Scott, J.A. et al. Relation between falciparum malaria and bacteraemia in Kenyan children: a population-based, case-control study and a longitudinal study. Lancet 378, 1316-1323

Kenya Medical Research Institute-Wellcome Trust Research Programme, Kilifi, Kenya. ascott@ikilifi .org
The Lancet (Impact Factor: 45.22). 09/2011; 378(9799):1316-23. DOI: 10.1016/S0140-6736(11)60888-X
Source: PubMed


Many investigators have suggested that malaria infection predisposes individuals to bacteraemia. We tested this hypothesis with mendelian randomisation studies of children with the malaria-protective phenotype of sickle-cell trait (HbAS).
This study was done in a defined area around Kilifi District Hospital, Kilifi, Kenya. We did a matched case-control study to identify risk factors for invasive bacterial disease, in which cases were children aged 3 months to 13 years who were admitted to hospital with bacteraemia between Sept 16, 1999, and July 31, 2002. We aimed to match two controls, by age, sex, location, and time of recruitment, for every case. We then did a longitudinal case-control study to assess the relation between HbAS and invasive bacterial disease as malaria incidence decreased. Cases were children aged 0-13 years who were admitted to hospital with bacteraemia between Jan 1, 1999, and Dec 31, 2007. Controls were born in the study area between Jan 1, 2006, and June 23, 2009. Finally, we modelled the annual incidence of bacteraemia against the community prevalence of malaria during 9 years with Poisson regression.
In the matched case-control study, we recruited 292 cases-we recruited two controls for 236, and one for the remaining 56. Sickle-cell disease, HIV, leucocyte haemozoin pigment, and undernutrition were positively associated with bacteraemia and HbAS was strongly negatively associated with bacteraemia (odds ratio 0·36; 95% CI 0·20-0·65). In the longitudinal case-control study, we assessed data from 1454 cases and 10,749 controls. During the study period, the incidence of admission to hospital with malaria per 1000 child-years decreased from 28·5 to 3·45, with a reduction in protection afforded by HbAS against bacteraemia occurring in parallel (p=0·0008). The incidence of hospital admissions for bacteraemia per 1000 child-years also decreased from 2·59 to 1·45. The bacteraemia incidence rate ratio associated with malaria parasitaemia was 6·69 (95% CI 1·31-34·3) and, at a community parasite prevalence of 29% in 1999, 62% (8·2-91) of bacteraemia cases were attributable to malaria.
Malaria infection strongly predisposes individuals to bacteraemia and can account for more than half of all cases of bacteraemia in malaria-endemic areas. Interventions to control malaria will have a major additional benefit by reducing the burden of invasive bacterial disease.
Wellcome Trust.

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    • "of the hemolytic infection in order to avoid exacerbated heme toxicity . The greatest reduction in co - morbidity will undoubtedly come from public health measures to control or eliminate the hemolytic infections . Malaria control is already known to produce dramatic decreases in the population burden of NTS bacteremia ( Mackenzie et al . , 2010 ; Scott et al . , 2011 ) and all - cause child mortality ( Kleinschmidt et al . , 2009 ) . Control of Carrion ' s disease appears more challenging , and indications of expanding geographical distribution suggest that co - infections may remain a problem for the foreseeable future ( Minnick et al . , 2014 ) ."
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    • "More recent community-based studies of the incidence of invasive bacterial infections in rural Gambia and Kenya have all documented a significant contribution to childhood morbidity and mortality in developing countries. One of the risk factors to develop invasive bacterial infections in Africa is Plasmodium falciparum malaria [Anthony et al., 2009; Scott et al., 2011; Bassat et al., 2009; Bronzan et al., 2007; Church et al., 2014]. "
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    • "HbSS is the only significant cause of SCD in Kenya [12]. Results of blood tests for HbS typing, conducted by either cellulose acetate hemoglobin electrophoresis (Helena Laboratories, Beaumont, TX, USA) or by high performance liquid chromatography (Variant Analyzer, BioRad, Hercules, CA, USA), were available for a subset of children who were either tested during the course of their admission to KDH or who were members of two prospective cohort studies: (i) the Kilifi Sickle Cell Disease (KSCD) study [13] or the Kilifi Genetic Birth Cohort (KGBC) study [14]. We quantified the contribution of SCD to childhood mortality according to VA, and validated the results in the subset of deaths in children who had been involved in any of these studies, and for whom there was therefore laboratory data that confirmed or refuted a diagnosis of SCD HbSS. "
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