Developing New Diagnostic Tests for Sleeping Sickness MAY2013

7/28/2019 Developing New Diagnostic Tests for Sleeping Sickness MAY2013

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Current status and future plans

Developing New Diagnostic Tests orHuman Arican Trypanosomiasis

foundation

for innovative new diagnostics


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FINDs purpose

FIND addresses the market ailures that result in the lack o appropriate diagnostic tools indisease-endemic countries. Our expertise is in the development o innovative, feld-adapteddiagnostics that have signifcant impact in low-resource settings. We demonstrate howimproved diagnostics save lives and resources, and we provide technical support or theirintroduction and implementation in national health systems. The process requires bringingtogether knowledge o the needs on the ground with technological know-how, and a sound

understanding o the intricacies o developing diagnostics.

Enrolment o participants in a clinical trial on a diagnostic test or sleeping sickness.


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Contents

Overview of FIND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2

The HAT & OND programme . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

Projects on diagnostics for HAT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

Problem and scope . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

Tests or screening . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

Tests or conrming cases. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

Miniature anion exchange centriugation technique (mAECT) . . . . . . . . . . . . . 7

Fluorescence microscopy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

LED FM on whole blood, and blood ater lysis and concentration . . . . . . . . 8

Molecular detection. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10

Tests or staging and conrmation o cure. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

Biological samples to support test development . . . . . . . . . . . . . . . . . . . . . . . . . . . 13

Funding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13

Agreements with partners . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13

Publications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14


4/202 Human Ar ican Trypanosomiasis

FIND was established in 2003 to bring diagnos-tic solutions to societies where treatable diseasesare rampant and where poverty and poor healthare closely intertwined. The diagnostics availablein disease-endemic countries are oten not welladapted or too costly or use in the eld. FINDaddresses these challenges by developing diagnostictests that are eld-adapted and aordable. During

the past 10 years, we have been developing diag-nostic approaches that have been proven in prin-ciple, transorming them into eective products oridentiying tuberculosis. Strong partnerships withacademia, public and private research institutes,

and industry have increased the scope o activitieswhich now includes diagnostics or human Aricantrypanosomiasis (HAT), malaria, HIV/AIDS, leish-maniasis and Chagas disease.

Since 2006, FIND has also been working to upgradehealthcare systems and laboratory standards, so thatthe new tools can be rolled out in low-resource

settings. The impact and eectiveness o theseimproved diagnostic tests is measured through acontinuous fow o inormation and eedback romthe eld.

Overview o FIND

CEO

BD SARMO CFO CSO CMO HRM SOO

C r o s s - c u t t i n g f u n c t i o n s

Leadership team members

Exec. Assist

STAFF:BD Business Development;SARMO Senior Advocacy & Resource Mobilization Officer;CFO Chief Financial Officer;CSO Chief Scientific Officer;CMO Chief Medical Officer;HR&AM Human Resources & Administration Manager; SOO Senior Operating OfficerOTHER: HAT Human African Trypanosomiasis; OND Other neglected diseases; AFS Acute febrile syndrome; SEA South-East Asia

Contracts & BD Advocacy

ResourceMobilizazion

Communications

Staff

Consultants

Administration

Finance

Legal Affairs

Logistics

IT

Field officesIndia & Uganda

Science &Technology

Opstream

Programmes

Acting TBHead

Clinical Trials

DownstreamProgrammes

Quality Mgmt &ISO Certification

Project Mgmt

Doc. Controlling

Grant Mgmt

RegulatoryAffairs

TB

HAT & OND

Malaria & AFS

Downstream Programmes

TB Diagnostics Implementation

Lab Systems Strengthening

TB Programme India & SEA

TB Programme Uganda

Figure 1: The FIND Organogram


5/203Overv iew o FIND

The organizations business model (gure 1) providesan environment or maximizing available expertiseacross diseases and technologies.

FINDs strategy is to ocus on developing diagnostictechnology platorms that can be applied to severaldiseases, thereby reducing product development costs,time and risk, while building on our experience in

acilitating ecient introduction o tests and trainingo health personnel. The diagnostic tools we work onare intended to improve patient care at an individuallevel, as well as disease control at a population level.The level o FINDs involvement in development oa technology is dictated by the stage the technologyis at on the value chain (gure 2), starting rom proo-o-concept to early implementation.

