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Epidemiology & Public Health Unit (epi@ipc) 2014 The 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, 2014. Scientific & activity report

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Page 1: Scientific & activity reportInfluenza IMMI case-control Viro/LABM Paanther 01 ANRS 12 229 Viro/LABM STATIS (implementation) Viro/LABM AMR ChARLI epi@ipc only ... Jul Prenatal care

Epidemiology & Public Health Unit (epi@ipc)

2014 The 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, 2014.

Scientific

& activity

report

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Scientific & activity Report

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Contents

Team members and functional structure of the Unit ..................................................................................................... 5

Timeline and significant events in 2014 ......................................................................................................................... 6

Students and training in the Unit ...................................................................................................................................... 6

Students ............................................................................................................................................................................ 6

Participation in training others ..................................................................................................................................... 6

AET and UHS training................................................................................................................................................ 6

Virology DES, School of Pharmacy, UHS .............................................................................................................. 6

International Pasteur course on Surveillance of ILI, HCMC, Vietnam Nov. 2014 .......................................... 6

Data management training, ECOMORE Myanmar ............................................................................................. 7

Knowledge transfer training, ECOMORE ECOMORE Vietnam, 1-2 August 2014, Hanoi, Vietnam ......... 7

GCP training, Sihanouk Hospital Center of Hope ............................................................................................... 7

Global Health Network, Oxford University ......................................................................................................... 7

Training ourselves ........................................................................................................................................................... 8

Networking and epi@ipc .................................................................................................................................................. 9

Partners in Cambodia .................................................................................................................................................... 9

Hospitals ...................................................................................................................................................................... 9

Institutions ..................................................................................................................................................................... 9

Partners within IPIN ........................................................................................................................................................ 9

Regional or International Partnerships ....................................................................................................................... 9

Scientific projects and advancement ............................................................................................................................. 10

Endemic ID (Dengue, influenza, CAP…) ................................................................................................................... 10

DENFREE ..................................................................................................................................................................... 10

IMMI ............................................................................................................................................................................ 11

Clinical research ............................................................................................................................................................ 11

ANRS 12229 PAANTHER 01 ................................................................................................................................. 11

STATIS ANRS 12290 ............................................................................................................................................... 11

ChARLI ........................................................................................................................................................................ 12

Emerging ID / zoonoses : A(H5N1), rabies, Chikungunya … .............................................................................. 12

A(H5N1) ..................................................................................................................................................................... 12

Rabies ......................................................................................................................................................................... 13

Other .......................................................................................................................................................................... 14

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South East Asia encephalitis project (SEAe) ............................................................................................................ 15

ECOMORE ...................................................................................................................................................................... 15

Cambodia .................................................................................................................................................................. 15

Myanmar ................................................................................................................................................................... 16

Prospective: flagship projects to be implemented in 2015 ...................................................................................... 16

Chikungunya strains and cross-protection ........................................................................................................... 17

Sick dogs exposure lookback and immune response study (RESIST) ............................................................. 17

Hepatitis B PMTCT ................................................................................................................................................... 17

Regional rabies course............................................................................................................................................ 18

Hepatitis in IPC patients ......................................................................................................................................... 18

Support to National authorities ...................................................................................................................................... 18

Scientific communications ................................................................................................................................................. 19

Peer-reviewed articles published .............................................................................................................................. 19

Accepted for publication ............................................................................................................................................ 20

Abstracts at conferences and meetings .................................................................................................................... 20

Available altmetrics for 8 articles in Plos or BMC journals ....................................................................................... 23

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Report prepared by Dr. Arnaud TARANTOLA based on material developed by the epi@ipc team.

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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), 2011-2014. Leader: Dr. Arnaud Tarantola

Figure 1: epi@ipc staff members in 2014

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; Sopheak Sorn ; Souv Kimsan; Saman Manil; Chanthy leng; Arnaud Tarantola

Clinical Research

Laurence Borand

Laurence Borand, Dim Bunnet; Sophea Suom; Sophie Goyet; Keo Monorea; Manil Saman; Chanthy Leng; Vorn Rany; Susan Rasmey; Nour SHAMAS; Thann Sreymom; Chon Thida; Meng Vatana; Arnaud Tarantola

Emerging infectious diseases / zoonoses

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

Support to authorities

Arnaud Tarantola Sophie Goyet ; Ly Sowath, 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 2014.

Unit Themes Studies / Projects IPC collaborationsDENFREE Viro

ECOMORE (with Chikungunya) Viro

Influenza IMMI case-control Viro/LABM

Paanther 01 ANRS 12 229 Viro/LABM

STATIS (implementation) Viro/LABM

AMR ChARLI epi@ipc only

Viro

Leptospirosis Burden eco-epidemiological study LABM

A(H5N1) Contact tracing; Market study Viro

Encephalitis SEA encephalitis ; Ev71; Nipah Viro

Antibiotics AGISAR epi@ipc only

Applied epi DHHS Seminar ; AET ; outbreaks Viro / LABM

Infectious diseases Viro

Zoonoses Viro

Dengue weekly bulletin Viro

epi@

ipc

Zoonoses and emerging risks

Programs

Rabies lookback ; dog survey ; economic studies

Assisting

Cambodian

authoritiesExpert groups

Endemic diseases Dengue

Clinical

research

Rabies

HIV/TB

T

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imeline and significant events in 2014 The Year 2014 was another intense year for epi@ipc: third year and data entry for DENFREE ; DHHS with several field investigations around identified A(H5N1) cases

until March 2014 ; continuation of the PAANTHER 12229 and IMMI studies; implementation of ChARLI and STATIS ...

Professor Vincent DEUBEL and Dr. Philippe BUCHY left IPC and were replaced by Pr. Didier FONTENILLE and Dr. Philippe DUSSART, respectively.

Some permanent staff members left the team (PHENG Phearavin, KEO Vanney, Mousumi RAHMAN) while others joined the team (Julia LEDIEN; PEAS Muslim; VORN Rany; THANN Sreymom; CHON Thida; MENG Vatana; PAK So Kreth in December). Sophie GOYET successfully sat her PhD in December 2014 (Université Montpellier 2).

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

Sophie GOYET successfully sat her PhD in December 2014 (Université Montpellier 2).

Following Natalie MOYEN's work in the Unit supervised by Dr. Julien CAPPELLE, Ms. Maud YAKOVLEFF continued the study of the introduction, the determinants and dynamics of Japanese Encephalitis in pig abattoirs in or near Phnom Penh.

As part of the requirements for her PhD at Université Montpellier 2, Sophie GOYET undertook an exhaustive literature review of publications on health research in Cambodia between 2002 and 2012. She oversaw the work of Messrs. SOCHEAT Touch and SAMAN Sovannchhorvin, both students from NIPH’s MPH program, who participated in this review.

