly allocated to 4 different interventions; 1/the standard LLIN, 2/ new LLIN, 3/combination standard LLIN and IRS with the long lasting insecticide and 4/ IRS with the new type of LLIN. The impact of the intervention on malaria prevalence and transmission, entomological inoculation rate and the selection of resistance will be evaluated for 2 years.

Olyset Duo® (a pyriproxyfen and permethrin mixture net): an experimental hut trial against pyrethroid resistant Anopheles gambiae and Culex quinquefasciatus in southern Benin.

LSHTM Investigators

Rowland.

External Investigators/Collaborators: Akogbeto Martin (Centre de

Recherches Entomologiques de Cotonou, Benin).

Funding:

control of pyrethroid resistant malaria vectors are urgently

reduces the fecundity and fertility of adult female mosquitoes.

mixture LN containing pyriproxyfen and permethrin, was evaluated in experimental huts in southern Benin against pyrethroid resistant Anopheles gambiae and Culex quinquefasciatus.

fed Anopheles gambiae from the control hut was 37%

laid eggs. The tunnel test results were consistent with the

resistant Culex quinquefasciatus although mortality rates

surviving blood-fed Culex quinquefasciatus. with the PPF-treated nets.

personal protection and killing of pyrethroid resistant Anopheles gambiae, and sterilized surviving blood-fed mosquitoes. Mixing pyrethroid and pyriproxyfen on a LN shows potential for malaria control and management of pyrethroid resistant vectors by preventing further selection of pyrethroid resistant phenotypes.



High level resistance in Anopheles gambiae to pyrethroid insecticides and reduced susceptibility to bendiocarb in North-Western Tanzania.

LSHTM Investigators

Wright, Philippa West, Immo Kleinschmidt & Mark

Rowland.

External Investigators/Collaborators: Johnson

Matowo, Reginald Kavishe, Robert Kaaya & Franklin

Mosha (Kilimanjaro Christian Medical Centre, Tanzania);

Robert Malima & William Kisinza, (The National Institute

for Medical Research, Tanzania).

Funding: President’s Malaria Initiative; The United

States Agency for International Development.

To control malaria, long lasting insecticide-

Tanzania. The main threat to these measures is the selection of insecticide resistance.

To monitor the rapidly evolving situation, the resistance status of Anopheles gambiae to different insecticides were investigated in North West Tanzania, an area that has been subject to several rounds of pyrethroid IRS since 2006.

Collections of mosquitoes were exposed to diagnostic dosages of pyrethroid and

resistance test kits and samples analysed for resistance mechanisms using real time PCR.

80% were Anopheles gambiae and 20% Anopheles arabiensis. No fewer than 60% were resistant in any survey. The kdr-eastern variant was present in 97% of Anopheles gambiae but was absent in Anopheles arabiensis. Anopheles gambiae also showed reduced susceptibility to the carbamate insecticide, bendiocarb.

Anopheles gambiae has developed a high frequency of resistance to pyrethroids

Unlike in coastal Tanzania, where the ratio of Anopheles gambiae to Anopheles arabiensis has decreased in response to vector control, Anopheles gambiae persists at high frequency in north-western Tanzania, probably due to selection of pyrethroid resistance, and this trend is likely to arise in other areas as resistance spreads or is subject to local selection from IRS or LLINs.

Use of indoor residual spraying and long-lasting insecticidal nets with synergist for control of malaria transmitted by pyrethroid resistant vectors in endemic Tanzania.

LSHTM Investigators: Natacha Protopopoff, Alexandra Wright,

Immo Kleinschmidt & Mark Rowland.




Tanzania).

Funding: The Medical Research Council; The Wellcome Trust; The

UK Department for International Development.

The massive scale-up of vector control measures has

prevention and vector control tools are long-lasting

Both rely on pyrethroid insecticides either to provide a repellent barrier between humans and mosquitoes

or to kill mosquitoes before they can transmit malaria. With the huge efforts being taken to provide universal coverage of LLINs to those at risk there is, unfortunately, enormous selection pressure on mosquitoes to develop resistance to pyrethroids. Resistance is now occurring in most countries and some forms appear to be so strong that vector mosquitoes survive contact and continue to transmit malaria. In the present trial we will evaluate a new types of LLIN that incorporate a chemical synergist that knocks out the resistance mechanism so the LLIN continues to protect and long-lasting non-pyrethroid insecticides that can be sprayed on walls and provide control for almost a year compared to standard LLIN

will be randomly allocated to 4 different interventions; 1/the standard LLIN, 2/ new LLIN, 3/combination standard LLIN and IRS with the long lasting insecticide and 4/ IRS with the new type of LLIN. The impact of the intervention on malaria prevalence and transmission, entomological inoculation rate and the selection of resistance will be evaluated for 2 years.

Olyset Duo® (a pyriproxyfen and permethrin mixture net): an experimental hut trial against pyrethroid resistant Anopheles gambiae and Culex quinquefasciatus in southern Benin.

LSHTM Investigators

Rowland.

External Investigators/Collaborators: Akogbeto Martin (Centre de

Recherches Entomologiques de Cotonou, Benin).

Funding:

control of pyrethroid resistant malaria vectors are urgently

reduces the fecundity and fertility of adult female mosquitoes.

mixture LN containing pyriproxyfen and permethrin, was evaluated in experimental huts in southern Benin against pyrethroid resistant Anopheles gambiae and Culex quinquefasciatus.

fed Anopheles gambiae from the control hut was 37%

laid eggs. The tunnel test results were consistent with the

resistant Culex quinquefasciatus although mortality rates

surviving blood-fed Culex quinquefasciatus. with the PPF-treated nets.

personal protection and killing of pyrethroid resistant Anopheles gambiae, and sterilized surviving blood-fed mosquitoes. Mixing pyrethroid and pyriproxyfen on a LN shows potential for malaria control and management of pyrethroid resistant vectors by preventing further selection of pyrethroid resistant phenotypes.



Mosquito nets treated with a mixture of the insecticides chlorfenapyr and alphacypermethrin control pyrethroid resistant Anopheles gambiae and Culex quinquefasciatus mosquitoes in West Africa.

LSHTM Investigators

Rowland.

External Investigators/Collaborators: Andreas Kudom, Pelagie

Boko & Abibathou Odjo (Centre de Recherche Entomologique

Consortium, UK).

Funding:

The effectiveness of insecticide treated nets is under

selection of pyrethroid resistance in Anopheles gambiae mosquitoes.

To maintain progress against malaria it is necessary to identify alternative residual insecticides for mosquito nets. Mixtures of pyrethroid and insecticides with novel mode of action provide scope for both improved control and management of resistance through concurrent exposure to unrelated insecticides.

The pyrrole chlorfenapyr and the pyrethroid alphacypermethrin were tested individually and as a mixture on mosquito nets in an experimental hut trial in southern Benin against pyrethroid resistant Anopheles

gambiae and Culex quinquefasciatus mosquitoes. The nets were deliberately holed to simulate the effect of wear and tear.

The nets treated with the mixture of chlorfenapyr 200mg/m2 and alphacypermethrin 25mg/m2 killed a proportion of Anopheles gambiae (77%, 95%CI:

nets treated with the mixture reduced mosquito biting and blood-feeding rates to the same level as the alphacypermethrin treated net, whereas the chlorfenapyr

mortality and blood feeding inhibition between treatments was observed among Culex quinquefasciatus to that seen among Anopheles gambiae, although the effects were

applied at 100mg/m2 had an effect similar to the mixture with chlorfenapyr at 200mg/m2.

The effectiveness of Iinsecticide treated nets against pyrethroid resistant mosquitoes was restored by the mixture: the alphacypermethrin component reduced human-vector contact while the chlorfenapyr controlled pyrethroid-resistant mosquitoes. The complementary action of these unrelated insecticides demonstrates that the mixture has potential for preventing malaria transmission in areas compromised by the spread of pyrethroid resistance.

Malaria prevention in schoolchildren: a cluster-randomised trial in schools in Mali.

LSHTM Investigators: Sian Clarke, Saba Rouhani, Rebecca Jones

& Simon Brooker.

External Investigators/Collaborators: Natalie Roschnik, Seybou

Diarra & Bamadio Modibo (Save the Children, Mali); Moussa Sacko,

Renion Saye & Diahara Traore (Ministry of Health, Mali); Matthew

Jukes (Room to Read, UK); Josselin Thuillez (Centre d’economie de

la Sorbonne, France).

Funding: Save the Children; The Wellcome Trust.

School-aged children are rarely targeted by malaria control, yet the prevalence of malaria infection in this age group often exceeds that seen in younger children and the consequences for health and school performance have yet to be fully investigated.

This cluster-randomised trial examined the impact of a teacher-led malaria control programme in schools in Mali which combined participatory education activities to promote the use of insecticide treated nets, with a single annual antimalarial treatment to clear malaria parasites from the blood at the end of the transmission season. The trial was conducted in 80 schools, with 40 schools randomised to receive the intervention.

The prevalence of malaria infection and anaemia in

to control schools. These differences were sustained until

Future work in Mali will examine the effect of malaria control on health and child development in pre-school children, with a focus on effects on cognitive foundation skills for early literacy.

Teachers administering an annual treatment to clear malaria infections in schoolchildren in Mali.

ChemopreventionWe are currently seeking to generate knowledge on the health impact, cost, feasibility and acceptability of chemoprevention and screening and treatment strategies in a number of target populations including children, school children and pregnant women.



Mosquito nets treated with a mixture of the insecticides chlorfenapyr and alphacypermethrin control pyrethroid resistant Anopheles gambiae and Culex quinquefasciatus mosquitoes in West Africa.

LSHTM Investigators

Rowland.

External Investigators/Collaborators: Andreas Kudom, Pelagie

Boko & Abibathou Odjo (Centre de Recherche Entomologique

Consortium, UK).

Funding:

The effectiveness of insecticide treated nets is under

selection of pyrethroid resistance in Anopheles gambiae mosquitoes.

To maintain progress against malaria it is necessary to identify alternative residual insecticides for mosquito nets. Mixtures of pyrethroid and insecticides with novel mode of action provide scope for both improved control and management of resistance through concurrent exposure to unrelated insecticides.

The pyrrole chlorfenapyr and the pyrethroid alphacypermethrin were tested individually and as a mixture on mosquito nets in an experimental hut trial in southern Benin against pyrethroid resistant Anopheles

gambiae and Culex quinquefasciatus mosquitoes. The nets were deliberately holed to simulate the effect of wear and tear.

The nets treated with the mixture of chlorfenapyr 200mg/m2 and alphacypermethrin 25mg/m2 killed a proportion of Anopheles gambiae (77%, 95%CI:

nets treated with the mixture reduced mosquito biting and blood-feeding rates to the same level as the alphacypermethrin treated net, whereas the chlorfenapyr

mortality and blood feeding inhibition between treatments was observed among Culex quinquefasciatus to that seen among Anopheles gambiae, although the effects were

applied at 100mg/m2 had an effect similar to the mixture with chlorfenapyr at 200mg/m2.

The effectiveness of Iinsecticide treated nets against pyrethroid resistant mosquitoes was restored by the mixture: the alphacypermethrin component reduced human-vector contact while the chlorfenapyr controlled pyrethroid-resistant mosquitoes. The complementary action of these unrelated insecticides demonstrates that the mixture has potential for preventing malaria transmission in areas compromised by the spread of pyrethroid resistance.

Malaria prevention in schoolchildren: a cluster-randomised trial in schools in Mali.

LSHTM Investigators: Sian Clarke, Saba Rouhani, Rebecca Jones

& Simon Brooker.

External Investigators/Collaborators: Natalie Roschnik, Seybou

Diarra & Bamadio Modibo (Save the Children, Mali); Moussa Sacko,

Renion Saye & Diahara Traore (Ministry of Health, Mali); Matthew

Jukes (Room to Read, UK); Josselin Thuillez (Centre d’economie de

la Sorbonne, France).

Funding: Save the Children; The Wellcome Trust.

School-aged children are rarely targeted by malaria control, yet the prevalence of malaria infection in this age group often exceeds that seen in younger children and the consequences for health and school performance have yet to be fully investigated.

This cluster-randomised trial examined the impact of a teacher-led malaria control programme in schools in Mali which combined participatory education activities to promote the use of insecticide treated nets, with a single annual antimalarial treatment to clear malaria parasites from the blood at the end of the transmission season. The trial was conducted in 80 schools, with 40 schools randomised to receive the intervention.

The prevalence of malaria infection and anaemia in

to control schools. These differences were sustained until

Future work in Mali will examine the effect of malaria control on health and child development in pre-school children, with a focus on effects on cognitive foundation skills for early literacy.

Teachers administering an annual treatment to clear malaria infections in schoolchildren in Mali.

ChemopreventionWe are currently seeking to generate knowledge on the health impact, cost, feasibility and acceptability of chemoprevention and screening and treatment strategies in a number of target populations including children, school children and pregnant women.



Impact of intermittent screening and treatment for malaria among school children in Kenya.

LSHTM Investigators: Simon Brooker, Katherine Halliday, Elizabeth

Allen, Caroline Jones, Thomas Drake, Lindsay Mangham & Kara

Hanson.

External Investigators/Collaborators: Matthew Jukes (Harvard

Research Institute, Kenya); Elizabeth Turner (Duke University, USA);

Hellen Inyega (University of Nairobi, Kenya); Kiambo Njagi (Ministry

of Public Health and Sanitation, Kenya); Margaret Dubeck (College

of Charleston, USA).

Funding: International Initiative for Impact Evaluation; Development

Impact Evaluation Initiative of the World Bank, The Wellcome Trust &

Partnership for Child Development.

School-based malaria control is recognized as an important potential component of integrated school-health packages.

on the health and education of school children in a low-moderate transmission setting in south coast, Kenya.

The intervention, screening once a term by health

treatment, for those positive for malaria parasiteamia, with artemether-lumefantrine, was delivered to children in 51 randomly selected primary schools with another 50 serving as control schools.

During the 2-year study period, 17.5% of children screened were RDT-positive. However, no difference was observed in the prevalence of anaemia at 12 or 24 months between children in intervention and control groups, nor was there any effect on malaria parasitaemia

based IST in this context to be relatively expensive at US$6.61 per child screened. While a qualitative stakeholder analysis indicated school-based IST to be widely acceptable, consideration of the various roles of teachers and health workers and use of simpler regimen anti-malarial drugs is important. This evaluation showed that IST is not an effective intervention in low-moderate malaria transmission settings. However, school screenings using RDTs could provide an operationally

for targeted community control.

‘School-based treatment with artemisinin-based combination therapy to reduce transmission’ (START): evaluation of the community impact of intermittent preventive treatment for malaria in Ugandan children: a cluster randomised trial.

LSHTM Investigators: Sarah Staedke, Chris Drakeley, Chi Eziefula

& Clare Chandler.


(University of California, UK); Steve Lindsay (Durham University,

Funding:

schoolchildren for malaria on malaria transmission at the community level in Jinja, Uganda.

school and the 100 nearest households, will be included in the trial; half will be randomised to the IPT intervention,

will be administered to schoolchildren monthly during one school year.

The evaluation will include:

after the intervention

end of the school year

implementation of the intervention;

In addition, we will conduct a qualitative study concurrently with the main trial. The primary outcome of the trial is the prevalence of parasitaemia in community

The baseline surveys will begin in February 2014 and the intervention will be delivered during the 2014 school year.

Extending the age range for seasonal malaria chemoprevention (SMC): effectiveness of SMC in children under 10 years of age delivered through the district health service in Senegal.

LSHTM Investigators: Badara Cisse, Catherine Pitt, Matthew Cairns, Colin Sutherland, Brian

External Investigators/Collaborators: El Hadj Ba, Jean-François Trape, Cheikh Sokhna

Funding:

Children under 5 years of age living in areas of seasonal transmission in the Sahel are recommended to receive seasonal malaria chemoprevention

transmission season, to prevent malaria. The purpose of this study was to evaluate the feasibility of delivering SMC

on a large scale by district health staff using community health workers, its safety and effectiveness, in Senegal. SMC was introduced in three districts

system was established to record all deaths and all malaria cases diagnosed at health facilities, and a pharmacovigilance system was established to detect adverse drug reactions. Coverage of SMC was independently assessed

documented courses of SMC had been administered by health workers. High coverage of three courses of treatment was achieved, and no serious adverse events attributable to the intervention were detected, despite a high

effectiveness of SMC in reducing malaria incidence in treated children, with a random effect to account for variation in incidence between health posts. To determine whether SMC was able to reduce malaria transmission, incidence of malaria in age groups too old to receive SMC, was compared between health posts in which SMC was delivered to children, and health posts without SMC, using random-effects Poisson regression.

Where SMC was delivered, the number of malaria cases in children under

age groups was reduced in areas where SMC was delivered to children, by 29%

SMC is recommended for children under <5yrs of age, but in some areas the age distribution of disease burden may justify extending this age limit, as has been done in Senegal. SMC with Sulfadoxine-Pyrimethamine plus

older children. Pharmacovigilance should be maintained in areas where SMC is implemented, and provision for strengthening national pharmacovigilance systems should therefore be included in plans for SMC implementation. When provided for a wider age range with high coverage, SMC may have an effect in reducing malaria transmission, and our results were consistent with such an effect.



Impact of intermittent screening and treatment for malaria among school children in Kenya.

LSHTM Investigators: Simon Brooker, Katherine Halliday, Elizabeth

Allen, Caroline Jones, Thomas Drake, Lindsay Mangham & Kara

Hanson.

External Investigators/Collaborators: Matthew Jukes (Harvard

Research Institute, Kenya); Elizabeth Turner (Duke University, USA);

Hellen Inyega (University of Nairobi, Kenya); Kiambo Njagi (Ministry

of Public Health and Sanitation, Kenya); Margaret Dubeck (College

of Charleston, USA).

Funding: International Initiative for Impact Evaluation; Development

Impact Evaluation Initiative of the World Bank, The Wellcome Trust &

Partnership for Child Development.

School-based malaria control is recognized as an important potential component of integrated school-health packages.

on the health and education of school children in a low-moderate transmission setting in south coast, Kenya.

The intervention, screening once a term by health

treatment, for those positive for malaria parasiteamia, with artemether-lumefantrine, was delivered to children in 51 randomly selected primary schools with another 50 serving as control schools.

During the 2-year study period, 17.5% of children screened were RDT-positive. However, no difference was observed in the prevalence of anaemia at 12 or 24 months between children in intervention and control groups, nor was there any effect on malaria parasitaemia

based IST in this context to be relatively expensive at US$6.61 per child screened. While a qualitative stakeholder analysis indicated school-based IST to be widely acceptable, consideration of the various roles of teachers and health workers and use of simpler regimen anti-malarial drugs is important. This evaluation showed that IST is not an effective intervention in low-moderate malaria transmission settings. However, school screenings using RDTs could provide an operationally

for targeted community control.

‘School-based treatment with artemisinin-based combination therapy to reduce transmission’ (START): evaluation of the community impact of intermittent preventive treatment for malaria in Ugandan children: a cluster randomised trial.

LSHTM Investigators: Sarah Staedke, Chris Drakeley, Chi Eziefula

& Clare Chandler.


(University of California, UK); Steve Lindsay (Durham University,

Funding:

schoolchildren for malaria on malaria transmission at the community level in Jinja, Uganda.

school and the 100 nearest households, will be included in the trial; half will be randomised to the IPT intervention,

will be administered to schoolchildren monthly during one school year.

The evaluation will include:

after the intervention

end of the school year

implementation of the intervention;

In addition, we will conduct a qualitative study concurrently with the main trial. The primary outcome of the trial is the prevalence of parasitaemia in community

The baseline surveys will begin in February 2014 and the intervention will be delivered during the 2014 school year.

Extending the age range for seasonal malaria chemoprevention (SMC): effectiveness of SMC in children under 10 years of age delivered through the district health service in Senegal.

LSHTM Investigators: Badara Cisse, Catherine Pitt, Matthew Cairns, Colin Sutherland, Brian

External Investigators/Collaborators: El Hadj Ba, Jean-François Trape, Cheikh Sokhna

Funding:

Children under 5 years of age living in areas of seasonal transmission in the Sahel are recommended to receive seasonal malaria chemoprevention

transmission season, to prevent malaria. The purpose of this study was to evaluate the feasibility of delivering SMC

on a large scale by district health staff using community health workers, its safety and effectiveness, in Senegal. SMC was introduced in three districts

system was established to record all deaths and all malaria cases diagnosed at health facilities, and a pharmacovigilance system was established to detect adverse drug reactions. Coverage of SMC was independently assessed

documented courses of SMC had been administered by health workers. High coverage of three courses of treatment was achieved, and no serious adverse events attributable to the intervention were detected, despite a high

effectiveness of SMC in reducing malaria incidence in treated children, with a random effect to account for variation in incidence between health posts. To determine whether SMC was able to reduce malaria transmission, incidence of malaria in age groups too old to receive SMC, was compared between health posts in which SMC was delivered to children, and health posts without SMC, using random-effects Poisson regression.

Where SMC was delivered, the number of malaria cases in children under

age groups was reduced in areas where SMC was delivered to children, by 29%

SMC is recommended for children under <5yrs of age, but in some areas the age distribution of disease burden may justify extending this age limit, as has been done in Senegal. SMC with Sulfadoxine-Pyrimethamine plus

older children. Pharmacovigilance should be maintained in areas where SMC is implemented, and provision for strengthening national pharmacovigilance systems should therefore be included in plans for SMC implementation. When provided for a wider age range with high coverage, SMC may have an effect in reducing malaria transmission, and our results were consistent with such an effect.



Maximising the impact of chemoprevention on the malaria burden in children in areas of seasonal transmission.

LSHTM Investigators: Matthew Cairns.


College London); Harry Tagbor (Kwame Nkrumah University of


a short rainy season, monthly courses of antimalarial drugs can prevent malaria in children very effectively.

This approach, called seasonal malaria

where malaria is transmitted for a larger part of the year. However, the impact in such areas is not well understood.

existing treatment regimens for long-acting artemisinin-

further malaria infections for several weeks. This may

transmission because repeated malaria attacks are likely to occur close together in time.

trial in Kumasi, Ghana, reanalysis of trial data and mathematical modelling

quantifying the burden of repeated malaria attacks and the heterogeneity in malaria risk in different epidemiological settings

to be advantageous, estimate the population at risk and the public health impact.

The costs of delivering seasonal malaria chemoprevention to children under ten at scale in Central Senegal.

LSHTM Investigators: Catherine Pitt, Badara Cisse & Paul Milligan.

External Investigators/Collaborators: Mouhamed N’Diaye &

(Institut de Recherche pour le Developpement, Dakar, Senegal);

Lesong Conteh (Imperial College London, UK).

Funding:

Preliminary results from this study were presented

contributed to its policy recommendation in March 2012 that SMC be given to children in areas of seasonal

costs of delivering SMC in a population of approximately

175,000 children aged 3 to 120 months in 45 health posts across four districts of central Senegal in 2010.

travelled door-to-door in pairs to administer sulphadoxine-pyramethamine and amodiaquine tablets over the course of several days in each of the three main months of the malaria season. We found that the costs were lower than in most previous studies of SMC, which can be attributed in part to economies of scale, as this was a much larger study than any previously conducted, as well as to the Ministry of Health’s leading role in implementation and the economies of scope achieved in extending the usual age range of SMC from children under 5 to children under 10. The SMC tablets themselves and the incentive payments

informed implementation of SMC in Senegal and several

A trial of intermittent screening and treatment as an alternative to intermittent preventive treatment with sulfadoxine-pyrimethamine for the control of malaria in pregnancy.

LSHTM Investigators: Matthew Cairns, Daniel Chandramohan,

External Investigators/Collaborators: Sheick Coulibaly

(University of Ouagadougou, Burkina Faso); John Williams

(University of Bamako, Mali); Kalifa Bojang (Medical Research

of Copenhagen, Denmark); Feiko ter Kuile (Liverpool School of

Tropical Medicine, UK).

Funding: The European & Developing Countries Clinical Trials

Partnership.

determine whether intermittent screening and treatment

infection of the placenta in pregnant women who slept under an insecticide treated bed net.

IST involved intermittent screening using a rapid diagnostic test at scheduled antenatal clinic visits and treatment of those who tested positive for maalaria with arthemether lumefantrine. Women in the standard SP-IPTp arm received two or three courses of SP in the second and third trimester. 5354 women were randomised into one of the two study arms . The prevalence of LBW was 15.1% in women in the IPT-SP group and 15.6% among those in the IST group. The mean haemoglobin concentration at the last clinic attendance before delivery was 10.97g/dL (SD 1.3g/

to IPTp-SP in preventing LBW and maternal anaemia according to criteria established prior to the trial. Thus IST is a potential alternative approach to control of malaria in pregnancy which may be especially valuable in areas where Plasmodium falciparum is highly resistant to SP.

Malaria knowledge and utilisation of chemoprophylaxis in the UK population and in UK passengers departing to malaria-endemic areas.LSHTM Investigators: Ron Behrens & Neal Alexander.

Funding: Sigma Tau Pharmaceutical.

The burden of imported malaria is predominantly

chemoprophylaxis is recognised as the most important factor. Understanding the reasons for failure was the basis of this study to explore whether knowledge and risk perception.

Two face-to-face questionnaire surveys were conducted; a survey of individuals representative of the UK population and a departure lounge survey of passengers departing to malarious regions.

had previously travelled to a malarious area. Five-hundred departing passengers were interviewed, of which 56% VFR’s and 42% were travelling to West

who had previously travelled or were travelling (63.8

similar in individuals who had and had not sought pre-travel advice and travellers using and not using chemoprophylaxis. Despite similar high knowledge

of malaria in the three groups, chemoprophylaxis

Malaria knowledge, perceived threat, travel experience, and quality of pre-travel advice appear unrelated to the use of chemoprophylaxis in passengers. Reducing malaria in VFR travellers will require strategies other than improving malaria knowledge and enhancing malaria risk awareness.



Maximising the impact of chemoprevention on the malaria burden in children in areas of seasonal transmission.

LSHTM Investigators: Matthew Cairns.


College London); Harry Tagbor (Kwame Nkrumah University of


a short rainy season, monthly courses of antimalarial drugs can prevent malaria in children very effectively.

This approach, called seasonal malaria

where malaria is transmitted for a larger part of the year. However, the impact in such areas is not well understood.

existing treatment regimens for long-acting artemisinin-

further malaria infections for several weeks. This may

transmission because repeated malaria attacks are likely to occur close together in time.

trial in Kumasi, Ghana, reanalysis of trial data and mathematical modelling

quantifying the burden of repeated malaria attacks and the heterogeneity in malaria risk in different epidemiological settings

to be advantageous, estimate the population at risk and the public health impact.

The costs of delivering seasonal malaria chemoprevention to children under ten at scale in Central Senegal.

LSHTM Investigators: Catherine Pitt, Badara Cisse & Paul Milligan.

External Investigators/Collaborators: Mouhamed N’Diaye &

(Institut de Recherche pour le Developpement, Dakar, Senegal);

Lesong Conteh (Imperial College London, UK).

Funding:

Preliminary results from this study were presented

contributed to its policy recommendation in March 2012 that SMC be given to children in areas of seasonal

costs of delivering SMC in a population of approximately

175,000 children aged 3 to 120 months in 45 health posts across four districts of central Senegal in 2010.

travelled door-to-door in pairs to administer sulphadoxine-pyramethamine and amodiaquine tablets over the course of several days in each of the three main months of the malaria season. We found that the costs were lower than in most previous studies of SMC, which can be attributed in part to economies of scale, as this was a much larger study than any previously conducted, as well as to the Ministry of Health’s leading role in implementation and the economies of scope achieved in extending the usual age range of SMC from children under 5 to children under 10. The SMC tablets themselves and the incentive payments

informed implementation of SMC in Senegal and several

A trial of intermittent screening and treatment as an alternative to intermittent preventive treatment with sulfadoxine-pyrimethamine for the control of malaria in pregnancy.

LSHTM Investigators: Matthew Cairns, Daniel Chandramohan,

External Investigators/Collaborators: Sheick Coulibaly

(University of Ouagadougou, Burkina Faso); John Williams

(University of Bamako, Mali); Kalifa Bojang (Medical Research

of Copenhagen, Denmark); Feiko ter Kuile (Liverpool School of

Tropical Medicine, UK).

Funding: The European & Developing Countries Clinical Trials

Partnership.

determine whether intermittent screening and treatment

infection of the placenta in pregnant women who slept under an insecticide treated bed net.

IST involved intermittent screening using a rapid diagnostic test at scheduled antenatal clinic visits and treatment of those who tested positive for maalaria with arthemether lumefantrine. Women in the standard SP-IPTp arm received two or three courses of SP in the second and third trimester. 5354 women were randomised into one of the two study arms . The prevalence of LBW was 15.1% in women in the IPT-SP group and 15.6% among those in the IST group. The mean haemoglobin concentration at the last clinic attendance before delivery was 10.97g/dL (SD 1.3g/

to IPTp-SP in preventing LBW and maternal anaemia according to criteria established prior to the trial. Thus IST is a potential alternative approach to control of malaria in pregnancy which may be especially valuable in areas where Plasmodium falciparum is highly resistant to SP.

Malaria knowledge and utilisation of chemoprophylaxis in the UK population and in UK passengers departing to malaria-endemic areas.LSHTM Investigators: Ron Behrens & Neal Alexander.

Funding: Sigma Tau Pharmaceutical.

The burden of imported malaria is predominantly

chemoprophylaxis is recognised as the most important factor. Understanding the reasons for failure was the basis of this study to explore whether knowledge and risk perception.

Two face-to-face questionnaire surveys were conducted; a survey of individuals representative of the UK population and a departure lounge survey of passengers departing to malarious regions.

had previously travelled to a malarious area. Five-hundred departing passengers were interviewed, of which 56% VFR’s and 42% were travelling to West

who had previously travelled or were travelling (63.8

similar in individuals who had and had not sought pre-travel advice and travellers using and not using chemoprophylaxis. Despite similar high knowledge

of malaria in the three groups, chemoprophylaxis

Malaria knowledge, perceived threat, travel experience, and quality of pre-travel advice appear unrelated to the use of chemoprophylaxis in passengers. Reducing malaria in VFR travellers will require strategies other than improving malaria knowledge and enhancing malaria risk awareness.



Using routine data to assess and improve the delivery of interventions to control malaria in pregnancy.

LSHTM Investigators: Jayne Webster, Jane Bruce & Lucy Paintain.

External Investigators/Collaborators: Jenny Hill (Liverpool School

of Tropical Medicine, UK); Kassoum Kayentao, Sory Diawara &

Samba Diarra (Malaria Research and Training Centre, Mali); Fady

Toure (Le Programme National de Lutte contre le Paludisme, Mali);

Balla Diarra (Baraoueli District team), Eric Onyango, Meghna

for Disease Control and Prevention, Kenya); Titus Kwambai & Tom

Arunga (Kisumu East Subcounty Health Management Team, Kenya)

& Dickens Onyango (County epidemiologist).

Funding:

Malaria in Pregnancy Consortium.

The aim of the study is to develop and evaluate an enhanced district and facility level data monitoring system for the ongoing evaluation of the delivery of malaria in pregnancy interventions.

Current data collection practices relating to

treatment, insecticide treated nets and malaria case management in pregnant women were assessed.

was collected and collated at the facility level and at the district level. In-depth interviews were used to determine the drivers of effective routine data collection at the facility and district levels.

routine data collection/monitoring tools integrated into the

district level. Data completeness and accuracy is currently assessed through quarterly data auditing and compared with completeness and accuracy of reporting on priority indicators at baseline.

Sustainability of the use of the enhanced monitoring as developed will depend to an extent upon its perceived utility and acceptability by those involved in its use. This will be assessed through in-depth interviews with health providers at the facility and district levels.

the development of routine monitoring modules for a toolkit for assessing coverage of malaria in pregnancy interventions, and a decision tool which will drive which

Field testing baseline household survey data collection using tablet PCs, Khunti district, Jharkhand, India.

Identifying and quantifying the major barriers to the scale-up and use of interventions for the control of malaria in pregnancy.

LSHTM Investigators: Jayne Webster & Jane Bruce.

External Investigators/Collaborators: Jenny Hill & Feiko ter Kuile

(Liverpool School of Tropical Medicine, UK); Kassoum Kayentao,

Sory Diawara & Samba Diarra (Malaria Research and Training

Centre, Mali); Stephanie Dellicour, Meghna Desai & Peter Ouma

Prevention, Kenya).

Funding:

Pregnancy Consortium.

In order to support global efforts to scale-up malaria control interventions greater attention must be given to implementation research in order to understand the obstacles to progress at the level of local decision makers.In this study we have provided evidence on the barriers to effective access, delivery and use of intermittent prevent treatment and long lasting insecticide-treated nets in one district of each of Mali and Kenya. Findings have highlighted blockages in delivery of preventative interventions, methodological anomalies in the way in which we are currently assessing coverage of interventions, and the strengths and weaknesses of survey techniques in providing information for programme

delivery and use of case management of malaria in pregnancy is ongoing and will be completed in 2014.

SToP MiP Indonesia: implementation research and cost effectiveness studies.


External Investigators/Collaborators: Feiko ter Kuile, Rukhsana

Ahmed & Jenny Hill, (Liverpool School of Tropical Medicine, UK);

Din Syafruddin, Puji Bud Asih & Rintis Noviyanti (Eijkman Institute

for Molecular Biology, Indonesia) & Jeanne Poespoprodjo (Timika

Research Facility, Indonesia).

Funding:

Council; The Department for International Development; The

Wellcome Trust via Liverpool School of Tropical Medicine.

This research is a sub-study running alongside a trial

effective than the current strategy of single screening

by long lasting insecticide treated nets in areas with relatively low Plasmodium falciparum and Plasmodium vivax transmission in Indonesia. The current status of the SSTp-DHP programme in Papua and Sumba will be evaluated using quantitative and qualitative techniques. The feasibility, acceptability and cost effectiveness of the alternate strategies will then be assessed for the context

acceptability of changing from a test and treat strategy to one of intermittent preventive treatment.



Using routine data to assess and improve the delivery of interventions to control malaria in pregnancy.

LSHTM Investigators: Jayne Webster, Jane Bruce & Lucy Paintain.

External Investigators/Collaborators: Jenny Hill (Liverpool School

of Tropical Medicine, UK); Kassoum Kayentao, Sory Diawara &

Samba Diarra (Malaria Research and Training Centre, Mali); Fady

Toure (Le Programme National de Lutte contre le Paludisme, Mali);

Balla Diarra (Baraoueli District team), Eric Onyango, Meghna

for Disease Control and Prevention, Kenya); Titus Kwambai & Tom

Arunga (Kisumu East Subcounty Health Management Team, Kenya)

& Dickens Onyango (County epidemiologist).

Funding:

Malaria in Pregnancy Consortium.

The aim of the study is to develop and evaluate an enhanced district and facility level data monitoring system for the ongoing evaluation of the delivery of malaria in pregnancy interventions.

Current data collection practices relating to

treatment, insecticide treated nets and malaria case management in pregnant women were assessed.

was collected and collated at the facility level and at the district level. In-depth interviews were used to determine the drivers of effective routine data collection at the facility and district levels.

routine data collection/monitoring tools integrated into the

district level. Data completeness and accuracy is currently assessed through quarterly data auditing and compared with completeness and accuracy of reporting on priority indicators at baseline.

Sustainability of the use of the enhanced monitoring as developed will depend to an extent upon its perceived utility and acceptability by those involved in its use. This will be assessed through in-depth interviews with health providers at the facility and district levels.

the development of routine monitoring modules for a toolkit for assessing coverage of malaria in pregnancy interventions, and a decision tool which will drive which

Field testing baseline household survey data collection using tablet PCs, Khunti district, Jharkhand, India.

Identifying and quantifying the major barriers to the scale-up and use of interventions for the control of malaria in pregnancy.


External Investigators/Collaborators: Jenny Hill & Feiko ter Kuile

(Liverpool School of Tropical Medicine, UK); Kassoum Kayentao,

Sory Diawara & Samba Diarra (Malaria Research and Training

Centre, Mali); Stephanie Dellicour, Meghna Desai & Peter Ouma

Prevention, Kenya).

Funding:


In order to support global efforts to scale-up malaria control interventions greater attention must be given to implementation research in order to understand the obstacles to progress at the level of local decision makers.In this study we have provided evidence on the barriers to effective access, delivery and use of intermittent prevent treatment and long lasting insecticide-treated nets in one district of each of Mali and Kenya. Findings have highlighted blockages in delivery of preventative interventions, methodological anomalies in the way in which we are currently assessing coverage of interventions, and the strengths and weaknesses of survey techniques in providing information for programme

delivery and use of case management of malaria in pregnancy is ongoing and will be completed in 2014.

SToP MiP Indonesia: implementation research and cost effectiveness studies.


External Investigators/Collaborators: Feiko ter Kuile, Rukhsana

Ahmed & Jenny Hill, (Liverpool School of Tropical Medicine, UK);

Din Syafruddin, Puji Bud Asih & Rintis Noviyanti (Eijkman Institute

for Molecular Biology, Indonesia) & Jeanne Poespoprodjo (Timika

Research Facility, Indonesia).

Funding:

Council; The Department for International Development; The

Wellcome Trust via Liverpool School of Tropical Medicine.

This research is a sub-study running alongside a trial

effective than the current strategy of single screening

by long lasting insecticide treated nets in areas with relatively low Plasmodium falciparum and Plasmodium vivax transmission in Indonesia. The current status of the SSTp-DHP programme in Papua and Sumba will be evaluated using quantitative and qualitative techniques. The feasibility, acceptability and cost effectiveness of the alternate strategies will then be assessed for the context

acceptability of changing from a test and treat strategy to one of intermittent preventive treatment.



Effective and safe interventions for prevention of malaria in pregnancy in India: an assessment of burden of malaria in pregnancy, implementability of a screening strategy and barriers to scaling up interventions.

LSHTM Investigators: Daniel Chandramohan, Jayne Webster, Irene


Mishra, Anupkumar Anvikar & B Shahi (National Malaria Research

Institute, India); Feiko ter Kuile (Liverpool School of Tropical

Medicine, UK).

Funding:


The current strategy for control of malaria in pregnancy

they report any sign or symptom suggestive for malaria.The current status of the SSTp-DHP programme in

Papua and Sumba will be evaluated using quantitative and qualitative techniques. The feasibility, acceptability and cost effectiveness of the alternate strategies will then be assessed for the context of both islands.

This strategy is probably inadequate to reduce the

burden of MiP because a substantial proportion of MiP cases remain asymptomatic. The aim of this study is to

component of the study is a cluster randomised controlled trial with two arms. Women in the IST arm are screened

arm are tested for malaria only if they have any sign or symptom of malaria. The primary outcome is placental

women have been enrolled by March 2014. The trIal is expected tobe completed by June 2015.

In a second component of the study, RDT based IST was implemented at pilot scale in a sub-district in

evaluate the implementability of IST including: a pre-post intervention household survey, health facility survey, focus group discussions, in-depth interviews and a costing study.

Economic analysis and evaluations for the Malaria in Pregnancy Consortium.

LSHTM Investigators: Kara Hanson, Silke Fernandes & Jayne

Webster.

External Investigators/Collaborators: Elisa Sicuri (Barcelona

Patrick Walker (Imperial College London, UK); Feiko ter Kuile &

Jenny Hill (Liverpool School of Tropical Medicine, UK).

Funding:


Sitting within the Public Health Impact activity of the

the economics contributions are:

prevention and case management interventions

interventions

Fieldwork was conducted over the course of the past 4 years in 11 countries located in 4 continents and is anticipated to end in early 2015. Data were collected using a variety of methods, including cross-sectional household and facility surveys, exit surveys

building on a recent meta-analysis of clinical trials found

cost-effective compared with two doses of SP. In 2014-15 we will focus our efforts on further data analysis, building cost effectiveness models of Intermittent Screening and

with intermittent preventive treatment and a model of the economic burden of MiP. This analysis will support the development of a map identifying those settings where ISTp may be a more appropriate strategy for preventing the consequences of malaria in pregnancy.

the age of 18 months. Twelve months after vaccination, -

cated and severe malaria was approximately 50% in chil-dren vaccinated when aged 5-17 months but less when it was given to infants aged 6-12 weeks at the same time as routine Expanded Program on Immunization vaccines. Further analysis undertaken 18 months after vaccination showed that protection had been sustained in the older group of children but had waned substantially in infants.

all centres regardless of the level of malaria transmission.

2014 when the majority of trial subjects will have been followed for 3-4 years. It is expected that a decision on registration of the vaccine will be made in 2015 and, if this

guidelines on its use shortly afterwards.

vaccine (257049)(RTS,S/AS01) against malaria disease caused by Plasmodium falciparum in infants and children in Africa.

LSHTM Investigators: Daniel Chandramohan, Chris Drakeley, Brian

External Investigators/Collaborators: The RTS,S Clinical Trials

Partnership.

Funding:

advanced malaria vaccine and is currently being evalu-ated in a phase three trial being conducted in 11 centres

-cruited and randomised to receive three doses of RTS,S/

regimen against plasmodium falciparum ma-laria infection in Senegalese adults.

LSHTM Investigators: Badara Cisse.


-

nostou, Nick Edwards, Babatunde Imoukhuede, Rachel Roberts,

Funding: The European and Developing Countries Clinical Trials

Extensive pre-clinical data indicate that protective im-munity to the liver-stage of malaria can be conferred by

been recently demonstrated in Kenya and it is important -

tween 2012 & 2013, we ran a phase IIb, controlled, single blinded, randomised vaccine trial in Guediawaye. The main objectives were to assess the safety, immunogenic-

We randomly allocated 120 healthy male adult vol-unteers to vaccination with either the vaccine candidate, or verorab as control. Immunogenicity was measured by

--

mia and conducted intensive PCR monitoring to identify new Plasmodium falciparum infections over an eight week follow-up period. Vaccine related adverse events were mild to moderate in intensity with 1 serious adverse event in the control group not related to the intervention.

-

days later as measured by Elispot. Peak immunogenicity was shown 7 days after the boost and was high at a geo-metric mean of 1266 Spots per million PBMCs (95% CI

dose vectored vaccination approach targeting the liver-stage of malaria shows promise as a candidate malaria vaccine.

Vaccine developmentSeveral of our staff have participated in the design, execution and evaluation of RTS,S candidate vaccine trials as well as a trial of a prime boost vaccine candidate in Senegal.



Effective and safe interventions for prevention of malaria in pregnancy in India: an assessment of burden of malaria in pregnancy, implementability of a screening strategy and barriers to scaling up interventions.

LSHTM Investigators: Daniel Chandramohan, Jayne Webster, Irene


Mishra, Anupkumar Anvikar & B Shahi (National Malaria Research

Institute, India); Feiko ter Kuile (Liverpool School of Tropical

Medicine, UK).