FINDs unding base includes, among others, theBill & Melinda Gates Foundation, UNITAID, theGlobal Fund to ght AIDS, tuberculosis and malaria,

the governments o the Netherlands, Germany andthe United Kingdom, WHO-TB Reach, USAID,and the UBS Optimus Foundation.

FeasibilityDevelopment Evaluation Demonstration Evidence for

scale-upand Scale-up

WHO

New diagnostic test prototype

developed and technical

specifications validated

New diagnostic test fully developed

(design lock) and manufacturing

process validated

Diagnostic accuracy and analytical

performance of new product validated

in clinical trials

Performance and operational characteristics

validated during uncontrolled routine use in

programmatic settings

Implementation in routine diagnostic services under quality

assurance followed by roll-out in high-endemic countries,

market surveillance and impact assessment

STAG/WHO

Endorsement into

global policy

Figure 2: FINDs basic diagnostics development value chain, which can be adapted depending on the disease



Human Arican trypanosomiasis (HAT) was the rstneglected tropical disease (NTD) to be included in

FINDs portolio in 2006. The programme was renamed

HAT & other neglected diseases (HAT & OND) aterthe addition o leishmaniasis in 2010 and Chagas

disease in 2012.

The HAT & OND programme

Status of various projects implemented under the HAT & OND programme

Human African Trypanosomiasis (HAT; sleeping sickness)

a) A test or screening populations that are at risk o inection

i. Further to the successul evaluation o the perormance o a prototype 1st generation rapid diagnostic test (RDT) using

native trypanosome antigens on more than 14,000 individuals in Angola, the Democratic Republic o the Congo (DRC)

and Central Arican Republic (CAR), the SD BIOLINE HAT test was launched in December 2012. Demonstration studies

to urther evaluate the perormance o the test and determine its cost eectiveness in various diagnostic algorithms

are ongoing.

ii. Development o a 2nd generation RDT using recombinant antigens, which could be eective or both Trypanosoma

brucei gambiense and T.b. rhodesiense HAT, is going on.

b) A test or confrming cases o HAT

i. The mini-anion exchange centriugation technique (mAECT) was improved and its production successully transerred

to the DRC.

ii. Evaluation o an LED fuorescence microscope has been completed in the DRC and demonstration studies are going on.iii. Evaluation o a molecular test based on loop-mediated isothermal amplication o DNA (LAMP) is going on in the DRC

and Uganda.

c) A test to determine i HAT patients have brain disease, and to monitor treatment

Development o an RDT or staging and monitoring treatment by measuring neopterin and/or CXCL13 in CSF

is in process.

Leishmaniasis

a) ELISA test or parasite antigens in urine

An ELISA assay or urinary antigens using polyclonal antibodies is being developed in collaboration with DNDi, Kalon

Biologicals (UK) and the Royal Tropical Institute (KIT, Netherlands). The test, to be used or case detection and monitoring

therapy, is perorming well.

b) LAMP test to detect parasite DNA

This test is being developed as part o expansion o the LAMP platorm, in collaboration with Eiken, KIT and the Institute

o Primate Research (IPR, Kenya). Prototype reagents are under evaluation.

Chagas Disease

LAMP test or congenital Chagas disease

Development o the test was initiated in January 2012, in collaboration with INGEBI-CONICET and a Colombian

multi-disciplinary team. Feasibility studies and optimization o sample preparation are going on.


7/205The HAT & ON D pro gramme

projects oN DIagNostIcsFor Hat

pblm nd

Human Arican trypanosomiasis (HAT) is a diseaseo poor rural communities caused by extracellular

protozoan parasites o the genus Trypanosoma. In earlyor Stage 1 inection when parasites are in the bloodand lymphatic system, treatment is relatively saeand cheap. During this phase, however, clinical signsare not suggestive o HAT, and diagnostic tests haveproblems o sensitivity and specicity. Many cases,thereore, remain undetected and with time, parasitesinvade the brain, resulting in late or Stage 2 disease.Treatments o Stage 2 HAT are either lengthy andexpensive, and dicult to administer, or cause poten-tially atal side eects. Currently, tests to determine

the stage o disease are non-specic and insensitive.