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

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 supervised her epidemiology dissertation on the data from the Dengue 2011 Kompong Cham study.

Thanks to a Bourse Pierre Leroux grant, Dr. Sophie BLANCHI was able to do an intership in the Unit to fulfill the requirements of her MSc in epidemiology (CNAM). Her work bore on using the IPC rabies database to identify optimally positioned forward vaccination centers for rabies prevention in Cambodia.

Other students and training programs are listed in Table 1 below.

Participation in training others

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

AET and UHS training

Dr. LY Sowath delivered two lectures within the Applied Epidemiology Training epidemiology students as well as eight lectures on bacterial pathogens for first-year USS medical students.

Virology DES, School of Pharmacy, UHS

Two presentations were delivered on 17 and 18 December by A. TARANTOLA, one on rabies and the other on drivers of emergence as part of the Virology module for the DES Biologie Médicale at the School of Pharmacy, University of Health Sciences, Phnom Penh.

International Pasteur course on Surveillance of ILI,

HCMC, Vietnam Nov. 2014

Data and experience from Cambodia were shared (A. TARANTOLA) with an international audience during a presentation on "Respiratory pathogen surveillance in the developing setting" during a course organized by Institut Pasteur HK and Institut Pasteur HCMC.

T

S

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Table 1: Students who received training at or in connection with epi@ipc in 2014.

Name Degree Institution Time period

Subject

Sophie BLANCHI MSc CNAM Montpellier 2 May-Oct Mapping rabies vaccination sites through modeling of non-attendance data

Julia LEDIEN Master Santé Int

ISPED Apr- Aug Using teledata for predicting high-risk zones for leptospîrosis

Marissa GRIPENBERG Intern LSHTM May -Nov Implementing ChARLI Caroline DE COURVILLE Pharmacie Université Lyon 1 Oct - Dec Nutritional supplementation using Spiruline

Emily McLEOD MSc Epi Australian National University

Jun - Aug Environmental, socioeconomic and behavioural risk factors for dengue in Kampong Cham, Cambodia.

Fanny THEBAULT Master 1 Université Paris 1 Apr - Jul Prenatal care in Phnom Penh

Maud YAKOVLEFF M2 Eco-biodiversité

Montpellier 2 Feb - Jun Modeling the circulation of JE virus in a Cambodian pig slaughterhouse

PAK So Kreth Internship Royal Uni PP Oct-Nov Biostatistical training

Camille AGOSTINI MD Residency CHU Montpellier Nov-Apr Clinical research

SEANG Sok Heng Master Drugs & PH

Toulouse III Feb - Aug ChARLI

Clara CHAMPAGNE MPH ENSAE May - Jun Dengue modelling

HOK Sal Biodiversity and Conservation Master

Royal University of Phnom Penh

Jan-Dec 2014

Diet Phenology of Flying Foxes

LIM Thona Reproductive phenology and roost selection of Insectivore bats in Southern Cambodia

HOEM Thavry Diet and Reproductive Phenology of Cave Nectar Bat (Eonycteris spelaea) in Cambodia

Data management training, ECOMORE Myanmar

Under the supervision of Dr. LY Sowath and with assistance from CHAN Malen and Sophie GOYET, Ms. May July received data management training in epi@ipc in April 2014. She is now responsible for data management for the ECOMORE Myanmar study.

Knowledge transfer training, ECOMORE ECOMORE

Vietnam, 1-2 August 2014, Hanoi, Vietnam

S. GOYET delivered a presentation on KT principles, and the way to influence policy changes to the ECOMORE team in Vietnam. This presentation was followed by a session on designing a plan of action using dynamic approaches connecting research and policy- processes and building trust and dialogue. During a second session, the group drafted an action plan after setting the objectives and identifying the expected outcomes of the ECOMORE project in Vietnam.

GCP training, Sihanouk Hospital Center of Hope

Dr. Laurence BORAND undertook training in good clinical practices for over 20 medical staff of Sihanouk Hospital in Nov. 2014.

Global Health Network, Oxford University

The slideset from IPC's Influenza Seminar1 - with added written commentary - was shared with Oxford's Global Health Network. These will be uploaded on the Global Health Training Center website2, maintained by Dr. Trudie LANG, Nuffield Department of Medicine, Oxford University, thanks to a grant from the Bill & Melinda Gates Foundation and within the framework of a Cooperation agreement between Institut Pasteur and Oxford University.

1 http://www.pasteur-kh.org/sng/ 2 https://globalhealthtrainingcentre.tghn.org/

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

Name Degree/Workshop Institution Date Subject

A. TARANTOLA DES BioMed UHS 17-18/12/2014 Rabies ; Emergence of infectious diseases

S. LY AET MoH /WHO April - May Chikungunya Kg Speu ; Case-control studies

S. LY Agents infectieux UHS May - July 8 lectures on bacterial pathogens

A. TARANTOLA ILI Surveillance Pasteur 17/11/2014 Respiratory pathogen surveillance in the developing setting

Training ourselves

The table below lists epi@ipc staff who received training or self-trained in 2014, 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.

Additionally, contribution to a qualitative

epidemiology study conducted by FHI360 in

collaboration with epi@ipc provided intensive on-

the-job training in qualitative research in Cambodia.

Table 3: Continuing training for epi@ipc staff in 2014

Name Training subject Course name / Institution Dates

Sophie GOYET Linkage research and health policy

Bridging the gap between research and health policy making”; School of Public Health, Hanoi, Vietnam

Jul–Aug 2014

DOUM Dyna GCP / Ethics IRB Training English Curriculum ; Collaborative Institutional Training Initiative (CITI)

Jun 2014

DOUM Dyna Entomology Double bednet collection, IP Lao May-Jun 2014

Mousumi RAHMAN GCP / Ethics IRB Training English Curriculum; Collaborative Institutional Training Initiative (CITI)

Aug 2014

KEO Monorea Data management Data Management for Clinical research ; Coursera July 2014

SORN Sopheak Clinical management Dengue Clinical Case Management ; CDC Learning Connection

July 2014

SOUV Kimsan Clinical management Dengue Clinical Case Management CDC Learning Connection

July 2014

CHAN Siam Clinical management Dengue Clinical Case Management CDC Learning Connection

July 2014

CHAN Malen Clinical management Dengue Clinical Case Management CDC Learning Connection

July 2014

KEO Monorea Clinical management Dengue Clinical Case Management CDC Learning Connection

July 2014

DOUM Dyna English Australian Centre for Education (ACE) 2014

KEO Monorea English Australian Centre for Education (ACE) 2014

THANN Sreymom English Australian Centre for Education (ACE) 2014

SORN Sopheak English Australian Centre for Education (ACE) 2014

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etworking and epi@ipc

Partners in Cambodia

Links with collaborating partners in Cambodia were further reinforced in 2014.

