Artemisinin resistant falciparum malaria, defined by remarkable decelerated clearance of the peripheral

blood parasitaemia after treatment with artemisinin containing therapies, first emerged in Western

Cambodia around a decade ago, but has since then spread and newly emerged to 5 countries of the

Greater Mekong Subregion (GMS). Artemisinin resistance selects for partner drug resistance in

artemisinin combination therapies, which subsequently results in high failure rates as observed in

Western Cambodia and the Myanmar-Thai border region. This is obviously a big threat to malaria

control. The recent discovery of a molecular marker facilitates surveillance of the spread and emergence

of artemisinin resistance, but should be interpreted with care. New antimalarial drugs are in the

pipeline, but it will take another 3 to 5 years before these will become available. As long as these new

drugs are notavailable, elimination of artemisinin resistance implies elimination of all falciparum malaria

in areas with resistance. This requires a multipartite regional responseaiming for elimination with a

sense of urgency. Several initiatives to curb the big threat of artemisinin resistance have now started. To

accelerate elimination, the asymptomatic parasite reservoir needs to be attacked, and targeted mass

drug administrations might be indicated to reach this goal.

Arjen Dondorp trained as an infectious diseases and intensive care

physicianin the Netherlands. He is aProfessor of Tropical Medicine at the

University of Oxford, U.K., and a visiting Professor of Clinical Tropical

Medicine at Mahidol University in Bangkok, Thailand. He is the Deputy

Director and Head of Malaria Research at the Mahidol Oxford Tropical

Medicine Research Unit in Bangkok, Thailand and chairs the Technical Expert

Group on Antimalarial Drug Resistance and Containment for the World

Health Organization. His main research interests include antimalarial drug

resistance, the pathophysiology and treatment of severe malaria, and care

for critically ill patients in resource poor settings.

Prof. Arjen M. Dondorp Infectious Diseases and Intensive Care Physician

Professor of Tropical Medicine University of Oxford Visiting Professor of Clinical Tropical Medicine Mahidol University

Deputy Director Mahidol Oxford Tropical Medicine Research Unit Faculty of Tropical Medicine Mahdiol University

420/6 Rajvithi Road Bangkok 10400

Thailand Tel. +662036303

Fax: 662 354 9169 E-mail: Arjen@tropmedres.ac

Mucormycosis: The challenges in Asian countries

Arunaloke Chakrabarti

Department of Medical Microbiology, Postgraduate Institute of Medical Education & Research, Chandigarh 160012, India

Mucormycosis is an important healthcare problem in Asia. The alarmingly high incidence of mucormycosis in uncontrolled diabetic population is a cause for concern. The majority of mucormycosis cases in Asia have been reported from India with few case series from Taiwan, Korea, Indonesia, and Japan. Using probabilistic modeling algorithms, mucormycosis is projected at 0.14 cases/1000 population in India. The majority of Asian people avoid periodic health checkup and it is reflected in the fact that 16-23% of our mucormycosis patients were unaware of background diabetes. Besides diabetes, Asian mucormycosis cases have certain unique features. In India and China a distinct group of population has been reported with isolated kidney involvement. The patients are young and immunocompetent. It is not clear how and why these patients acquire isolated renal mucormycosis. The spectrum of agents causing mucormycosis in Asia is also wide. Though Rhizopus oryzae is the commonest agent isolated, Apophysomyces variabilis is the second frequent agent. Other new species isolated in Asia include Saksenaea vasiformis, Rhizopus homothallicus, Mucor irregularis, Thamnostylum lucknowense. These rare agents were isolated from the soil from India. Low nitrogen content of the soil and alkalinity help in the growth of A. variabilis. The major diagnostic challenge in mucormycosis is suspicion of the disease and collection of material from deep tissue. In immunosuppressed the disease should be suspected when galactomannan is negative. Lack of serological and molecular diagnosis makes conventional techniques only options for diagnosis. Imaging may help when reverse halo sign or >10 nodular infiltrates is present. Nearly 30-50% cases culture fail to grow the fungus. Direct microscopy using optical brightener and histopathology help in early diagnosis. Occasionally small hyphae without any characteristic features may create problem in diagnosis. Immunohistochemistry or detection of DNA and sequencing helps in diagnosis of such cases. The management of mucormycosis has major problem due to aggressive nature of the disease and associated life-threatening underlying conditions. Aggressive surgery wherever possible, prompt antifungal therapy with liposomal amphotericin B, reversal of underlying disease and attempt to improve immue functions are the four pronged strategies to manage mucormycosis. A large section of Asian patients fail to afford liposomal amphotericin B and is managed with conventional amphotericin B deoxycholate. The mortality remained >50% in majority series on this disease. Therefore, more studies on early diagnosis and better antifungal agents to treat the disease may overcome the gap in knowledge of mucormycosis in Asia.

Arunaloke Chakrabarti • Arunaloke Chakrabarti is a student in the field of medical mycology for last 28

years. He earned his MD in Microbiology from Postgraduate Institute of Medical Education & Research, Chandigarh, India in 1985 and is presently working as Professor and Head, Department of Medical Microbiology at the same Institute.

• He is currently the Chair of ‘Asian Fungal Working Group’, Chair of ‘Fungal Infection Study Forum’, Coordinator of the International Society of Human & Animal Mycology (ISHAM) working groups on ‘Fungal sinusitis’ and ‘ABPA in asthmatics’, and member of two more ISHAM working groups. ISHAM has recognized him as ‘Global opinion leader in the field of medical mycology’. He is international advisor of ‘Leading International Fungal Education’. He was Vice-President of ISHAM during 2009-2012. He was President to two important associations – Indian Association of Medical Microbiologists (2011-2012), Society of Indian Human and Animal Mycologists (2010-2012). He is Editor/Associate Editor/Deputy Editor of four international journals – Medical Mycology, Journal of Medical Microbiology, Mycoses, and Medical Mycology Case Report. He is Editorial Board member of Indian Journal of Medical Microbiology.

• He has published 218 papers in the field of Medical Mycology and delivered lectures in >100 medical conferences and societies. He wrote chapters in 13 books. He recently edited the book ‘Fungal Infections in Asia-The Eastern Frontier of Mycology’. His major contribution is in the field of epidemiology of fungal sinusitis, mucormycosis, and hospital acquired fungal infections. His laboratory identified the endemic regions of fungal rhinosinusitis, sporotrichosis, penicilliosis, source of Cryptococcus gattii in India, emergence of Apophysomyces elegans and Candida tropicalis in tropical countries. His laboratory investigated many nosocomial fungal outbreaks in developing countries, and developed molecular identification and typing methods of zygomycetes. He delivered many orations and received multiple awards from National Societies, Academies of India, and was awarded the Fellow of National Academy of Medical Sciences, Fellow of The National Academy of Sciences, India; and Fellow of Infectious Disease Society of America. He received three awards from Indian Association of Medical Microbiologists – S C Agarwal Award, IAMM Endowment Award, Pankajalakshmi Venugopal award in mycology. He delivered multiple orations in different national bodies.

• He has consistently helped in the development of the discipline of Medical Mycology and laboratories in India. His laboratory is now recognized as ‘Center of Advanced Research in Medical Mycology’ in India, ‘WHO Collaborating Center for Reference and Research on Fungi of Medical Importance’. Recently ‘National Culture Collection of Pathogenic Fungi’ and nodal center for ‘Antifungal resistance surveillance network’ have been added to his laboratory.

History and Epidemiology of Plasmodium knowlesi Balbir Singh Malaria Research Centre, Faculty of Medicine & Health Sciences, Universiti Malaysia Sarawak Malaria in humans was thought to be caused mainly by four species of Plasmodium: P. falciparum, P. vivax, P. malariae and P. ovale. Naturally acquired simian malaria infections were considered extremely rare until we utilized molecular detection methods and described a large focus of human P. knowlesi infections in the Kapit Division of Sarawak, Malaysian Borneo in 2004. Cases have subsequently been described throughout Malaysia and in Singapore, Indonesian Borneo, the Philippines, Thailand, Myanmar, Vietnam, Cambodia, and in the Andaman and Nicobar Islands of India. Consequently, P. knowlesi is recognized as the fifth species of Plasmodium that can cause human malaria. The talk will begin with a description of the studies of Knowles and Das Gupta following their isolation of P. knowlesi from a long-tailed macaque in 1931, and of other early studies leading to the discovery of the large focus of human infections in Sarawak in 2004. More recent epidemiological and entomological data will be presented, together with results of molecular characterisation of P. knowlesi isolates derived from humans and macaques, which indicate that knowlesi malaria is primarily a zoonosis; forest-dwelling mosquitoes belonging to the Anopheles leucosphyrus group are the vectors and long-tailed and pig-tailed macaques are the main reservoir hosts. The widespread distribution of human cases, some resulting in fatal outcomes, underscores the public health importance of human P. knowlesi infections in Southeast Asia.

BRIEF CURRICULUM VITAE

BALBIR SINGH

Address: Faculty of Medicine & Health Sciences, Universiti Malaysia Sarawak, Jalan Tun Ahmad Zaidi Adruce, 93150 Kuching, Sarawak, Malaysia.

Telephone: +6 082 292256 (Office), +6 082 292170 (Lab) E-mail: bskhaira55@gmail.com Qualifications PhD. Immunology/Microbiology. University of Liverpool, Liverpool, UK (1980-1984). MSc. Applied Parasitology & Medical Entomology, University of Liverpool, UK (1979-1980). BSc. Honours, Biochemistry. University of Liverpool, Liverpool, UK (1976-1979). Present & Previous Appointments Director, Malaria Research Centre (since Feb 2006), Faculty of Medicine & Health Sciences,

Universiti Malaysia Sarawak, Kuching, Sarawak, Malaysia. Professor (since Oct. 2000) & Associate Professor (Jan. 1999 - Sept. 2000) Faculty of Medicine

& Health Sciences, Universiti Malaysia Sarawak, Kuching, Sarawak, Malaysia. Lecturer (Jan. 1992 - Dec. 1998). Department of Medical Microbiology & Parasitology, School of

Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia. Beit Medical Fellow (Oct.1988 - Nov.1991). Liverpool School of Tropical Medicine, Liverpool, UK. Postdoctoral Senior Research Assistant (June 1984 - Sept.1988). Liverpool School of Tropical

Medicine, Liverpool, UK. Research & academic achievements Prof Balbir’s research has been aimed at obtaining a greater understanding of the epidemiology, evolutionary history, population genetics and pathophysiology of malaria. A landmark discovery by his research team has been of a large focus of human infections of Plasmodium knowlesi, a simian malaria parasite. They have subsequently made several other key discoveries which have highlighted knowlesi malaria as a major, life-threatening zoonotic disease in Southeast Asia. His research has been funded by local and international funding agencies including the Wellcome Trust and the Medical Research Council, UK. Prof Balbir has published in leading international journals including The Lancet, Clinical Microbiology Reviews, PLoS Pathogens, Clinical Infectious Diseases and Emerging Infectious Diseases. He has reviewed manuscripts from numerous international journals including Lancet Infectious Diseases, Clinical Infectious Diseases, Emerging Infectious Diseases, Journal of Internal Medicine, Trends in Parasitology, Journal of Infectious Diseases and Infection & Immunity. He has served on the Editorial Boards of the Malaria Journal, Open Parasitology Letters and Malaria Research & Treatment. He has reviewed grant proposals from international funding agencies and was a temporary advisor to WHO. Prof Balbir’s research on knowlesi malaria has also attracted considerable media attention, including being featured in an Australian Broadcasting Corporation television documentary entitled ‘Monkey Malaria’ and in a news feature by Al Jazeera.

CV

Naoko Chiba

Current post

Fellowshipresearcher, Department of Infectious Diseases, Keio University School of

Medicine

Education

Mar 2005Graduated from Kitasato University Graduate School of Infection Control Sciences

(MSc; Infection control)

Mar 2010 Graduated from Kitasato University Graduate School of Infection Control

Sciences (PhD; Infection control)

Employment

Apr 2005 Research associate, Kitasato University Kitasato Institute for Life Sciences

Jul 2013 to date Research associate, Department of Infectious Diseases, Keio University

School of Medicine

Memberships

The Japanese Association for Infectious Diseases

The Japanese Society of Chemotherapy

The Japanese Society for Clinical Microbiology

The Japanese Society for vaccinology

Awards and Grant

2009 Journal of Infection and Chemotherapy Award

2011 Ueda memorial award/research fellowship of Japanese Society of Chemotherapy

2014 Japan Society for the Promotion of Science, Grant-in-Aid for young Scientists (B)

DrGraham Harrison has trained and practiced as a specialist in public health medicine in

New Zealand. He has formal qualifications in Medicine, Public Health and Public Policy. His

areas of interest are health policy, regulation, purchasing and health systems. He has

worked for WHO as Regional Adviser, Health Systems in the Western Pacific Regional Office

(2000-2006); Health System Adviser based in Viet Nam (2006-2012); Acting WHO

Representative to Viet Nam (2011-2012). He is currently appointed as WHO Representative

to Malaysia, Brunei Darussalam and Singapore (from 2012), based in Kuala Lumpur.

2014年11月4日

21:09

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Main barriers for implementing stewardship in hospitals

Gabriel Levy Hara.Infectious Diseases Unit, Hospital Durand, Buenos Aires, Argentina.Chair, International Society of Chemotherapy Antimicrobial Stewardship Working Group.

In most hospitals from Latin America, Asia and Africa, as well as in many institutions of Europe and North America, many essential human and material resources needed for implementing sustainable Antimicrobial Stewardship (AS) Programs are scarce. Main barriers can be summarized as follows:

a) Suboptimal microbiology laboratory diagnostic tools (with seldom species identification, and antibiotic susceptibility tests)

b) Lack of human resources (poor availability of different specialists to maintain a functional AS team)

c) Poor knowledge/ education of rational antibiotic use among health care professionals (suboptimal undergraduate training; limited continuous medical education programs for physicians, microbiologists and pharmacists, and influence of pharmaceutical companies on prescriptions’ behavior);

c) Issues regarding prescribing practices (‘therapeutic freedom’ highly valued among many physicians, and lack of stable drug supply);

d) Issues regarding guidelines and recommendations (multitude of guidelines present, often outdated or inappropriate; lack of locally relevant guidelines and lack of access to up-to-date information)

e) Insufficient infection control practices (poor availability of doctors and nurses for IC team; poor interest, knowledge and compliance of health care workers with basic IC practices, insufficient budget for IC activities, and structural deficiencies of the institution).

