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

SAMUEL S. MALAMBA Centers for Disease Control and Prevention–Uganda, Global AIDS Program, National Center for HIV, STD and TB Prevention, Entebbe, Uganda; Division of Epidemiology, School of Public Health, University of California, Berkeley, California: Department of Medicine, San Francisco General Hospital, University of California, San Francisco, California

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JONATHAN MERMIN Centers for Disease Control and Prevention–Uganda, Global AIDS Program, National Center for HIV, STD and TB Prevention, Entebbe, Uganda; Division of Epidemiology, School of Public Health, University of California, Berkeley, California: Department of Medicine, San Francisco General Hospital, University of California, San Francisco, California

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ARTHUR REINGOLD Centers for Disease Control and Prevention–Uganda, Global AIDS Program, National Center for HIV, STD and TB Prevention, Entebbe, Uganda; Division of Epidemiology, School of Public Health, University of California, Berkeley, California: Department of Medicine, San Francisco General Hospital, University of California, San Francisco, California

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JOHN R. LULE Centers for Disease Control and Prevention–Uganda, Global AIDS Program, National Center for HIV, STD and TB Prevention, Entebbe, Uganda; Division of Epidemiology, School of Public Health, University of California, Berkeley, California: Department of Medicine, San Francisco General Hospital, University of California, San Francisco, California

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ROBERT DOWNING Centers for Disease Control and Prevention–Uganda, Global AIDS Program, National Center for HIV, STD and TB Prevention, Entebbe, Uganda; Division of Epidemiology, School of Public Health, University of California, Berkeley, California: Department of Medicine, San Francisco General Hospital, University of California, San Francisco, California

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RAY RANSOM Centers for Disease Control and Prevention–Uganda, Global AIDS Program, National Center for HIV, STD and TB Prevention, Entebbe, Uganda; Division of Epidemiology, School of Public Health, University of California, Berkeley, California: Department of Medicine, San Francisco General Hospital, University of California, San Francisco, California

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AMINAH KIGOZI Centers for Disease Control and Prevention–Uganda, Global AIDS Program, National Center for HIV, STD and TB Prevention, Entebbe, Uganda; Division of Epidemiology, School of Public Health, University of California, Berkeley, California: Department of Medicine, San Francisco General Hospital, University of California, San Francisco, California

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BEN M. HUNT Centers for Disease Control and Prevention–Uganda, Global AIDS Program, National Center for HIV, STD and TB Prevention, Entebbe, Uganda; Division of Epidemiology, School of Public Health, University of California, Berkeley, California: Department of Medicine, San Francisco General Hospital, University of California, San Francisco, California

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ALAN HUBBARD Centers for Disease Control and Prevention–Uganda, Global AIDS Program, National Center for HIV, STD and TB Prevention, Entebbe, Uganda; Division of Epidemiology, School of Public Health, University of California, Berkeley, California: Department of Medicine, San Francisco General Hospital, University of California, San Francisco, California

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PHILIP J. ROSENTHAL Centers for Disease Control and Prevention–Uganda, Global AIDS Program, National Center for HIV, STD and TB Prevention, Entebbe, Uganda; Division of Epidemiology, School of Public Health, University of California, Berkeley, California: Department of Medicine, San Francisco General Hospital, University of California, San Francisco, California

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GRANT DORSEY Centers for Disease Control and Prevention–Uganda, Global AIDS Program, National Center for HIV, STD and TB Prevention, Entebbe, Uganda; Division of Epidemiology, School of Public Health, University of California, Berkeley, California: Department of Medicine, San Francisco General Hospital, University of California, San Francisco, California

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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.

Author Notes

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