Hospitals

The implementation of the STATIS study following GCP, informed consent process and clnical trial management training reinforced close cooperation with teams at

Sihanouk Center of Hope hospital, Phnom Penh.

The ECOMORE project is being successfully conducted in

cooperation with clinical teams from eight hospitals in Cambodia. Several workshops and trainings further reinforced ties with clinicians and PHD staff as well as CNM.

Institutions

The participation of epi@ipc to the Battambang HIV cluster in December 2014 further strengthened long-

and deep-running ties with NCHADS.

The ChARLI study set up a collaboration with the Provincial hospital, a health center and health

authorities in Kompong Speu Province, opening a new

field site for IPC projects, as well as with the National

Pediatric Hospital and the Khema Clinic.

Entomologists from Namru-2 kindly participated to the ECOMORE entomological study (October 2014).

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.

Collaborative work on A(H5N1) deepened ties and fostered trust during an A(H5N1) influenza

coordination meeting with US-CDC at the US Embassy

on Feb 6th, 2014, as well as the USAID-sponsored Viet Nam and Cambodia Bilateral Meeting on H5N1 at Raffles, March 24, 2014.

Partners within IPIN

Successes of the DENFREE and other studies conducted by IPC staff led to A. TARANTOLA being invited to join

the Scientific Advisory Board of the Pasteur Dengue

Taskforce. This group aims to identify collaborative research projects to answer research gaps.

A visit around May 19 of the coordinators for Project

REACTING and Pasteur's Center for Global Health (CGH) enabled epi@ipc to present their work. During a visit

in April 2014, collaborations on articles and data analyses were established with S. CAUCHEMEZ at the

Analysis and Modeling of Epidemic Dynamics Unit, IP Paris.

Thanks to the Division International in IP Paris, an ACIP grant was obtained for a workshop on rabies at IP Paris in Jan 2014 with colleagues from Paris (France), Dakar (Sénégal), Abidjan (Côte d'Ivoire), Yaoundé (Cameroon), Antananarivo (Madagascar) and Phnom Penh (Cambodia). The exchange of data and ideas were synthesized into the ambitious "Rabies elimination support through integrative science and salvage

therapy (RESIST)" rabies research program. This was summarized in a 10-page document for advocacy and funding.

The Institut Pasteur in Laos kindly accepted to train Mr. DOUM Dyna in mosquito sampling techniques. Epi@ipc hopes to be able to return the favor.

As an epidemiologist who worked on Dengue at IPC over the past years, Arnaud TARANTOLA was invited to be a member of the Institut Pasteur Dengue Taskforce's Scientific committee.

Regional or International Partnerships

J. CAPPELLE, S. LY and A. TARANTOLA participated to the "Companion Approach for cross-sectoral Collaboration in health risk management in SEA”

COMACROSS meeting, Bangkok 30/04-2 May 2014. Epi@ipc is a founding partner of this project led by CIRAD at Kasetsart University, which secured EuropeAid funding. A follow-up workshop was held at IPC in Phnom Penh specifically on JEV epidemiology and control in October 2014.

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

Initial collaborations were implemented with the

Australian National University (Pr. David HARLEY; Dr. Elvin VIENNET) through the mentoring of an Epidemiology Masters student, Ms. Emily McLEOD, who worked on and analyzed the 2011 Kampong Cham Dengue study database.

The STATIS study also reinforced links with Pham Ngoc Tach Hospital, HCMC.

A teleconference with DNDi on 13/11/2014 gave us an opportunity to discuss future research options.

N

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With the exception of

some One-Health

projects, all epi@ipc

studies follow the same

paradigm: They begin

and end with the patient.

Figure 3: epi@ipc long-term partnerships and shorter-term collaborations, 2013-2014

cientific projects and advancement

Projects were initiated in 2014 or continued from 2013. These projects

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

With the exception of some One-Health projects exploring pathogens in animals or insects, all follow the same paradigm: They begin with the patient, whether recruited by surveillance, clinical research, prospective studies or outbreak investigations. They also end with the patient, with a willful effort to provide data or recommendations to inform patient management or public health response.

Endemic ID (Dengue, influenza, CAP…)

DENFREE

Epi@ipc team leaders Ly S, A. Tarantola

Objective and summary of results The DENFREE program, an ambitious 3-year study, is coming to a close in terms of collection of field data. 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 site. Data from 2012 and 2013

S

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found a total of 556 (67%) confirmed dengue cases among 830 patients in 3 hospitals and 38 (8%) confirmed dengue cases among 463 febrile cases in 21 villages gave rise to 200 completed investigations in 3,066 households (confirmation by NS1 rapid test or by PCR) of 135 villages. In these houses, 8125 persons aged ≤ 30 years agreed to participate and 363 (4.5%) tested positively for dengue by PCR (no NS1 testing of these samples). Of these confirmed dengue participants, 334 (92%) presented symptomatic infection by DENV and 29 (8% of 363 positive participants) presented truly asymptomatic infection; infection status was not available for 3 positive participants.

Epi@ipc has been responsible for finalizing the database and is interfacing with modeling experts to answer specific research questions at varying geographical scales.

Financial support Funded by EU-FP7.

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 2014, a total of 1291 patients were screened in Cambodia. Of these, 253 (19.6%) were tested positive by RDT. Subsequently 14 refused or had no further testing and 239 were found positive by PCR (46 cases and 140 controls from Takeo ; 18 cases and 35 controls from Calmette). The viral strains involved were A(H1N1)pdm, A(H3N2) and Influenza B. There were 128 influenza B-infected patients.

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

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, 2014 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, 2014 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).

STATIS ANRS 12290

Epi@ipc team leaders

L. Borand

Objective and summary of results

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Despite the initiation of HAART, many patients die of tuberculosis 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 of severe bacterial infection (incl. TB) at 6 months in severely immunodeficient 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 endorsed by NCHADS and CENAT will be conducted at the Sihanouk Center of Hope Hospital. Ethics committee approval (#0195NEHCR) was obtained on 30 June 2014.

Financial support ANRS

ChARLI

Epi@ipc team leaders S. Goyet ; L. Borand

Objective and summary of results The ChARLI (Children’s Antibiotic Resistant infections in Low Income Countries) study is a multi-country study which began in Madagascar in Sept 2012, with more than 800 subjects included to date. In Cambodia a pilot phase was first implemented and will be scaled up in 2015. To December 15, 2014, a total of 65 women who have given birth to 40 newborns (1 stillbirth and 1 death) have been included in rural Kompong Speu. The aim of this prospective study is to estimate the incidence of bacterial infections and of their antimicrobial resistance to antibiotics: neonatal infections (<28 days of life), infections in infants and young children (28 days to <2 years). Secondary aims are : To estimate the incidence of bacterial neonatal

infections (both sensitive and resistant to antimicrobials); to describe the bacterial etiologies and severity of neonatal infections in LICs ; To assess the vertical transmission of multi-resistant bacteria from mother-to-child, versus infections contracted via the environment and from relatives; To analyze the medical and economic burden of antimicrobial resistance, in view of the available treatments and current therapeutic recommendations in Cambodia.

