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Epidemiology & Public Health Unit (epi@ipc) 2013The scientific activity report of the Epidemiology & Public Health Unit of the Institut Pasteur du Cambodge (epi@ipc) for the period January 1st to December 31st, 2013.

Scientific activity report

epi@ipc 2013 Scientific activity Report

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Contents Team members and functional structure of the Unit ..................................................................................................... 3 Timeline and significant events in 2013 ......................................................................................................................... 4 Students and training in the Unit ...................................................................................................................................... 4

Students ............................................................................................................................................................................ 4 Participation in training others ..................................................................................................................................... 5

National Seminar on Influenza, May 2013 .......................................................................................................... 5 CREPIN, November 2013 ......................................................................................................................................... 6 International Pasteur Rabies course, Dec. 2013 .................................................................................................. 6

Training ourselves ........................................................................................................................................................... 7 Networking and epi@ipc .................................................................................................................................................. 8

Partners in Cambodia .................................................................................................................................................... 8 Partners within IPIN ........................................................................................................................................................ 8 Partnerships at the Regional or International level ................................................................................................. 8

Scientific projects and advancement ............................................................................................................................... 9 Endemic ID (Dengue, influenza, CAP…) ..................................................................................................................... 9

DENFREE ....................................................................................................................................................................... 9 IMMI ............................................................................................................................................................................ 10

HIV/TB clinical research .............................................................................................................................................. 10 ANRS 12229 PAANTHER 01 ................................................................................................................................. 10 VCCT clinic data ....................................................................................................................................................... 10

Emerging ID / zoonoses (Leptospirosis, Chikungunya, rabies …) ....................................................................... 11 A(H5N1) ..................................................................................................................................................................... 11 Chikungunya .............................................................................................................................................................. 12 Rabies ......................................................................................................................................................................... 12 Other .......................................................................................................................................................................... 13

Prospective: flagship projects to be implemented ..................................................................................................... 14 South East Asia encephalitis project (SEAe) ............................................................................................................ 14 ECOMORE ...................................................................................................................................................................... 15

Cambodia .................................................................................................................................................................. 15 Myanmar ................................................................................................................................................................... 15

ChARLI ............................................................................................................................................................................. 16 STATIS ANRS 12290 ................................................................................................................................................... 16 Testing for genetic susceptibility to A(H5N1) ......................................................................................................... 16

Support to National authorities ...................................................................................................................................... 17 Scientific communications ................................................................................................................................................. 17

Peer-reviewed articles published .............................................................................................................................. 17 Accepted for publication ............................................................................................................................................ 18 Abstracts at conferences and meetings .................................................................................................................... 19


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eam members and functional structure of the Unit Below is a Schematic representation of functional structure of research at the Epidemiology & Public Health unit, Institut Pasteur du Cambodge (epi@ipc), 2011-2013. Leader: Dr. Arnaud Tarantola

Figure 1: epi@ipc staff members in 2013

Head of Epidemiology and Public Health Unit: Arnaud Tarantola ; Admin Assistant Mr. Try RIthy

Legend Group leader Permanent team members

Endemic diseases

Sowath Ly Nguon Kunthy ; Chan Siam; Keo Vanney ; Sopheak Sorn ; Souv Kimsan; Saman Manil; Chanthy leng; Arnaud Tarantola

Clinical Research

Laurence Borand Laurence Borand, Dim Bunnet, Pheng Phearavin; Men Nimul Roat; Phalla Chea; Te Naisim; Sophea Suom; Sophie Goyet; Keng Monorea; Manil Saman; Chanthy Leng; Arnaud Tarantola

Emerging infectious diseases / zoonoses

Arnaud Tarantola Ly Sowath; Julien Cappelle; Laurence Borand ; Pho Yaty; Chan Malen; Mousumi Rahman; Doum Dyna; Yoann Crabol; Arnaud Tarantola

Support to authorities

Arnaud Tarantola Sophie Goyet ; Souv Kimsan (bulletin) ; otherwise ad hoc

PhD student: Sophie Goyet

ANRS representative: Hubert Barennes

CIRAD guest researcher: Julien Cappelle

Figure 2: A functional diagram of the epi@ipc activities and collaborations in 2013.

Unit Themes Studies / Projects IPC collaborationsDENFREE ViroECOMORE (with Chikungunya) Viro

Influenza IMMI case-control Viro/LABM

Paanther 01 ANRS 12 229 Viro/LABM

EFV studies epi@ipc only

EFV & pregnancies epi@ipc only

Chikungunya Sequelar joint pains ; R0 epi@ipc only

Viro

Leptospirosis Incidence/multivariate/eco-epidemiological LABM

A(H5N1) Market study Viro

Encephalitis SEA encephalitis ; Ev71; Nipah Viro

Antibiotics Caliban ; AGISAR epi@ipc only

Applied epi DHHS Seminar ; AET ; outbreaks Viro / LABM

Infectious diseases ViroZoonoses Viro

Dengue weekly bulletin Viro

Programs

Zoonoses and emerging risks

epi@

ipc

Rabies lookback ; dog survey ; economic studies

Assisting Cambodian authorities Expert groups

Endemic diseases Dengue

Clinical research

Rabies

HIV/TB

T


imeline and significant events in 2013 The Year 2013 for epi@ipc was marked by several large-scale and labor-intensive projects: second year of DENFREE ; DHHS with a national seminar on influenza ; continuation

of the PAANTHER 12229 and IMMI studies; implementation of ECOMORE ; development of the SEA encephalitis project. Some permanent staff members left the team (PHENG Phearavin, KEO Vanney) while others joined the team (Mousumi RAHMAN; DOUM Dyna; TRY Rithy; KEO Monorea ; Yoann CRABOL). Laurence BORAND successfully sat her PhD in November 2013 (Université Pierre et Marie Curie, Paris). 2013 was an important year for increased collaboration in the Region.

tudents and training in the Unit The unit has a mandate to undertake training in and outside IPC, constantly improving staffs’ skills and helping in the ongoing development of Cambodia and the Region through capacity building.

Students Laurence BORAND successfully sat her PhD in November 2013 (Université Pierre et Marie Curie, Paris).

Sopheak HEM successfully sat her Doctorate of Pharmacy on December 23rd (University of Health Sciences, Phnom Penh). Her thesis subject was “Etude de la morbidité due à la Leptospirose dans des communautés rurales à Kampong Cham, Cambodge”. Her co-supervisors were Dr. CHOU Monidarin (UHS) and Dr. Arnaud TARANTOLA (epi@ipc).

Natalie MOYEN worked in the Unit in January-March 2013 in collaboration with Drs. Julien CAPPELLE and A. TARANTOLA, laying the grounds for an in-depth study of the introduction, the determinants and

dynamics of Japanese Encephalitis in the urban setting. She went on to join the Veterinary Epidemiology program at the Royal Veterinary College, London and will return in 2014.

Beatriz GALATAS, a student of the Epi MsC program at the London School of Hygiene and Tropical Medicine (University College London) did her Summer Project dissertation on “Chikungunya Virus in Cambodia: An Analysis of its Clinical Presentation, Risk Factors and Predictors of Chronic Disease”.

As part of the requirement for his second year of SAEPS Master (Université de Montpellier) Ludovic CHIFFOT undertook a field project on “Perception des rongeurs et des risques sanitaires associés dans les zones rurales du Cambodge : application de méthodes participatives”.