Despite all these barriers, there is an urgent need to start or improve already ongoing initiatives towards a better use of antimicrobials.

In fact, many of the barriers are not strictly related to the scarce of human resources or funding to develop effective AMS programmes. One of the essential caveats lie in subjective issues: low to non- perception of the problem and its impact, poor interest of many of potential main actors (managers, Chief of Units, prescribers, etc) and limited education and training on the huge problem of ATB use and misuse.

Summary of main current positions Dr. Gabriel Levy Hara Buenos Aires, Argentina

Professor Dr. Gabriel Levy Hara graduated from the University of Buenos Aires, Argentina in 1985, and obtained his specialty degree in Infectious Diseases in 1989 while completing the residence at the Hospital of Infectious Diseases Francisco J.Muñiz, Buenos Aires. Since 1989, he has been in charge of Units of Infectious Diseases belonging to several institutions of Buenos Aires City, being Hospital Carlos G Durand the main one. He has conducted several training initiatives both as Professor in Infectious Diseases as well as Director of many distance learning courses for all Latin American countries.

His main current and/or recently past most important positions are briefly summarized as follows:

• Chief of Infectious Diseases Unit, Department of Internal Medicine, Hospital Carlos G Durand, Buenos Aires, Argentina

• Head Professor of Clinical Microbiology and Infectious Diseases, School of Medicine, Maimónides University, Buenos Aires, Argentina.

• Coordinator of Infectious Diseases Network of Public Hospitals of Buenos Aires City, Ministry of Health, Buenos Aires.

• Coordinator of Committee for Continuous Medical Education, Pan American Association for Infectious Diseases (API).

• Coordinator of Distance Learning Courses on Antiretrovirals, Antimicrobials and Pharmacosurveillance, PAHO/WHO 2008-11

• Coordinator of Distance Learning Courses on Antimicrobials, Pan American Association for Infectious Diseases (API), 2009-2012

• Coordinator of Distance Learning Course for Committees of Pharmacotherapy, PAHO/WHO 2010-2011

• Coordinator of Distance Learning Courses on Pharmacovigillance, PAHO/WHO 2010-2013

• Director of Course on Infectious Diseases, Argentinean Medical Society, 2011-2013.

• Coordinator of the Antimicrobial Stewardship Program, School of Medicine, University of Buenos Aires, Argentina

• Member of the International Society of Chemotherapy UTI Commission. • Chair of International Society of Chemotherapy Antimicrobial Stewardship

Working Group. • Member of the Executive Board, International Society of Chemotherapy. • Member of the Advisory Committee of the World Alliance Against Antibiotic

Resistance (WAAAR). • Chair of the Distance Learning Course for Africa: Infection Prevention Control

and Antimicrobial Stewardship, organized by ISC and Infection Control African Network (ICAN)

Rotavirus infections and vaccines: burden of illness and potential impact

of vaccination

Gagandeep Kang, Christian Medical College, Vellore

Two live, attenuated, orally administered rotavirus vaccines - a monovalent human

rotavirus vaccine (Rotarix™ (GSK Biologicals, Rixensart, Belgium)) and a pentavalent

bovine-human reassortant vaccine (RotaTeq® (Merck and Co, Inc, Pennsylvania)) -

are licensed for use in more than 100 countries worldwide. The vaccines were

originally licensed based on promising clinical trial data from the United States of

America (USA), Latin America, and Europe. Recently, India and Vietnam have

licensed two monovalent live attenuated rotavirus vaccines that may become

available for use in national programmes.

The World Health Organization (WHO) recommended in 2006 that rotavirus vaccines

be introduced into the national programmes of countries in regions where clinical

trial data are available. In 2009, following additional clinical trials in low income

countries and the availability of post-marketing data from early introducing

countries in the Americas, Europe, and Australia, WHO extended its

recommendation to include rotavirus vaccines in the routine immunization programs

in all countries globally and particularly those countries with high child mortality due

to diarrhea. Following further analysis, in 2013, the WHO recommended that all

countries consider immunization along with the primary immunization series at

whatever age the series is administered. Since 2006, over 50 countries have

introduced rotavirus vaccine into their national immunization programs.

Of the estimated 453,000 annual deaths due to rotavirus diarrhea in children <5

years of age globally, at least 35% occur in Asia and rotavirus causes significant

childhood morbidity resulting in large healthcare costs. The potential health and

economic impact of a rotavirus vaccination programme in Asia is immense.

Widespread experience with rotavirus vaccines under conditions of routine use in

many countries worldwide coupled with clinical trial data provide much insight into

the performance, impact, safety, and cost-effectiveness of rotavirus vaccines.

Countries that have introduced rotavirus vaccine, such as Brazil, Mexico, Australia,

and the USA, have documented large declines in hospitalizations due to rotavirus

disease. A low rate of intussusception (1 in 20,000 to 1 in 50,000 vaccinees) has

been identified in several settings in post-marketing surveillance, but risk-benefit

analyses in several countries that have introduced rotavirus vaccine into their

national immunization programs have found that the benefits of rotavirus

vaccination greatly outweigh the risk. However, each country must weigh its own

benefit-risk scenario prior to vaccine introduction.

Studies to examine rotavirus vaccine impact and safety can help answer many of

these questions and provide support for sustained use of rotavirus vaccines in Asia.

Name Gagandeep Kang, MD, PhD, FRCPath, FAAM, FASc, FNASc

Address Professor and Head, The Wellcome

Trust Research Laboratory, Division of

Gastrointestinal Sciences, Christian Medical

College, Vellore 632 004, Tamil Nadu, India

Tel: 0091-416-228-2052

E-mail: gkang@cmcvellore.ac.in

Website: www.cmcwtrl.in

Gagandeep Kang received her training in medicine and microbiology at the Christian Medical College,

Vellore in southern India and is currently Professor of Microbiology and Head of the Wellcome Trust

Research Laboratory and the Division of Gastrointestinal Sciences at the Christian Medical College,

Vellore. She works on enteric infections in children, particularly on transmission and immune

responses, in order to design effective interventions. Current studies include active hospital and

community based surveillance and clinical trials of new and existing vaccines, with use of molecular

based assays to study the diversity of pathogens and the immune response of children with viral and

parasitic enteric infections.

Dr. Glen Hansen is the Medial Director of Clinical Microbiology and Molecular Diagnostics at Hennepin County Medical Center. Glen obtained his Ph.D. in Clinical Microbiology and Immunology at Royal University Hospital and the University of Saskatchewan in Saskatoon Canada under the mentorship of Dr. Joe Blondeau before undertaking post-doctoral research in Molecular Diagnostics at New York Public Health Research Institute and New York University. Dr. Hansen has formal fellowship training in clinical microbiology at the University or Washington in Seattle Washington under the mentorship of Ferric Fang, and Jill Clarridge. Dr. Hansen is the former Director of Microbiology and Molecular Diagnostics for Peace Health Hospital system in Eugene Oregon. Dr. Hansen is fellow of the Canadian College of Microbiology and a Diplomat of the American Board of Medical Microbiology and is an active member of the American Society for Microbiology (ASM) the Academy of Clinical Laboratory Physicians and Scientists (ACLPS), and the Association for Molecular Pathology (AMP), the Pan American Society for Clinical Virology, the Infectious Disease Society of North America (IDSA) and the Association of Medical Microbiology and Infectious Diseases of Canada (AMMI). Dr. Hansen is well published in the areas of antimicrobial resistance, emerging diagnostics, and sepsis with a specific focus on intra-abdominal and surgical site infections for which is has also served as a guideline author.

Antimicrobial susceptibility testing – Updates from EUCAST Gunnar Kahlmeter

In Europe at the beginning of this century, there were 6 national breakpoint

committees. The European Committee on Antimicrobial Susceptibility Testing

(EUCAST), was formed to organise the national breakpoint committees and to

create a common European system for antimicrobial susceptibility testing;

breakpoints and standardized methods.

EUCAST is organized by the European Society of Clinical Microbiology and

Infectious Diseases (ESCMID) and the European Centre for Disease prevention

and Control (ECDC). It acts as the advisory breakpoint committee to the

European Medicines Agency (EMA) and ECDC and determines breakpoints as an

integrated part of the approval process for new agents. Over the last 10 years

agents such as daptomycin, tigecycline, ceftaroline, ceftobiprole, bedaquiline and

more have received breakpoints through EUCAST.

EUCAST has reviewed, revised and harmonised breakpoints for all antibacterial

and antifungal agents widely used in Europe. Older agents replaced by safer,

more efficient agents in the same group, and where the evidence for their

efficacy and safety is lacking, were not given breakpoints and were not placed in

the EUCAST breakpoint tables and it is the intention of EUCAST that

practitioners should seriously question the continued use of these agents.

Over the last five years EUCAST breakpoints were made available in systems for

semiautomatic susceptibility testing. Furthermore, EUCAST has developed

recommendations for disk diffusion with descriptions of methods, new media,

validation of inhibition zone diameters to the ISO agreed reference broth

microdilution method for MIC determination, quality control criteria and with

relevant documents translated to several languages.

Currently European countries are gradually switching from national or CLSI

(Clinical Laboratory Standards Institute, U.S.A.) recommendations to EUCAST

recommendations and methods. Also several countries outside Europe, such as

Australia, South Africa, Morocco and others have joined this process.

Countries outside Europe are welcome to join the EUCAST General Committee

once they have found a means of officially appointing a national representative.

A description of how this can be done and all other EUCAST recommendations,

including breakpoint tables and manuals, are freely available and regularly

updated on the Internet at www.eucast.org.

Gunnar Kahlmeter, Sweden o Gunnar Kahlmeter, M.D., Ph.D. (born 1949).

o Education - M.D. at the Medical faculty, Lund University, Lund, Sweden, 1981

- Specialist in Medical Microbiology, 1984.

- Ph.D. at the Medical faculty, Lund University, Lund, Sweden, 1979.

o Position and professional affiliation:

- Head of Depts of Clinical Microbiology, Växjö and Karlskrona, Sweden 1985 - contd - Head of Dept External Swedish Reference Laboratory of Antimicrobial Resistance 1985 -

contd - Expert, Swedish Institute for Infectious Disease Control (20%) 2001 - contd - Professor of Clinical Bacteriology, Dept of Clinical Bacteriology, Medical faculty, Uppsala

University, Uppsala. - Head of the EUCAST Development Laboratory, Växjö, Sweden

o Offices - SRGA (Swedish reference Group of Antibiotics), member 1986 - 2010 - Chairman of SRGA-M (The Swedish Reference Group on Antibiotics – Methodology) 1986 -

2010 - Chairman of EUCAST (The European Committee on Antimicrobial Susceptibility Testing)

2001 – 2012, Steering Committee member 2013 - contd - The BSAC Working Party on Antimicrobial Susceptibility Testing 2002 – contd - European Advisor to the National Committee for Clinical Laboratory Standards NCCLS, later

Clinical Laboratory Standards Institute (CLSI, USA) 2002 – contd - EARSS Advisory Board 2002 – 2010 and EARS-NET Advisory board, ECDC 2010 - contd - Member of the NEQAS (Central Public Health Laboratory, Colindale, UK) steering committee

for microbiology and its subcommittee on antimicrobial susceptibility testing 2004 – contd - Professional Affairs Officer Clinical Microbiology, ESCMID Board, co-opted 2007 - 2009 - ESCMID Executive Committee 2006 - contd - ESCMID President Elect 2010 – 12, President 2012 – 14, Past President 2014 - 16

o Research interests

- Antimicrobial resistance, antimicrobial resistance surveillance, antimicrobial susceptibility testing, diagnostics in microbiology..

o Publications (see Pubmed for list) – more than 100 publications - Publications and book chapters within the fields of Aminoglycoside toxicity,

pharmacokinetics, concentration determination methods, Antimicrobial susceptibility testing, Antimicrobial resistance and resistance surveillance, Pharmacokinetics, Quality assurance, UTI, General Bacteriology.

- Lectures at International Congresses (the first at ICC, London, 1975) within the fields of Aminoglycoside toxicity, pharmacokinetics, antibiotic concentration determination methodology, Antimicrobial susceptibility testing, Antimicrobial resistance and resistance surveillance, Pharmacokinetics, Quality assurance, General Bacteriology, Standardisation.

• Married to Annika since 1979, children Johan (35), Anna (33) and Jenny

(29)

Antibiotic resistance among human pathogens now occurs in almost every bacterial species for

which antibiotic therapies exist. The mmeasurementof antimicrobial susceptibility of clinical isolates is

crucial for the optimal antimicrobial therapy of infected patients. Emerging patterns of drug resistance

serve to highlight the importance of prompt and accurate assessment of bacterial susceptibility profiles

which are essential in the management of patients and aid in reducing the spread of resistant organisms

or resistance genes throughout hospital and community settings.Despite advances in diagnostic

technologies, research into new and novel susceptibility protocols are required to keep pace with

current and emerging bacterial resistance and novel methods used to evaluate antimicrobial

susceptibility are required. The Mutant prevention concentration (MPC) has been proposed as a new

measure of antibiotic potency by which the ability to restrict selection of resistant mutants is evaluated.

In principle, the MPC measurement also represents a dosing threshold above which mutants should

rarely arise; use of MPC would add consideration of the development of resistance to the traditional

goal of clearing infection. Evaluation of heterogeneous bacterial populations, often representative at

the site of clinical infection, allows for an assessment of the resistance selection in a method not

employed in routine clinical laboratories.This data can be used as a guide for choosingand eventually

administering antimicrobials to significantly reduce the development of resistance. This review will on

the concept and analytical measurement of MPC measurement as well as its role within contemporary

PK/PD modeling. Contemporary data regarding the potential role that the MPC measurement might

play in testing of gram-negative enzymatic resistant will also be explored.