The study is due to begin in the urban areas in January, 2015.

Financial support Funded by IP Paris.

Emerging ID / zoonoses : A(H5N1), rabies,

Chikungunya …

A(H5N1)

Epi@ipc team leaders

S. Ly and A. Tarantola

Outbreak investigations and contact tracing

Between January 1st and March 31st, 2014, a total of 9 index (confirmed) patients have given rise to 8 investigations (co-investigation by IPC-MoH-WHO), totaling 219 contacts designated by MoH RRT teams.

Seroprevalence studies

Seroprevalence study 1: This investigation was conducted in a village in Kratie province from which originated two children of two different households with confirmed A(H5N1) infection within the 2nd week of Feb 2014. The 1st child died some days after his (untested) sister died with a similar presentation and the 2nd child survived the infection. Visit 1 was conducted by 4 teams (30 investigators in total) and took place on 18-21 February, bearing on 272 persons in 116 households. Follow-up Visit 2 was conducted on 19-22 March by 4 teams totaling 15 investigators (no questionnaire needed) and blood samples were taken from 238 participants (15 refusals and 18 subjects away from home).

Seroprevalence study 2: This study was conducted in a larger village where only one case was diagnosed in Feb 2014, but in which cases were also diagnosed in April 2007 and in Dec 2009, making it one of the World’s

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Modeling studies on the

referrals at the Rabies

Prevention Center allowed

for the identification of

underserved areas where

secondary rabies prevention

sites could be positioned

A(H5N1) hotspots. During the 12-16 March investigation by 4 teams (34 investigators in total), 690 people were interviewed and sampled. Visit 2 of the investigation was carried out during 07-11 April 2014 by 4 teams totaling 21 people, collecting samples from 643 participants (12 refusals, 1 failure to sample and 34 subjects away from home).

In total, these four sampling visits totaled 14 days, collecting 1,843 samples from 962 persons after informed consent forms and questionnaire completion, and a total of 104 investigators spending 369 investigator-days in the field.

Rabies

Identifying and meeting needs

for advanced rabies

vaccination sites in Cambodia

Epi@ipc team leaders A. Tarantola

Objective and summary of results The two main rabies prevention centers accessible to the public in Cambodia are located in Phnom Penh, the capital. This leads to great difficulties in access to post exposure treatment for rural populations, the majority in this country and those most at risk of potentially infective dog bites. The objective of our retrospective, descriptive and analytical study was to identify geographical areas independently associated with vaccine protocol non-completion, in which secondary vaccination centers could be positioned. It was conducted on the database of the rabies prevention center of the Institut Pasteur in Cambodia, Phnom Penh (rpc@ipc) from 2009 to 2013, inclusive, based on a multivariate analysis of determinants of vaccine noncompletion using a logistical regression model. The influence of distance by road was estimated using a boosted regression tree model. Districts independently associated to vaccine noncompletion were identified using a hot Spot analysis. The global frequency of noncompletion was estimated at 7.8%. Factors independently associated to vaccine noncompletion was the patient’s district of

residence, male gender, age between 15 and 49, rice harvest at the initial visit, the status of the dog and a full vaccination protocol requiring more than three sessions. The distance by road from the center of the district to rpc@ipc was significantly associated with the fourth session being missed, with an estimated threshold at 150 km. Four geographical areas (clusters of districts with high noncompletion) were identified: Operational Districts of Kampong Cham, Ang rokar, Battambang and Neak Loeung (Prey Veng).

Financial support The internship of Dr. Sophie BLANCHI was funded by a grant from Fondation Pierre LEDOUX.

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 routine canine

vaccination has been implemented to date. A limited canine rabies vaccination campaign was held in December 2012 – January 2014 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

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between Jan-Aug. The total dog population was 1,068 in January 2013 and 1,312 in August 2014, 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 2014 and 1 : 2.5 (1312 dogs, 3338 humans) in August 2014. The vaccination coverage declared by interviewees was 63.2% (total 675 living vaccinated dogs) in January 2014 and 36.7% (481 living vaccinated dogs) in August 2014, for a 26.5% vaccine coverage decrease over a 6-months period..

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

Other

Ecology of Flying foxes and the risk of Nipah

virus emergence in Cambodia

Epi@ipc team leaders J. Cappelle

Objective and summary of results Two main research programs related to bat-borne disease eco-epidemiology were implemented in 2014 at epi@ipc.

The first program comprises several studies aiming at assessing the risk of emergence of Nipah virus from Pteropus lylei populations. It combines ecological, epidemiological, virological and sociological components such as:

Monthly censuses - to describe the population dynamic of the colony

A behavior study - to describe the different phases of the reproduction cycle of the colony

Urine sampling during the post-partum period - to maximize the likelihood of virus detection

Description and analysis of foraging behavior from feces - to identify potential overlap with human activities

Description and analysis of the genetic structure of Pteropus populations in SEA - from ADN extraction in feces

and a preliminary anthropological study aiming

at understanding the perception of risks associated with bats by local population and agricultural practices that may increase human contact with bats.

Preliminary results show that Nipah virus circulated within the colony in May, one to two months after birth peak. The analysis of conditions and determinants of bat/human interface will help identify people and domestic animals at risk of Nipah infection, thus targeting serostudies using a test currently being developed at IPC (granted by ComAcross project).

The second program focuses on the ecology of cave bats as reservoir of potential emerging infectious encephalitides. Monthly trapping began in March 2014 in two caves in Kampot province. These trapping were performed by two Master students (Biodiversity and

Conservation, Royal University of Phnom Penh). The goal is to identify the main species living in these caves, to describe their reproduction cycle and their feeding behavior. Around 80 bats from different species were sampled (blood and oral and rectal swabs) during the first session in October 2014. Samples collected during this first study will be analysed in 2015.

Main Partners:

Coordination by epi@ipc and CIRAD

In Cambodia: Forestry Administration, , Royal University of Phnom Penh (RUPP), Fauna and Flora International (FFI)

In Thailand: Prince of Songkla University, Chulalongkorn University

Financial support

SEAe (below) and ComAcross projects

Japanese encephalitis in a peri-urban pig slaughterhouse of Cambodia : A deterministic meta-population model to quantify the risk of transmission to humans

Flying Fox (photo J. Cappelle)

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Jointly with CNM and CDC at

the Ministry of Health, IPC is

implementing ECOMORE, an

important project on the

improvement of monitoring of

disease emergence and

progression related to

changes in human

demographics and

transportation in Cambodia.