Funding:


The current strategy for control of malaria in pregnancy

they report any sign or symptom suggestive for malaria.The current status of the SSTp-DHP programme in

Papua and Sumba will be evaluated using quantitative and qualitative techniques. The feasibility, acceptability and cost effectiveness of the alternate strategies will then be assessed for the context of both islands.

This strategy is probably inadequate to reduce the

burden of MiP because a substantial proportion of MiP cases remain asymptomatic. The aim of this study is to

component of the study is a cluster randomised controlled trial with two arms. Women in the IST arm are screened

arm are tested for malaria only if they have any sign or symptom of malaria. The primary outcome is placental

women have been enrolled by March 2014. The trIal is expected tobe completed by June 2015.

In a second component of the study, RDT based IST was implemented at pilot scale in a sub-district in

evaluate the implementability of IST including: a pre-post intervention household survey, health facility survey, focus group discussions, in-depth interviews and a costing study.

Economic analysis and evaluations for the Malaria in Pregnancy Consortium.

LSHTM Investigators: Kara Hanson, Silke Fernandes & Jayne

Webster.

External Investigators/Collaborators: Elisa Sicuri (Barcelona

Patrick Walker (Imperial College London, UK); Feiko ter Kuile &

Jenny Hill (Liverpool School of Tropical Medicine, UK).

Funding:


Sitting within the Public Health Impact activity of the

the economics contributions are:

prevention and case management interventions

interventions

Fieldwork was conducted over the course of the past 4 years in 11 countries located in 4 continents and is anticipated to end in early 2015. Data were collected using a variety of methods, including cross-sectional household and facility surveys, exit surveys

building on a recent meta-analysis of clinical trials found

cost-effective compared with two doses of SP. In 2014-15 we will focus our efforts on further data analysis, building cost effectiveness models of Intermittent Screening and

with intermittent preventive treatment and a model of the economic burden of MiP. This analysis will support the development of a map identifying those settings where ISTp may be a more appropriate strategy for preventing the consequences of malaria in pregnancy.

the age of 18 months. Twelve months after vaccination, -

cated and severe malaria was approximately 50% in chil-dren vaccinated when aged 5-17 months but less when it was given to infants aged 6-12 weeks at the same time as routine Expanded Program on Immunization vaccines. Further analysis undertaken 18 months after vaccination showed that protection had been sustained in the older group of children but had waned substantially in infants.

all centres regardless of the level of malaria transmission.

2014 when the majority of trial subjects will have been followed for 3-4 years. It is expected that a decision on registration of the vaccine will be made in 2015 and, if this

guidelines on its use shortly afterwards.

vaccine (257049)(RTS,S/AS01) against malaria disease caused by Plasmodium falciparum in infants and children in Africa.

LSHTM Investigators: Daniel Chandramohan, Chris Drakeley, Brian

External Investigators/Collaborators: The RTS,S Clinical Trials

Partnership.

Funding:

advanced malaria vaccine and is currently being evalu-ated in a phase three trial being conducted in 11 centres

-cruited and randomised to receive three doses of RTS,S/

regimen against plasmodium falciparum ma-laria infection in Senegalese adults.

LSHTM Investigators: Badara Cisse.


-

nostou, Nick Edwards, Babatunde Imoukhuede, Rachel Roberts,

Funding: The European and Developing Countries Clinical Trials

Extensive pre-clinical data indicate that protective im-munity to the liver-stage of malaria can be conferred by

been recently demonstrated in Kenya and it is important -

tween 2012 & 2013, we ran a phase IIb, controlled, single blinded, randomised vaccine trial in Guediawaye. The main objectives were to assess the safety, immunogenic-

We randomly allocated 120 healthy male adult vol-unteers to vaccination with either the vaccine candidate, or verorab as control. Immunogenicity was measured by

--

mia and conducted intensive PCR monitoring to identify new Plasmodium falciparum infections over an eight week follow-up period. Vaccine related adverse events were mild to moderate in intensity with 1 serious adverse event in the control group not related to the intervention.

-

days later as measured by Elispot. Peak immunogenicity was shown 7 days after the boost and was high at a geo-metric mean of 1266 Spots per million PBMCs (95% CI

dose vectored vaccination approach targeting the liver-stage of malaria shows promise as a candidate malaria vaccine.

Vaccine developmentSeveral of our staff have participated in the design, execution and evaluation of RTS,S candidate vaccine trials as well as a trial of a prime boost vaccine candidate in Senegal.

66 Treatment of malaria Treatment of malaria 67


Summary

Malaria Centre members continue to investigate how best to treat malaria, responding to shifting and localised dynamics in parasitological, epidemiological, systemic and political economic contexts.

2012-14 across a range of issues in malaria

treatment, grappling with how interventions

interact with a variety of contextual

methods.

Malaria treatment studies within the Malaria

Centre include attention to antimalarial drugs

effectiveness; strong focus on how antimalarials

are used and how best to support access and

appropriate use through different programmes;

and emphasis on wider case management

questions, with a keen interest in the use of

targeting of antimalarial drugs.

These studies have been carried out across

a range of contexts – in different countries

on different health care providers, including

community volunteers, private retailers and

school teachers as well as formal health facilities.

In so-doing, these studies have contributed to

an increased evidence base of the effects of

different programmes to improve antimalarial

and diagnostic use across a variety of settings.

The studies also explicitly investigate and aim to

antimalarial and diagnostic use, for example

in the context of patients taking antiretroviral

drugs for HIV, or where patients may have

is unreliable, or where knowledge of local

epidemiology of malaria-like illnesses is poor.

Through a lens of research on malaria treatment,

this collection of studies therefore goes beyond

a perspective of drugs as a simple solution,

to investigate how best to implement these in

complex and varied situations of health care

seeking and health care delivery.

To address these topics of research,

the Malaria Centre’s strengths in multiple

disciplines, and interdisciplinary working, are

powerfully displayed. Many of the studies

operate through teams of investigators from

different backgrounds who contribute different

understanding malaria treatment, designing

interventions to support access and use of

biomedical tools, and evaluating interventions to

make a robust contribution to the evidence base

in a way amenable for use by policy makers and

programme managers.

In the studies presented in this section,

answers to research questions have been

conceptual frameworks and modelling allow us

to learn from previous experience and predict

future scenarios; surveys and qualitative studies

of existing situations allow us to learn where

needs are greatest and how best to intervene, as

well as providing a platform for evaluation; and

intervention trials allow us to test solutions in a

implementation research.

These studies provide strong evidence on

a range of questions around how best to treat

malaria across a range of settings with different

biological, infrastructural and social scenarios.

Taken together, they show the importance of

interdisciplinary work and integration of malaria

care seeking and health care systems. This set

of studies represents a substantial contribution

to national and global policy and programme

making.



Summary

Malaria Centre members continue to investigate how best to treat malaria, responding to shifting and localised dynamics in parasitological, epidemiological, systemic and political economic contexts.

2012-14 across a range of issues in malaria

treatment, grappling with how interventions

interact with a variety of contextual

methods.

Malaria treatment studies within the Malaria

Centre include attention to antimalarial drugs

effectiveness; strong focus on how antimalarials

are used and how best to support access and

appropriate use through different programmes;

and emphasis on wider case management

questions, with a keen interest in the use of

targeting of antimalarial drugs.

These studies have been carried out across

a range of contexts – in different countries

on different health care providers, including

community volunteers, private retailers and

school teachers as well as formal health facilities.

In so-doing, these studies have contributed to

an increased evidence base of the effects of

different programmes to improve antimalarial

and diagnostic use across a variety of settings.

The studies also explicitly investigate and aim to

antimalarial and diagnostic use, for example

in the context of patients taking antiretroviral

drugs for HIV, or where patients may have

is unreliable, or where knowledge of local

epidemiology of malaria-like illnesses is poor.

Through a lens of research on malaria treatment,

this collection of studies therefore goes beyond

a perspective of drugs as a simple solution,

to investigate how best to implement these in

complex and varied situations of health care

seeking and health care delivery.

To address these topics of research,

the Malaria Centre’s strengths in multiple

disciplines, and interdisciplinary working, are

powerfully displayed. Many of the studies

operate through teams of investigators from

different backgrounds who contribute different

understanding malaria treatment, designing

interventions to support access and use of

biomedical tools, and evaluating interventions to

make a robust contribution to the evidence base

in a way amenable for use by policy makers and

programme managers.

In the studies presented in this section,

answers to research questions have been

conceptual frameworks and modelling allow us

to learn from previous experience and predict

future scenarios; surveys and qualitative studies

of existing situations allow us to learn where

needs are greatest and how best to intervene, as

well as providing a platform for evaluation; and

intervention trials allow us to test solutions in a

implementation research.

These studies provide strong evidence on

a range of questions around how best to treat

malaria across a range of settings with different

biological, infrastructural and social scenarios.

Taken together, they show the importance of

interdisciplinary work and integration of malaria

care seeking and health care systems. This set

of studies represents a substantial contribution

to national and global policy and programme

making.



The ACT Consortium: a research consortium to optimise the delivery of effective anti-malarial treatment.

Drug studies

Fake artemisinin-based combination therapies –where are they?


External Investigators/Collaborators: Facundo Fernandez

Prevention USA).

Funding:

Consortium.

Reports of ad hocthat up to 50% of the artesunate monotherpy sold

monotherapies and artemisinin-based combination

where the predominant species is the potentially fatal Plasmodium falciparum. Resource poor countries do not

to inspect and police the drug supply.

public and private healthcare providers in Rwanda,

database, the packages scanned and, tablets weighed and measured, followed with qualitative (mass

environmental impact, we are investigating the ageing of

studies, with quantitative analysis carried out at regular intervals. Characterisation of the degradation products is underway.

varying sample collections methods, have been analysed and most have been found to contain the stated active

in the samples between the three collaborating bio analytical laboratories (London School of Hygiene and Tropical Medicine, Georgia Technical School of Chemistry

Counterfeit, medicinal products.

Antimalarial drug samples.

Malaria centre members carry out research related to malaria diagnosis and treatment

effectiveness modelling.

LSHTM Investigators: Evelyn Ansah, Katia Bruxwoort,

Matthew Cairns, Clare Chandler, Daniel Chandramohan, Sian

Harparkash Kaur, Sham Lal, Toby Leslie, Seth Owusu-Agyei,

Hugh Reyburn, Mark Rowland, David Schellenberg, Sarah

Staedke , Rebecca Thomson, Jayne Webster, Christopher

External Investigators/Collaborators: US Centres for

Disease Control and Prevention,USA; College of Medicine,

University of Malawi, Malawi; College of Medicine, University

Institute of Technology, USA; Health Protection and Research

Organisation, Afghanistan; Healthnet, Afghanistan; Ifakara

Health Institute, Tanzania; Karolinska Institutet, Sweden;

Kilimanjaro Christian Medical Centre, Tanzania; Kintampo

Tropical Medicine, UK; Makerere University, Uganda; Merlin,

Afghanistan; National Malaria Control Programme, Cambodia;

National Institute for Medical Research, Tanzania; National

Malaria Control Programme, Tanzania; Ministry of Health,

Kampala, Uganda; University of California, San Francisco,

USA; University of Cape Town, South Africa; University of

Funding:

an international research collaboration aiming to maximise the public health impact of artemisinin-

quality, policy-driven, multidisciplinary operational research. We work on 25 projects in 10 countries and with partners worldwide, using a variety of study of methods to address research questions about:

for those who most need them

through the deployment of rapid diagnostic tests

sub-standard and counterfeit artemisinin drugs

conditions, especially in high risk groups and when used in combination with other drugs.

We conduct formative research, cluster randomised trials, cohort and descriptive studies, and impact evaluation, as well as economic and anthropological assessments



The ACT Consortium: a research consortium to optimise the delivery of effective anti-malarial treatment.

Drug studies

Fake artemisinin-based combination therapies –where are they?


External Investigators/Collaborators: Facundo Fernandez

Prevention USA).

Funding:

Consortium.

Reports of ad hocthat up to 50% of the artesunate monotherpy sold

monotherapies and artemisinin-based combination

where the predominant species is the potentially fatal Plasmodium falciparum. Resource poor countries do not

to inspect and police the drug supply.

public and private healthcare providers in Rwanda,

database, the packages scanned and, tablets weighed and measured, followed with qualitative (mass

environmental impact, we are investigating the ageing of

studies, with quantitative analysis carried out at regular intervals. Characterisation of the degradation products is underway.

varying sample collections methods, have been analysed and most have been found to contain the stated active

in the samples between the three collaborating bio analytical laboratories (London School of Hygiene and Tropical Medicine, Georgia Technical School of Chemistry

Counterfeit, medicinal products.

Antimalarial drug samples.

Malaria centre members carry out research related to malaria diagnosis and treatment

effectiveness modelling.

LSHTM Investigators: Evelyn Ansah, Katia Bruxwoort,

Matthew Cairns, Clare Chandler, Daniel Chandramohan, Sian

Harparkash Kaur, Sham Lal, Toby Leslie, Seth Owusu-Agyei,

Hugh Reyburn, Mark Rowland, David Schellenberg, Sarah

Staedke , Rebecca Thomson, Jayne Webster, Christopher

External Investigators/Collaborators: US Centres for

Disease Control and Prevention,USA; College of Medicine,

University of Malawi, Malawi; College of Medicine, University

Institute of Technology, USA; Health Protection and Research

Organisation, Afghanistan; Healthnet, Afghanistan; Ifakara

Health Institute, Tanzania; Karolinska Institutet, Sweden;

Kilimanjaro Christian Medical Centre, Tanzania; Kintampo

Tropical Medicine, UK; Makerere University, Uganda; Merlin,

Afghanistan; National Malaria Control Programme, Cambodia;

National Institute for Medical Research, Tanzania; National

Malaria Control Programme, Tanzania; Ministry of Health,

Kampala, Uganda; University of California, San Francisco,

USA; University of Cape Town, South Africa; University of

Funding:

an international research collaboration aiming to maximise the public health impact of artemisinin-

quality, policy-driven, multidisciplinary operational research. We work on 25 projects in 10 countries and with partners worldwide, using a variety of study of methods to address research questions about:

for those who most need them

through the deployment of rapid diagnostic tests

sub-standard and counterfeit artemisinin drugs

conditions, especially in high risk groups and when used in combination with other drugs.

We conduct formative research, cluster randomised trials, cohort and descriptive studies, and impact evaluation, as well as economic and anthropological assessments



Surveillance approaches to detect the quality of antimalarial drugs in Senegal.

LSHTM Investigators: Mirza Lalani, Harparkash Kaur, Sian Clarke

& Jayne Webster.

External Investigators/Collaborators: Aminata Dior Ndiaye (Uni-

versity of Cheikh Anta Diop, Senegal).

Funding:

Fund.

The aim of this study was to establish the perceptions of stakeholders relating to their institutional roles and responsibilities for assuring the quality of drugs and the perceived strengths and weaknesses of the drug quality surveillance system in Senegal.

In-depth qualitative interviews were conducted with key stakeholders; representatives of the surveillance sys-tem authorities and treatment providers in the regulated public and private health sectors. The interview guide focussed on two main aspects; system context including challenges faced and institutional roles and responsibili-

increase the risk of poor quality antimalarials in Senegal. Within this a health systems lens was applied allowing for inductive expansion of emergent themes relating to the six building blocks of health systems.

Preliminary analysis of the data indicates that all stakeholders perceive that the system operates effectively

authorities and between authorities and treatment pro-viders is perceived to be a problem. Perceptions of the quality of antimalarials are related to their cost, country of

-ditions and the informal drug sector are seen as the two main risk factors for poor quality antimalarials in Senegal.

Stringent drug regulation and a secure drug supply

the quality of antimalarials available Senegal. However a lack of funding, issues of governance, inadequate human resource and an absence of monitoring of the informal sector (due to concerns that acknowledgment would le-

that has been made by national authorities and external partners in assuring drug quality in Senegal.

sub-study focussing on one component of a drug quality surveillance system - drug quality analysis is in progress. Data collection was undertaken at the Laboratoire Natio-nale de Contrôle des Medicaments in Dakar, Senegal. The sub-study focussed on the practical utility and per-ceptions of usefulness of a drug quality screening test the

Use of artemether-lumefantrine in the treatment of asymptomatic malaria in HIV-positive and HIV-negative Nigerian adults.

LSHTM Investigators: Ifeyinwa Nwogo Chijioke-Nwauche, Mary

Oguike, Khalid Beshir, Harparkash Kaur & Colin Sutherland.

External Investigators/Collaborators: Chijioke Nwauche (Univer-

sity of Port Harcourt, Nigeria).

Funding: Rivers State Sustainable Development Agency; the MA-

LACTRES Consortium.

in the treatment of asymptomatic-malaria in HIV-positive and HIV-negative Nigerian adults.

Plasmodium falciparum and the use of medication for HIV management

-mether-lumefantrine and antiretroviral drugs

-mether-lumefantrine and other antimalarial drugs

-ymptomatic infections completely, as judged by post hoc PCR. HIV-positive people on nevirapine harbour higher concentrations of peripheral blood lumefantrine on day 7 post-treatment, and were also more likely to harbour par-asitaemia before and after treatment. There was a strong selection for the N allele in those with PCR-detectable parasitaemia at day 3. This allele has previ-

T was observed especially in the HIV-positive group, indicating that CQ resistant parasites are common in this setting. Primary diagnosis of parasite infections was performed locally by

a high rate of false positives, and thus over-estimation of the number of malaria infections. Future studies will be carried out to include children and pregnant women in a

will be carried out at multiple sites around Port Harcourt

need to invest in equipment and training of personnel for improved quality of malaria diagnosis.

artemisinin-based combination therapies in four endemic sites in Africa – the WANECAM Consortium.

LSHTM Investigators: Colin Sutherland & Khalid Beshir.

External Investigators/Collaborators: West African Network for

Clinical trials of AntiMalarial drugs; Malaria Research and Training

et de Formation sur le Paludisme, Burkina Faso; Institut de Re-

-

-

nard, France; Karolinska Institutet, Sweden; University of Heidelberg

Funding: European and Developing Countries Clinical Trials Part-

nership Programme through the West African Network for Clinical

trials of AntiMalarial drugs.

To overcome the challenge of frequent sampling and lack of microscopic sensitivity, we have developed a rapid and

-

We have recently shown that the presence of persis--

cantly associated with presence of gametocyte on day-7, infectiousness to mosquitoes and recrudescent parasites 28- or 42-days after treatment in Kenyan children (Beshir

infectivity was a step in the development of resistance to the old anti-malarial drugs chloroquine and sulphadoxine pyrimethamine.

-ing qPCR.

treatment arms

clearance and gametocyte carriage, infectivity to mos-quito and recurrent parasitemia

episode-1 and episode-2

clearance and candidate molecular markers (pfcrt and

technique, and in analysis of trial data

Khalid Beshir on his visit to Abdoulaye Djimde’s laboratory in Mali and staff who received training on measurement of malaria parasitemia using quantitative real-time PCR.

Modelling the cost-effectiveness of options for the radical cure of Plasmodium vivax.

LSHTM Investigators


Thailand).

Funding:

Plasmodium vivax causes a huge burden of disease Plasmodium falciparum, it

forms hypnozoites which can cause repeated relapses. The only class of drugs effective against hypnozoites is 8-aminoquinolones however, these have the potential to cause life-threatening haemolysis in patients with G6PD

The aim of this project is to examine the cost-effectiveness of adding an 8-aminoquinolone with or

cure of symptomatic infection with Plasmodium vivax.We used a combination of a decision tree model with

Markov cycle, to model the cost-effectiveness of different strategies managing symptomatic patients ie with and without an 8-aminoquinolone, and with and without prior

The model results are very sensitive to key uncertainties such as the level of adherence to primaquine and the likelihood of heamolysis in patients. However, when adherence levels were high, in most scenarios treatment with an 8-aminoquinolone with prior G6PD testing came out as the most cost-effective option.



Surveillance approaches to detect the quality of antimalarial drugs in Senegal.

LSHTM Investigators: Mirza Lalani, Harparkash Kaur, Sian Clarke

& Jayne Webster.

External Investigators/Collaborators: Aminata Dior Ndiaye (Uni-

versity of Cheikh Anta Diop, Senegal).

Funding:

Fund.

The aim of this study was to establish the perceptions of stakeholders relating to their institutional roles and responsibilities for assuring the quality of drugs and the perceived strengths and weaknesses of the drug quality surveillance system in Senegal.

In-depth qualitative interviews were conducted with key stakeholders; representatives of the surveillance sys-tem authorities and treatment providers in the regulated public and private health sectors. The interview guide focussed on two main aspects; system context including challenges faced and institutional roles and responsibili-

increase the risk of poor quality antimalarials in Senegal. Within this a health systems lens was applied allowing for inductive expansion of emergent themes relating to the six building blocks of health systems.

Preliminary analysis of the data indicates that all stakeholders perceive that the system operates effectively

authorities and between authorities and treatment pro-viders is perceived to be a problem. Perceptions of the quality of antimalarials are related to their cost, country of

-ditions and the informal drug sector are seen as the two main risk factors for poor quality antimalarials in Senegal.

Stringent drug regulation and a secure drug supply

the quality of antimalarials available Senegal. However a lack of funding, issues of governance, inadequate human resource and an absence of monitoring of the informal sector (due to concerns that acknowledgment would le-

that has been made by national authorities and external partners in assuring drug quality in Senegal.

sub-study focussing on one component of a drug quality surveillance system - drug quality analysis is in progress. Data collection was undertaken at the Laboratoire Natio-nale de Contrôle des Medicaments in Dakar, Senegal. The sub-study focussed on the practical utility and per-ceptions of usefulness of a drug quality screening test the

Use of artemether-lumefantrine in the treatment of asymptomatic malaria in HIV-positive and HIV-negative Nigerian adults.

LSHTM Investigators: Ifeyinwa Nwogo Chijioke-Nwauche, Mary

Oguike, Khalid Beshir, Harparkash Kaur & Colin Sutherland.

External Investigators/Collaborators: Chijioke Nwauche (Univer-

sity of Port Harcourt, Nigeria).

Funding: Rivers State Sustainable Development Agency; the MA-

LACTRES Consortium.

in the treatment of asymptomatic-malaria in HIV-positive and HIV-negative Nigerian adults.

Plasmodium falciparum and the use of medication for HIV management

-mether-lumefantrine and antiretroviral drugs

-mether-lumefantrine and other antimalarial drugs

-ymptomatic infections completely, as judged by post hoc PCR. HIV-positive people on nevirapine harbour higher concentrations of peripheral blood lumefantrine on day 7 post-treatment, and were also more likely to harbour par-asitaemia before and after treatment. There was a strong selection for the N allele in those with PCR-detectable parasitaemia at day 3. This allele has previ-

T was observed especially in the HIV-positive group, indicating that CQ resistant parasites are common in this setting. Primary diagnosis of parasite infections was performed locally by

a high rate of false positives, and thus over-estimation of the number of malaria infections. Future studies will be carried out to include children and pregnant women in a

will be carried out at multiple sites around Port Harcourt

need to invest in equipment and training of personnel for improved quality of malaria diagnosis.

artemisinin-based combination therapies in four endemic sites in Africa – the WANECAM Consortium.

LSHTM Investigators: Colin Sutherland & Khalid Beshir.

External Investigators/Collaborators: West African Network for

Clinical trials of AntiMalarial drugs; Malaria Research and Training

et de Formation sur le Paludisme, Burkina Faso; Institut de Re-

-

-

nard, France; Karolinska Institutet, Sweden; University of Heidelberg

Funding: European and Developing Countries Clinical Trials Part-

nership Programme through the West African Network for Clinical

trials of AntiMalarial drugs.

To overcome the challenge of frequent sampling and lack of microscopic sensitivity, we have developed a rapid and

-

We have recently shown that the presence of persis--

cantly associated with presence of gametocyte on day-7, infectiousness to mosquitoes and recrudescent parasites 28- or 42-days after treatment in Kenyan children (Beshir

infectivity was a step in the development of resistance to the old anti-malarial drugs chloroquine and sulphadoxine pyrimethamine.

-ing qPCR.

treatment arms

clearance and gametocyte carriage, infectivity to mos-quito and recurrent parasitemia

episode-1 and episode-2

clearance and candidate molecular markers (pfcrt and

technique, and in analysis of trial data

Khalid Beshir on his visit to Abdoulaye Djimde’s laboratory in Mali and staff who received training on measurement of malaria parasitemia using quantitative real-time PCR.

Modelling the cost-effectiveness of options for the radical cure of Plasmodium vivax.

LSHTM Investigators


Thailand).

Funding:

Plasmodium vivax causes a huge burden of disease Plasmodium falciparum, it

forms hypnozoites which can cause repeated relapses. The only class of drugs effective against hypnozoites is 8-aminoquinolones however, these have the potential to cause life-threatening haemolysis in patients with G6PD

The aim of this project is to examine the cost-effectiveness of adding an 8-aminoquinolone with or

cure of symptomatic infection with Plasmodium vivax.We used a combination of a decision tree model with

Markov cycle, to model the cost-effectiveness of different strategies managing symptomatic patients ie with and without an 8-aminoquinolone, and with and without prior

The model results are very sensitive to key uncertainties such as the level of adherence to primaquine and the likelihood of heamolysis in patients. However, when adherence levels were high, in most scenarios treatment with an 8-aminoquinolone with prior G6PD testing came out as the most cost-effective option.



ivermectin to prevent malaria transmission after treatment: a double-blind, randomised clinical trial.

LSHTM Investigators: Teun Bousema & Chris Drakeley.


Edith Bougouma, Issa Nebie, Maurice San Ouattara, Sodiomon

Sirima (Centre National de Recherche et de Formation sur le

Sauerwein (Radboud University Medical Center, Netherlands);

Kevin Kobylinski (Walter Reed Army Institute of Research, USA);

Lawrence Fleckenstein (University of Iowa, USA) & Hannah Slater,

Thomas Churcher (Imperial College London, UK).

Funding: The Radboud University Medical Center; The Bill &

by Novartis.

asexual malaria parasites and immature gametocytes but does not prevent post-treatment malaria transmission.

killing mosquitoes that take blood meals from IVM treated humans. In a double-blinded placebo-controlled trial, 120

asymptomatic Plasmodium falciparum parasite carriers were randomised to receive artemether-lumefantrine

feeding was performed 1, 3, and 7 days after initiation of treatment to determine Anopheles gambiae and Anopheles funestus survival and infection rates. IVM resulted in a 4 to 7-fold increased mortality in mosquitoes

levels were positively associated with body mass index

until 7 days after a single dose of IVM (hazard rate ratio

evidence that IVM reduced Plasmodium infection rates among surviving mosquitoes, the mosquitocidal effect

reductions in the patients contribution to transmission

respectively. We conclude that IVM can be safely given

malaria transmission by reducing the lifespan of feeding mosquitoes. Future work should aim to maximise the duration of the mosquitocidal effect.

-

Community-based case managementA key area of our work focuses on understanding and evaluating interventions to improve case management of malaria and the use of artemisinin-based combination therapy in the community (private retail outlets, community health workers and schools) as well as evaluation of the Affordable Medicines Facility for malaria.

Village Malaria Worker Access to Treatment (VIMWAT) study.

LSHTM Investigators

Edith Patouillard & Tom Drake.

External Investigators/Collaborators: Chea Nguon & Poly Teng

(National Malaria Control Programme, Cambodia).

Funding: Clinton Health Access Initiative; The Department for

through the ACT Consortium.

In Cambodia the national malaria control programme

in 2004. VMWs are community volunteers who perform

malaria cases with artemisinin-based combination

In selected villages, VMWs have an expanded role to diagnose and treat acute respiratory infections and

diarrhoea with antibiotics or oral rehydration salts and Zinc respectively for children under 5 years.

effectiveness and cost of the VMW programme in delivering prompt access to appropriate diagnosis and

in children. In Kampot province, 1,152 households in villages with malaria only VMWs, expanded role VMWs or no VMWs were followed up over 6 months in order to capture information on illnesses experienced and health seeking behaviour. Total annual programme costs were calculated from 2004 to 2010.

The number of reported suspected malaria episodes

the selected province However for individuals who did report suspected malaria, those from villages with VMWs were more likely to receive appropriate diagnosis with a blood test, than in villages without VMWs.



ivermectin to prevent malaria transmission after treatment: a double-blind, randomised clinical trial.

LSHTM Investigators: Teun Bousema & Chris Drakeley.


Edith Bougouma, Issa Nebie, Maurice San Ouattara, Sodiomon

Sirima (Centre National de Recherche et de Formation sur le

Sauerwein (Radboud University Medical Center, Netherlands);

Kevin Kobylinski (Walter Reed Army Institute of Research, USA);

Lawrence Fleckenstein (University of Iowa, USA) & Hannah Slater,

Thomas Churcher (Imperial College London, UK).

Funding: The Radboud University Medical Center; The Bill &

by Novartis.

asexual malaria parasites and immature gametocytes but does not prevent post-treatment malaria transmission.

killing mosquitoes that take blood meals from IVM treated humans. In a double-blinded placebo-controlled trial, 120

asymptomatic Plasmodium falciparum parasite carriers were randomised to receive artemether-lumefantrine

feeding was performed 1, 3, and 7 days after initiation of treatment to determine Anopheles gambiae and Anopheles funestus survival and infection rates. IVM resulted in a 4 to 7-fold increased mortality in mosquitoes

levels were positively associated with body mass index

until 7 days after a single dose of IVM (hazard rate ratio

evidence that IVM reduced Plasmodium infection rates among surviving mosquitoes, the mosquitocidal effect

reductions in the patients contribution to transmission

respectively. We conclude that IVM can be safely given

malaria transmission by reducing the lifespan of feeding mosquitoes. Future work should aim to maximise the duration of the mosquitocidal effect.

-

Community-based case managementA key area of our work focuses on understanding and evaluating interventions to improve case management of malaria and the use of artemisinin-based combination therapy in the community (private retail outlets, community health workers and schools) as well as evaluation of the Affordable Medicines Facility for malaria.

Village Malaria Worker Access to Treatment (VIMWAT) study.

LSHTM Investigators

Edith Patouillard & Tom Drake.

External Investigators/Collaborators: Chea Nguon & Poly Teng

(National Malaria Control Programme, Cambodia).

Funding: Clinton Health Access Initiative; The Department for


In Cambodia the national malaria control programme

in 2004. VMWs are community volunteers who perform

malaria cases with artemisinin-based combination

In selected villages, VMWs have an expanded role to diagnose and treat acute respiratory infections and

diarrhoea with antibiotics or oral rehydration salts and Zinc respectively for children under 5 years.

effectiveness and cost of the VMW programme in delivering prompt access to appropriate diagnosis and

in children. In Kampot province, 1,152 households in villages with malaria only VMWs, expanded role VMWs or no VMWs were followed up over 6 months in order to capture information on illnesses experienced and health seeking behaviour. Total annual programme costs were calculated from 2004 to 2010.

The number of reported suspected malaria episodes

the selected province However for individuals who did report suspected malaria, those from villages with VMWs were more likely to receive appropriate diagnosis with a blood test, than in villages without VMWs.



Independent evaluation of the Affordable Medicines Facility – malaria (AMFm).

LSHTM Investigators: Barbara Willey, Sarah Tougher, Andrea

Mann, Rebecca Thomson, Sergio Torres Rueda, Didier Diallo, Katia

External Investigators/Collaborators: ICF-International;

ACTwatch; Population Services International, Kenya; Ifakara Health

Health Research Centre, Kenya; Centre de Recherche pour le

Recherches sur les Populations Africaines, Niger.

Funding:

Consortium.

Medicines Facility – malaria to increase the access and use of quality-assured artemisinin-based combination

factory gate price subsidies, and supporting interventions such as communications campaigns. We conducted an evaluation of the programme to estimate its impact

Ghana, Kenya, Madagascar, Niger, Nigeria, Uganda, and

Data included nationally representative baseline and endline surveys of public and private sector outlets stocking antimalarials, and key informant interviews and document reviews to record contextual factors and the implementation process.

In all pilots except Niger and Madagascar, there

were seen in the PFP sector in six pilots, ranging from

where it was not minimal at baseline. We concluded that subsidies combined with

supporting interventions can be eff ective in rapidly improving availability, price, and market share of

Mystery clients and drug cocktails.

LSHTM Investigators

Mikhael Dsouza.

External Investigators/Collaborators: Facundo Fernandez &

& Ouk Rada (National Malaria control programme, Cambodia).

Funding:

Consortium.

In Cambodia, as in other countries in Southeast asia, it is common practice for patients seeking treatment for fever to be sold little packets containing a colourful combination of different tablets and capsules. However, the content of these “drug cocktails” is largely unknown.

This study aimed to identify the contents of these drug cocktails through a mystery client study where

to drug shops and pharmacies, seeking treatment for

an experienced pharmacist. Two hundred and ten providers were visited from

whom 191 drug cocktails were bought. The median

of tablets were for symptomatic relief (anti-pyretic, anti-

commonly found, as were antimalarials and occasionally steroids. This has important implications both for individual patients and public health in terms of the inappropriate use of antimicrobials and drug resistance.

An economic analysis of the Affordable Medicines Facility - malaria (AMFm).

LSHTM Investigators: Sarah Tougher, Kara Hanson & Catherine


Poyer, Julius Njogu, Illah Evance, Meghan Littrell, & Desmond

Chavasse (ACTwatch & Population Services International); Jennifer

Anyanti & Ekundayo Arogundade (Society for Family Health); Perter

Buyungo & Henry Kaula (PACE, Uganda).

Funding:

sector, subsidies for artemisinin-based combination

endemic countries, have been implemented in a number

other treatments. The largest initiative of this type was the

was implemented at a national scale in eight pilots in seven countries from 2010-2013.

share in six of the eight pilots. However, little is known about the causes of inter- and intra- country variations in performance, or the equity impact of the programme.

This study uses existing outlet and household survey data to establish the impact of market structure on performance of markets for antimalarials in three

to model provider decisions to stock and set prices for subsidized medicines, as these aspects of provider behavior are critical to a subsidy programme’s success. The household survey data will be used to assess the

Evidence from this study will be available in 2014,

and the types of supporting interventions and their targeting that are most appropriate.



Independent evaluation of the Affordable Medicines Facility – malaria (AMFm).

LSHTM Investigators: Barbara Willey, Sarah Tougher, Andrea


External Investigators/Collaborators: ICF-International;

ACTwatch; Population Services International, Kenya; Ifakara Health

Health Research Centre, Kenya; Centre de Recherche pour le

Recherches sur les Populations Africaines, Niger.

Funding:

Consortium.

Medicines Facility – malaria to increase the access and use of quality-assured artemisinin-based combination

factory gate price subsidies, and supporting interventions such as communications campaigns. We conducted an evaluation of the programme to estimate its impact

Ghana, Kenya, Madagascar, Niger, Nigeria, Uganda, and

Data included nationally representative baseline and endline surveys of public and private sector outlets stocking antimalarials, and key informant interviews and document reviews to record contextual factors and the implementation process.

In all pilots except Niger and Madagascar, there

were seen in the PFP sector in six pilots, ranging from

where it was not minimal at baseline. We concluded that subsidies combined with

supporting interventions can be eff ective in rapidly improving availability, price, and market share of

Mystery clients and drug cocktails.

LSHTM Investigators

Mikhael Dsouza.

External Investigators/Collaborators: Facundo Fernandez &

& Ouk Rada (National Malaria control programme, Cambodia).

Funding:

Consortium.

In Cambodia, as in other countries in Southeast asia, it is common practice for patients seeking treatment for fever to be sold little packets containing a colourful combination of different tablets and capsules. However, the content of these “drug cocktails” is largely unknown.

This study aimed to identify the contents of these drug cocktails through a mystery client study where

to drug shops and pharmacies, seeking treatment for

an experienced pharmacist. Two hundred and ten providers were visited from

whom 191 drug cocktails were bought. The median

of tablets were for symptomatic relief (anti-pyretic, anti-

commonly found, as were antimalarials and occasionally steroids. This has important implications both for individual patients and public health in terms of the inappropriate use of antimicrobials and drug resistance.

An economic analysis of the Affordable Medicines Facility - malaria (AMFm).

LSHTM Investigators: Sarah Tougher, Kara Hanson & Catherine


Poyer, Julius Njogu, Illah Evance, Meghan Littrell, & Desmond

Chavasse (ACTwatch & Population Services International); Jennifer

Anyanti & Ekundayo Arogundade (Society for Family Health); Perter

Buyungo & Henry Kaula (PACE, Uganda).

Funding:

sector, subsidies for artemisinin-based combination

endemic countries, have been implemented in a number

other treatments. The largest initiative of this type was the

was implemented at a national scale in eight pilots in seven countries from 2010-2013.

share in six of the eight pilots. However, little is known about the causes of inter- and intra- country variations in performance, or the equity impact of the programme.

This study uses existing outlet and household survey data to establish the impact of market structure on performance of markets for antimalarials in three

to model provider decisions to stock and set prices for subsidized medicines, as these aspects of provider behavior are critical to a subsidy programme’s success. The household survey data will be used to assess the

Evidence from this study will be available in 2014,

and the types of supporting interventions and their targeting that are most appropriate.



A cost-consequences analysis of the Affordable Medicines Facility - malaria (AMFm).

LSHTM Investigators: Fiona Cianci, Daniel Cobos, Sarah Tougher,

Funding:

In 2010 the Global Fund launched national scale

assured artemisinin-based combination therapies

involved manufacturer price negotiations, factory gate price subsidies, and supporting interventions such as

Communicating the Affordable Medicines Facility - malaria (AMFm) message: exploring the effect of communication and training

awareness and knowledge related to a multi-country anti-malarial subsidy intervention.

LSHTM Investigators



Arnold, Ruilin Ren & Abdinasir Amin (ICF International, USA); The

Johanes, Charles Festo & Admirabilis Kalolella (Ifakara Health

Institute, Tanzania); Idrissa Kourgueni, Moctar Seydou & Oumarou

Malam (Institut National de la Statistique, Niger); John Amuasi,

Samuel Blay Nguah & Daniel Ansong (Komfo Anokye Teaching

Population and Health Research Center, Kenya); Mark Taylor

(Trnava University, Slovakia); Salif Ndiaye (Centre de Recherche

for Neglected Diseases initiative, Switzerland); Catherine Adegoke

(Phar-Mark Consultants, Nigeria).

Funding:

Central and ACTwatch surveys in three countries.

or territories, subsidized quality-assured artemisinin

campaigns to support implementation and promote appropriate anti-malarial use. This project reports private

of appropriate malaria treatment, based on nationally representative surveys of outlets stocking anti-malarials

Based on data from over 19,500 outlets, results show that in four of eight settings, where communication campaigns were implemented for 5–9 months, 76%-94%

80% awareness of the correct recommended retail price

remaining four settings where communication campaigns were implemented for three months or less, levels were substantially lower. In six of eight settings, increases

uncomplicated malaria were seen; and in three of these the levels of knowledge achieved at endline were over 80%.

The results support the interpretation that, in addition

communication campaigns may have contributed to

communications campaigns. We conducted a cost-consequences analysis of

Nigeria and Madagascar. Data were collected in the

secretariat in Geneva. Cost data were collected through

Consequences data were collated through literature review.

Results will be available in late 2014, providing

the consequences in terms of a range of outcomes, and

in other settings.

School-based programme of malaria diagnosis and treatment in Malawi.

LSHTM Investigators: Simon Brooker, Katherine Halliday, Stefan

Witek-McManus, Elizabeth Allen & Rebecca Jones.

External Investigators/Collaborators: Don Mathanga (Malaria

Alert Centre, College of Medicine, Malawi); Doreen Ali & John Sande

(National Malaria Control Programme, Ministry of Health, Malawi);

Reuben Mwenda (Health Technical Support Services-Diagnostics,

Ministry of Health, Malawi); Charles Mazinga (Ministry of Education,

Science and Technology, Malawi); Austin Mtali & Tiyese Chimuna

(Save the Children International, Malawi); Natalie Roschnik (Save

the Children International, USA).

Funding: International Initiative for Impact Evaluation & Save the

Children Sponsorship funds.

With increasing levels of attendance, schools present a credible and pragmatic opportunity to improve the access of school children to timely diagnosis and treatment of clinical malaria, increasingly recognised as a major

evaluating the impact of a programme of teacher-based diagnosis and treatment for uncomplicated malaria on primary school attendance in 58 schools in Zomba, Malawi.

The pilot programme, implemented by the National Malaria control Programme in conjunction with Save the Children, involves training teachers in 29 randomly

artemether-lumefantrine to treat uncomplicated malaria.

the programme is ongoing in the schools with oversight

Researchers at the London School of Hygiene &

evaluating the programme, with ongoing monitoring of attendance throughout the school year. Secondary

nested process evaluation employing mixed methods will evaluate the cost effectiveness, feasibility and community acceptability of the school-based programme

Investigating the determinants of demand for antimalarial medicines in Benin, Nigeria, Uganda and Zambia.

LSHTM Investigators: Benjamin Palafox & Kara Hanson.

Funding: The Economic and Social Research Council

By 2008, all malaria endemic countries had adopted

particularly among children under 5 years of age for whom presumptive treatment continues to be widely accepted and practised where access to diagnostic testing is limited. Price is a critical barrier to their wider

prices including the national-level subsidy programme,

Maximising the impact of these investments and

requires an understanding of how responsive demand is to price and other determinants. To do this, we are using econometric demand models to analyse the determinants

of antimalarial choice in Benin, Madagascar, Uganda and Zambia. We are also examining changes in treatment seeking behaviour over time, making use of multiple rounds of household survey data.

In each country, data were collected through nationally representative surveys of households that experienced a recent paediatric febrile episode. This was complemented by survey data from all possible public and private sources of antimalarial medicines in the

artemisinin monotherapies, non-artemisinin therapies, and no treatment. The range of determinants being studied include the price of various treatment components



A cost-consequences analysis of the Affordable Medicines Facility - malaria (AMFm).

LSHTM Investigators: Fiona Cianci, Daniel Cobos, Sarah Tougher,

Funding:

In 2010 the Global Fund launched national scale

assured artemisinin-based combination therapies

involved manufacturer price negotiations, factory gate price subsidies, and supporting interventions such as

Communicating the Affordable Medicines Facility - malaria (AMFm) message: exploring the effect of communication and training

awareness and knowledge related to a multi-country anti-malarial subsidy intervention.

LSHTM Investigators



Arnold, Ruilin Ren & Abdinasir Amin (ICF International, USA); The

Johanes, Charles Festo & Admirabilis Kalolella (Ifakara Health

Institute, Tanzania); Idrissa Kourgueni, Moctar Seydou & Oumarou

Malam (Institut National de la Statistique, Niger); John Amuasi,

Samuel Blay Nguah & Daniel Ansong (Komfo Anokye Teaching

Population and Health Research Center, Kenya); Mark Taylor

(Trnava University, Slovakia); Salif Ndiaye (Centre de Recherche

for Neglected Diseases initiative, Switzerland); Catherine Adegoke

(Phar-Mark Consultants, Nigeria).