As part of the requirements for her PhD at Université Montpellier 2, Sophie GOYET undertook an exhaustive literature review and oversaw the work of Messrs. SOCHEAT Touch and SAMAN Sovannchhorvin, both students from NIPH’s MPH program.

Camille AGOSTINI joined the unit in November 2013 for a 6-months Residency in Public Health (Montpellier Medical Univ.).

Ms. Emily McLEOD is a student from the Epidemiology program at the Australian National University. In collaboration with Dr. David HARLEY and Dr. Elvina VIENNET, A. Tarantola will help supervise her epidemiology dissertation on the data from the Dengue 2011 Kompong Cham study.

In 2013, A. Tarantola mentored Mr. SOUN Chen, a student of the Applied Epidemiology Program, a national field epidemiology training program (MoH & WHO).

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Table 1: Students who received training at or in connection with epi@ipc in 2013.

Name Degree Institution Time period Subject

Ludovic CHIFFOT MSc SAEPS Montpellier 2 March-Jun 2013

Perception of rodents and risks of disease: a participatory approach

Chen SOUN

Epi Cambodia’s AET

Jan – Aug 2013

MOH, WHO and CDC-supported Applied field epi training for Provincial epidemiologists

HUL Vibol

MS Biodiv.& Conservation

IPC-Viro, Royal University of Phnom Penh

July-Nov 2013

Ecology of Flying Foxes (Pteropus sp) and Assessment of the Risk of Emergence of Nipah virus in Battambang and Kandal provinces, Cambodia

Nathalie MOYEN - IPC Jan-March 2013

Qualitative Risk analysis of JE amplification by pigs transiting in a Phnom Penh slaughter house and potential human infections

Sébastien REVEL DVM internship

ENV de Toulouse

July-Aug. 2013

Ecology of Pteropus sp bats and risk of Nipah virus emergence in Cambodia

Camille AGOSTINI

MD internship CHRU Montpellier

Nov 2013-Jul 2014

Clinical research

HEM Sopheak Pharm D USS, Phnom Penh

Jan.-Dec 2013

PhamrD thesis on leptospirosis in the Cambodian rural setting

TOUCH Socheat MPH NIPH March – May

2013 Systematic review on human health research production in Cambodia. SAMAN

Sovannchhorvin

Stéphanie GUILLET

MD internship ANRS Nov 2012 – Apr. 2013

Initial viral load to screen resistance mutations for pretreated patients in the ESTHER program of Calmette Hospital, Phnom Penh, Cambodia, and update on epidemiology of HBVin Cambodia

Participation in training others The epi@ipc team was involved in or conducted several trainings, workshops or lectures.

National Seminar on Influenza, May 2013 Thanks to DHHS funding, a National seminar on influenza was set up by epi@ipc in collaboration with the Ministry of Health’s Center for Communicable Diseases Control. As part of strengthening IHR, the overarching aim of this training was to provide Cambodian clinical and epidemiologist colleagues with updated, state-of-the-art knowledge on seasonal, pandemic and avian influenza in a format and language easily understood, to serve as an easily-accessible reference for the next few years. The MOH/IPC National Seminar on Influenza was held in the Crystal Ballroom of the Phnom Penh Hotel, Phnom Penh, Cambodia, from 20 to 23 May 2013, inclusive. The invitees were the head physicians of all the provincial reference hospitals in Cambodia and the epidemiologists coordinating the MoH Rapid

Response Teams (RRT) in each of Cambodia’s 23 provinces and Municipality of Phnom Penh. The Municipality of Phnom Penh having several reference hospitals, the head physicians of all these important hospitals were invited. In total, 49 persons attended the seminar (25 clinicians; 24 epidemiologists), of which 47 attended all 8 sessions. The material has been made freely available on the web1 and was used for training on influenza in Cameroon.

1 http://www.pasteur-kh.org/sng/


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CREPIN, November 2013 The first Clinical Research in the Institut Pasteur International Network Course (CREPIN) was held at the Institut Pasteur in Cambodia because nearly ¼ (10/44) of clinical research projects conducted in or with the IPIN and examined by the CoRC between 2010 and 2012 were conducted in Asia. Of these, 8 involved the IPC team directly. Drawing on French experts’ in-depth knowledge of ethics regulations and the frontline experience acquired by epi@ipc teams, this course provided state-of-the-art training for 18 RIIP and other participants from Cambodia, Vietnam and China from November 25-29, 2013.

International Pasteur Rabies course, Dec. 2013 Staff from epi@ipc participated in the Workshop on Surveillance and Control of Rabies2 held at the Institut Pasteur de Dakar in collaboration with WHO from December 03-14, 2013. The purpose of this course was to provide practical training on rabies with a special focus on Africa for students and professionals of animal and human public health sectors. The course emphasized the need for a multidisciplinary approach and intersectoral cooperation. Epi@ipc contributed a presentation, participation to a round table and a case study on rabies risk management.

2 http://www.pasteur.sn/index.php?option=com_content&view=article&id=176:atelier-rage&catid=45:actualites


Table 2: Training and workshops to which epi@ipc staff contributed (presentations…)

Name Degree Institution Date Subject A. TARANTOLA MSc Epi vet Cirad 12/11/13 Surveillance and detection of

emerging infectious diseases S. LY AET MoH / WHO 28/01/2013 Zoonoses A. TARANTOLA AET MoH / WHO 04/05/2013 Public Health Literature Review

A. TARANTOLA Pasteur Rabies

course IP / WHO / OIE 05/12/13 Presenting rabies data,

roundtables, case studies A. TARANTOLA DHHS

workshop Cameroon

RIIP 04/10/13 Scientific communication with a presentation on A(H5N1) epidemiology

A. TARANTOLA Training workshop

RIIP 08/10/2013 Epidemiology and surveillance: Fundamentals and the example of Chikungunya

L. BORAND Training workshop

PHPT Chiang Mai 12/03/2013 Introduction to clinical Research

L. BORAND CREPIN IPC Several days Good clinical Practice S. LY AET MoH / WHO 30/01/2013 Presentation of Trapeang Roka

Chikungunya investigation J. CAPPELLE DVM Royal University of

Agriculture 19-20 /06/2013 1st International Consultative

Workshop on Development and Implementation of DVM Program in RUA

Training ourselves The table below lists epi@ipc staff who received training in 2013, including in the seminars and courses outlined above. In-house academic training is a challenge in an Epidemiology and

Public Health Unit with staff of diverse levels, missions and areas of expertise. A strategic choice was therefore made to promote self-training through cost-free web-based educational offers. All epi@ipc staff member has received CITI certification.

Table 3: Continuing training for epi@ipc staff in 2013

Name Provider Institution Duration Time period Subject S. GOYET Coursera Uni of Michigan 9 weeks Social network analysis M. CHAN Coursera Princeton University 12

weeks May 2013 Statistics

A. TARANTOLA Coursera Uni. Pennsylvannia 8 weeks Sept-Oct 2013 Vaccines M. SAMAN Uni of Michigan M. RAHMAN Coursera 9 weeks Social network analysis A. TARANTOLA GRC 1 week July 7-12, 2013 Encephalitis S. GOYET CREPIN IP / PIC 1 week 15-29/11/13 GCP and clinical Research B. DIM CREPIN IP / PIC 1 week 15-29/11/13 GCP and clinical Research P. CHEA CREPIN IP / PIC 1 week 15-29/11/13 GCP and clinical Research S. SUOM CREPIN IP / PIC 1 week 15-29/11/13 GCP and clinical Research M. KEO CREPIN IP / PIC 1 week 15-29/11/13 GCP and clinical Research D. DOUM MPH NIPH 2 years Ongoing Epidemiology & PH


etworking and epi@ipc

Partners in Cambodia Ties are being developed with researchers

from the Institute of Tropical Medicine in Antwerp, Belgium, both through publications and tentative collaborations on clinical research projects at the Sihanouk Center for Hope Hospital.