Epi@ipc team leaders J. Cappelle

Objective and summary of results Cambodia has been facing high population growth in urban areas, associated with an increase of pork consumption, and consequently, the implantation of pig slaughterhouse in peri-urban areas. Due to the presence of Cx quinquefasciatus, a Japanese Encephalitis (JE) competent mosquito vector, in peri-urban areas, and in a country where JE vaccination is not available countrywide, the risk of JE urban transmission is increasing.

We developed a deterministic meta-population model, combining a Susceptible, Exposed, Infectious (SEI) model for mosquitoes, a Susceptible Infectious Removed (SIR) model for pigs and a Susceptible Removed (SR) model for humans, where the flows between each compartment was described by differential equations. To estimate the model parameters, we used (i) for pigs, a flow dynamic survey associated with a serological survey performed in the pilot slaughterhouse, (ii) for mosquitoes, a longitudinal trapping survey in the pilot site, (iii) and literature data.

According to this preliminary model, the slaughterhouse-induced annual incidence was estimated to be very low. Further analyses are ongoing to further refine the model.

Main Partners:

Coordination by epi@ipc and CIRAD

Financial support

SEAe project

South East Asia encephalitis project (SEAe)

The South East Asia encephalitis has been implemented. In Cambodia, it is conducted at the Kantha Bopha hospital, Phnom Penh, as well as Mahosot Hospital, Vientiane, Lao PDR, and National Hospital for Pediatrics, Hanoi, Vietnam. National Ethics Committee on Human Research

approval #0156 NEHCR was granted on 26/08/2103.

This study brings 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) is 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. To date, the pilot study has included 26 patients in Lao PDR, 24 patients in Vietnam and 50 patients in Cambodia.

ECOMORE

Cambodia

Epi@ipc team leaders

J. Cappelle, A. Tarantola

Objective and summary of results 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 conducted in close collaboration with CNM 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. National Ethics Committee on, Human Research approval #0144 NEHCR was granted on 26/08/2013.

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 assesses the existing dengue surveillance in the new hospitals to provide a set of recommendations to improve the system, if

needed. Task 2 monitors dengue cases and virus strains in 8 public sector surveillance sites along

major road axes in Cambodia. Task 3 initiated in December 2014 aims to extend a robust syndromic surveillance system in cooperation

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with the private healthcare sector to provide a more accurate burden of dengue-like disease

cases. 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. Some entomological data

collection was initiated in 2014.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.

To 31st Dec 2014, the joint CNM/ECOMORE project has audited and helped capacitate the sentinel hospital network, extending it by 50%. Surveillance methods have been standardized and inter-sectoral collaborations strengthened. Feedback to participating sites and health departments has been improved for all components, increasing the acceptability of the system. SOP were formalized and distributed. Sentinel data was collected for the 2014 Dengue season. The first phase of entomological collection was conducted during 15 days (13th to 17th October), trapping and describing between 5300 and 27 100 over a 3-weeks period. The collection of data from the private sector began in Dec. 2014.

Myanmar

Epi@ipc contributes to an ECOMORE project in Myanmar (WP Leader: Dr. Philippe Buchy). The project is capacitating 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.

The lab is being capacitated through purchase of equipment and introduction or reagents and processes. In the near future, a Yangon, ICU-based sentinel surveillance in Yangon Children Hospital and in Yankin Children Hospital 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 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 IHR3.

Financial support Agence Française de Développement.

Prospective: flagship projects to be

implemented in 2015

A(H5N1) clinical review

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

Objective and summary of study In 2013 a clinical review workshop on A(H5N1) influenza provided an opportunity to compile and carefully review clinical, biological and radiological data in confirmed A(H5N1) cases. These data were all drawn from hospital clinical records using a single, complex but thorough questionnaire 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). These data are now being updated, verified and entered to perform a thorough analysis of clinical characteristics of A(H5N1) cases in 2013 compared to earlier years, as part of the assessment of the 2013 spike in confirmed cases.

Financial support None.

Poultry market and avian influenza study

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

Objective and summary of study A(H5N1) is now enzootic to Cambodia, with a local clade being increasingly identified in poultry cases. Thanks to renewed DHHS funding, a prospective 12-months cohort study poultry workers at baseline and follow-up will be

3 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

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implemented in Cambodian poultry markets. This study conducted in limited sites will document the risk of reassortment between strains found in poultry and environment samples.

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

Chikungunya strains and cross-protection

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

Objective and summary of study The investigation in Trapeang Roka in 2012 and 2013 showed that persons aged 35 or above were comparably protected compared to others. This is likely due to the Asian strain of Chikungunya circulating in Cambodia until 1975 when the Khmer Rouge Communist regime ended free circulation of humans and viruses, providing indirect evidence that antibodies against the Asian strain lasted several decades and were cross-protective for the Esat-Central African strain. These hypotheses will be tested in the laboratory setting.

Financial support To be determined.

Sick dogs exposure lookback and immune response

study (RESIST)

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

Objective and summary of study

The Lookback study 1 on the outcome in persons bitten by confirmed rabid dogs between 2000 and 2010 found no measurable difference in outcome between (ERIG +) 5 and 3 sessions at this point. The aim is to see whether this remains true even when no ERIG are used. Although always indicated in case of deep bite with bleeding, ERIG is in short supply worldwide. Its use has therefore been prioritized for children, bites by confirmed rabid dogs and bites to the face and hands. Many bites do not benefit from ERIG in developing countries.

Data is available showing that the immune response at D14 after a one-week protocol of three ID injections at D0, D3 and D7 is comparable to a 5-dose regimen. The number of doses administered in the one-week, three

session protocol, however, remains high at 12 ID-doses. Clinical, epidemiological and biological data will be gathered to estimate whether the existing IM and ID protocol can be shortened (no D28 session) and reduced in doses (2 doses per session) in PrEP and in PEP protocols, at no risk to patients.

This will entail :

- a retrospective and prospective study on patients' outcomes, by dog status (confirmed rabid, apparently sick, apparently healthy) and by vaccination protocol completion (whether they came for a complete protocol or interrupted the protocol early; no shortening of recommended protocols for study purposes).

- as well as a targeted serological study in patients bitten by confirmed rabid dogs, to study antibody responses in the same patients after 3 sessions compared to 4 sessions (no shortening of recommended protocols for study purposes).

