[show abstract][hide abstract] ABSTRACT: There exists great disparity in the number of clinical P. falciparum episodes among children of the same age and living in similar conditions. The epidemiological determinants of such disparity are unclear. We used a data-mining approach to explore a nineteen-year longitudinal malaria cohort study dataset from Senegal and identify variables associated with increased risk of malaria episodes. These were then verified using classical statistics and replicated in a second cohort. In addition to age, we identified a novel high-risk group of children in whom the history of P. falciparum clinical episodes greatly increased risk of further episodes. Age and a high number of previous falciparum clinical episodes not only play major roles in explaining the risk of P. falciparum episodes but also are risk factors for different groups of people. Combined, they explain the majority of falciparum clinical attacks. Contrary to what is widely believed, clinical immunity to P. falciparum does not de facto occur following many P. falciparum clinical episodes. There exist a sub-group of children who suffer repeated clinical episodes. In addition to posing an important challenge for population stratification during clinical trials, this sub-group disproportionally contributes to the disease burden and may necessitate specific prevention and control measures.
PLoS ONE 01/2013; 8(2):e55666. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: Substantial reductions in malaria have been reported in several African countries after distribution of insecticide-treated bednets and the use of artemisinin-based combination therapies (ACTs). Our aim was to assess the effect of these policies on malaria morbidity, mosquito populations, and asymptomatic infections in a west African rural population.
We did a longitudinal study of inhabitants of Dielmo village, Senegal, between January, 2007, and December, 2010. We monitored the inhabitants for fever during this period and we treated malaria attacks with artesunate plus amodiaquine. In July, 2008, we offered longlasting insecticide (deltamethrin)-treated nets (LLINs) to all villagers. We did monthly night collections of mosquitoes during the whole study period, and we assessed asymptomatic carriage from cross-sectional surveys. Our statistical analyses were by negative binomial regression, logistic regression, and binomial or Fisher exact test.
There were 464 clinical malaria attacks attributable to Plasmodium falciparum during 17,858 person-months of follow-up. The incidence density of malaria attacks averaged 5·45 (95% CI 4·90-6·05) per 100 person-months between January, 2007, and July, 2008, before the distribution of LLINs. Incidence density decreased to 0·41 (0·29-0·55) between August, 2008, and August, 2010, but increased back to 4·57 (3·54-5·82) between September and December, 2010--ie, 27-30 months after the distribution of LLINs. The rebound of malaria attacks were highest in adults and children aged 10 years or older: 45 (63%) of 71 malaria attacks recorded in 2010 compared with 126 (33%) of 384 in 2007 and 2008 (p<0·0001). 37% of Anopheles gambiae mosquitoes were resistant to deltamethrin in 2010, and the prevalence of the Leu1014Phe kdr resistance mutation increased from 8% in 2007 to 48% in 2010 (p=0·0009).
Increasing pyrethroid resistance of A gambiae and increasing susceptibility of older children and adults, probably due to decreasing immunity, caused the rebound and age shift of malaria morbidity. Strategies to address the problem of insecticide resistance and to mitigate its effects must be urgently defined and implemented.
Institut de Recherche pour le Développement and the Pasteur Institute of Dakar.
The Lancet Infectious Diseases 08/2011; 11(12):925-32. · 19.97 Impact Factor
[show abstract][hide abstract] ABSTRACT: Despite considerable success of genome wide association (GWA) studies in identifying causal variants for many human diseases, their success in unraveling the genetic basis to complex diseases has been more mitigated. Pathogen population structure may impact upon the infectious phenotype, especially with the intense short-term selective pressure that drug treatment exerts on pathogens. Rigorous analysis that accounts for repeated measures and disentangles the influence of genetic and environmental factors must be performed. Attempts should be made to consider whether pathogen diversity will impact upon host genetic responses to infection.We analyzed the heritability of two Plasmodium falciparum phenotypes, the number of clinical malaria episodes (PFA) and the proportion of these episodes positive for gametocytes (Pfgam), in a family-based cohort followed for 19 years, during which time there were four successive drug treatment regimes, with documented appearance of drug resistance. Repeated measures and variance components analyses were performed with fixed environmental, additive genetic, intra-individual and maternal effects for each drug period. Whilst there was a significant additive genetic effect underlying PFA during the first drug period of study, this was lost in subsequent periods. There was no additive genetic effect for Pfgam. The intra-individual effect increased significantly in the chloroquine period.The loss of an additive genetic effect following novel drug treatment may result in significant loss of power to detect genes in a GWA study. Prior genetic analysis must be a pre-requisite for more detailed GWA studies. The temporal changes in the individual genetic and the intra-individual estimates are consistent with those expected if there were specific host-parasite interactions. The complex basis to the human response to malaria parasite infection likely includes dominance/epistatic genetic effects encompassed within the intra-individual variance component. Evaluating their role in influencing the outcome of infection through host genotype by parasite genotype interactions warrants research effort.