Through his continuing work on the ecology of fruit bats in Cambodia, J. CAPPELLE has deepened ties between the Unit and the Centre for Biodiversity Conservation, Royal University of Phnom Penh.

Researchers from the US-CDC participated in the National Seminar on Influenza and delivered presentations.

Partners within IPIN Funding was obtained from Pasteur Paris to hold a 3-day meeting among IPs active in the field of the study and prevention of rabies. Many collaborations have been undertaken between the Instituts Pasteur in Antananarivo, Dakar, Paris and Phnom Penh in the past years, helping improve patient management, scientific knowledge and giving rise to publications. This could now be extended to include Cameroon. The focal points have expressed their interest in rabies collaborations, reaching a consensus on the need to meet to exchange experiences, views on issues, to share tools and to begin formulating a structured research program for rabies epidemiologists and virologists across some Pasteur Institutes. This would be done with backing from Dr. H. Bourhy’s WHO collaborating Centre for Reference and Research on Rabies as a scientific point of reference. Without anticipating the conclusions of discussions and debates, preliminary exchanges bear on an overarching objective: the possibility of conducting well-targeted and well-structured integrated research to support the reduction and control of rabies worldwide. Only a handful of centers around the world, associating epidemiological + virological capabilities + rabies clinics + endemic setting (est. 30 000 referrals, >230 confirmed rabid bites/year) are capable of generating enough cases in a reasonably short time to conduct such projects effectively.

Similarly, contacts are being made across Institut

Pasteur epidemiology units in Dengue-or Rabies endemic areas to identify collaborative research projects to answer research gaps.

Initial contacts were made with S. CAUCHEMEZ at the Analysis and Modeling of Epidemic Dynamics Unit, IP Paris.

Partnerships at the Regional or International level A. TARANTOLA was co-leader of the GREASE network Bangkok reunion in January 2013. A presentation was delivered as part of a workshop on how to apply risk assessment/risk analysis to rodent borne diseases data in order to evaluate zoonotic risks and its perception. Epi@ipc was a partner of the applicant participating in the action led by CIRAD at Kasetsart University, which secured EuropeAid funding and is the focal point at IPC for the “ComAcross – Companion Approach for cross-sectoral Collaboration in health risk management in SEA” project.

The GAVI Alliance Board meeting was held in November 2013 in Phnom Penh. This was an opportunity for a “field visit” on 20/11/13 by a number of the GAVI Alliance Board members to IPC, with special interest in rabies and rabies prevention implementation studies. A leaflet on IPC research on vaccine-preventable diseases was edited.

Epidemiological findings and issues were discussed during a visit by the Executive Director of the Clinton Health Initiative (CHI) on 27/06/13 and during a meeting dedicated to the A(H5N1) situation in Cambodia with Dr. Dennis CARROLL from USAID on 15/11/13.

Contacts were made with PREVENT for increased collaboration during field studies focusing on A(H5N1) risks in affected Cambodian villages.

J. Cappelle undertook a one-month mission to support the WHO China office in Beijing in April 2013 at the height of the A(H7N9) emergence crisis.

Laurence Borand supervised monitoring activities in a clinical research conducted in Vietnam in collaboration with the International Union Against tuberculosis and Lung Disease.

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Field data collection for DENFREE, a major Dengue study, has been completed.

Figure 3: epi@ipc long-term partnerships and shorter-term collaborations

cientific projects and advancement Projects were initiated in 2013 or continued from 2012. These projects and activities are

in the line of the strategy defined for epi@ipc and described in Figure 2.

Endemic ID (Dengue, influenza, CAP…)

DENFREE

Epi@ipc team leaders Ly S, A. Tarantola

Objective and summary of results IPC is participating in DENFREE, an ambitious 3-year study. Samples from Cambodia will be analyzed and shared with an extensive network of world-renowned research laboratories to assess the various determinants associated with asymptomatic Dengue infection. The DENFREE study began on 24/06/2012 in the Kampong

Cham study site3. From 01/01 to 31/12/2013, a total of 401 (53.7%) confirmed dengue cases among 747 patients in 3 hospitals and 26 (15.0%) confirmed dengue cases among 173 febrile cases in 21 villages gave rise to 102 completed investigations in 2,086 households (confirmation by NS1 rapid test or by PCR) of 77 villages. In these houses, 5,614 persons aged ≤ 30 years agreed to participate and 269 (4.8%) tested positively for dengue by PCR (no

NS1 testing of these samples). Of these confirmed dengue participants, 221 (82.2%) presented symptomatic infection by DENV and 45 (0.8% of 5,614 participants, 16.7% of 269 positive participants) presented truly asymptomatic infection; infection status was not available for 3 positive participants.

Financial support Funded by EU-FP7.

3 In 2012, a total of 169 confirmed dengue cases in 3 hospitals and 12 confirmed dengue cases in 7 villages gave rise to 98 completed investigations in 1002 houses of 46 villages. In these 1002 houses, 3090 persons aged ≤ 40 years agreed to participate and 111 (3.6 %) were tested positive for dengue by NS1 rapid test or by PCR. Of these tested participants, 90 (81.1%) presented symptomatic infection by DENV and 21 (0.7% of 3090 participants, 18.9% of 111 positive participants) presented asymptomatic infection.

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Early analyses across the entire PAANTHER dataset to Oct 25th, 2013 suggest that GenXpert testing is performant for diagnosing TB in HIV-infected children compared to culture, and that standard and alternative samples seem to perform in the same way.

IMMI

Epi@ipc team leaders M. Saman, A. Tarantola

Objective and summary of results A prospective case-control study is under way to compare factors associated with influenza-like illness (ILI, outpatients) versus severe acute respiratory illness (SARI, inpatients). This study aims to identify the epidemiological, clinical, bacteriological, virological and immunological determinants of influenza severity, including A(H1N1)pdm infection, in a developing country. It is being conducted in Asia (Cambodia) and Africa (Cameroon & Madagascar). From September 2011 to December 2013, a total of 1042 patients were screened in Cambodia. Of these, 210 (20.1%) were tested positive by RDT, seven refused further testing and 203 were tested by PCR: 2 (1%) were PCR-negative and 201 (99%) were laboratory-confirmed influenza virus (RT-PCR positive). These 156 and 45 patients from Takeo and Calmette hospitals, respectively, were severe in 54 cases and outpatients in 147 cases. The viral strains involved were A(H1N1)pdm, A(H3N2) and Influenza B. There were 13 influenza B-infected patients found to be co-infected with Bocavirus, Coronavirus, Respiratory Syncytial Virus, Rhinovirus and Adenovirus; 1 influenza A(H3N2)-infected patient was co-infected with human Metapneumovirus. Viral coinfection status of 21 other patients is still being determined.

Financial support Funded by Institut de Microbiologie et des Maladies Infectieuses (IMMI).

