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), the SARS coronavirus, and the dengue virus.
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 agents who recently covered new geographical areas (e.g., dengue virus).
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.
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, has just obtained renewed funding (2006-8) through ANRS (genetic epidemiology in collaboration with Laurent Abel, INSERM U550 and study of acute hepatitis C) and the Wellcome Trust (study of the association between hepatitis C and atherosclerosis in collaboration with Lish Chaturvedi, Imperial College, London). The project is based at two study sites: 1) a cohort study on HCV incidence and progression in a village north-west of cairo and 2) a surveillance system for acute hepatitis C in Cairo.
2) EPISARS: prevention of SARS re-emergence (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 prevention of SARS re-emergence in human population; and 3) the study of long-term clinical complications and humoral immunity in Chinese convalescent patients. 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 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. Trial enrolment has started in September 2005.
4) DENFRAME : Innovative Diagnostic Tools and therapeutic approaches for dengue disease'. (Coordination: L Baril et P Despres).
Dengue is a vector (Aedes) borne disease affecting most tropical areas. WHO estimates that 100 million cases take place every year, leading to 50 000 deaths. This project, DENFRAME, is funded by the EC (FP6-2003-INCO-DEV2) for 3 years (Nov 2005-Oct 2008). Thirteen institutions are involved, including 5 from the International Network of Instituts Pasteur (IP Paris, IP Ho Chi Minh Ville, IP Cambodge, Centre Pasteur de Hong Kong et IP de la Guyane). A clinical study involving families of patients with proven symptomatic dengue is being started in 4 countries (Cambodia, Vietnam, Brasil, and French Guyana). The objective is to better describe the immunological characteristics, particularly the innate immunity, among persons with symptomatic and pauci-symptomatic dengue in order to better understand the physiopathological mechanisms leading to fatal hemorrhagic manifestations. The project also aims at improving diagnostic tools and developing antiviral therapy.
5) 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. Results have shown a lower response to all vaccines in children infected with HIV, suggesting that the immunisation schedule may need strengthening in these children. Longitudinal follow-up of infected children is considered to confirm these results (conditional on additional funding).
6) Response to HAART among HIV-infected patients in Cambodia (A. Fontanet et Y. Madec)
This project is carried out in collaboration with Médecins Sans Frontières (MSF) and Epicentre. It uses data from the treatment program run by MSF for HIV-infected patients in Phnom Penh, Cambodia. The analysis of data from the patients' cohort allows an assessment of the efficacy of HAART in developing countries.
7) HIV epidemic modelling in South Africa (M. Garenne, P. Leclerc and A Matthews).
Sub-saharan African countries account for 80% of HIV mortality in the world. In some areas of the South of Africa, 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, dengue