PLoS ONE 01/2011; 6(11):e26364. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: Complex, high-dimensional data sets pose significant analytical challenges in the post-genomic era. Such data sets are not exclusive to genetic analyses and are also pertinent to epidemiology. There has been considerable effort to develop hypothesis-free data mining and machine learning methodologies. However, current methodologies lack exhaustivity and general applicability. Here we use a novel non-parametric, non-euclidean data mining tool, HyperCube®, to explore exhaustively a complex epidemiological malaria data set by searching for over density of events in m-dimensional space. Hotspots of over density correspond to strings of variables, rules, that determine, in this case, the occurrence of Plasmodium falciparum clinical malaria episodes. The data set contained 46,837 outcome events from 1,653 individuals and 34 explanatory variables. The best predictive rule contained 1,689 events from 148 individuals and was defined as: individuals present during 1992-2003, aged 1-5 years old, having hemoglobin AA, and having had previous Plasmodium malariae malaria parasite infection ≤10 times. These individuals had 3.71 times more P. falciparum clinical malaria episodes than the general population. We validated the rule in two different cohorts. We compared and contrasted the HyperCube® rule with the rules using variables identified by both traditional statistical methods and non-parametric regression tree methods. In addition, we tried all possible sub-stratified quantitative variables. No other model with equal or greater representativity gave a higher Relative Risk. Although three of the four variables in the rule were intuitive, the effect of number of P. malariae episodes was not. HyperCube® efficiently sub-stratified quantitative variables to optimize the rule and was able to identify interactions among the variables, tasks not easy to perform using standard data mining methods. Search of local over density in m-dimensional space, explained by easily interpretable rules, is thus seemingly ideal for generating hypotheses for large datasets to unravel the complexity inherent in biological systems.
PLoS ONE 01/2011; 6(9):e24085. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: This study gives the report of an epidemiological investigation of seven death cases in a police force headquarters by pesticide poisoning diagnosed by the decrease of the enzyme choline esterase activity. A case control study with an environmental description has been realized, permitting the establishment of temporarily dynamic relationships among the death cases. In Africa, there are many incidents of domestic or professional poisoning with a fatal ending for which, few data are available. The aetiological orientations are discussed in the African context and the difficulties to reach the analysis of toxicology in sub-Saharan Africa are underlined.
Journal of Agricultural Biotechnology and Sustainable Development. 05/2010; 2:51-55.
[show abstract][hide abstract] ABSTRACT: In 2006, the Senegalese National Malaria Control Programme (NMCP) has recommended artemisinin-based combination therapy (ACT) as the first-line treatment for uncomplicated malaria and, in 2007, mandated testing for all suspected cases of malaria with a Plasmodium falciparum HRP-2-based rapid diagnostic test for malaria (RDT(Paracheck). Given the higher cost of ACT compared to earlier anti-malarials, the objectives of the present study were i) to study the accuracy of Paracheck compared to the thick blood smear (TBS) in two areas with different levels of malaria endemicity and ii) analyse the cost-effectiveness of the strategy of the parasitological confirmation of clinically suspected malaria cases management recommended by the NMCP.
