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

Abstract

SummaryBackgroundMany 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).MethodsThis 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.ResultsIn 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.InterpretationMalaria 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.FundingWellcome Trust.

Co-circulation of Plasmodium and Bacterial DNAs in Blood of Febrile and Afebrile Children from Urban and Rural Areas in Gabon

“…38 The induction of HO-1 is, indeed, essential to reduce heme-mediated tissue damage in hemolytic diseases such as malaria, but inhibits oxidative burst in granulocytes and favors bacterial survival within these cells; 3) malaria can increase the iron content in macrophages as a result of enhanced erythrophagocytosis, thus favoring the survival of iron-dependent bacteria such as non-typhi Salmonella within these cells. It can also increase the response to inflammatory stimuli from bacteria, contributing to overall disease severity 38 ; 4) accumulation of the hemozoin pigment in monocytes impairs the function of various macrophages, inhibiting expression of adhesion molecules-1, integrin CD11C, and major histocompatibility complex class II antigens and delaying differentiation into functional antigen-presenting cells and stimulatory proinflammatory cytokines and chemokines; each of these functions plays a significant role in antibacterial immunity 39 ; 5) finally, those children who are homozygous for β s -globin genes (HbSS) are common in malaria-endemic areas and are predisposed to bacterial invasive diseases. However, the HbAS form protects against malaria in 50-90% of cases, as well as against bacteria.…”

“…Unfortunately, in the absence of malaria, this phenotype fails to protect against pneumococcal diseases related to HbSS. 39 Dysfunction of spleen activities during malaria also leads to bacteria entering and their co-infections with Plasmodium in patients. 40 Overall, the presence of co-infections raised several questions about the role of each microorganism in the febrile episode.…”

Induction of Amodiaquine Metabolism by Rifampicin Following Concurrent Administration in Healthy Volunteers

“…5 This can potentially contribute to morbidity and mortality in impoverished populations in the tropics. 6 Moreover, concurrent infections involving TB and malaria have been reported to modify immune response in the coinfection situation and to increase antibacterial intolerance, 7 which may be detrimental to the prognosis of TB. 6 In addition, malaria infection can result in rapid increase in parasite burden if there is a delay in or application of ineffective treatment, with reported case fatality rates of 10% to 20%.…”

“…6 Moreover, concurrent infections involving TB and malaria have been reported to modify immune response in the coinfection situation and to increase antibacterial intolerance, 7 which may be detrimental to the prognosis of TB. 6 In addition, malaria infection can result in rapid increase in parasite burden if there is a delay in or application of ineffective treatment, with reported case fatality rates of 10% to 20%. 8 Therefore, a treatment goal for TB patients with malaria will be the prevention or effective treatment of malaria in TB patients in order to reduce overall morbidity and mortality.…”

Simultaneous Quantification of Ciprofloxacin, Quinine and 3-hyrdoxyquinine in Human Plasma using a HPLC Method

“…Similarly, bacterial infections are ravaging in this same region since a large number of hospital visits results from bacterial infections. A study in Kenya provided evidence that Plasmodium falciparum infection increases the risk for bacteraemia, particularly for gram-negative invasive infections 2,3 . Co-morbidity of malaria and bacterial infections could warrant co-administration of antimalarial and antibacterial drugs.…”