Financial support Division International

Hepatitis B PMTCT

Epi@ipc team leaders L. Borand, A. Tarantola

Objective and summary of study

Despite effective primary prophylaxis, HBV remains a substantial health problem both internationally and in Cambodia where neonatal transmission, unfortunately, still occurs. Failure of immunoprophylaxis or ‘breakthrough’ infection, is defined as persistent HBV infection of the newborn despite vaccination and/or HBIG. Reported failure rates range from 1 – 14%, despite serovaccination. Factors associated with failure include HBeAg positivity and high HBV DNA VLs in the mother.

As proportion of cases of mother-to-child HBV transmissions are not all prevented despite joint serovaccination as outlined above, antiviral agents can be utilized to further decrease the risk of vertical transmission, especially in areas where WHO-recommended HBIG are financially or operationally inaccessible. Several antiviral agents are currently presently used for this purpose. They are typically initiated in the late second or third trimester of pregnancy.

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Financial support Will be submitted in March 2015 to ANRS.

Regional rabies course

Epi@ipc team leaders A. Tarantola

Objective and summary of study Cambodia animal health and human health authorities have committed themselves, alongside Vietnam, to eliminate canine rabies by the Year 2020.

Thanks to funding obtained from PREDEMICS, RIIP and WHO, the Pasteur course on Rabies and Rabies control. This international course has previously been conducted successfully in Shanghai, Ho Chi Minh and Dakar. When conducted in 2015 in Cambodia it will train 30 students from the Asian region and will be conducted by international and national experts. This will provide invaluable assistance to Cambodian and other stakeholders as they strive to meet their engagements and the 2020 deadline.

Financial support PREDEMICS, RIIP and WHO.

Hepatitis in IPC patients

Epi@ipc team leaders A. Tarantola ; L. Borand

Objective and summary of study There are very limited data on HCV prevalence in various Cambodian population subgroups, and only a few recent ones in Cambodia. Many of those studies have examined prevalence and risk factors among HIV patients or have concluded to transmission risks associated with health care before 2000. Increasing evidence points to sexual transmission as an important factor for HCV transmission, including in countries with a high prevalence linked with nosocomial risks.

We propose to estimate the prevalence of HCV through a retrospective study in anonymous VCCT samples available for 2013 and 2014 to explore documented socio-economic and sexual risk factors for possible significant association.

Institut Pasteur du Cambodge’s medical analyses laboratory (Laboratoire d’analyses médicales, LABM) has identified 95 persons from the end of 2009 to October 2014 with a positive HCV

screening test. Genotyping identified 10 HCV genotypes, with two representing 28% each of the total (1b and 6e). These subjects are identified by a laboratory code, enabling us to find their telephone number in IPC’s invoice system. We propose to contact all positive cases residing in Phnom Penh and three times that number of seronegative persons, matched for age group and sex and also residing in Phnom Penh to undertake viral load titration in HCV-positives and explore documented socio-economic and sexual risk factors for possible significant association.

These studies will be submitted to NECHR for ethical approval.

upport to National authorities

In 2014, epi@ipc continued to actively support the national public health authorities.

Representatives from the unit regularly participated to Technical Working Group (TWG) meetings with MoH and MAFF and

international stakeholders. 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, 2014.

In March and May 2014, we were invited to join the group of policymakers from five ministries who drafted and finalized an important set of health policies: the first National Policy and 5-year Strategic Plan to Combat Antimicrobial resistance (AMR) in the country, under the authority of the Ministry of Health (MoH) and the World Health Organization (WHO).

Epi@ipc and the vaccination teams mobilized alongside NIPH and the Cambodian authorities on World Rabies Day (September 28, 2014) when a national press conference was held at IPC. A Facebook page with prevention messages was launched.

In close cooperation with the Virology unit, epi@ipc also actively developed a strategy to document the impact of mutated, reassorted strains of A(H5N1)

S

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avian influenza viruses on human health. Although available data have shown higher levels of transmission to humans in Cambodia than elsewhere in the past, updated data suggest that 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 MERS-CoV in the Middle-East was developed and maintained until en of October 2014. This was shared with the authorities to help guide

public response, especially in anticipation of the Hadj.

At the request of NCHADS and the Ministry of Health, epi@ipc participated alongside the HIV/Hepatitis laboratory to the response taskforce assembled to deal with the Battambang HIV cluster. This exceptionally serious and intense event in terms of HIV epidemiology is currently being investigated, in support of national stakeholders and in partnership with international partners.

cientific communications Below are presented all scientific articles published in peer-reviewed journals between January 1st and December 31st, 2014 with one or several epi@ipc staff members as coauthors.

Peer-reviewed articles published

1. Barennes H, Guillet S, Limsreng S, Him S, Nouhin J, Hak C, Srun C, Viretto G, Ouk V, Delfraissy JF, Ségéral O. Virological failure and HIV-1 drug resistance mutations among naive and antiretroviral pre-treated patients entering the ESTHER program of Calmette Hospital in Cambodia. PLoS One. 2014 Aug 28;9(8):e105736.

2. Barennes H, Pussard E. Improving the Management of Dysglycemia in Children in the Developing World. Am J Trop Med Hyg. 2014 Oct 13. pii: 14-0212. [Epub ahead of print] PubMed PMID: 25311692.

3. Barennes H, Slesak G, Buisson Y, Odermatt P. Paragonimiasis as an important alternative misdiagnosed disease for suspected acid-fast bacilli sputum smear-negative tuberculosis. Am J Trop Med Hyg. 2014 Feb;90(2):384-5.

4. Barennes H, Tat S, Reinharz D, Vibol U. Perceived stigma by children on antiretroviral treatment in Cambodia. BMC Pediatr. 2014 Dec 10;14(1):300. [Epub ahead of print] PubMed PMID: 25492301.

5. Bertrand J, Verstuyft C, Chou M, Borand L, Chea P, Nay KH, Blanc FX, Mentré F, Taburet AM; 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. 2014 Feb 1;209(3):399-408

6. Borand L, Madec Y, Laureillard D, Chou M, Marcy O, Pheng P, Prak N, Kim C, Lak KK, Hak C, Dim B, Nerrienet E, Fontanet A, Sok T, Goldfeld AE, Blanc FX, Taburet AM. Plasma concentrations, efficacy and safety of efavirenz in HIV-infected adults treated for tuberculosis in Cambodia (ANRS 1295-CIPRA KH001 CAMELIA trial). PLoS One. 2014 Mar 7;9(3):e90350.

7. Chea N, Yi SD, Rith S, Seng H, Ieng V, Penh C, Mardy S, Laurent D, Richner B, Sok T, Ly S, Kitsutani P, Asgari N, Roces MC, Buchy P, Tarantola A. Two clustered cases of confirmed influenza A(H5N1) virus infection, Cambodia, 2011.Euro Surveill. 2014 Jun 26;19(25). pii: 20839.

