Unit: Epidemiology of Emerging Diseases

Director: FONTANET Arnaud

The Emerging Diseases Epidemiology Unit was founded on 1 July 2001. The main research topics of the Unit are: 1) transmission modes of and means of prevention against emerging disease agents; and 2) clinical research, in particular natural history cohorts and clinical trials. Most research projects take place in developing countries, preferably in collaboration with institutes from the International Network of Pasteur Institutes, and deal with the epidemiology of HIV, hepatitis C virus (HCV), hepatitis B virus (HBV), and the SARS coronavirus.

Introduction

The Emerging Diseases Epidemiology Unit was founded on 1 July, 2001.

The main research topics of the unit are 1) the transmission modes of and means of prevention against emerging diseases agents; and 2) clinical research, and particularly natural history cohorts and clinical trials of treatments against the HIV, HCV, and HBV. "Emerging disease agents" are agents recently spread via epidemics in human populations (e.g., HIV), agents recently identified (e.g., HCV), and re-emerging agents (e.g., P.falciparum and M.tuberculosis).

Areas of expertise in the Unit include: contributing to the strategic thinking of the Institute in areas where epidemiology takes a leading role; providing epidemiological and biostatistical assistance to other research units of the Institute; and in participating in the teaching activities in epidemiology locally and as part of the international network. In this context, special effort has been dedicated to the preparation of epidemiology and biostatistics curriculum for the Pasteur School of Infectiology, and to the initiation of a training scheme in clinical research for institutes of the network.

Most of the Unit's research projects take place in developing countries, preferably in collaboration with institutes of the international Network of Pasteur Institutes.

On-going projects

1) Epidemiology and treatment of HCV infection in Egypt (A. Fontanet and C. Rekacewicz)

Egypt is the country with the highest HCV prevalence in the world, reaching 45% among adults older than 40 years of age in rural areas. The number of people infected with HCV was estimated at around 8 million in 1999 by the Egyptian Ministry of Health and Population. The origin of this epidemic has been attributed to mass treatment campaigns of intravenous injections for bilharziosis from 1960 to1982.

This project, headed by A. Fontanet and M.K. Mohamed, is funded by the European Commission (2001-2005) and by the French National Agency for Research on AIDS (ANRS) (2002-2004 with possibility for extension). The project has several components: 1) the establishment of a cohort study on HCV incidence and infection progression in a rural population (n=4000); 2) the validation of blood donors as a sentinel population for monitoring HCV trends in the general population; 3) the identification of risk factors for HCV infection in urban areas through a case-control study comparing exposures in patients with acute hepatitis C with those of controls; 4) a study of the efficacy of pegylated interferon and ribavirin in the treatment of chronic hepatitis C in Egypt (genotype 4); and 5) a study of the efficacy of pegylated interferon in the treatment of acute hepatitis C. Our partners in this project are the unit INSERM U444 (Director: AJ Valleron) which coordinated the European part of the project (B. Larouzé) and the mixed unit Pasteur/INSERM U370 of C. Bréchot for its expertise in the virological and clinical aspects of HCV. Egyptian partners of this project are Ain Shams University in Cairo (Mostafa K. Mohamed) and the Egyptian Ministry of Health (Saeed Aoun).

2) Epidemiology of the SARS coronavirus (Coordination: A. Fontanet and L. Baril)

Following the SARS outbreak in China, a project funded by the European Commission, the French Ministry of Foreign Affairs and the Chinese Ministry of Science and Technology has been initiated to study the epidemiology of the SARS coronavirus. The main objectives of the project include: 1) the search for an animal reservoir for the SARS-like coronavirus; 2) the study of long-term clinical complications and humoral immunity in Chinese convalescent patients and; 3) the factors associated with the spread of the epidemic in Beijing in March-June 2003. The research work for the search of an animal reservoir is carried out in close collaboration with the National Museum of Natural History (G. Véron) and the French Agency for Food Safety (F. Moutou). Other partners at Institut Pasteur are the CIBU (JC Manuguerra) and the Hong-Kong Pasteur Centre (R. Altmeyer).

