Relation between falciparum malaria and bacteraemia in Kenyan children: a population-based, case-control study and a longitudinal study.

Kenya Medical Research Institute-Wellcome Trust Research Programme, Kilifi, Kenya. ascott@ikilifi .org
The Lancet (Impact Factor: 39.21). 09/2011; 378(9799):1316-23. DOI: 10.1016/S0140-6736(11)60888-X
Source: PubMed

ABSTRACT 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.

1 Bookmark
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In nature, organisms are commonly infected by an assemblage of different parasite species or by genetically distinct parasite strains that interact in complex ways. Linked to co-infections, pathocoenosis, a term proposed by M. Grmek in 1969, refers to a pathological state arising from the interactions of diseases within a population and to the temporal and spatial dynamics of all of the diseases. In the long run, malaria was certainly one of the most important component of past pathocoenoses. Today this disease, which affects hundreds of millions of individuals and results in approximately one million deaths each year, is always highly endemic in over 20% of the world and is thus co-endemic with many other diseases. Therefore, the incidences of co-infections and possible direct and indirect interactions with Plasmodium parasites are very high. Both positive and negative interactions between malaria and other diseases caused by parasites belonging to numerous taxa have been described and in some cases, malaria may modify the process of another disease without being affected itself. Interactions include those observed during voluntary malarial infections intended to cure neuro-syphilis or during the enhanced activations of bacterial gastro-intestinal diseases and HIV infections. Complex relationships with multiple effects should also be considered, such as those observed during helminth infections. Moreover, reports dating back over 2000 years suggested that co- and multiple infections have generally deleterious consequences and analyses of historical texts indicated that malaria might exacerbate both plague and cholera, among other diseases. Possible biases affecting the research of etiological agents caused by the protean manifestations of malaria are discussed. A better understanding of the manner by which pathogens, particularly Plasmodium, modulate immune responses is particularly important for the diagnosis, cure, and control of diseases in human populations.
    Frontiers in Physiology 11/2014; 5:441.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Controversy surrounds the precise numbers of malaria deaths and clinical episodes in Africa. This would not have surprised malariologists working in Africa 60 years ago as they began to unravel the enigma that is ‘malaria’. Malaria is a complex disease manifesting as a multitude of symptoms, degrees of severity and indirect morbid consequences. Clinical immunity develops quickly and the presence of infection cannot always be used to distinguish between malaria and other illnesses. During the 1950s and 1960s parasite prevalence was used in preference to statistics on malaria mortality and morbidity. An argument is made for a resurrection of this measure of the quantity of malaria across Africa as a more reliable means to understand the impact of control.
    BMC Medicine 12/2014; 12(1). · 7.28 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background The burden of bloodstream infections is insufficiently studied in children in Africa and many healthcare facilities lack the capacity to identify invasive disease. Often studies have been limited to febrile patients or patients admitted to hospital.Methods Blood cultures and malaria diagnostics was performed on 372 consecutive children presenting with tachycardia and/or fever to a referral paediatric emergency department in Bissau, Guinea-Bissau. Bacterial species detection, antimicrobial susceptibility testing and molecular typing were performed. The capacity of clinical parameters to identify bacteraemia was evaluated.ResultsThe prevalence of bloodstream infection was 12% (46/372) and in 46% (21/46) of the infections the child was non-febrile at presentation to the hospital. The predictive value for bacteraemia was poor for all assessed clinical parameters. Staphylococcus aureus accounted for 54% (26/48) of the isolates followed by non-typhoidal Salmonella, 10% (5/48), Streptococcus pneumoniae, 8% (4/48), and Salmonella Typhi, 6% (3/48). Among S. aureus there was a large diversity of spa types and 38% produced Pantone-Valentine leukocidin. Antibiotic resistance was low, however two out of three Klebsiella pneumoniae isolates produced extended-spectrum beta-lactamases. Malaria was laboratory confirmed in only 5% of the children but 64% (237/372) received a clinical malaria diagnosis.Conclusions Bacteraemia was common irrespective of the presence of fever among children presenting to the hospital. The high prevalence of Staphylococcus aureus may be due to contamination. There is an imminent need to improve microbiological diagnostic facilities and to identify algorithms that can identify children at risk of bloodstream infections in Africa.
    BMC Infectious Diseases 12/2014; 14(1):715. · 2.56 Impact Factor

Full-text (2 Sources)

Available from
May 15, 2014