Antimicrobial Resistance in Emerging Economies: An Urgency to Intervene

Antimicrobial resistance is a major global health threat. In the European Union

an estimated 25,000 deaths occur annually secondary to multi-drug-resistant

infections. No reliable estimates for developing countries exist, but figures are

likely to be higher. Strategies to contain antimicrobial resistance were

comprehensively set forth by the World Health Organization (WHO) in 2001.

However, implementation in low- and middle-income countries, where the need

for effective antimicrobials is greatest, has thus far proved problematic [3],[4].

In Viet Nam, where resistance rates are among the highest in Asia, the challenge

is urgent and great. A large population, high infectious disease burden, and

unrestricted access to antimicrobials make Viet Nam a hotspot for the

emergence of drug resistance. Adequate legislation to tackle antimicrobial

resistance in Viet Nam already exists, but a lack of resources prevents effective

policy enforcement.

Growing global consensus that antimicrobial resistance must be tackled provides

opportunity to intervene. Interventions must account for limited resources

available in many regions with the highest resistance burdens. In response to

this we launched the Viet Nam Resistance (VINARES) project, a capacity-building

initiative designed to strengthen antimicrobial stewardship in Viet Nam. The

framework of VINARES may be transferable to other settings, and emerging

economies in particular. During my talk I will present our findings during the

VINARES project.

Summary Points

• Antimicrobial stewardship has been difficult to implement globally, and in

emerging economies it is usually absent or inadequate.

• Implementation of antibiotic stewardship programmes need not wait for

“perfect local data” or funding. There is often sufficient local expertise to

start a programme in the absence of additional resources. No immediate

impact on resistance levels should be expected.

• Antibiotic resistance is partly the result of a dysfunctional health system.

Long-term commitment is necessary to improve healthcare infrastructure

in order to establish a successful antibiotic stewardship programme and

reduce resistance rates.

• Healthcare professionals, preferably “respected” figures, should

coordinate stewardship programmes. The programmes should be

contextualised and compatible with local practices to encourage

engagement and compliance of all healthcare workers.

Heiman Wertheim, MD PhD,currently is the director of the Oxford University Clinical Research Unit (OUCRU) in Hanoi, based at the National Hospital for Tropical Diseases. He did his medical training at Leiden University in the Netherlands. After his medical degree he was trained as a clinical microbiologist at Erasmus University Medical Center in Rotterdam and did his PhD research on Staphylococcus aureusinfections, including MRSA. Since 2007 he started his scientific work in Vietnam and is a Research Lecturer at Oxford University in the UK. He is principal investigator for several infectious disease research projects in Vietnam and other Asian countries. One of the main research programs is related to antibiotic resistance and respiratory infections. He leads the activities of the Global Antibiotic Resistance Partnership (GARP) in Vietnam, which recently finished a situation analysis on antibiotic use and resistance in Vietnam. GARP is currently initiating several local projects to increase our understanding of antibiotic use and resistance in Vietnam. Currently he is leading the VINARES project that is undertaking hospital-acquired infection and antibiotic resistance surveillance activities across 16 hospitals in Vietnam. He has authored or co-authored numerous scientific papers, a bookand two book chapters, and he is editor forfour medical journals.

Acinetobacter baumannii– a successful drug-resistant pathogen

Abstract

Acinetobacter baumannii has swiftly emerged over the past three decades as a

major nosocomial opportunistic pathogen, causing infections in debilitated

patients especially in the intensive care unit (ICU) setting. It is the 10th most

frequently isolated pathogen in US hospitals but ranks among the top 5

pathogens in tropical hospitals including Singapore. The major issue with A.

baumannii is that the organism has rapidly developed resistance to many

antibiotics - as an example, within a single decade (1995 to 2004) in US hospitals,

carbapenem resistance in A. baumannii increased from 9% to 40%. Extensively-

drug-resistant (XDR)A. baumannii has now been described causing infections in

hospitals worldwide. One major reasonfor the widespread development of

carbapenem-resistant A. baumannii and consequent outbreaks arises from its

ability to acquire carbapenem-hydrolysing β-lactamases, specifically the Ambler

class B metallo-β-lactamases and class D oxacillinases. Other than the likely

antibiotic selection pressure caused by increasing antibiotic use – particularly in

the ICU setting – the emergence and international spread of XDR-A. baumannii is

linked to the success of a small number of epidemic clones, particularly global

clones I and II.

DrLi YangHsu is an infectious diseases physician who had spent the past decade

researching and managing patients with multidrug-resistant bacterial as well as

invasive fungal infections prior to establishing his own private practice

partnership in 2014.

He graduated from the National University of Singapore (NUS) School of

Medicine in 1998, and completed his advanced specialist training in infectious

diseases at the Singapore General Hospital in 2005 prior to taking on the role of

an academic physician in NUS/National University Hospital (NUH) in 2006. In

the interim, he obtained a Diploma in Tropical Medicine & Hygiene from the

Gorgas Memorial Institute in 2005, and also completed a Masters in Public

Health at the Harvard School of Public Health in 2007. In 2009, Dr Hsu was

awarded the National Medical Research Council (NMRC) Research Fellowship

and worked at the Wellcome Trust Sanger Institute for a year, studying bacterial

genomics and bioinformatics.

During his time in the public sector, Dr Hsu has served in several Ministry of

Health committees, in particular promoting the causes of antimicrobial

stewardship, and better control of antimicrobial resistance as well as

tuberculosis. He has also served as a technical advisor on surveillance of

antimicrobial resistance to the western pacific regional office of the World

Health Organization. He was the founding director of the Centre for Infectious

Disease & Research (CIDER) at the Saw Swee Hock School of Public Health.

At this point, Dr Hsu continues to serve as a visiting consultant to the

Department of Pathology at SGH, the Communicable Diseases Centre and

Singapore Tuberculosis Elimination Programme at Tan Tock Seng Hospital, St

Luke’s Hospital, and the Department of Medicine at NUH. He is an adjunct

associate professor to the schools of medicine and public health at NUS, and also

the Institute of Bioengineering & Nanotechnology at A*STAR. He has published

more than 100 peer-reviewed papers to date.

15th

Asia Pacific Congress on Clinical Microbiology and Infection

Taming Dengue with Vaccine

This year saw the publication of 3 phase 3 trials with a Tetravalent Dengue vaccine. The first

was the ASEAN study involving 10,272 from 2-14 years of age. The primary endpoint was

protective efficacy against virologically confirmed Dengue beyond 28 days from the last of 3

doses of the vaccine. The secondary endpoints looked at efficacy by serotype, Immunogenicity

and reactogenicity in a subset involving 10% of subjects. Exploratory objectives included

efficacy by age strata, protection against severe dengue and relative risk of hospitalization.

98.8% of subjects completed the study. The per protocol analysis was 56.5% (95% CI 43.8-66.4)

However the serotype specific vaccine efficacy varied from 35% for Dengue 2 to 78.4% for

Dengue 3. However when exploring the more severe spectrum of disease, there was a 88.5%

efficacy against Dengue Hemorrhagic Fever, 80.8% efficacy against severe dengue and a 67.2%

reduction in hospitalization.

These results have been reinforced by the more recent publication of the Central American

study involving 20,689 subjects. The overall vaccine efficacy in this study was 60.8%. The

efficacy against severe dengue was 91.7% and there was a 80.3% decrease in hospitalization.

Both studies documented a good safety profile for the vaccine.

With the publication of these studies we now have a powerful tool in the battle against dengue.

Used in conjunction with ongoing public health initiatives this should have a major impact in

combating Dengue

CURRICULUM VITAE

Name : Hussain Imam bin Hj Md Ismail Titles : Dato’ Dr Date of birth : 30.7.1956, Place of birth : Penang. Identity Card Number: 560730-07-5211 Address : 3, Jesselton Avenue, 10450, Penang, Malaysia. (33A-17-6 Villa Putra Condo, 50480, KL) High School : Penang Free School Basic Degree : M.B., B.S., University of Malaya 1980 Post Graduate : MRCP, United Kingdom, February 1986

DCH, London - March 1986 FRCP (Edin.) –1996 AM 1998, FAMM 2001. FRCPCH(UK) 2010 Honours received: DJN Penang state 1998 JMN Federal government 2007 DSPN Penang state 2012 Working Experience: 1. Medical Officer 1980-1984

Alor Setar General Hospital, Sungai Petani District Hospital

2. Registrar (Paediatrics) 1984-1985 Penang General Hospital

3. Paediatrician, Dept. of Paediatrics, Penang General Hospital, 1/4/86-31/3/89.

4. Consultant Paediatrician, Dept. of Paediatrics, Kuala Lumpur General Hospital 1/3/91-30/11/98

5. Head of Paediatric Neurology Unit, Paediatric Institute, Kuala Lumpur General Hospital, January 1992 - November 1998

6. Consultant Paediatric Neurologist and Head, Dept. of Paediatrics Penang Hospital from 1/12/98 – 14/7/03

7. Senior Consultant and Head of Department, Dept of Paediatrics, Institute Paediatric, Kuala Lumpur Hospital, 15/7/03 –

8. Head, Paediatric Institute, Hospital Kuala Lumpur, 15/7/03- 9. Head of Paediatric Services in Ministry of Health, Malaysia 15/7/03-

Ian M Gould born 1953 BSc, MBChB Edinburgh, PhD, FRCP(E), FRCPath Married with 3 children Graduated in Medicine 1976, Edinburgh, UK. Since 1986: Consultant Clinical Microbiologist and Director of Medical Microbiology at Aberdeen

Royal Infirmary. Honorary Professor of Public Health, Epidemiology and Microbiology

at the University of Trnava. Trained in Clinical Microbiology and Infectious Diseases in

UK, Canada and Africa. Editor or Board member of several international journals and

Chairman of various national/international working parties, learned societies and

advisory boards on Antibiotic Policies and Resistance. Advisor on antibiotic resistance

and prescribing to the Scottish and UK Departments of Health, Alliance for the Prudent

Use of Antibiotics, The International Organisation for Epizoonosis, European

Commission, WHO, and Government agencies abroad. Co-ordinator of the European

Union projects ESAR and ARPAC on antibiotic prescribing and resistance. President of

the International Society of Chemotherapy. Chair of the Scottish National Program on

Antibiotic Susceptibility Testing and Antibiotic Resistance Surveillance working group

Over 300 published scientific papers on antibiotic resistance in peer-reviewed journals,

standard texts and specialist books.

Optimising what is left

Professor Jason A Roberts, PhD

The University of Queensland

Abstract

Antibiotic resistance is now an issue of global urgency. Deaths from infections

caused by pathogens to which the marketed antibiotics are ineffective are

becoming increasingly common. The World Health Organsation, as well as many

national governments including the USA and the United Kingdom, have

recognized the danger that antibiotic resistance is presenting to our current

ability to provide healthcare and are launching initiatives that reward

development of new antibiotics. However, advances in this regard are

constrained by time and results.

An equally important advance is the reinvigoration of previously

forgotten antibiotics. This avenue represents the option which can most

rapidlygenerate different therapeutic options for extensively and pan-drug

resistant organisms. Agents such as fosfomycin and those within the

polymyxinclass are being subject to increasing levels of research so that previous

concerns of these drugs from a safety and efficacy perspective are being

overcome. Clinical experiences with the drugs are showing favourable results in

the treatment of resistant pathogens as well.

Another area representing an area of much research relates to how

different antibiotic exposures can result in greater rates and extent of bacterial

killing as well as the suppression of antibiotic resistance.Indeed, this work

focuses on how we can optimize what therapeutic options are left, both

marketed antibiotics and the previously forgotten antibiotics discussed above.

Other research has highlighted how combination therapy can also deliver better

antibiotic outcomes.

The approach for increasing our understanding of how to best optimize

available antibiotics involves studies with pre-clinical laboratory models,

population pharmacokinetic studies and clinical use of therapeutic drug

monitoring. Specificallyadvances in pre-clinical laboratory models including

hollow fiber infection models and animal models are providing new knowledge

on the effect of different antibiotic exposures on the development of resistance

over the course ofwhilst animal models are also helping identify the contribution

of the immune system to bacterial killing and suppression of antibiotic

resistance.Utilizing each of these aspects can help the procurement of optimized

the antibiotic therapy of the agents in our anti-infective armamentarium that are

left.

Using PK/PD to optimize antibiotic dosing in the critically ill

Professor Jason A Roberts, PhD

The University of Queensland

Abstract

Antibiotic administration is extremely common in critically ill patients with over

50% of patients deemed infected at any point in time. Similarly the outcomes of

treatment of severe infections is poor with persisting high morbidity and

mortality rates. Data over the past 10 years has highlighted associations with

achieving therapeutic antibiotic concentrations and improved antibiotic effects.

Unfortunately, the profound pathophysiological changes that occur in critical

illness cause severe alterations in antibiotic pharmacokinetics. These changes

mean that dosing regimens derived from non-critically ill patients are much less

likely to achieve the desired therapeutic exposures of antibiotic. An

understanding of pharmacokinetics/pharmacodynamics (PK/PD) can be used by

critical care clinicians to predict which dose adjustments should be used in

different critically ill patients to increase the likelihood of achieving exposures

that are associated with better patient outcomes.

From a pharmacokinetic perspective, parameters that help describe

changing concentrations, clearance and volume of distribution, can both be

altered. Significant fluid resuscitation and fluid extravasation can both lead to an

increased Vd which is associated with lowerplasma antibiotic concentrations.

For clearance, augmented renal clearance can result in lower concentrations,

whilst renal and hepatic dysfunction can lead to higher concentrations.

Extracorporeal modalities including renal replacement therapy and

extracorporeal membrane oxygenation can have varied effects depending on the

settings used and the drug in question.

From a pharmacodynamics perspective, differing concentration-time

profiles can result in different activities against bacteria. Knowledge of whether

an antibiotic is most effective when high peak concentrations are achieved or

whether sustained concentrations are present, can help procure altered dosing

strategies that account for altered pharmacokinetics but still achieve antibiotic

exposures that will have maximum effect against a pathogen.

