title: Plasmodium falciparum dihydrofolate reductase and dihyropteroate synthase mutations and the use of trimethoprim-sulfamethoxazole prophylaxis among persons infected with human immunodeficiency virus.
abstract: 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.
authors.affiliation: Global AIDS Program, National Center for HIV, STD and TB Prevention, Centers for Disease Control and Prevention-Uganda, Entebbe, Uganda. malambas@gmail.com
authors.forename: Samuel
authors.initials: S
authors.lastname: Malamba
authors.forename: Taylor
authors.initials: T
authors.lastname: Sandison
authors.forename: John
authors.initials: J
authors.lastname: Lule
authors.forename: Arthur
authors.initials: A
authors.lastname: Reingold
authors.forename: Jordan
authors.initials: J
authors.lastname: Walker
authors.forename: Grant
authors.initials: G
authors.lastname: Dorsey
authors.forename: Jonathan
authors.initials: J
authors.lastname: Mermin
mesh_terms: 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
chemical_list: D000962:Antimalarials; D005493:Folic Acid Antagonists; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D005492:Folic Acid; D013762:Tetrahydrofolate Dehydrogenase; D004094:Dihydropteroate Synthase