A. Spiegel

Genetic determination and linkage mapping of Plasmodium falciparum malaria related traits in Senegal.

Plasmodium falciparum malaria episodes may vary considerably in their severity and clinical manifestations. There is good evidence that host genetic factors contribute to this variability. To date, most genetic studies aiming at the identification of these genes have used a case/control study design for severe malaria, exploring specific candidate genes. Here, we performed a family-based genetic study of falciparum malaria related phenotypes in two independent longitudinal survey cohorts, as a first step towards the identification of genes and mechanisms involved in the outcome of infection. We studied two Senegalese villages, Dielmo and Ndiop that differ in ethnicity, malaria transmission and endemicity. We performed genome-scan linkage analysis of several malaria-related phenotypes both during clinical attacks and asymptomatic infection. We show evidence for a strong genetic contribution to both the number of clinical falciparum malaria attacks and the asymptomatic parasite density. The asymptomatic parasite density showed linkage to chromosome 5q31 (LOD = 2.26, empirical p = 0.0014, Dielmo), confirming previous findings in other studies. Suggestive linkage values were also obtained at three additional chromosome regions: the number of clinical malaria attacks on chromosome 5p15 (LOD = 2.57, empirical p = 0.001, Dielmo) and 13q13 (LOD = 2.37, empirical p = 0.0014 Dielmo), and the maximum parasite density during asymptomatic infection on chromosome 12q21 (LOD = 3.1, empirical p<10−4, Ndiop). While regions of linkage show little overlap with genes known to be involved in severe malaria, the four regions appear to overlap with regions linked to asthma or atopy related traits, suggesting that common immune related pathways may be involved.

Investigation on a pertussis outbreak in a military school: risk factors and approach to vaccine efficacy.

INTRODUCTION Pertussis (whooping cough) is a toxic bacterial infection caused mainly by Bordetella pertussis. In mid-January 2006, several cases of pertussis were diagnosed in a military boarding-school. An investigation was carried out at the end of January to identify the risk factors for infection and to evaluate the efficacy of vaccination. SUBJECTS AND METHODS Three definitions were used to distinguish the cases; confirmed biologically, confirmed epidemiologically and suspected cases. The risk factor study was carried out after the exclusion of suspect cases. Vaccine efficacy (VE) was evaluated from a case-control study where only biologically confirmed cases were included. For each case, five controls were matched according to age, sex and class. A logistic regression and a conditional logistic regression were performed for the risk factor study and vaccine efficacy, respectively. Statistical analysis was carried out using Stata 9.2 software. RESULTS A total of 206 cases were included, 17 of them biologically confirmed, 66 epidemiologically and 123 suspected cases. The attack rate was 17.8 per 100. Girls were 1.8 times more likely to catch pertussis (p=0.04), pupils in the first year of college, as well as those in high school were at 5 times greater risk of catching pertussis (p=0.008) than those in the second year of college. For pupils who benefited from at least 5 doses, the VE was at 80% when the last dose dated from less than 6 years earlier. DISCUSSION/CONCLUSION The attack rate observed in our study was similar to those normally seen during epidemics occurring within a community. Vaccine efficacy declined depending on the time lapse since the last vaccination. Since April 2008, the Public Health Authorities have planned to provide pertussis booster vaccinations for children aged 16-18 who missed those for 11-13-year-old, and for adults aged 26-27 and those who have not been vaccinated for more than 10 years.