This presentation will address the above issues and review different

interventions that have been studied to try and improve patient outcomes from

optimized dosing including the use of therapeutic drug monitoring and

administration of beta-lactam antibiotics by extended and/or continuous

infusion.

CURRICULUM VITAE EXTRACT Name: Jason Alexander Roberts Email Address: j.roberts2@uq.edu.au Phone No.: 0409-769-397 Date of Birth: July 11th, 1976 Place of Birth: Hobart, Australia Nationality: Australia OVERVIEW Professor, Pharmacist Consultant and NHMRC Career Development Research Fellow Publications in peer reviewed journals - 156 Book Chapters - 9 Total Communications (Presentations and Papers) – 322 h-index – 18 (ISI Web of Science); Q-index 45.5 Current postgraduate supervision – 11 PhD (11 completed Confirmation); 3 MPhil Completed postgraduate supervision – 9 (2 PhD; 2 MPhil; 3 M Clin Pharm; 2 Hons) Grants - $12,564,116 Reviews - peer-reviewed journals or Ethics Committees - 184 CURRENT APPOINTMENTS • Professor, School of Medicine, The University of

Queensland (2014-) • Pharmacist Consultant, Royal Brisbane and Women’s

Hospital (2003-) • NHMRC Career Development Fellow (2013-) • Clinical Director and Adjunct Professor, AusHSI,

Queensland University of Technology EDUCATION • Doctor of Philosophy (2009) School of Medicine, The

University of Queensland • Bachelor of Pharmacy (Hons I) (2002) in Pharmacy

Practice, University of Sydney • Bachelor of Applied Science (1999), Queensland

University of Technology PROGRAM OF RESEARCH Prof Roberts has significant experience in conducting pharmacokinetic studies and is internationally recognised for his work in this area. He designed, coordinated and analysed a large multicentre European pharmacokinetic study (DALI Study, Clin Infect Dis 2014) of over 60 ICUs through The University of Queensland and the European Society of Intensive Care Medicine. He was also involved in the design and analysis of the pharmacokinetic study in the RENAL study (Crit Care Med). He has also designed and completed pharmacokinetic studies at Erasme and Ghent Hospitals (Belgium) Royal Darwin Hospital and the Gold Coast Hospital in his NHMRC research role. He is also CIA on the mulitnational SMARRT Study (NHMRC APP1044941).

MAJOR FUNDING SUPPORT Prof Roberts currently has been awarded over 60 grants over the past 10 years on the topic of drug dose optimisation, 40 of those over the last 5 years valued at over AUD $12 million. He is a NHMRC Career Development Fellow and is a CI on NHMRC Project Grants investigating antibiotic dose optimisation in patients on renal replacement therapies APP1044941 (CIA); APP1062040 (CIA); APP1022460 (CIC); APP1026921 (CIB). He is also CIC on a Wellcome Trust Seeding Drug Discovery Grant investigating new treatments for MDR bacteria. INVITED INTERNATIONAL CONFERENCE PRESENTATIONS (38) INVITED NATIONAL AND STATE CONFERENCE PRESENTATIONS (35)

HONOURS AND AWARDS (4 of 18) • Australian Clinical Pharmacist of the Year Award

(SHPA), 2012. • Australasian Society of Clinical and Experimental

Pharmacologists and Toxicologists Denis Wade Johnson & Johnson Young Investigator Award, 2011

• The University of Queensland Foundation Research Excellence Award, 2011

• Awarded the prestigious Dean’s Award for Outstanding Research Higher Degree from The University of Queensland, 2010.

CAREER BEST PUBLICATIONS (10 of 156; 95 IN LAST 3 YEARS) • Roberts JA, et al. Lancet Inf Dis 2014; 14: 498-

509. Large review of altered pharmacokinetics in critically ill patients and the use of altered dosing approaches to improve antibiotic exposures.

• Roberts JA, et al. Int J Antimicrob Agents 2010;36:332-9. World first large scale prospective study evaluating the utility of therapeutic drug monitoring of β-lactam antibiotics in critically ill patients.

• Roberts JA, et al Clin Infect Dis 2014; 58(8): 1072–83. The DALI Study – a large pharmacokinetic study across 68 ICUs demonstrating the association of lack of attainment of therapeutic antibiotic exposures and clinical failure.

• Roberts JA, et al. Crit Care Med 2009; 37: 2071-8. Meta-analysis of studies in hospitalized patients, no mortality or clinical outcome benefit for continuous infusion of β-lactam antibiotics was apparent. Studies in critically ill patients, suggest that advantages for continuous infusion may exist.

• Roberts JA, et al. J Antimicrob Chemother 2007;59:285-91. Randomised controlled trial demonstrating that continuous infusion has superior clinical outcomes to bolus dosing in ICU patients.

WHONET – 25 years on

Microbes move – between people, hospitals, animals, continents – and evolve. Clinical

laboratories should serve as a window into these dynamic microbial populations, yet

effective collection and exploitation of this largely untapped information resource has been

limited. Since the 1960s, the mission of our work has been the development of free, user-

friendly data management tools to mobilize, share, and utilize data to guide timely and

effective public health action. WHONET is a free informatics tool used to support

surveillance of microbes and their resistance to antimicrobial agents in over 2,000 human,

animal, and veterinary laboratories in over 110 countries worldwide developed and

supported by our team at the WHO Collaborating Centre for Surveillance of Antimicrobial

Resistance in Boston. The two primary objectives of the software are: 1) the thorough

analysis of locally generated data to delineate and respond to emerging threats by clinical,

infection control, antimicrobial stewardship, and public health professionals; and 2) the

collaborative sharing of data and experiences to support national, regional, and global

initiatives for tracking the geographic spread of antimicrobial resistant elements and

containing them. With modern advances in web-based information technology, WHONET

will support the WHO Global Action Plan for Containment of Antimicrobial Resistance to

build a global collaborative for surveillance of antimicrobial resistance surveillance.

Antimicrobial Resistance Surveillance – The Way Forward

Infectious diseases and resistance to antimicrobial agents grow as threats to human and

animal welfare worldwide and drain limited resources. To contain and manage infecting

microbes and their resistance genes, we need to know where they are and where they are

going. Tens of thousands of microbiology laboratories worldwide reporting results daily to

healthcare providers should be viewed as infectious disease sensors, rich sentinel windows

into the world’s evolving microbial populations. At present, analysis of susceptibility test

data is limited in many facilities unfortunately only to a rudimentary annual "antibiograms"

– simple tabulations of %Resistance and %Susceptibility. Looking ahead, new information

technologies permit dynamic collection, analysis, and reporting of findings of public health

importance with automated notifications of new threats, outbreaks, and deficiencies in

laboratory testing supporting timely investigation and response by clinical staff, infection

control practitioners, and national authorities. There is new momentum for local, national,

regional, and global collaboration, and the 2014 call by the World Health Assembly for a

Global Action Plan for the containment of antimicrobial resistance demands urgent action.

Dr. John Siu Lun Tam, Ph.D.

Director and Chairman, Asia-Pacific Alliance for the Control of Influenza (APACI)

Dr.John Tam has recently taken up the position of Director and Chairman of the Asia-

Pacific Alliance for the Control of Influenza, a position he held over 10 years ago as the

founding chairman. He had recently worked as Technical Officer of the Initiative for

Vaccine Research at the World Health Organization (WHO), Geneva, Switzerland and

was responsible for the global research and development of seasonal and pandemic

influenza vaccines as well as the focal point for influenza policy development under

SAGE. He also served as Scientist at the Global Influenza Programme of WHO and was

responsible for the development and implementation of the WHO Public Health

Research Agenda for Influenza including the coordination of influenza vaccine research

and global seasonal influenza vaccine recommendations. John also worked in a leading

role in the pharmaceutical industry on vaccine research and development. Prior to

these, he was Professorin the Department of Microbiology, Faculty of Medicine, The

Chinese University of Hong Kongfor 15 years.Dr. Tam received his B.Sc. and M.Sc.

degrees from the University of Toronto majoring in virology, microbiology and

biochemistry, and his Ph.D. degree from the University of Hong Kong on virology. John

has been active in the field of medical virology and his interest included influenza and

other viral respiratory tract infections, viral diarrhoeal diseases and virus-associated

cancers. He had published over 170 peer-reviewed articles relating to his fields of

interest. During the outbreak of avian influenza in Hong Kong in 1997 and the SARS

outbreak in Asia in 2003, John had served as advisor to the WHO, the Hong Kong

government and other regional health authorities. He received the Bronze Bauhinia Star

(B.B.S.) medal from the Government of Hong Kong SAR in 2004 for his “long and

outstanding contribution to the medical services sector, particularly during the outbreak

of SARS”.

Abstract

Long lasting and broad spectrum influenza vaccine - coming soon or mirage? John S. Tam, Asia-Pacific Alliance for the Control of Influenza (APACI) Influenza viruses remain a serious threat to public health, due to their ability to escape

the human immune system through frequent antigenic drift and occasional antigenic

shift. The continuous circulation of highly pathogenic avian influenza (HPAI) A H5N1

influenza virus and the recent emergence of avian influenza A(H7N9) in China

underscore the pandemic potential of HPAI viruses. The emergence of the 2009

pandemic H1N1 influenza virus (A(H1N1)pdm09) also illustrated the risk of emergence

of a new pandemic from an animal influenza virus and the lengthy production timeline

of a strain-specific pandemic vaccine. Current seasonal trivalent inactivated vaccines

(TIV) show only 50-70% protective effectiveness in adults, with lower effectiveness in

the elderly and young infants. It is thus highly desirable to develop influenza vaccines

that offer broadly cross-subtype protection, such as the “universal vaccines” approach

to combat any possible new pandemic influenza A virus.

The development of universal influenza vaccines remains challenging, requiring in-depth

knowledge of conserved epitopes on viral proteins that can elicit cross-protective

antibody (Ab) responses. Identified epitopes included those located in the virus matrix

protein 2 (M2) and especially its 23 amino acids N-terminal ectodomain (M2e) and in

the highly conserved HA2 region of the hemagglutinin (HA) and neuraminidase (NA)

surface proteins. Potentially cross-protective epitopes for T cell responses were also

identifies from viral internal proteins, primarily the matrix protein 1 (M1) and

nucleoprotein (NP). These new approaches shown promisesin pre-clinical animal models

for the development of influenza vaccines that elicit broad heterosubtypic protective

immune responses. However, there remains limited information as to their potential in

humans as these vaccines progress to humantrials leading to licensure. The prospect on

the eventual availability of an improved influenza vaccine that provides long-lasting

immunity and broadly protective is advancing as multiple approaches including new

formulations and novel approaches in vaccine delivery are being developed.

Clinical implications of different breakpoints

John Turnidge With the emergence of EUCAST as a credible alternative to CLSI for routine susceptibility test, the question of comparability has inevitably arisen, particularly around the issue of differences in breakpoints, where they exist. Methodologically the methods are quite similar, and both are calibrated to the international ISO reference standard ISO 20776. Some differences exist in disk strengths for disk diffusion testing, and EUCAST has settled on a single medium for the common fastidious organisms rather than the range specified by CLSI. For both organizations, breakpoint setting has become a very sophisticated process involving the collection, analysis and consideration of a broad range of data including MIC distributions, in vitro and in vivo pharmacodynamics and clinical outcome data. When breakpoints are different between the two organizations, it can be due to a number of reasons. For MIC breakpoints, it is often due to differences in standard dosing regimens between European countries and the United States. It is sometimes due to differences in the weighting applied to the various types of data used to set breakpoints. For zone diameter breakpoints, the main reason for differences is the difference in disk strengths. This alone does not necessarily result in different interpretations of “S”, “I”, and “R”. In recent years both organizations have moved closer to having the same breakpoints. Nevertheless, there are still some obvious breakpoint differences. Surprisingly for most people those differences are likely to have a minimal impact on patient care. The principal reason is that there are usually very few strains whose MICs fall into the gap between the two breakpoints. For example, there is a noticeable difference in Enterobacteriaceae MIC breakpoints for ceftazidime: EUCAST uses “S” <= 1 mg/L, “R” > 4mg/L, while CLSI uses “S” <= 1mg/L, and “R” >=16 mg/L. breakpoint using the EUCAST the MIC distribution database. Of the 15,126 E. coli isolates in the database, 4.6% had an MIC of >1 mg/L (I or R be EUCAST criteria), while 2.8% had an MIC >4 mg/L (I or R by CLSI criteria). Thus, only 2.2% (1 in 50 strains) of all the isolates that were S by CLSI criteria would have been called non-S by EUCAST criteria. In other examples, the percentage of discrepancy is often lower. Users of either system also need to be aware of what dosing regimen is used in their institution/country when considering which breakpoints more closely reflect those dosing regimens.

Critical issues in in vitro susceptibility testing of polymyxins

John Turnidge With the increasing need for the clinical use of the polymyxinscolistin and polymyxin B, there is now much greater need for standardized laboratory testing and interpretation of these agents. Recently, CLSI and EUCAST formed a joint working group to review the breakpoints for these agents using the newly generated in vitro, pharmacodynamic and clinical data. As a first step, the working group reviewed the broth microdilution reference method for susceptibility testing. Information was emerging at this time of the ability of polymyxins to ‘adhere’ to plastics and other materials. A small number of studies had shown significant adherence to plastics such as those used in microtiter tray, especially at the lower concentrations in a typical dilution series. This has been attributed to the fact that these agents are polycationic in solution, while the plastics often have a net negative surface charge. Emulating work done previously for some lipopeptide antimicrobials, the CLSI undertook a quality control study for the two polymyxins in the presence and absence of 0.002% polysorbate 80 (P80). It was clear from this work, as well as from some small in house studies, that MICs were significantly reduced in the presence of polysorbate 80.Initially attributed to the ability of P80 to reduce adherence of the polymyxins, when the experiment was repeated using trays with a non-stick surface, it was shown that the MICS were similarly reduced. The conclusion was that the P80 effect was due to a drug-P80 interaction and not to reduced adherence. Both CLSI and EUCAST have agreed that the broth microdilution reference method should be done without the addition of P80 to the medium. An additional observation in MIC susceptibility testing is the appearance of skip wells. While yet to be fully characterized, the skip well phenomenon is related to the species being tested and the inoculum, as is likely the result of the random selection resistant subpopulations above an otherwise ‘true’ MIC. As yet, no guidance has been developed about how to interpret this phenomenon for reporting results. The other major problem with the polymyxins is the failure of effective disk diffusion. While disks are available, and it is possible to observe zones around polymyxin disks, the distinction between ‘susceptible’ and ‘resistant’ strains is fraught with problems. Novel approaches will be required to develop effective disk diffusion methods for the future.