3) Randomised clinical trial for the treatment of chronic hepatitis B in Senegal (Coordination: M. Vray and P.S. Mbaye).

HBV infection is a major public health problem in Senegal, where 15% of the population is chronically infected. The goal of the project is to assess a pragmatic treatment strategy appropriate for resource-poor countries. HEPADAK2 is an open randomised trial comparing the efficacy of the combination of lamivudine plus vaccinotherapy (12 intradermal Engerix B injections over 6 months) versus lamivudine alone. Patients enrolment should start in January 2005 and last 12 to 18 months. Patients will then be treated for one year, and then followed another year without treatment as part of the protocol. The study is carried out together with the Institut Pasteur de Dakar, and is funded by ANRS.

4) Immunogenicity of EPI immunisations in HIV-infected children in Africa (Coordination: L. Baril, I. Gouandjika, M.C. Teijokem).

This project aims at assessing the response to vaccines used in the EPI among HIV-infected children compared to non-infected children in Sub-Saharan Africa. The project is done in collaboration with the Centre Pasteur du Cameroun and the Institut Pasteur de Bangui.

5) Management of infectious lung disease among adults with HIV/AIDS in Africa (Dakar, Bangui) and South-East Asia (Phnom Penh, Ho Chi Minh) (Principal Investigators: Y. Germani and P. Lehr) (C. Rekacewicz, M. Vray, A. Fontanet).

This project concerns infectious etiologies of lung disease among hospitalised HIV-infected patients. Broncho-fibroscopy will be used in non-tubercular patients depending on radiological aspects and response to conventional antibiotic treatment. Study sites are Dakar (Senegal), Bangui (Central African Republic), Phnom Penh (Cambodia) and Ho Chi Minh (Vietnam). Institutes from the International Network are fully involved in this multicentric study coordinated by Y. Germani (Bangui) and P. Lehr (Paris) and funded by ANRS.

6) HCV epidemiology in Cambodia (Principal Investigators: A Sall and A Fontanet).

This project aims to improve assays used for the diagnosis of HCV infection and to better characterize the molecular epidemiology of HCV in South-East Asia. The scientific coordinators of the project are A. Sall, Virologist at the Pasteur Institute in Dakar with two years of experience at the Pasteur Institute in Cambodia and A. Fontanet. Our Unit is responsible for the epidemiological and biostatistical aspects of the study. This project is part of an ACIP and a PTR coordinated by Penelope Mavromara (IP in Greece).

7) Management of cryptococcosis in Cambodia (R. Micol and A. Fontanet).

This study is assessing the usefulness of screening for serum cryptococcal antigen among HIV-infected patients in Cambodia. A cost-effectiveness analysis will compare several strategies for the management of cryptococcosis among HIV-infected patients in Cambodia: 1) no systematic screening; 2) primary chemoprophylaxis among patients with less than 200 CD4 counts; 3) systematic screening with serum cryptococcal antigen and ambulatory treatment of patienst with positive antigen. This work is done in collaboration with the Institut Pasteur du Cambodge (B. Sarr), the Unité Postulante de Mycologie Moléculaire (F. Dromer and O. Lortholary), and hospitals in charge of patients in Cambodia. This project is partially funded by SIDACTION.

8) HIV epidemic modelling in South Africa (M. Garenne and P. Leclerc).

South Africa is one of the countries with the highest HIV prevalence in the world. In some areas, close to 50% of women aged 25 years are infected. Such prevalence rates are not compatible with available knowledge on HIV transmission rates and data on number of sexual partners among these women. Innovative modelling strategies will be tested to reproduce the HIV epidemiological profile observed in these areas.

Keywords: epidemiology, clinical research, developing countries, HIV, HCV, HBV, SARS


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