HIV/TB clinical research

ANRS 12229 PAANTHER 01

Epi@ipc team leaders L. Borand

Objective and summary of results Diagnosing tuberculosis if difficult in children, especially in case of HIV/TB coinfection (paucibacillary disease and low specificity of clinical and radiological findings). ANRS 12229 PAANTHER 01 seeks to improve TB diagnosis in HIV infected children. It evaluates diagnostic effectiveness and feasibility of GenXpert MTB/RIF testing in HIV-infected children with suspected TB in 8 hospitals in Burkina Faso, Cambodia, Cameroon and Vietnam. The following samples are collected, cultured and tested by GenXpert MTB/RIF: 1) standard samples: 2 gastric aspirates (GA) or spontaneous expectorates (SE); 2) alternate sampling: 1 nasopharyngeal aspirate (NPA), 1

stool sample and 1 string test (ST) in children aged ≥4 years. Unwanted effects (UE) and tolerance (FLACC behavioral scale) of GA, NPA and ST were assessed. To December 1st, 2013 there were 317 inclusions in total in the 4 countries (75% of the targeted 420 inclusions). There have been 85 inclusions in Vietnam, 37 in Burkina Faso and 73 in Cameroon. In Cambodia, a total of 122 children were included since 27 April 2012 (86% of the

targeted 140 inclusions). In Cambodia, median age is 8 years (5.9 – 10.4); 56 are girls (47.5%); 84 are malnourished with a weight-for-age z score < -2 (68.9%). 79 were receiving ART at admission (64.7%). Early analyses across the entire study dataset to Oct 25th, 2013 suggests that GenXpert testing is performant (Se 90.0% ; Sp: 98.7%) for diagnosing TB in HIV-infected children compared to culture and that standard and alternative samples seem to perform in the same way.

Financial support Funded by Agence Nationale de Recherche contre le Sida et les Hépatites (ANRS).

VCCT clinic data

Epi@ipc team leaders A. Tarantola

Objective and summary of results IPC implemented the first HIV counseling and testing center (VCCT / CDAG) in Cambodia in


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The analysis of the 15- year VCCT database from a single and vantage point provides a unique viewpoint on the HIV/AIDS epidemic in Cambodia.

1995 (there are now 250+ thanks to the national AIDS program). Over the years, the same questionnaire was administered to people before testing. In 2012 we performed a cross-sectional analysis of the anonymized VCCT database, assessing risk factors’ progression as the epidemic evolved over 15 years (April 1996

- December 2011, inclusive). The progression of risk ratios for sociodemographic and self-declared risk behavior associated with a positive result were analyzed. Logistic regression models were used for uni- / multivariate analyses to assess overall risk factors of HIV positivity using hierarchical

modeling. The database contained 83810 HIV-tested individuals; 13295 (15.9%) tested positive. HIV positivity among VCCT users decreased from 14.2% in 1996 to 6.5% in 2011. Factors associated with HIV positivity were being aged 35-44, being female, being tested early in the study period, being illiterate, residing outside the capital city, occupations (police & military, basic workers, sex industry), being “Vietnamese” (likely proxy), not living with partner, age The analysis of the 15- year VCCT database from a single and vantage point provides a unique viewpoint. Documented seroprevalence is high compared to the general population, but trends in factors’ risk ratios were documented as the epidemic unfolded and changed over a 15-year period. IDUs, blood transfusion recipients and children of positive parents remain at increased risk and could benefit from further interventions. The database is being shared with the national partners and will be used to document changes associated with prevention strategies in population subgroups.

Financial support Self funded.

Emerging ID / zoonoses (Leptospirosis, Chikungunya, rabies …)

A(H5N1)

Clinical review

Epi@ipc team leaders S. Ly, A. Tarantola

Objective and summary of results A national seminar on influenza provided an opportunity to compile and carefully review clinical, biological and radiological data in confirmed A(H5N1) cases. The data presented and discussed during a workshop on May 7, 2013, involving all stakeholders were all drawn from the hospital clinical records using a single, complex but thorough questionnaire. This questionnaire is based on the ISARIC/WHO initial clinical form, completed with some items from an earlier IPC questionnaire (to include details on pulmonary auscultation, Glasgow scores and poultry exposure). This questionnaire was presented to partners who will strive to use this clinical tool to document confirmed cases from now on, as part of a MOH-sponsored effort to standardize case documentation and data collection in the health care setting.

Financial support Funded by Department of Health and Human Services (DHHS).

Market study


Objective and summary of results A(H5N1) is now enzootic to Cambodia, with a local clade being increasingly identified in poultry cases. Previous research showed that increased risk is associated with poultry commerce before big celebrations such as the lunar New Year, Khmer New Year and Pchum Ben. Thanks to DHHS funding, a prospective 12-months cohort study in 125 poultry workers at baseline and/in 4 poultry sites was undertaken to determine the baseline prevalence and increases due to poultry trade and to determine A(H5N1) exposure levels and consequences in poultry workers. A total of 4 sampling campaigns (V1-V4) were undertaken, including a baseline. To December 1st, 2013, a total of


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1068.30 person-months of exposure were documented in these workers. Testing of V4 samples is ongoing, but one case with elevated antibody was identified during V2 at O-Russey market (poultry worker). To 25 June 2013 (all V3 samples have been tested) the exposure period (persons x days between visits) is 17,793 person-days (593.1 person-months or 49.4 person-years). The preliminary estimated incidence rate is therefore calculated at 1.7 p. 1000 person-month [Poisson CI95%: 0.2 – 12.0%] or 20.4 cases per 1000 person-years [Poisson CI95%: 13.2 – 31.5%].

Financial support Funded by Department of Health and Human Services (DHHS).

Chikungunya

Joint pain one year after Chikungunya emergence


Objective and summary of results IPC conducted the first full documentation of a re-emergent Chikungunya outbreak in Asia. The outbreak’s R0 has been computed and is being published. The team returned to the outbreak site at 1 year to assess the prevalence and intensity of sequelar joint pains. Of the 190 CHIKV IgM or PCR positive individuals in 74 households identified during the 2012 outbreak investigation, 172 (90.5%) individuals in 63 (85%) households were surveyed again at the one-year follow up. 73/165 (42%) individuals (7 undocumented) said they had arthralgia at one year, and 143/172 (83%) reported arthralgia during the 2012 outbreak. After one year, fatigue (51%), arthralgia (49%), sleeping disorders (32%) and myalgia (30%) were the symptoms most frequently reported among patients found CHIKV positive in 2012. Arthralgia was most severe in the knees (43%), ankles (31%), wrists (25%) and hands (23%). Middle age, males

(adjOR 1.54, 95%CI 0.92-2.74), middle socio-economic status and using a traditional latrine (adjOR 6.20, 95%CI 1.1-34.3) were associated with higher odds of CHIKV infection, while indoor occupations (adjOR 0.31, 95%CI 0.12-0.82) were associated with lower odds. There was no evidence of an association between arthralgia at time of infection and sequelar arthralgia (adjOR=1.11, 95%CI 0.34-3.60, p-0.83) after adjusting for age, sex, occupation, socioeconomic status and flavivirus co-infection. The results from this analysis are in line with previous research conducted on the re-emerging strain of CHIKV. Its clinical presentation and debilitating sequelae demonstrate the potentially negative social an economical impact of the virus on newly endemic populations.

Financial support Self-funded (study cost = 900 USD)

Rabies

Rabies exposure lookback study


Objective and summary of results

During 2000-2010, the team at Institut Pasteur du Cambodge (IPC)'s Rabies Prevention Center administered post-exposure prophylaxis (PEP) to some 168,980 persons. About 1,650 (1.0%) of these persons brought a dog’s head for testing at IPC's virology unit, Cambodia’s national reference laboratory for rabies, and the dog’s head was confirmed positive in about 50% of cases. Of these persons exposed to a confirmed rabid dog, 1,198 received ID Verorab, of which

345 (28.8%) received <5 sessions Verorab ± ERIG. The objective of this study was to document the outcome in PEP patients bitten by confirmed rabies-positive dogs, by number of vaccine sessions.