John Turnidge Senior Staff Specialist, Microbiology and Infectious Diseases, SA Pathology, based at Women’s and Children’s Hospital, North Adelaide, South Australia, Affiliate Professor, School of Molecular and Biomedical Sciences, Clinical Professor of School of Health Sciences (Pathology and Paediatrics), University of Adelaide Research Interests: Antimicrobial resistance: phenotypic and genotypic Antimicrobial pharmacodynamics: laboratory Antimicrobial susceptibility testing Staphylococcus aureus sepsis. Biographical Details:

Dr Turnidge completed his training in Infectious Diseases and laboratory Microbiology at the Flinders Medical Centre in Adelaide, South Australia . He subsequently undertook research with William A Craig, MD, in Madison, WI, on the early stages of development of the science of antimicrobial pharmacodynamics. He spent eight years at Monash Medical Centre in Melbourne before returning to Adelaide as head of Microbiology and Infectious Diseases, and then as chief of the Laboratory Medicine division at the Women’s and Children’s Hospital. For the last 3 years he has been Clinical Director of Microbiology and Infectious Diseases for SA Pathology, while continuing to be based at the Women’s and Children’s. His research career have led to over 260 publications and a range of editorial boards and leadership positions. He has chaired the Australian Joint Expert Technical Advisory Committee on Antibiotic Resistance and the Expert Advisory Group on Antimicrobial Resistance. He is currently a member of the Subcommittees on Antimicrobial Susceptibility Testing and Veterinary Antimicrobial Susceptibility Testing of the Clinical and Laboratory Standards Institute, and chairs the NHMRC’s Antimicrobial Resistance Advisory Committee. He was President of the Australian Society of Microbiology from 2010 to 2012. He now also works as a Senior Medical Advisor at the Australian Commission fo9r Safety and Quality in Health Care, responsible for implementing national surveillance for antimicrobial resistance and usage in human health.

Curriculum Vitae and Abstract of Special Lecture

Shigeru Kohno, M.D., Ph.D.

Director, Nagasaki University Hospital

Employment Record

1974-1976 Internship. 2nd Department of Internal Medicine, Nagasaki University School of Medicine

1980-1982 Research associate, Department of Pathology, University of New Mexico, U.S.A.

1983-1984 Sasebo General Hospital

1984-1985 Nagasaki Municipal Medical Center

1985-1990 Assistant Professor, 2nd Department of Internal Medicine, Nagasaki University School of Medicine

1990-1996 Lecturer (between assistant and associate professor), 2nd Department of Internal Medicine, Nagasaki

University School of Medicine

1993-1994 Visiting scientist, National Institute of Allergy and Infectious Diseases, National Institutes of Health,

U.S.A.

1996-2000.3 Professor, 2nd Department of Internal Medicine, Nagasaki University School of Medicine

2000.4- Professor, Division of Molecular & Clinical Microbiology, Department of Molecular Microbiology &

Immunology, Nagasaki University Graduate School of Medical Sciences

2005-2006 Vice director, Nagasaki University Hospital Medicine and Dentistry

2006-2009.3 Dean, Nagasaki University School of Medicine

2009.4-2014.9 Director, Nagasaki University Hospital

2014.10-present Vice-president, Nagasaki University

Academic Honors/Award

1994 Futaki Award (Japanese Association of Infectious Diseases)

2002 Medical Mycology Award (Japanese Society for Medical Mycology)

2005 The Uehara Memorial Foundation Research Aid (The Uehara Memorial Foundation)

ABSTRCAT OF SPECIAL LECTURE

New management Strategies for Invasive Fungal Infections in critical care

Nagasaki University

Shigeru KOHNO, MD, PhD.

The recent advances in chemotherapy, medical devices and techniques including organ transplantation boost the

number of immunocompromised hosts, which resulted in remarkable increase of the patients with invasive fungal

infections. The study from analysis of Japanese autopsy cases by Suzuki et al (Med Mycol. 2013 Jan 17) indicated the

unique aspect of trend of deep-seated mycosis in Japan. The total number of fungal infections is increasing year by

year recently. Aspergillosis is the most frequent fungal infection and candidiasis is decreasing in Japan. Though

cryptococcosis has not been increasing past thirty years, there is a possibility that it might be turned into increasing in

the near future due to the increasing HIV/AIDS patients. The number of estimated life-threatening infections per year

in the world is over 200,000 (aspergillosis), 1,000,000 (cryptococcosis) and 400,000 (pneumocystosis), respectively.

The most significant finding for these infections is high mortality rates such as 30-95 % (aspergillosis), 20-70%

(cryptococcosis) and 20-80% (pneumocystosis), respectively. On the other hand, the financial budget for scientific

research for medical mycology field is very limited and extensive research has been required.

The new antifungals are rarely developed recently and only few posters were presented in recent conference such as

ICAAC. Additionally, issue regarding drug resistance in fungal infections becomes major topic as same as bacterial

infection. The situation regarding management of invasive fungal infections is becoming in miserable status due to 1)

increasing patients, 2) limited new antifungals and 3) drug-resistance. What we need to overwhelm this infection is to

develop new antifungal agents and novel treatment strategies that do not rely solely on antifungals. A challenge to

control the virulence factors of causative fungal agents may be one of the options for future treatment.

Clinical guideline for management of deep-seated mycosis in Japan was originally published in 2000 and revised in

2007 and this year. This guideline is unique comparing to other guidelines in U.S and Europe. The chapters are

divided to each clinical department (e.g., hematology, internal medicine, organ transplantation and so on) and simple

charts of each mycosis are placed in every chapter. As the utility of this domestic guideline is well evaluated by

Japanese clinicians, I would also like to introduce outline of the newest version of Japanese guidelines for

management of invasive fungal infections comparing with the IDSA and ESCMID guidelines.

S4 Genetic Basis of Host Susceptibility to Infections

Louis Chai, National University Health System, Singapore

Historically, the acquisition of infectious diseases has been studied in the context of pathogen virulence. In the recent years, advances have been made into the insight of the complex interaction between the host immune response and the microbe. We are now able to dissect the pathways by which receptors on the host immune cells recognize the signatures of pathogen and in turn activate host defence mechanisms. In turn, specific genetically-determined inter-individual variations in host immune responses have been elicited and found to be linked to predisposition to various infections. Using invasive fungal infections as an example, we provide a state-of-the-art review on host immune recognition mechanisms and the relevance of genetic markers in management strategies against difficult-to-treat infections.

Name: Louis Chai NRIC/Passport no. S7325062E Office mailing address Department of Medicine, National University Health System, 1E Kent Ridge Road, Singapore 119228 Email louis_chai@nuhs.edu.sg Contact no 67723914 Fax no 68724130 Current position Senior Consultant, Division of Infectious Diseases, University Medicine Cluster, NUHS Principal Investigator, Opportunisitc Infections Group, Department of Medicine, NUHS Past employment Ministry of Health (1997-1999) Singapore Armed Forces Medical Corps (1999-2001) Singapore Health Services (SingHealth) (2002-2004) Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands (2007-2010) National Healthcare Group/National University Health System (2004 till now) Academic qualifications MBBS (S’pore), 1997 MRCP (Royal College of Physicians), 2003 Specialist Accreditation in Infectious Diseases, 2006 PhD (Nijmegen), 2010 Research interests Infectious diseases, mycology, immunology Time in Singapore 100% Sample publications in this field 1. Lim JH, Ravikumar S, Wang YM, Thamboo TP, Ong LZ, Chen J, Goh JG, Tay SH, Lufei C, Win

MS, Leong W, Lau T, Foo R, Mirza H, Tan KS, Sethi S, Khoo AL, Chng WJ, Motomi O, Netea MG, Wang Y, Chai LY. Bimodal influence of vitamin D in host response to systemic Candida infection – vitamin D dose matters. J Infect Dis. 2014 (accepted) [IF 6.0]

2. Liu X, Pang L, Sim SH, Goh KT, Ravikumar S, Win MS, Tan G, Cook AR, Fisher D, Chai LY. Melioidosis and Its Association with Weather Conditions in Singapore, 2003-2012. Emerg Infect Dis.2014 (in press)[IF 7.3]

3. Liu X, Foo G, Lim WP, Ravikumar S, Sim SH, Win MS, Goh JG, Lim JH, Ng YH, Fisher D, Khoo CM, Tan G, Chai LY. Sulphonylurea usage in melioidosis is associated with severe disease and suppressed immune response.PLoS Negl Trop Dis. 2014 Apr 24;8(4):e2795. [IF 4.8]

4. Chai LY, Kullberg BJ, Earnest A, Johnson EM, Teerenstra S, Vonk AG, Schlamm HT, Herbrecht R, Netea MG, Troke PF. Voriconazole or amphotericin B as primary therapy yields distinct early serum galactomannan trends related to outcomes in invasive aspergillosis. PLoS One. 2014 Feb 28;9(2):e90176.[IF 3.7]

5. Chai LY, Netea MG, Tai BC, Khin LW, Vonk AG, Teo BW, Schlamm HT, Herbrecht R, Donnelly JP, Troke PF, Kullberg BJ. An elevated pro-inflammatory cytokine response is linked to development of amphotericin B-induced nephrotoxicity. J Antimicrob Chemother. 2013 Jul;68(7):1655-9[IF 5.4]

6. South East Asia Infectious Disease Clinical Research Network. Effect of double dose oseltamivir on clinical and virological outcomes in children and adults admitted to hospital with severe influenza: double blind randomised controlled trial.BMJ. 2013 May 30; 346:f3039.[IF 16.3]

7. Chai LY, Kullberg BJ, Johnson EM, Teerenstra S, Khin LW, Vonk AG, Maertens J, Lortholary O, Donnelly PJ, Schlamm HT, Troke PF, Netea MG, Herbrecht R. Early serum galactomannan trend as a predictor of outcome of invasive aspergillosis. J Clin Microbiol. 2012;50:2330-6. [IF 4.2]

Brief CV Nordiah Awang Jalil MD, MSc.

Dr Nordiah Awang Jalil is Professor of Medical Microbiology and Head of Infection Control Unit, UKM Medical Centre.

She was a founder member and executive member of the Asia Pacific Society of Infection Control. Her interests are in infection prevention and control, antimicrobial stewardship, improving the quality of patient care and patient safety. She is involved extensively in infection prevention and control education throughout Malaysia, as well an invited speaker at several International Infection Control Congresses including Singapore, Hong Kong, Shanghai, Macau, Indonesia, Australia, Saudi Arabia and ICAAC Congress in Washington DC and Colorado, USA

In 2011 she received the Excellent Achievement in Research and Development Award and she also served as a 2010 Society for Healthcare Epidemiology of America International Ambassador.

In 2011/2012 she was a visiting research scholar at the Division of Infectious Diseases, Washington University School of Medicine, USA.

Environmental disinfection and control of MRO Professor Dr NordiahAwangJalil

Department of Medical Microbiology & Immunology UniversitiKebangsaan Malaysia Medical Centre, Malaysia

Contamination of environmental surfaces in healthcare settings plays an important role in the transmission of MRO when healthcare workers contaminate their hands or gloves by touching contaminated surfaces, or when patients come into direct contact with contaminated surfaces.MRO from colonized or infected patients frequently contaminate the surface environment and medical equipment and survive well in the environment for a prolonged period of time. Additionally cleaning practices are often suboptimaland auditing of cleaning is mostly done through visual assessment. This presentation will appraise the best practices for environmental cleaning and disinfection in the healthcare settings for the prevention and control of MRO infections.

15th APCCMI Meeting, Kuala Lumpur, Malaysia

Patrick R. Murray, PhD

BD Diagnostics

Sparks, Maryland USA

Abstract for address: “What is New in Clinical Microbiology”

This is an exciting time for the clinical microbiologist with the introduction of many new diagnostic tests, testing methods, and insights into disease pathogenesis. This lecture will focus on four specific technologies and their medical implications: MALDI TOF mass spectrometry for organism identification, molecular diagnostic platforms for nucleic acid amplification, diagnostic and therapeutic implications of the microbiome research, and laboratory automation.

MALDI TOF mass spectrometry is rapidly replacing all biochemical, immunological and gene sequencing tests for identification of bacteria, mycobacteria, and fungi. This technology is faster, more accurate, and less expensive than the traditional identification methods. Molecular diagnostic platforms are now bench top instruments that do not require testing in specialized lab facilities or use of highly trained technologists. With these platforms, assays have been developed for not only performing high volume screening tests, but also diagnostics for a variety of hospital-acquired infections and multiplex assays for diseases of the respiratory, gastrointestinal, and genitourinary tracts. The rapidly evolving knowledge of the human microbiome is opening opportunities for both diagnostic and therapeutic tests. Finally, automation allows the laboratory to not only do what it currently does more efficiently but also to do diagnostics in novel ways, such as performing colony enumeration and discrimination with high analytical precision, providing earlier time to results and improved healthcare outcomes.

Biography: Dr. Patrick R. Murray is the Worldwide Director of Scientific Affairs for Becton Dickinson Diagnostics. He received his Ph.D. degree in Microbiology at UCLA, postgraduate training in Clinical Microbiology at the Mayo Clinic in Rochester MN, and was director of the Clinical Microbiology Laboratories at Barnes Hospital from 1976-1999 and Professor of Pathology and Medicine at the Washington University School of Medicine. In 1999 he moved to Baltimore to assume the position of Director of the Clinical Microbiology Laboratories at the University of Maryland Medical Center, and two years later moved to the National Institutes of Health as Chief of Microbiology and Senior Scientist at the NIH Clinical Center. In July 2011 he accepted his current position at BD Diagnostics. He is the former Editor-in-Chief of the ASM Manual of Clinical Microbiology and serves on numerous editorial boards. He has authored more than 260 research articles and 18 books. He is the recipient of numerous awards including the ASM Becton Dickinson Award for Research in Clinical Microbiology (1993), ASM BioMerieux-Sonnenwirth Award for Leadership in Clinical Microbiology (2002), ASM Founders Distinguished Service Award (2010), and ABMM/ABMLI Professional Recognition Award (2011), as well as the Pasteur Award (Illinois Branch of ASM, 2007), NIH Clinical Center Director's Awards for Patient Care (2006) and Research (2010), and NIH Director's Award for Research (2007).

