Plasmodium falciparum dihydrofolate reductase and dihyropteroate synthase mutations and the use of trimethoprim-sulfamethoxazole prophylaxis among persons infected with human immunodeficiency virus.
A prospective cohort design was used to measure the association between daily cotrimoxazole-prophylaxis and infection with Plasmodium falciparum containing mutations associated with antifolate resistance among persons infected with human immunodeficiency virus (HIV) in Tororo and Busia District, in eastern Uganda. Of 149 cases of P. falciparum parasitemia diagnosed, 147 (99%) (smears from participants taking prophylaxis = 91 and smears from those not taking cotrimoxazole prophylaxis = 56) were successfully assessed for mutations in the dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) mutations associated with antifolate resistance. Prevalences of the dhfr pure triple mutant (74% and 70%; P = 0.71), the dhps pure double mutant (95% and 88%; P = 0.21), and the dhfr/dhps pure quintuple mutant (73% and 64%; P = 0.36), were not significantly different between those taking and those not taking cotrimoxazole-prophylaxis, respectively. The overall prevalence of the pure quintuple mutant in this study was 69%, which is among the highest in Africa. Although resistance rates of P. falciparum to antifolate drugs are high, cotrimoxazole-prophylaxis in HIV-infected persons was not associated with a higher prevalence of mutations associated with antifolate resistance.
Malamba
Samuel
S
Global AIDS Program, National Center for HIV, STD and TB Prevention, Centers for Disease Control and Prevention-Uganda, Entebbe, Uganda. malambas@gmail.com
Sandison
Taylor
T
Lule
John
J
Reingold
Arthur
A
Walker
Jordan
J
Dorsey
Grant
G
Mermin
Jonathan
J
D000293:Adolescent; D000328:Adult; D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004094:Dihydropteroate Synthase / Q000235:genetics* / Q000378:metabolism; D004351:Drug Resistance / Q000235:genetics; D005260:Female; D005492:Folic Acid / Q000494:pharmacology; D005493:Folic Acid Antagonists / Q000494:pharmacology; D015658:HIV Infections / Q000150:complications* / Q000453:epidemiology; D006801:Humans; D016778:Malaria, Falciparum / Q000453:epidemiology / Q000469:parasitology / Q000517:prevention & control*; D008297:Male; D009154:Mutation; D010963:Plasmodium falciparum / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000008:administration & dosage / Q000627:therapeutic use; D014454:Uganda / Q000453:epidemiology; D055815:Young Adult
D000962:Antimalarials; D005493:Folic Acid Antagonists; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D005492:Folic Acid; D013762:Tetrahydrofolate Dehydrogenase; D004094:Dihydropteroate Synthase