Funding:

Central and ACTwatch surveys in three countries.

or territories, subsidized quality-assured artemisinin

campaigns to support implementation and promote appropriate anti-malarial use. This project reports private

of appropriate malaria treatment, based on nationally representative surveys of outlets stocking anti-malarials

Based on data from over 19,500 outlets, results show that in four of eight settings, where communication campaigns were implemented for 5–9 months, 76%-94%

80% awareness of the correct recommended retail price

remaining four settings where communication campaigns were implemented for three months or less, levels were substantially lower. In six of eight settings, increases

uncomplicated malaria were seen; and in three of these the levels of knowledge achieved at endline were over 80%.

The results support the interpretation that, in addition

communication campaigns may have contributed to

communications campaigns. We conducted a cost-consequences analysis of

Nigeria and Madagascar. Data were collected in the

secretariat in Geneva. Cost data were collected through

Consequences data were collated through literature review.

Results will be available in late 2014, providing

the consequences in terms of a range of outcomes, and

in other settings.

School-based programme of malaria diagnosis and treatment in Malawi.

LSHTM Investigators: Simon Brooker, Katherine Halliday, Stefan

Witek-McManus, Elizabeth Allen & Rebecca Jones.

External Investigators/Collaborators: Don Mathanga (Malaria

Alert Centre, College of Medicine, Malawi); Doreen Ali & John Sande

(National Malaria Control Programme, Ministry of Health, Malawi);

Reuben Mwenda (Health Technical Support Services-Diagnostics,

Ministry of Health, Malawi); Charles Mazinga (Ministry of Education,

Science and Technology, Malawi); Austin Mtali & Tiyese Chimuna

(Save the Children International, Malawi); Natalie Roschnik (Save

the Children International, USA).

Funding: International Initiative for Impact Evaluation & Save the

Children Sponsorship funds.

With increasing levels of attendance, schools present a credible and pragmatic opportunity to improve the access of school children to timely diagnosis and treatment of clinical malaria, increasingly recognised as a major

evaluating the impact of a programme of teacher-based diagnosis and treatment for uncomplicated malaria on primary school attendance in 58 schools in Zomba, Malawi.

The pilot programme, implemented by the National Malaria control Programme in conjunction with Save the Children, involves training teachers in 29 randomly

artemether-lumefantrine to treat uncomplicated malaria.

the programme is ongoing in the schools with oversight

Researchers at the London School of Hygiene &

evaluating the programme, with ongoing monitoring of attendance throughout the school year. Secondary

nested process evaluation employing mixed methods will evaluate the cost effectiveness, feasibility and community acceptability of the school-based programme

Investigating the determinants of demand for antimalarial medicines in Benin, Nigeria, Uganda and Zambia.

LSHTM Investigators: Benjamin Palafox & Kara Hanson.

Funding: The Economic and Social Research Council

By 2008, all malaria endemic countries had adopted

particularly among children under 5 years of age for whom presumptive treatment continues to be widely accepted and practised where access to diagnostic testing is limited. Price is a critical barrier to their wider

prices including the national-level subsidy programme,

Maximising the impact of these investments and

requires an understanding of how responsive demand is to price and other determinants. To do this, we are using econometric demand models to analyse the determinants

of antimalarial choice in Benin, Madagascar, Uganda and Zambia. We are also examining changes in treatment seeking behaviour over time, making use of multiple rounds of household survey data.

In each country, data were collected through nationally representative surveys of households that experienced a recent paediatric febrile episode. This was complemented by survey data from all possible public and private sources of antimalarial medicines in the

artemisinin monotherapies, non-artemisinin therapies, and no treatment. The range of determinants being studied include the price of various treatment components



Introducing rapid diagnostic tests in drug shops to improve the targeting of malaria treatment.

LSHTM Investigators: Sian

Clarke, Kristian Hansen, Clare

Chandler & Sham Lal.

External Investigators/

Collaborators: Anthony Mbonye

(Ministry of Health, Kampala,

Uganda); Pascal Magnussen

(University of Copenhagen,

Denmark).

Funding: The Wellcome Trust; The


conducted in 59 registered drug shops in Uganda to assess the feasibility of introducing rapid diagnostic

shops in order to promote the rational and correct use of artemisinin-based

drugs when managing cases of malaria.

Drug shop vendors were also trained on malaria case

rectal artesunate pre-referral treatment, and when to refer. The trial compared treatment practices in shops trained to base malaria treatment on an RDT test result with the current approach of treating patients based solely on their symptoms, To examine whether RDTs improved targeting of

patient determined by expert microscopy on a research blood slide collected at the time of drug shop visit.The study found that the vast majority of patients accepted purchasing a rapid diagnostic test, and that over 85%

qualitative evaluation conducted alongside the trial found diagnostic testing was popular with both patients and providers, and fundamentally transformed the perception and role of drug shops.

Pictorial job aid used by drug shop vendors to guide treatment for drug shops in Uganda.

Use of rapid diagnostic tests in Uganda to improve malaria treatment in the community.

LSHTM Investigators: Sian Clarke, Kristian Hansen, Clare


External Investigators/Collaborators: Richard Ndyomugyenyi

(National Malaria Control Programme, Uganda); Pascal Magnussen

(Univeristy of Copenhagen, Denmark).

Funding:

Consortium.

This randomised trial aims to assess whether the use of rapid diagnostic tests by community health workers

managing cases of malaria in the community. The trial compared home-based management of

malaria based on the results of rapid diagnostic tests

based solely on their symptoms, in two areas of high

were also trained on malaria case management including

to refer. To determine whether use of RDTs improved

by CHWs were evaluated against the malaria parasite infection status of the patient as detected by expert microscopy on a research blood slide collected at the time of consultation.

Early analysis suggests that over 85% of the community medicine distributors complied with the results of rapid diagnostic tests. The community were also aware that not all fever is caused by malaria, which increased

Introducing rapid diagnostic tests into the private health sector: a cost-effectiveness analysis among registered drug shops in Mukono district, Uganda.

LSHTM Investigators: Kristian Hansen, Sian Clarke & Sham Lal.

External Investigators/Collaborators: Anthony Mbonye (Ministry

of Health, Kampala, Uganda); Pascal Magnussen (University of

Copenhagen, Denmark).

Funding:


It is common in Uganda for people to seek treatment for malaria in private drug shops where parasitological diagnosis to guide malaria treatment is not usually

to perform and have high accuracy, these tests could feasibly be offered in drug shops.

a cluster-randomised trial in Mukono district, Uganda, where drug shops were randomised either to prescribe

perspective incorporating provider costs (training,

health care seeking for malaria treatment. Preliminary results suggest that the total cost of providing malaria services in drug shops with access to RDT diagnosis was at least 15% higher than in drug shops providing presumptive diagnosis. However, the share of appropriately treated fever patients was much higher in RDT drug shops compared to drug shops with

the incremental cost of replacing presumptive diagnosis by RDT diagnosis in drug shops could therefore still be as low as US$2-3 per additional patient appropriately treated.



Introducing rapid diagnostic tests in drug shops to improve the targeting of malaria treatment.

LSHTM Investigators: Sian

Clarke, Kristian Hansen, Clare


External Investigators/

Collaborators: Anthony Mbonye

(Ministry of Health, Kampala,

Uganda); Pascal Magnussen

(University of Copenhagen,

Denmark).

Funding: The Wellcome Trust; The


conducted in 59 registered drug shops in Uganda to assess the feasibility of introducing rapid diagnostic

shops in order to promote the rational and correct use of artemisinin-based

drugs when managing cases of malaria.

Drug shop vendors were also trained on malaria case

rectal artesunate pre-referral treatment, and when to refer. The trial compared treatment practices in shops trained to base malaria treatment on an RDT test result with the current approach of treating patients based solely on their symptoms, To examine whether RDTs improved targeting of

patient determined by expert microscopy on a research blood slide collected at the time of drug shop visit.The study found that the vast majority of patients accepted purchasing a rapid diagnostic test, and that over 85%

qualitative evaluation conducted alongside the trial found diagnostic testing was popular with both patients and providers, and fundamentally transformed the perception and role of drug shops.

Pictorial job aid used by drug shop vendors to guide treatment for drug shops in Uganda.

Use of rapid diagnostic tests in Uganda to improve malaria treatment in the community.

LSHTM Investigators: Sian Clarke, Kristian Hansen, Clare



(National Malaria Control Programme, Uganda); Pascal Magnussen

(Univeristy of Copenhagen, Denmark).

Funding:

Consortium.

This randomised trial aims to assess whether the use of rapid diagnostic tests by community health workers

managing cases of malaria in the community. The trial compared home-based management of

malaria based on the results of rapid diagnostic tests

based solely on their symptoms, in two areas of high

were also trained on malaria case management including

to refer. To determine whether use of RDTs improved

by CHWs were evaluated against the malaria parasite infection status of the patient as detected by expert microscopy on a research blood slide collected at the time of consultation.

Early analysis suggests that over 85% of the community medicine distributors complied with the results of rapid diagnostic tests. The community were also aware that not all fever is caused by malaria, which increased

Introducing rapid diagnostic tests into the private health sector: a cost-effectiveness analysis among registered drug shops in Mukono district, Uganda.





Funding:


It is common in Uganda for people to seek treatment for malaria in private drug shops where parasitological diagnosis to guide malaria treatment is not usually

to perform and have high accuracy, these tests could feasibly be offered in drug shops.

a cluster-randomised trial in Mukono district, Uganda, where drug shops were randomised either to prescribe

perspective incorporating provider costs (training,

health care seeking for malaria treatment. Preliminary results suggest that the total cost of providing malaria services in drug shops with access to RDT diagnosis was at least 15% higher than in drug shops providing presumptive diagnosis. However, the share of appropriately treated fever patients was much higher in RDT drug shops compared to drug shops with

the incremental cost of replacing presumptive diagnosis by RDT diagnosis in drug shops could therefore still be as low as US$2-3 per additional patient appropriately treated.



Perceptions and impact of introducing rapid diagnostic tests in drug shops in Uganda.

LSHTM Investigators: Clare Chandler, Eleanor Hutchinson, Sian

Clarke, Kristian Hansen & Sham Lal.




Funding:


This research study was conducted alongside a trial in which workers in drug shops were trained to carry out

were perceived and used by the local constituents of the trial.

Twenty one focus group discussions were carried out with clients, drug shop vendors and local health facility staff. While RDTs were valued as diagnostic tools they also had unintended consequences. The availability of RDTs was interpreted as a marker of quality care, raising the overall status of drug shops in the local health care system and enabling drug shops appear to offer services similar to primary health care centres. Drug shop vendors used RDTs to demonstrate biomedical skill and increase

seller. The system of referral was largely unsuccessful in its attempt to establish a professional link between the formal health system and the drug shops.Drug shop in Mukono district, Uganda.

The role of rapid diagnostic tests for Malaria for the targeting of artemisinin-based combination therapies at community level: a cluster randomized controlled trial in Ghana.

LSHTM Investigators: Christopher Whitty.


Funding:

Foundation through the Malaria Capacity Development Consortium.

We conducted a cluster randomized trial in the Dangme West District of Ghana among clients reporting to a chemical shop complaining of fever or requesting an

antimalarial. Shops were randomly allocated to standard practice or dispensing informed by rapid diagnostic test

double-read research slides. The proportion of slide negative clients, who received any antimalarial was

control arm, received appropriate treatment based on double-read research slide results.

Introducing rapid diagnostic tests into com-munity-based management of malaria: a cost-effectiveness analysis among community medicine distributors in two areas of high and low transmission in Uganda.



(Ministry of Health, Kampala, Uganda); Pascal Magnussen (Univer-

sity of Copenhagen, Denmark).

Funding: -

tion through the ACT Consortium.

Treatment of malaria by trained community members has been seen as a way of increasing access to health care in remote and underserved areas. Rapid diagnostic tests

-agnosis in remote locations where community members with limited training may be able to perform RDTs and

The inSCALE Project: Integrated Community Case Management of Common Childhood Dis-eases: Mozambique and Uganda.

LSHTM Investigators -

sall, Frida Kasteng & Seyi Soremekun.

External Investigators/Collaborators: James Tibenderana (Ma-

laria Consortium Africa, Uganda); Sylvia Meek & Karin Kallander

(University of London Institute of Child Health, UK).

Funding:

Programmes involved in the integrated community case management of malaria, diarrhoea and pneumonia

health care for hard-to-reach communities. iCCM pro-

trained to diagnose and treat malaria, diarrhoea and pneumonia and to carry out preventative health activities. In order to minimise the common problems of poor super-vision and motivation, and the low retention rates that can occur in CHW programmes, a partnership of academics and public health practitioners at the London School of Hygiene & Tropical Medicine, University College London and the Malaria Consortium have designed two innova-tive intervention packages aimed at strengthening CHW

The project will evaluate the impact of providing CHWs with mobile phones and accessories (‘technology

treat accordingly.-

side a cluster-randomised trial to assess the impact of introducing RDTs to improve malaria diagnosis and treat-

sub-counties with contrasting transmission in Rukungiri District, Uganda. Costs were collected from a societal perspective. Provider costs incorporated the cost of com-munity sensitisation, training of CMDs, development of training material, allowances for CMDs and the commod-

cost was captured through interviews with a sample of patients treated by CMDs incorporating household cost of treatment-seeking for fever including the direct costs of transport, diagnosis and drugs and opportunity cost of lost time. Finally, while CMDs were unpaid volunteers, the extent of time utilised by CMDs was estimated through

of data collected is ongoing.

coverage of appropriately treated children with malaria, diarrhoea and pneumonia in Uganda and Mozambique. The interventions have been successfully implemented

-ogy intervention a total of 100 CHW supervisors and 1400

accessories to aid them in their work through digital as-sistance with diagnosis, receipt of regular motivational messages and feedback, and through free communica-

880 CHWs in Uganda are involved in the setting up and running of village health clubs which are open to all com-munity members to help raise the awareness in the com-munity of the CHW programme and to mobilise members to solve local health problems.The impact of both these additions to the iCCM programme will be assessed af-

comparison with CHWs in areas with routine iCCM in a cluster-randomised controlled design. In addition to de-termining the impact on the coverage of children who are appropriately treated for malaria, diarrhoea and pneumo-nia, we will also assess the effects of the interventions on CHW motivation, performance and retention. Information on implementation and running costs, and on the cost-effectiveness of the interventions will also be collected and analysed in order to provide complete and informed policy advice to government and academic stakeholders post-evaluation.



Perceptions and impact of introducing rapid diagnostic tests in drug shops in Uganda.

LSHTM Investigators: Clare Chandler, Eleanor Hutchinson, Sian

Clarke, Kristian Hansen & Sham Lal.




Funding:


This research study was conducted alongside a trial in which workers in drug shops were trained to carry out

were perceived and used by the local constituents of the trial.

Twenty one focus group discussions were carried out with clients, drug shop vendors and local health facility staff. While RDTs were valued as diagnostic tools they also had unintended consequences. The availability of RDTs was interpreted as a marker of quality care, raising the overall status of drug shops in the local health care system and enabling drug shops appear to offer services similar to primary health care centres. Drug shop vendors used RDTs to demonstrate biomedical skill and increase

seller. The system of referral was largely unsuccessful in its attempt to establish a professional link between the formal health system and the drug shops.Drug shop in Mukono district, Uganda.

The role of rapid diagnostic tests for Malaria for the targeting of artemisinin-based combination therapies at community level: a cluster randomized controlled trial in Ghana.

LSHTM Investigators: Christopher Whitty.


Funding:

Foundation through the Malaria Capacity Development Consortium.

We conducted a cluster randomized trial in the Dangme West District of Ghana among clients reporting to a chemical shop complaining of fever or requesting an

antimalarial. Shops were randomly allocated to standard practice or dispensing informed by rapid diagnostic test

double-read research slides. The proportion of slide negative clients, who received any antimalarial was

control arm, received appropriate treatment based on double-read research slide results.

Introducing rapid diagnostic tests into com-munity-based management of malaria: a cost-effectiveness analysis among community medicine distributors in two areas of high and low transmission in Uganda.



(Ministry of Health, Kampala, Uganda); Pascal Magnussen (Univer-

sity of Copenhagen, Denmark).

Funding: -

tion through the ACT Consortium.

Treatment of malaria by trained community members has been seen as a way of increasing access to health care in remote and underserved areas. Rapid diagnostic tests

-agnosis in remote locations where community members with limited training may be able to perform RDTs and

The inSCALE Project: Integrated Community Case Management of Common Childhood Dis-eases: Mozambique and Uganda.

LSHTM Investigators -

sall, Frida Kasteng & Seyi Soremekun.

External Investigators/Collaborators: James Tibenderana (Ma-

laria Consortium Africa, Uganda); Sylvia Meek & Karin Kallander

(University of London Institute of Child Health, UK).

Funding:

Programmes involved in the integrated community case management of malaria, diarrhoea and pneumonia

health care for hard-to-reach communities. iCCM pro-

trained to diagnose and treat malaria, diarrhoea and pneumonia and to carry out preventative health activities. In order to minimise the common problems of poor super-vision and motivation, and the low retention rates that can occur in CHW programmes, a partnership of academics and public health practitioners at the London School of Hygiene & Tropical Medicine, University College London and the Malaria Consortium have designed two innova-tive intervention packages aimed at strengthening CHW

The project will evaluate the impact of providing CHWs with mobile phones and accessories (‘technology

treat accordingly.-

side a cluster-randomised trial to assess the impact of introducing RDTs to improve malaria diagnosis and treat-

sub-counties with contrasting transmission in Rukungiri District, Uganda. Costs were collected from a societal perspective. Provider costs incorporated the cost of com-munity sensitisation, training of CMDs, development of training material, allowances for CMDs and the commod-

cost was captured through interviews with a sample of patients treated by CMDs incorporating household cost of treatment-seeking for fever including the direct costs of transport, diagnosis and drugs and opportunity cost of lost time. Finally, while CMDs were unpaid volunteers, the extent of time utilised by CMDs was estimated through

of data collected is ongoing.

coverage of appropriately treated children with malaria, diarrhoea and pneumonia in Uganda and Mozambique. The interventions have been successfully implemented

-ogy intervention a total of 100 CHW supervisors and 1400

accessories to aid them in their work through digital as-sistance with diagnosis, receipt of regular motivational messages and feedback, and through free communica-

880 CHWs in Uganda are involved in the setting up and running of village health clubs which are open to all com-munity members to help raise the awareness in the com-munity of the CHW programme and to mobilise members to solve local health problems.The impact of both these additions to the iCCM programme will be assessed af-

comparison with CHWs in areas with routine iCCM in a cluster-randomised controlled design. In addition to de-termining the impact on the coverage of children who are appropriately treated for malaria, diarrhoea and pneumo-nia, we will also assess the effects of the interventions on CHW motivation, performance and retention. Information on implementation and running costs, and on the cost-effectiveness of the interventions will also be collected and analysed in order to provide complete and informed policy advice to government and academic stakeholders post-evaluation.



Optimal price subsidies for appropriate malaria testing and treatment behaviour.

LSHTM Investigators: Kristian Hansen.

External Investigators/Collaborators: Tine Hjernø Lesner & Lars

Peter Østerdal (University of Southern Denmark, Denmark).

Funding:

Consortium.

Malaria continues to be a serious public health problem

do not receive an effective antimalarial while at the same time a large proportion of people receiving treatment for malaria does not suffer from malaria.

proposed to subsidise artemisinin-based combination

effective antimalarial available. Such a scheme

recommends that all individuals suspected of having malaria should receive a parasitological test before

research project is investigating what may be the optimal

cheaper, less effective antimalarials, a model describing health-seeking behaviour of customers with suspected malaria was developed. Preliminary results in the form of numerical simulations of this model suggest that a more optimal use of funds would be to redirect some of the

Interventions to improve community case management of malaria in sub-Saharan Africa: a systematic review.

LSHTM Investigators: Lucy Paintain, Barbara Willey, David

Schellenberg & Jayne Webster .


Ngashi Ngongo & Alyssa Sharkey (UNICEF, USA)

Funding: UNICEF.

In total, 33 papers covering a total of 36 studies in 15

alone, 16 of these by presumptive diagnosis and 11 by

malaria CCM integrated with other basic health services.

Six main strategies emerged from the review as being important determinants of the success of malaria CCM for children:

packaging of medicines in appropriate doses

to health facility level

Due to the multi-faceted nature of many of the

directly link outcomes to individual components of the intervention. Nevertheless, all of these strategies play some part in the success of a community health worker programme and their impact if implemented in combination is likely to be greater.

Village malaria workers and the management of malaria and childhood illnesses in rural Cambodia: knowledge, perceptions, and preferences of caregivers.

LSHTM Investigators

External Investigators/Collaborators: Chea Nguon (National

Malaria Control Programme, Cambodia).

Funding: The Department for International Development through

Consortium.

trained and deployed to diagnose suspected malaria

patients to the nearest public health facility. In addition, VMWs in selected villages have also been trained to provide treatment for diarrhoea and acute respiratory

The VMW programme continues to expand but questions remain about the way in which the scaling up of interventions should be implemented and how utilisation of VMWs can be increased.

This qualitative study aimed to understand the community’s health seeking practices in one province in Cambodia. In 2013, eighty in-depth interviews were carried out with carers of children, village authorities, malaria workers, and mobile and migrant workers,

reveal tensions, limitations and opportunities that should be considered in the scaling-up of the VMW programme.

Commumnity Health Worker walking through mud with his motorcycle.Patient undergoing a rapid diagnostic test for malaria.



Optimal price subsidies for appropriate malaria testing and treatment behaviour.

LSHTM Investigators: Kristian Hansen.

External Investigators/Collaborators: Tine Hjernø Lesner & Lars

Peter Østerdal (University of Southern Denmark, Denmark).

Funding:

Consortium.

Malaria continues to be a serious public health problem

do not receive an effective antimalarial while at the same time a large proportion of people receiving treatment for malaria does not suffer from malaria.

proposed to subsidise artemisinin-based combination

effective antimalarial available. Such a scheme

recommends that all individuals suspected of having malaria should receive a parasitological test before

research project is investigating what may be the optimal

cheaper, less effective antimalarials, a model describing health-seeking behaviour of customers with suspected malaria was developed. Preliminary results in the form of numerical simulations of this model suggest that a more optimal use of funds would be to redirect some of the

Interventions to improve community case management of malaria in sub-Saharan Africa: a systematic review.

LSHTM Investigators: Lucy Paintain, Barbara Willey, David

Schellenberg & Jayne Webster .


Ngashi Ngongo & Alyssa Sharkey (UNICEF, USA)

Funding: UNICEF.

In total, 33 papers covering a total of 36 studies in 15

alone, 16 of these by presumptive diagnosis and 11 by

malaria CCM integrated with other basic health services.

Six main strategies emerged from the review as being important determinants of the success of malaria CCM for children:

packaging of medicines in appropriate doses

to health facility level

Due to the multi-faceted nature of many of the

directly link outcomes to individual components of the intervention. Nevertheless, all of these strategies play some part in the success of a community health worker programme and their impact if implemented in combination is likely to be greater.

Village malaria workers and the management of malaria and childhood illnesses in rural Cambodia: knowledge, perceptions, and preferences of caregivers.

LSHTM Investigators

External Investigators/Collaborators: Chea Nguon (National

Malaria Control Programme, Cambodia).

Funding: The Department for International Development through

Consortium.

trained and deployed to diagnose suspected malaria

patients to the nearest public health facility. In addition, VMWs in selected villages have also been trained to provide treatment for diarrhoea and acute respiratory

The VMW programme continues to expand but questions remain about the way in which the scaling up of interventions should be implemented and how utilisation of VMWs can be increased.

This qualitative study aimed to understand the community’s health seeking practices in one province in Cambodia. In 2013, eighty in-depth interviews were carried out with carers of children, village authorities, malaria workers, and mobile and migrant workers,

reveal tensions, limitations and opportunities that should be considered in the scaling-up of the VMW programme.

Commumnity Health Worker walking through mud with his motorcycle.Patient undergoing a rapid diagnostic test for malaria.



Facility-based case management

Barriers to effectiveness: artemisinin-based combination therapies and health systems.

LSHTM Investigators: Bhargavi Rao & David Schellenberg plus

-

becca Thomson).


Lucy Okell (Imperial College London, UK).

Funding:


--

pered by weak health systems and a poorly controlled

-sion model to include dimensions of access to sources of

in order to estimate the impact of overcoming health sys-tems barriers on malaria mortality and transmission risk. We parameterised out model using data from 3 different

We found that systems interventions resulted in

proportionately greater clinical impact than epidemiologi-cal, with the greatest relative impact at low transmission settings. Modelling policies such as the rollout of rapid

prevalence despite reducing treatment of non-malarial

uncomplicated malaria and reducing transmission. How-ever investment would be required across case manage-ment in the private sector to improve the quality of care delivered. The impact of packages of systems interven-tions was highly dependent on existing health systems provision and population references as well as epidemi-

-prove progress towards targets set by Roll Back malaria or to approach elimination.

Future work will include including considerations of cost-effectiveness, synergies with other control interven-tions and modelling appropriate treatment for NMFI. We

-ments at a local level and consider the application of this model in unstable and elimination settings.

IMPACT2: evaluating policies in Tanzania to improve malaria diagnosis and treatment.

LSHTM Investigators

Rebecca Thomson & Matthew Cairns.

External Investigators/Collaborators: Patrick Kachur, Denise

Roth Allen & Melissa Briggs (US Centers for Disease Control and

Prevention, USA); Salim Abdulla, Admirabilis Kalolella, Charles

Festo, Boniface Johanes, Happy Nchimbi & Clarence Mkoba


Funding:

Consortium.

This set of evaluation studies assesses the effectiveness of two policies implemented by the government of Tanzania to improve the accessibility and targeting of malaria treatment.

Quantitative surveys and qualitative methods were used in public health facilities, antimalarial outlets and households to assess the impact of these initiatives on treatment availability, affordability, targeting and use. The effect of text message reminders targeted at drug shop

dispensers to improve patients’ adherence to treatment was studied as part of a cluster randomised controlled trial.

The study has highlighted some key implications for policy:

appropriateness of antimalarial provision in public facilities. However, public sector stockouts of drugs and diagnostics are a key challenge for successful implementation of malaria control

subsidies are an effective way to improve availability, reduce price and increase market share of quality

shops, further investigation is required of steps to improve quality of care in these outlets

and private outlets, but the text message reminder intervention did not improve adherence among private sector clients, highlighting the need for further intervention development

We carry out a number of studies in health facilities including several large randomised control trials of interventions aimed at improving malaria diagnosis and treatment through health facilities in Africa and Asia.

Mobilize Against Malaria: interventions to im-prove the delivery of rtemisinin-based com-bination therapies in Ghana, Kenya and Sen-egal.

LSHTM Investigators: Jayne Webster, Caroline Jones, Jane Bruce,

Lucy Paintain, Alexandra Hyde & Manuela Claite.

External Investigators/Collaborators: Kwame Adogboba, Nana

Enyimayew, Sofo Ali, Kwadwo Koram & David Ofori-Adjei (Health

Diallo (IntraHealth Senegal).

Funding:

and 20012 by partners in Ghana, Kenya and Senegal. The aim of the programme was to reduce malaria morbid-ity and mortality through the implementation of different models of delivery of artemisinin-based combination ther-apies through retail, public and community sectors.

The study has demonstrated the viability of improved

and maintaining community-run health huts in Senegal and tested the effectiveness of health worker training and mass communications in Kenya.

Cross cutting issues emerging from the opportunity of having conducted evaluations across three delivery mod-els in three sectors of three countries are in process and will be completed in 2014

Health worker carries out malaria rapid diagnostic test with child in Tanzania.



Facility-based case management

Barriers to effectiveness: artemisinin-based combination therapies and health systems.

LSHTM Investigators: Bhargavi Rao & David Schellenberg plus

-

becca Thomson).


Lucy Okell (Imperial College London, UK).

Funding:


--

pered by weak health systems and a poorly controlled

-sion model to include dimensions of access to sources of

in order to estimate the impact of overcoming health sys-tems barriers on malaria mortality and transmission risk. We parameterised out model using data from 3 different

We found that systems interventions resulted in

proportionately greater clinical impact than epidemiologi-cal, with the greatest relative impact at low transmission settings. Modelling policies such as the rollout of rapid

prevalence despite reducing treatment of non-malarial

uncomplicated malaria and reducing transmission. How-ever investment would be required across case manage-ment in the private sector to improve the quality of care delivered. The impact of packages of systems interven-tions was highly dependent on existing health systems provision and population references as well as epidemi-

-prove progress towards targets set by Roll Back malaria or to approach elimination.

Future work will include including considerations of cost-effectiveness, synergies with other control interven-tions and modelling appropriate treatment for NMFI. We

-ments at a local level and consider the application of this model in unstable and elimination settings.

IMPACT2: evaluating policies in Tanzania to improve malaria diagnosis and treatment.

LSHTM Investigators

Rebecca Thomson & Matthew Cairns.

External Investigators/Collaborators: Patrick Kachur, Denise

Roth Allen & Melissa Briggs (US Centers for Disease Control and

Prevention, USA); Salim Abdulla, Admirabilis Kalolella, Charles

Festo, Boniface Johanes, Happy Nchimbi & Clarence Mkoba


Funding:

Consortium.

This set of evaluation studies assesses the effectiveness of two policies implemented by the government of Tanzania to improve the accessibility and targeting of malaria treatment.

Quantitative surveys and qualitative methods were used in public health facilities, antimalarial outlets and households to assess the impact of these initiatives on treatment availability, affordability, targeting and use. The effect of text message reminders targeted at drug shop

dispensers to improve patients’ adherence to treatment was studied as part of a cluster randomised controlled trial.

The study has highlighted some key implications for policy:

appropriateness of antimalarial provision in public facilities. However, public sector stockouts of drugs and diagnostics are a key challenge for successful implementation of malaria control

subsidies are an effective way to improve availability, reduce price and increase market share of quality

shops, further investigation is required of steps to improve quality of care in these outlets

and private outlets, but the text message reminder intervention did not improve adherence among private sector clients, highlighting the need for further intervention development

We carry out a number of studies in health facilities including several large randomised control trials of interventions aimed at improving malaria diagnosis and treatment through health facilities in Africa and Asia.

Mobilize Against Malaria: interventions to im-prove the delivery of rtemisinin-based com-bination therapies in Ghana, Kenya and Sen-egal.

LSHTM Investigators: Jayne Webster, Caroline Jones, Jane Bruce,

Lucy Paintain, Alexandra Hyde & Manuela Claite.

External Investigators/Collaborators: Kwame Adogboba, Nana

Enyimayew, Sofo Ali, Kwadwo Koram & David Ofori-Adjei (Health

Diallo (IntraHealth Senegal).

Funding:

and 20012 by partners in Ghana, Kenya and Senegal. The aim of the programme was to reduce malaria morbid-ity and mortality through the implementation of different models of delivery of artemisinin-based combination ther-apies through retail, public and community sectors.

The study has demonstrated the viability of improved

and maintaining community-run health huts in Senegal and tested the effectiveness of health worker training and mass communications in Kenya.

Cross cutting issues emerging from the opportunity of having conducted evaluations across three delivery mod-els in three sectors of three countries are in process and will be completed in 2014

Health worker carries out malaria rapid diagnostic test with child in Tanzania.



REACT Cameroon: cost-effectiveness of interventions to support the introduction of malaria rapid diagnostic tests in Cameroon.

LSHTM Investigators

Jefferies, Bonnie Cundill & Clare Chandler.

External Investigators/Collaborators: Wilfred Mbacham, Olivia

Obinna Onwujekwe (University of Nigeria, Nigeria).

Funding:

Consortium.

This 3-arm cluster randomised trial aims to support the use of rapid diagnostic tests and adherence to their results in Cameroon.

We worked with the Ministry of Health to design basic and enhanced rapid diagnostic test training courses. Both trainings explained how to use the test and how to treat uncomplicated malaria. The enhanced course contained additional interactive methods – such as drama and problem solving exercises – to encourage health workers

to test for malaria and to prescribe treatment based on the results.

We have published papers that describe problems in malaria case management: malaria testing was available but under-used and many health workers prefer to prescribe an antimalarial even if the malaria test has a negative result.

In addition, we are submitting effectiveness and cost-

being prepared, including one that describes the process of designing and implementing the interventions.

provide an important basis for comparison across different

well as different treatment seeking practices by ethnic and socioeconomic groups. Perhaps most interesting, these intervention trials will allow comparison between sites where currently microscopy testing is widely available

Card games as part of training to use malaria rapid diagnostic tests.

REACT Nigeria: costs and effects of strategies to improve malaria diagnosis and treatment in Nigeria.

LSHTM Investigators


External Investigators/Collaborators: Obinna Onwujekwe,

BSC Uzochukwu, Ogo Ibe, Emmanuel Nwala, Eloka Uchegbu &

Chinelo Enemuo (University of Nigeria, Nigeria); Wilfred Mbacham

Funding:

Consortium.

This cluster randomised trial aims to assist Nigerian policy-makers in deciding which types of provider and community interventions should support the roll-out of rapid diagnostic tests in Nigeria, especially in the private sector which is a major source of malaria treatment in the country.

Working with the state malaria control programme,

selected public health centres, pharmacies and drug stores. In the control arm, the tests were supplied and providers were shown how they should be used. In the

provider intervention arm, rapid diagnostic tests were also supplied and providers received two-day training and monthly support visits. In the third arm, the provider intervention was supplemented by a school-based programme to raise community awareness about malaria, RDTs and artemisinin-based combination therapies as the recommended antimalarial.

The research team have published papers that describe problems in malaria case management: malaria testing was available but under-used and many health workers prefer to prescribe an antimalarial even if the malaria test has a negative result. We also published a study protocol. In addition, the team is conducting the


and different treatment seeking practices by ethnic and socioeconomic groups. Perhaps most interesting, these intervention trials will allow comparison between sites where currently microscopy testing is widely available

Comparing adherence to artemisinin-based combination therapies for the treatment of uncomplicated malaria in Freetown, Sierra Leone.

LSHTM Investigators: Kristin Banek, Clare Chandler, Toby Leslie,

Daniel Chandramohan & Sarah Staedke.

External Investigators/Collaborators: Samuel Juana Smith, Anitta

Kamara & Musa Sillah Kanu (National Malaria Control Programme,

Sierra Leone).

Funding: This study was primarily self-funded. Amodiaquine-

Fund through the National Malaria Control Program. Equipment

Scholarship. Kristin Banek is supported by an American Association

of University Women Dissertation Fellowship.

Increasing access to and targeting of artemisinin-based

ensure adequate treatment outcomes, health worker and patient/caregiver adherence to treatment guidelines is essential.

This was an open-labelled randomised controlled study conducted in two public health facilities in urban Freetown, Sierra Leone with the aim to measure and compare the level of provider compliance with malaria treatment guidelines and patient/caregiver adherence to

facilities for the treatment of fever were randomised to

of prescription. Health worker compliance to treatment guidelines were assessed through direct observation and interviews. Caregivers’ adherence to the prescribed drugs and factors associated with adherence were assessed though short exit interviews at the health facility and during follow-up at their home on day four post-prescription.

The study took place between July 2013 and January

inclusion criteria and were enrolled in the study, of which

on-going and results are expected to be available by late 2014.



REACT Cameroon: cost-effectiveness of interventions to support the introduction of malaria rapid diagnostic tests in Cameroon.

LSHTM Investigators


External Investigators/Collaborators: Wilfred Mbacham, Olivia

Obinna Onwujekwe (University of Nigeria, Nigeria).

Funding:

Consortium.

This 3-arm cluster randomised trial aims to support the use of rapid diagnostic tests and adherence to their results in Cameroon.

We worked with the Ministry of Health to design basic and enhanced rapid diagnostic test training courses. Both trainings explained how to use the test and how to treat uncomplicated malaria. The enhanced course contained additional interactive methods – such as drama and problem solving exercises – to encourage health workers

to test for malaria and to prescribe treatment based on the results.

We have published papers that describe problems in malaria case management: malaria testing was available but under-used and many health workers prefer to prescribe an antimalarial even if the malaria test has a negative result.

In addition, we are submitting effectiveness and cost-

being prepared, including one that describes the process of designing and implementing the interventions.


well as different treatment seeking practices by ethnic and socioeconomic groups. Perhaps most interesting, these intervention trials will allow comparison between sites where currently microscopy testing is widely available

Card games as part of training to use malaria rapid diagnostic tests.

REACT Nigeria: costs and effects of strategies to improve malaria diagnosis and treatment in Nigeria.

LSHTM Investigators


External Investigators/Collaborators: Obinna Onwujekwe,

BSC Uzochukwu, Ogo Ibe, Emmanuel Nwala, Eloka Uchegbu &

Chinelo Enemuo (University of Nigeria, Nigeria); Wilfred Mbacham

Funding:

Consortium.

This cluster randomised trial aims to assist Nigerian policy-makers in deciding which types of provider and community interventions should support the roll-out of rapid diagnostic tests in Nigeria, especially in the private sector which is a major source of malaria treatment in the country.

Working with the state malaria control programme,

selected public health centres, pharmacies and drug stores. In the control arm, the tests were supplied and providers were shown how they should be used. In the

provider intervention arm, rapid diagnostic tests were also supplied and providers received two-day training and monthly support visits. In the third arm, the provider intervention was supplemented by a school-based programme to raise community awareness about malaria, RDTs and artemisinin-based combination therapies as the recommended antimalarial.

The research team have published papers that describe problems in malaria case management: malaria testing was available but under-used and many health workers prefer to prescribe an antimalarial even if the malaria test has a negative result. We also published a study protocol. In addition, the team is conducting the


and different treatment seeking practices by ethnic and socioeconomic groups. Perhaps most interesting, these intervention trials will allow comparison between sites where currently microscopy testing is widely available

Comparing adherence to artemisinin-based combination therapies for the treatment of uncomplicated malaria in Freetown, Sierra Leone.

LSHTM Investigators: Kristin Banek, Clare Chandler, Toby Leslie,

Daniel Chandramohan & Sarah Staedke.

External Investigators/Collaborators: Samuel Juana Smith, Anitta

Kamara & Musa Sillah Kanu (National Malaria Control Programme,

Sierra Leone).

Funding: This study was primarily self-funded. Amodiaquine-

Fund through the National Malaria Control Program. Equipment

Scholarship. Kristin Banek is supported by an American Association

of University Women Dissertation Fellowship.

Increasing access to and targeting of artemisinin-based

ensure adequate treatment outcomes, health worker and patient/caregiver adherence to treatment guidelines is essential.

This was an open-labelled randomised controlled study conducted in two public health facilities in urban Freetown, Sierra Leone with the aim to measure and compare the level of provider compliance with malaria treatment guidelines and patient/caregiver adherence to

facilities for the treatment of fever were randomised to

of prescription. Health worker compliance to treatment guidelines were assessed through direct observation and interviews. Caregivers’ adherence to the prescribed drugs and factors associated with adherence were assessed though short exit interviews at the health facility and during follow-up at their home on day four post-prescription.

The study took place between July 2013 and January

inclusion criteria and were enrolled in the study, of which

on-going and results are expected to be available by late 2014.



Cost-effectiveness analysis of introducing rapid diagnostic tests for malaria diagnosis as compared to microscopy and presumptive diagnosis in public health centres in Ghana.

LSHTM Investigators: Kristian Hansen, Christopher Whitty &

External Investigators/Collaborators: Evelyn Ansah & Michael

Funding:

Consortium.

The present research project assessed the cost-effectiveness of introducing malaria rapid diagnostic tests

which is a rural area of Ghana. In one setting, the population had access to a health

centre with a microscope and suspected malaria patients

were randomly assigned to a diagnosis by either an RDT or a microscopy and subsequent treatment by health centre staff. In the other setting, the population had access to health centres without a microscope and suspected malaria patients were randomly assigned to diagnosis by an RDT or based on clinical signs. Cost of offering diagnostic services and outpatient services in three public health centres was collected as well as the household cost of treatment-seeking. It was found that the introduction of RDTs increased the proportion of patients who were correctly treated in relation to treatment with antimalarials, from 42% to 65% at an incremental societal

patient in the setting where malaria diagnosis was currently presumptive. In the setting where the health centre had a microscope, there was no advantage to replacing microscopy by RDT as the cost and proportion of correctly treated patients were similar.

Comparative cost-effectiveness of malaria rapid diagnostic tests, microscopy and presumptive diagnosis in public health centres in Afghanistan.

LSHTM Investigators

& Mark Rowland.

External Investigators/Collaborators: Ismail Mayan, Nader

Mohammed & Asif Alokozai (Health Protection and Research

Organisation, Afghanistan); Mohammed Anwar (HealthNet TPO,

Jalalabad, Afghanistan); Sayed Bakhtash (Merling, Kunduz,

Afghanistan).

Funding:

Consortium.

The study was conducted within a randomised trial of three different approaches to malaria diagnosis. The

for malaria and the control arms were either microscopy or clinical diagnosis based on signs and symptoms alone. We enrolled around 6000 patients in the study and assessed the proportion of patients with fever who were appropriately treated for malaria.

appropriate malaria drug, and those with no malaria not receiving any antimalarial drug. We also examined the use of antibiotics and other treatments.

costs of each approach to identify which approach was the most cost-effective. These included costs to the health service (including training, staff time, commodities,

Initial analysis indicates that RDTs are cost-effective when compared to microscopy or clinical diagnosis in low and moderate transmission settings. The result will

roll out RDTs.

Training Afghan health workers on the use of malaria rapid diagnostic tests. Photo: Sayed Bakhtash.

Strategies for expanding access to quality malaria diagnosis in south-central Asia where malaria incidence is low.

LSHTM Investigators: Mark Rowland, Toby Leslie, Chris Whitty &

Amy Mikhail.

External Investigators/Collaborators: Ismail Mayan (Health

Protection and Research Organization, Afghanistan) Nader

Mohammed & Anwar Hasanzai (HealthNet-TPO, Afghanistan);

Sayed Habib Baktash (Medical Emergency Relief International,

Afghanistan).

Funding:

Consortium.

Diagnosis is unavailable in most places where fever is common, so clinicians cannot distinguish the symptoms of malaria from other causes of fever. This results in a huge

overtreatment of malaria. We conducted a series of studies to test how effective

different diagnostic and treatment methods are under

treating malaria.First, we tested the accuracy of a rapid test that can

distinguish the two malaria species and accurately identify negative patients. We found that one brand was the most accurate, and this was subsequently introduced as the

We then conducted two randomised trials, one in clinics and one amongst community health workers, comparing the use of rapid diagnostic tests and microscopy. These studies will provide robust evidence for the most effective diagnostic tool, and allow both clinicians and community health workers to apply malaria treatments according to diagnostic results.

Health worker carries out parasitological diagnosis of malaria in Afghanistan.



Cost-effectiveness analysis of introducing rapid diagnostic tests for malaria diagnosis as compared to microscopy and presumptive diagnosis in public health centres in Ghana.