Interactive session: More and more MRSA

Methicillin resistant Staphylococcus aureus has been with us in the Asia Pacific for more

than three decades. During this time, there have been numerous attempts to control the

pathogen but it continues to plague us. Three interesting cases of complicated MRSA

infection will be presented to illustrate some of the complexities of managing infections with

MRSA. Audience participation is critical to determine the best outcome for our patients!

My brief bio is below:

Dr Paul AnanthTambyah is currently Professor of Medicine and Senior Consultant Infectious

Diseases Physician at the National University of Singapore and National University Hospital.

After completing medical school at NUS and national service, he went on to postgraduate

studies at the University of Wisconsin. Since returning, he has served in a number of national

and international capacities including as Assistant Dean at the Yong Loo Lin School of

Medicine to 2007, founding head of the Division of Infectious Diseases to 2009 and a Board

Member of the Society of Healthcare Epidemiology in America to 2009. He is currently

President of the Society of Infectious Diseases (Singapore) and Secretary General of the Asia

Pacific Society of Clinical Microbiology and Infection. His main research interests are device

associated infections and emerging infectious diseases. In his extra-curricular activities

Controlling Pertussis in Asia Pacific

Professor Usa Thisyakorn

Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand

The pattern of global pertussis epidemiology has shifted over recent years with increased incidence seen in adolescents, adults and young infants. Factors contributing to this changing epidemiological pattern include waning immunity, atypical or unrecognized presentation of the disease, improved diagnostic testing, increased awareness and surveillance. Adults and adolescents can suffer substantial morbidity with pertussis illness, and represent a significant source of infection for susceptible infants.

Asia Pacific is one of the most densely populated areas around the world and suffers from

large disease burdens of common infectious diseases including pertussis. In this area, the largest

burden of pertussis is borne by children below 5 years of age, but adolescent and adult disease has

either been detected or is suspected.

The Global Pertussis Initiative (GPI) is an expert, scientific forum that seeks to analize the

status of pertussis globally. The consensus revealed that pertussis is a global problem and endemic

even in countries with high vaccine coverage. The disease was under-recognized and under-

reported. In infants, it is a serious and growing public health concern. It poses a significant health

burden in adolescents and adults in whom it is increasingly recognized. Adolescents and adults are

particularly concerned because they are sources of infection for unimmunized or incompletely

immunized infants.

To reduce the global incidence of pertussis, the GPI recommends

• Universal immunization of adults

• Selective immunization of new mothers, family, and close contacts of newborns

• Selective immunization of healthcare and childcare workers

• Universal immunization of adolescents

• Fourth or fifth booster dose for all pre-school children (4-6 years of age)

• Reinforce and/or improve current infant and toddler immunization strategies

Pertussis vaccination practices differ across Asia Pacific, with only some countries

recommending booster dosing. To make informed health policy decisions on pertussis prevention,

more robust epidemiological data are needed.

The following fundamentals are needed in order to reach the control of pertussis in Asia

Pacific:

• Robust surveillance practices

• Improve clinical diagnosis across all age groups

• Educate the public, health care professionals and government officials on pertussis

• Increase adherence to vaccination strategies

Health care is not uniform among Asia Pacific countries, issues with physical access to

costs associated with disease prevention exist. Pertussis control can be more effective once

sufficient surveillance evidence is available.

Usa Thisyakorn, M.D.

� Professor of Pediatrics, Chulalongkorn University

� Advisor: Faculty of Tropical Medicine, Mahidol UniversityDepartment of Health, Bangkok Metropolitan AdministrationHRH Princess Maha Chakri Sirindhorn Medical Center, Faculty ofHRH Princess Maha Chakri Sirindhorn Medical Center, Faculty of

Medicine, Srinakarinwirot UniversityFaculty of Medicine, Thammasat University

� Other positions: President, International Society of Tropical Pediatrics Secretary General, Asian Society for Pediatric Infectious DiseasesStanding Committee Member, International Pediatric AssociationPresident, Pediatric Infectious Diseases Society of Thailand

� Area of interest:� Dengue � HIV� Vaccines� Pediatric Infectious Diseases

Ray Hachem,MD. FIDSA. is a Professor of Medicine and Director of Extramural Education Program in the Department of Infectious Diseases, Infection Control and Employee health at The University of Texas M. D. Anderson Cancer Center, Houston, Texas. Dr. Hachem earned a Bachelor of Science in Chemical and Biomedical Engineering from the University of Texas at Austin. His M.D. was received from the University of Santiago, where he also completed his internship. Dr. Hachem joined M. D. Anderson in March 1988 as a fellow and currently he serves as Principal Investigator on a number of protocols. He has received numerous national scientific and professional honors.He is also a Co-Inventor on several U. S. patents which have been granted. DrHachem has authored over 160 peer reviewed articles published in prestigious journals such asNew England Journal of Medicine, Lancet Infectious Diseases,Clinical Infectious Diseases, Antimicrobial Agents and Chemotherapy, andCancere. Dr. Hachem is currently examining new strategies for the management of device related infections by lock therapy or coating catheters with unique antiseptic combinations .

Dr. Hachem served as the chairman of the Division of Internal Medicine Research Committee.The national president of the American Lebanese Medical Association (ALMA).The director of the World Institute of Medical Education (WIME). He also serves on the Institutional Review Board (IRB), the Institutional Research Grant (IRG) Committee, and the Ad Hoc Committee of the Infection Control Committee for the Prevention of Fungal Infections. He is an active member of the Harris County Medical Society, Texas Infectious Diseases (TIDS), American Society for Microbiology (ASM), Society for Healthcare Epidemiology of America (SHEA), the American College of Physicians (ACP) and the Infectious Diseases Society of America (IDSA).

“Updates from the CLSI”

The CLSI M100 tables that list suggestions for agents to test/report, interpretive criteria, and QC ranges are updated annually. It is important for clinical microbiologists to implement the new recommendations into their procedures, as appropriate, to optimize detection and reporting of antimicrobial resistance. This presentation will highlight some of the newest CLSI recommendations by using specific cases and examples.Topics to be covered will include the new interpretive criteria for cefepime and the Enterobacteriaceae, use of cefazolin to predict susceptibility of oral cephalosporins, and azithromycin interpretive criteria for Salmonella.

Romney M. Humphries, PhD D(ABMM) November 2014

1

Romney M Humphries, PhD (D)ABMM

Los Angeles, California, 90049

E-mail: rhumphries@mednet.ucla.edu

Licensure

Diplomate, American Board of Medical Microbiology 2011

M(ASCP)CM

, ASCP090994 2010

Education

Ph.D. (Microbiology & Infectious Diseases) 2008

University of Calgary, Calgary, Alberta

B.Sc. (Biochemistry) 2003

University of Lethbridge, Lethbridge, Alberta

Professional Appointments Section Chief, Clinical Microbiology 2012- present

UCLA Medical Center, Los Angeles

Assistant Clinical Professor, Step II 2011-present

Department of Pathology and Laboratory Medicine, University of California, Los Angeles

Invited Lectures, International Meetings “Clostridium difficile disease and the role of laboratory testing in diagnosis”

Australian Society for Microbiology, Annual Scientific MeetingBrisbane, Australia 2012

Select Invited Lectures, National Meetings 1. “Microbiology for the wee ones: best practices in pediatric microbiology”

American Society for Microbiology Annual Meeting, Boston, MA 2014

2. “Clinical Microbiology Board Review Course”

American Society for Microbiology Annual Meeting Workshop, Denver, CO 2013

3. “Clinical Microbiology Board Review Course”

American Society for Microbiology Annual Meeting Workshop, Boston, MA 2014

National Committee Representation Clinical Laboratory and Standards Institute, Advisor 2013-present

Subcommittee on Antimicrobial Susceptibility Testing

Select Research Publications 44. Deak E, Miller S and Humphries RM (2014) Journal of Clinical Microbiology52:960-3.

45. Sakoulas G, Rose W, Nonejuie P, Olson J, Pogliano J, Humphries R and Nizet V (2014)

AAC58:1494-500.

46. Tewhey R, Gu, B, Kelesidis T, Giltner C, Bobenchik A, Hindler J and Humphries RM (2014).

mBio5:e894-14.

47. Humphries RM and Hindler JA (2014) Journal of Clinical Microbiology52:2177-80.

48. Charlton CL, Hindler JA, Turnidge J and Humphries RM (2014) Journal of Clinical

Microbiology. In press

49. Pollett S, Miller S, Hindler JA, and Humphries RM (2014) Journal of Clinical Microbiology In

press.

CURRICULUM VITAE

PERSONAL DETAILS Name : SHARIFAH FARIDAH BINTI SYED OMAR Position Title : Senior Lecturer of Medicine and Infectious Diseases Department of Medicine Faculty of Medicine University of Malaya Place of Current Practice : University Malaya Medical Centre Office Address : Department of Medicine Faculty of Medicine University of Malaya

50603 Kuala Lumpur Malaysia

Contact Information : Telephone – 0379493641, Fax – 0379494625 E-mail Address : sfaridah@ummc.edu.my Nationality : Malaysian National Specialist Registrar: 128831 (Internal Medicine and Infectious Diseases) MMC Registration number : MPM37384 Annual Practicing Certificate : 2777/2013 EDUCATION AND TRAINING Bachelor of Medicine and Surgery (MBChB), 1999 University of Manchester Masters of Internal Medicine 2007 University Malaya POSTGRADUATE TRAINING AND APPOINTMENTS Pre-registration House Officer Feb 2000-Feb 2001 Yeovil Hospital United Bristol Health Trust (UBHT): Frenchay Hospital/ Southmead Hospital, United Kingdom Senior Medical Officer Feb 2001-Aug 2001 Accident and Emergency Department, Bristol Royal Infirmary, United Kingdom Medical Officer Feb 2002-Apr 2002

Antifungal drug resistance:from bench to bedside S. C-A. Chen. Centre for Infectious Diseases and Microbiology, Westmead Hospital, Sydney, Australia

Failure of antifungal therapy to eradicate invasive fungal disease (IFD) is not uncommon.Antifungal drug resistance is one cause of failure yet its position in clinical failures is poorly defined. Drug resistance is an interplay of host and fungal factors. Other than pathogens which have intrinsic resistance to antifungal drugs, our increased understanding of the epidemiology of IFD has identified a number of areas of concernglobally: (i) azole, as well as echinocandin, resistance in Candida species, and (ii) azole resistance in Aspergillus spp. In Australia, about 8-9% of Candida spp. arefluconazole-resistant whilst in India and in Europe, resistance may be as high as 30-50%.Rates of resistance are higher amongst C. glabrata (15-60%) with resistance extending across all azoles, but resistance is not confined to C. glabrata. Genetic mechanisms of resistance are important but have imperfect correlation with outcomes and cannot be easily routinely implemented at the “bedside”. Hence MIC determinations remain the mainstay of identifying resistant strains. The new CLSI and EUCAST MIC breakpoints are appropriate for C. albicans, C. tropicalis and C. parapsilosis. For C. glabrata, a “susceptible-dose dependent” result is recommended for isolates with MICs of ≤32 mg/l; however in vivooutcome data documenting isolates with these MICs respond to fluconazole are sparse. For voriconazole, lack of relationship between MIC and outcomes has precluded a MIC breakpoint to guide therapy. Echinocandin resistance rates in Candida spp. also vary between regions.Amongst C.glabrata, they are as high as 15-20% with many isolates co-resistant to azoles. Resistance correlates with presence of FKS gene mutations and in turn, with clinical failure. Detection of FKS gene mutations is more reliable than MIC determination for identifying resistance. This opens up the question of whether MIC values should be used as a “screen” for resistance which can then be confirmed by molecular techniques. Azole resistance amongst Aspergillusisolates is high in Europe and in regions in India and the Middle East (3-37%). This resistance has been seen particularly in patients with chronic lung disease, with long-term azole exposure but can also occurde novo.The presence of CYP51Amutations, and the presence of the L98H mutation in the tandem repeat promoter region of this gene (termed the TR34/L98H mutation) correlates with clinical resistance. Routine detection remains dependent on MIC or ECOFF (epidemiological cut off point) determinations. An agar method to screen for azole resistance may be used. Although the overall prevalence of antifungal resistance is not high, clinical resistance is emerging. Resistant strains are a reservoir for evolving resistance through increased drug exposure.

Sharon Chen is the Director, Centre for Infectious Diseases and Microbiology Laboratory Services (CIDMLS), Institute for Clinical Pathology and Medical Research,Westmead Hospital, Sydney. CIDMLSincorporates reference laboratories in Bacteriology, Mycology, Parasitology, Virology and public health.

She is an Associate Professor at the University of Sydney, senior Infectious Diseases physician at Westmead Hospital and the Head of Clinical Mycology. She is also the medical consultant for the Molecular Mycology Research Laboratory, Westmead Millennium Institute, University of Sydney.

Her commitments outside the hospital include the immediate past scientific chair of the Australia and New Zealand Mycoses Interest Group (ANZMIG), member of the ASID Clinical Trials Network Steering Committee, member of National Antimicrobial Committee of Australia, and member of the National Scientific Advisory Committee for the Australian Society for Microbiology. She is also an active member of the International Society for Human and Animal Mycology (ISHAM), co-convenor of the ISHAM working group on Scedosporium and scedosporiosisand co-organiser of the forthcoming 19th ISHAM Congress, Melbourne, Australia (May 4-8 2015). Dr. Chen has an active research interest in medical mycology and in modern laboratory methods and technologies. These include (i) clinical and molecular epidemiology of fungalinfections, especially in immunocompromised hosts, in critically ill persons and those with chronic lung disease; (ii) noveldiagnostic methods for fungal and bacterial infections (iii) systematics of classification of fungi and bacteria (iv) novel antifungal agents and resistance to antifungal agents (v) laboratory automation and technology She has a number of nationally funded grants as a co-chief investigator and over 150 publications in peer reviewed journals. She has co-authored chapters in microbiology authoritative textbooks including one on “Aspergillus and Penicillium” in the Manual of Clinical Microbiology, ASM, 11th Edition (in Press). She is currently supervising two post-graduate research students.