FIND and partners are developing and implement-ing tests or early and accurate diagnosis and stagingo HAT patients, in order to ensure sae treatment.Other tests or early detection o treatment ailurewill ensure proper re-treatment, reduced transmis-sion and accelerated control o the disease.

t nin

FIND and Standard Diagnostics (SD) have developed

a lateral fow rapid diagnostic test (RDT) to screen or

T.b. gambiense HAT that is cheap and easy to use. Thetests are packed individually and are stable at 40C or

up to 25 months; they are perormed on resh bloodobtained rom a nger prick, and no instrument or elec-

tricity is required. The RDT detects host antibodiesto inection in populations that are at risk, or in sus-

pect individuals. Positive cases are subjected to urther

conrmatory methods to identiy HAT patients.

The new rapid diagnostic test kit or HAT developed by FIND and Standard Diagnostics; the RDTs on the right show a negative (1 line)

and a positive (3 lines) result



The new RDT is an alternative to the card aggluti-nation test or trypanosomiasis (CATT), the primaryscreening tool used by control programmes in areaswhere T.b. gambiense HAT is endemic.

Current status1st generation test Field evaluation o the proto-type has been successully completed on more than

14,000 individuals at sites in Angola, Central AricanRepublic (CAR) and the Democratic Republic othe Congo (DRC). Job Aids and a manual or train-ing health workers on proper use o the new RDT(in English and French) have also been made.

The SD HAT BIOLINE test was launched at a work-shop hosted by the Ministry o Health o the Demo-cratic Republic o the Congo on 6th December 2012in Kinshasa. Demonstration studies to urther evalu-ate the perormance o the test and determine itscost-eectiveness in various diagnostic algorithmsare ongoing.

2nd generation test The 1st generation RDTis made using native antigens generated rompathogenic trypanosomes, and is not applicable orT.b. rhodesiense HAT. Eorts are thereore beingmade by FIND and SD to develop a 2nd generation

The study monitor discusses a point with the principal investigator

(right) during clinical evaluation of the new rapid diagnostic test for

sleeping sickness in a village in the Democratic Republic of the Congo.

The blood sample taken rom a nger prick is introduced into the

sample well o the rapid diagnostic test. The results o the test are

read ater only 15 minutes.

Children ollow activities during active screening o a community

in the Democratic Republic o the Congo, when clinical trials on

the new rapid test or HAT were being carried out.

A technician takes blood ater a nger prick during clinical

evaluation o the new rapid diagnostic test or sleeping sickness

in rural Democratic Republic o the Congo.



RDT using recombinant antigens. Such a test would beeasier and cheaper to manuacture, thus reducing the

cost o the nal product. Eight recombinant antigens(GM6, 4 ISGs and 3 VSGs) are being investigated.

Antigen detection test A test that detects parasiteantigens is a better indicator o inection than onethat detects host antibodies, and could also be useul

or monitoring treatment. The challenge has been inthe identication o target antigens, since the oneson the surace o the parasite are variable or mutable.Current eorts are ocused on using nanobodies, smallcamel antibodies that are particularly thermostableand that can penetrate the parasite surace coat anddetect invariable antigens. Work carried out in col-laboration with the Flanders Interuniversity Instituteor Biotechnology (VIB) at the University o Brusselshas identied a number o promising nanobodies.Their potential in development o a test is being

determined in collaboration with SD.

Future plans

Conductdemonstrationstudiesofthe 1st generation RDT

Rolloutthe1stgenerationRDTincollaboration with partners

Developa2ndgenerationRDTbasedonrecombinant antigens

Developa1stgenerationantigendetectiontest based on nanobodies

t nfmin

Demonstration o parasites in body fuids is the most

accurate way to conrm HAT, and is critical in orderto avoid the risk o exposing healthy suspects to poten-

tially dangerous therapy. For most T. b. rhodesiensepatients, parasitaemia is usually high enough or para-sites to be seen by direct examination o blood under

a light microscope. However, the number o parasites

in T.b. gambiense inections is oten below the limito detection o the most sensitive methods that are in

clinical use. In the cerebrospinal fuid (CSF), parasitesexist in very low numbers, and have to be concen-

trated beore they can be viewed. The most sensitivemethods or detecting trypanosomes in blood that

are in clinical use include the mini anion exchangecentriugation technique (mAECT) and the capillary

tube centriugation (CTC) method, while the modi-ed single centriugation (MSC) technique is used todetect trypanosomes in CSF. Although CTC is widely

used due to its simplicity and low cost, widespread useo mAECT has been constrained by the high costs

associated with it, and by the need or a cold chain.

