Impact of trimethoprim-sulfamethoxazole prophylaxis on falciparum malaria infection and disease.


Journal Article

BACKGROUND: Trimethoprim-sulfamethoxazole (TS) prophylaxis is recommended for persons living with human immunodeficiency virus infection and acquired immunodeficiency syndrome in Africa. TS and the antimalarial combination sulfadoxine-pyrimethamine (SP) share mechanisms of action and resistance patterns, and concerns about the impact of TS resistance on SP efficacy have contributed to reluctance to implement TS prophylaxis in Africa. METHODS: To determine whether TS prophylaxis impairs SP efficacy for treatment of uncomplicated falciparum malaria, we conducted a randomized, controlled, open-label study of TS prophylaxis. Two hundred and forty children 5-15 years old were randomized in a 2 : 1 fashion to receive either thrice-weekly TS for 12 weeks or no prophylaxis and were treated with SP for subsequent episodes of malaria. The incidence of malaria, SP efficacy, and the prevalence of parasite mutations that confer antifolate drug resistance were measured. RESULTS: TS prophylaxis had a 99.5% protective efficacy against episodes of clinical malaria, with 97% efficacy against infection. Four SP treatment failures occurred in the control group, and none occurred in the TS group. No evidence was seen for selection by TS of antifolate resistance-conferring mutations in parasite dihydrofolate reductase or dihydropteroate synthase during subclinical infections. CONCLUSIONS: In this setting of low antifolate resistance, TS was highly effective in preventing falciparum malaria infection and disease and did not appear to select for SP-resistant parasites.

Full Text

Duke Authors

Cited Authors

  • Thera, MA; Sehdev, PS; Coulibaly, D; Traore, K; Garba, MN; Cissoko, Y; Kone, A; Guindo, A; Dicko, A; Beavogui, AH; Djimde, AA; Lyke, KE; Diallo, DA; Doumbo, OK; Plowe, CV

Published Date

  • November 15, 2005

Published In

Volume / Issue

  • 192 / 10

Start / End Page

  • 1823 - 1829

PubMed ID

  • 16235184

Pubmed Central ID

  • 16235184

International Standard Serial Number (ISSN)

  • 0022-1899

Digital Object Identifier (DOI)

  • 10.1086/498249


  • eng

Conference Location

  • United States