Pneumococcal vaccination and disease epidemiology

Stuart C. Clarke

1 University of Southampton Malaysia Campus

2Faculty of Medicine, University of Southampton, UK

Pneumococcal disease remains a global problem despite the availability of effective conjugate

vaccines. This is due to serotype replacement disease in the developed world and delayed

implementation in the developing world. The 10-valent and 13-valent pneumococcal conjugate

vaccines (PCV10 and PCV13) are second generation PCV’s that extend the valency of the seven-

valentPCV by including three and six additional serotypes respectively. The supplementary serotypes

are highly associated with invasive pneumococcal disease and many have also been implicated in

PCV7 non-vaccine type replacement disease since PCV7 introduction. PCV10 and PCV13 have been

approved and launched in more than 100 countries worldwide, many of which have included PCV’s

as part of their paediatric national immunisation programs. The speaker will discuss the current

epidemiology of pneumococcal disease in South East Asia and elsewhere, the advances in our

understanding of carriage and disease, and the promise of next generation pneumococcal vaccines.

CURRICULUM VITAE Name: Stuart C. Clarke Present appointments: Associate Professor in Infectious Disease Epidemiology, University of Southampton Faculty of Medicine Honorary Consultant in Health Protection, HPA Southampton Visiting Professor, Faculty of Medicine, University Teknologi MARA, Kuala Lumpur Adjunct Associate Professor, School of Medicine, National University of Singapore Qualifications: 2008 Fellowship of the Faculty of Public Health of the Royal Colleges of Physicians of the

United Kingdom (Public Health) 2007 Fellowship of the Royal College of Pathologists (Medical Microbiology) 2005 MSc, DLSHTM Public Health, London School of Hygiene and Tropical Medicine 1999 PhD Medical Microbiology, University of Leicester 1995 MSc Medical Microbiology, University of Surrey Recent relevant publications: 1. Jefferies JM, Tee NW, Clarke SC. Molecular analysis of Streptococcus pneumoniae

clones causing invasive disease in Singapore. J Med Microbiol 2011; 60:750-5. 2. Tocheva AS, Jefferies JM, Rubery H, Bennett J, Afimeke G, Garland J, Christodoulides

M, Faust SN and Clarke SC. Declining serotype coverage of new pneumococcal conjugate vaccines relating to the carriage of Streptococcus pneumoniae in young children. Vaccine 2011; 29: 4400-4.

3. Ibarz-Pavon AB, MacLennan J, Andrews NJ, Gray SJ, Urwin R, Clarke SC, Walker M, Evans MR, Kroll JS, Ala’Aldeen D, Crook DW, Cann K, Harrison S, Cunningham R, Baxter D, Kaczmarski E, McCarthy ND, Jolley KA, Cameron JC, Stuart JM and Maiden MCJ. Changes in serogroup and genotype prevalence among carried meningococci in the United Kingdom during vaccine implementation. Journal of Infectious Diseases 2011; 204: 1046-53.

4. Gamblin J, Jefferies JM, Harris S, Ahmad N, Marsh P, Faust SN, Fraser S, Moore M, Roderick P, Blair I and Clarke SC. Nasal self-swabbing for estimating the prevalence of Staphylococcus aureus in the community. Journal of Medical Microbiology 2013; 62: 437-440.

5. Loman NJ, Gladstone RA, Constantinidou C, Tocheva AS, Jefferies JMC, Faust SN, O’Connor L, Chan J, Pallen MJ, Clarke SC. Clonal Expansion within Pneumococcal Serotype 6C after Use of Seven-Valent Vaccine. PLOS One, e64731.

6. Jeevajothi Nathan J, Mohd Desa MN, Thong KL, Clarke SC, Masri SN, Md Yasin R, Mohd Taib N. Genotypic characterization of Streptococcus pneumoniae serotype 19F in Malaysia. Infect Genet Evol. 2014; 21: 391-4.

7. Richardson A, Morris DE, Clarke SC. Vaccination in Southeast Asia-reducing meningitis, sepsis and pneumonia with new and existing vaccines. Vaccine 2014; 32(33): 4119-23.

8. Jefferies JM, Mohd Yusof MY, Devi Sekaran S, Clarke SC. Novel clones of Streptococcus pneumoniae causing invasive disease in Malaysia. PLOS One 2014; 9(6): e97912.

9. Cruickshank HC, Jefferies JM, Clarke SC. Lifestyle risk factors for invasive pneumococcal disease: a systematic review. BMJ Open 2014; 4(6): e005224.

10. Letouze D, Yao G, Clarke SC. The costs associated with the public health management of a cluster of meningococcal infection in England. Vaccine. 2014; 32(43): 5549-51.

Abstract: Challenges in management of severe dengue

Dengue is the most important mosquito-borne infection which has become one of the

fastest-growing global health threats. In the last 50 years, it’s incidence has increased 30-

fold. As the disease expands geographically and with the disease burden shifted to the

adults, the applicability of the 1997 case definitions was increasingly found to be limited. A

new dengue case-definition which classified the illness into dengue (with and without

warning signs) and severe dengue was henceissued by WHO in 2009based on the findings

of the DENCO study that evaluated the 1997 case definitions.For determining severe dengue,

this new classification has a higher sensitivity and specificity (up to 98% and 99%

respectively) as compared to the 1997 classification (only up to 74% in sensitivity but 100%

in specificity) in prospective studies. The main emphasis of dengue/severe denguein this new

classification help clinicians to identify and manage cases of severe dengue timely. However,

despite this, challenges in management of severe dengue remained.

Conventionally, plasma leakage has been the key feature that definessevere dengue. The

main cause of mortality isusually associated with the failure of recognition and inadequate

understanding of this uniquephenomenon in dengue. Improper assessment and

understanding ofthe perfusion stateof the patients as the disease progresses through it’s

critical phase often resulted in the delay in recognition of shock, inadequate or overzealous

fluid therapy, refractory shock and ultimately massive bleeding and death. On the other

hand, undue emphasis on bleeding as the old name denotes has also confused the patients

as well the clinicians too. Unnecessary multiple platelet and / or fresh frozen plasma

transfusion in anticipation of bleeding not only resulting in fluids overload but also not

uncommonly transfusion related lung injury too. In contrast, delay in recognition of

significant bleeding, delay in appropriate and timely red cells transfusion have also resulted

in poor outcome.

Of late, the evidence on immune activation playing an important role in determining severe

dengue are emerging. Haemophagocytic syndrome, the full blown form of immune

activation in association with severe dengue are increasingly reported. Hyperferritinemia, a

hallmark of immune activation / haemophagocytic syndrome,not only can be used as a

marker to discriminate between dengue and other febrile illnesses but also useful for disease

monitoring. Adjuvant immunotherapy may be indicated in those with severe immune

activation complicated with severe multi-organ dysfunction. Further studies are needed

urgently to deal with these immune activation issues to help delineate the appropriate

treatment approach in future.

Tan LianHuat Infectious Diseases Consultant, Sunway Medical Centre, Malaysia

Brief Curriculum Vitae

Dr Tan LianHuatgraduated from University Kebangsaan Malaysia in 1994 with a Doctor of Medicine degree. He then went on to receive a Master of Internal Medicine degree from the University of Malaya in 2001.

From 2001 – 2005, Dr Tan worked as a Clinical Specialist in the Infectious Diseases Division, at Department of Medicine, University of Malaya Medical Center. He was appointed as Senior Lecturer/Consultant in the same division from 2005 – 2008, before moving to Sunway Medical Center and assuming his current position.

Dr Tan has vast experience in dealing with both community acquired infections as well as hospital acquired infections. He has consulted on several dengue-related projects both nationally and internationally. He was involved with the WHO International Study on Dengue Case Classification and Case Management (DENCO). He is one of the lead authors for “ Chapter 2: Clinical management and delivery of clinical services” in the New edition (2009) of WHO “Dengue guidelines for diagnosis, treatment, prevention and control”. He also co-authored “Handbook for clinical management of dengue. WHO, TDR 2012”.

Last 5 years publications:

1. Yee-Ling Lau, Wenn-Chyau Lee, Lian-Huat Tan, AdeebaKamarulzaman, SharifahFaridah Syed Omar, Mun-Yik Fong, Fei-Wen Cheong, Rohela Mahmud. Acute respiratory distress syndrome and acute renal failure from Plasmodium ovale infection with fatal outcome. Malaria Journal 2013, 12:389

2. Handbook for clinical management of dengue. WHO, TDR 2012. Co-author.

3. Tan LH, Lum LC, Omar SF, Kan FK. Hemophagocytosis in dengue: Comprehensive report of six cases. J ClinVirol. 2012 Sep;55(1):79-82. Epub 2012 Jul 11.

4. Akbar NA, Allende I, Balmaseda A, Coelho IC, da Cunha RV, Datta B, Shamala Devi S, Farrar J, Gaczkowski R, Guzman MG, Harris E, Hien TT, Horstick O, Hung NT, Jänisch T, Junghanss T, Kroeger A, Laksono IS, Lum LC, Maron GM, Martinez E, Mishra A, Ooi EE, Pleités EB, Ramirez G, Rosenberger K, Simmons CP, Siqueira JB Jr, Soria C, Tan LH, Thuy TT, Villalobos I, Villegas E, Wills B. Regarding "Dengue--How Best to Classify It" Clin Infect Dis. 2012 Apr 26.

5. Lau Y-L, Tan L-H, Chin L-C, Fong M-Y, Noraishah Abdul-Aziz M, Rohela M. Plasmodium knowlesi Reinfection in Human (Letter).Emerging Infectious Diseases 2011 July; Vol. 17, No. 7.

6. Tan LH, Fong MY, Mahmud R, Muslim A, Lau YL,

KamarulzamanA.ZoonoticBrugiapahangifilariasis in a suburbia of Kuala Lumpur City, Malaysia. Parasitol Int. 2011 Jan; 60 (1) : 111-3. Epub 2010 Oct

14.

7. Unusual manifestation of cutaneous toxoplasmosis in a HIV-positive patient. Fong MY, Wong KT, Rohela M, Tan LH, Adeeba K, Lee YY, Lau YL. Trop Biomed. 2010 Dec; 27(3) : 447-50.

8. Jacqueline Deen, Lucy Lum, Eric martinez, LianHuat Tan. Chapter 2: Clinical

management and delivery of clinical services. Dengue guidelines for diagnosis, treatment, prevention and control. New edition 2009, WHO/TDR. Pages: 23-55.

9. R. Santamaria, E. Martinez, S. Kratochwill, C. Soria, L.H. Tan, A. Nuñez, E.

Dimaano, E. Villegas, H. Bendezú, A. Kroeger, I. Castelobranco, J.B. Siqueira, T. Jaenisch, O. Horstick, L.C.S. Lum. Comparison and critical appraisal of dengue clinical guidelines and their use in Asia and Latin America. International Health, Volume 1, Issue 2, December 2009, Pages 133-140.

10. Cost of dengue cases in eight countries in the Americas and Asia: a

prospective study. Suaya JA, Shepard DS, Siqueira JB, Martelli CT, Lum LC, Tan LH, Kongsin S, Jiamton S, Garrido F, Montoya R, Armien B, Huy R, Castillo L, Caram M, Sah BK, Sughayyar R, Tyo KR, Halstead SB. Am J Trop Med Hyg. 2009 May;80(5):846-55.

11. Differential expression of aldolase, alpha tubulin and thioredoxin peroxidase in

peripheral blood mononuclear cells from dengue fever and dengue hemorrhagic fever patients. Thayan R, Huat TL, See LL, Khairullah NS, Yusof R, Devi S. Southeast Asian J Trop Med Public Health. 2009 Jan;40(1):56-65.

12. The use of two-dimension electrophoresis to identify serum biomarkers from

patients with dengue haemorrhagic fever. Thayan R, Huat TL, See LL, Tan CP, Khairullah NS, Yusof R, Devi S. Trans R Soc Trop Med Hyg. 2009 Apr;103(4):413-9. Epub 2009 Feb 8.

Interferon free regimes in chronic HCV - achievements and prospects.

According to the WHO, there are approximately 130-150 million people infected with hepatitis C virus (HCV) and in each year 350 000 to 500 000 die from HCV-related liver diseases. The treatment for hepatitis C is rapidly evolving with several new drugs approved and many others in early and late phases of development. In 2011, two new direct acting anti-virals (DAAs), the first generation of HCV-NS3/NS4A serine protease inhibitors (inhibit HCV polyprotein maturation) Telaprevir and Boceprevir were approved for treatment of genotype 1 HCV in combination with the existing backbone of pegylated interferon and ribavirin. A few more DAAs were approved more recently; Sofosbuvir, a nucleotide analog NS5B polymerase inhibitor (false substrates for the HCVRNA-dependent RNA polymerase when incorporated into viral RNA cause chain termination) which is effective against HCV genotypes 1, 2, 3 and 4, Simeprevir, second wave of the first generation NS3/NS4A protease inhibitor is approved for HCV genotype 1, Asunaprevir, a second generation NS3/4A protease inhibitor is approved to be used with Daclatasvir, a NS5A inhibitor (block NS5A ability to regulate HCV replication) in genotype 1 and Ledipasvir another NS5A inhibitor is approved as a fixed dose combination with Sofosbuvir for genotype 1. All oral, interferon free combinations of drugs are now available for genotypes 1, 2 and 3 patients. In certain combinations and categories of patients, ribavirin is also not required. These regimes offer shorter treatment duration with less side-effects and higher sustained virological response rates of > 90%. The prospect of eradicating HCV with these effective HCV therapies will face many challenges like the issues of cost, diagnosing HCV infection which is a silent disease until the late stage when complications from liver cirrhosis emerge and access to care.