8. Goyet S, Barennes H, Libourel T, van Griensven J, Frutos R, Tarantola A. Knowledge translation: a case study on pneumonia research and clinical guidelines in a low- income country. Implement Sci. 2014 Jun 26;9:82.

9. 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 Behav. 2014 Mar;18(3):495-504.

10. Goyet S, Vlieghe E, Kumar V, Newell S, Moore CE, Bousfield R, Leang HC, Chuop S, Thong P, Rammaert B, Hem S, van Griensven J, Rachmat B, Fassier T, Lim K, Tarantola A. Etiologies and Resistance Profiles of Bacterial Community-Acquired Pneumonia in Cambodian and Neighboring Countries’ Health Care Settings: A Systematic Review (1995 to 2012). PLoS One. 2014 Mar 13;9(3):e89637 4

4 This article was recommended on March 28, 2014 by the Faculty of 1000 (http://f1000.com/prime/718310949) and viewed 1656 times in 2014.

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11. Goyet S, Vlieghe E, Lim K, van Griensven J, Borand L, Thong P, Rammaert B, Marcy O, Tarantola A. Fluoroquinolone resistance and Mycobacterium tuberculosis: CAP guidelines play an important role. Int J Tuberc Lung Dis. 2014 May;18(5):628-30.

12. Haridas V, Pean P, Jasenosky LD, Madec Y, Laureillard D, Sok T, Sath S, Borand L, Marcy O, Chan S, Tsitsikov E, Delfraissy JF, Blanc FX, Goldfeld AE. TB-IRIS and remodelling of the T-cell compartment in highly immunosuppressed HIV+ patients with TB: the CAPRI-T (ANRS-12614) study. AIDS. 2014 Dec 6. [Epub ahead of print] .

13. Horm SV, Mardy S, Rith S, Ly S, Heng S, Vong S, Kitsutani P, Ieng V, Tarantola A, Ly S, Sar B, Chea N, Sokhal B, Barr I, Kelso A, Horwood PF, Timmermans A, Hurt A, Lon C, Saunders D, Ung SA, Asgari N, Roces MC, Touch S, Komadina N, Buchy P. Epidemiological and virological characteristics of influenza viruses circulating in Cambodia from 2009 to 2011.PLoS One. 2014 Oct 23;9(10):e110713.

14. Lan NT, Thu NT, Barrail-Tran A, Duc NH, Lan NN, Laureillard D, Lien TT, Borand L, Quillet C, Connolly C, Lagarde D, Pym A, Lienhardt C, Dung NH, Taburet AM,Harries AD. Randomised pharmacokinetic trial of rifabutin with lopinavir/ritonavir-antiretroviral therapy in patients with HIV-associated tuberculosis in Vietnam. PLoS One. 2014 Jan 22;9(1):e84866.

15. Lover AA, Buchy P, Rachline A, Moniboth D, Huy R, Meng CY, Leo YS, Yuvatha K, Sophal U, Chantha N, Y B, Duong V, Goyet S, Brett JL, Tarantola A, Cavailler P. Spatial epidemiology and climatic predictors of paediatric dengue infections captured via sentinel site surveillance, Phnom Penh Cambodia 2011- 2012.BMC Public Health. 2014 Jun 28;14:658.

16. Marcy O, Laureillard D, Madec Y, Chan S, Mayaud C, Borand L, Prak N, Kim C,Lak KK, Hak C, Dim B, Sok T, Delfraissy JF, Goldfeld AE, Blanc FX; CAMELIA (ANRS 1295-CIPRA KH001) Study Team. Causes and determinants of mortality in HIV-infected adults with tuberculosis: an analysis from the CAMELIA ANRS 1295-CIPRA KH001 randomized trial. Clin Infect Dis. 2014 Aug;59(3):435-45.

17. Rammaert B; Goyet S; Tarantola A. Melioidosis Requires Better Data Sharing for Improved Diagnosis and Management in the Mekong Region. Am. J. Trop. Med. Hyg., 90(2), 2014, p. 383.

18. Rith S, Davis CT, Duong V, Sar B, Horm SV, Chin S, Ly S, Laurent D, Richner B, Oboho I, Jang Y, Davis W, Thor S, Balish A, Iuliano AD, Sorn S, Holl D, Sok T, Seng H, Tarantola A, Tsuyuoka R, Parry A, Chea N, Allal L, Kitsutani P, Warren D, Prouty M, Horwood P, Widdowson MA, Lindstrom S, Villanueva J, Donis R, Cox N, Buchy P. Identification of molecular markers associated with alteration of receptor-binding specificity in a novel genotype of highly pathogenic avian influenza A(H5N1) viruses detected in Cambodia in 2013. J Virol. 2014 Sep 10. pii: JVI.01887-14. [Epub ahead of print]

19. Robinson M°, Conan A°, Duong V, Ly S, Ngan C, Buchy P, Tarantola A*, Rodó X*. A model for a Chikungunya outbreak in a rural Cambodian setting: implications for disease control in uninfected areas.PLoS Negl Trop Dis. 2014 Sep 11;8(9):e3120.

20. 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. PLoS Negl Trop Dis 8(1): e2533.

Accepted for publication

21. Dim, B; Kerleguer, A; Kim, P; Pean, P; Phuong, V; Heng, N; Peng, Y; Borand, L; Tarantola, A. Necrotic tuberculin skin (Mantoux) test reaction: a case report and an estimation of frequency. Accepted for publication in CHEST.

Abstracts at conferences and meetings

1. Cappelle J , V Hul, V Duong, A Tarantola, P Buchy. Ecology of Flying foxes and the risk of Nipah virus emergence in Cambodia. Regional Symposium on Emerging Infectious Diseases in SEA. 11-12 March 2014, Phnom Penh, Cambodia.

2. Dommar CJ, Marguerite Robinson, Rachel Lowe, Anne Conan, Philippe Buchy, Arnaud Tarantola, and Xavier Rodó. Climate-driven mathematical models to understand the spatio-temporal heterogeneity of a chikungunya outbreak in the presence of widespread asymptomatic infection. EGU2014-4055 Poster in Session HS7.3/CL3.6/NP1.4. European Geosciences Union General Assembly 2014. Vienna, Austria, 27 April – 02 May 2014

3. Goyet S. Erika Vlieghe, Varun Kumar, Steven Newell, Catrin E. Moore, Rachel Bousfield, Heng C. Leang, Sokheng Chuop, Phe Thong, Blandine Rammaert, Sopheak Hem, Johan van Griensven, Agus Rachmat, Thomas Fassier, Kruy Lim, Arnaud Tarantola. CALIBAN : Revue des étiologies bactériennes et des profils d’antibio-résistance des Pneumonies Communautaires Acquises au Cambodge. Congrès Cambodgien des maladies respiratoires et de chirurgie thoracique, 14-15 Nov. 2014, Université des Sciences de la Santé, Phnom Penh.

