title: Relation between falciparum malaria and bacteraemia in Kenyan children: a population-based, case-control study and a longitudinal study.
abstract: BACKGROUND
  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).
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  Wellcome Trust.
authors: Kenya Medical Research Institute-Wellcome Trust Research Programme, Kilifi, Kenya. ascott@ikilifi .org
authors: J Anthony G
authors: JA
authors: Scott
authors: James A
authors: JA
authors: Berkley
authors: Isaiah
authors: I
authors: Mwangi
authors: Lucy
authors: L
authors: Ochola
authors: Sophie
authors: S
authors: Uyoga
authors: Alexander
authors: A
authors: Macharia
authors: Carolyne
authors: C
authors: Ndila
authors: Brett S
authors: BS
authors: Lowe
authors: Salim
authors: S
authors: Mwarumba
authors: Evasius
authors: E
authors: Bauni
authors: Kevin
authors: K
authors: Marsh
authors: Thomas N
authors: TN
authors: Williams
mesh_terms: D000293:Adolescent; D016470:Bacteremia / Q000453:epidemiology* / Q000382:microbiology; D016022:Case-Control Studies; D002648:Child; D015362:Child Nutrition Disorders / Q000453:epidemiology; D002675:Child, Preschool; D015658:HIV Infections / Q000453:epidemiology; D006420:Hemeproteins / Q000032:analysis; D006801:Humans; D015994:Incidence; D007223:Infant; D007630:Kenya / Q000453:epidemiology; D008137:Longitudinal Studies; D016778:Malaria, Falciparum / Q000453:epidemiology*; D010343:Patient Admission / Q000706:statistics & numerical data; D011159:Population Surveillance; D012307:Risk Factors; D012805:Sickle Cell Trait / Q000453:epidemiology
chemical_list: D006420:Hemeproteins; C020753:hemozoin