Impact of trimethoprim-sulfamethoxazole prophylaxis on falciparum malaria infection and disease.
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.
Thera
Mahamadou A
MA
Bandiagara Malaria Project, Malaria Research and Training Center, University of Bamako, Mali.
Sehdev
Paul S
PS
Coulibaly
Drissa
D
Traore
Karim
K
Garba
Mamane N
MN
Cissoko
Yacouba
Y
Kone
Abdoulaye
A
Guindo
Ando
A
Dicko
Alassane
A
Beavogui
Abdoul H
AH
Djimde
Abdoulaye A
AA
Lyke
Kirsten E
KE
Diallo
Dapa A
DA
Doumbo
Ogobara K
OK
Plowe
Christopher V
CV
D000293:Adolescent; D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use*; D018890:Chemoprevention; D002648:Child; D002675:Child, Preschool; D004351:Drug Resistance / Q000235:genetics; D005260:Female; D005493:Folic Acid Antagonists / Q000494:pharmacology; D006801:Humans; D016778:Malaria, Falciparum / Q000517:prevention & control*; D008297:Male; D009154:Mutation; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics; D015995:Prevalence; D016896:Treatment Outcome; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000627:therapeutic use*
D000962:Antimalarials; D005493:Folic Acid Antagonists; D015662:Trimethoprim, Sulfamethoxazole Drug Combination