{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T05:53:38Z","timestamp":1790402018337,"version":"4.1.0"},"reference-count":38,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2014,7,8]],"date-time":"2014-07-08T00:00:00Z","timestamp":1404777600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1U01AI069924"],"award-info":[{"award-number":["1U01AI069924"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["WT084289MA"],"award-info":[{"award-number":["WT084289MA"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Tropical Med Int Health"],"published-print":{"date-parts":[[2014,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>Cotrimoxazole prophylactic treatment (<jats:styled-content style=\"fixed-case\">CPT<\/jats:styled-content>) prevents opportunistic infections in <jats:styled-content style=\"fixed-case\">HIV<\/jats:styled-content>\u2010infected or <jats:styled-content style=\"fixed-case\">HIV<\/jats:styled-content>\u2010exposed children, but estimates of the effectiveness in preventing malaria vary. We reviewed studies that examined the effect of <jats:styled-content style=\"fixed-case\">CPT<\/jats:styled-content> on incidence of malaria in children in sub\u2010Saharan Africa.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We searched PubMed and <jats:styled-content style=\"fixed-case\">EMBASE<\/jats:styled-content> for randomised controlled trials (<jats:styled-content style=\"fixed-case\">RCT<\/jats:styled-content>s) and cohort studies on the effect of <jats:styled-content style=\"fixed-case\">CPT<\/jats:styled-content> on incidence of malaria and mortality in children and extracted data on the prevalence of sulphadoxine\u2010pyrimethamine resistance\u2013conferring point mutations. Incidence rate ratios (<jats:styled-content style=\"fixed-case\">IRR<\/jats:styled-content>) from individual studies were combined using random effects meta\u2010analysis; confounder\u2010adjusted estimates were used for cohort studies. The importance of resistance was examined in meta\u2010regression analyses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Three <jats:styled-content style=\"fixed-case\">RCT<\/jats:styled-content>s and four cohort studies with 5039 children (1692 <jats:styled-content style=\"fixed-case\">HIV<\/jats:styled-content>\u2010exposed; 2800 <jats:styled-content style=\"fixed-case\">HIV<\/jats:styled-content>\u2010uninfected; 1486 <jats:styled-content style=\"fixed-case\">HIV<\/jats:styled-content>\u2010infected) were included. Children on <jats:styled-content style=\"fixed-case\">CPT<\/jats:styled-content> were less likely to develop clinical malaria episodes than those without prophylaxis (combined <jats:styled-content style=\"fixed-case\">IRR<\/jats:styled-content> 0.37, 95% confidence interval: 0.21\u20130.66), but there was substantial between\u2010study heterogeneity (<jats:italic>I<\/jats:italic>\u2010squared\u00a0=\u00a094%, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001). The protective efficacy of <jats:styled-content style=\"fixed-case\">CPT<\/jats:styled-content> was highest in an <jats:styled-content style=\"fixed-case\">RCT<\/jats:styled-content> from Mali, where the prevalence of antifolate resistant plasmodia was low. In meta\u2010regression analyses, there was some evidence that the efficacy of <jats:styled-content style=\"fixed-case\">CPT<\/jats:styled-content> declined with increasing levels of resistance. Mortality was reduced with <jats:styled-content style=\"fixed-case\">CPT<\/jats:styled-content> in an <jats:styled-content style=\"fixed-case\">RCT<\/jats:styled-content> from Zambia, but not in a cohort study from C\u00f4te d'Ivoire.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Cotrimoxazole prophylactic treatment reduces incidence of malaria and mortality in children in sub\u2010Saharan Africa, but study designs, settings and results were heterogeneous. <jats:styled-content style=\"fixed-case\">CPT<\/jats:styled-content> appears to be beneficial for <jats:styled-content style=\"fixed-case\">HIV<\/jats:styled-content>\u2010infected and <jats:styled-content style=\"fixed-case\">HIV<\/jats:styled-content>\u2010exposed as well as <jats:styled-content style=\"fixed-case\">HIV<\/jats:styled-content>\u2010uninfected children.<\/jats:p><\/jats:sec>","DOI":"10.1111\/tmi.12352","type":"journal-article","created":{"date-parts":[[2014,7,8]],"date-time":"2014-07-08T08:46:51Z","timestamp":1404809211000},"page":"1057-1067","source":"Crossref","is-referenced-by-count":33,"title":["Cotrimoxazole prophylactic treatment prevents malaria in children in sub\u2010Saharan Africa: systematic review and meta\u2010analysis"],"prefix":"10.1111","volume":"19","author":[{"given":"Nyanyiwe M.","family":"Mbeye","sequence":"first","affiliation":[{"name":"College of Medicine University of Malawi Blantyre Malawi"},{"name":"Liverpool School of Tropical Medicine Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feiko O.","family":"ter Kuile","sequence":"additional","affiliation":[{"name":"Liverpool School of Tropical Medicine Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary\u2010Ann","family":"Davies","sequence":"additional","affiliation":[{"name":"School of Public 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