Epidémiologie des Maladies Emergentes : Projets

Funding : DCI Monaco.

In collaboration with epidemiologists from the Centre de Recherche Médicale et Sanitaire (CERMES) in Niamey, we are using recent advances in Geographic Information Systems and statistical methodology to investigate the spatio-temporal dynamics of meningitis epidemics in Niger at a fine geographic scale (health centres) and the associated risk factors (project funded by the Office of International Cooperation of the Principality of Monaco ; Scientific Coordinator: Arnaud Fontanet).
Spatial analyses first revealed the highly localized nature of these annual epidemics, constituted by small spatial clusters of cases (Paireau et al, PLoS Negl Trop Dis, 2012). We identified heterogeneous spatio-temporal patterns, with emergence of outbreaks in different areas from year to year, followed by spread in variable geographic directions. We also showed that surveillance at a fine spatial scale would be more efficient for public health response: outbreaks would be detected earlier and reactive vaccination would be better targeted. The factors that could explain the observed spatio-temporal patterns at the health centre scale are still poorly understood and statistical models are under development in our group, integrating jointly climatic, environmental, socio-demographic and vaccination data.
Our findings should help to improve control of meningitis in sub-Saharan Africa, especially in the context of introduction of a new meningococcal A conjugate vaccine.

Funding: ANR, Fondation Raoul Follereau, Fondation SANOFI Espoir.   

In this new research program, we will conduct for the first time the simultaneous collection of environmental (plants and insects) and human samples in two historically endemic regions located in different climates (equatorial and subtropical in Cameroon and Benin, respectively) and one newly discovered endemic focus close to a dam (in Cameroon).  Samples will be analysed for the presence of M.ulcerans, and characterised phylogenetically, to offer better understanding of the circulation of M.ulcerans across ecological niches.  Maps of M. ulcerans presence probability, as well as of M. ulcerans exposure risk, will be produced at the regional scale and tentatively expanded at the national scale, to target more efficiently diagnostic and care resources.

We will also focus on the role of peri-domestic insects in M.ulcerans transmission.  Indeed, two studies of our group suggest that individuals sleeping under mosquito nets are at a lower risk of Buruli ulcer than those who do not.  Knowing that in Australia, mosquitoes are considered as potential vectors for M.ulcerans (Lavender C.J. et al., PLoS NTD, 2011), and repellents are recommended for protection against Buruli ulcer, we seek to expand our initial studies by capturing insects around houses and using PCR to search for M.ulcerans DNA in these insects.

Accounting for HIV serological status in patients is critically important for effective malaria prevention. CTX is recommended for preventing opportunistic infections in HIV positive women with CD4 count < 350 clls/mm3. The efficacy of CTX as a prophylaxis for P. falciparum malaria is well known. A clinical trial (CTX versus SP) undertaken among children in Bandiagara, Mali reported a protective efficacy of 99.7%. The WHO and the Central African Republic (CAR) recommend intermittent SP as malaria prophylaxis for pregnant women. Therefore it is superfluous and contraindicated to provide SP and CTX together in HIV-positive persons when CD4 is <350 cells/mm3. In contrast, few studies until now have described the efficacy of CTX in the prevention of malaria among pregnant women, and particularly its efficacy in an environment in which frequent therapeutic failures of SP are on the rise, as is the case in the CAR. Finally, although existing studies have not confirmed this hypothesis, there remain persistent concerns about the possible development of cross-resistance in P. falciparum to both CTX and SP because of their similar modes of action.

The principal objective of this randomized, open label trial, carried out under real-life conditions of care, is to demonstrate the superiority of CTX (administered as a daily dose until childbirth) over SP (administered as directly observed treatment of three doses) on placental malaria parasitaemia in HIV-positive pregnant women whose CD4 count > 350 cells/mm3. This study will also permit to compare the two treatments in terms of the incidence of malaria episodes during pregnancy, profiles of resistant parasites isolated during these malaria episodes and in the placenta during childbirth, material anemia, birth weight, and infant anemia. An evaluation of adherence to the CTX treatment will be conducted at each prenatal visit; women included in the trial will be asked to report the number of pills remaining in their possession. We plan to recruit 150 women in each group.

Expected results:

The principal hypothesis is that CTX is more efficacious than SP on placental malaria parasitaemia. This result could be explained by higher plasma levels among those taking CTX. The verification of this hypothesis will permit the recommendation of CTX as a prophylactic treatment for malaria among HIV-positive women, regardless of CD4 count.  

The primary aim is to test the acceptability and feasibility of an intervention package for the community management of childhood malaria. The package includes rapid diagnostic testing, coartem and referral of serious cases to the nearest health care center; pre-treatment of serious cases is currently being analysed. Beginning in mid-2013, the community management strategy will be carried out by trained community health workers and medical personnel. For the qualitative part of this study, our primary interest is to investigate the changing ways that parents in southwestern Burkina Faso have understood the etiologies, treatment and control of local categories of illnesses that are related to “malaria” but not understood in precisely the same way. The aim of this research question is to tailor the use of the intervention package in such a way that it is meaningful to southwestern Burkinabe populations.

Publication