Mini nin xhnniin hniq (maect)The mAECT is carried out in two stages, including

chromatography o samples, then concentration o theeluate by low speed centriugation and viewing under low

magnication microscopy. Similarly with MSC, CSF iscollected rom a lumbar puncture and centriuged beore

viewing. Both mAECT and MSC were, until 2006,manuactured at the Institute o Tropical Medicine(ITM) in Belgium and then shipped to endemic coun-

tries a process that was untenable due to the associ-ated high costs. A partnership between FIND, the ITM

and the Institut National de Recherche Biomdicale(INRB) in DRC not only improved components o

both mAECT and MSC, but by 2008 had successullytranserred their production to Kinshasa, DRC.

Current status

Production o mAECT and MSC is done at theINRB. The largest percentage o kits produced isused locally in the DRC, mainly in clinical trials.

Future plans

Explorecheaperandmorepracticalmethodsofseparating parasites



Fln miyFluorescence microscopy (FM) is known to increasethe sensitivity, speed and ease o demonstration otrypanosomes. In the quantitative buy coat (QBC)method, blood is collected in capillary tubes thatare pre-coated with acridine orange and examinedusing a microscope with a special objective lens.Implementation o the QBC method has, however,

been impossible or HAT due to the high cost othe equipment. FIND has been exploring cheaperoptions to improve detection o parasites using anLED fuorescence microscope.

LeD FM n hl bld, nd bld lyi nd nninThe Primo Star iLED fuorescence microscope wasdeveloped jointly by FIND and Carl Zeiss.

The microscope has high-grade optics, usesrefected rather than transmitted blue light or fuo-rescence applications, and permits easy switchingbetween fuorescent and bright light viewing. It canbe operated on battery power, does not need a darkroom, and uses an inexpensive bulb with a lie omore than 10,000 hours.

The Primo Star iLED was initially evaluated usingexperimental inections by a number o laboratoriesin Arica, including the National Livestock Resources

Research Institute (NALIRRI) and MakerereUniversity in Uganda, University o Kinshasa andINRB in DRC. Acridine orange, a common fuoro-chrome stain, was used or staining trypanosomes.The studies showed that the speed o reading andsensitivity are higher with this method, when com-pared with common bright eld microscopy using

Components o the miniature anion exchange centriugation technique (mAECT) or separation and demonstration o trypanosomes.

350l o resh blood or buy coat is ltered through a DEAE cellulose column, into a collector tube (A). Parasites are concentrated at

the bottom o the collector tube (B) by low-speed centriugation, and the tip examined or motile parasites under a microscope (C&D).

The dual purpose Primo Star iLED microscope developed by FIND and Carl Zeiss is easily switched to view samples by either bright or

fuorescent light. PanelAshows a thin smear made rom inected blood and stained with acridine orange. In panel B, the red blood cells

have been lysed beore preparation o the smear.

a B c D

a

B



Giemsa staining. The diagnostic capacity o themethod is signicantly enhanced when staining osamples is preceded by lysis o red blood cells usingammonium chloride or commercial lysis buer.

Current status

Clinical evaluation o the LED microscope usingthe red blood cell lysis and acridine orange stain-

ing methods has been completed at several sitesin DRC and Uganda. The trial in the DRC wasdone in collaboration with the national HATcontrol programme and the SwissTPH, while theone in Uganda was done in collaboration withMakerere University and Lwala hospital. Basedon the excellent results rom these studies, theMinistry o Health o DRC approved the use othese new methods or routine diagnosis o HAT on7th December 2012.

Future plans

Demonstration/earlyimplementationofLEDmicroscopy in diagnosis o HAT

Mll dinDetection o trypanosome DNA rom body fuids o

a HAT patient could be a signicant improvement

on parasitological examination. Loop-mediated iso-thermal amplication (LAMP) o DNA is a promisingmolecular technique that shows high sensitivity and

specicity.

The test amplies target DNA at a constant tempera-

ture, meaning that it can be carried out with minimalequipment. Furthermore, positive samples fuoresceunder LED light. The test can be perormed by stawith minimal experience in molecular biology.

Carl Zeiss has developed a plastic box that enables easy and sae transportation o the microscope during active screening programmes

(C&D). Panel E shows a technician operating an LED fuorescence microscope using solar energy in eastern Democratic Republic o the

Congo. (Photos C&D are courtesy o Carl Zeiss AG)

The LoopampTM LF-160 incubator (A) used to perorm the HAT LAMP reaction. Ater extraction o DNA, the LAMP reaction is kept at a

constant temperature o 65C or 40 minutes. The results are visualized under LED light (B). PC- Positive control, NC- Negative control.