Tan Soek Siam, MD, MRCP Tan Soek Siam, MD, MRCP, is a senior consultant at and head of the department of hepatology, Selayang Hospital (Malaysia) and the national head of hepatology service for Malaysia’s Ministry of Health. Dr. Tan earned her medical degree at Trinity College, Dublin (Ireland), conducted her housemanship and senior housemanship in Ireland. After passing her postgraduate exams in 1995, she returned to serve as a clinical specialist at both Ipoh Hospital and Kuala Lumpur Hospital (Malaysia), in the latter hospital she started her training in Hepatology. She completed her training with a clinical fellowship at the Institute of Liver Study at King’s College Hospital (UK). Dr Tan is the honorary secretary of the Malaysian Society of Gastroenterology and Hepatology. A council member of the Malaysian Liver Foundation and the College of Physicians at the Academy of Medicine in Malaysia, she is also a member of the Asia Pacific Association for the Study of the Liver and the Malaysian Transplant Society. Dr. Tan’s research interests include acute liver failure, acute-on-chronic liver failure, chronic hepatitis B and C, autoimmune liver disease and Wilson’s disease. She is the principal investigator of numerous viral hepatitis B and C clinical trials. She is a member of the Asia Pacific Association for the Study of the Liver (APASL)-ACLF working party and author of eleven publications in peer review journals and a few book chapters.

A clinical perspective on C.difficile infection

Clostridium difficile infection is a major cause of morbidity and mortality especially with the

emergence of virulent strains which have been reported primarily in Europe and North

America. Locally, there have been reports of virulent strains and severe disease but it is

often difficult to separate out the clinical manifestations of severe C.difficile infection from

the numerous comorbidities that patients with C.diff inevitably have. There are many cases

of C.difficile from the community which have been identified as well as some in individuals

without traditional risk factors. We have learned a lot from the molecular biology of

C.difficile and how this informs clinical management and infection control. Finally, there are

a lot of novel therapies being tried including fecal transplants which are emerging as an

important therapeutic measure for refractory disease.

The epidemiology of malaria in Malaysia has undergone significant change over the last decade with P. knowlesi, formerly a relatively unknown simian parasite rapidly becoming the most predominant malaria species to infect humans in Malaysia. Infection with P.knowlesi malaria can cause significant morbidity and mortality . Studies have shown that it has 3 times higher risk of causing severe malaria compared to P.falciparum malaria. Chloroquine has been shown to be very effective in treating non severe P.knowlesi malaria. However due to frequent microscopic misdiagnosis of P.knowlesi with other species of malaria and vice versa mean that a common policy for treating all malaria species of non severe malaria with Artemesinin Combination Therapy should be advocated. The results of Prospective Study Comparing Artemesinin Combination Therapy versus Chloroquine for the treatment for non severe P.knowlesi malaria (ACTKNOW) will be presented.

Dr. Timothy William

Dr.Timothy William MBBS (Malaya) FRCP (Edin) is currently the Infectious Disease Consultant for

Queen Elizabeth Hospital Kota Kinabalu. He also has a keen interest in Malaria, TB, Meningitis,

Melioidosis and CA MRSA. His research collaborators and him have published important papers on

P.knowlesi malaria in the leading journals in Infectious Diseases. He also has much experience

managing this disease. Currently he is the Principal investigator of a number of International

Collaborative Research Projects in Malaria, TB and Meningoencephalitis. He sits on the national

management guideline committees in Infection Control, Antimicrobials, Adult Vaccination, HIV and

Malaria.

Treatment Options for Carbapenem Resistant Non-Fermenters Visanu Thamlikitkul Faculty of Medicine Siriraj Hospital Mahidol University, Bangkok, Thailand

Acinetobacter baumannii and Pseudomonas aeruginosa are the most common non-fermenters causing infections in hospitalized patients in Asia. The prevalence of carbapenem resistance rates of A.baumannii and P.aeruginosa are 50%-70% and 15%-30%, respectively. Most of carbapenem-resistant A.baumannii and P.aeuginosa are also extensively drug-resistant strains that are usually only susceptible to polymyxins and tigecycline. Evidence to date suggests that polymyxins (colistin and polymyxin B) constitute the backbone of therapy. Clinical responses of infections caused by carbapenem-resistant A.baumannii and P.aeuginosa are 40% to 70%. The reasons for observing such modest clinical responses include: the infections caused by carbapenem-resistant non-fermenters are usually very severe, polymyxins are usually given very late after the patients do not respond to conventional antibiotics, polymyxins dosing regimens are inappropriate leading to insufficient colistin level in blood and site of infection, and polymyxins are given as monotherapy. Colistimethate sodium (CMS) is an inactive prodrug of colistin and a loading dose of CMS should be given in order to achieve sufficient level of formed colistin in blood and site of infection as soon as possible. Many vitro studies reveal the synergy between colistin and many antibiotics. Randomized controlled trials of colistin plus rifampicin and colistin plus fosfomycin did not show a significant benefit in reducing mortality of the patients when compared with colistin alone. Randomized controlled trials of colistin plus carbapenem versus colistin alone are ongoing. Inhaled antibiotics for adjunctive therapy for MDR Gram negative ventilator-associated pneumonia showed no benefit on mortality in small randomized controlled studies. Intraventricular or intrathecal colistin for therapy of carbapenem-resistant A.baumannii ventriculitis or meningitis is rather safe and very effective. Nephrotoxicity is found in 30% to 60% of the patients treated with polymyxins and it is the major limitation of using polymyxins. P.aeuginosa is always resistant to tigecycline. A matched retrospective cohort study in adults with MDR A.baumannii pneumonia who received tigecycline-based therapy and colistin-based therapy revealed that the tigecycline-based therapy group had a significant excess mortality when compared with colistin-based therapy group. Therefore, polymyxins are and will be the mainstay antibiotics for therapy of carbapenem-resistant A.baumannii and P.aeuginosa infections for many years to come given that new and effective antibiotics for these resistant bacteria are not yet available.

Professor Visanu Thamlikitkul, MD, MSc Siriraj Hospital, Mahidol University Bangkok, Thailand

Professor Visanu Thamlikitkul is based in Bangkok, Thailand, where he is Head of the Department of Research and Development, and Division of Infectious Diseases and Tropical Medicine, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University.

Professor Thamlikitkul received his medical degree from the Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand and a Clinical Fellowship in Infectious Diseases from the University of Cincinnati, USA. He also holds an MSc in Clinical Epidemiology from McMaster University, Canada. Professor Thamlikitkul’s research interests lie in infectious diseases and evidence-based medicine, including research and development on treatment and prevention of antimicrobial resistance.

Widening Challenge of ESBL

Yonghong Xiao

State Key Laboratory for Diagnosis & Treatment of Infectious Diseases, 1st

Hospital,

Zhejiang University, Hangzhou 310003, China

Xiao-yonghong@163.com

The infections coursed by extended-spectrum beta-lactamase(ESBL)

producing Enterobacteriaceae is still a great challenge for clinicians and

the situation is getting worse and threaten is widening with the following

characteristics, which makes the bacterial resistance a more difficultly

tackled crisis.

1. The incidence and prevalence of ESBL (+) Enterobacteriaceae

continues to increase, with around 50-70% incidences in Asia-Pacific

area.

2. The resistant spectrum of ESBL (+) Enterobacteriaceae is getting

wider and wider, which was led by multiple resistant elements in on

germ, such as the co-exist of ESBL, Qnr,

aminoglycoside-modification enzyme genes in one plasmide and the

synergizing mechanisms of active efflux and outer membrane

protein deficiency.

3. The evaluations of ESBLs lead to the resistance not only to

beta-lactams but to beta-lactamase inhibitors.

4. ESBL(+) Enterobacteriaceae spreads widely from hospitals to

communities, which makes the antibiotic therapy of common

community-acquired infection, such as UTI, AECOPD and SSSI, more

problematic.

The universal spread and widening threaten from ESBLs will contributed

higher morbidity and mortality of patients and need urgent action to

curb the challenge.

Yonghong Xiao,MD, PhD

Yonghong Xiao. Professor and tutor for doctoral graduate, PI, Vice-director,

State Key Laboratory of Diagnosis & Treatment of Infectious Diseases, 1st

Affiliated Hospital, School of Medicine, Zhejiang University. Professor Xiao

graduated from Chongqing University of Medical Sciences with MD in 1985

and PhD in 1994. He worked in Department of Infectious Diseases, the First

Affiliated Hospital, Chongqing University of Medical Sciences, from 1985 to

2001, he took the position of department director from 1996-2001. He moved

to Institute of Clinical Pharmacology, Peking University and took the position of vice director till

2008. And he re-moved to the present hospital in 2010. Professor Xiao’s major interesting includes

infectious disease, basic and clinical research in antimicrobial agents, bacterial resistant

surveillance and mechanisms, clinical pharmacology and rational use of antibiotics. He is the

project leader of MOH national antibacterial resistant investigation net (Mohnarin) from 2005 on,

which have more than 1300 member hospitals. Up to now, professor Xiao completed more than 20

national funded studies and over 50 clinical trials of new antimicrobial agents. More than 250

peer-review papers and 20 books were published. Professor Xiao is taking more than 20 society

positions at present. He is editors or reviewers of 20 journals, too.

Contact:

State Key Lab for Diagnosis & Treatment of Infectious Diseases

1st Affiliated Hospital, School of Medicine

Zhejiang University

79#, Qingchun Road, Hangzhou, 31003, Zhejiang

e-mail: xiao-yonghong@163.com

CV Katsunori Yanagihara

Current post Professor, Nagasaki University Graduate School of Biomedical Sciences

Head, Laboratory Medicine, Nagasaki University Hospital 1991 Graduated from Nagasaki University School of Medicine 1991 Employed at the Second Department of Internal Medicine, Nagasaki University Hospital 1992 Employed at Sasebo City General Hospital 1993 Entered Nagasaki University School of Medicine Graduate School (Internal Medicine) 1997 Graduated from Nagasaki University School of Medicine Graduate School (Internal Medicine) 1997 Researcher at the Biochemistry and Molecular Biology classroom, University of Nebraska 1999 Assistant Professor at the Second Department of Internal Medicine, Nagasaki University School of

Medicine 2002 Assistant Professor at Nagasaki University Graduate School of Biomedical Sciences 2006-2011 Lecturer at Laboratory Medicine, Nagasaki University Hospital 2007-2012 Vice-director at Nagasaki University Infection Control and Education Center 2011-2012 Associate professor at Nagasaki University Graduate School of Biomedical Sciences 2013 to date Professor at Nagasaki University Graduate School of Biomedical Sciences,

Head at the Laboratory Medicine, Nagasaki University Hospital Fields of Specialty Infectious diseases, Clinical microbiology, Laboratory Medicine, Specialist physician Certified physician/supervisory physician, the Japanese Society of Internal Medicine Specialist physician/supervisory physician/ ICD (Infection control doctor), the Japanese

Association for Infectious Diseases Antibiotic chemical treatment supervisory physician, Japan Society of Chemotherapy Clinical laboratory specialist physician, Japanese Society of Laboratory Medicine

Activities at academic societies Asia Pacific society of Clinical Microbiology and Infection (director, treasurer)

Japanese Society for Clinical Microbiology (director) Japanese Society of Environmental Infections (director) Japanese Association for Infectious Diseases (councilor) Japanese Society of Chemotherapy (councilor)

Awards received 2001 Ueda memorial award/research fellowship of Japanese Society of

Chemotherapy 2005 Best poster award of the International Congress of Chemotherapy and Infection for community-acquired pneumonia 2006 Incentive award of the Japanese Society of Internal Medicine 2011 Scholarly award of Japanese Society of Laboratory Medicine

Evaluation of a multiplex nucleic acid test for detection of gastrointestinal pathogens;

Utility of Luminex xTAG GPP

K. Yanagihara

Department of Laboratory Medicine, Nagasaki University Graduate School of

Biomedical Sciences, Nagasaki, Japan

Background

Gastroenteritis is a common disease but sometimes becomes a serious problem for

individuals and the community. Because of the variety of potential pathogens, it is

difficult to detect the causative pathogens effectively using traditional diagnostic

methods. The microbiological diagnostic testing processhas several problems,

including: long time to results, lengthy amount of technician time, and often requires

multiple methods. Physiciansoften fail to orderthe correcttests for detecting the

causative microorganisms. On the other hand, microbiology laboratory staff may have

poor knowledge and experience for rareorganisms. These issues can lead to an

underestimation of the burden of gastroenteritis.

Molecular diagnostic testingaffords a faster, more comprehensive, and more sensitive

approach, resulting in identificaoin of pathogens which would have been difficult to

detect with traditional methods. Therefore, we evaluated the prevalence of

gastroenteritis-causing pathogens in a routine clinical microbiology using a qualitative

multiplex nucleic acid test, Luminex’sxTAG Gastrointestinal Pathogen Panel (GPP).

Methods

This study was performed at the Nagasaki University Hospital, a tertiary hospital with

about 850 beds, and approved by the ethics committee. The fecal specimens that were

submitted for the usual microbiological testing were prospectively collected between

June 8th and December 31st, 2012. After extraction of nucleic acid from the specimens,

15 clinicaly-relevant targets were analyzed by xTAG GPP. The results were checked

against results in the clinical microbiology laboratory database.

Results

Three hundred and six samples collected from 217 patients were enrolled. These

samples included 17 (5.6%) with positive results by traditionalmethods ordered by

clinicians (Clostridium difficile, 15; Norovirus, 1; Escherichia coli, 1). In contrast,

xTAG GPP showed positive results in 49 (16.0%) samples and detected 54 pathogens.

Shigella, Vibrio cholerae, Yersinia enterocolitica, rotavirus A and Entamoebahistolytica

were not detected. There were no specimens negative by xTAG GPP but positive by

usual testing.

Conclusions

xTAG GPP can comprehensively detect important pathogens that are overlooked in

gastroenteritis and may contribute to appropriate antimicrobial therapy selection and

enhance infection control practices.