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

  • 1

    Wiktor SZ, Sassan-Morokro M, Grant AD, Abouya L, Karon JM, Maurice C, Djomand G, Ackah A, Domoua K, Kadio A, Yapi A, Combe P, Tossou O, Roels TH, Lackritz EM, Coulibaly D, De Cock KM, Coulibaly IM, Greenberg AE. 1999. Efficacy of trimethoprim-sulphamethoxazole prophylaxis to decrease morbidity and mortality in HIV-1-infected patients with tuberculosis in Abidjan, Cote d’Ivoire: a randomised controlled trial. Lancet 353 :1469–1475.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2

    Anglaret X, Chêne G, Attia A, Toure S, Lafont S, Combe P, Manlan K, 1999. N’Dri-Yoman T, Salamon R: Early chemo-prophylaxis with trimethoprim-sulphamethoxazole for HIV-1-infected adults in Abidjan, Côte d’Ivoire: a randomised trial. Lancet 353 :1463–1468.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3

    Mermin J, Lule J, Ekwaru JP, Downing R, Hughes P, Bunnell R, Malamba S, Ransom R, Kaharuza F, Coutinho A, Kizogi A, Quick R, 2005. Cotrimoxazole prophylaxis by HIV-infected persons in Uganda reduces morbidity and mortality among HIV-uninfected family members. AIDS 19 :1035–1042.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4

    Chintu C, Bhat G, Walker A, Mulenga V, Sinyinza F, Farrelly L, Kagangson N, Zumla A, Gillespie SH, Nunn A, Gibb DM, CHAP Trial Team, 2004. Cotrimoxazole as prophylaxis against opportunistic infections as HIV-infected Zambian children (CHAP): a chap double-blind randomized placebo-controlled trial. Lancet 364 :1865–1871.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5

    UNAIDS/WHO, 2000. Provisional WHO/UNAIDS Secretariat Recommendations on the Use of Cotrimoxazole Prophylaxis in Adults and Children Living with HIV/AIDS in Africa. Geneva: World Health Organization.

    • PubMed
    • Export Citation
  • 6

    Boeree MJ, Harries AD, Zijlstra EE, Taylor TE, Molyneu ME, 1999. Cotrimoxazole in HIV-1 infection. Lancet 354 :334.

  • 7

    Whitty CJ, Jaffar S, 2002. Plasmodium falciparum cross resistance. Lancet 359 :80.

  • 8

    Greenwood BM, Bojang K, Whitty CJ, Targett GA, 2005. Malaria. Lancet 365 :1487–1498.

  • 9

    Eskild P, 1987. In vitro susceptibility of Plasmodium falciparum malaria to pyrimethamine, sulfadoxine, trimethoprim and sulfamethaxazole singly and in combination. Trans R Soc Trop Med Hyg 81 :238–241.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10

    Dorsey G, Dokomajilar C, Kiggundu M, Staedke SG, Kamya MR, Rosenthal PJ, 2004. Principal role of dihydropteroate synthase mutations in mediating resistance to sulfadoxine-pyrimethamine in single-drug and combination therapy of uncomplicated malaria in Uganda. Am J Trop Med Hyg 71 :758–763.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11

    Lyer JK, Milhous WK, Cortese JF, Kublin JG, Plowe CV, 2001. Plasmodium falciparum cross-resistance between trimethoprim and pyrimethamine. Lancet 358 :1066–1067.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12

    Anglaret X, 2001. Trimethoprim-sulfamethoxazole prophylaxis in sub-Saharan Africa. Lancet 358 :1027–1028.

  • 13

    Sibley CH, Hyde JE, Sims PFG, Plowe CV, Kublin JG, Mberu EK, Cowman AF, Winstanley PA, Watkins WM, Nzila AM, 2001. Pyrimethamine-sulfadoxine resistance in Plasmodium falciparum: what next? Trends Parasitol 17 :582–588.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14

    Plowe CV, Djimde A, Bouare M, Doumbo O, Wellems T, 1995. Pyrimethamine and proguanil resistance-conferring mutations in Plasmodium falciparum dihydrofolate reductase: polymerase chain reaction methods for surveillance in Africa. Am J Trop Med Hyg 52 :565–568.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15

    Kyabayinze D, Cattamanchi A, Kamya M, Rosenthal PJ, Dorsey G, 2003. Validation of a simplified method for using molecular markers to predict sulfadoxine-pyrimethamine treatment failure in African children with falciparum malaria. Am J Trop Med Hyg 69 :247–252.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16

    Duraisingh MT, Curtis J, Warhurst DC, 1998. Plasmodium falciparum: detection of polymorphisms in the dihydrofolate reductase and dihydropteroate synthetase genes by PCR and restriction digestion. Exp Parasitol 89 :1–8.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17

    EpiInfo, 2005. A Database and Statistics Program for Public Health Professionals. Atlanta: Centers for Disease Control and Prevention.

    • PubMed
    • Export Citation
  • 18

    Mander A, Clayton D, 1997. Hotdeck Imputation Method. College Station, TX: Stata Corporation.

    • PubMed
    • Export Citation
  • 19

    Omar SA, Bakari A, Owiti A, Adugu IS, Warhurst DC, 2001. Cotrimoxazole compared with sulfadoxine-pyrimethamine in the treatment of uncomplicated malaria in Kenyan children. Trans R Soc Trop Med Hyg 95 :657–660.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20

    Jelinek T, Kilian AH, Curtis J, Duraisingh MT, Kabagambe G, von Sonnenburg F, Warhurst DC, 1999. Plasmodium falciparum: selection of serine 108 of dihydrofolate reductase during treatment of uncomplicated malaria with cotrimoxazole in Ugandan children. Am J Trop Med Hyg 61 :125–130.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21

    Kofoed PE, Alfrangis M, Poulsen A, Rodrigues A, Gjedde SB, Ronn A, Rombo L, 2004. Genetic markers of resistance to pyrimethamine and sulfonamides in Plasmodium falciparum parasites compared with the resistance patterns in isolates of Escherichia coli from the same children in Guinea-Bissau. Trop Med Int Health 9 :171–177.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22

    Roper C, Pearce R, Bredenkamp B, Gumede J, Drakeley C, Mosha F, Chandramohan D, Sharp B, 2003. Antifolate anti-malarial resistance in southeast Africa: a population-based analysis. Lancet 361 :1174–1181.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23

    Mermin J, Lule J, Ekwaru JP, Malamba S, Downing R, Ransom R, Kaharuza F, Culver D, Kizito F, Bunnell R, Kigozi A, Nakanjako D, Wafula W, Quick R, 2004. Effect of cotrimoxazole prophylaxis on morbidity, mortality, CD4-cell count, and viral load in HIV infection in rural Uganda. Lancet 364 :1428–1434.

    • PubMed
    • Search Google Scholar
    • Export Citation
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