(Photo on the right is courtesy o E. Matovu)

c D e

a B



In 2008, FIND signed a development agreement withEiken Chemical Company, Ltd. (Japan), the owner othe patent rights to LAMP, and completed develop-ment o a LAMP kit or HAT in 2011. The reagentsor LAMP are dried on the inside part o the capo the reaction tube, which can be stored at roomtemperature. When test samples are added, the tubesare heated at constant temperature in an incubator,

and the results read visually using LED light. The testcan be perormed on blood, either resh or dried onlter papers, or buy coat, or microscopy slides.

Current status

Clinical evaluation o the HAT LAMP kit is beingcarried out at multiple sites in the DRC and Uganda.Prospects o using the same test in drug screen-ing studies, and or monitoring treatment, are alsobeing explored.

Future plans

Demonstration/earlyimplementationstudies Cost-effectivenessstudiestoguidenovelstrategies or introduction o LAMP indiagnosis o HAT

A technician takes blood rom a nger prick during clinical evaluation o the new LAMP test or sleeping sickness in Bandundu province,

Democratic Republic o the Congo.



t in ndnfmin

Determining what stage o disease a HAT patientis in is crucial or deciding what treatment shouldbe given. In early or Stage 1 disease, the inectionis conned to the haemolymphatic system. In lateor Stage 2 disease, parasites have penetrated the cen-

tral nervous system (CNS) and, depending on theduration o the inection, the CNS would be at vari-ous stages o damage. To distinguish the two stages, alumbar puncture is perormed and the CSF examinedor presence o parasites, and the number o whitecells counted. These parameters, however, suer rominsucient sensitivity and, in the case o white cellcount, o specicity as well. Because o these short-comings, the invasive character o a lumbar punc-ture and toxicity o the drugs used to treat late stagedisease, improved markers or staging are needed.

Ater treatment, patients are ollowed up or 24 months

to conrm cure or detect relapses. Since relapsesare mainly o CNS origin, and parasites are otendicult to nd in blood, ollow-up largely relies onlumbar puncture and CSF examination.

Current status

FIND partners, led by scientists at the University

o Geneva, have identied and validated uniquemolecules in the CSF o HAT patients that havegreat potential in determining the stage o disease.The concentration o these molecules in the CSFalso alls quickly in patients whose treatment is suc-cessul. Based on these ndings, FIND, StandardDiagnostics, and other partners are exploring the ea-

sibility o using either neopterin or CXCL13, whichwere among the best markers or T.b. gambienseHAT, to develop a dual purpose rapid test or bothstaging and monitoring treatment.

Further preliminary studies at the Universityo Geneva have led to identication o blood bio-markers that could be used to conrm cure and detect

relapses. I certied, the use o these markers couldeliminate the need or lumbar punctures duringollow-up.

Future plans

CompletedevelopmentandevaluationofanRDT or staging and monitoring treatment

Furtherworktoidentifybloodbiomarkersformonitoring eectiveness o therapy

Blood samples collected on lter paper rom suspected cases

o HAT during active screening are held to dry using clips on a

specially designed stand to prevent them rom being blown away.

Dry samples are stored individually in plastic pouches containing

a desiccant, and sent to a LAMP centre or testing.



A technician applies blood rom a participant on a lter paper at a rural health centre in the Democratic Republic o the Congo during

clinical evaluation o LAMP or the diagnosis o HAT. The sample is let to dry at ambient temperature, then stored in a plastic pouch

containing a desiccant, beore being sent to a LAMP centre or testing.

A technician reads the results of LAMP at a rural hospital in Uganda, where the test is being evaluated for the diagnosis of T.b. rhodesiense HAT.



Bilil ml dvlmn

A critical obstacle in development o improvedassays or HAT is access to careully collected andstored biological materials.

Current status

FIND and the World Health Organization (WHO)have addressed this problem by establishing a HATspecimen bank, which is owned by the WHO. TheInstitut Pasteur in Paris hosts the WHO specimenbank, storing samples and dispatching them toresearch institutions and other users ater approvalby an Exit Committee o WHO.

Additional specimen collections are available at theInstitute o Tropical Neurology (INT) in LimogesFrance, and Makerere University in Uganda, or

use on FIND-supported activities. The number osamples in these collections is increasing as newclinical studies are carried out.