Patients were identified retrospectively, contacted by telephone using a specifically developed strategy and house visits were organized

for cases that could not be identified by name through phone calls to village chiefs. The last visit was on July 5th, 2013.


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As of Dec. 31st, 2013, a total of 1,063 (88.7%) patients were traceable, of which 13 had died (1.2%). Among these, 3 were compatible with a rabies deaths. A total of 135 (11.3%) patients remained untraceable. They include 131 patients that were truly lost to follow-up as they could not be identified by phone call to village chiefs and by visit to their resident village (including 62 Phnom Penh residents), 4 patients whose names were known by locals but whose health status information could not be retrieved. Follow-up at 6 months continues prospectively (519 patients from January 2011 to 31st June 2013; 1 death). Preliminary data find no measurable difference in outcome between (ERIG +) 5 and 3 sessions at this point.

Financial support ACIP

Dogcount survey

Epi@ipc team leaders J. Cappelle, A. Tarantola

Objective and summary of results Cambodia is a highly rabies-endemic country where an estimated 810 human lives were lost to rabies in 2007 for an estimated incidence of 5.8/100,000 (95% CI 2.8-11.5). No canine vaccination has been implemented to date. A limited canine rabies vaccination campaign was held in December 2012 – January 2013 in 15 Cambodian villages using a donation of vaccines by US-CDC in Bangkok. Such a campaign offers a much-needed opportunity for research in Cambodia, where canine rabies vaccination is not routine. In order to monitor the evolution of the vaccination coverage rate of dogs after a vaccination campaign, the epi@ipc team conducted a survey in collaboration with NAVRI of all the households of the five villages included in the campaign in Takeo province, six months after vaccination. A 1-page questionnaire was administered in each of 644 households interviewed over two days. Data were double-entered at epi@ipc and the database cleaned. Among the 644 households, 362 (56.2%) had vaccinated dogs, 161 (25.0%) had unvaccinated dogs and

121 (18.8%) had no dogs. A total of 532 dogs entered the population and 288 dogs exited the population between Jan-Aug. The total dog population was 1,068 in January 2013 and 1,312 in August 2013, for a 244-dog (23%) increase over a 6-months period. The total dog : humans ratio was 1 : 3 (1068 dogs, 3338 humans) in January 2013 and 1 : 2.5 (1312 dogs, 3338 humans) in August 2013. The vaccination coverage declared by interviewees was 63.2% (total 675 living vaccinated dogs) in January 2013 and 36.7% (481 living vaccinated dogs) in August 2013, for a 26.5% vaccine coverage decrease over a 6-months period. A repeat survey will be conducted at one year, in January 2014.

Financial support Self-funded (study cost = 448.86 USD).

Other

A participatory approach to assess villagers’ knowledge & perception of rodent-borne diseases

Epi@ipc team leaders J. Cappelle, A. Tarantola

Objective and summary of results Cambodia is currently undergoing intense anthropisation. Increasing contacts between wildlife and humans raises the question of related risks for public health. Previous studies proved the existence of pathogens in rodents, which can be transmitted to humans, in Mondulkiri and Sihanouk provinces of Cambodia. Our study, focused on risks related to leptospirosis, aimed to assess the perception of villagers about the rodents and associated

health risks. A participatory approach was chosen to meet study objectives, focused on the importance of zoonoses among other diseases, and the perception of rodents and associated practices. For each province, eight villages were involved in the study, and meetings were organized with the villagers. The “Q method”, used in sociology and applied in epidemiology, was implemented

during our fieldwork to enhance data on villagers’ knowledge and management of risks.


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During the meetings, only two zoonoses were clearly named and identified by villagers: rabies and avian influenza. These diseases were ranked with a low importance compared to other diseases. In addition, rodents are considered as pests, and no species are differentiated, except in the case of Mondulkiri. The villagers did not identify any risk related to rodents, and they have a lot of unsafe practices in terms of leptospirosis. These results emphasize the urgency and the need to inform human health and animal health local actors and villagers about health risks related to rodents and how to prevent them.

Funding Cirad

Participation to M. bovis study

Epi@ipc team leaders F. Goutard, A. Tarantola

Objective and summary of results A study was undertaken by CIRAD, in collaboration with IPC to ascertain the disease burden of M. tuberculosis in Cambodian cattle.

Every morning, at the time of slaughter, two lymph nodes (mediastinal and bronchial) and a certain amount of blood on dry tubes were collected per carcass in a convenience sample. The date of slaughter, sex, age, species, and the province of origin of the animal were also collected. The collection was made 5 days a week for 5 weeks and until 396 lymph nodes and 376 blood samples (16 samples were hemolyzed at the beginning of the collection, and one sample was not exploitable serum). 3 Blood samples were found using Rose Bengal. In all, 168 lymph nodes were cultured. Among these, 85 cultures remained negative, 37 were positive for mycobacteria (33 for M. bovis; 4 were culture-positive for NTM) and 6 were contaminated. The samples are currently being sequenced at INSERM in Montpellier, France.

Funding Cirad

Ecology of Flying foxes and the risk of Nipah virus emergence in Cambodia

Epi@ipc team leaders J. Cappelle

Objective and summary of results IPC initiated an eco-epidemiological study of Flying foxes, reservoir of the Nipah virus. We monitored the reproduction phenology of a population of Lyle’s flying foxes (Pteropus Lylei) using two different census methods to target the surveillance of NiV. Our results showed a synchronized reproduction of the flying foxes population at our study site with a pulse of juveniles in April-May. A first batch of 129 samples collected in these months was tested for NiV. Two samples were positive. We thus detected NiV in Pteropid bats with a limited number of samples tested, showing that ecologically-targeted surveillance may help optimize the detection of emerging pathogens in wildlife. Our study suggests a peak of NiV circulation in Flying Foxes between April and June. Future research at IPC will focus on assessing the risk of emergence of Nipah in humans and domestic animals during that period of increased risk of transmission in relation with the potential routes of transmission identified such as hunting, fruit contamination, market contamination or palm sap drinking.

Financial support SEAe project

Prospective: flagship projects to be implemented

South East Asia encephalitis project (SEAe) The surveillance and investigation of acute encephalitis syndrome are of utmost public health importance, both locally in SEA and globally. This new initiative is called the sea project, for South East Asia encephalitis. In Cambodia, it will be conducted based on patients recruited at the Kantha Bopha hospital, Phnom Penh. This study will bring together clinical and epidemiological data, lab data, state-of-the-art virology and wider perspectives from the social sciences and ecoepidemiology. Work Package 1 (Clinical and Field Epidemiology) will be responsible for the rigorous identification and inclusion of infectious encephalitis cases, the collection and storage of clinical data and forwarding of biological samples to the lab for microbiological diagnosis. Clusters of cases or identified new pathogens will trigger field investigations, in close


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Jointly with CNM and CDC at the Ministry of Health, IPC is implementing ECOMORE, a project on the improvement of monitoring of disease emergence and progression related to changes in human demographics and transportation in Cambodia.

collaboration with public health authorities. Work Package 1 (Laboratory Diagnosis) will improve the microbiological diagnosis of known pathogens by strengthening capacities in the selected clinical site in order to provide the clinicians with state-of-the-art and timely laboratory diagnosis for the microorganisms accessible to treatment. Molecular diagnostic tools will be implemented. This WP will also include the detection and characterization of new or unusual pathogens in the samples of unknown etiology by using a combined approach: pan-generic PCRs, cell cultures, electron microscopy, High Throughput Sequencing (HTS). Work Package 3 (Ecoepidemiology) will document and analyze collective and environmental risk factors related to cases in order to improve the understanding of human infectious encephalitis epidemiology in Cambodia and the rest of the participating Southeast Asian countries, integrating potential environmental, epidemiological and sociological factors, and provide the authorities with knowledge to inform adapted surveillance, control and outbreak investigation methodologies. National Ethics Committee on, Human Research approval #0156 NEHCR was granted on 26/08/2103. The study in Cambodia should last three years.