LSHTM Investigators: Kristian Hansen, Christopher Whitty &

External Investigators/Collaborators: Evelyn Ansah & Michael

Funding:

Consortium.

The present research project assessed the cost-effectiveness of introducing malaria rapid diagnostic tests

which is a rural area of Ghana. In one setting, the population had access to a health

centre with a microscope and suspected malaria patients

were randomly assigned to a diagnosis by either an RDT or a microscopy and subsequent treatment by health centre staff. In the other setting, the population had access to health centres without a microscope and suspected malaria patients were randomly assigned to diagnosis by an RDT or based on clinical signs. Cost of offering diagnostic services and outpatient services in three public health centres was collected as well as the household cost of treatment-seeking. It was found that the introduction of RDTs increased the proportion of patients who were correctly treated in relation to treatment with antimalarials, from 42% to 65% at an incremental societal

patient in the setting where malaria diagnosis was currently presumptive. In the setting where the health centre had a microscope, there was no advantage to replacing microscopy by RDT as the cost and proportion of correctly treated patients were similar.

Comparative cost-effectiveness of malaria rapid diagnostic tests, microscopy and presumptive diagnosis in public health centres in Afghanistan.

LSHTM Investigators

& Mark Rowland.

External Investigators/Collaborators: Ismail Mayan, Nader

Mohammed & Asif Alokozai (Health Protection and Research

Organisation, Afghanistan); Mohammed Anwar (HealthNet TPO,

Jalalabad, Afghanistan); Sayed Bakhtash (Merling, Kunduz,

Afghanistan).

Funding:

Consortium.

The study was conducted within a randomised trial of three different approaches to malaria diagnosis. The

for malaria and the control arms were either microscopy or clinical diagnosis based on signs and symptoms alone. We enrolled around 6000 patients in the study and assessed the proportion of patients with fever who were appropriately treated for malaria.

appropriate malaria drug, and those with no malaria not receiving any antimalarial drug. We also examined the use of antibiotics and other treatments.

costs of each approach to identify which approach was the most cost-effective. These included costs to the health service (including training, staff time, commodities,

Initial analysis indicates that RDTs are cost-effective when compared to microscopy or clinical diagnosis in low and moderate transmission settings. The result will

roll out RDTs.

Training Afghan health workers on the use of malaria rapid diagnostic tests. Photo: Sayed Bakhtash.

Strategies for expanding access to quality malaria diagnosis in south-central Asia where malaria incidence is low.

LSHTM Investigators: Mark Rowland, Toby Leslie, Chris Whitty &

Amy Mikhail.

External Investigators/Collaborators: Ismail Mayan (Health

Protection and Research Organization, Afghanistan) Nader

Mohammed & Anwar Hasanzai (HealthNet-TPO, Afghanistan);

Sayed Habib Baktash (Medical Emergency Relief International,

Afghanistan).

Funding:

Consortium.

Diagnosis is unavailable in most places where fever is common, so clinicians cannot distinguish the symptoms of malaria from other causes of fever. This results in a huge

overtreatment of malaria. We conducted a series of studies to test how effective

different diagnostic and treatment methods are under

treating malaria.First, we tested the accuracy of a rapid test that can

distinguish the two malaria species and accurately identify negative patients. We found that one brand was the most accurate, and this was subsequently introduced as the

We then conducted two randomised trials, one in clinics and one amongst community health workers, comparing the use of rapid diagnostic tests and microscopy. These studies will provide robust evidence for the most effective diagnostic tool, and allow both clinicians and community health workers to apply malaria treatments according to diagnostic results.

Health worker carries out parasitological diagnosis of malaria in Afghanistan.



The effectiveness of interventions delivered at scale to improve the delivery of health services by front-line workers in low-income countries: a systematic review.

LSHTM Investigators: Barbara Willey, Joanna Schellenberg,



London, UK).

Funding: The Department for International Development.

The aim of this study was to identify evidence for the effectiveness of interventions to strengthen national health service delivery in countries with low and lower-middle incomes. The focus was on supply-side interventions to improve the ability of front-line workers to deliver health services, including treatment of malaria,

and evidence from evaluations of interventions delivered at scale.

In total, 21 papers covering 12 studies were included, eight of which had a malaria focus. The evidence base for

for survival impact was limited to two studies of IMCI; both found weak evidence of a positive effect on under-5

Between-study heterogeneity precluded meta-analysis. However, studies which strengthened other elements of the health service delivery in addition to technical guidance, as well as community mobilisation and interventions at the health sector policy and strategic management level showed more consistent improvement on quality of care and counselling than those using technical guidance alone.

Availability of evidence from a systematic review of the effectiveness of supply-side interventions to improve health services in low and middle income countries.

evaluating the impact of an intervention implemented in public health centres on management of malaria and health outcomes of children using a cluster-randomised design in Tororo, Uganda.

LSHTM Investigators: Sarah Staedke & Clare Chandler.

External Investigators/Collaborators: Moses Kamya (Makerere

California, San Francisco, USA).

Funding:

Consortium.

The PRIME study was designed to evaluate the impact of an intervention delivered at public health centres in Tororo, Uganda.

Twenty lower-level public health centres were included in this cluster-randomised trial; 10 were randomly assigned to the intervention and 10 to control. The intervention had four components including:

evaluation, was also conducted alongside the main

understanding about why the PRIME intervention is effective, or not.

Formative research was done in 2009-2010. The

Evaluation activities were conducted from 2010 to 2013. The PRIME intervention was implemented

successfully, although not all health workers received the training. The intervention appeared to improve malaria case management, communication between health workers and patients, and patient satisfaction with care.

impact on health outcomes of community children. Introducing RDTs did not appear to change treatment of malaria or fever outcomes in this very high malaria transmission setting.

Health workers receive training to use malaria rapid diagnostic tests.



The effectiveness of interventions delivered at scale to improve the delivery of health services by front-line workers in low-income countries: a systematic review.

LSHTM Investigators: Barbara Willey, Joanna Schellenberg,



London, UK).


The aim of this study was to identify evidence for the effectiveness of interventions to strengthen national health service delivery in countries with low and lower-middle incomes. The focus was on supply-side interventions to improve the ability of front-line workers to deliver health services, including treatment of malaria,

and evidence from evaluations of interventions delivered at scale.

In total, 21 papers covering 12 studies were included, eight of which had a malaria focus. The evidence base for

for survival impact was limited to two studies of IMCI; both found weak evidence of a positive effect on under-5

Between-study heterogeneity precluded meta-analysis. However, studies which strengthened other elements of the health service delivery in addition to technical guidance, as well as community mobilisation and interventions at the health sector policy and strategic management level showed more consistent improvement on quality of care and counselling than those using technical guidance alone.

Availability of evidence from a systematic review of the effectiveness of supply-side interventions to improve health services in low and middle income countries.

evaluating the impact of an intervention implemented in public health centres on management of malaria and health outcomes of children using a cluster-randomised design in Tororo, Uganda.

LSHTM Investigators: Sarah Staedke & Clare Chandler.

External Investigators/Collaborators: Moses Kamya (Makerere

California, San Francisco, USA).

Funding:

Consortium.

The PRIME study was designed to evaluate the impact of an intervention delivered at public health centres in Tororo, Uganda.

Twenty lower-level public health centres were included in this cluster-randomised trial; 10 were randomly assigned to the intervention and 10 to control. The intervention had four components including:

evaluation, was also conducted alongside the main

understanding about why the PRIME intervention is effective, or not.

Formative research was done in 2009-2010. The

Evaluation activities were conducted from 2010 to 2013. The PRIME intervention was implemented

successfully, although not all health workers received the training. The intervention appeared to improve malaria case management, communication between health workers and patients, and patient satisfaction with care.

impact on health outcomes of community children. Introducing RDTs did not appear to change treatment of malaria or fever outcomes in this very high malaria transmission setting.

Health workers receive training to use malaria rapid diagnostic tests.



Targeting artemisinin-based combination therapiy drugs to patients with a positive result with a malaria rapid diagnostic test in Ghana.

LSHTM Investigators: Daniel Chandramohan, Jayne Webster &

Jane Bruce.

External Investigators/Collaborators: Seth Owusu-Agyei & Frank

Funding:

In this study we have tested the effects of providing

patients who had a positive result in a rapid diagnostic test.

This approach could improve the treatment of malaria, as well as support health services to better

example is pneumonia, which is often misdiagnosed as malaria in children. Finally, this system could also reduce the use of anti-malarials and the risk of developing drug resistance.

We have assessed the accuracy of rapid diagnostic tests and the outcomes of treatment based on rapid diagnostic test results in 32 health facilities. The team conducted interviews with health providers to understand their diagnostic and treatment decisions, as well as exit

presenting fever to assess their satisfaction with the treatment received.

This study has made it possible for us to know with greater certainty the effect of restricting antimalarial to

how frequently they will get malaria or anaemia, and how this will impact on the prescriptions of other drugs.

A health worker performs malaria rapid diagnostic test.

Targeting artemisinin-based combination therapy drugs in Tanzania: the TACT trial.

LSHTM Investigators: Hugh Reyburn, Christopher Whitty & Clare

Chandler.

External Investigators/Collaborators: Renata Mandike (Malaria

Control Programme, Tanzania); Hilda Mbakilwa, (Joint Malaria

Programme, Tanzania); Raimos Olomi (Kilimanjaro Christian Medical

Centre, Tanzania); Steven Magesa (National Institute for Medical

Research, Tanzania).

Funding:

Consortium.

Because of their accuracy, rapid diagnostic tests are a potential cost-effective solution for malaria overdiagnosis. However, this method only works if health professionals

Training to improve use of malaria diagnostic tools, Tanzania.

are trained and supervised.

that may be useful in improving both the management of malaria cases and the treatment of other diseases that also cause fever. The control group of facilities received rapid diagnostic tests and basic training in how to use

at the workplace, messages from senior staff and monthly

workers and community members with the same package as well as a community-based intervention to modify the expectations of patients.



Targeting artemisinin-based combination therapiy drugs to patients with a positive result with a malaria rapid diagnostic test in Ghana.

LSHTM Investigators: Daniel Chandramohan, Jayne Webster &

Jane Bruce.

External Investigators/Collaborators: Seth Owusu-Agyei & Frank

Funding:

In this study we have tested the effects of providing

patients who had a positive result in a rapid diagnostic test.

This approach could improve the treatment of malaria, as well as support health services to better

example is pneumonia, which is often misdiagnosed as malaria in children. Finally, this system could also reduce the use of anti-malarials and the risk of developing drug resistance.

We have assessed the accuracy of rapid diagnostic tests and the outcomes of treatment based on rapid diagnostic test results in 32 health facilities. The team conducted interviews with health providers to understand their diagnostic and treatment decisions, as well as exit

presenting fever to assess their satisfaction with the treatment received.

This study has made it possible for us to know with greater certainty the effect of restricting antimalarial to

how frequently they will get malaria or anaemia, and how this will impact on the prescriptions of other drugs.

A health worker performs malaria rapid diagnostic test.

Targeting artemisinin-based combination therapy drugs in Tanzania: the TACT trial.

LSHTM Investigators: Hugh Reyburn, Christopher Whitty & Clare

Chandler.

External Investigators/Collaborators: Renata Mandike (Malaria

Control Programme, Tanzania); Hilda Mbakilwa, (Joint Malaria

Programme, Tanzania); Raimos Olomi (Kilimanjaro Christian Medical

Centre, Tanzania); Steven Magesa (National Institute for Medical

Research, Tanzania).

Funding:

Consortium.

Because of their accuracy, rapid diagnostic tests are a potential cost-effective solution for malaria overdiagnosis. However, this method only works if health professionals

Training to improve use of malaria diagnostic tools, Tanzania.

are trained and supervised.

that may be useful in improving both the management of malaria cases and the treatment of other diseases that also cause fever. The control group of facilities received rapid diagnostic tests and basic training in how to use

at the workplace, messages from senior staff and monthly

workers and community members with the same package as well as a community-based intervention to modify the expectations of patients.

94 Malaria moving forward Malaria moving forward 95


Summary

Malaria Centre members are actively involved in research to set future priorities for malaria control and development.

The role of surveillance, monitoring and evalua-

-

sential to improved malaria control and eventual

number of metrics have been used to measure

the intensity of malaria transmission including

the revitalisation of the approach of using serol-

ogy to gain insights into the dynamics of malaria

various measures and a study from Uganda eval-

uates operational experience of using different

approaches. Malaria Centre members also rec-

ognise the increasing importance of school-age

-

other approach to assessing malaria transmission

which are resistant to the currently recommended

importance of surveillance for drug resistance and

a framework for decision-making to improve ma-

laria control in the context of resistance.

There is growing appreciation of the importance

of sub-patent malaria infections – that is infections

which are below the detectable limit of conven-

– as a pool for the reservoir of malaria transmis-

sion. Work in the Philippines and Burkina Faso

has attempted to understand the extent to which

sub-patent infections contribute to transmission.

The recognition in recent years that Plasmodium

knowlesi

has lead to extensive epidemiological studies in

Malaysia and the use of mathematical model-

transmission.

-

neous nature of its transmission becomes in-

creasingly apparent. Understanding how to iden-

tify foci of transmission is important for targeting

control activities. Malaria control in boarder areas

is a particular challenge and operational studies

involving cross-border transmission control have

been conducted in Namibia, informed by studies

of population movement based on data from mo-

bile phones.

-

ingly apparent that non-malaria considerations

will impact the effectiveness and acceptability of

control strategies. The roll-out of RDTs means

alike have to accept that not all fevers are due to

malaria. It becomes important to identify the non-

malaria causes of fever and to understand how

targeted malaria control likely to improve.

The importance for effective malaria control

of development of whole economies is becom-

ing clear through macro-economic modeling. The

challenge of eliminating malaria, even on a small

island, is being captured through operational re-

search in Bioko Island. Malaria is recognised as

a cause of poverty but also a result of poverty.

Malaria Centre members are also evaluating the

extent to which socio-economic development can

be considered an intervention against malaria and

are taking a multi-sectoral approach to framing

control of this disease.

The last decade has seen major gains in ma-

laria control, leading to increased coverage of key

interventions and a corresponding decrease in

the incidence of malaria disease and death. How-

ever, these changes have not been consistent

across different settings, and the role of socio-

economic development in shaping disease bur-

den remains clear. The future of malaria control

therefore requires a multi-sectoral and focalized

approach to intervention, which can be guided

by careful observation of changes and hot spots

in disease transmission. The roll-out of RDTs

and mobile telephony sets the scene for step-

improves, it will become increasingly important to

understand the utility of novel markers of malaria

transmission through surveillance and response

systems. It will be important to understand the

broad economic health and social determinants

this information is transmitted to key policy mak-

ers at global and national levels.



Summary

Malaria Centre members are actively involved in research to set future priorities for malaria control and development.

The role of surveillance, monitoring and evalua-

-

sential to improved malaria control and eventual

number of metrics have been used to measure

the intensity of malaria transmission including

the revitalisation of the approach of using serol-

ogy to gain insights into the dynamics of malaria

various measures and a study from Uganda eval-

uates operational experience of using different

approaches. Malaria Centre members also rec-

ognise the increasing importance of school-age

-

other approach to assessing malaria transmission

which are resistant to the currently recommended

importance of surveillance for drug resistance and

a framework for decision-making to improve ma-

laria control in the context of resistance.

There is growing appreciation of the importance

of sub-patent malaria infections – that is infections

which are below the detectable limit of conven-

– as a pool for the reservoir of malaria transmis-

sion. Work in the Philippines and Burkina Faso

has attempted to understand the extent to which

sub-patent infections contribute to transmission.

The recognition in recent years that Plasmodium

knowlesi

has lead to extensive epidemiological studies in

Malaysia and the use of mathematical model-

transmission.

-

neous nature of its transmission becomes in-

creasingly apparent. Understanding how to iden-

tify foci of transmission is important for targeting

control activities. Malaria control in boarder areas

is a particular challenge and operational studies

involving cross-border transmission control have

been conducted in Namibia, informed by studies

of population movement based on data from mo-

bile phones.

-

ingly apparent that non-malaria considerations

will impact the effectiveness and acceptability of

control strategies. The roll-out of RDTs means

alike have to accept that not all fevers are due to

malaria. It becomes important to identify the non-

malaria causes of fever and to understand how

targeted malaria control likely to improve.

The importance for effective malaria control

of development of whole economies is becom-

ing clear through macro-economic modeling. The

challenge of eliminating malaria, even on a small

island, is being captured through operational re-

search in Bioko Island. Malaria is recognised as

a cause of poverty but also a result of poverty.

Malaria Centre members are also evaluating the

extent to which socio-economic development can

be considered an intervention against malaria and

are taking a multi-sectoral approach to framing

control of this disease.

The last decade has seen major gains in ma-

laria control, leading to increased coverage of key

interventions and a corresponding decrease in

the incidence of malaria disease and death. How-

ever, these changes have not been consistent

across different settings, and the role of socio-

economic development in shaping disease bur-

den remains clear. The future of malaria control

therefore requires a multi-sectoral and focalized

approach to intervention, which can be guided

by careful observation of changes and hot spots

in disease transmission. The roll-out of RDTs

and mobile telephony sets the scene for step-

improves, it will become increasingly important to

understand the utility of novel markers of malaria

transmission through surveillance and response

systems. It will be important to understand the

broad economic health and social determinants

this information is transmitted to key policy mak-

ers at global and national levels.



On the estimation of malaria transmission intensity using serology data.

LSHTM Investigators: Nuno Sepúlveda &

Chris Drakeley.


Malaria transmission intensity is typi-cally assessed by parasite preva-lence or entomological infection rate.

seroprevalence data of parasite spe-

catalytic models.In this modelling approach, the

individuals become seropositive upon parasite exposure and may revert to a seronegative state after parasite clearance. The rate by which individuals convert to a sero-positive state is of particular interest for epidemiologists because it can be used as a proxy of the underly-ing malaria transmission intensity. This project aims to perform power calculations using different reverse catalytic models and study designs. We are particularly interested in de-termining the minimum sample size required to:

with a given precision-

laria transmission occurred in the past or

disease dynamics after an interven-tion

We also aim to correct the es-timates for putative biases while maintaining other good statistical properties, such as consistency and low mean square error.

Measuring changes in Plasmodium falciparum transmission: precision, accuracy and costs of metrics.

LSHTM Investigators: Lucy Tusting, Chris Drakeley & Teun

Bousema.

External Investigators/Collaborators: David Smith (Johns Hopkins

Bloomberg School of Public Health, USA); Diadier Diallo (PATH

Funding:

Reliable methods to evaluate the effect of interventions and control programmes on malaria transmission are needed.

To help guide the design of trials to evaluate transmission-reducing interventions, this project assessed

evaluating their accuracy, precision and methods and costs of collection. We also reviewed the nonlinear

transmission: the entomological inoculation rate, force of infection, sporozoite rate, parasite rate and the basic reproductive number, R0. We found that although the entomological inoculation rate is widely considered the gold standard metric of malaria transmission, and may be necessary for measuring changes in transmission in highly endemic areas, it has limited precision and accuracy and more standardised collection methods are needed. In areas of low transmission, parasite rate, seroconversion rates and molecular metrics including

Programme for Resistance, Immunology, Surveillance and Modeling of Malaria in Uganda (PRISM): malaria transmission, infection and disease at three sites with varied transmission intensity in Uganda: implications for malaria control.

LSHTM Investigators: Sarah Staedke & Chris Drakeley.


California, San Francisco, USA); Moses Kamya, Harriet Mayanja-

Kizza, Samuel Nsobya & Fred Wabwire-Mangen (Makerere

University, Uganda); David Smith & Andy Tatem (University of

Florida, USA); Martin Donnelly (Liverpool School of Tropical

Medicine, UK); Steve Lindsay (Durham University, UK).

Funding: USA National Institutes of Health.

This project aims to address the complexity of interactions between the mosquito vector, malaria parasite, and human host.

sub-counties of interest to provide a sampling frame for comprehensive surveillance activities. In each sub-county, 100 houses were randomly selected for measures of malaria transmission, infection and disease over a 2-year period. For transmission, the entomological inoculation

CDC light traps. Cohorts of children aged 0.5-11 years received all care from study clinics open 7 days/week

with routine blood smears done every 3 months and passive surveillance for malaria for measures of infection

of malaria were promptly treated with an artemisinin-

across the 3 sites with estimated EIRs of 3, 32, and 299 infected bites per person year for Jinja, Kanungu and Tororo respectively.

Parasite prevalence was 8.8% in Jinja, 15.0% in

differences when comparing the 1st and 2nd years of observation. The incidence of malaria per person year was 0.48 in Jinja, 1.67 in Kanungu and 3.52 in Tororo with

met criteria for complicated disease and there were no

excellent with only 3 episodes required rescue therapy within 3 days and 31 required repeat therapy within

until 2017, and continue to utilise samples collected for immunology and resistance projects

Surveillance, monitoring and evaluation

A. Proportion of tests that rejected the single force-of-infection reverse catalytic model using an age-adjusted cross-sectional

Effective surveillance, monitoring and evaluation (SME) is required to monitor progress with control and to inform the targeting of resources to where they are most needed. Malaria Centre members are actively engaged in a range of activities to improve SME.



On the estimation of malaria transmission intensity using serology data.

LSHTM Investigators: Nuno Sepúlveda &

Chris Drakeley.


Malaria transmission intensity is typi-cally assessed by parasite preva-lence or entomological infection rate.

seroprevalence data of parasite spe-

catalytic models.In this modelling approach, the

individuals become seropositive upon parasite exposure and may revert to a seronegative state after parasite clearance. The rate by which individuals convert to a sero-positive state is of particular interest for epidemiologists because it can be used as a proxy of the underly-ing malaria transmission intensity. This project aims to perform power calculations using different reverse catalytic models and study designs. We are particularly interested in de-termining the minimum sample size required to:

with a given precision-

laria transmission occurred in the past or

disease dynamics after an interven-tion

We also aim to correct the es-timates for putative biases while maintaining other good statistical properties, such as consistency and low mean square error.

Measuring changes in Plasmodium falciparum transmission: precision, accuracy and costs of metrics.

LSHTM Investigators: Lucy Tusting, Chris Drakeley & Teun

Bousema.

External Investigators/Collaborators: David Smith (Johns Hopkins

Bloomberg School of Public Health, USA); Diadier Diallo (PATH

Funding:

Reliable methods to evaluate the effect of interventions and control programmes on malaria transmission are needed.

To help guide the design of trials to evaluate transmission-reducing interventions, this project assessed

evaluating their accuracy, precision and methods and costs of collection. We also reviewed the nonlinear

transmission: the entomological inoculation rate, force of infection, sporozoite rate, parasite rate and the basic reproductive number, R0. We found that although the entomological inoculation rate is widely considered the gold standard metric of malaria transmission, and may be necessary for measuring changes in transmission in highly endemic areas, it has limited precision and accuracy and more standardised collection methods are needed. In areas of low transmission, parasite rate, seroconversion rates and molecular metrics including

Programme for Resistance, Immunology, Surveillance and Modeling of Malaria in Uganda (PRISM): malaria transmission, infection and disease at three sites with varied transmission intensity in Uganda: implications for malaria control.

LSHTM Investigators: Sarah Staedke & Chris Drakeley.


California, San Francisco, USA); Moses Kamya, Harriet Mayanja-

Kizza, Samuel Nsobya & Fred Wabwire-Mangen (Makerere

University, Uganda); David Smith & Andy Tatem (University of

Florida, USA); Martin Donnelly (Liverpool School of Tropical

Medicine, UK); Steve Lindsay (Durham University, UK).

Funding: USA National Institutes of Health.

This project aims to address the complexity of interactions between the mosquito vector, malaria parasite, and human host.

sub-counties of interest to provide a sampling frame for comprehensive surveillance activities. In each sub-county, 100 houses were randomly selected for measures of malaria transmission, infection and disease over a 2-year period. For transmission, the entomological inoculation

CDC light traps. Cohorts of children aged 0.5-11 years received all care from study clinics open 7 days/week

with routine blood smears done every 3 months and passive surveillance for malaria for measures of infection

of malaria were promptly treated with an artemisinin-

across the 3 sites with estimated EIRs of 3, 32, and 299 infected bites per person year for Jinja, Kanungu and Tororo respectively.

Parasite prevalence was 8.8% in Jinja, 15.0% in

differences when comparing the 1st and 2nd years of observation. The incidence of malaria per person year was 0.48 in Jinja, 1.67 in Kanungu and 3.52 in Tororo with

met criteria for complicated disease and there were no

excellent with only 3 episodes required rescue therapy within 3 days and 31 required repeat therapy within

until 2017, and continue to utilise samples collected for immunology and resistance projects

Surveillance, monitoring and evaluation

A. Proportion of tests that rejected the single force-of-infection reverse catalytic model using an age-adjusted cross-sectional

Effective surveillance, monitoring and evaluation (SME) is required to monitor progress with control and to inform the targeting of resources to where they are most needed. Malaria Centre members are actively engaged in a range of activities to improve SME.



endemicity in Pará state, Brazil.

LSHTM Investigators: Nuno Sepúlveda, Patrick Corran, Eleanor

Riley & Chris Drakeley.

External Investigators/Collaborators: Maristela Cunha

(Universidade Federal do Pará, Brazil).


Parasite prevalence or entomologic infection rate are typically used to assess malaria transmission on a given study area.

to different parasite antigens as a way of assessing past or recent malaria exposure. This approach has been successfully used to monitor Plasmodium falciparum transmission dynamics. To test whether the same approach could be applied to Plasmodium vivax

epidemiology, we collected serology data on ~1,330

region, where Plasmodium vivax infections predominate. In each site, we found parasite prevalences less than 5.0%. Conversely the seroprevalences to Plasmodium vivax antigens or to Plasmodium falciparum antigens vary considerably across sites (e.g, 19.6% in Belém to 77.5% in Goianésia do Pará for Plasmodium vivax

Brazilian Ministry of Public Health. When we analysed the data with the reverse catalytic models, we found statistical evidence for a change in Plasmodium falciparum transmission in sites close to Jacareacanga and occurred around 30 years ago. We concluded that, irrespective of the malaria species, serological data could detect not only heterogeneity of the sites in terms of malaria endemicity but also putative temporal changes in disease dynamics

Malaria in school-aged children in areas of highly seasonal transmission: epidemiological risk, disease burden and strategies for control.

LSHTM Investigators: Sian Clarke, Daniel Chandramohan, Badara

Cisse, Saba Rouhani, Rebecca Jones & Simon Brooker.

External Investigators/Collaborators: Jean-Francois Trape

& Cheikh Sokna (Institut de recherche pour le developpement,

Anta Diop, Senegal); Malick Sembene, Aliou Dia & Khady Diallo

(Division of School Health, Ministry of Education, Senegal); Fatou

Ba Fall (National Malaria Conbtrol Programme, Ministry of Health,

Senegal); Natalie Roschnik, Seybou Diarra & Bamadio Modibo

(Save the Children, Mali); Moussa Sacko & Renion Saye (National

Institute for Public Health Research, Ministry of Health, Mali);

Diahara Traore (National Malaria Control Programme, Ministry of

Health, Mali); Matthew Jukes (Room to Read, UK); Josselin Thuillez

(Centre d’economie de la Sorbonne, France).

Funding: The Wellcome Trust & Save the Children.

The risk of malaria is greatest in early childhood and most research and control has focussed on young children. There is now increasing evidence that malaria can also

adversely affect schoolchildren, though the consequences for health and school performance have yet to be fully investigated.

To characterise the epidemiological burden and impact of malaria in school-aged children living in areas

series of studies were conducted in Senegal and Mali between 2010 and 2014. Epidemiological investigations were undertaken across a range of transmission settings including low-moderate seasonal, intense seasonal and intense year-round transmission. The incidence of clinical attacks, prevalence of asymptomatic infections, anaemia and cognitive function were examined in children aged 6 months to 14 years, including children below school age and children enrolled in primary school. Randomised trials in schools examined the impact of intermittent parasite clearance on malaria, anaemia and cognitive performance. The research is intended to inform the development of malaria control strategies for school-aged children in areas of highly seasonal transmission.

Future work will also examine the effects of malaria control on child development in pre-school children, with a focus on cognitive foundation skills for early literacy.

Reliability of school surveys in estimating geographic variation in malaria transmission in the western Kenyan Highlands.

LSHTM Investigators

Jonathan Cox.


of Notre Dame, USA) & Chrispin Owaga, Elizabeth Marube,

Wycliffe Odongo, Albert Okoth, Pauline China & Robin Oriango

Prevention, Kenya).

Funding:

Malaria Transmission Consortium.

School surveys provide an operational approach to assess malaria transmission through parasite prevalence however, there is limited evidence on how well these estimates compare to those from the surrounding community.

Concurrent school and community cross-sectional surveys were conducted in 46 school/community clusters

36.4% of school children sampled resided within 600 m of their school with the mean distance of 793 m (IQR:

consistently higher than those from community surveys

the school population was restricted to those residing

seroconversion rates were similar between school and

prevalence rates measured during school surveys have been directly compared to those in the surrounding community. Ultimately, school-based estimates can be used as a reliable indicator of malaria transmission intensity in the wider community and may provide a basis for identifying priority areas for malaria control and be used to measure or monitor changes in transmission intensity.



endemicity in Pará state, Brazil.

LSHTM Investigators: Nuno Sepúlveda, Patrick Corran, Eleanor

Riley & Chris Drakeley.

External Investigators/Collaborators: Maristela Cunha

(Universidade Federal do Pará, Brazil).


Parasite prevalence or entomologic infection rate are typically used to assess malaria transmission on a given study area.

to different parasite antigens as a way of assessing past or recent malaria exposure. This approach has been successfully used to monitor Plasmodium falciparum transmission dynamics. To test whether the same approach could be applied to Plasmodium vivax

epidemiology, we collected serology data on ~1,330

region, where Plasmodium vivax infections predominate. In each site, we found parasite prevalences less than 5.0%. Conversely the seroprevalences to Plasmodium vivax antigens or to Plasmodium falciparum antigens vary considerably across sites (e.g, 19.6% in Belém to 77.5% in Goianésia do Pará for Plasmodium vivax

Brazilian Ministry of Public Health. When we analysed the data with the reverse catalytic models, we found statistical evidence for a change in Plasmodium falciparum transmission in sites close to Jacareacanga and occurred around 30 years ago. We concluded that, irrespective of the malaria species, serological data could detect not only heterogeneity of the sites in terms of malaria endemicity but also putative temporal changes in disease dynamics

Malaria in school-aged children in areas of highly seasonal transmission: epidemiological risk, disease burden and strategies for control.

LSHTM Investigators: Sian Clarke, Daniel Chandramohan, Badara

Cisse, Saba Rouhani, Rebecca Jones & Simon Brooker.

External Investigators/Collaborators: Jean-Francois Trape

& Cheikh Sokna (Institut de recherche pour le developpement,

Anta Diop, Senegal); Malick Sembene, Aliou Dia & Khady Diallo

(Division of School Health, Ministry of Education, Senegal); Fatou

Ba Fall (National Malaria Conbtrol Programme, Ministry of Health,

Senegal); Natalie Roschnik, Seybou Diarra & Bamadio Modibo

(Save the Children, Mali); Moussa Sacko & Renion Saye (National

Institute for Public Health Research, Ministry of Health, Mali);

Diahara Traore (National Malaria Control Programme, Ministry of

Health, Mali); Matthew Jukes (Room to Read, UK); Josselin Thuillez

(Centre d’economie de la Sorbonne, France).

Funding: The Wellcome Trust & Save the Children.

The risk of malaria is greatest in early childhood and most research and control has focussed on young children. There is now increasing evidence that malaria can also

adversely affect schoolchildren, though the consequences for health and school performance have yet to be fully investigated.

To characterise the epidemiological burden and impact of malaria in school-aged children living in areas

series of studies were conducted in Senegal and Mali between 2010 and 2014. Epidemiological investigations were undertaken across a range of transmission settings including low-moderate seasonal, intense seasonal and intense year-round transmission. The incidence of clinical attacks, prevalence of asymptomatic infections, anaemia and cognitive function were examined in children aged 6 months to 14 years, including children below school age and children enrolled in primary school. Randomised trials in schools examined the impact of intermittent parasite clearance on malaria, anaemia and cognitive performance. The research is intended to inform the development of malaria control strategies for school-aged children in areas of highly seasonal transmission.

Future work will also examine the effects of malaria control on child development in pre-school children, with a focus on cognitive foundation skills for early literacy.

Reliability of school surveys in estimating geographic variation in malaria transmission in the western Kenyan Highlands.

LSHTM Investigators

Jonathan Cox.


of Notre Dame, USA) & Chrispin Owaga, Elizabeth Marube,

Wycliffe Odongo, Albert Okoth, Pauline China & Robin Oriango

Prevention, Kenya).

Funding:

Malaria Transmission Consortium.

School surveys provide an operational approach to assess malaria transmission through parasite prevalence however, there is limited evidence on how well these estimates compare to those from the surrounding community.

Concurrent school and community cross-sectional surveys were conducted in 46 school/community clusters

36.4% of school children sampled resided within 600 m of their school with the mean distance of 793 m (IQR:

consistently higher than those from community surveys

the school population was restricted to those residing

seroconversion rates were similar between school and

prevalence rates measured during school surveys have been directly compared to those in the surrounding community. Ultimately, school-based estimates can be used as a reliable indicator of malaria transmission intensity in the wider community and may provide a basis for identifying priority areas for malaria control and be used to measure or monitor changes in transmission intensity.



Analysis of multiplicity of infection and clonal diversity in paired human blood and mosquito oocyst samples from Burkina Faso.

LSHTM Investigators

Drakeley.

External Investigators/Collaborators: Kerstin Lanke & Will

Stone (Radboud University Nijmegen Medical Center, Nijmegen,

et de Formation sur le Paludisme, Burkina Faso).

Funding:

The aim of the project was to investigate the clonal diversity and the number of clones that are transmitted when a mosquito takes a blood meal from an individual infected with Plasmodium falciparum malaria.

to the clones found in mosquito midguts.

We recorded 4 different outcomes:

various combinations of matching clones detected in the

various combinations of different clones (not present in

The work is ongoing and we are now planning to test samples from the 4th outcome for recombination using a cloning and sequencing strategy. In addition, we also have data on asexual parasite density, gametocytaemia and number of oocysts in the midgut. Further analysis is needed to understand the relevance of clonal diversity and number in transmission from humans to the mosquito vector.

Bioko Island Malaria Control Project.

LSHTM Investigators: Immo Kleinschmidt, Chris Drakeley, Colin

Sutherland, Andrea Rehman, John Bradley & Jo Lines.

External Investigators/Collaborators: Christopher Schwabe

(Medical Care Development International); Michel Slotman (Texas

A&M University, USA); Janet Hemingway (Liverpool School of

Consortium).

Funding: Marathon Oil Company through Medical Care

Development International.

Comprehensive malaria control measures were introduced in Bioko, Equatorial Guinea, in 2004. The

rate , malaria related disease burden, child mortality and sero-positivity to malarial antigens have been observed. These reductions have been uneven and marked by substantial variation in prevalence of infection between

island. In a programmatic setting, a number of questions

related to malaria control and elimination are being investigated. These include evaluation of:

uniformly applied interventions

conversion, insecticide treated net and indoor residual

kdr gene in Anopheles gambiae on the effectiveness of pyrethroid based vector control

community participation

durability and utilization

Identifying Anopheles breeding sites, Bioko Island.



Analysis of multiplicity of infection and clonal diversity in paired human blood and mosquito oocyst samples from Burkina Faso.

LSHTM Investigators

Drakeley.

External Investigators/Collaborators: Kerstin Lanke & Will

Stone (Radboud University Nijmegen Medical Center, Nijmegen,

et de Formation sur le Paludisme, Burkina Faso).

Funding:

The aim of the project was to investigate the clonal diversity and the number of clones that are transmitted when a mosquito takes a blood meal from an individual infected with Plasmodium falciparum malaria.

to the clones found in mosquito midguts.

We recorded 4 different outcomes:

various combinations of matching clones detected in the

various combinations of different clones (not present in

The work is ongoing and we are now planning to test samples from the 4th outcome for recombination using a cloning and sequencing strategy. In addition, we also have data on asexual parasite density, gametocytaemia and number of oocysts in the midgut. Further analysis is needed to understand the relevance of clonal diversity and number in transmission from humans to the mosquito vector.

Bioko Island Malaria Control Project.

LSHTM Investigators: Immo Kleinschmidt, Chris Drakeley, Colin

Sutherland, Andrea Rehman, John Bradley & Jo Lines.

External Investigators/Collaborators: Christopher Schwabe

(Medical Care Development International); Michel Slotman (Texas

A&M University, USA); Janet Hemingway (Liverpool School of

Consortium).

Funding: Marathon Oil Company through Medical Care

Development International.

Comprehensive malaria control measures were introduced in Bioko, Equatorial Guinea, in 2004. The

rate , malaria related disease burden, child mortality and sero-positivity to malarial antigens have been observed. These reductions have been uneven and marked by substantial variation in prevalence of infection between

island. In a programmatic setting, a number of questions

related to malaria control and elimination are being investigated. These include evaluation of:

uniformly applied interventions

conversion, insecticide treated net and indoor residual

kdr gene in Anopheles gambiae on the effectiveness of pyrethroid based vector control

community participation

durability and utilization

Identifying Anopheles breeding sites, Bioko Island.



Tracking Resistance to Artemisinins Collaboration.

LSHTM Investigators

External Investigators/Collaborators: Elizabeth Ashley & Nick

White (Mahidol Oxford Research Unit, Thailand); Siv Sovannaroth,

Malaria Control Programme, Cambodia); Ric Fairhust, & Chanaki

Amaratunga (National Institutes of Health, USA); Sethavudh

Kaewviset & Sasithon Pukrittayakamee (Mahidol University,

Thailand); Abdul Faiz (Chittagong Medical School, Bangladesh);

Khin Maung Lwin and Francois Nosten (Shoklo Malaria Research

Unit, Thailand); Olugbenga Mokuolu (University of Ilorin Teaching

Hospital, Nigeria).


is a multi-country multi-disciplinary collaboration. The

was completed in 2013 after recruiting a total of 1241

of spread of artemisinin resistance.

The School team was responsible for a range of studies exploring the demand, use and quality of antimalarial drugs and the implications for the development and control of drug resistance. Patients enrolled in the clinical studies in 9 sites participated in an additional study aimed a collecting additional behavioural and epidemiological data. In addition the locations of their homes and likely places of transmission were mapped.

Cambodia, Laos, Thailand, Myanmar and Nigeria for

Consortium drug quality project. Finally, in Cambodia structured and in-depth

interviews were carried out with communities at risk including mobile and migrant workers, in order to understand their demand for and use of fever treatments and to identify possible interventions for improving the use of antimalarial medicines.

Malaria, drug resistance and mobile and migrants population in Cambodia: a framework of planning.

LSHTM Investigators

External Investigators/Collaborators: Chea Nguon & Char Meng

Chuor (National Malaria Control Programme, Cambodia) & Sara

Canavati & Arantxa Roca (Malaria Consortium).

Funding: The Department for International Development .

The movement of populations in malaria-endemic areas poses a major threat to the spread of artemisinin

activities are simultaneously a high risk group for malaria and a “hard to reach” population.

We have developed the parasite multiplication factor

and populated it with activities conducted by population in

seasonal workers; construction/mine workers; forest workers; security personnel and visitors and four related indices: a vulnerability index, a forest/exposure index, an access index and a summary malaria risk index. The PMF also suggests relevant packages of interventions

The National Malaria Control Programme and other stakeholders were directly engaged in the development of the framework to maximize the relevance and utility of the framework. Challenges remain in the need to adapt research results, their complexity and the dynamic aspects of MMP to be combined with the need of a clear and relatively static strategy for programmatic and implementation purposes.

Sub-patent malaria, a challenge to diagnostics for malaria elimination in Mindanao islands, the Philippines.

LSHTM Investigators

Sutherland.

External Investigators/Collaborators: Judeline Dimalibot

(University of the Philippines Los Banos, Philippines); Christine

Candari (Philippines National Malaria Control Program, Philippines);

Fatima Pir Allian (Sinhaya Sinkawman, Philippines); Sukarno Asri &

Funding: Ford Foundation International Fellowships Program;

Chadwick Trust; University of the Philippines System Doctoral

Studies Fund; Philippine Council for Health Research and

Development.

We focused on three endemic provinces of Sarangani, South Cotabato and Tawi-Tawi in Mindanao islands,

which are aiming for continued reduction in malaria cases to achieve the Philippines’ goal of malaria elimination by 2020. In these provinces we screened malaria infection in 2595 individuals using microscopy and/or rapid diagnostic

and serological screening of exposure to P. falciparum and Plasmodium vivax infections.

Using the nested PCR assay as the gold standard,

pLDH-based RDT failed to diagnose subpatent P. falciparum and P. vivax infections in these provinces. We will complement our PCR diagnoses with serological data to locate residual transmission foci. The presence of subpatent malaria in Sarangani, South Cotabato and Tawi-Tawi recommends a review of existing policies on

adopting a more sensitive molecular method that can be deployed in these transmission settings.



Tracking Resistance to Artemisinins Collaboration.

LSHTM Investigators

External Investigators/Collaborators: Elizabeth Ashley & Nick

White (Mahidol Oxford Research Unit, Thailand); Siv Sovannaroth,

Malaria Control Programme, Cambodia); Ric Fairhust, & Chanaki

Amaratunga (National Institutes of Health, USA); Sethavudh

Kaewviset & Sasithon Pukrittayakamee (Mahidol University,

Thailand); Abdul Faiz (Chittagong Medical School, Bangladesh);

Khin Maung Lwin and Francois Nosten (Shoklo Malaria Research

Unit, Thailand); Olugbenga Mokuolu (University of Ilorin Teaching

Hospital, Nigeria).


is a multi-country multi-disciplinary collaboration. The

was completed in 2013 after recruiting a total of 1241

of spread of artemisinin resistance.

The School team was responsible for a range of studies exploring the demand, use and quality of antimalarial drugs and the implications for the development and control of drug resistance. Patients enrolled in the clinical studies in 9 sites participated in an additional study aimed a collecting additional behavioural and epidemiological data. In addition the locations of their homes and likely places of transmission were mapped.

Cambodia, Laos, Thailand, Myanmar and Nigeria for

Consortium drug quality project. Finally, in Cambodia structured and in-depth

interviews were carried out with communities at risk including mobile and migrant workers, in order to understand their demand for and use of fever treatments and to identify possible interventions for improving the use of antimalarial medicines.

Malaria, drug resistance and mobile and migrants population in Cambodia: a framework of planning.

LSHTM Investigators

External Investigators/Collaborators: Chea Nguon & Char Meng

Chuor (National Malaria Control Programme, Cambodia) & Sara

Canavati & Arantxa Roca (Malaria Consortium).