FuNDINg

The current unders or HAT diagnostics at FINDinclude the Bill & Melinda Gates Foundation,EU-FP7 Programme, DFID (UK), UBS OptimusFoundation and the German government.

agreeMeNts wItH partNers

Most activities with our partners are based on con-tractual agreements. FIND has, in addition to suchagreements, signed a Memorandum o Understand-ing with the ollowing strategic organizations, amongothers:WorldHealthOrganization PanAfricanTsetseandTrypanosomiasis

Eradication Campaign (PATTEC)MdecinsSansFrontiresSpain



1. Tiberti N., Matovu E., Hainard A.,Enyaru J.C., Lejon V., Robin X., Turck N.,

Ngoyi D.M., Krishna S., Bisser S.,Courtioux B., Bscher P., Kristensson K.,

Ndung'u J.M., and Sanchez J.C. (2013).New biomarkers or stage determination inTrypanosoma brucei rhodesiense sleeping sicknesspatients. Clinical and Translational Medicine

http://www.clintransmed.com/content/2/1/1.

2. Tiberti N., Lejon V., Hainard A., Courtioux B.,Robin X., Turck N., Kristensson K., Matovu E.,Enyaru J.C., Ngoyi D.M., Krishna S., Bisser S.,

Ndung'u J.M., Bscher P. and Sanchez J.C.(2013) Neopterin is a cerebrospinal fuidmarker or treatment outcome evaluationin patients aected by Trypanosoma brucei

gambiense sleeping sickness. PLoS Neglected

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specimen biobank: a necessary tool to supportresearch o new diagnostics. PLoS NeglectedTropical Diseases 6(6): e1571. doi:10.1371/journal.pntd.0001571

5. Tiberti N., Hainard A., Lejon V.,Courtioux B., Matovu E., Enyaru J.C.,

Robin X, Turck N., Kristensson K.,Ngoyi D.M., Vatunga G M.L., Krishna S.,Bscher P., Bisser S., Ndung'u J. M. andSanchez J-C. (2012). Neopterin or the stagingand ollow-up o sleeping sickness patients:evidence rom a multi-centric cohort.PLoS One 7(7) e40909.

6. Matovu E., Kazibwe A.J., Mugasa C.M.,Ndungu J.M. and Njiru Z.K. (2012).

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7. Biler S., Matovu E., Mitashi P., Ssewannyana E.,Karhemere Bi Shamamba S., Bessell P.R. and

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17/2015Publ icat ions

9. Hainard, A., Tiberti, N., Robin, X.,Ngoyi, D.M., Matovu, E., Enyaru J.C.K.,Mller, M., Turck, N., Ndungu, J.M.,Lejon, V., and Sanchez, J.C. (2010). Matrixmetalloproteinase-9 and intercellular adhesionmolecule 1 are powerul staging markers orhuman Arican trypanosomiasis. TropicalMedicine & International Health 16:119126.

10. Ndungu JM., Bieler S. and Roscigno G.(2010). Piggy-backing on diagnosticplatorms brings hope to neglected diseases:the case o sleeping sickness. PLoS NeglectedTropical Diseases 4(5): e715. doi:10.1371/journal.pntd.0000715.

11. Molyneux, D., Ndungu J.M. and Maudlin I.

(2010). Controlling sleeping sickness whenwill they ever learn? PLoS Neglected TropicalDiseases 4(5): e609. doi:10.1371/ journal.pntd.0000609

12. Gibson W., Nemetschke L. and Ndung'u J.(2010). Conserved sequence o the TgsGPgene in Group 1 Trypanosoma brucei gambiense.Inection, Genetics and Evolution, 10:453-458.

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14. Bscher, P. Mumba Ngoyi, D. Kabor,J. Lejon, V. Robays, J. Jamonneau, V. Bebronne,

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FIND provides the necessary expertise, capacity and facilities

needed to drive the R&D process, through partnerships with

academia, industry and endemic country governments. We

also help create the necessary conditions for widespread

implementation of these tools through collection of evidence,

sharing knowledge and technology transfer.

Viewing the results o a HAT LAMP test in Eastern DRC.

foundationfor innovative new diagnostics


19/20

Partnering or better diagnosis or all


20/20

foundationfor innovative new diagnostics

FIND 2013

Production and editing: FIND Communications

Authors: HAT & OND team

Design: www.latitudesign.com

Printer: NBmedia

All photos except three are courtesy o Joseph M. Ndungu

Documents

Developing New Diagnostic Tests for Sleeping Sickness MAY2013