4. Hem S, Paraye R,Tarantola A, Kerleguer A. Six years overview of Multi Drug Resistant Bacteria isolated in “Institut Pasteur du Cambodge”. Regional Symposium on Emerging Infectious Diseases in SEA. 11-12 March 2014, Phnom Penh, Cambodia.

5. Horm SV, S Rith, S Sorn, S Ly, T Sok, S Ly, R Tsuyuoka, W Kalpravidh, D Holl, MD Van Kerkhove, L Allal, A Tarantola, P Buchy. Human, environmental and animal surveillance of influenza A(H5N1) virus in Cambodian live poultry markets. Regional Symposium on Emerging Infectious Diseases in SEA. 11-12 March 2014, Phnom Penh, Cambodia.

6. Horm SV, S Rith, S Sorn, S Ly, T Sok, S Ly, R Tsuyuoka, W Kalpravidh, D Holl, MD Van Kerkhove, L Allal, A Tarantola, P Buchy. Human, environmental and animal surveillance of influenza A(H5N1) virus in Cambodian live poultry markets. Scientific Symposium of the Institut Pasteur International Network,Paris, September 10-13, 2014

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7. Horwood P, Horm Srey Viseth, Rith Sareth, Ly Sowath, Arnaud Tarantola, Philippe Buchy. A(H5N1) in Cambodia. 10th Australian Influenza Symposium, 12th-13th November 2014, Melbourne Australia

8. Ly S & V. Duong for the DENFREE task force. Clinical Dengue and Asymptomatic Infections in Rural Cambodia, Denfree Study 2012-2013 – Preliminary Results. Scientific Symposium of the Institut Pasteur International Network,Paris, September 10-13, 2014

9. Ly S, Ph. Buchy & A. Tarantola for the Rabies Prevention Group. In natura assessment of the effectiveness of various preventive regimens in persons exposed to confirmed rabid dogs in Cambodia, 2000-2010 : the IPC rabies lookback study. Scientific Symposium of the Institut Pasteur International Network,Paris, September 10-13, 2014

10. Marcy O, Mathurin Tejiokem, Huy Dung Nguyen, Laurence Borand, Philippe Msellati, Boubacar Nacro, Sophie Goyet, Arnaud Tarantola, Sylvain Godreuil, Christophe Delacourt, Stéphane Blanche, Vibol Ung, Groupe de Travail ANRS 12229 PAANTHER 01. Performance des tests Xpert MTB/RIF pour le diagnostic de la tuberculose chez les enfants infectés par le VIH. 7e Conférence Internationale Francophone VIH / Hépatites - AFRAVIH 2014 • Résumé : A-608-0006-0134.

11. Tarantola A & Buchy P. for the Rabies Prevention Group. In natura assessment of the effectiveness of various preventive regimens in persons exposed to confirmed rabid dogs in Cambodia, 2000-2010 : the IPC rabies lookback study. Regional Symposium on Emerging Infectious Diseases in SEA. 11-12 March 2014, Phnom Penh, Cambodia.

12. Tarantola A. Presentation on Kg Chhnang non-transmission of rabies from mother to child. 10th AREB meeting Manila 19-23 January.

13. Tor P, Paraye R, Tarantola A, Kerleguer A. First case of visceral Leishmaniasis reported in Cambodia. Regional Symposium on Emerging Infectious Diseases in SEA. 11-12 March 2014, Phnom Penh, Cambodia. J Cappelle , V Hul, V Duong, A Tarantola, P Buchy. Ecology of Flying foxes and the risk of Nipah virus emergence in Cambodia. Regional Symposium on Emerging Infectious Diseases in SEA. 11-12 March 2014, Phnom Penh, Cambodia.

14. M. Yakovleff, J. Cappelle, D. Prasetyo, V. Duong, S. Ong, S. Sorn, R. Duboz, A. Tarantola, P. Buchy, V. Chevallier. Japanese encephalitis in a peri-urban pig slaughterhouse of Cambodia : A deterministic meta-population model to quantify the risk of transmission to humans. 12th International Conference on Molecular Epidemiology and Evolutionary Genetics of Infectious Diseases; 11-13 December, 2014, The Royal River Hotel, Bangkok

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Impact Factor for 20 epi@ipc publications in 2014

ERA 2010 scores for 20 epi@ipc publications in 2014*5

5 http://www.arc.gov.au/era/era_2012/archive/era_journal_list.htm ; http://lamp.infosys.deakin.edu.au/era/?page=fordet10&selfor=1117

0

1

2

3

4

5

6

7

8

9

10

16%

31%

32%

16%

5%

A* (top 5%): "Virtually all papers they publish will be of a very high quality"

A (next 15%): "The majority of papers in a Tier A journal will be of very high quality"

B (next 30%): "Generally, in a Tier B journal, one would expect only a few papers of very high quality"

C (next 50%): Journals "that do not meet the criteria of higher tiers"

Unrated in 2010 (Eurosurveillance)

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Available altmetrics for 8 articles in Plos or BMC journals (to 10 Jan. 2015)

Indicators HTML Page

Views

PDF Down-loads

XML Down-loads

Totals

1. Virological Failure and HIV-1 Drug Resistance Mutations among Naive and Antiretroviral Pre-Treated Patients Entering the ESTHER Program of Calmette Hospital in Cambodia

495 117 10 622

2. Etiologies and Resistance Profiles of Bacterial Community-Acquired Pneumonia in Cambodian and Neighboring Countries’ Health Care Settings: A Systematic Review (1995 to 2012)

1347 293 19 1659

3. Plasma concentrations efficacy and safety of efavirenz in HIV-infected adults treated for tuberculosis in Cambodia (ANRS 1295-CIPRA KH001 CAMELIA trial

750 174 24 948

4. Epidemiological and virological characteristics of influenza viruses circulating in Cambodia from 2009 to 2011 332 87 23 442

5. Randomised pharmacokinetic trial of rifabutin with lopinavir/ritonavir-antiretroviral therapy in patients with HIV-associated tuberculosis in Vietnam 1726 313 24 2063

6. Spatial epidemiology and climatic predictors of paediatric dengue infections captured via sentinel site surveillance Phnom Penh Cambodia 2011- 2012 1371

7. A model for a Chikungunya outbreak in a rural Cambodian setting: implications for

disease control in uninfected areas 3066 301 21 3388

8. Estimating the Burden of Japanese Encephalitis Virus and Other Encephalitides in Countries of the Mekong Region

5355 451 25 5831

Total 14442 1736 146 14953

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