Funding: The Department for International Development .

The movement of populations in malaria-endemic areas poses a major threat to the spread of artemisinin

activities are simultaneously a high risk group for malaria and a “hard to reach” population.

We have developed the parasite multiplication factor

and populated it with activities conducted by population in

seasonal workers; construction/mine workers; forest workers; security personnel and visitors and four related indices: a vulnerability index, a forest/exposure index, an access index and a summary malaria risk index. The PMF also suggests relevant packages of interventions

The National Malaria Control Programme and other stakeholders were directly engaged in the development of the framework to maximize the relevance and utility of the framework. Challenges remain in the need to adapt research results, their complexity and the dynamic aspects of MMP to be combined with the need of a clear and relatively static strategy for programmatic and implementation purposes.

Sub-patent malaria, a challenge to diagnostics for malaria elimination in Mindanao islands, the Philippines.

LSHTM Investigators

Sutherland.

External Investigators/Collaborators: Judeline Dimalibot

(University of the Philippines Los Banos, Philippines); Christine

Candari (Philippines National Malaria Control Program, Philippines);

Fatima Pir Allian (Sinhaya Sinkawman, Philippines); Sukarno Asri &

Funding: Ford Foundation International Fellowships Program;

Chadwick Trust; University of the Philippines System Doctoral

Studies Fund; Philippine Council for Health Research and

Development.

We focused on three endemic provinces of Sarangani, South Cotabato and Tawi-Tawi in Mindanao islands,

which are aiming for continued reduction in malaria cases to achieve the Philippines’ goal of malaria elimination by 2020. In these provinces we screened malaria infection in 2595 individuals using microscopy and/or rapid diagnostic

and serological screening of exposure to P. falciparum and Plasmodium vivax infections.

Using the nested PCR assay as the gold standard,

pLDH-based RDT failed to diagnose subpatent P. falciparum and P. vivax infections in these provinces. We will complement our PCR diagnoses with serological data to locate residual transmission foci. The presence of subpatent malaria in Sarangani, South Cotabato and Tawi-Tawi recommends a review of existing policies on

adopting a more sensitive molecular method that can be deployed in these transmission settings.



Characterisation of the cryptic reservoir of malaria infections: a study from Burkina Faso.

LSHTM Investigators

Bousema.


(Centre National de Recherche et de Formation sur le Paludisme,

Burkina Faso) & Robert Sauerwein & Adrian Luty (Radboud

university medical center, Netherlands).

Funding: Netherlands Organization for Higher Education in the

Man-to-mosquito malaria transmission depends on the presence of mature gametocytes in the peripheral blood; however only a small proportion of infected individuals have patent gametocytes.

The contribution of infections with subpatent gametocytes to onward malaria transmission is unknown. In this study, we assessed the importance of this cryptic reservoir of infections. Infectiousness of 130 individuals living in a malaria endemic area in Burkina Faso was determined at the start/peak of transmission season and in the subsequent dry season by membrane feeding

were ~3 times more infectious than individuals with subpatent gametocytes. Throughout the study, most infectious individuals had subpatent gametocytes. Most infected mosquitoes fed on blood with submicroscopic

mosquito infections in the community but at least 15% of

that submicroscopic gametocytes are a major source of mosquito infection and that all ages contribute to the infectious reservoir.

submicroscopic gametocytes to malaria transmission during the transition between dry and wet season and to

vector exposure in natural populations.

Infectiousness by season, age and gametocyte status. The stacked bars represent the total population in each age group and at each time

microscopy; hatched bars indicate the proportion of individuals who

bars indicate the proportion of individuals who do not infect mosquitoes

Border malaria and approaches to local elimination in Namibia.

LSHTM Investigators: Immo Kleinschmidt.


Sturrock (The University of California, San Francisco, USA); Davis

Mumbengegwi (University of Namibia, Namibia) & Stark Katokele

(National Malaria Program, Namibia).

Funding:

Malaria incidence has declined to low levels in Namibia, and the country has set 2020 as the target for malaria elimination. Many of the residual cases occur in the

Malaria transmission may be associated with

to determine risk factors for malaria, including cross-border travel, intervention coverage and compliance, and local factors that may be linked to transmission of malaria. By mapping cases and controls, and testing for sub-patent infections and antibody seroconversions in the neighbourhood of each case and each control, the study will investigate the existence of any hotspots of transmission.

which will evaluate targeted parasite and vector control in the neighbourhood of cases.

Quantifying travel behaviour for infectious disease research: A comparison of data from surveys and mobile phones.

LSHTM Investigators

Drakeley & Jonathan Cox.

External Investigators/Collaborators: Amy Wesolowski (Carnegie

Mellon University, USA.; Nathan Eagle & Caroline Buckee (Harvard

School of Public Health, USA); Jennifer Stevenson (Kenya Medical

Kenya & Johns Hopkins Bloomberg School of Public Health, USA);

Chrispin Owaga & Elizabeth Marube (Kenya Medical Research

Funding:


Human travel impacts the spread of infectious diseases across spatial and temporal scales, with broad implications for the biological and social sciences.

obtain, particularly in low-income countries.Travel survey data provide detailed demographic

information, but sample sizes are often small and travel histories are hard to validate. Mobile phone records can provide vast quantities of spatio-temporal travel data, but vary in spatial resolution and explicitly do not include individual information in order to protect the privacy of subscribers. We have compared and contrasted both

sources of data over the same time period in a rural area of Kenya. Mobile phone records reporting an order

indicates that people with phones are more likely to travel and the primary motivation for traveling is visiting family

broad travel patterns, distinguish regional differences in travel, and are able to identify the main routes of malaria importation. Ultimately, each data source provides different insights that can be combined to form a more detailed picture of travel in low-income settings to understand the spread of infectious diseases.



Characterisation of the cryptic reservoir of malaria infections: a study from Burkina Faso.

LSHTM Investigators

Bousema.


(Centre National de Recherche et de Formation sur le Paludisme,

Burkina Faso) & Robert Sauerwein & Adrian Luty (Radboud

university medical center, Netherlands).

Funding: Netherlands Organization for Higher Education in the

Man-to-mosquito malaria transmission depends on the presence of mature gametocytes in the peripheral blood; however only a small proportion of infected individuals have patent gametocytes.

The contribution of infections with subpatent gametocytes to onward malaria transmission is unknown. In this study, we assessed the importance of this cryptic reservoir of infections. Infectiousness of 130 individuals living in a malaria endemic area in Burkina Faso was determined at the start/peak of transmission season and in the subsequent dry season by membrane feeding

were ~3 times more infectious than individuals with subpatent gametocytes. Throughout the study, most infectious individuals had subpatent gametocytes. Most infected mosquitoes fed on blood with submicroscopic

mosquito infections in the community but at least 15% of

that submicroscopic gametocytes are a major source of mosquito infection and that all ages contribute to the infectious reservoir.

submicroscopic gametocytes to malaria transmission during the transition between dry and wet season and to

vector exposure in natural populations.

Infectiousness by season, age and gametocyte status. The stacked bars represent the total population in each age group and at each time

microscopy; hatched bars indicate the proportion of individuals who

bars indicate the proportion of individuals who do not infect mosquitoes

Border malaria and approaches to local elimination in Namibia.

LSHTM Investigators: Immo Kleinschmidt.


Sturrock (The University of California, San Francisco, USA); Davis

Mumbengegwi (University of Namibia, Namibia) & Stark Katokele

(National Malaria Program, Namibia).

Funding:

Malaria incidence has declined to low levels in Namibia, and the country has set 2020 as the target for malaria elimination. Many of the residual cases occur in the

Malaria transmission may be associated with

to determine risk factors for malaria, including cross-border travel, intervention coverage and compliance, and local factors that may be linked to transmission of malaria. By mapping cases and controls, and testing for sub-patent infections and antibody seroconversions in the neighbourhood of each case and each control, the study will investigate the existence of any hotspots of transmission.

which will evaluate targeted parasite and vector control in the neighbourhood of cases.

Quantifying travel behaviour for infectious disease research: A comparison of data from surveys and mobile phones.

LSHTM Investigators

Drakeley & Jonathan Cox.

External Investigators/Collaborators: Amy Wesolowski (Carnegie

Mellon University, USA.; Nathan Eagle & Caroline Buckee (Harvard

School of Public Health, USA); Jennifer Stevenson (Kenya Medical

Kenya & Johns Hopkins Bloomberg School of Public Health, USA);

Chrispin Owaga & Elizabeth Marube (Kenya Medical Research

Funding:


Human travel impacts the spread of infectious diseases across spatial and temporal scales, with broad implications for the biological and social sciences.

obtain, particularly in low-income countries.Travel survey data provide detailed demographic

information, but sample sizes are often small and travel histories are hard to validate. Mobile phone records can provide vast quantities of spatio-temporal travel data, but vary in spatial resolution and explicitly do not include individual information in order to protect the privacy of subscribers. We have compared and contrasted both

sources of data over the same time period in a rural area of Kenya. Mobile phone records reporting an order

indicates that people with phones are more likely to travel and the primary motivation for traveling is visiting family

broad travel patterns, distinguish regional differences in travel, and are able to identify the main routes of malaria importation. Ultimately, each data source provides different insights that can be combined to form a more detailed picture of travel in low-income settings to understand the spread of infectious diseases.



period.

Which factors increase the risk for acquiring Plasmodium knowlesi malaria in Sabah, Malaysia.

LSHTM Investigators: Christopher Drakeley, Jon Cox & Kimberly

Fornace.


Australia); Timothy William (Sabah Department of Health, Malaysia).


Council; The Economic and Social Research Council; The Medical

Research Council; The Natural Environment Research Council.

Human malaria due to the simian parasite Plasmodium knowlesi

Pk transmission has been linked to factors such as individual forest and seasonal

rainfall, detailed environmental, behavioural and genetic risk factors have not been systematically evaluated.

This population-based case control study aims to detect and describe factors which predispose individuals to Pk symptomatic infection in Sabah, Malaysia. Three controls from the same village will be matched for each case detected. Cases and controls will be interviewed on demographics, malaria history and prevention activities, travel history and movement patterns and interactions with macaques. Blood sampling will be done for PCR

cases and 508 controls have been recruited to date and enrolment is expected to continue through early 2015.

Transmission and control of Plasmodium knowlesi: a mathematical modelling study.

LSHTM Investigators: Christopher Drakeley.

External Investigators/Collaborators: Natsuko Imai, Michael

Plasmodium knowlesi is a zoonotic malaria but now

humans come into increasing contact with the reservoir

deforestation, assessing the potential for a shift from zoonotic to sustained Plasmodium knowlesi transmission between humans is of major importance.

developed, taking into account the three areas (forest,

occur. Latin hypercube sampling of model parameters was utilised to identify parameter sets consistent with plausible prevalence in macaques and humans inferred from observed data. We then explore the consequences of increasing human-macaque contact in the farm, the likely impact of rapid treatment, and the use of long-

spread of this emerging infection.

transmission being sustained by the macaque population with spill over infections in the human population and with

The extent to which macaques forage for food in the farms had a non-linear relationship with human infection prevalence, with the highest prevalence occurring when

frequently to the forest where they experience higher contact with vectors and hence sustain transmission.

sustained human to human transmission in the absence of macaques, although with a low human reproduction

rapid treatment provide personal protection to humans with maximal estimated reductions in human prevalence of 42% and 95%, respectively.

This model simulates conditions where Plasmodium knowlesi transmission may occur and the potential impact of control measures. Predictions suggest that

the risk of infection in humans, but they must be actively implemented if Plasmodium knowlesi is to be controlled. More data to better parameterise models is needed.

Schematic distribution of forest, farm, villages, and the movement of macaques and humans between the 3 areas, and the hypothesised transmission cycle of Plasmodium knowlesi in Malaysia and Southeast Asia. Adapted from the yellow fever transmission cycle observed in Africa.



period.

Which factors increase the risk for acquiring Plasmodium knowlesi malaria in Sabah, Malaysia.

LSHTM Investigators: Christopher Drakeley, Jon Cox & Kimberly

Fornace.


Australia); Timothy William (Sabah Department of Health, Malaysia).


Council; The Economic and Social Research Council; The Medical

Research Council; The Natural Environment Research Council.

Human malaria due to the simian parasite Plasmodium knowlesi

Pk transmission has been linked to factors such as individual forest and seasonal

rainfall, detailed environmental, behavioural and genetic risk factors have not been systematically evaluated.

This population-based case control study aims to detect and describe factors which predispose individuals to Pk symptomatic infection in Sabah, Malaysia. Three controls from the same village will be matched for each case detected. Cases and controls will be interviewed on demographics, malaria history and prevention activities, travel history and movement patterns and interactions with macaques. Blood sampling will be done for PCR

cases and 508 controls have been recruited to date and enrolment is expected to continue through early 2015.

Transmission and control of Plasmodium knowlesi: a mathematical modelling study.

LSHTM Investigators: Christopher Drakeley.

External Investigators/Collaborators: Natsuko Imai, Michael

Plasmodium knowlesi is a zoonotic malaria but now

humans come into increasing contact with the reservoir

deforestation, assessing the potential for a shift from zoonotic to sustained Plasmodium knowlesi transmission between humans is of major importance.

developed, taking into account the three areas (forest,

occur. Latin hypercube sampling of model parameters was utilised to identify parameter sets consistent with plausible prevalence in macaques and humans inferred from observed data. We then explore the consequences of increasing human-macaque contact in the farm, the likely impact of rapid treatment, and the use of long-

spread of this emerging infection.

transmission being sustained by the macaque population with spill over infections in the human population and with

The extent to which macaques forage for food in the farms had a non-linear relationship with human infection prevalence, with the highest prevalence occurring when

frequently to the forest where they experience higher contact with vectors and hence sustain transmission.

sustained human to human transmission in the absence of macaques, although with a low human reproduction

rapid treatment provide personal protection to humans with maximal estimated reductions in human prevalence of 42% and 95%, respectively.

This model simulates conditions where Plasmodium knowlesi transmission may occur and the potential impact of control measures. Predictions suggest that

the risk of infection in humans, but they must be actively implemented if Plasmodium knowlesi is to be controlled. More data to better parameterise models is needed.

Schematic distribution of forest, farm, villages, and the movement of macaques and humans between the 3 areas, and the hypothesised transmission cycle of Plasmodium knowlesi in Malaysia and Southeast Asia. Adapted from the yellow fever transmission cycle observed in Africa.



A cluster-randomised trial of targetted control to eliminate malaria in central Senegal: study design and acceptability of the interventions.

LSHTM Investigators: Badara Cisse, Clare Flach, Matt Cairns,

External Investigators/Collaborators: Abdoulaye Diallo, Fassiath

Tairou, Ousmane Sy, Jean-Louis Ndiaye, Tidiane Ndoye, Lansana

Diop, Senegal); El-Hadj Ba & Cheikh Sokhna (Institut de Recherche

Funding: The Wellcome Trust; The Medical Research Council;

The Department for International Development Clinical Trials

Control and Elimination Partnership in Africa.

The purpose of this trial is to evaluate the extent to which a targetted malaria control strategy combining

chemotherapy, delivered by district health staff to villages reporting clinical cases, can reduce the transmission of malaria, in a region where scaling up of control measures has been effective in reducing the incidence of malaria.

The trial will also determine whether, as part of this strategy, chemotherapy should be delivered to all

The unit of randomisation is the health post and the population of approximately 10,000 people that it serves. 40 health posts were randomized, 15 to receive targeted

Interventions are delivered over two years, the primary outcomes are the incidence of malaria in the second year and the prevalence of parasitaemia just after the main peak period of transmission in the second year. To assess effects on transmission, incidence in non-targetted areas in each cluster will be compared. In intervention

reported the previous year. In 30 clusters, all households in hotspot villages were targetted to receive IRS with

were screened using a malaria rapid diagnostic test

coverage was topped-up by providing persons diagnosed with malaria with a LLIN.Results will be available in 2015.

Identifying and characterising foci of malaria transmission in potential malaria elimination settings in rural Senegal.

LSHTM Investigators

Milligan.

External Investigators/Collaborators: Ernest Faye, El hadj Ba, El Hadj Diouf,

Funding: The Malaria Capacity Development Consortium.

programmes in Senegal is threatened by resistance to insecticides.We determined the effectiveness of LLIN use by the individual

and in the local community in reducing the incidence of malaria.

the district of Fatick, central Senegal, in an area covered by a

uncomplicated malaria presenting at health posts in the district

study. For each case, one or two controls of the same age group, selected by random sampling from the DSS listing for the district, were recruited concurrently if a malaria rapid diagnostic test was negative. For cases and controls, and members of their households and of surrounding households, bednet use and approximate age was recorded after inspecting sleeping places. Information about bednet use was also obtained for all households in the district when visited in demographic surveillance rounds from January to December 2011. Conditional logistic regression was used to estimate the rate ratio associated with use of LLIN, and with the level of local coverage of LLINs in the community grouped by quintiles, adjusted for potential confounding factors including distance to health facility, socio-economic status, and distance to mosquito breeding sites.

540 malaria case-control pairs were recruited. Sleeping under an LLIN, and local coverage of LLINs, were independently associated with reduced malaria incidence. Malaria incidence for individuals in communities with coverage in the upper quintile (>81% of persons

LLINs remain effective in central Senegal but high coverage is required to maximise impact. LLIN distribution programmes should target communities with low coverage.

Bio assays on LLINs of 12 to 15 months of use show strong correlation between level of malaria transmission and mosquitos mortality rates after exposition to LLINs.

The project also allowed an extension of the malaria surveillance initiated in 2008 in central Senegal where malaria transmission remains patchy with many communities free of clinical cases over 5 years of follow-up.



A cluster-randomised trial of targetted control to eliminate malaria in central Senegal: study design and acceptability of the interventions.

LSHTM Investigators: Badara Cisse, Clare Flach, Matt Cairns,

External Investigators/Collaborators: Abdoulaye Diallo, Fassiath

Tairou, Ousmane Sy, Jean-Louis Ndiaye, Tidiane Ndoye, Lansana

Diop, Senegal); El-Hadj Ba & Cheikh Sokhna (Institut de Recherche

Funding: The Wellcome Trust; The Medical Research Council;

The Department for International Development Clinical Trials

Control and Elimination Partnership in Africa.

The purpose of this trial is to evaluate the extent to which a targetted malaria control strategy combining

chemotherapy, delivered by district health staff to villages reporting clinical cases, can reduce the transmission of malaria, in a region where scaling up of control measures has been effective in reducing the incidence of malaria.

The trial will also determine whether, as part of this strategy, chemotherapy should be delivered to all

The unit of randomisation is the health post and the population of approximately 10,000 people that it serves. 40 health posts were randomized, 15 to receive targeted

Interventions are delivered over two years, the primary outcomes are the incidence of malaria in the second year and the prevalence of parasitaemia just after the main peak period of transmission in the second year. To assess effects on transmission, incidence in non-targetted areas in each cluster will be compared. In intervention

reported the previous year. In 30 clusters, all households in hotspot villages were targetted to receive IRS with

were screened using a malaria rapid diagnostic test

coverage was topped-up by providing persons diagnosed with malaria with a LLIN.Results will be available in 2015.

Identifying and characterising foci of malaria transmission in potential malaria elimination settings in rural Senegal.

LSHTM Investigators

Milligan.

External Investigators/Collaborators: Ernest Faye, El hadj Ba, El Hadj Diouf,

Funding: The Malaria Capacity Development Consortium.

programmes in Senegal is threatened by resistance to insecticides.We determined the effectiveness of LLIN use by the individual

and in the local community in reducing the incidence of malaria.

the district of Fatick, central Senegal, in an area covered by a

uncomplicated malaria presenting at health posts in the district

study. For each case, one or two controls of the same age group, selected by random sampling from the DSS listing for the district, were recruited concurrently if a malaria rapid diagnostic test was negative. For cases and controls, and members of their households and of surrounding households, bednet use and approximate age was recorded after inspecting sleeping places. Information about bednet use was also obtained for all households in the district when visited in demographic surveillance rounds from January to December 2011. Conditional logistic regression was used to estimate the rate ratio associated with use of LLIN, and with the level of local coverage of LLINs in the community grouped by quintiles, adjusted for potential confounding factors including distance to health facility, socio-economic status, and distance to mosquito breeding sites.

540 malaria case-control pairs were recruited. Sleeping under an LLIN, and local coverage of LLINs, were independently associated with reduced malaria incidence. Malaria incidence for individuals in communities with coverage in the upper quintile (>81% of persons

LLINs remain effective in central Senegal but high coverage is required to maximise impact. LLIN distribution programmes should target communities with low coverage.

Bio assays on LLINs of 12 to 15 months of use show strong correlation between level of malaria transmission and mosquitos mortality rates after exposition to LLINs.

The project also allowed an extension of the malaria surveillance initiated in 2008 in central Senegal where malaria transmission remains patchy with many communities free of clinical cases over 5 years of follow-up.



national humanitarian assistance is greatest but also during chronic emergencies when there is no fully rec-ognised government but opportunity for providing more comprehensive assistance improves. The handbook

-tors with practical advice on designing and implement-ing measures in both man-made and natural disasters. The handbook is organised into ten chapters covering coordination and ad-vocacy, assessment and operational plan-ning, surveillance outbreak response, diagnosis and case management, ap-proaches for vector control and personal protection, commu-nity and refugee par-ticipation, monitoring and evaluation, and operational research to improve the effectiveness of prevention and treat-ment in humanitarian emergencies.

Malaria control and development

Methodological development of whole-economy modelling of infectious disease: Plasmodium falciparum malaria control in Africa.

LSHTM Investigators: Richard Smith, Marcus Keogh-Brown,

Michael Bretscher & Chris Drakeley.

External Investigators/Collaborators: Henning Tarp Jensen

(University of Copenhagen, Denmark).

Funding: Medical Research Council Methodology.

to develop epidemiological models of malaria, and to estimate cost-effectiveness of interventions and malaria control. However, interactions between malaria, demographic characteristics and the national economy have received little attention. Many economic studies of malaria take a partial equilibrium approach which

interventions.

takes an economy-wide approach to estimating full

capture many important economic aspects of population health including morbidity and mortality effects on labour supply, long-term cognitive effects of child morbidity, and public budget implications of prevention, treatment, and basic care for the sick and dying. Existing applications of

Malaria, but do not capture interaction or feedback effects between epidemiology, demographics and the economy.

model of malaria transmission which captures multiplicity

simulation framework for Ghana and for Tanzania has been produced and policy simulations will soon be implemented.

Socioeconomic development as an intervention against malaria.

LSHTM Investigators: Lucy Tusting, Barbara Willey, Richard Smith

& Steve Lindsay.

External Investigators/Collaborators: Hmooda Toto Kafy

(National Malaria Control Programme, Sudan); Henry Lucas & John

Thompson (Institute of Development Studies, UK).


Future progress in malaria control may be hampered by the development of resistance to drugs and insecticides and by the contraction of aid budgets. Historically, control

This project aimed to assess whether socioeconomic development can contribute to malaria control. We

did a systematic review and meta-analysis to assess whether the risk of malaria in children aged 0–15 years

reviewed, 20 met the criteria for inclusion in the qualitative analysis, and 15 of these reported the necessary data for inclusion in the meta-analysis. The odds of malaria infection were higher in the poorest children than in the

existing malaria control efforts, increased investment in interventions to support socioeconomic development is warranted, since such interventions could prove highly effective and sustainable against malaria in the long term.

Malaria control in humanitarian emergencies: an inter-

LSHTM Investigators: Natasha Howard, Mark Rowland &

Toby Leslie.

External Investigators/Collaborators: A writing committee of

malaria experts coordinated by Jose Nkuni, Natasha Howard

and Abraham Mnzava produced the draft of this second ver-

sion.

Funding: The World Health Organisation.

This second edition is a comprehensive interagency manual on how to control malaria in countries af-

authorship by staff at the School who have broad experience of working in emergencies the handbook represents a thorough review of the literature and knowledge gained during the last decade. The struc-

an additional chapter on humanitarian coordination.

best practices, improvements in technologies, avail-ability of new tools, and changes in World Health

The interagency handbook is designed to set out malaria control responses in humanitarian emergen-cies, in both the acute phase when reliance on inter-

Malaria Centre members are evaluating the role of events and interventions beyond the health sector in shaping malaria risks and responses.



national humanitarian assistance is greatest but also during chronic emergencies when there is no fully rec-ognised government but opportunity for providing more comprehensive assistance improves. The handbook

-tors with practical advice on designing and implement-ing measures in both man-made and natural disasters. The handbook is organised into ten chapters covering coordination and ad-vocacy, assessment and operational plan-ning, surveillance outbreak response, diagnosis and case management, ap-proaches for vector control and personal protection, commu-nity and refugee par-ticipation, monitoring and evaluation, and operational research to improve the effectiveness of prevention and treat-ment in humanitarian emergencies.

Malaria control and development

Methodological development of whole-economy modelling of infectious disease: Plasmodium falciparum malaria control in Africa.

LSHTM Investigators: Richard Smith, Marcus Keogh-Brown,

Michael Bretscher & Chris Drakeley.

External Investigators/Collaborators: Henning Tarp Jensen

(University of Copenhagen, Denmark).

Funding: Medical Research Council Methodology.

to develop epidemiological models of malaria, and to estimate cost-effectiveness of interventions and malaria control. However, interactions between malaria, demographic characteristics and the national economy have received little attention. Many economic studies of malaria take a partial equilibrium approach which

interventions.

takes an economy-wide approach to estimating full

capture many important economic aspects of population health including morbidity and mortality effects on labour supply, long-term cognitive effects of child morbidity, and public budget implications of prevention, treatment, and basic care for the sick and dying. Existing applications of

Malaria, but do not capture interaction or feedback effects between epidemiology, demographics and the economy.

model of malaria transmission which captures multiplicity

simulation framework for Ghana and for Tanzania has been produced and policy simulations will soon be implemented.

Socioeconomic development as an intervention against malaria.

LSHTM Investigators: Lucy Tusting, Barbara Willey, Richard Smith

& Steve Lindsay.

External Investigators/Collaborators: Hmooda Toto Kafy

(National Malaria Control Programme, Sudan); Henry Lucas & John

Thompson (Institute of Development Studies, UK).


Future progress in malaria control may be hampered by the development of resistance to drugs and insecticides and by the contraction of aid budgets. Historically, control

This project aimed to assess whether socioeconomic development can contribute to malaria control. We

did a systematic review and meta-analysis to assess whether the risk of malaria in children aged 0–15 years

reviewed, 20 met the criteria for inclusion in the qualitative analysis, and 15 of these reported the necessary data for inclusion in the meta-analysis. The odds of malaria infection were higher in the poorest children than in the

existing malaria control efforts, increased investment in interventions to support socioeconomic development is warranted, since such interventions could prove highly effective and sustainable against malaria in the long term.

Malaria control in humanitarian emergencies: an inter-

LSHTM Investigators: Natasha Howard, Mark Rowland &

Toby Leslie.

External Investigators/Collaborators: A writing committee of

malaria experts coordinated by Jose Nkuni, Natasha Howard

and Abraham Mnzava produced the draft of this second ver-

sion.

Funding: The World Health Organisation.

This second edition is a comprehensive interagency manual on how to control malaria in countries af-

authorship by staff at the School who have broad experience of working in emergencies the handbook represents a thorough review of the literature and knowledge gained during the last decade. The struc-

an additional chapter on humanitarian coordination.

best practices, improvements in technologies, avail-ability of new tools, and changes in World Health

The interagency handbook is designed to set out malaria control responses in humanitarian emergen-cies, in both the acute phase when reliance on inter-

Malaria Centre members are evaluating the role of events and interventions beyond the health sector in shaping malaria risks and responses.



Mapping causes of non-malarial fever in Africa and Asia.

LSHTM Investigators

Schellenberg.

External Investigators/Collaborators: Heidi Hopkins & David Bell

Funding:

Consortium.

The successful introduction of malaria rapid tests into routine health services is challenged by the lack of lo-cal knowledge of the probability of alternative causes of febrile illness. To address this we searched databases of peer reviewed publications to identify studies that had

described the prevalence of infection among patients with undifferentiated fever.

papers met criteria of blood culture or csf series in undif-

Both sets of data suggest a large variation in quality be-

for laboratory or antibiotic sensitivity data. It is hoped to -

malarial Resistance Network and that this will be used by public health authorities. The longer term future and link-age with other mapping initiatives is under discussion.

Future priorities

Knowing insects: hosts, vectors and companions of science.

The contribution of the Malaria Centre to policy making for malaria treatment and control.

LSHTM Investigators: Ann Kelly

External Investigators/Collaborators: Noemi Tousignant

(University of Cambridge, UK); Uli Beisel (Bayreuth University,

Researchers at the School carried out social analy-sis of insects as disease vectors in Tanzania, The Gambia, Senegal and Ghana. Reading insects not simply as vectors of disease, but equally as hosts, vectors and companions of science, their work opens up the epistemic, biopolitical and social dimensions of human–insect connections. By parsing these inter-sections, they suggest we can begin to understand the kinds of knowledge made possible and elusive by insects’ capacity to connect and carry, inscribe and destabilize, disgust and inspire. Thinking with insects allows us to re-examine how life produces

-cal, institutional and experimental relations. Studying both insect and disease control programmes and the diverse kinds of knowledge scientists make with and through insects has led these researchers to explore the different ways in which insect-mediated science shapes understandings of the natural and social

world. While insects are studied predominantly to know, manipulate and transform the natural world in order to minimise diseases, insects also resist

-laria control policies, Kelly and Beisel have further-more excavated “neglected malarias”, the kinds of malaria control practices that fall outside of much of contemporary global health policy. Critiquing the predominant rationale of malaria elimination, they chart malaria as the outcome of a complex rela-tional exchange of unpredictable proximities. In this understanding malaria control is not a war to be won, but a moving target. They underline that ma-

for putting more emphasis on modest practices of control. Techniques that are place-sensitive and re-quire precise and continuous effort; techniques that do not understand malaria in an integrated, over-arching socio-ecological model, but that instead

mosquito-parasite entanglements.

of infectious diseases, including malaria. The way

prevention of malaria was reorganised recently. In

was established and an open competition held for places on this committee. Meetings of the committee are open and its discussions and conclusions are reported with a few months of each meeting in the

control. TEGs and ERGs are tasked with gather-ing and reviewing the evidence that could support a change in policy and presenting this information to

-mendations for the introduction of seasonal malaria chemoprevention in appropriate epidemiological situ-ations, increasing the number of doses of intermittent preventive treatment during pregnancy and lowering the dose of primaquine given to kill gametocytes.

Members of the Malaria Centre contribute to several aspects of the policy-making process. Brian

ERG on malaria in pregnancy, David Schellenberg chairs the TEG on surveillance, monitoring and evalu-ation and Peter Smith chaired an ERG on measuring the burden of malaria. Jo Lines and Mark Rowland are members of the TEG that addresses issues in Vector Control such as the use of new insecticides and insecticide treated materials. The setting of stan-

work is supported by Mark Rowland.

out a plan to accelerate progress in malaria control in the period 2015-2030. The Roll Back Malaria Partner-ship is preparing a supportive action plan to ensure that the technical strategy is implemented and to sus-tain advocacy and funding for malaria control. Several members of the Malaria Centre have contributed to the development of both of these key documents.

Ensuring that research conducted by members of the School helps to inform policy is a key part of the activities of the Malaria Centre.

It is important to understand the political economics of malaria control efforts, and mem-bers of the Malaria Centre actively participate in shaping these efforts, working to ensure



Mapping causes of non-malarial fever in Africa and Asia.

LSHTM Investigators

Schellenberg.

External Investigators/Collaborators: Heidi Hopkins & David Bell

Funding:

Consortium.

The successful introduction of malaria rapid tests into routine health services is challenged by the lack of lo-cal knowledge of the probability of alternative causes of febrile illness. To address this we searched databases of peer reviewed publications to identify studies that had

described the prevalence of infection among patients with undifferentiated fever.

papers met criteria of blood culture or csf series in undif-

Both sets of data suggest a large variation in quality be-

for laboratory or antibiotic sensitivity data. It is hoped to -

malarial Resistance Network and that this will be used by public health authorities. The longer term future and link-age with other mapping initiatives is under discussion.

Future priorities

Knowing insects: hosts, vectors and companions of science.

The contribution of the Malaria Centre to policy making for malaria treatment and control.

LSHTM Investigators: Ann Kelly

External Investigators/Collaborators: Noemi Tousignant

(University of Cambridge, UK); Uli Beisel (Bayreuth University,

Researchers at the School carried out social analy-sis of insects as disease vectors in Tanzania, The Gambia, Senegal and Ghana. Reading insects not simply as vectors of disease, but equally as hosts, vectors and companions of science, their work opens up the epistemic, biopolitical and social dimensions of human–insect connections. By parsing these inter-sections, they suggest we can begin to understand the kinds of knowledge made possible and elusive by insects’ capacity to connect and carry, inscribe and destabilize, disgust and inspire. Thinking with insects allows us to re-examine how life produces

-cal, institutional and experimental relations. Studying both insect and disease control programmes and the diverse kinds of knowledge scientists make with and through insects has led these researchers to explore the different ways in which insect-mediated science shapes understandings of the natural and social

world. While insects are studied predominantly to know, manipulate and transform the natural world in order to minimise diseases, insects also resist

-laria control policies, Kelly and Beisel have further-more excavated “neglected malarias”, the kinds of malaria control practices that fall outside of much of contemporary global health policy. Critiquing the predominant rationale of malaria elimination, they chart malaria as the outcome of a complex rela-tional exchange of unpredictable proximities. In this understanding malaria control is not a war to be won, but a moving target. They underline that ma-

for putting more emphasis on modest practices of control. Techniques that are place-sensitive and re-quire precise and continuous effort; techniques that do not understand malaria in an integrated, over-arching socio-ecological model, but that instead

mosquito-parasite entanglements.

of infectious diseases, including malaria. The way

prevention of malaria was reorganised recently. In

was established and an open competition held for places on this committee. Meetings of the committee are open and its discussions and conclusions are reported with a few months of each meeting in the

control. TEGs and ERGs are tasked with gather-ing and reviewing the evidence that could support a change in policy and presenting this information to

-mendations for the introduction of seasonal malaria chemoprevention in appropriate epidemiological situ-ations, increasing the number of doses of intermittent preventive treatment during pregnancy and lowering the dose of primaquine given to kill gametocytes.

Members of the Malaria Centre contribute to several aspects of the policy-making process. Brian

ERG on malaria in pregnancy, David Schellenberg chairs the TEG on surveillance, monitoring and evalu-ation and Peter Smith chaired an ERG on measuring the burden of malaria. Jo Lines and Mark Rowland are members of the TEG that addresses issues in Vector Control such as the use of new insecticides and insecticide treated materials. The setting of stan-

work is supported by Mark Rowland.

out a plan to accelerate progress in malaria control in the period 2015-2030. The Roll Back Malaria Partner-ship is preparing a supportive action plan to ensure that the technical strategy is implemented and to sus-tain advocacy and funding for malaria control. Several members of the Malaria Centre have contributed to the development of both of these key documents.

Ensuring that research conducted by members of the School helps to inform policy is a key part of the activities of the Malaria Centre.

It is important to understand the political economics of malaria control efforts, and mem-bers of the Malaria Centre actively participate in shaping these efforts, working to ensure

Publications 2012-14 115


114 Publications 2012-14


Adu-Gyasi, D., Adams, M., Amoako, S.,

Mahama, E., Nsoh, M., Amenga-Etego,

-

laria parasite density: assumed white blood

-

ate measure in Central Ghana. Malaria

Journal, 11, 238.

among HIV seropositve clinic attendants

12, 382.

Adams, M., Dosoo, D., Dery, D., Wilson,

Agyei, S.

Plasmodium falciparum infections among

asymptomatic residents in the middle belt

of Ghana. Malaria Journal, 12, 22.

Allan, R., Howard, N., Lines, J., Mac-

donald, M., Maes, P., Mnzava, A., Nkuni,

J., Renshaw, M. & Rowland, M.

Chapter 7 Prevention. In: Howard, N. &

humanitarian emergencies: an interagency

Allan, R., Howard, N., Macdonald, M.,

Maes, P., Renshaw, M. & Rowland, M.

and associated routine monitoring. In: n:

-

laria control in humanitarian emergencies:

Allen, E., Chandler, C., Mandimika, N.,

Evaluating harm associated with anti-

malarial drugs: a survey of methods used

by clinical researchers to elicit, assess and

record participant-reported adverse events

and related data. Malaria Journal, 12:325.

Allen, E., Mushi, A., Massawe, I., Vester-

gaard, L., Lemnge, M., Staedke, S.,

process of eliciting adverse event, medical

history and concomitant medication reports

in antimalarial and antiretroviral interaction

trials. BMC Medical Research Methodology,

13, 140.

Amambua-Ngwa, A., Park, D., Volkman,

P., Van Tyne, D., Ndiaye, D., Wirth, D.,

Conway, D., Neafsey, D. & Schaffner, S.

Signatures of Selection in a Deep Sample

Malaria Parasites. Molecular Biology and

M., Gomez-Escobar, N., Stewart, L.,

Deerhake, M., Cheeseman, I., Newbold,

Population genomic scan for candidate

signatures of balancing selection to guide

antigen characterization in malaria para-

sites. Plos Genetics, 8, e1002992.

Das, A., Hamade, P., Howard, N., Moham-

6 Case management. Malaria control in

Ansah, E., Epokor, M., Whitty, C., Yeung,

-

Malaria Diagnosis as Compared to Micros-

copy and Presumptive Diagnosis in Central

and Peripheral Public Health Facilities in

Medicine and Hygiene, 89, 724-36.

middle-income countries: a systematic lit-

erature review. Health Policy and Planning,

16: doi: 10.1093/heapol/czu034.

-

-

no, J.

Plasmodium falciparum Circumsporozoite

Protein Likely Due to Protein-Protein Inter-

A., Dodoo, T., Mahama, E., Amoako, N.,

Chandramohan, D. -

laria and the Risk of Malaria in Infants in a

Infectious Diseases, 208, 1504-1513.

Assefa, S., Preston, M., Campino, S.,

infection using parasite deep sequencing

Athrey, G., Hodges, T., Reddy, M.,

-

schmidt, I., Caccone, A. & Slotman, M.

malaria mosquitoes: large impact of vector

control. Plos Genetics, 8, e1003097.

Maslen, G., Mangano, V., Alcock, D., Ma-

-

D.

Plasmodium falciparum Diversity Using

Next-Generation Sequence Data. Plos

Auburn, S., Marfurt, J., Maslen, G.,

Campino, S., Ruano Rubio, V., Manske,

-

-

-

D. & Price, R. -

tion of Plasmodium vivax Field Isolates for

High-Throughput Whole Genome Sequenc-

-

vura, M., Delmini, R., Amenga-Etego,

D.

combination therapy to test positive malaria

in a high-transmission setting in Ghana - a

cluster-randomised trial. Tropical Medicine

& International Health, 2013; 18:74-74.

& Webster, J.

diagnostic test-based management of Ma-

-

-

D. -

ia and treatment outcomes for malaria and

-

Molyneux, M., Taylor, T., Ndila, C., Pe-

D., Andrews, R., Edkins, S., Gray, E.,

J., Spencer, C. & ¶, M. G. E. N.

Imputation-based meta-analysis of severe

malaria in three african populations. PloS

Genetics, 9, e1003509.

Chandramohan, D.

to artemisinin-based combination therapy

for the treatment of malaria: a systematic

review of the evidence. Malaria Journal,

13, 7.

-

buguzi, C., Diliberto, D., Taaka, L., Chan-

dler, C. & Staedke, S.

case management of malaria: exploring

support, capacity and motivation of commu-

nity medicine distributors in Uganda. Health

Policy and Planning. 0:czu033v1-czu033

-

-

tion Therapy: Challenges and Perspectives

e1001590.

-

laria knowledge and utilization of chemo-

prophylaxis in the UK population and in UK

passengers departing to malaria-endemic

areas. Malaria Journal, 12, 461.

S., Abdulla, S. & Ghani, A. -

cacy of RTS,S malaria vaccines: individual-

participant pooled analysis of phase 2

data. The Lancet Infectious Diseases, 13,

319-27.

epidemiological analysis of febrile malaria

in Coastal Kenya showing hotspots within

hotspots. Elife, 3, e02130.

-

haire, A., Arinaitwe, M., Adriko, M., Mwe-

Sutherland, C. & Stothard, J. -

tection of persistent Plasmodium spp. infec-

tions in Ugandan children after artemether-

lumefantrine treatment. Parasitology, 1-11.

Crump, J.

Transmission Intensity in Tanzania. Clinical


& Dinglasan, R.

mosquito feeding assays be used for evalu-

ating transmission-blocking interventions?

Drakeley, C.

for falciparum malaria. The Lancet Infec-

tious Diseases, 14, 677.

Drakeley, C. & Cox, J.

of hotspot-targeted interventions on malaria

transmission: study protocol for a cluster-

randomized controlled trial. Trials, 14, 36.

Vargas, D., Monti, F., Ela, C., Riloha, M.

-

lence of malaria infection in children living

in houses with window screening or closed

eaves on bioko island, equatorial Guinea.

-

anti, M., Nugraheni, D., Widyastuti, A.,

Lobo, N., Hawley, W., Cook, J. & Drake-

ley, C. -

dium falciparum transmission intensity us-

ing serological cohort data from Indonesian

schoolchildren. Malaria Journal, 12, 21.

-

of Malaria Parasitemia and Purchase of

Thompson, E., Sebastian, S., Volkmann,

Phosphoinositide Metabolism Links cGMP-

Dependent Protein Kinase G to Essential

Ca2+ Signals at Key Decision Points in the

Life Cycle of Malaria Parasites. PloS Biol-

ogy, 12, e1001806.





Adu-Gyasi, D., Adams, M., Amoako, S.,

Mahama, E., Nsoh, M., Amenga-Etego,

-

laria parasite density: assumed white blood

-

ate measure in Central Ghana. Malaria

Journal, 11, 238.

among HIV seropositve clinic attendants

12, 382.

Adams, M., Dosoo, D., Dery, D., Wilson,

Agyei, S.

Plasmodium falciparum infections among

asymptomatic residents in the middle belt

of Ghana. Malaria Journal, 12, 22.

Allan, R., Howard, N., Lines, J., Mac-

donald, M., Maes, P., Mnzava, A., Nkuni,

J., Renshaw, M. & Rowland, M.

Chapter 7 Prevention. In: Howard, N. &

humanitarian emergencies: an interagency

Allan, R., Howard, N., Macdonald, M.,

Maes, P., Renshaw, M. & Rowland, M.

and associated routine monitoring. In: n:

-

laria control in humanitarian emergencies:

Allen, E., Chandler, C., Mandimika, N.,

Evaluating harm associated with anti-

malarial drugs: a survey of methods used

by clinical researchers to elicit, assess and

record participant-reported adverse events

and related data. Malaria Journal, 12:325.