ECOMORE

Cambodia Road use, Outbreak Amplification and Disease Surveillance (Roads) is the implementation of the ECOnomic Development, ECOsystem MOdifications and Emerging Infectious Diseases Risk Evaluation (ECOMORE) project in Cambodia. It is a 3-year project aiming to stimulate and federate a dynamic of national collaborations to strengthen the Cambodian surveillance capacity on emerging vector-borne diseases, using Chikungunya and Dengue as proxy. Five tasks have been identified to achieve this goal. Eight cities at crossroads in Cambodia have been selected as study sites: Takeo, Phnom Penh, Kampong Cham, Kampot, Battambang,

Kratie, Kampong Chnang and Kampong Speu. Task 1 will assess the national dengue surveillance system to provide a set of recommendations to improve the system, if needed. Task 2 will aim at monitoring dengue cases and virus strains in 8 public sector surveillance sites along major road axes in Cambodia to better analyze the potential role of the development of transportation

means in the spread of diseases. Task 3 aims to extend a robust syndromic surveillance system in cooperation with the private healthcare sector to provide a more accurate burden of dengue-like disease cases. This will be done after Task 2 has helped build trust between stakeholders. Task 4 plans to develop and test a simple entomological tool to assess whether sporadic increases of vector population are linked with outbreaks, in order to provide early warning of dengue

outbreaks. Task 5 will use the above mentioned data to develop a mathematical model of infectious processes associated with their environmental and socioeconomic factors in order to better predict vector-borne disease transmission. The studies will be organized in referral hospitals, private clinics and neighboring villages of selected cities by IPC in collaboration with the National Dengue Control Program, CNM and the department for Communicable Disease Control at MoH. National Ethics Committee on, Human Research approval #0144 NEHCR was granted on 26/08/2013. The data collection in Cambodia should last two years.

Myanmar Epi@ipc contributes to an ECOMORE project in Myanmar (WP Leader: Dr. Philippe Buchy). The project aims to capacitate the National Health Laboratory for the diagnosis of viral and bacteriological pathogens of public health interest. This improved/strengthened competence will immediately benefit individual and public health by being applied to the surveillance of some infectious diseases causing SARI which are major causes of morbidity and mortality, particularly in children.

A Yangon, ICU-based sentinel surveillance will document 600 to 800 SARI in children and test 17 viruses, some atypical or sensitive bacteria and all common bacteria causing severe respiratory diseases


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over a period of 2 years. This will allow early detection of new / emerging pathogens or outbreaks related to SARI in Yangon, including potential public health events of international concern (PHEIC) which are notifiable under the Revised IHR4.

Epi@ipc will also contribute by training some colleagues from Myanmar in surveillance and data management.

ChARLI The objective of the Children’s Antibiotic Resistant infections in Low Income Countries (ChARLI) project is to estimate the incidence of antimicrobial-resistant bacteria in the first two years of life, their risk factors and their consequences. A pilot phase in Madagascar began in September 2012. In Cambodia, this program will be rolled out in two phases (pilot phase 2014-2015 and complete phase after 2016). Women would be recruited in their last trimester of pregnancy an their children followed up immediately after birth. Any febrile illness will be explored bacteriologically. The initial study area may be a provincial hospital. After ethics committee approval, inclusions are expected to begin in May 2014.

STATIS ANRS 12290 In high-prevalence countries, tuberculosis can be difficult to diagnose and remains a leading cause of death among HIV-infected patients, especially in cases of profound immune suppression. Despite the initiation of HAART, many patients die within the first month of treatment. The STATIS (Systematic vs. Test-guided Anti-tuberculosis Treatment Impact in Severely immuno-suppressed HIV-infected adults initiating antiretroviral therapy with CD4 cell counts <100/mm3) is a randomized controlled trial aiming to compare two experimental strategies to reduce the mortality and the occurrence

4 A 5-year memorandum of understanding was signed between The Institut Pasteur International Network on September 13, 2012 to contribute to the sustainable improvement of laboratory services and networks, strengthen preparedness, surveillance, threat detection and response, and thereby contribute to national and global health security

of severe bacterial infection (incl. TB) at 6 months in severely immunosuppressed adults infected with HIV (CD4 < 100/mm3): 1/ a strategy for intensive screening and repeated tuberculosis through workable tests during the day (Xpert MTB / RIF, LAM urinary, chest radiography); and, 2/ a simple strategy of systematic empirical anti -tuberculosis treatment initiated two weeks before the start of HAART. STATIS will also compare the occurrence of severe illness (AIDS, severe non-AIDS diseases, IRIS, adverse events grade 3 or 4), the number of lost to follow-up, healthcare costs, immuno- virological efficacy of ARVs , the efficacy and tolerance of TB and drug resistance and the cost-effectiveness study strategies. This study has been endorsed by NCHADS and CENAT and will be conducted at the Sihanouk Center of Hope Hospital. After ethics committee approval, inclusions are expected to begin in June 2014.

Testing for genetic susceptibility to A(H5N1) To December 31st, 2013, there have been 47 confirmed human A (H5N1) cases in Cambodia, of which 35 have died. The number of cases documented in 2013 (n=26) has increased nearly threefold as compared to the highest circulation in

previous years. An important surveillance bias may be the cause. It is of vital importance, however, to rule out increased transmission linked with changes in viruses’ characteristics. Preliminary studies conducted internationally have identified genetic polymorphisms in confirmed human cases, thought to be associated with higher vulnerability to A(H5N1) infection as compared to the rest of the community. This genetic study will be integrated to case identification, contact tracing around those cases and larger-scale

prevalence studies around the cases. Prospective inclusion and genetic testing of successive cases versus controls will help document if this association also applies in the Cambodian population and whether this polymorphism is associated with infection by this reassortant virus and inform public health. The confirmation of a genetic polymorphism in diagnosed cases would provide important insights into transmission and vulnerability profiles. Approval from the National Ethics Committee on Human Research was obtained on 20/12/2103 (#0241 NEHCR).


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upport to National authorities

In 2013, epi@ipc continued to actively support the national public health authorities.

Representatives from the unit participated to MoH and MAFF meetings. This was an opportunity to offer support, expertise and

advice when requested, delivered within the scope of operational meetings or lengthier workshops aiming to assess IHR preparedness with WPRO on 30/04/13 (Asia Pacific Strategic Plan for Emerging Disease - APSED) or to develop the Cambodian Zoonotic Disease Strategic Plan held by USAID on June 24 - 27, 2013.

Arnaud TARANTOLA mentored a Provincial epidemiologist through the MoH-WHO Applied Epidemiology Training program (Dec 2012 – July 2013).

Epi@ipc and the vaccination teams mobilized alongside NIPH and the Cambodian authorities on World Rabies Day (September 28, 2013) when a national press conference was held at IPC. A

Facebook page with prevention messages was launched.

