title: Cotrimoxazole prophylactic treatment prevents malaria in children in sub-Saharan Africa: systematic review and meta-analysis.
abstract: OBJECTIVE
  Cotrimoxazole prophylactic treatment (CPT) prevents opportunistic infections in HIV-infected or HIV-exposed children, but estimates of the effectiveness in preventing malaria vary. We reviewed studies that examined the effect of CPT on incidence of malaria in children in sub-Saharan Africa.
  
  
  METHODS
  We searched PubMed and EMBASE for randomised controlled trials (RCTs) and cohort studies on the effect of CPT on incidence of malaria and mortality in children and extracted data on the prevalence of sulphadoxine-pyrimethamine resistance-conferring point mutations. Incidence rate ratios (IRR) from individual studies were combined using random effects meta-analysis; confounder-adjusted estimates were used for cohort studies. The importance of resistance was examined in meta-regression analyses.
  
  
  RESULTS
  Three RCTs and four cohort studies with 5039 children (1692 HIV-exposed; 2800 HIV-uninfected; 1486 HIV-infected) were included. Children on CPT were less likely to develop clinical malaria episodes than those without prophylaxis (combined IRR 0.37, 95% confidence interval: 0.21-0.66), but there was substantial between-study heterogeneity (I-squared = 94%, P < 0.001). The protective efficacy of CPT was highest in an RCT from Mali, where the prevalence of antifolate resistant plasmodia was low. In meta-regression analyses, there was some evidence that the efficacy of CPT declined with increasing levels of resistance. Mortality was reduced with CPT in an RCT from Zambia, but not in a cohort study from Côte d'Ivoire.
  
  
  CONCLUSIONS
  Cotrimoxazole prophylactic treatment reduces incidence of malaria and mortality in children in sub-Saharan Africa, but study designs, settings and results were heterogeneous. CPT appears to be beneficial for HIV-infected and HIV-exposed as well as HIV-uninfected children.
authors.affiliation: College of Medicine, University of Malawi, Blantyre, Malawi; Liverpool School of Tropical Medicine, Liverpool, UK.
authors.forename: Nyanyiwe M
authors.initials: NM
authors.lastname: Mbeye
authors.forename: Feiko O
authors.initials: FO
authors.lastname: ter Kuile
authors.forename: Mary-Ann
authors.initials: MA
authors.lastname: Davies
authors.forename: Kamija S
authors.initials: KS
authors.lastname: Phiri
authors.forename: Matthias
authors.initials: M
authors.lastname: Egger
authors.forename: Gilles
authors.initials: G
authors.lastname: Wandeler
mesh_terms: D017954:Africa South of the Sahara / Q000453:epidemiology; D000962:Antimalarials / Q000627:therapeutic use*; D002648:Child; D004338:Drug Combinations; D004351:Drug Resistance / Q000235:genetics; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D008288:Malaria / Q000150:complications / Q000401:mortality / Q000517:prevention & control*; D009154:Mutation; D011739:Pyrimethamine / Q000627:therapeutic use*; D013413:Sulfadoxine / Q000627:therapeutic use*; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000627:therapeutic use*
chemical_list: D000962:Antimalarials; D004338:Drug Combinations; C001205:fanasil, pyrimethamine drug combination; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D013413:Sulfadoxine; D011739:Pyrimethamine
keywords: Afrique subsaharienne; Malaria; children; cotrimoxazole prophylaxis; enfants; malaria; niños; paludisme; profilaxis con cotrimoxazol; prophylaxie au cotrimoxazole; sub-Saharan Africa; África subsahariana