Allen, E., Mushi, A., Massawe, I., Vester-

gaard, L., Lemnge, M., Staedke, S.,

process of eliciting adverse event, medical

history and concomitant medication reports

in antimalarial and antiretroviral interaction

trials. BMC Medical Research Methodology,

13, 140.

Amambua-Ngwa, A., Park, D., Volkman,

P., Van Tyne, D., Ndiaye, D., Wirth, D.,

Conway, D., Neafsey, D. & Schaffner, S.

Signatures of Selection in a Deep Sample

Malaria Parasites. Molecular Biology and

M., Gomez-Escobar, N., Stewart, L.,

Deerhake, M., Cheeseman, I., Newbold,

Population genomic scan for candidate

signatures of balancing selection to guide

antigen characterization in malaria para-

sites. Plos Genetics, 8, e1002992.

Das, A., Hamade, P., Howard, N., Moham-

6 Case management. Malaria control in

Ansah, E., Epokor, M., Whitty, C., Yeung,

-

Malaria Diagnosis as Compared to Micros-

copy and Presumptive Diagnosis in Central

and Peripheral Public Health Facilities in

Medicine and Hygiene, 89, 724-36.

middle-income countries: a systematic lit-

erature review. Health Policy and Planning,

16: doi: 10.1093/heapol/czu034.

-

-

no, J.

Plasmodium falciparum Circumsporozoite

Protein Likely Due to Protein-Protein Inter-

A., Dodoo, T., Mahama, E., Amoako, N.,

Chandramohan, D. -

laria and the Risk of Malaria in Infants in a


Assefa, S., Preston, M., Campino, S.,

infection using parasite deep sequencing

Athrey, G., Hodges, T., Reddy, M.,

-

schmidt, I., Caccone, A. & Slotman, M.

malaria mosquitoes: large impact of vector

control. Plos Genetics, 8, e1003097.

Maslen, G., Mangano, V., Alcock, D., Ma-

-

D.

Plasmodium falciparum Diversity Using

Next-Generation Sequence Data. Plos

Auburn, S., Marfurt, J., Maslen, G.,

Campino, S., Ruano Rubio, V., Manske,

-

-

-

D. & Price, R. -

tion of Plasmodium vivax Field Isolates for

High-Throughput Whole Genome Sequenc-

-

vura, M., Delmini, R., Amenga-Etego,

D.

combination therapy to test positive malaria

in a high-transmission setting in Ghana - a

cluster-randomised trial. Tropical Medicine


& Webster, J.

diagnostic test-based management of Ma-

-

-

D. -

ia and treatment outcomes for malaria and

-

Molyneux, M., Taylor, T., Ndila, C., Pe-

D., Andrews, R., Edkins, S., Gray, E.,

J., Spencer, C. & ¶, M. G. E. N.

Imputation-based meta-analysis of severe

malaria in three african populations. PloS

Genetics, 9, e1003509.

Chandramohan, D.

to artemisinin-based combination therapy

for the treatment of malaria: a systematic

review of the evidence. Malaria Journal,

13, 7.

-

buguzi, C., Diliberto, D., Taaka, L., Chan-

dler, C. & Staedke, S.

case management of malaria: exploring

support, capacity and motivation of commu-

nity medicine distributors in Uganda. Health

Policy and Planning. 0:czu033v1-czu033

-

-

tion Therapy: Challenges and Perspectives

e1001590.

-

laria knowledge and utilization of chemo-

prophylaxis in the UK population and in UK

passengers departing to malaria-endemic

areas. Malaria Journal, 12, 461.

S., Abdulla, S. & Ghani, A. -

cacy of RTS,S malaria vaccines: individual-

participant pooled analysis of phase 2

data. The Lancet Infectious Diseases, 13,

319-27.

epidemiological analysis of febrile malaria

in Coastal Kenya showing hotspots within

hotspots. Elife, 3, e02130.

-

haire, A., Arinaitwe, M., Adriko, M., Mwe-

Sutherland, C. & Stothard, J. -

tection of persistent Plasmodium spp. infec-

tions in Ugandan children after artemether-

lumefantrine treatment. Parasitology, 1-11.

Crump, J.

Transmission Intensity in Tanzania. Clinical


& Dinglasan, R.

mosquito feeding assays be used for evalu-

ating transmission-blocking interventions?

Drakeley, C.

for falciparum malaria. The Lancet Infec-

tious Diseases, 14, 677.

Drakeley, C. & Cox, J.

of hotspot-targeted interventions on malaria

transmission: study protocol for a cluster-

randomized controlled trial. Trials, 14, 36.

Vargas, D., Monti, F., Ela, C., Riloha, M.

-

lence of malaria infection in children living

in houses with window screening or closed

eaves on bioko island, equatorial Guinea.

-

anti, M., Nugraheni, D., Widyastuti, A.,

Lobo, N., Hawley, W., Cook, J. & Drake-

ley, C. -

dium falciparum transmission intensity us-

ing serological cohort data from Indonesian

schoolchildren. Malaria Journal, 12, 21.

-

of Malaria Parasitemia and Purchase of

Thompson, E., Sebastian, S., Volkmann,

Phosphoinositide Metabolism Links cGMP-

Dependent Protein Kinase G to Essential

Ca2+ Signals at Key Decision Points in the

Life Cycle of Malaria Parasites. PloS Biol-

ogy, 12, e1001806.





-

& Snow, R.

coinfection and its sources of heterogeneity

-

tious Diseases, 205, 841-52.

-

chur, S., Goodman, C. & Schellenberg,

D.

Message Reminders to Retail Staff in Tan-

Lumefantrine: Effect on Dispenser Knowl-

Journal of Tropical Medicine and Hygiene,

pii: 14-0126.

& Schellenberg, D.

take malaria treatment: a systematic review

of the literature on adherence to antima-

-

mara, S., Takken, W., Carnevale, P. & Al-

lan, R.

Sheeting for Emergency Malaria Prevention

and Shelter among Displaced Populations:

-


87, 242-50.

Milligan, P.

complete protection in malaria cohort stud-

ies. Malaria Journal, 12, 355.

Cairns, M., Roca-Feltrer, A., Garske, T.,

Wilson, A., Diallo, D., Milligan, P., Ghani,

the potential public health impact of sea-

children. Nature Communications, 3, 881.

J., Conway, D. & Della Torre, A.

triggered by habitat discontinuities across

a riverine landscape. Molecular Ecology,

23:18, 4574–4589.

-

Indian monsoon. Nature Climate Change,

3, 502-507.

-

Dürrheim, D.

of malaria vector control using routine sur-

veillance data in Zambia: implications for

monitoring and evaluation. Malaria Journal,

11, 437.

V. -

aging lab results, you are managing the

patient’: How the enactment of malaria at

health facilities in Cameroon compares with

74, 1528-35.

Chandler, C., Meta, J., Ponzo, C., Nasu-

A. & Reyburn, H.

of effective behaviour change interventions

to support the use of malaria rapid diagnos-

tic tests by Tanzanian clinicians. Implemen-

tation Science, 9, 83.

C.

imported falciparum malaria in the United

Kingdom over 20 years: an observational

study. British Medical Journal (Clinical re-

J.

determine the safety of the topical insect

Parasites and Vectors, 7, 173.

S. & Lindsay, S.

Randomised Controlled Trial of the Insect

Chico, R., Mayaud, P., Ariti, C., Mabey,

D., Ronsmans, C. & Chandramohan, D.

transmitted and reproductive tract infec-

-

quito infection from Plasmodium falciparum

gametocyte density and estimating the res-

ervoir of infection. Elife, 2, e00626.

Clarke, S., Ly, A., Ndiaye, J., Fall, F., Dial-

children: epidemiology, disease burden

and control approaches in areas of highly

seasonal transmission. Tropical Medicine

152-152.

Clemente, A., Fadigati, G., Caporale, R.,

Marchese, D., Castronovo, G., Sannella,

A., Severini, C., Verra, F., Garaci, E., Coz-

zolino, F. & Torcia, M.

-

es by Plasmodium falciparum Schizont

Extracts: Role of Myeloid Dendritic Cells

in Effector and Regulatory Functions of

-

nity, 81, 1842-1851.

Collins, C., Hackett, F., Strath, M., Penzo,

cGMP-dependent Protein Kinase Regulates

Discharge and Egress. Plos Pathogens, 9.

Committee, W. M. P. A. & Secretariat

-

Journal, 12, 213.

Cox, S., Nweneka, C., Doherty, C., Ful-

ford, A., Moore, S. & Prentice, A.

Randomised controlled trial of weekly

chloroquine to re-establish normal erythron

-

malarial anaemia. British Medical Journal,

Crawley, J., Sismanidis, C., Goodman,

T. V. -

tive treatment for malaria during infancy

on serological responses to measles and

other vaccines used in the Expanded Pro-

randomised controlled trials. Lancet, 380,

1001-10.

Craft, J., Shin, C., Fleckenstein, L.,

-

view of pyronaridine anti-malarial properties

and product characteristics. Malaria Jour-

nal, 11, 270.

S., Riley, E. & Walther, M. -

parison of parasite sequestration in uncom-

plicated and severe childhood plasmodium

falciparum malaria. The Journal of infection,

Cunnington, A., De Souza, J., Walther,

M. & Riley, E. -

sistance to Salmonella through heme- and

heme oxygenase-dependent dysfunctional

granulocyte mobilization. Nature Medicine,

18, 120-7.

Takem, E., Riley, E. & Walther, M.

Prolonged Neutrophil Dysfunction after

Plasmodium falciparum Malaria Is Related

-

duction. Journal of Immunology (Baltimore,

Md, 189, 5336-46.

Cunnington, A., Riley, E. & Walther, M.

Plasmodium falciparum malaria. The Jour-

nal of Infectious Diseases.

Strengthening the policy setting process

for global malaria control and elimination.

Malaria Journal, 11, 28.

Da Silva Santos, S., Clark, T., Campino,

-

Investigation of host candidate malaria-

associated risk/protective SNPs in a Brazil-

e36692.

-

bazi, E., Nabukeera, D., Ssemmondo,

E., Gonahasa, S., Tumwebaze, P., Dilib-

erto, D., Maiteki-Sebuguzi, C., Staedke,

S. & Drakeley, C.

the WST8/1-methoxy-PMS enzymatic as-

say in Uganda. Malaria Journal, 12, 210.

De Savigny, D., Webster, J., Agyepong,

-

ducing vouchers for malaria prevention in

Ghana and Tanzania: context and adoption

of innovation in health systems. Health

Policy and Planning, 27, 32-43.

De Souza, J.

against malaria after vaccination. Parasite

S. & Nefzi, A.

cytotoxic activities of chiral triamines. Bio-

organic & Medicinal Chemistry Letters, 23,

4579-4582.

-

ma, T. & Sutherland, C.

detection of Plasmodium falciparum, P.

malariae, P. ovale curtisi and P. ovale wal-

Ghanaian school-children. International

Journal for Parasitology-Drugs and Drug

Resistance, 3, 45-50.

-

J., Sene, P., Ahouidi, A., Dieye, T., Gaye,

-

-

I., Gomis, J., Mather, F., Sissako, A., Di-

-

R., Duraisingh, M., Muskavitch, M.,

D’alessandro, U., Conway, D., Volkman,

Drakeley, C. & Lines, J.

long haul: 20 years of malaria surveillance.

The Lancet Infectious Diseases, 14, 445-

446.

Mukabana, W., Lindsay, S. & Fillinger, U.

Teo, Y., Thai, C., Hang, N., Jeffreys, A.,

-

rar, J., Phu, N., Hien, T. & Consortium, M.

are associated with severe malaria in the

Vietnamese. Genes and Immunity, 13,

503-8.

drug quality assessment. Tropical Medicine


El Chaar, M., Atwal, S., Freimanis, G.,

-

irradiation. Transfusion, 53, 3174-83.


-

land, C. & Allain, J.





-

& Snow, R.

coinfection and its sources of heterogeneity

-

tious Diseases, 205, 841-52.

-

chur, S., Goodman, C. & Schellenberg,

D.

Message Reminders to Retail Staff in Tan-

Lumefantrine: Effect on Dispenser Knowl-


pii: 14-0126.

& Schellenberg, D.

take malaria treatment: a systematic review

of the literature on adherence to antima-

-

mara, S., Takken, W., Carnevale, P. & Al-

lan, R.

Sheeting for Emergency Malaria Prevention

and Shelter among Displaced Populations:

-


87, 242-50.

Milligan, P.

complete protection in malaria cohort stud-

ies. Malaria Journal, 12, 355.

Cairns, M., Roca-Feltrer, A., Garske, T.,

Wilson, A., Diallo, D., Milligan, P., Ghani,

the potential public health impact of sea-

children. Nature Communications, 3, 881.

J., Conway, D. & Della Torre, A.

triggered by habitat discontinuities across

a riverine landscape. Molecular Ecology,

23:18, 4574–4589.

-

Indian monsoon. Nature Climate Change,

3, 502-507.

-

Dürrheim, D.

of malaria vector control using routine sur-

veillance data in Zambia: implications for

monitoring and evaluation. Malaria Journal,

11, 437.

V. -

aging lab results, you are managing the

patient’: How the enactment of malaria at

health facilities in Cameroon compares with

74, 1528-35.

Chandler, C., Meta, J., Ponzo, C., Nasu-

A. & Reyburn, H.

of effective behaviour change interventions

to support the use of malaria rapid diagnos-

tic tests by Tanzanian clinicians. Implemen-

tation Science, 9, 83.

C.

imported falciparum malaria in the United

Kingdom over 20 years: an observational

study. British Medical Journal (Clinical re-

J.

determine the safety of the topical insect

Parasites and Vectors, 7, 173.

S. & Lindsay, S.

Randomised Controlled Trial of the Insect

Chico, R., Mayaud, P., Ariti, C., Mabey,

D., Ronsmans, C. & Chandramohan, D.

transmitted and reproductive tract infec-

-

quito infection from Plasmodium falciparum

gametocyte density and estimating the res-

ervoir of infection. Elife, 2, e00626.

Clarke, S., Ly, A., Ndiaye, J., Fall, F., Dial-

children: epidemiology, disease burden

and control approaches in areas of highly

seasonal transmission. Tropical Medicine

152-152.

Clemente, A., Fadigati, G., Caporale, R.,

Marchese, D., Castronovo, G., Sannella,

A., Severini, C., Verra, F., Garaci, E., Coz-

zolino, F. & Torcia, M.

-

es by Plasmodium falciparum Schizont

Extracts: Role of Myeloid Dendritic Cells

in Effector and Regulatory Functions of

-

nity, 81, 1842-1851.

Collins, C., Hackett, F., Strath, M., Penzo,

cGMP-dependent Protein Kinase Regulates

Discharge and Egress. Plos Pathogens, 9.

Committee, W. M. P. A. & Secretariat

-

Journal, 12, 213.

Cox, S., Nweneka, C., Doherty, C., Ful-

ford, A., Moore, S. & Prentice, A.

Randomised controlled trial of weekly

chloroquine to re-establish normal erythron

-

malarial anaemia. British Medical Journal,

Crawley, J., Sismanidis, C., Goodman,

T. V. -

tive treatment for malaria during infancy

on serological responses to measles and

other vaccines used in the Expanded Pro-

randomised controlled trials. Lancet, 380,

1001-10.

Craft, J., Shin, C., Fleckenstein, L.,

-

view of pyronaridine anti-malarial properties

and product characteristics. Malaria Jour-

nal, 11, 270.

S., Riley, E. & Walther, M. -

parison of parasite sequestration in uncom-

plicated and severe childhood plasmodium

falciparum malaria. The Journal of infection,

Cunnington, A., De Souza, J., Walther,

M. & Riley, E. -

sistance to Salmonella through heme- and

heme oxygenase-dependent dysfunctional

granulocyte mobilization. Nature Medicine,

18, 120-7.

Takem, E., Riley, E. & Walther, M.

Prolonged Neutrophil Dysfunction after

Plasmodium falciparum Malaria Is Related

-

duction. Journal of Immunology (Baltimore,

Md, 189, 5336-46.

Cunnington, A., Riley, E. & Walther, M.

Plasmodium falciparum malaria. The Jour-

nal of Infectious Diseases.

Strengthening the policy setting process

for global malaria control and elimination.


Da Silva Santos, S., Clark, T., Campino,

-

Investigation of host candidate malaria-

associated risk/protective SNPs in a Brazil-

e36692.

-

bazi, E., Nabukeera, D., Ssemmondo,

E., Gonahasa, S., Tumwebaze, P., Dilib-

erto, D., Maiteki-Sebuguzi, C., Staedke,

S. & Drakeley, C.

the WST8/1-methoxy-PMS enzymatic as-

say in Uganda. Malaria Journal, 12, 210.

De Savigny, D., Webster, J., Agyepong,

-

ducing vouchers for malaria prevention in

Ghana and Tanzania: context and adoption

of innovation in health systems. Health

Policy and Planning, 27, 32-43.

De Souza, J.

against malaria after vaccination. Parasite

S. & Nefzi, A.

cytotoxic activities of chiral triamines. Bio-

organic & Medicinal Chemistry Letters, 23,

4579-4582.

-

ma, T. & Sutherland, C.

detection of Plasmodium falciparum, P.

malariae, P. ovale curtisi and P. ovale wal-

Ghanaian school-children. International

Journal for Parasitology-Drugs and Drug

Resistance, 3, 45-50.

-

J., Sene, P., Ahouidi, A., Dieye, T., Gaye,

-

-

I., Gomis, J., Mather, F., Sissako, A., Di-

-

R., Duraisingh, M., Muskavitch, M.,

D’alessandro, U., Conway, D., Volkman,

Drakeley, C. & Lines, J.

long haul: 20 years of malaria surveillance.


446.

Mukabana, W., Lindsay, S. & Fillinger, U.

Teo, Y., Thai, C., Hang, N., Jeffreys, A.,

-

rar, J., Phu, N., Hien, T. & Consortium, M.

are associated with severe malaria in the

Vietnamese. Genes and Immunity, 13,

503-8.

drug quality assessment. Tropical Medicine



-

irradiation. Transfusion, 53, 3174-83.


-

land, C. & Allain, J.





of Plasmodium Falciparum-Infected Whole

Blood With Mirasol. Vox Sanguinis, 103,

137-137.

Exploring health providers’ and community

perceptions and experiences with malaria

tests in South-East Nigeria: a critical step

towards appropriate treatment. Malaria

Journal, 11, 368.

Wanzira, H., Mpimbaza, A., Nsobya, S.,

White, N., Webb, E., Staedke, S. & Drake-

ley, C.

clearance of Plasmodium falciparum game-

tocytes in children with uncomplicated ma-

laria in Uganda: a randomised, controlled,

double-blind, dose-ranging trial. The Lancet

Infectious Diseases.14:2, 130 - 139.

Eziefula, A., Gosling, R., Hwang, J.,

I. A. D.

transmission. Malaria Journal, 11, 360.

Hallett, R., Vennerstrom, J., Duong, S.,

Ringwald, P., Wellems, T., Plowe, C. &

Dondorp, A.

-

ties, and Public Health Implications. The

Hygiene, 87, 231-241.

Fancony, C., Gamboa, D., Sebastiao,

Y., Hallett, R., Sutherland, C., Sousa-

Figueiredo, J. & Nery, S.

pfcrt and pfmdr1 Genotypes of Plasmodium

falciparum Cocirculate with P. malariae, P.

56, 5271-5277.

Community perceptions of a malaria vac-

cine in the Kintampo districts of Ghana.


N., De Souza, J., Grady, L., Saris, C.,

signalling regulates memory CD4+ T cell

populations and suppresses rapid in-

malaria infection. Infection and Immunity,

M., Riley, E. & Walther, M.

thaw lysates of P. falciparum-infected red

blood cells induce differentiation of func-

tionally competent regulatory T cells from

memory T cells. European Journal of Im-

parasite epigenetics: when virulence and

romance collide. Cell Host & Microbe, 16,

148-50.

Franco, A., Gomes, M., Rowland, M.,

Coleman, P. & Davies, C. -

trolling Malaria Using Livestock-Based

Gadalla, N., Abdallah, T., Atwal, S.,

Sutherland, C. & Adam, I. -

tion of pfdhfr/pfdhps alleles and declining

artesunate/sulphadoxine-pyrimethamine ef-

years after deployment in eastern Sudan.


Gatton, M., Chitnis, N., Churcher, T.,

Donnelly, M., Ghani, A., Godfray, H.,

Gould, F., Hastings, I., Marshall, J.,

Ranson, H., Rowland, M., Shaman, J.

& Lindsay, S.

-

1218-1230.

Gaudart, J., Huiart, L., Milligan, P., Thie-

baut, R. & Giorgi, R. -

ibility issues in science, is P value really the

only answer? Proceedings of the National

Gayer, M., Golaz, A., Howard, N. & Schil-

peroord, M. -

nation. In: Howard, N. & Clements-Hunt,

-

book, 2nd Edition. Geneva: World Health


peroord, M. -

ment and operational planning. In: oward,

-

Lietman, T. -

mycin Distribution on Malaria Parasitemia

during the Low-Transmission Season in

-

Etego, L., Anyorigiya, T., Hodgson, A.,

D. -

moglobin C and haemoglobin S and the

dynamics of the evolutionary response to

malaria in Kassena-Nankana District of

Ghumra, A., Semblat, J., Ataide, R.,

M., Amambua-Ngwa, A., Walther, M.,

Virulent Malaria Parasites. Plos Pathogens,

8, e1002665.

Plasmodium infection, anaemia and mos-

quito net use among school children across

different settings in Kenya. Tropical Medi-

cine & International Health, 17, 858-70.

-

S.

in Malaria School Surveys in Kenya:

Does their Under-performance Matter for


C. & Chiodini, P.

malaria prevention advice to Public Health

England, Malaria Reference Labora-

Travel Medicine and Infectious Disease,

vaccination to global health: past, present

and future. Philosophical Transactions of

the Royal Society of London Series B, Bio-

consortium approach to malaria research

and capacity development. Tropical Medi-

much to do. Lancet, 383, 1703-4.

Grigg, M., William, T., Drakeley, C., Jelip,

Factors that are associated with the risk

of acquiring Plasmodium knowlesi malaria

in Sabah, Malaysia: a case-control study

e006004.

G., Renia, L., De Souza, J. & Riley, E.

-

hibitory Pathways Independently Regulate

Host Resistance to Plasmodium-induced

8, e1002504.

-

modium falciparum, anaemia and cogni-

tive and educational performance among

school children in an area of moderate

malaria transmission: baseline results of

a cluster randomized trial on the coast of

Kenya. Tropical Medicine & International

Health, 17, 532-549.

-

Impact of Intermittent Screening and Treat-

ment for Malaria among School Children in

Medicine, 11, e1001594.

& Comm, S.

New England Journal of Medicine, 366,

765-766.

-

sen, P. & Clarke, S. -

to Prevent Malaria in Pregnancy in an area

of low transmission in Uganda. Interna-

tional Health, 4, 38-46.

& Yeung, S.

for a rapid malaria diagnostic test and

artemisinin-based combination therapy

from private drug shops in Mukono district,

Uganda. Health Policy and Planning, 28,

185-96.

Matowo, N., Lorenz, L., Devine, G. &

its potential use in malaria control. Para-

sites & Vectors, 6: :144.

-

-

murine immune memory. Parasite Immunol-

ogy, 36, 199-206.

Hemingway, J., Vontas, J., Poupardin,

R., Raman, J., Lines, J., Schwabe, C.,

Country-level operational implementation of

the Global Plan for Insecticide Resistance

Management. Proceedings of the National

Hendriksen, I., Maiga, D., Lemnge, M.,

Mtove, G., Gesase, S., Reyburn, H.,

Lindegardh, N., Day, N., Von Seidlein,

L., Dondorp, A., Tarning, J. & White, N.

pharmacodynamic properties of intramus-

cular quinine in Tanzanian children with

Gesase, S., Reyburn, H., Lemnge, M.,


L., White, N., Dondorp, A. & Tarning, J.

with severe malaria: implications for a prac-

tical dosing regimen. Clinical Pharmacology

and Therapeutics, 93, 443-50.

Directional selection at the pfmdr1, pfcrt,

pfubp1 and pfap2mu loci of Plasmodium

falciparum in Kenyan children treated with

pii: jiu358.

Herrera-Varela, M., Lindh, J., Lindsay, S.

& Fillinger, U. -

lato - a push-pull system. Malaria Journal,

13, 133.





of Plasmodium Falciparum-Infected Whole

Blood With Mirasol. Vox Sanguinis, 103,

137-137.

Exploring health providers’ and community

perceptions and experiences with malaria

tests in South-East Nigeria: a critical step

towards appropriate treatment. Malaria

Journal, 11, 368.

Wanzira, H., Mpimbaza, A., Nsobya, S.,

White, N., Webb, E., Staedke, S. & Drake-

ley, C.

clearance of Plasmodium falciparum game-

tocytes in children with uncomplicated ma-

laria in Uganda: a randomised, controlled,

double-blind, dose-ranging trial. The Lancet

Infectious Diseases.14:2, 130 - 139.

Eziefula, A., Gosling, R., Hwang, J.,

I. A. D.

transmission. Malaria Journal, 11, 360.

Hallett, R., Vennerstrom, J., Duong, S.,

Ringwald, P., Wellems, T., Plowe, C. &

Dondorp, A.

-

ties, and Public Health Implications. The

Hygiene, 87, 231-241.

Fancony, C., Gamboa, D., Sebastiao,

Y., Hallett, R., Sutherland, C., Sousa-

Figueiredo, J. & Nery, S.

pfcrt and pfmdr1 Genotypes of Plasmodium

falciparum Cocirculate with P. malariae, P.

56, 5271-5277.

Community perceptions of a malaria vac-

cine in the Kintampo districts of Ghana.


N., De Souza, J., Grady, L., Saris, C.,

signalling regulates memory CD4+ T cell

populations and suppresses rapid in-

malaria infection. Infection and Immunity,

M., Riley, E. & Walther, M.

thaw lysates of P. falciparum-infected red

blood cells induce differentiation of func-

tionally competent regulatory T cells from

memory T cells. European Journal of Im-

parasite epigenetics: when virulence and

romance collide. Cell Host & Microbe, 16,

148-50.

Franco, A., Gomes, M., Rowland, M.,

Coleman, P. & Davies, C. -

trolling Malaria Using Livestock-Based

Gadalla, N., Abdallah, T., Atwal, S.,

Sutherland, C. & Adam, I. -

tion of pfdhfr/pfdhps alleles and declining

artesunate/sulphadoxine-pyrimethamine ef-

years after deployment in eastern Sudan.


Gatton, M., Chitnis, N., Churcher, T.,

Donnelly, M., Ghani, A., Godfray, H.,

Gould, F., Hastings, I., Marshall, J.,

Ranson, H., Rowland, M., Shaman, J.

& Lindsay, S.

-

1218-1230.

Gaudart, J., Huiart, L., Milligan, P., Thie-

baut, R. & Giorgi, R. -

ibility issues in science, is P value really the

only answer? Proceedings of the National


peroord, M. -

nation. In: Howard, N. & Clements-Hunt,

-

book, 2nd Edition. Geneva: World Health


peroord, M. -

ment and operational planning. In: oward,

-

Lietman, T. -

mycin Distribution on Malaria Parasitemia

during the Low-Transmission Season in

-

Etego, L., Anyorigiya, T., Hodgson, A.,

D. -

moglobin C and haemoglobin S and the

dynamics of the evolutionary response to

malaria in Kassena-Nankana District of

Ghumra, A., Semblat, J., Ataide, R.,

M., Amambua-Ngwa, A., Walther, M.,

Virulent Malaria Parasites. Plos Pathogens,

8, e1002665.

Plasmodium infection, anaemia and mos-

quito net use among school children across

different settings in Kenya. Tropical Medi-

cine & International Health, 17, 858-70.

-

S.

in Malaria School Surveys in Kenya:

Does their Under-performance Matter for


C. & Chiodini, P.

malaria prevention advice to Public Health

England, Malaria Reference Labora-

Travel Medicine and Infectious Disease,

vaccination to global health: past, present

and future. Philosophical Transactions of

the Royal Society of London Series B, Bio-

consortium approach to malaria research

and capacity development. Tropical Medi-

much to do. Lancet, 383, 1703-4.

Grigg, M., William, T., Drakeley, C., Jelip,

Factors that are associated with the risk

of acquiring Plasmodium knowlesi malaria

in Sabah, Malaysia: a case-control study

e006004.

G., Renia, L., De Souza, J. & Riley, E.

-

hibitory Pathways Independently Regulate

Host Resistance to Plasmodium-induced

8, e1002504.

-

modium falciparum, anaemia and cogni-

tive and educational performance among

school children in an area of moderate

malaria transmission: baseline results of

a cluster randomized trial on the coast of

Kenya. Tropical Medicine & International

Health, 17, 532-549.

-

Impact of Intermittent Screening and Treat-

ment for Malaria among School Children in

Medicine, 11, e1001594.

& Comm, S.


765-766.

-

sen, P. & Clarke, S. -

to Prevent Malaria in Pregnancy in an area

of low transmission in Uganda. Interna-


& Yeung, S.

for a rapid malaria diagnostic test and

artemisinin-based combination therapy

from private drug shops in Mukono district,

Uganda. Health Policy and Planning, 28,

185-96.

Matowo, N., Lorenz, L., Devine, G. &

its potential use in malaria control. Para-

sites & Vectors, 6: :144.

-

-

murine immune memory. Parasite Immunol-

ogy, 36, 199-206.

Hemingway, J., Vontas, J., Poupardin,

R., Raman, J., Lines, J., Schwabe, C.,

Country-level operational implementation of

the Global Plan for Insecticide Resistance

Management. Proceedings of the National

Hendriksen, I., Maiga, D., Lemnge, M.,

Mtove, G., Gesase, S., Reyburn, H.,


L., Dondorp, A., Tarning, J. & White, N.

pharmacodynamic properties of intramus-

cular quinine in Tanzanian children with

Gesase, S., Reyburn, H., Lemnge, M.,


L., White, N., Dondorp, A. & Tarning, J.

with severe malaria: implications for a prac-

tical dosing regimen. Clinical Pharmacology

and Therapeutics, 93, 443-50.

Directional selection at the pfmdr1, pfcrt,

pfubp1 and pfap2mu loci of Plasmodium

falciparum in Kenyan children treated with

pii: jiu358.

Herrera-Varela, M., Lindh, J., Lindsay, S.

& Fillinger, U. -

lato - a push-pull system. Malaria Journal,

13, 133.





Hill, J., D’mello-Guyett, L., Hoyt, J., Van

for the Case Management of Malaria during

Smith, H. & Webster, J.

affecting the delivery, access, and use of

interventions to prevent malaria in preg-

review and meta-analysis. PLoS Medicine,

10, e1001488.

-

-

Effectiveness of antenatal clinics to deliver

intermittent preventive treatment and insec-

ticide treated nets for the control of malaria

in pregnancy in mali: a household survey.

P. & Lindsay, S.

Mosquito House Entry in the Lao PDR.

Hopkins, H., Gonzalez, I., Polley, S.,

Angutoko, P., Ategeka, J., Asiimwe, C.,

Sensitive Detection of Malaria Parasitemia

in a Malaria-Endemic Setting: Performance

-

The Journal of Infectious Diseases, 208,

645-652.

The role of cGMP signalling in regulating

life cycle progression of Plasmodium. Mi-

crobes and Infection / Institut Pasteur.

Hopp, C., Flueck, C., Solyakov, L., Tobin,

Functional Characterisation of the Plasmo-

dium falciparum cGMP-Dependent Protein

-

ingu, J., Dekker, D., Leach, A., Moris, P.,

Cohen, J., Vekemans, J., Villafana, T.,

Seidlein, L. & Riley, E.

NK Cell Responses after Immunization of

Malaria Vaccine. Journal of Immunology

(Baltimore, Md, 188, 5054-62.

Horowitz, A. & Riley, E.

of human NK cells by Plasmodium-infected

red blood cells. Methods in Molecular Biol-

Howard, N. & Clements-Hunt, A.

Malaria control in humanitarian emergen-

-

tion.

Chea, N., Yok, S., Top, S., Ros, S., So-

phal, U., Thompson, M., Mellor, S., Ariey,

Duong, S., Newman, R. & Menard, D.

Malaria Parasite Carriers and Contain Drug

Resistant P. falciparum, Pailin, Cambodia.

-

G.

the proportion of human exposure to ma-

laria vector populations occurring indoors in

-

Imai, N., White, M., Ghani, A. & Drake-

ley, C.

Modelling Study. PLoS Neglected Tropical

Diseases, 8, e2978.

M. & Cameron, M.

nonanal-trimethylamine lure for collection of

in gravid traps. Journal of Medical Entomol-

ogy, 50, 619-23.

Jallow, M., Casals-Pascual, C., Acker-

M., Sisay-Joof, F., Usen, S., Abubakar, I.,

Clinical features of severe malaria associ-

ated with death: a 13-year observational

Jaramillo Ramirez, G., Logan, J., Loza-

Reyes, E., Stashenko, E. & Moores, G.

e48698.

Jarvis, J., Coltart, C., Pule, M., Chiodini,

P. & Doherty, T.

and severe delayed haemolysis. Lancet,

382, 180.

Magesa, S.

of Tanzania. Tropical Medicine & Interna-

tional Health, 19:3.

-

Protopopoff, N., Magesa, S., Mosha,

spread of pyrethroid and DDT resistance

Tanzania. Medical and Veterinary Entomol-

commitment tosexual development in ma-

laria parasites. Nature, 507, 248–252.

-

he, R., Perlmann, H., Takeo, S., Tsuboi,

Drakeley, C.

Distribution of Plasmodium vivax Infections

-

Alegana, V., Nyandigisi, A., Pandit, J.,

Fegan, G., Todd, J., Snow, R. & Good-

man, C.

malarial subsidy programme on the quality

of service provision of artemisinin-based

combination therapy in Kenya: a cluster-

randomized, controlled trial. Malaria Jour-

nal, 12.

-

burn, H., Agbenyega, T., Taylor, T.,

Epilepsia, 54, 990-1001.

-

sion patterns in Navrongo demographic

surveillance site, northern Ghana. Malaria

Journal, 12, 63.

-

J., Roper, C. & Alifrangis, M.

Surveillance of artemether-lumefantrine as-

sociated Plasmodium falciparum multidrug

resistance protein-1 gene polymorphisms in

Tanzania. Malaria Journal, 13, 264.

Naidoo, I., Roper, C., Mulokozi, A.,

Macarthur, J., Luntamo, M., Ashorn,

Intermittent Preventive Therapy for Malaria

During Pregnancy Using 2 vs 3 or More

Doses of Sulfadoxine-Pyrimethamine and

-

594-604.

S., Snow, R. & Goodman, C.

Understanding the Impact of Subsidizing

Focus Group Discussions in Rural Kenya.

hosting vectors. The Journal of the Royal

or Waiting? Topologies of the Breeding

Ground in Malaria Control. Science as Cul-

ture, 22, 86-107.

-

-

wanyi, A., Smith, E., Somi, M., Lyimo, T.,

artemisinin-based combination treatment

prevalence in Tanzania: an observational

study. Malaria Journal, 11, 140.

H., Magesa, S., Mosha, F., Rowland, M.

& Logan, J. -

perimental hut evaluation of a long-lasting

insecticide treated blanket for protection

against mosquitoes. Parasites and Vectors,

7, 129.

indicators for eliminating malaria transmis-

sion. Biology Letters, 8, 874-877.

Staedke, S. & Chandler, C. -

proving access to health care for malaria

-

tracts patients. Malaria Journal, 11.

Lauinger, I., Vivas, L., Perozzo, R.,

Pham, D., Esguerra, C., Crawford, A.,

Maes, L. & Tasdemir, D.

of Lichen Secondary Metabolites against

Plasmodium Liver Stage Parasites with

Natural Products, 76, 1064-1070.

Leslie, T., Mikhail, A., Mayan, I., Cundill,

& Rowland, M.

tests to improve treatment of malaria and

other febrile illnesses: patient randomised

effectiveness trial in primary care clinics in

-

-

for treatment policy in the region. Malaria

Journal, 12, 230.

-

bining malaria vector control interventions:

some trial design issues. Pathogens and

global health, 107, 1-4.

S., Hashim, R., Maxwell, C., Chandramo-

han, D. & Gosling, R.

among Young Children and Mosquito Vec-

tor Numbers? Evidence from Korogwe,

Plenderleith, L., Malenke, J., Sunda-

raraman, S., Ramirez, M., Crystal, P.,

Locatelli, S., Esteban, A., Mouacha, F.,

S., Sanz, C., Morgan, D., Gonder, M.,

Muller, M., Piel, A., Stewart, F., Wilson,





Hill, J., D’mello-Guyett, L., Hoyt, J., Van

for the Case Management of Malaria during

Smith, H. & Webster, J.

affecting the delivery, access, and use of

interventions to prevent malaria in preg-

review and meta-analysis. PLoS Medicine,

10, e1001488.

-

-

Effectiveness of antenatal clinics to deliver

intermittent preventive treatment and insec-

ticide treated nets for the control of malaria

in pregnancy in mali: a household survey.

P. & Lindsay, S.

Mosquito House Entry in the Lao PDR.

Hopkins, H., Gonzalez, I., Polley, S.,

Angutoko, P., Ategeka, J., Asiimwe, C.,

Sensitive Detection of Malaria Parasitemia

in a Malaria-Endemic Setting: Performance

-


645-652.

The role of cGMP signalling in regulating

life cycle progression of Plasmodium. Mi-

crobes and Infection / Institut Pasteur.

Hopp, C., Flueck, C., Solyakov, L., Tobin,

Functional Characterisation of the Plasmo-

dium falciparum cGMP-Dependent Protein

-

ingu, J., Dekker, D., Leach, A., Moris, P.,

Cohen, J., Vekemans, J., Villafana, T.,

Seidlein, L. & Riley, E.

NK Cell Responses after Immunization of

Malaria Vaccine. Journal of Immunology

(Baltimore, Md, 188, 5054-62.

Horowitz, A. & Riley, E.

of human NK cells by Plasmodium-infected

red blood cells. Methods in Molecular Biol-

Howard, N. & Clements-Hunt, A.

Malaria control in humanitarian emergen-

-

tion.

Chea, N., Yok, S., Top, S., Ros, S., So-

phal, U., Thompson, M., Mellor, S., Ariey,

Duong, S., Newman, R. & Menard, D.

Malaria Parasite Carriers and Contain Drug

Resistant P. falciparum, Pailin, Cambodia.

-

G.

the proportion of human exposure to ma-

laria vector populations occurring indoors in

-

Imai, N., White, M., Ghani, A. & Drake-

ley, C.

Modelling Study. PLoS Neglected Tropical

Diseases, 8, e2978.

M. & Cameron, M.

nonanal-trimethylamine lure for collection of

in gravid traps. Journal of Medical Entomol-

ogy, 50, 619-23.

Jallow, M., Casals-Pascual, C., Acker-

M., Sisay-Joof, F., Usen, S., Abubakar, I.,

Clinical features of severe malaria associ-

ated with death: a 13-year observational

Jaramillo Ramirez, G., Logan, J., Loza-

Reyes, E., Stashenko, E. & Moores, G.

e48698.

Jarvis, J., Coltart, C., Pule, M., Chiodini,

P. & Doherty, T.

and severe delayed haemolysis. Lancet,

382, 180.

Magesa, S.

of Tanzania. Tropical Medicine & Interna-

tional Health, 19:3.

-

Protopopoff, N., Magesa, S., Mosha,

spread of pyrethroid and DDT resistance

Tanzania. Medical and Veterinary Entomol-

commitment tosexual development in ma-

laria parasites. Nature, 507, 248–252.

-

he, R., Perlmann, H., Takeo, S., Tsuboi,

Drakeley, C.

Distribution of Plasmodium vivax Infections

-

Alegana, V., Nyandigisi, A., Pandit, J.,

Fegan, G., Todd, J., Snow, R. & Good-

man, C.

malarial subsidy programme on the quality

of service provision of artemisinin-based

combination therapy in Kenya: a cluster-

randomized, controlled trial. Malaria Jour-

nal, 12.

-

burn, H., Agbenyega, T., Taylor, T.,

Epilepsia, 54, 990-1001.

-

sion patterns in Navrongo demographic

surveillance site, northern Ghana. Malaria

Journal, 12, 63.

-

J., Roper, C. & Alifrangis, M.

Surveillance of artemether-lumefantrine as-

sociated Plasmodium falciparum multidrug

resistance protein-1 gene polymorphisms in

Tanzania. Malaria Journal, 13, 264.

Naidoo, I., Roper, C., Mulokozi, A.,

Macarthur, J., Luntamo, M., Ashorn,

Intermittent Preventive Therapy for Malaria

During Pregnancy Using 2 vs 3 or More

Doses of Sulfadoxine-Pyrimethamine and

-

594-604.

S., Snow, R. & Goodman, C.

Understanding the Impact of Subsidizing

Focus Group Discussions in Rural Kenya.

hosting vectors. The Journal of the Royal

or Waiting? Topologies of the Breeding

Ground in Malaria Control. Science as Cul-

ture, 22, 86-107.

-

-

wanyi, A., Smith, E., Somi, M., Lyimo, T.,

artemisinin-based combination treatment

prevalence in Tanzania: an observational

study. Malaria Journal, 11, 140.

H., Magesa, S., Mosha, F., Rowland, M.

& Logan, J. -

perimental hut evaluation of a long-lasting

insecticide treated blanket for protection

against mosquitoes. Parasites and Vectors,

7, 129.

indicators for eliminating malaria transmis-

sion. Biology Letters, 8, 874-877.

Staedke, S. & Chandler, C. -

proving access to health care for malaria

-

tracts patients. Malaria Journal, 11.

Lauinger, I., Vivas, L., Perozzo, R.,

Pham, D., Esguerra, C., Crawford, A.,

Maes, L. & Tasdemir, D.

of Lichen Secondary Metabolites against

Plasmodium Liver Stage Parasites with

Natural Products, 76, 1064-1070.

Leslie, T., Mikhail, A., Mayan, I., Cundill,

& Rowland, M.

tests to improve treatment of malaria and

other febrile illnesses: patient randomised

effectiveness trial in primary care clinics in

-

-

for treatment policy in the region. Malaria

Journal, 12, 230.

-

bining malaria vector control interventions:

some trial design issues. Pathogens and

global health, 107, 1-4.

S., Hashim, R., Maxwell, C., Chandramo-

han, D. & Gosling, R.

among Young Children and Mosquito Vec-

tor Numbers? Evidence from Korogwe,

Plenderleith, L., Malenke, J., Sunda-

raraman, S., Ramirez, M., Crystal, P.,

Locatelli, S., Esteban, A., Mouacha, F.,

S., Sanz, C., Morgan, D., Gonder, M.,

Muller, M., Piel, A., Stewart, F., Wilson,





A., Sutherland, C., Nolder, D., Hart, J.,

-

E., Delaporte, E., Carter, R., Culleton, R.,

Shaw, G., Rayner, J., Peeters, M., Hahn,

malaria parasite Plasmodium vivax. Nature

Communications, 5, 3346.

