Cotrimoxazole prophylactic treatment prevents malaria in children in sub‐Saharan Africa: systematic review and meta‐analysis

• Published in: Tropical medicine & international health 2014-09, Vol.19 (9), p.1057-1067
• Main Authors: Mbeye, Nyanyiwe M., Kuile, Feiko O., Davies, Mary‐Ann, Phiri, Kamija S., Egger, Matthias, Wandeler, Gilles
• Format: Article
• Language: English
• Subjects: Africa South of the Sahara - epidemiology; Afrique subsaharienne; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antimalarials - therapeutic use; Biological and medical sciences; Child; children; Children & youth; cotrimoxazole prophylaxis; Drug Combinations; Drug Resistance - genetics; enfants; General aspects; HIV; HIV Infections - complications; Human immunodeficiency virus; Human protozoal diseases; Humans; Infectious diseases; Malaria; Malaria - complications; Malaria - mortality; Malaria - prevention & control; Medical sciences; Mutation; niños; paludisme; Parasitic diseases; Pharmacology. Drug treatments; Preventive medicine; profilaxis con cotrimoxazol; prophylaxie au cotrimoxazole; Protozoal diseases; Pyrimethamine - therapeutic use; sub‐Saharan Africa; Sulfadoxine - therapeutic use; Systematic review; Trimethoprim, Sulfamethoxazole Drug Combination - therapeutic use; África subsahariana
• ISSN: 1360-2276; 1365-3156
• DOI: 10.1111/tmi.12352

Objectives 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