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Randomized Controlled Trial
. 2005 Nov 15;192(10):1823-9.
doi: 10.1086/498249. Epub 2005 Oct 13.

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

Mahamadou A Thera  1 , Paul S Sehdev, Drissa Coulibaly, Karim Traore, Mamane N Garba, Yacouba Cissoko, Abdoulaye Kone, Ando Guindo, Alassane Dicko, Abdoul H Beavogui, Abdoulaye A Djimde, Kirsten E Lyke, Dapa A Diallo, Ogobara K Doumbo, Christopher V Plowe
Affiliations
Randomized Controlled Trial

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

Mahamadou A Thera et al. J Infect Dis. .

Abstract

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.

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Conflict of interest statement

Potential conflicts of interest: none reported.

Figures

Figure 1
Figure 1
Kaplan-Meier curves showing time to first episode of clinical malaria. TS, trimethoprim-sulfamethoxazole.
Figure 2
Figure 2
Prevalences of dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS) mutations in Plasmodium falciparum parasites infecting the children in the trimethoprim-sulfamethoxazole (TS) group at baseline (microscopy-positive asymptomatic infections) and after 1 month of TS prophylaxis (microscopy-negative, polymerase chain reaction–positive asymptomatic infections).
See this image and copyright information in PMC

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