Liu, Y., Auburn, S., Cao, J., Trimarsanto,

structure of Plasmodium vivax in Central

China. Malaria Journal, 13, 262.

Tine, R., Abiola, A., Ndiaye, M., Ndiaye,

J., Ndiaye, D., Sokhna, C., Gomis, J.,

Cairns, M., Hallett, R., Sutherland, C. &

markers of drug resistance in an area of

seasonal malaria chemoprevention in chil-

dren in Senegal. Malaria Journal, 12, 137.

C., Seeholzer, L., Mseka, A., Simfukwe,

Moore, S.

directional movement of mosquitoes to ol-

factory cues. Parasites and Vectors, 6, 131.

Lover, A. & Coker, R.

Effect of Geographic Location on Epidemi-

ology of Plasmodium vivax Malaria. Emerg-

ing Infectious Diseases, 19, 1058-65.

Lover, A. & Coker, R. -

ing the relationship between sporozoite

dose and incubation period in Plasmodium

vivax malaria: a systematic re-analysis.

Parasitology, 141, 859-868.

Lubell, Y., White, L., Varadan, S., Drake,

T., Yeung, S., Cheah, P., Maude, R., Don-

dorp, A., Day, N., White, N. & Parker, M.

primaquine to reduce falciparum malaria

transmission in asymptomatic populations.

PLoS Medicine, 11, e1001704.

-

nasar, D., Durrheim, D., Seocharan,

-

schmidt, I.

779-83.

-

we, E., Turner, E. & Moore, S.

Topical Repellents Divert Mosquitoes within

a Community? - Health Equity Implications

of Topical Repellents as a Mosquito Bite

Tapily, A., Campino, S., Sepulveda, N.,

-

Receptor IIa- H131R polymorphism and

malaria susceptibility in sympatric ethnic

groups, Fulani and Dogon of Mali. Scandi-


Risley, P., Silva, N., Corran, P., Rockett,

-

phisms in sympatric ethnic groups differing

8, e75675.

Malima, R., Tungu, P., Mwingira, V., Max-

& Rowland, M.

long-lasting insecticidal net Interceptor LN:

laboratory and experimental hut studies

against anopheline and culicine mosquitoes

in northeastern Tanzania. Parasites and

Vectors, 6, 296.

-

preference for the treatment of uncompli-

cated malaria? Social Science & Medicine

Ambebila, J., Lele, A., Metoh, T., Ndive,

J. & Mbacham, W. -

lence and treatment of febrile patients at

health facilities and medicine retailers in

Cameroon. Tropical Medicine & Interna-


Mtove, G., Wangai, H., Sepulveda, N.,

M., Riley, E., Reyburn, H. & Drakeley, C.

-

phisms and severe malaria in a tanzanian

Auburn, S., Almagro-Garcia, J., Maslen,

Amaratunga, C., Fairhurst, R., Socheat,

D., Nosten, F., Imwong, M., White, N.,

Sanders, M., Anastasi, E., Alcock, D.,

Ruano-Rubio, V., Jyothi, D., Amenga-

Etego, L., Hubbart, C., Jeffreys, A.,

Mangano, V., Modiano, D., Tan, J., Fer-

dig, M., Amambua-Ngwa, A., Conway, D.,

Takala-Harrison, S., Plowe, C., Rayner,

-

kowski, D.

falciparum diversity in natural infections by

deep sequencing. Nature, 487, 375-9.

Marks, M., Armstrong, M., Suvari, M.,

-

inghan, G. & Doherty, J.

imported falciparum malaria among adults

requiring intensive care: a retrospective

study at the hospital for tropical diseases,

London. BMC Infectious Diseases, 13, 118.

Matowo, N., Moore, J., Mapua, S., Mad-

-

a new odour-baited device to explore op-

tions for luring and killing outdoor-biting

malaria vectors: a report on design and

Box. Parasites & Vectors, 6:137.

Mbacham, W., Mangham-Jefferies, L.,

Ambebila, J., Nkwescheu, A., Forsah-

Achu, D., Ndiforchu, V., Tchekountouo,

Wiseman, V.

clinician training to improve adherence to

malaria treatment guidelines: a cluster-

randomised trial in two areas of Cameroon.

Lancet Global Health, 2, E346-E358.

evaluation of lethal and sub-lethal effects of

slow release pyriproxyfen granules (Sumi-

Malaria Journal, 12: 94.

Mbogo, G., Nankoberanyi, S., Tukwa-

Tappero, J., Staedke, S., Dorsey, G.,

Temporal Changes in Prevalence of Mo-

Resistance in a High Malaria Transmission

61.

Treatment of fevers prior to introducing

rapid diagnostic tests for malaria in regis-

tered drug shops in Uganda. Malaria Jour-

nal, 12:131.

Menaca, A., Pell, C., Manda-Taylor, L.,

Chatio, S., Afrah, N., Were, F., Hodgson,

Pool, R.

their relevance for the prevention and con-

trol of malaria during pregnancy in Ghana,

-

parative qualitative study. Malaria Journal,

12, 257.

Amambua-Ngwa, A., Gomez-Escobar, N.,

Walther, M., Conway, D. & Duraisingh,

M.

Virulence Gene Expression in Severe Plas-

modium falciparum Malaria. The Journal of


Messenger, L., Matias, A., Manana, A.,

Rowland, M.

of insecticide-treated durable wall lining in

358.

Messenger, L., Miller, N., Adeogun, A.,

Awolola, T. & Rowland, M.

development of insecticide-treated durable

wall lining for malaria control: insights from

Nigeria. Malaria Journal, 11, 332.

Mills, A.

low- and middle-income countries. The


552-7.

Mills, A. -

San Diego: Elsevier.

Mills, A. & Hsu, J.

in Low- and Middle-Income Countries:

Financing, Payment, and Provision. In:

Economics. San Diego: Elsevier.

Mimche, P., Thompson, E., Taramelli, D.

& Vivas, L.

non-opsonic phagocytosis of Plasmodium

falciparum through up-regulation of CD36

surface expression on monocytes/macro-

-

-

S., Sreng, S., Anderson, J., Duong, S.,

Nguon, C., Chuor, C., Saunders, D., Se,

Y., Lon, C., Fukuda, M., Amenga-Etego,

L., Hodgson, A., Asoala, V., Imwong, M.,

Ringwald, P., Ariey, F., Dolecek, C., Hien,

-

ers, M., Hubbart, C., Maslen, G., Ruano-

D., Dondorp, A., Plowe, C., Fairhurst, R.

-

tions of artemisinin-resistant Plasmodium

falciparum in Cambodia. Nature Genetics,

45, 648-55.

Lusingu, J., Drakeley, C., Fay, M., Long,

C. & Vekemans, J. -

gested human antibodies induced by RTS,

Plasmodium falciparum oocyst formation

and sporogony in mosquitoes. Malaria

Journal, 13, 263.

Mobegi, V., Duffy, C., Amambua-Ngwa,

-

-

way, D.

selection on the malaria parasite Plasmo-

of differing infection endemicity. Molecular

Satoguina, J., Nwakanma, D., Amambua-





A., Sutherland, C., Nolder, D., Hart, J.,

-

E., Delaporte, E., Carter, R., Culleton, R.,

Shaw, G., Rayner, J., Peeters, M., Hahn,

malaria parasite Plasmodium vivax. Nature

Communications, 5, 3346.

Liu, Y., Auburn, S., Cao, J., Trimarsanto,

structure of Plasmodium vivax in Central

China. Malaria Journal, 13, 262.

Tine, R., Abiola, A., Ndiaye, M., Ndiaye,

J., Ndiaye, D., Sokhna, C., Gomis, J.,

Cairns, M., Hallett, R., Sutherland, C. &

markers of drug resistance in an area of

seasonal malaria chemoprevention in chil-

dren in Senegal. Malaria Journal, 12, 137.

C., Seeholzer, L., Mseka, A., Simfukwe,

Moore, S.

directional movement of mosquitoes to ol-

factory cues. Parasites and Vectors, 6, 131.

Lover, A. & Coker, R.

Effect of Geographic Location on Epidemi-

ology of Plasmodium vivax Malaria. Emerg-

ing Infectious Diseases, 19, 1058-65.

Lover, A. & Coker, R. -

ing the relationship between sporozoite

dose and incubation period in Plasmodium

vivax malaria: a systematic re-analysis.

Parasitology, 141, 859-868.

Lubell, Y., White, L., Varadan, S., Drake,

T., Yeung, S., Cheah, P., Maude, R., Don-

dorp, A., Day, N., White, N. & Parker, M.

primaquine to reduce falciparum malaria

transmission in asymptomatic populations.

PLoS Medicine, 11, e1001704.

-

nasar, D., Durrheim, D., Seocharan,

-

schmidt, I.

779-83.

-

we, E., Turner, E. & Moore, S.

Topical Repellents Divert Mosquitoes within

a Community? - Health Equity Implications

of Topical Repellents as a Mosquito Bite


-

Receptor IIa- H131R polymorphism and

malaria susceptibility in sympatric ethnic

groups, Fulani and Dogon of Mali. Scandi-


Risley, P., Silva, N., Corran, P., Rockett,

-

phisms in sympatric ethnic groups differing

8, e75675.

Malima, R., Tungu, P., Mwingira, V., Max-

& Rowland, M.

long-lasting insecticidal net Interceptor LN:

laboratory and experimental hut studies

against anopheline and culicine mosquitoes

in northeastern Tanzania. Parasites and

Vectors, 6, 296.

-

preference for the treatment of uncompli-

cated malaria? Social Science & Medicine

Ambebila, J., Lele, A., Metoh, T., Ndive,

J. & Mbacham, W. -

lence and treatment of febrile patients at

health facilities and medicine retailers in

Cameroon. Tropical Medicine & Interna-


Mtove, G., Wangai, H., Sepulveda, N.,

M., Riley, E., Reyburn, H. & Drakeley, C.

-

phisms and severe malaria in a tanzanian

Auburn, S., Almagro-Garcia, J., Maslen,

Amaratunga, C., Fairhurst, R., Socheat,

D., Nosten, F., Imwong, M., White, N.,

Sanders, M., Anastasi, E., Alcock, D.,

Ruano-Rubio, V., Jyothi, D., Amenga-

Etego, L., Hubbart, C., Jeffreys, A.,

Mangano, V., Modiano, D., Tan, J., Fer-

dig, M., Amambua-Ngwa, A., Conway, D.,

Takala-Harrison, S., Plowe, C., Rayner,

-

kowski, D.

falciparum diversity in natural infections by

deep sequencing. Nature, 487, 375-9.

Marks, M., Armstrong, M., Suvari, M.,

-

inghan, G. & Doherty, J.

imported falciparum malaria among adults

requiring intensive care: a retrospective

study at the hospital for tropical diseases,

London. BMC Infectious Diseases, 13, 118.

Matowo, N., Moore, J., Mapua, S., Mad-

-

a new odour-baited device to explore op-

tions for luring and killing outdoor-biting

malaria vectors: a report on design and

Box. Parasites & Vectors, 6:137.

Mbacham, W., Mangham-Jefferies, L.,

Ambebila, J., Nkwescheu, A., Forsah-

Achu, D., Ndiforchu, V., Tchekountouo,

Wiseman, V.

clinician training to improve adherence to

malaria treatment guidelines: a cluster-

randomised trial in two areas of Cameroon.

Lancet Global Health, 2, E346-E358.

evaluation of lethal and sub-lethal effects of

slow release pyriproxyfen granules (Sumi-

Malaria Journal, 12: 94.

Mbogo, G., Nankoberanyi, S., Tukwa-

Tappero, J., Staedke, S., Dorsey, G.,

Temporal Changes in Prevalence of Mo-

Resistance in a High Malaria Transmission

61.

Treatment of fevers prior to introducing

rapid diagnostic tests for malaria in regis-

tered drug shops in Uganda. Malaria Jour-

nal, 12:131.

Menaca, A., Pell, C., Manda-Taylor, L.,

Chatio, S., Afrah, N., Were, F., Hodgson,

Pool, R.

their relevance for the prevention and con-

trol of malaria during pregnancy in Ghana,

-

parative qualitative study. Malaria Journal,

12, 257.

Amambua-Ngwa, A., Gomez-Escobar, N.,

Walther, M., Conway, D. & Duraisingh,

M.

Virulence Gene Expression in Severe Plas-

modium falciparum Malaria. The Journal of


Messenger, L., Matias, A., Manana, A.,

Rowland, M.

of insecticide-treated durable wall lining in

358.

Messenger, L., Miller, N., Adeogun, A.,

Awolola, T. & Rowland, M.

development of insecticide-treated durable

wall lining for malaria control: insights from

Nigeria. Malaria Journal, 11, 332.

Mills, A.

low- and middle-income countries. The


552-7.

Mills, A. -

San Diego: Elsevier.

Mills, A. & Hsu, J.

in Low- and Middle-Income Countries:

Financing, Payment, and Provision. In:

Economics. San Diego: Elsevier.

Mimche, P., Thompson, E., Taramelli, D.

& Vivas, L.

non-opsonic phagocytosis of Plasmodium

falciparum through up-regulation of CD36

surface expression on monocytes/macro-

-

-

S., Sreng, S., Anderson, J., Duong, S.,

Nguon, C., Chuor, C., Saunders, D., Se,

Y., Lon, C., Fukuda, M., Amenga-Etego,

L., Hodgson, A., Asoala, V., Imwong, M.,

Ringwald, P., Ariey, F., Dolecek, C., Hien,

-

ers, M., Hubbart, C., Maslen, G., Ruano-

D., Dondorp, A., Plowe, C., Fairhurst, R.

-

tions of artemisinin-resistant Plasmodium

falciparum in Cambodia. Nature Genetics,

45, 648-55.

Lusingu, J., Drakeley, C., Fay, M., Long,

C. & Vekemans, J. -

gested human antibodies induced by RTS,

Plasmodium falciparum oocyst formation

and sporogony in mosquitoes. Malaria

Journal, 13, 263.

Mobegi, V., Duffy, C., Amambua-Ngwa,

-

-

way, D.

selection on the malaria parasite Plasmo-

of differing infection endemicity. Molecular

Satoguina, J., Nwakanma, D., Amambua-





Ngwa, A. & Conway, D.

genetic structure of Plasmodium falciparum

across a region of diverse endemicity in

F., Alifrangis, M., Reyburn, H., Roper, C.

-

quine resistance marker, Pfcrt-K76T muta-

tion ten years after chloroquine withdrawal

in Tanzania. Malaria Journal, 12, 415.

Medical Journal, 103, 801-6.

Moore, S., Mordue Luntz, A. & Logan, J.

73.

Hill, N. & And Cameron, M.

Malaria in China: Use of Personal Protec-

tion by Minority Populations. BMC Public

Health 8:344.

Moorthy, V., Newman, R., Duclos, P.,

-


282.

Hung, N., Coosemans, M., D’alessandro,

U. & Mills, A.

of Long-Lasting Insecticide-Treated Ham-

mocks in Preventing Malaria in South-Cen-

-

ling, R.

Plasmodium falciparum infection: implica-

tions for detection of hotspots with imper-

fect diagnostics. Malaria Journal, 12:221.

Sutherland, C., Gadalla, N., Atwal, S.,

D. & Gosling, R.

a comparison of spatial statistical methods

to predict prospective malaria infections.


Moyes, C., Henry, A., Golding, N., Huang,

-

Plasmodium knowlesi Reservoir. PLoS Ne-

glected Tropical Diseases, 8, e2780.

-

-

vation for providing intermittent preventive

treatment of malaria during pregnancy in

Tanzania: evidence from two rural districts.

Malaria Journal 11:48.

-

Felger, I.

to understanding the epidemiology of Plas-

modium falciparum malaria in Papua New

Guinean children. Proceedings of the Na-

-

aging malaria in tuberculosis patients on

-

sessing the risk of QT prolongation. The

International Journal of Tuberculosis and

Lung Disease, 16, 144-149.

-

land, M.

-

permethrin Control Pyrethroid Resistant

-

9, e87710.

N’guessan, R. & Rowland, M.

Indoor residual spraying for prevention of

malaria. The Lancet Infectious Diseases,

12:8, 581 - 582.

an update for physicians. Infectious Dis-

-

Reyburn, H.

-

ted to the Hospital with Febrile Illness in

Naidoo, I. & Roper, C.

‘partially resistant’, ‘fully resistant’, and ‘su-

per resistant’ malaria. Trends in Parasitol-

ogy, 29:10, 505–515.

Jayaraman, J., Traherne, J., Elliott, A.,

-

in a Ugandan population. Immunogenetics,

65, 765-775.

-

fett, A. & Mirembe, F. -

-

spective Cohort Study at Mulago Hospital,

Treatment With Dihydroartemisinin-Piper-

aquine on Malaria in Ugandan Schoolchil-

Trial. Clinical Infectious Diseases, 58,

1404-1412.

S.

Infection and Cognition among Primary

Schoolchildren in a High Malaria Trans-


Alifrangis, M. -

malarial Drug Resistance after Intermit-

tent Preventive Treatment of Infants and

Journal of Tropical Medicine and Hy-

-

& Schellenberg, D.

case management in malaria: review and

perspectives after four years of operational

experience in Saraya district, south-east

Senegal. Malaria Journal, 12, 240.

Ndibazza, J., Webb, E., Lule, S., Mpair-

Akurut, H., Muhangi, L., Magnussen, P.,

-

sociations between maternal helminth and

malaria infections in pregnancy and clinical

malaria in the offspring: a birth cohort in

entebbe, Uganda. The Journal of Infectious

Diseases, 208, 2007-16.

-

ported malaria-related healthcare services

malaria chemoprophylaxis reduce imported


Ngufor, C., N’guessan, R., Fagbohoun,

Rowland, M. -

Experimental Hut Trial against Pyrethroid

quinquefasciatus in Southern Benin. Plos

N’fale, S., Dabire, R., Johnson, P., Ran-

son, H. & Rowland, M.

Long-lasting Insecticidal Nets for Improved

Nielsen, C., White, M., Goodier, M. &

Riley, E.

CD57 Expression on Human NK Cells and

Relevance to Disease. Frontiers in Immu-

nology, 4, 422.

events resulting from use of drugs with

sulphonamide-containing anti-malarials and

incidence and household costs from three

districts with routine demographic surveil-

lance systems in rural Tanzania. Malaria

Journal, 12: 236.

H., Niyazi, H., Smith, V., Chiodini, P. &

Sutherland, C.

study of malaria in British travellers: Plas-

modium ovale wallikeri and Plasmodium

-

ration of latency. British Medical Journal

Nwakanma, D., Duffy, C., Amambua-

M., Drakeley, C., Sutherland, C., Mil-

resistance in an endemic population over

a 25-year period with resulting genomic

evidence of selection. The Journal of Infec-

Nwakanma, D., Neafsey, D., Jawara,

M., Adiamoh, M., Lund, E., Rodrigues,

Awolola, T., Muskavitch, M. & Conway,

D.

Genetics, 193, 1221-31.

Phou, M., Dysoley, L., Yeung, S., Allen,

H. & Littrell, M. -

cestor that knock us out” and other tales.

-

ment in Cambodia. Malaria Journal, 11,

335.

& Johnson, J.

of Plasmodium infections by conventional

microscopy and the impact of remedial

-

laria Journal, 12, 113.

-

-

& Montgomery, J.

scans provide evidence of adaptive evolu-

tion in Malawian Plasmodium falciparum

isolates. The Journal of Infectious Diseas-

es, pii: jiu349.

-

sitological evaluation of the heterogeneity

of malaria infection in the Gambia. Malaria

Journal, 12, 222.





Ngwa, A. & Conway, D.

genetic structure of Plasmodium falciparum

across a region of diverse endemicity in

F., Alifrangis, M., Reyburn, H., Roper, C.

-

quine resistance marker, Pfcrt-K76T muta-

tion ten years after chloroquine withdrawal

in Tanzania. Malaria Journal, 12, 415.

Medical Journal, 103, 801-6.

Moore, S., Mordue Luntz, A. & Logan, J.

73.

Hill, N. & And Cameron, M.

Malaria in China: Use of Personal Protec-

tion by Minority Populations. BMC Public

Health 8:344.

Moorthy, V., Newman, R., Duclos, P.,

-


282.

Hung, N., Coosemans, M., D’alessandro,

U. & Mills, A.

of Long-Lasting Insecticide-Treated Ham-

mocks in Preventing Malaria in South-Cen-

-

ling, R.

Plasmodium falciparum infection: implica-

tions for detection of hotspots with imper-

fect diagnostics. Malaria Journal, 12:221.

Sutherland, C., Gadalla, N., Atwal, S.,

D. & Gosling, R.

a comparison of spatial statistical methods

to predict prospective malaria infections.


Moyes, C., Henry, A., Golding, N., Huang,

-

Plasmodium knowlesi Reservoir. PLoS Ne-

glected Tropical Diseases, 8, e2780.

-

-

vation for providing intermittent preventive

treatment of malaria during pregnancy in

Tanzania: evidence from two rural districts.

Malaria Journal 11:48.

-

Felger, I.

to understanding the epidemiology of Plas-

modium falciparum malaria in Papua New

Guinean children. Proceedings of the Na-

-

aging malaria in tuberculosis patients on

-

sessing the risk of QT prolongation. The

International Journal of Tuberculosis and

Lung Disease, 16, 144-149.

-

land, M.

-

permethrin Control Pyrethroid Resistant

-

9, e87710.

N’guessan, R. & Rowland, M.

Indoor residual spraying for prevention of

malaria. The Lancet Infectious Diseases,

12:8, 581 - 582.

an update for physicians. Infectious Dis-

-

Reyburn, H.

-

ted to the Hospital with Febrile Illness in

Naidoo, I. & Roper, C.

‘partially resistant’, ‘fully resistant’, and ‘su-

per resistant’ malaria. Trends in Parasitol-

ogy, 29:10, 505–515.

Jayaraman, J., Traherne, J., Elliott, A.,

-

in a Ugandan population. Immunogenetics,

65, 765-775.

-

fett, A. & Mirembe, F. -

-

spective Cohort Study at Mulago Hospital,

Treatment With Dihydroartemisinin-Piper-

aquine on Malaria in Ugandan Schoolchil-

Trial. Clinical Infectious Diseases, 58,

1404-1412.

S.

Infection and Cognition among Primary

Schoolchildren in a High Malaria Trans-


Alifrangis, M. -

malarial Drug Resistance after Intermit-

tent Preventive Treatment of Infants and

Journal of Tropical Medicine and Hy-

-

& Schellenberg, D.

case management in malaria: review and

perspectives after four years of operational

experience in Saraya district, south-east

Senegal. Malaria Journal, 12, 240.

Ndibazza, J., Webb, E., Lule, S., Mpair-

Akurut, H., Muhangi, L., Magnussen, P.,

-

sociations between maternal helminth and

malaria infections in pregnancy and clinical

malaria in the offspring: a birth cohort in

entebbe, Uganda. The Journal of Infectious

Diseases, 208, 2007-16.

-

ported malaria-related healthcare services

malaria chemoprophylaxis reduce imported


Ngufor, C., N’guessan, R., Fagbohoun,

Rowland, M. -

Experimental Hut Trial against Pyrethroid

quinquefasciatus in Southern Benin. Plos

N’fale, S., Dabire, R., Johnson, P., Ran-

son, H. & Rowland, M.

Long-lasting Insecticidal Nets for Improved

Nielsen, C., White, M., Goodier, M. &

Riley, E.

CD57 Expression on Human NK Cells and

Relevance to Disease. Frontiers in Immu-

nology, 4, 422.

events resulting from use of drugs with

sulphonamide-containing anti-malarials and

incidence and household costs from three

districts with routine demographic surveil-

lance systems in rural Tanzania. Malaria

Journal, 12: 236.

H., Niyazi, H., Smith, V., Chiodini, P. &

Sutherland, C.

study of malaria in British travellers: Plas-

modium ovale wallikeri and Plasmodium

-

ration of latency. British Medical Journal

Nwakanma, D., Duffy, C., Amambua-

M., Drakeley, C., Sutherland, C., Mil-

resistance in an endemic population over

a 25-year period with resulting genomic

evidence of selection. The Journal of Infec-

Nwakanma, D., Neafsey, D., Jawara,

M., Adiamoh, M., Lund, E., Rodrigues,

Awolola, T., Muskavitch, M. & Conway,

D.

Genetics, 193, 1221-31.

Phou, M., Dysoley, L., Yeung, S., Allen,

H. & Littrell, M. -

cestor that knock us out” and other tales.

-

ment in Cambodia. Malaria Journal, 11,

335.

& Johnson, J.

of Plasmodium infections by conventional

microscopy and the impact of remedial

-


-

-

& Montgomery, J.

scans provide evidence of adaptive evolu-

tion in Malawian Plasmodium falciparum

isolates. The Journal of Infectious Diseas-

es, pii: jiu349.

-

sitological evaluation of the heterogeneity

of malaria infection in the Gambia. Malaria

Journal, 12, 222.





-

draogo, A., Ghani, A. & Drakeley, C.

of submicroscopic malaria infections and

their relevance for control. Nature Commu-

nications, 3, 1237.

-

-

ferring Mutations in Plasmodium falciparum

57:9, 4595-4598.

-

lock, M., Sangusangu, R., Ligamba, G.,

Russell, T. & Moore, S. -

responses of disease-transmitting mos-

quitoes to indoor interventions: the Ifakara

-

noglobulin-like receptors and falciparum

malaria in southwest Nigeria. Human Im-

-

ventive treatment for malaria in pregnancy

Journal, 11, 82.

delivery of intermittent preventive treatment

-

ence of provider factors. Malaria Journal,

11, 317.

A., Edwards, T., Fegan, G., Molyneux, S.

& Goodman, C.

of patient charges at primary care facilities

in Kenya: implications of low adherence

to user fee policy for users and facility

revenue. Health Policy and Planning: doi:

10.1093/heapol/czu026.

-

Malaria Cases with or without Laboratory

Diagnosis: The Experience in a District

doi:10.1371/journal.pone.0058107.

I. & Slotman, M. -

Bioko Island, Equatorial Guinea. Parasites

and Vectors, 5, 253.

Feston, E., Matowo, J., Mosha, F. & Row-

land, M.

-

plication of micro-encapsulated pirimiphos-

13, 37.

Fragile Gains: The Need to Maintain Cover-

age with Long-Lasting Insecticidal Nets for

Malaria Control and Likely Implications of

-

Chavasse, D. -

vate sector antimalarial distribution chains:

a cross-sectional mixed methods study in

9, e93763.

Pates, H., Curtis, C. & Takken, W.

Hybridization studies to modify the host

and Veterinary Entomology, 28, 68-74.

-

Comparative analysis of two methods for

measuring sales volumes during malaria

medicine outlet surveys. Malaria Journal,

12, 311.

F., Alonso, P., Tanner, M., Mshinda, H.,

Roper, C. & Schellenberg, D.

community-randomised evaluation of the

effect of IPTi on anti-malarial drug resis-

tance in southern Tanzania. The Journal of


-

L.

of malaria in children: a qualitative study of

community perceptions and recommenda-

7, e32900.

E., Armstrong, M., Gray, C., Perkins, M.,

Y., Mori, Y., Chiodini, P. & Sutherland,

C.

Imported Malaria. The Journal of Infectious

Diseases, 208, 637-44.

Prentice, A. & Cox, S.

malaria interactions: research needs from

Prentice, A., Verhoef, H. & Cerami, C.

Preston, M., Campino, S., Assefa, S.,

Ngwa, A., Stewart, L., Conway, D.,

-

ley, C., Fairhurst, R., Sutherland, C.,

Roper, C. & Clark, T.

organellar genome polymorphisms identi-

falciparum strains. Nature Communica-

tions, 5, 4052.

Egwang, T., Corran, P., Ronca, R., Arcà,

a cohort exposed to intense malaria trans-

mission in northern Uganda. Parasite Im-

Protopopoff, N., Matowo, J., Malima, R.,

F. & Rowland, M.

-

biae to pyrethroid insecticides and reduced

susceptibility to bendiocarb in north-west-

ern Tanzania. Malaria Journal, 12, 149.

Pullan, R., Gitonga, C., Mwandawiro, C.,

-

ing the relative contribution of parasitic

infections and nutrition for anaemia among

school-aged children in Kenya: a subna-

tional geostatistical analysis. British Medi-

Rao, V., Schellenberg, D. & Ghani, A.

-

ers to successful malaria treatment. Trends

in Parasitology, 29, 164-180.

-

schmidt, I., Ridl, F., Powell, J., Caccone,

A. & Slotman, M. -

-

ventions in Continental Equatorial Guinea.

Rehman, A., Mann, A., Schwabe, C.,

Reddy, M., Roncon Gomes, I., Slotman,

M., Yellott, L., Matias, A., Caccone, A.,

continental region, Equatorial Guinea. Ma-


Reynolds, J., Mangesho, P., Lemnge, M.,

Vestergaard, L. & Chandler, C.

in the project they really care for us’: Mean-

ing and experiences of participating in a

-

laria and HIV in Tanzanian adults. Global

Reynolds, J., Wood, M., Mikhail, A.,

Chandler, C. & Leslie, T.

Qualitative Health Research, 23, 579-91.

Riley, E. & Grencis, R.

Immunology embraces 21st century pub-

lishing: moving to online-only publication.

Parasite Immunology, 36, 1-2.

-

Aide, P., Lanaspa, M., Aponte, J., Mache-

Macete, E., Alonso, P., Abdulla, S., Salim,

A., Mtoro, A., Hamad, A., Mutani, P., Tan-

ner, M., Tinto, H., D’alessandro, U., Sorg-

-

-

E., Chandramohan, D., Greenwood,

E., Malle, L., Lemnge, M., Theander, T.,

Drakeley, C., Ansong, D., Agbenyega, T.,

J., Sylverken, J., Sambian, D., Sarfo, A.,

Agyekum, A., Martinson, F., Hoffman,

-

J., Guerra, Y., Jongert, E., Lapierre, D.,

D., Sillman, M. & Vansadia, P.

-

Journal of Medicine, 367, 2284-95.

Saeed, S., Carter, V., Tremp, A. & Des-

sens, J.

controls temporal expression of the Plas-

modium berghei LCCL protein complex.

Molecular and Biochemical Parasitology,

189, 38-42.

Sawa, P., Shekalaghe, S., Drakeley, C.,

L., Schallig, H., Sauerwein, R., Hallett,

-

Randomized Trial. The Journal of Infectious

Diseases, 207, 1637-1645.

-

keeto, S., Sserwanga, A., Staedke, S.,

-

mya, M. & Dorsey, G.

prescription practices among outpatients

setting of a health facility-based sentinel

site surveillance system in Uganda. Malaria

Journal, 12.

Sepúlveda, N., Campino, S., Assefa,

S., Sutherland, C., Pain5, A. & Clark, T.

approach to detecting copy number varia-

tion in sequence coverage data. BMC Ge-

nomics, 14, 128.





-

draogo, A., Ghani, A. & Drakeley, C.

of submicroscopic malaria infections and

their relevance for control. Nature Commu-

nications, 3, 1237.

-

-

ferring Mutations in Plasmodium falciparum

57:9, 4595-4598.

-

lock, M., Sangusangu, R., Ligamba, G.,

Russell, T. & Moore, S. -

responses of disease-transmitting mos-

quitoes to indoor interventions: the Ifakara

-

noglobulin-like receptors and falciparum

malaria in southwest Nigeria. Human Im-

-

ventive treatment for malaria in pregnancy

Journal, 11, 82.

delivery of intermittent preventive treatment

-

ence of provider factors. Malaria Journal,

11, 317.

A., Edwards, T., Fegan, G., Molyneux, S.

& Goodman, C.

of patient charges at primary care facilities

in Kenya: implications of low adherence

to user fee policy for users and facility

revenue. Health Policy and Planning: doi:

10.1093/heapol/czu026.

-

Malaria Cases with or without Laboratory

Diagnosis: The Experience in a District

doi:10.1371/journal.pone.0058107.

I. & Slotman, M. -

Bioko Island, Equatorial Guinea. Parasites

and Vectors, 5, 253.

Feston, E., Matowo, J., Mosha, F. & Row-

land, M.

-

plication of micro-encapsulated pirimiphos-

13, 37.

Fragile Gains: The Need to Maintain Cover-

age with Long-Lasting Insecticidal Nets for

Malaria Control and Likely Implications of

-

Chavasse, D. -

vate sector antimalarial distribution chains:

a cross-sectional mixed methods study in

9, e93763.

Pates, H., Curtis, C. & Takken, W.

Hybridization studies to modify the host

and Veterinary Entomology, 28, 68-74.

-

Comparative analysis of two methods for

measuring sales volumes during malaria

medicine outlet surveys. Malaria Journal,

12, 311.

F., Alonso, P., Tanner, M., Mshinda, H.,

Roper, C. & Schellenberg, D.

community-randomised evaluation of the

effect of IPTi on anti-malarial drug resis-

tance in southern Tanzania. The Journal of


-

L.

of malaria in children: a qualitative study of

community perceptions and recommenda-

7, e32900.

E., Armstrong, M., Gray, C., Perkins, M.,

Y., Mori, Y., Chiodini, P. & Sutherland,

C.

Imported Malaria. The Journal of Infectious

Diseases, 208, 637-44.

Prentice, A. & Cox, S.

malaria interactions: research needs from

Prentice, A., Verhoef, H. & Cerami, C.

Preston, M., Campino, S., Assefa, S.,

Ngwa, A., Stewart, L., Conway, D.,

-

ley, C., Fairhurst, R., Sutherland, C.,

Roper, C. & Clark, T.

organellar genome polymorphisms identi-

falciparum strains. Nature Communica-

tions, 5, 4052.

Egwang, T., Corran, P., Ronca, R., Arcà,

a cohort exposed to intense malaria trans-

mission in northern Uganda. Parasite Im-

Protopopoff, N., Matowo, J., Malima, R.,

F. & Rowland, M.

-

biae to pyrethroid insecticides and reduced

susceptibility to bendiocarb in north-west-

ern Tanzania. Malaria Journal, 12, 149.

Pullan, R., Gitonga, C., Mwandawiro, C.,

-

ing the relative contribution of parasitic

infections and nutrition for anaemia among

school-aged children in Kenya: a subna-

tional geostatistical analysis. British Medi-

Rao, V., Schellenberg, D. & Ghani, A.

-

ers to successful malaria treatment. Trends

in Parasitology, 29, 164-180.

-

schmidt, I., Ridl, F., Powell, J., Caccone,

A. & Slotman, M. -

-

ventions in Continental Equatorial Guinea.

Rehman, A., Mann, A., Schwabe, C.,

Reddy, M., Roncon Gomes, I., Slotman,

M., Yellott, L., Matias, A., Caccone, A.,

continental region, Equatorial Guinea. Ma-


Reynolds, J., Mangesho, P., Lemnge, M.,

Vestergaard, L. & Chandler, C.

in the project they really care for us’: Mean-

ing and experiences of participating in a

-

laria and HIV in Tanzanian adults. Global

Reynolds, J., Wood, M., Mikhail, A.,

Chandler, C. & Leslie, T.

Qualitative Health Research, 23, 579-91.

Riley, E. & Grencis, R.

Immunology embraces 21st century pub-

lishing: moving to online-only publication.

Parasite Immunology, 36, 1-2.

-

Aide, P., Lanaspa, M., Aponte, J., Mache-

Macete, E., Alonso, P., Abdulla, S., Salim,

A., Mtoro, A., Hamad, A., Mutani, P., Tan-

ner, M., Tinto, H., D’alessandro, U., Sorg-

-

-

E., Chandramohan, D., Greenwood,

E., Malle, L., Lemnge, M., Theander, T.,

Drakeley, C., Ansong, D., Agbenyega, T.,

J., Sylverken, J., Sambian, D., Sarfo, A.,

Agyekum, A., Martinson, F., Hoffman,

-

J., Guerra, Y., Jongert, E., Lapierre, D.,

D., Sillman, M. & Vansadia, P.

-

Journal of Medicine, 367, 2284-95.

Saeed, S., Carter, V., Tremp, A. & Des-

sens, J.

controls temporal expression of the Plas-

modium berghei LCCL protein complex.

Molecular and Biochemical Parasitology,

189, 38-42.

Sawa, P., Shekalaghe, S., Drakeley, C.,

L., Schallig, H., Sauerwein, R., Hallett,

-

Randomized Trial. The Journal of Infectious

Diseases, 207, 1637-1645.

-

keeto, S., Sserwanga, A., Staedke, S.,

-

mya, M. & Dorsey, G.

prescription practices among outpatients

setting of a health facility-based sentinel

site surveillance system in Uganda. Malaria

Journal, 12.

Sepúlveda, N., Campino, S., Assefa,

S., Sutherland, C., Pain5, A. & Clark, T.

approach to detecting copy number varia-

tion in sequence coverage data. BMC Ge-

nomics, 14, 128.





C. & Clark, T.

of Multiple Imputation Based on Chained

Equations in Tackling Missing Data of the

-

ics, 78, 277-89.

Fe

a complementary age grading and species

-

tors. Parasites and Vectors, 3:49.

Yadeta, D., Ruiz Carrascal, D. & Pascual,

M.

Incidence in Highlands of Ethiopia and

1154-1158.

L. & Ghani, A.

of adding Ivermectin to a mass treatment

intervention to reduce malaria transmission:

a modelling study. The Journal of Infectious

Diseases, pii: jiu351.

Smallegange, R., Van Gemert, G., Van De

Sauerwein, R. & Logan, J.

Infected Mosquitoes Express Enhanced

e63602.

Smith, D., Perkins, T., Tusting, L., Scott,

T. & Lindsay, S. -

tion regulation and larval source manage-

ment in heterogeneous environments. Plos

Smith Paintain, L., Awini, E., Addei, S.,

Manyei, A., Yayemain, D., Rusamira, E.,

Mangham-Jefferies, L.

of a universal long-lasting insecticidal net

effectiveness of distribution and hang-up

activities. Malaria Journal, 13, 71.

J., Schellenberg, D. & Ngongo, N.

Community Health Workers and Stand-

Staedke, S., Chandler, C., Diliberto, D.,

Maiteki-Sebuguzi, C., Nankya, F., Webb,

PRIME trial protocol: evaluating the impact

of an intervention implemented in public

health centres on management of malaria

and health outcomes of children using a

cluster-randomised design in Tororo, Ugan-

da. Implementation Science, 8, 114.

-

bach, R., Cox, J. & Drakeley, C.

Novel vectors of malaria parasites in the

Western highlands of kenya. Emerging


Stevenson, J., Stresman, G., Gitonga, C.,

-

Cox, J.

in estimating geographic variation in ma-

laria transmission in the Western kenyan

Nets for Control of Pyrethroid-Resistant

-

sase, S., Hashim, R., Gosling, R., Car-

neiro, I., Chandramohan, D., Theander,

Drakeley, C.

Detect Variation in Exposure to Malaria

e40170.

Stone, W., Churcher, T., Graumans,

-

ment of Plasmodium falciparum transmis-

sion in the standard membrane feeding as-

say using transgenic parasites expressing

GFP-luciferase. The Journal of Infectious

Diseases, doi: 10.1093/infdis/jiu271.

Stone, W., Eldering, M., Van Gemert,

Graumans, W., Roeffen, W., Drakeley, C.,

relevance and applicability of oocyst preva-

lence as a read-out for mosquito feeding

Sturrock, H., Hsiang, M., Cohen, J.,

& Gosling, R. -

atic malaria infections: active surveillance

in control and elimination. PloS Medicine,

10, e1001467.

malarial serine protease SUB1 plays an es-

sential role in parasite liver stage develop-

ment. Plos Pathogens, 9, e1003811.

Takala-Harrison, S., Clark, T., Jacob,

A., Fukuda, M., Nosten, F., Noedl, H.,

Tyner, S., Saunders, D., Socheat, D., Ari-

ey, F., Phyo, A., Starzengruber, P., Fueh-

Flegg, J., Arze, C., Cerqueira, G., Silva,

J., Ricklefs, S., Porcella, S., Stephens,

Plowe, C.

with delayed clearance of Plasmodium

falciparum following artemisinin treatment

-

Takala-Harrison, S., Jacob, C., Arze, C.,

Cummings, M., Silva, J., Dondorp, A.,

Fukuda, M., Hien, T., Mayxay, M., No-

Tyner, S., Saunders, D., Ariey, F., Mer-

-

D., White, N., Ringwald, P. & Plowe, C.

-

modium falciparum artemisinin resistance

Infectious Diseases, pii: jiu491.

Takem, E., Affara, M., Amambua-Ngwa,

Clifford, C., Taal, M., Sowe, M., Suso,

P., Mendy, A., Mbaye, A., Drakeley, C. &

D’alessandro, U.

Malaria Transmission with School Surveys:

Takem EN, Affara M, Amambua-Ngwa

-

tecting Foci of Malaria Transmission with

-

journal.pone.0067108.

Juma, E., Logedi, J., Nyandigisi, A.,

Mulenga, M., Mbacham, W., Roper, C.,

Guerin, P., Dalessandro, U. & Snow., R.

-

for enhanced wide coverage malaria drug

resistance surveillance and response sys-

888–896.

Tanomsing, N., Imwong, M., Sutherland,

C., Dolecek, C., Hien, T., Nosten, F., Day,

N., White, N. & Snounou, G. -

genotyping of Plasmodium ovale curtisi

and Plasmodium ovale wallikeri. Journal of

Clinical Microbiology, 51, 4213-6.

-

committee. Malaria Journal, 12, 362.

-

Mathanga, D., Mårtensson, A., Ngasala,

A., Moormann, A., Vulule, J., Doumbo,

& Juliano, J.

Plasmodium falciparum artemisinin resis-

molecular epidemiologic study. The Journal

of Infectious Diseases: doi: 10.1093/infdis/

jiu467.

Temu, E., Coleman, M., Abilio, A. &

of Malaria in Zambezia, Mozambique: The

Protective Effect of IRS versus Increased

Risks Due to Pig-Keeping and House Con-

G., Drought, L., Failly, M., Martin, C.,

of antibodies to newly described Plasmodi-

um falciparum merozoite antigens supports

MSPDBL2 as a predicted target of naturally

acquired immunity. Infection and Immunity,

-

ment of a Transgenic Plasmodium berghei

cGMP-Dependent Protein Kinase, a Novel

e96923.

Theisen, M., Roeffen, W., Singh, S.,

Andersen, G., Amoah, L., Van De Vegte-

-

egiel, M., Christiansen, M. & Sauerwein,

R.

candidate targeting both transmission and

asexual parasite life-cycle stages. Vaccine,

-

maprasad, A., Nwakanma, D., Fischer,

Journal of Proteome Research, 12, 1211-

1222.