The unit also actively participated in developing a strategy to document the impact of mutated, reasserted strains of A(H5N1) avian influenza viruses on human health. Although available data have shown higher levels of transmission to humans in Cambodia than elsewhere in the past, more and updated data are needed to guide risk assessment and ascertain that current circulating strains – and notably the two strains with (different) mutations - are not more transmissible to humans and from one human to another than viruses detected in Cambodia during previous years.

Through epidemic intelligence a slideset on data and lessons learned on emergent A(H7N9) in China was developed and maintained until June 2013. Along with the 4-day influenza course slideset, this was shared with the authorities to help guide public response.

cientific communications Below are presented all scientific articles published in peer-reviewed journals between January 1st and December 31st, 2013 with one or several epi@ipc staff members as coauthors.

Peer-reviewed articles published 1. Arnott A, Vong S, Rith S, Naughtin M, Ly S, Guillard B, Deubel V, Buchy P. Human bocavirus amongst an all‐

ages population hospitalised with acute lower respiratory infections in Cambodia. Influenza Other Respir Viruses. 2013 Mar;7(2):201‐10. doi: 10.1111/j.1750‐2659.2012.00369.x. Epub 2012 Apr 25.

2. Arnott A, Vong S, Sek M, Naughtin M, Beauté J, Rith S, Guillard B, Deubel V, Buchy P. Genetic variability of human metapneumovirus amongst an all ages population in Cambodia between 2007 and 2009. Infect Genet Evol. 2013 Apr;15:43‐52. Epub 2011 Feb 1.

3. Baron S, Goutard F, Nguon K, Tarantola A. Use of a text message‐based pharmacovigilance tool in Cambodia: pilot study. J Med Internet Res. 2013 Apr 16;15(4):e68.

4. Bertrand J, Verstuyft C, Chou M, Borand L, Chea P, Nay KH, Blanc FX, Mentré F, Taburet AM; the CAMELIA (ANRS 1295‐CIPRA KH001) Study Group. Dependence of Efavirenz‐ and Rifampicin‐Isoniazid‐Based Antituberculosis Treatment Drug‐Drug Interaction on CYP2B6 and NAT2 Genetic Polymorphisms: ANRS 12154 Study in Cambodia. J Infect Dis. 2013 Oct 16. [Epub ahead of print]

5. Borand L, Laureillard D, Madec Y, Chou M, Pheng P, Marcy O, Sok T, Goldfeld AE, Taburet AM, Blanc FX, , the CAMELIA (ANRS 1295‐CIPRA KH001) study team. Plasma concentrations of efavirenz with a 600 mg standard‐dose in Cambodian HIV‐infected adults treated for tuberculosis with a body weight above 50 kg. Antivir Ther. 2013;18(3):419‐23. Epub 2012 Dec 12

6. Borand L, Pheng P, Saman M, Leng C, Chea P, Sarady Ay S, Suom S, Roat Men N, Nerrienet E, Marcy O. [Tuberculosis and HIV co‐infection: clinical trial under the coordination of the Institut Pasteur in Cambodia]. Med Sci (Paris). 2013 Oct;29(10):908‐11.

7. Conan A, Goutard FL, Holl D, Ra S, Ponsich A, Tarantola A, Sorn S, Vong S. Cluster randomised trial of the impact of biosecurity measures on poultry health in backyard flocks. Vet J. 2013 Dec;198(3):649‐55.

S

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8. Conan A; Ponsich A.; Goutard F; Khiev R.; Tarantola A; San S; Vong S. A Community‐based Education Trial to Improve Backyard Poultry Biosecurity in Rural Cambodia. Acta Trop. 2013 Mar;125(3):294‐302. Epub 2012 Dec 19

9. Duong V, Henn MR, Simmons C, Ngan C, Y B, Gavotte L, Viari A, Ong S, Huy R, Lennon NJ, Ly S, Vong S, Birren BW, Farrar JJ, Deubel V, Frutos R, Buchy P. Complex dynamic of dengue virus serotypes 2 and 3 in Cambodia following series of climate disasters. Infect Genet Evol. 2013 Apr;15:77‐86. Epub 2012 Jun 5.

10. Duong V, Simmons C, Gavotte L, Viari A, Ong S, Chantha N, Lennon NJ, Birren BW, Vong S, Farrar JJ, Henn MR, Deubel V, Frutos R, Buchy P. Genetic diversity and lineage dynamic of dengue virus serotype 1 (DENV‐1) in Cambodia. Infect Genet Evol. 2013 Apr;15:59‐68. Epub 2011 Jul 2.

11. Goyet S, Lerolle N, Fournier‐Nicolle I, Ken S, Nouhin J, Sowath L, Barennes H, Hak C, Ung C, Viretto G, Delfraissy JF, Khuon P, Segeral O. Risk Factors for Hepatitis C Transmission in HIV Patients, Hepacam Study, ANRS 12267 Cambodia. AIDS and Behavior: 1‐10. 2013 Apr 24. [Epub ahead of print]

12. Guerrier G, Goyet S, Chheng ET, Rammaert B, Borand L, Te V, Try PL, Sareth R, Cavailler P, Mayaud C, Guillard B, Vong S, Buchy P, Tarantola A. Acute Viral Lower Respiratory Tract Infections in Cambodian Children: Clinical and Epidemiological Characteristics. Pediatr Infect Dis J. 2013 Jan;32(1):e8‐13. 2012 Aug 24. [Epub ahead of print]

13. Hanna M, Minga A, Fao P, Borand L, Diouf A, Mben J‐M, Gad R, Anglaret X, Bazin B, Chene G, and the [Quali‐PED] ANRS 12175 study group. Development of a checklist of quality indicators for clinical trials in resource‐limited countries: The French National Agency for Research on AIDS and viral hepatitis (ANRS) experience. Clin Trials. 2013 Apr;10(2):300‐18

14. Laureillard D, Marcy O, Madec Y, Chea S, Chan S, Borand L, Fernandez M, Prak N, Kim C, Dim B, Nerrienet E, Sok T, Delfraissy JF, Goldfeld AE, Blanc FX; CAMELIA (ANRS 1295 – CIPRA KH001) Study Team. Paradoxical tuberculosis‐associated immune reconstitution inflammatory syndrome after early initiation of antiretroviral therapy in a randomized clinical trial. AIDS. 2013 Oct 23;27(16):2577‐86.

15. N. T. N. Lan, N. T. N. Thu, N. H. Duc, N. N. Lan, T. T. X. Lien, N. H. Dung, A‐M. Taburet, D. Laureillard, L. Borand, C. Quillet, D. Lagarde, A. Pym, C. Connolly, C. Lienhardt, C. Rekacewicz, A. D. Harries. The ethics of a clinical trial when the protocol clashes with international guidelines. Public Health Action, Volume 3, Number 2, 21 June 2013, pp. 97‐102(6).

16. Rammaert B, Goyet S, Tarantola A, Hem S, Rith S, Cheng S, Te V, Try PL, Guillard B, Vong S, Mayaud C, Buchy P, Borand L. Acute lower respiratory infections on lung sequelae in Cambodia, a neglected disease in highly tuberculosis‐endemic country. Respir Med. 2013 Oct;107(10):1625‐32.