A cross-sectional study was undertaken in the villages of Dielmo and Ndiop (Senegal) nested in a cohort study of about 800 inhabitants. For all the individuals consulting between October 2008 and January 2009 with a clinical diagnosis of malaria, a questionnaire was filled and finger-prick blood samples were taken both for microscopic examination and RDT. The estimated costs and cost-effectiveness analysis were made considering five scenarios, the recommendations of the NMCP being the reference scenario. In addition, a sensitivity analysis was performed assuming that all the RDT-positive patients and 50% of RDT-negative patients were treated with ACT.
A total of 189 consultations for clinically suspected malaria occurred during the study period. The sensitivity, specificity, positive and negative predictive values were respectively 100%, 98.3%, 80.0% and 100%. The estimated cost of the reference scenario was close to 700 euros per 1000 episodes of illness, approximately twice as expensive as most of the other scenarios. Nevertheless, it appeared to us cost-effective while ensuring the diagnosis and the treatment of 100% of malaria attacks and an adequate management of 98.4% of episodes of illness. The present study also demonstrated that full compliance of health care providers with RDT results was required in order to avoid severe incremental costs.
A rational use of ACT requires laboratory testing of all patients presenting with presumed malaria. Use of RDTs inevitably has incremental costs, but the strategy associating RDT use for all clinically suspected malaria and prescribing ACT only to patients tested positive is cost-effective in areas where microscopy is unavailable.
[show abstract][hide abstract] ABSTRACT: Two cases of Crimean-Congo haemorrhagic fever (CCHF) occurred in two French tourists during their visit in Senegal in November 2004. Febrile and hemorrhagic syndrome with ulorrhagia, petechiae, haematemesis, haematomas associated with biological signs of disseminated intramuscular coagulation were observed. For the first case who had a medical evacuation to France before diagnosis, Crimean-Congo virus infection was revealed by laboratory tests performed by the National Reference Center for Hemorrhagic Fevers (NRCHF, Institut Pasteur, Lyon) and secondly by the Centre de Référence OMS sur la Recherche des Arbovirus et des virus des Fièvres Hémorragiques (CRORA) in the Dakar Pasteur Institute (DPI). The second case diagnosed by the CRORA died after clinical deterioration with liver failure and severe haemorrhages. Healthcare workers and family members who had contact with tissue or blood from patients were followed up after the putative exposure either in France or in Senegal.
Bulletin de la Société de pathologie exotique 09/2009; 102(3):159-61.
[show abstract][hide abstract] ABSTRACT: The relationship between Plasmodii transmission, infection, morbidity, genetic susceptibility and acquisition of natural immunity is studied among two cohorts in the Senegalese villages of Dielmo (300 inhabitants) and Ndiop (350 inhabitants) where malaria is holoendemic (about 200 P. falciparum infective bites/person/year) and mesoendemic (about 20 P. falciparum infective bites/person/year), respectively. The populations are under a daily active clinical survey. Blood samples are collected at least once per month. Plasma and red blood cells are stored in bio-libraries that allow longitudinal studies of the immune responses against plasmodial antigens and the investigation of the natural history of P. falciparum infections by molecular genotyping methods.
Revue d Épidémiologie et de Santé Publique 03/2003; 51(1 Pt 2):175-82. · 0.69 Impact Factor
[show abstract][hide abstract] ABSTRACT: Plasmodium falciparum has a complex transmission cycle. Public health planning and research would benefit from the ability of a calibrated model to predict the epidemiologic characteristics of populations living in areas of malaria endemicity. This paper describes the application of Bayesian calibration to a malaria transmission model using longitudinal data gathered from 176 subjects in Ndiop, Senegal, from July 1, 1993, to July 31, 1994. The model was able to adequately predict P. falciparum parasitemia prevalence in the study population. Further insight into the dynamics of malaria in Ndiop was provided. During the dry season, the estimated fraction of nonimmune subjects goes down to 20% and then increases up to 80%. The model-predicted time-weighted average incidences contributed by nonimmune and immune individuals are 0.52 cases per day and 0.47 cases per day, respectively. The median times needed to acquire infection (conversion delay) for nonimmune and immune individuals are estimated at 39 days and 285 days, respectively.
American Journal of Epidemiology 11/2000; 152(8):760-70. · 4.78 Impact Factor