title: Effect of cotrimoxazole prophylaxis taken by human immunodeficiency virus (HIV)-infected persons on the selection of sulfadoxine-pyrimethamine-resistant malaria parasites among HIV-uninfected household members.
abstract: The purpose of this prospective cohort study was to assess the effect of cotrimoxazole prophylaxis taken by human immunodeficiency virus (HIV)-infected persons on the selection of sulfadoxine-pyrimethamine (SP)-resistant malaria parasites among HIV-uninfected household members. A total of 2,567 HIV-uninfected persons from 605 households were followed and blood specimens were collected each time an episode of Plasmodium falciparum malaria was diagnosed. Study participants were living in households where HIV-infected persons were either taking (exposed) or not taking (unexposed) cotrimoxazole prophylaxis. From all malaria episodes diagnosed, 50% of the specimens were randomly selected and tested for the presence of five key mutations known to mediate resistance to SP (dihydrofolate reductase [dhfr] Asn-108, Ile-51, and Arg-59, and dihydropteroate synthase [dhps] Gly-437 and Glu-540). Plasmodium falciparum isolates were recovered from 163 specimens in the exposed households and 113 specimens in the unexposed households, with similar proportions containing the dhfr triple mutant (37% versus 45%; P = 0.18), the dhps double mutant (64% versus 62%; P = 0.81), and the dhfr/dhps quintuple mutant (30% versus 32%; P = 0.74). The HIV-uninfected persons living with HIV-infected household members taking cotrimoxazole prophylaxis had a lower incidence of malaria (incidence rate ratio [IRR] = 0.64, 95% confidence interval [CI] = 0.50-0.83, P = 0.001) and fewer malaria episodes due to parasites containing the dhfr/dhps quintuple mutant (IRR = 0.61, 95% CI = 0.41-0.91, P = 0.014). Cotrimoxazole prophylaxis taken by HIV-infected persons did not select for SP-resistant malaria parasites among HIV-uninfected household members, and was associated with a lower overall incidence of SP-resistant malaria among household members.
authors.affiliation: Centers for Disease Control and Prevention-Uganda, Global AIDS Program, National Center for HIV, STD and TB Prevention, Entebbe, Uganda. malambas@berkeley.edu
authors.forename: Samuel S
authors.initials: SS
authors.lastname: Malamba
authors.forename: Jonathan
authors.initials: J
authors.lastname: Mermin
authors.forename: Arthur
authors.initials: A
authors.lastname: Reingold
authors.forename: John R
authors.initials: JR
authors.lastname: Lule
authors.forename: Robert
authors.initials: R
authors.lastname: Downing
authors.forename: Ray
authors.initials: R
authors.lastname: Ransom
authors.forename: Aminah
authors.initials: A
authors.lastname: Kigozi
authors.forename: Ben M
authors.initials: BM
authors.lastname: Hunt
authors.forename: Alan
authors.initials: A
authors.lastname: Hubbard
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Rosenthal
authors.forename: Grant
authors.initials: G
authors.lastname: Dorsey
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use*; D015331:Cohort Studies; D004338:Drug Combinations; D004351:Drug Resistance / Q000235:genetics; D005190:Family; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy*; D009154:Mutation; D010963:Plasmodium falciparum / Q000187:drug effects; D011739:Pyrimethamine / Q000627:therapeutic use*; D013413:Sulfadoxine / Q000627:therapeutic use*; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000627:therapeutic use*
chemical_list: D000962:Antimalarials; D004338:Drug Combinations; C001205:fanasil, pyrimethamine drug combination; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D013413:Sulfadoxine; D011739:Pyrimethamine