17. Tarantola A; Ly S; In S; Deubel V; Buchy P. Re: Only a sixth of animal bite victims in India get antirabies treatment. BMJ 2013; 347 (E‐pub 13 October 2013)

18. Tourdjman M, Le Hello S, Gossner C, Delmas G, Tubiana S, Fabre L, Kerléguer A, Tarantola A, Fruth A, Friesema I, Thorstensen Brandal L, Lawrence J, Fisher I, Dufour M, Weill FX, de Valk H. Unusual increase in reported cases of paratyphoid A fever among travellers returning from Cambodia, January to September 2013. Euro Surveill. 2013 Sep 26;18(39).

19. Vong S, Guillard B, Borand L, Rammaert B, Goyet S, Te V, Lorn Try P, Hem S, Rith S, Ly S, Cavailler P, Mayaud C, Buchy P. Acute lower respiratory infections in ≥ 5 year ‐old hospitalized patients in Cambodia, a low‐income tropical country: clinical characteristics and pathogenic etiology. BMC Infect Dis. 2013 Feb 22;13 (1):97.

20. Goyet S, Rammaert B, McCarron M, Khieu V, Fournier I, Kitsutani P, Ly S, Mounts A, Letson WG, Buchy P, Vong S. Mortality in Cambodia: an18‐month prospective community‐based surveillance of all‐age deaths using verbal autopsies. Asia‐Pacific Journal of Public Health.dec. 2013. doi: 10.1177/1010539513514433

Accepted for publication 21. Tarantola A; Goutard F; Newton P; de Lamballerie X; Lortholary O; Cappelle J; Buchy P. Estimating the burden of

Japanese encephalitis virus and other encephalitides in countries of the Mekong Region". Accepted for publication PLOS Neglected Tropical Diseases

22. Rammaert B; Goyet S; Tarantola A. Melioidosis requires better data sharing for improved diagnosis and management in the Mekong Region. Accepted for publication Am J Trop Med Hyg.

23. Netrabukkana P, Cappelle J, Trevennec C, Roger F, Goutard F, Buchy P, Robertson I and Fenwick S. Epidemiological analysis of influenza A infection in Cambodian pigs and recommendations for surveillance strategies Transbound Emerg Dis. (2013). Accepted


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Abstracts at conferences and meetings 1. Sowath Ly, Veasna Duong, Sopheak Sorn, Bunthin Y, Kunthy Nguon, Vanney Keo, Tum Buth, Lim Veung, Kimsrorn Kim,

Chantha Ngan, Anavaj Sakuntabhai, Philippe Buchy, Arnaud Tarantola. Epidemiology of clusters in identified dengue cases’ households in rural cambodia, 2013 – preliminary results. The Third International Conference on Dengue and Dengue Haemorrhagic Fever 2013 (Dengue 2013), 21‐23 October 2013. http://www.dengue2013bangkok.com/home/index/en

2. Veasna Duong, Sreyrath Lay, Sowath Ly, Bunthin Y, Kacey Long, Vincent Deubel, Arnaud Tarantola, Tomas W Scott, Louis Lambrechts, Philippe Buchy. Evaluation of direct skin feeding and membrane‐feeding methods of aedes aegypti on patients with dengue virus infection. The Third International Conference on Dengue and Dengue Haemorrhagic Fever 2013 (Dengue 2013), 21‐23 October 2013. http://www.dengue2013bangkok.com/home/index/en

3. V. Phuong, Z. Tun, L. Borand, D. Douk, E. Soeur, K. Nong, E. Webb, I. Fournier, C. Mean, J.F. Delfraissy, F. Barré‐Sinoussi, A. Tarantola. Fifteen Years Of HIV Positivity And Trends Of Associated Risk Factors Documented At The Institut Pasteur Du Cambodge. Poster session II – Abstract 94/15PS. 30 years of HIV science : Imagine the future. 21‐23 May 2013, Paris

4. Chen Soun, P. Has, S. Kham, B.Siea, V. Ieng, S. Din, M.C. Roces, A.E. Parry and A. Tarantola. Acute Gastroenteritis Outbreak following a Wedding in a Rural Village – Oddor Meanchey, Cambodia, May 2013. 7th TEPHINET bi‐regional Scientific Conference. Da nang, Vietnam, 12‐14 November, 2103

5. Vannara Hoy, P. Has, V. Som, S.D. Yi, B. Sor, N. Chea, P. Kitsutani, M.C. Roces, N. Asgari‐Jirhandeh, T. Wakui, Y. Arima and A.Tarantola. Investigation of severe neuro‐respiratory disease among children in Cambodia, 2012. 7th TEPHINET bi‐regional Scientific Conference. Da nang, Vietnam, 12‐14 November, 2103

6. Vandy Som, L. Som, P. Has, R. Pen, C. Heng, S. Ly, S. Newell, P. Buchy, M. Roces and A. Tarantola. Chikungunya Fever Outbreak in a Rural Village – Kampong Speu, Cambodia, March 2012. 7th TEPHINET bi‐regional Scientific Conference. Da nang, Vietnam, 12‐14 November, 2103

7. Goyet Sophie & Tarantola Arnaud for the CALIBAN group. Etiologies and antibioresistance of bacterial Community‐Acquired Pneumonia in Cambodia and neighboring countries. University of Health Sciences, 21‐22 October 2013, Phnom Penh, Cambodia.

8. S.Goyet, N.Lerolle, I.Fournier‐Nicolle, S.Ken, J.Nouhin, L.Sowath, H.Barennes, C.Hak, C.Ung, G.Viretto, JF.Delfraissy, P.Khuon, O.Segeral, Risk factors of Hepatitis C transmission in HIV infected Patients in Cambodia, HEPACAM Study ANRS 12267, ANRS‐ESTHER Scientific Symposium ‐ Hanoi 30 Sept ‐ 2 Oct. 2013, oral presentation.

9. Borand L. “Diagnosis of tuberculosis in children with HIV, ANRS 12229 – PAANTHER 01 study.” Research for Primary and Secondary Prevention of HIV associated Infections and Cancers in South East Asia, September 10th, 2013, Chiang Mai, Thailand.

10. N. Huy Dung, A. Barrail‐Tran, N. Thi Ngoc Lan, N. Hong Duc, N. Thi Nguyet Thu, N. Ngoc Lan, D. Laureillard, T. Thi Xuan Lien, L. Borand, C. Quillet, C. Connolly, D. Lagarde, A.Pym, C. Lienhardt, A.‐M. Taburet, A.D. Harries. “Rifabutin pharmacokinetics when coadministered with lopinavir/ritonavir in HIV‐infected patients with tuberculosis in Viet Nam: results of the ANRS 12150b cross‐over clinical trial”. IAS 2013, June 30th ‐ July 3rd 2013, Kuala Lumpur, Malaysia.

11. V. Haridas, P. Polidy, L. D. Jasenosky, Y. Madec, D. Laureillard, L. Borand, O. Marcy, S. Thim, F‐X Blanc, and A. E. Goldfeld. “Impact of Tuberculosis‐Associated IRIS on T Cell Activation and Reconstitution in Highly Immunosuppressed HIV/TB Co‐Infected Patients Starting ART”. 20th conference on retroviruses and opportunistic infections, CROI, March 6th, 2013, Atlanta, USA.

12. S. Ly, V. Duong, A. Rachmat, C. Yasuda, C. Ngan, R. Huy, S. Ong, W. Rogers, P. Buchy, A. Tarantola. Dengue Attack Rates and Proportion of Asymptomatic Infections in the Kampong Cham Prospective Community Study, 2011. Scientific Seminar on Dengue Clinical Care, 26 février 2013, Phnom Penh. Communication orale.

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