-

schmidt, I., Ye, Y., Mann, A., Ren, R., Wil-

& Goodman, C. -

-

let and Household Surveys before and after

South-west burkina faso: comparison of

active and passive case detection methods.

-

-

ogbeto, M. -

age and effective use rate of long-lasting

insecticidal nets after nation-wide scale up

of their distribution in Benin. Parasites and

Vectors. 2013; 6: 265.

Souza, J., Liu, F., Riley, E. & Rabinovich,

G.





C. & Clark, T.

of Multiple Imputation Based on Chained

Equations in Tackling Missing Data of the

-

ics, 78, 277-89.

Fe

a complementary age grading and species

-

tors. Parasites and Vectors, 3:49.

Yadeta, D., Ruiz Carrascal, D. & Pascual,

M.

Incidence in Highlands of Ethiopia and

1154-1158.

L. & Ghani, A.

of adding Ivermectin to a mass treatment

intervention to reduce malaria transmission:

a modelling study. The Journal of Infectious

Diseases, pii: jiu351.

Smallegange, R., Van Gemert, G., Van De

Sauerwein, R. & Logan, J.

Infected Mosquitoes Express Enhanced

e63602.

Smith, D., Perkins, T., Tusting, L., Scott,

T. & Lindsay, S. -

tion regulation and larval source manage-

ment in heterogeneous environments. Plos

Smith Paintain, L., Awini, E., Addei, S.,

Manyei, A., Yayemain, D., Rusamira, E.,

Mangham-Jefferies, L.

of a universal long-lasting insecticidal net

effectiveness of distribution and hang-up

activities. Malaria Journal, 13, 71.

J., Schellenberg, D. & Ngongo, N.

Community Health Workers and Stand-

Staedke, S., Chandler, C., Diliberto, D.,

Maiteki-Sebuguzi, C., Nankya, F., Webb,

PRIME trial protocol: evaluating the impact

of an intervention implemented in public

health centres on management of malaria

and health outcomes of children using a

cluster-randomised design in Tororo, Ugan-

da. Implementation Science, 8, 114.

-

bach, R., Cox, J. & Drakeley, C.

Novel vectors of malaria parasites in the

Western highlands of kenya. Emerging


Stevenson, J., Stresman, G., Gitonga, C.,

-

Cox, J.

in estimating geographic variation in ma-

laria transmission in the Western kenyan

Nets for Control of Pyrethroid-Resistant

-

sase, S., Hashim, R., Gosling, R., Car-

neiro, I., Chandramohan, D., Theander,

Drakeley, C.

Detect Variation in Exposure to Malaria

e40170.

Stone, W., Churcher, T., Graumans,

-

ment of Plasmodium falciparum transmis-

sion in the standard membrane feeding as-

say using transgenic parasites expressing

GFP-luciferase. The Journal of Infectious

Diseases, doi: 10.1093/infdis/jiu271.

Stone, W., Eldering, M., Van Gemert,

Graumans, W., Roeffen, W., Drakeley, C.,

relevance and applicability of oocyst preva-

lence as a read-out for mosquito feeding

Sturrock, H., Hsiang, M., Cohen, J.,

& Gosling, R. -

atic malaria infections: active surveillance

in control and elimination. PloS Medicine,

10, e1001467.

malarial serine protease SUB1 plays an es-

sential role in parasite liver stage develop-

ment. Plos Pathogens, 9, e1003811.

Takala-Harrison, S., Clark, T., Jacob,

A., Fukuda, M., Nosten, F., Noedl, H.,

Tyner, S., Saunders, D., Socheat, D., Ari-

ey, F., Phyo, A., Starzengruber, P., Fueh-

Flegg, J., Arze, C., Cerqueira, G., Silva,

J., Ricklefs, S., Porcella, S., Stephens,

Plowe, C.

with delayed clearance of Plasmodium

falciparum following artemisinin treatment

-

Takala-Harrison, S., Jacob, C., Arze, C.,

Cummings, M., Silva, J., Dondorp, A.,

Fukuda, M., Hien, T., Mayxay, M., No-

Tyner, S., Saunders, D., Ariey, F., Mer-

-

D., White, N., Ringwald, P. & Plowe, C.

-

modium falciparum artemisinin resistance

Infectious Diseases, pii: jiu491.

Takem, E., Affara, M., Amambua-Ngwa,

Clifford, C., Taal, M., Sowe, M., Suso,

P., Mendy, A., Mbaye, A., Drakeley, C. &

D’alessandro, U.

Malaria Transmission with School Surveys:

Takem EN, Affara M, Amambua-Ngwa

-

tecting Foci of Malaria Transmission with

-

journal.pone.0067108.

Juma, E., Logedi, J., Nyandigisi, A.,

Mulenga, M., Mbacham, W., Roper, C.,

Guerin, P., Dalessandro, U. & Snow., R.

-

for enhanced wide coverage malaria drug

resistance surveillance and response sys-

888–896.

Tanomsing, N., Imwong, M., Sutherland,

C., Dolecek, C., Hien, T., Nosten, F., Day,

N., White, N. & Snounou, G. -

genotyping of Plasmodium ovale curtisi

and Plasmodium ovale wallikeri. Journal of

Clinical Microbiology, 51, 4213-6.

-

committee. Malaria Journal, 12, 362.

-

Mathanga, D., Mårtensson, A., Ngasala,

A., Moormann, A., Vulule, J., Doumbo,

& Juliano, J.

Plasmodium falciparum artemisinin resis-

molecular epidemiologic study. The Journal

of Infectious Diseases: doi: 10.1093/infdis/

jiu467.

Temu, E., Coleman, M., Abilio, A. &

of Malaria in Zambezia, Mozambique: The

Protective Effect of IRS versus Increased

Risks Due to Pig-Keeping and House Con-

G., Drought, L., Failly, M., Martin, C.,

of antibodies to newly described Plasmodi-

um falciparum merozoite antigens supports

MSPDBL2 as a predicted target of naturally

acquired immunity. Infection and Immunity,

-

ment of a Transgenic Plasmodium berghei

cGMP-Dependent Protein Kinase, a Novel

e96923.

Theisen, M., Roeffen, W., Singh, S.,

Andersen, G., Amoah, L., Van De Vegte-

-

egiel, M., Christiansen, M. & Sauerwein,

R.

candidate targeting both transmission and

asexual parasite life-cycle stages. Vaccine,

-

maprasad, A., Nwakanma, D., Fischer,

Journal of Proteome Research, 12, 1211-

1222.

-

schmidt, I., Ye, Y., Mann, A., Ren, R., Wil-

& Goodman, C. -

-

let and Household Surveys before and after

South-west burkina faso: comparison of

active and passive case detection methods.

-

-

ogbeto, M. -

age and effective use rate of long-lasting

insecticidal nets after nation-wide scale up

of their distribution in Benin. Parasites and

Vectors. 2013; 6: 265.

Souza, J., Liu, F., Riley, E. & Rabinovich,

G.





R., Goodman, C., Mann, A., Ren, R., Wil-

-

S., Nguah, S., Seydou, M., Taylor, M.,

Rueda, S., Wamukoya, M., Arnold, F. &

availability, price, and market share of qual-

ity-assured artemisinin-based combination

therapies in seven countries: a before-and-

after analysis of outlet survey data. Lancet,

380, 1916-26.

Tougher, S., Ye, Y., Goodman, C., Arnold,

-

thors’ reply. Lancet, 381, 1095-6.

-

-

severe malaria in a Malian population. Plos

-

& Molez, J.

Policies and Child Mortality in Senegal:

Reaching Millennium Development Goal 4.


672-679.

Tremp, A., Carter, V., Saeed, S. & Des-

sens, J. -

modium zoites is uncoupled from tensile

strength. Molecular Microbiology, 89, 552-

64.

population in KwaZulu-Natal negates the

need for policies to prevent malaria in preg-

103, 172-5.

Drakeley, C.

in Plasmodium falciparum Transmission:

Tusting, L., Thwing, J., Sinclair, D.,

-

tomley, C. & Lindsay, S.

larval source management for controlling

malaria. Cochrane Database Syst Rev, 8,

CD008923.

-

intervention against malaria: a systematic

review and meta-analysis. Lancet, 382,

963-72.

treatment and insecticide-treated nets for

the control of malaria during pregnancy in

analysis of national survey data, 2009-11.


42.

-

-

& Sutherland, C.

Plasmodium falciparum isolates from UK

travellers: in vitro drug sensitivity, clonality

and drug resistance markers. Malaria Jour-

nal, 12, 320.

Venkatesan, M., Gadalla, N., Stepniews-

Moriera, C., Price, R., Mårtensson, A.,

Rosenthal, P., Dorsey, G., Sutherland,

-

-

berg, G., Grivoyannis, A., Hamour, S.,

-

ras, P., Malmberg, M., Mwai, L., Ngasala,

Sibley, C. -

modium falciparum Chloroquine Resistance

Transporter and Multidrug Resistance 1


pii: 14-0031.

Villegas-Mendez, A., De Souza, J.,

Lavelle, S., Gwyer Findlay, E., Shaw, T.,

-

ceptor Signalling Restricts the Formation of

Pathogenic, Terminally Differentiated Th1

Cells during Malaria Infection by Repress-

ing IL-12 Dependent Signals. Plos Patho-

gens, 9, e1003293.

Villegas-Mendez, A., Greig, R., Shaw, T.,

De Souza, J., Gwyer Findlay, E., Stum-

?-Producing CD4+ T Cells Promote Ex-

perimental Cerebral Malaria by Modulating

Villegas-Mendez, A., Gwyer Findlay, E.,

De Souza, J., Grady, L., Saris, C., Lane,

to the Liver during Malaria Infection by

Repressing Chemokine-Independent Path-

Von Seidlein, L., Auburn, S., Espino,

A., Vestergaard, L., Green, J., Domingo,

G., Yeung, S. & Price, R.

of key knowledge gaps in glucose-6-phos-

with regard to the safe clinical deployment

of 8-aminoquinoline treatment regimens: a

workshop report. Malaria Journal, 12, 112.

Ranson, H., Lindsay, S., Lengeler, C.,

Hamon, N., Mclean, T. & Hemingway, J.

and adoption of new vector control tools.

-

Ghani, A. -

dent immunity to placental malaria. Nature

Communications, 4:1609.

-

dazzi, I., Cunnington, A., Deininger, S.,

Takem, E., Ebonyi, A., Weis, S., Walton,

R., Rowland-Jones, S., Sirugo, G., Wil-

liams, S. & Conway, D.

levels are associated with severe malaria

in Gambian children. Plos Pathogens, 8,

e1002579.

J., Tivura, M., Delmini, R., Amenga-

Agyei, S.

health centres of rural Ghana. Malaria Jour-

nal, 13, 261.

Diawara, S., Abathina, A., Haiballa, A.,

-

tion of malaria in pregnancy with intermit-

tent preventive treatment and insecticide

treated nets in mali: a quantitative health

8, e67520.

West, P., Protopopoff, N., Rowland, M.,

Cumming, E., Rand, A., Drakeley, C.,

Malaria risk factors in north west Tanzania:

the effect of spraying, nets and wealth. Plos

& Ghani, A. -

against Plasmodium falciparum Infection.

A. -

sponse to Plasmodium falciparum infection

White, M., Nielsen, C., Mcgregor, R.,

Riley, E. & Goodier, M.

subsets during recall responses to vaccine

antigens. Immunology, 142, 140-150.

Whitty, C., Chiodini, P. & Lalloo, D.

-

ported malaria in non-endemic countries.

British Medical Journal (Clinical research

Car, J. & Schellenberg, J. -

gies for delivering insecticide-treated nets

at scale for malaria control: a systematic

-

zation, 90, 672-684E.

-

-

gueni, I., Amuasi, J., Ren, R., Wamukoya,

M., Rueda, S., Taylor, M., Seydou, M.,

-

sage: exploring the effect of communication

and training interventions on private for-

related to a multi-country anti-malarial sub-

sidy intervention. Malaria Journal, 13, 46.

C. & Mbacham, W. -

tiveness analysis of provider interventions

to improve health worker practice in provid-

ing treatment for uncomplicated malaria in

Cameroon: a study protocol for a random-

ized controlled trial. Trials, 13, 4.

Withers-Martinez, C., Suarez, C., Fulle,

-

and function of a pan-malaria drug target.

International Journal for Parasitology, 42,

597-612.

I., Mzilahowa, T., Irving, H., Ndula, M.,

Hemingway, J. -

throid resistance on operational malaria

control in Malawi. Proceedings of the Na-

Yindom, L., Forbes, R., Aka, P., Janha,

& Walther, M. -

globulin-like receptors and malaria caused

by Plasmodium falciparum in The Gambia.

J., Malishee, A., Stevenson, J., Sulisty-

awati, Collins, F. & Madey, G.

Based Geo-Tagged Malaria-Related Survey

Azindow, I., Amenga-Etego, S., Tchum,

Agyei, S.

on malaria incidence in infants and young

children in Ghana: a randomized trial.





R., Goodman, C., Mann, A., Ren, R., Wil-

-

S., Nguah, S., Seydou, M., Taylor, M.,

Rueda, S., Wamukoya, M., Arnold, F. &

availability, price, and market share of qual-

ity-assured artemisinin-based combination

therapies in seven countries: a before-and-

after analysis of outlet survey data. Lancet,

380, 1916-26.

Tougher, S., Ye, Y., Goodman, C., Arnold,

-

thors’ reply. Lancet, 381, 1095-6.

-

-

severe malaria in a Malian population. Plos

-

& Molez, J.

Policies and Child Mortality in Senegal:

Reaching Millennium Development Goal 4.


672-679.

Tremp, A., Carter, V., Saeed, S. & Des-

sens, J. -

modium zoites is uncoupled from tensile

strength. Molecular Microbiology, 89, 552-

64.

population in KwaZulu-Natal negates the

need for policies to prevent malaria in preg-

103, 172-5.

Drakeley, C.

in Plasmodium falciparum Transmission:

Tusting, L., Thwing, J., Sinclair, D.,

-

tomley, C. & Lindsay, S.

larval source management for controlling

malaria. Cochrane Database Syst Rev, 8,

CD008923.

-

intervention against malaria: a systematic

review and meta-analysis. Lancet, 382,

963-72.

treatment and insecticide-treated nets for

the control of malaria during pregnancy in

analysis of national survey data, 2009-11.


42.

-

-

& Sutherland, C.

Plasmodium falciparum isolates from UK

travellers: in vitro drug sensitivity, clonality

and drug resistance markers. Malaria Jour-

nal, 12, 320.

Venkatesan, M., Gadalla, N., Stepniews-

Moriera, C., Price, R., Mårtensson, A.,

Rosenthal, P., Dorsey, G., Sutherland,

-

-

berg, G., Grivoyannis, A., Hamour, S.,

-

ras, P., Malmberg, M., Mwai, L., Ngasala,

Sibley, C. -

modium falciparum Chloroquine Resistance

Transporter and Multidrug Resistance 1


pii: 14-0031.

Villegas-Mendez, A., De Souza, J.,

Lavelle, S., Gwyer Findlay, E., Shaw, T.,

-

ceptor Signalling Restricts the Formation of

Pathogenic, Terminally Differentiated Th1

Cells during Malaria Infection by Repress-

ing IL-12 Dependent Signals. Plos Patho-

gens, 9, e1003293.

Villegas-Mendez, A., Greig, R., Shaw, T.,

De Souza, J., Gwyer Findlay, E., Stum-

?-Producing CD4+ T Cells Promote Ex-

perimental Cerebral Malaria by Modulating

Villegas-Mendez, A., Gwyer Findlay, E.,

De Souza, J., Grady, L., Saris, C., Lane,

to the Liver during Malaria Infection by

Repressing Chemokine-Independent Path-

Von Seidlein, L., Auburn, S., Espino,

A., Vestergaard, L., Green, J., Domingo,

G., Yeung, S. & Price, R.

of key knowledge gaps in glucose-6-phos-

with regard to the safe clinical deployment

of 8-aminoquinoline treatment regimens: a

workshop report. Malaria Journal, 12, 112.

Ranson, H., Lindsay, S., Lengeler, C.,

Hamon, N., Mclean, T. & Hemingway, J.

and adoption of new vector control tools.

-

Ghani, A. -

dent immunity to placental malaria. Nature

Communications, 4:1609.

-

dazzi, I., Cunnington, A., Deininger, S.,

Takem, E., Ebonyi, A., Weis, S., Walton,

R., Rowland-Jones, S., Sirugo, G., Wil-

liams, S. & Conway, D.

levels are associated with severe malaria

in Gambian children. Plos Pathogens, 8,

e1002579.

J., Tivura, M., Delmini, R., Amenga-

Agyei, S.

health centres of rural Ghana. Malaria Jour-

nal, 13, 261.

Diawara, S., Abathina, A., Haiballa, A.,

-

tion of malaria in pregnancy with intermit-

tent preventive treatment and insecticide

treated nets in mali: a quantitative health

8, e67520.

West, P., Protopopoff, N., Rowland, M.,

Cumming, E., Rand, A., Drakeley, C.,

Malaria risk factors in north west Tanzania:

the effect of spraying, nets and wealth. Plos

& Ghani, A. -

against Plasmodium falciparum Infection.

A. -

sponse to Plasmodium falciparum infection

White, M., Nielsen, C., Mcgregor, R.,

Riley, E. & Goodier, M.

subsets during recall responses to vaccine

antigens. Immunology, 142, 140-150.

Whitty, C., Chiodini, P. & Lalloo, D.

-

ported malaria in non-endemic countries.

British Medical Journal (Clinical research

Car, J. & Schellenberg, J. -

gies for delivering insecticide-treated nets

at scale for malaria control: a systematic

-

zation, 90, 672-684E.

-

-

gueni, I., Amuasi, J., Ren, R., Wamukoya,

M., Rueda, S., Taylor, M., Seydou, M.,

-

sage: exploring the effect of communication

and training interventions on private for-

related to a multi-country anti-malarial sub-

sidy intervention. Malaria Journal, 13, 46.

C. & Mbacham, W. -

tiveness analysis of provider interventions

to improve health worker practice in provid-

ing treatment for uncomplicated malaria in

Cameroon: a study protocol for a random-

ized controlled trial. Trials, 13, 4.

Withers-Martinez, C., Suarez, C., Fulle,

-

and function of a pan-malaria drug target.

International Journal for Parasitology, 42,

597-612.

I., Mzilahowa, T., Irving, H., Ndula, M.,

Hemingway, J. -

throid resistance on operational malaria

control in Malawi. Proceedings of the Na-

Yindom, L., Forbes, R., Aka, P., Janha,

& Walther, M. -

globulin-like receptors and malaria caused

by Plasmodium falciparum in The Gambia.

J., Malishee, A., Stevenson, J., Sulisty-

awati, Collins, F. & Madey, G.

Based Geo-Tagged Malaria-Related Survey

Azindow, I., Amenga-Etego, S., Tchum,

Agyei, S.

on malaria incidence in infants and young

children in Ghana: a randomized trial.

Members 133


132 Members


Members

Central Services

Anne Mills:

Health Economics and Policy

Diseases

Dawn Britten:

Paul Lansdell:

Sue Passarelli:

Ranjan Ramasamy: Distance Learning

Module Reviewer

Claire Rogers: Head of Teaching and

Julie Tucker:

Emma Victory:

Cheryl Whitehorn:

John Williams: Clinical Scientist

Department of Clinical Research

Robin Bailey: Professor of Tropical

Medicine, Professor Consultant Physician

in Infectious Diseases and Tropical

Medicine, Hospital for Tropical Diseases

Ron Behrens: Senior Lecturer & Research

Degree co-ordinator

Michael Brown: Senior lecturer in

infectious diseases and tropical medicine

Bianca DSouza: Manager, ACT

Consortium

Peter Chiodini: Honorary Professor

Alison Elliott: Professor of Tropical

Medicine

Chris Drakeley

Malaria Centre Director Professor of Infection and Immunity

Steering Committee

David Baker: Reader in Parasite Molecular

Biology

Amit Bhasin: Manager, Malaria Capacity

Development Consortium

Clare Chandler: Lecturer in Social Science

Daniel Chandramohan: Professor of

Public Health

Brian Greenwood: Professor of Clinical

Tropical Medicine

Immo Kleinschmidt: Reader in

Epidemiology

Paul Milligan: Reader in Epidemiology and

Medical Statistics

Eleanor Riley: Professor of Immunology

David Schellenberg: Professor of Malaria

& International Health, ACT Consortium

Director, MCDC Deputy Director

Mark Rowland: Professor of Medical

Entomology and Malaria Control

Colin Sutherland: Head of Department

of Immunology and Infection, Reader in

Parasitology

Peter Godfrey-Faussett: Professor of

International Health (Currently seconded to

UNAIDS)

Heidi Hopkins: Consultant SCALE

Coordinator, ACT Consortium

Benjamin Judkewitz: Sir Henry Wellcome

Postdoctoral Fellow

Harparkash Kaur: Lecturer of

Pharmacology

David Mabey: Professor of Communicable

Diseases

Naiela Malik:

Research and Control Technician

Alexandra Miller: Programme Manager

Behzad Nadjm: Lecturer

Paul Newton: Honorary Senior Lecturer

Seth Owusu-Agyei: Research Fellow

Sarah Staedke: Senior Lecturer

Rebecca Tremain: PA to ACT Consortium

Director

Catherine Goodman

Malaria Centre Deputy Director Senior Lecturer in Health Economics and Policy

Dalia Iskander

Malaria Centre Coordinator

Karen Williams


Philippe Verstraete: Assistant Manager,

ACT Consortium

Christopher Whitty: Professor of public &

International Health

Department of Disease Control

Patricia Aiyenuro: Research Assistant

Helen Allwood: Assistant Manager,

Malaria Capacity Development Consortium

David Bradley: Professor

Simon Brooker: Professor of

Epidemiology

Jane Bruce: Lecturer

Mary Cameron: Senior Lecturer

Ilona Carneiro: Lecturer, Distance

Learning Tutor Public Health

Matthew Chico: Lecturer of Maternal,

Newborn and Child Health

Badara Cisse: Lecturer in Epidemiology

Manuela Claite: Overseas Project

Coordinator

Sian Clarke: Senior Lecturer in Malaria

Research and Control

Frank Cox:

Jonathan Cox: Senior Lecturer

Diadier Diallo: Lecturer

Caterina Fanello: Honorary Lecturer

Ulrike Fillinger: Research Fellow Medical

Entomology & Malaria Control

Caroline Jones: Senior Lecturer

Mojca Kristan: Research Fellow

Matt Kirby: Lecturer of Medical

Entomology

Sham Lal: Research Fellow

Toby Leslie: Lecturer, ACT Consortium

Steve Lindsay: Professor of Public Health

Entomology

Jo Lines: Reader in Malaria Control &

James Logan: Senior Lecturer in Medical

arctec

Lena Lorenz: Research Fellow in Medical

Entomology

Caroline Lynch: Lecturer Programme

Design and Evaluation

Tanya Marchant: Senior Lecturer

Debora Miranda: Technical

Hazel Mccullough: Professional

Development and Educational

Advisor,Malaria Capacity Development

Consortium

Sarah Moore: Lecturer in Medical

Entomology Corine Ngufor: Research

Assistant in Medical Entomology

Raphael N’Guessan: Research Fellow in

Medical Entomology

Terri O’Halloran: Overseas Project

Administrator

Richard Oxborough: Research Fellow

Lucy Paintain: Lecturer

Rachel Pullan: Lecturer

Hugh Reyburn: Senior Lecturer in Clinical

Epidemiology

Ailie Robinson: Research Assistant

Joanna Schellenberg: Head of

Deapartment of Department of Disease

Control; Reader in Epidemiology &


Wolf-Peter Schmidt: Lecturer in

Epidemiology

Karen Slater:

Nina Stanczyk: Research Fellow

Jennifer Stevenson: Research Fellow

Harry Tagbor: Clinical Lecturer, MiP Trial

Coordinator

Lien Tran: Project Administrator, Malaria

Capacity Development Consortium

Jayne Webster: Senior Lecturer

Khalid Beshir: Research Fellow

Teun Bousema: Senior Lecturer

Michael Bretscher:

Fellow

Hollie Burrell-Saward: Research Assistant

Rebekah Burrow:

Patrick Corran: Honorary Senior Lecturer

Simon Croft: Professor of Parasitology

Aubrey Cunnington:

Research Fellow

Rebecca Dabbs:

Brian deSouza: Honorary Senior Lecturer,

Module Organizer for Distance learning

Hazel Dockrell: Professor of Immunology

Elizabeth Downe: Project Administrator

Kimberley Fornace: Research Fellow

Matt Gibbins: Research Assistant

Bronner Goncalves: Research Fellow

Julius Hafalla: Senior Lecturer in

Immunology, Royal Society University

Research Fellow

Tom Hall: Research Assistant

Helena Helmby: Senior Lecturer

Lou Herman:

Mary Oguike: Research Fellow

Carolyn Stanley: Laboratory Manager

Geoff Targett: Emeritus Professor of

Immunology of Parasitic Diseases

Don Van Schalkwyk: Research Fellow

Department of Pathogen Molecular

Biology

Samuel Assefa: Research Fellow in

Mike Blackman: Professor

Paul Bowyer: Research Fellow

David Conway: Professor of Biology

Johannes Dessens: Senior Lecturer in

Parasite Cell Biology

Craig Duffy: Research Fellow

Christian Flueck: Research Fellow

John Kelly: Professor of Molecular

Biology, Head of Department of Pathogen

Molecular Biology

Michael Miles: Professor of Medical

Protozoology

Debbie Nolder:

in Molecular Diagnostics

Mark Preston: Research Fellow

Cally Roper: Senior Lecturer in Malaria

Lindsay Stewart: Laboratory Technician

Kevin Tetteh: Lecturer

Eloise Thompson:

Annie Tremp: Research Assistant

David Warhurst: Emeritus Professor of

Protozoan Chemotherapy

Members 133


132 Members


Members

Central Services

Anne Mills:

Health Economics and Policy

Diseases

Dawn Britten:

Paul Lansdell:

Sue Passarelli:

Ranjan Ramasamy: Distance Learning

Module Reviewer

Claire Rogers: Head of Teaching and

Julie Tucker:

Emma Victory:

Cheryl Whitehorn:

John Williams: Clinical Scientist

Department of Clinical Research

Robin Bailey: Professor of Tropical

Medicine, Professor Consultant Physician

in Infectious Diseases and Tropical

Medicine, Hospital for Tropical Diseases

Ron Behrens: Senior Lecturer & Research

Degree co-ordinator

Michael Brown: Senior lecturer in

infectious diseases and tropical medicine

Bianca DSouza: Manager, ACT

Consortium

Peter Chiodini: Honorary Professor

Alison Elliott: Professor of Tropical

Medicine

Chris Drakeley

Malaria Centre Director Professor of Infection and Immunity

Steering Committee

David Baker: Reader in Parasite Molecular

Biology

Amit Bhasin: Manager, Malaria Capacity

Development Consortium

Clare Chandler: Lecturer in Social Science

Daniel Chandramohan: Professor of

Public Health

Brian Greenwood: Professor of Clinical

Tropical Medicine

Immo Kleinschmidt: Reader in

Epidemiology

Paul Milligan: Reader in Epidemiology and

Medical Statistics

Eleanor Riley: Professor of Immunology

David Schellenberg: Professor of Malaria

& International Health, ACT Consortium

Director, MCDC Deputy Director

Mark Rowland: Professor of Medical

Entomology and Malaria Control

Colin Sutherland: Head of Department

of Immunology and Infection, Reader in

Parasitology

Peter Godfrey-Faussett: Professor of

International Health (Currently seconded to

UNAIDS)

Heidi Hopkins: Consultant SCALE

Coordinator, ACT Consortium

Benjamin Judkewitz: Sir Henry Wellcome

Postdoctoral Fellow

Harparkash Kaur: Lecturer of

Pharmacology

David Mabey: Professor of Communicable

Diseases

Naiela Malik:

Research and Control Technician

Alexandra Miller: Programme Manager

Behzad Nadjm: Lecturer

Paul Newton: Honorary Senior Lecturer

Seth Owusu-Agyei: Research Fellow

Sarah Staedke: Senior Lecturer

Rebecca Tremain: PA to ACT Consortium

Director

Catherine Goodman

Malaria Centre Deputy Director Senior Lecturer in Health Economics and Policy

Dalia Iskander


Karen Williams


Philippe Verstraete: Assistant Manager,

ACT Consortium

Christopher Whitty: Professor of public &


Department of Disease Control

Patricia Aiyenuro: Research Assistant

Helen Allwood: Assistant Manager,

Malaria Capacity Development Consortium

David Bradley: Professor

Simon Brooker: Professor of

Epidemiology

Jane Bruce: Lecturer

Mary Cameron: Senior Lecturer

Ilona Carneiro: Lecturer, Distance

Learning Tutor Public Health

Matthew Chico: Lecturer of Maternal,

Newborn and Child Health

Badara Cisse: Lecturer in Epidemiology

Manuela Claite: Overseas Project

Coordinator

Sian Clarke: Senior Lecturer in Malaria

Research and Control

Frank Cox:

Jonathan Cox: Senior Lecturer

Diadier Diallo: Lecturer

Caterina Fanello: Honorary Lecturer

Ulrike Fillinger: Research Fellow Medical

Entomology & Malaria Control

Caroline Jones: Senior Lecturer

Mojca Kristan: Research Fellow

Matt Kirby: Lecturer of Medical

Entomology

Sham Lal: Research Fellow

Toby Leslie: Lecturer, ACT Consortium

Steve Lindsay: Professor of Public Health

Entomology

Jo Lines: Reader in Malaria Control &

James Logan: Senior Lecturer in Medical

arctec

Lena Lorenz: Research Fellow in Medical

Entomology

Caroline Lynch: Lecturer Programme

Design and Evaluation

Tanya Marchant: Senior Lecturer

Debora Miranda: Technical

Hazel Mccullough: Professional

Development and Educational

Advisor,Malaria Capacity Development

Consortium

Sarah Moore: Lecturer in Medical

Entomology Corine Ngufor: Research

Assistant in Medical Entomology

Raphael N’Guessan: Research Fellow in

Medical Entomology

Terri O’Halloran: Overseas Project

Administrator

Richard Oxborough: Research Fellow

Lucy Paintain: Lecturer

Rachel Pullan: Lecturer

Hugh Reyburn: Senior Lecturer in Clinical

Epidemiology

Ailie Robinson: Research Assistant

Joanna Schellenberg: Head of

Deapartment of Department of Disease

Control; Reader in Epidemiology &


Wolf-Peter Schmidt: Lecturer in

Epidemiology

Karen Slater:

Nina Stanczyk: Research Fellow

Jennifer Stevenson: Research Fellow

Harry Tagbor: Clinical Lecturer, MiP Trial

Coordinator

Lien Tran: Project Administrator, Malaria

Capacity Development Consortium

Jayne Webster: Senior Lecturer

Khalid Beshir: Research Fellow

Teun Bousema: Senior Lecturer

Michael Bretscher:

Fellow

Hollie Burrell-Saward: Research Assistant

Rebekah Burrow:

Patrick Corran: Honorary Senior Lecturer

Simon Croft: Professor of Parasitology

Aubrey Cunnington:

Research Fellow

Rebecca Dabbs:

Brian deSouza: Honorary Senior Lecturer,

Module Organizer for Distance learning

Hazel Dockrell: Professor of Immunology

Elizabeth Downe: Project Administrator

Kimberley Fornace: Research Fellow

Matt Gibbins: Research Assistant

Bronner Goncalves: Research Fellow

Julius Hafalla: Senior Lecturer in

Immunology, Royal Society University

Research Fellow

Tom Hall: Research Assistant

Helena Helmby: Senior Lecturer

Lou Herman:

Mary Oguike: Research Fellow

Carolyn Stanley: Laboratory Manager

Geoff Targett: Emeritus Professor of

Immunology of Parasitic Diseases

Don Van Schalkwyk: Research Fellow

Department of Pathogen Molecular

Biology

Samuel Assefa: Research Fellow in

Mike Blackman: Professor

Paul Bowyer: Research Fellow

David Conway: Professor of Biology

Johannes Dessens: Senior Lecturer in

Parasite Cell Biology

Craig Duffy: Research Fellow

Christian Flueck: Research Fellow

John Kelly: Professor of Molecular

Biology, Head of Department of Pathogen

Molecular Biology

Michael Miles: Professor of Medical

Protozoology

Debbie Nolder:

in Molecular Diagnostics

Mark Preston: Research Fellow

Cally Roper: Senior Lecturer in Malaria

Lindsay Stewart: Laboratory Technician

Kevin Tetteh: Lecturer

Eloise Thompson:

Annie Tremp: Research Assistant

David Warhurst: Emeritus Professor of

Protozoan Chemotherapy

Members 135


134 Members


Health

Department of Infectious Disease

Epidemiology

Neal Alexander: Reader in Medical

Statistics and Epidemiology

John Bradley: Research Fellow

Matthew Cairns: Lecturer in Epidemiology

Taane Clark:

Epidemiology and Statistics

Simon Cousens: Professor of

Epidemiology and Medical Statistics

Bonnie Cundill: Lecturer in Medical

Statistics & Epidemiology

John Edmunds: Dean of Faculty;

Professor

Clare Flach: Research Fellow

Paul Fine: Professor of Communicable

Disease Epidemiology

Neil French: Reader in Infectious Disease

Epidemiology

David Heymann: Chair of the Health

Protection Agency

DiTanna GianLuca: Lecturer in Medical


Baptiste Leurent: Lecturer in Medical


Andrea Mann: Distance Learning Tutor,

MSc Epidemiology (Distance Learning)

Joshua Mendelsohn: Research Fellow

Maureen OLeary: Research Fellow

Nuno Sepulveda: Research Fellow in

Susana Scott : Lecturer

Peter Smith: Professor of Tropical

Epidemiology

Paul Snell: Data Manager, ACT

Consortium

Emily Webb: Senior Lecturer in


Intervention Research

Paula Dominguez-Salas: Research Fellow

of Public Health Nutrition

Seyi Soremekun: Lecturer of

Epidemiology

Hans Verhoef: Senior Lecturer

Department of Population Health

Richard Mutemwa: Research Fellow

Jani Puradiredja: Research Fellow

Jim Todd: Reader Applied Biostatistics

Department of Medical Statistics

Diana Elbourne: Professor of Healthcare

Evaluation

Richard Smith: Dean of Faculty;

Professor of Health System Economics

Development

Uli Beisel: Postdoctoral Research Fellow

Richard Coker: Professor of Public Health

Eleanor Grieve: Research Fellow in Health

Economics

Senior Lecturer in Health

Economics

Philippe Guyant: Research Fellow Project

Manager

Kristian Hansen: Lecturer in Health

Economics

Kara Hanson: Reader in Health System

Economics

Natasha Howard:

Eleanor Hutchinson: Research Fellow

Frida Kasteng: Research Fellow in Health

Economics

Ann Kelly: Honorary Lecturer in

Anthropology

Marcus Keogh-Brown: Lecturer

Harriet Lawford: Research Fellow

Marco Liverani: Lecturer in Health Policy

Lindsay Mangham-Jefferies: Lecturer in

Health Economics

Benjamin Palafox: Research Fellow in

Pharmaceutical Policy & Economics

Edith Patouillard: Lecturer in Health

Economics and Systems Analysis

Catherine Pitt: Lecturer in Health

Economics

Andreia Santos: Lecturer

Annemarie terVeen: Distance Learning

Lecturer in Infectious & Tropical Diseases;

Sergio TorresRueda: Research Fellow

Sarah Tougher: Research Fellow in


Barbara Willey: Lecturer in Epidemiology

Shunmay Yeung: Senior Lecturer

Nayantara Wijayanandana: Research

Fellow Epidemiology

Department of Health Services Research

Andreia Santos: Lecturer in Health

Economics

Department of Non-communicable


Lorna Gibson: Lecturer

Dorothea Nitsch: Senior Lecturer (Clinical)

Research degree studentsI Ifeyinwa Aniebo

Harvey Aspeling-Jones

El Hadj Ba

Kristin Banek

Katia Bruxvoort

Vanessa Chen-Hussey

Ifeyinwa Chijioke-Nwauche

Bianca D’Souza

Mary Grace Dacuma

Deborah DiLiberto

Bismarck Dinko

Paul Divis

Laura Drought

Christina Due

Chi Eziefula

Kimberly Fornace

Matt Gibbins

Bronner Goncalves

Katherine Halliday

Luke Harman

Gisela Henriques

Lou Herman

Manuela Herrera-Varela

Lauren Hutchinson

Natasha Howard

Sophie Jones

Ronnie Kasirye

Sham Lal

Mirza Lalani

Marie Lamy

Inke Lubis

Jenny Luchavez

Zawadi Mageni

Oscar Mbare

Louisa Messenger

Lee Murray

Inbarani Naidoo

Corine Ngufor

Enesia Ngulube

Enesia Ngulube

Mike Okal

Richard Oxborough

Benjamin Palafox

Bhargavi Rao

Joanna Reynolds

Ailie Robinson

Maha Saeed

Gillian Stresman

Asia Sophia-Wolf

Ebako Takem

Katherine Theiss-Nyland

Eloise Thompson

Samuel Thorburn

Sarah Tougher

Patrick Tungu

Lucy Tusting

Philippa West

John Williams

Issaka Zongo

MCDC linked PhD stu-dents

Gifty Antwi

Jovin Kitau

Johnson Matowo

Jacklin Mosha

Joaniter Nankabirwa

Youssoupha Ndiaye

Juliet Ndibazza

Harold Ocholla

Joseph Osarfo

Alberta Amu Quartey

To mark the centenary of World War One, and inspired by LSHTM’s summer exhibition Improving Health in War Time, this year’s World Mosquito Day celebrations focused on Sir Ronald Ross’s contribution to the War Effort in his role as Consulting Physician in tropical diseases.

Members 135


134 Members


Health

Department of Infectious Disease

Epidemiology

Neal Alexander: Reader in Medical


John Bradley: Research Fellow

Matthew Cairns: Lecturer in Epidemiology

Taane Clark:

Epidemiology and Statistics

Simon Cousens: Professor of


Bonnie Cundill: Lecturer in Medical


John Edmunds: Dean of Faculty;

Professor

Clare Flach: Research Fellow

Paul Fine: Professor of Communicable


Neil French: Reader in Infectious Disease

Epidemiology

David Heymann: Chair of the Health

Protection Agency

DiTanna GianLuca: Lecturer in Medical


Baptiste Leurent: Lecturer in Medical


Andrea Mann: Distance Learning Tutor,

MSc Epidemiology (Distance Learning)

Joshua Mendelsohn: Research Fellow

Maureen OLeary: Research Fellow

Nuno Sepulveda: Research Fellow in

Susana Scott : Lecturer

Peter Smith: Professor of Tropical

Epidemiology

Paul Snell: Data Manager, ACT

Consortium

Emily Webb: Senior Lecturer in


Intervention Research

Paula Dominguez-Salas: Research Fellow

of Public Health Nutrition

Seyi Soremekun: Lecturer of

Epidemiology

Hans Verhoef: Senior Lecturer

Department of Population Health

Richard Mutemwa: Research Fellow

Jani Puradiredja: Research Fellow

Jim Todd: Reader Applied Biostatistics

Department of Medical Statistics

Diana Elbourne: Professor of Healthcare

Evaluation

Richard Smith: Dean of Faculty;

Professor of Health System Economics

Development

Uli Beisel: Postdoctoral Research Fellow

Richard Coker: Professor of Public Health

Eleanor Grieve: Research Fellow in Health

Economics

Senior Lecturer in Health

Economics

Philippe Guyant: Research Fellow Project

Manager

Kristian Hansen: Lecturer in Health

Economics

Kara Hanson: Reader in Health System

Economics

Natasha Howard:

Eleanor Hutchinson: Research Fellow

Frida Kasteng: Research Fellow in Health

Economics

Ann Kelly: Honorary Lecturer in

Anthropology

Marcus Keogh-Brown: Lecturer

Harriet Lawford: Research Fellow

Marco Liverani: Lecturer in Health Policy

Lindsay Mangham-Jefferies: Lecturer in

Health Economics

Benjamin Palafox: Research Fellow in


Edith Patouillard: Lecturer in Health

Economics and Systems Analysis

Catherine Pitt: Lecturer in Health

Economics

Andreia Santos: Lecturer

Annemarie terVeen: Distance Learning

Lecturer in Infectious & Tropical Diseases;

Sergio TorresRueda: Research Fellow

Sarah Tougher: Research Fellow in


Barbara Willey: Lecturer in Epidemiology

Shunmay Yeung: Senior Lecturer

Nayantara Wijayanandana: Research

Fellow Epidemiology

Department of Health Services Research

Andreia Santos: Lecturer in Health

Economics

Department of Non-communicable


Lorna Gibson: Lecturer

Dorothea Nitsch: Senior Lecturer (Clinical)

Research degree studentsI Ifeyinwa Aniebo

Harvey Aspeling-Jones

El Hadj Ba

Kristin Banek

Katia Bruxvoort

Vanessa Chen-Hussey

Ifeyinwa Chijioke-Nwauche

Bianca D’Souza

Mary Grace Dacuma

Deborah DiLiberto

Bismarck Dinko

Paul Divis

Laura Drought

Christina Due

Chi Eziefula

Kimberly Fornace

Matt Gibbins

Bronner Goncalves

Katherine Halliday

Luke Harman

Gisela Henriques

Lou Herman

Manuela Herrera-Varela

Lauren Hutchinson

Natasha Howard

Sophie Jones

Ronnie Kasirye

Sham Lal

Mirza Lalani

Marie Lamy

Inke Lubis

Jenny Luchavez

Zawadi Mageni

Oscar Mbare

Louisa Messenger

Lee Murray

Inbarani Naidoo

Corine Ngufor

Enesia Ngulube

Enesia Ngulube

Mike Okal

Richard Oxborough

Benjamin Palafox

Bhargavi Rao

Joanna Reynolds

Ailie Robinson

Maha Saeed

Gillian Stresman

Asia Sophia-Wolf

Ebako Takem

Katherine Theiss-Nyland

Eloise Thompson

Samuel Thorburn

Sarah Tougher

Patrick Tungu

Lucy Tusting

Philippa West

John Williams

Issaka Zongo

MCDC linked PhD stu-dents

Gifty Antwi

Jovin Kitau

Johnson Matowo

Jacklin Mosha

Joaniter Nankabirwa

Youssoupha Ndiaye

Juliet Ndibazza

Harold Ocholla

Joseph Osarfo

Alberta Amu Quartey

To mark the centenary of World War One, and inspired by LSHTM’s summer exhibition Improving Health in War Time, this year’s World Mosquito Day celebrations focused on Sir Ronald Ross’s contribution to the War Effort in his role as Consulting Physician in tropical diseases.

Documents

Malaria Centre Report 2012-14