The Effects of ACT Treatment and TS Prophylaxis on Plasmodium falciparum Gametocytemia in a Cohort of Young Ugandan Children

Abel Kakuru Infectious Diseases Research Collaboration, Kampala, Uganda; Department of Medicine, San Francisco General Hospital, University of California, San Francisco, California; Institute for Global Health, University of California, San Francisco, California; Department of Medicine, Makerere University College of Health Sciences, Kampala, Uganda; Global AIDS Program, Centers for Disease Control and Prevention, Atlanta, Georgia

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Prasanna Jagannathan Infectious Diseases Research Collaboration, Kampala, Uganda; Department of Medicine, San Francisco General Hospital, University of California, San Francisco, California; Institute for Global Health, University of California, San Francisco, California; Department of Medicine, Makerere University College of Health Sciences, Kampala, Uganda; Global AIDS Program, Centers for Disease Control and Prevention, Atlanta, Georgia

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Emmanuel Arinaitwe Infectious Diseases Research Collaboration, Kampala, Uganda; Department of Medicine, San Francisco General Hospital, University of California, San Francisco, California; Institute for Global Health, University of California, San Francisco, California; Department of Medicine, Makerere University College of Health Sciences, Kampala, Uganda; Global AIDS Program, Centers for Disease Control and Prevention, Atlanta, Georgia

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Humphrey Wanzira Infectious Diseases Research Collaboration, Kampala, Uganda; Department of Medicine, San Francisco General Hospital, University of California, San Francisco, California; Institute for Global Health, University of California, San Francisco, California; Department of Medicine, Makerere University College of Health Sciences, Kampala, Uganda; Global AIDS Program, Centers for Disease Control and Prevention, Atlanta, Georgia

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Mary Muhindo Infectious Diseases Research Collaboration, Kampala, Uganda; Department of Medicine, San Francisco General Hospital, University of California, San Francisco, California; Institute for Global Health, University of California, San Francisco, California; Department of Medicine, Makerere University College of Health Sciences, Kampala, Uganda; Global AIDS Program, Centers for Disease Control and Prevention, Atlanta, Georgia

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Victor Bigira Infectious Diseases Research Collaboration, Kampala, Uganda; Department of Medicine, San Francisco General Hospital, University of California, San Francisco, California; Institute for Global Health, University of California, San Francisco, California; Department of Medicine, Makerere University College of Health Sciences, Kampala, Uganda; Global AIDS Program, Centers for Disease Control and Prevention, Atlanta, Georgia

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Emmanuel Osilo Infectious Diseases Research Collaboration, Kampala, Uganda; Department of Medicine, San Francisco General Hospital, University of California, San Francisco, California; Institute for Global Health, University of California, San Francisco, California; Department of Medicine, Makerere University College of Health Sciences, Kampala, Uganda; Global AIDS Program, Centers for Disease Control and Prevention, Atlanta, Georgia

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Jaco Homsy Infectious Diseases Research Collaboration, Kampala, Uganda; Department of Medicine, San Francisco General Hospital, University of California, San Francisco, California; Institute for Global Health, University of California, San Francisco, California; Department of Medicine, Makerere University College of Health Sciences, Kampala, Uganda; Global AIDS Program, Centers for Disease Control and Prevention, Atlanta, Georgia

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Moses R. Kamya Infectious Diseases Research Collaboration, Kampala, Uganda; Department of Medicine, San Francisco General Hospital, University of California, San Francisco, California; Institute for Global Health, University of California, San Francisco, California; Department of Medicine, Makerere University College of Health Sciences, Kampala, Uganda; Global AIDS Program, Centers for Disease Control and Prevention, Atlanta, Georgia

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Jordan W. Tappero Infectious Diseases Research Collaboration, Kampala, Uganda; Department of Medicine, San Francisco General Hospital, University of California, San Francisco, California; Institute for Global Health, University of California, San Francisco, California; Department of Medicine, Makerere University College of Health Sciences, Kampala, Uganda; Global AIDS Program, Centers for Disease Control and Prevention, Atlanta, Georgia

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Grant Dorsey Infectious Diseases Research Collaboration, Kampala, Uganda; Department of Medicine, San Francisco General Hospital, University of California, San Francisco, California; Institute for Global Health, University of California, San Francisco, California; Department of Medicine, Makerere University College of Health Sciences, Kampala, Uganda; Global AIDS Program, Centers for Disease Control and Prevention, Atlanta, Georgia

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Artemisinin-based combination therapies (ACTs) and trimethoprim-sulfamethoxazole (TS) prophylaxis are important tools for malaria control, but there are concerns about their effect on gametocytes, the stage of the parasite responsible for transmission. We conducted a longitudinal clinical trial in a cohort of HIV-infected and uninfected children living in an area of high malaria transmission intensity in Uganda. Study participants were randomized to artemether-lumefantrine (AL) or dihydroartemisinin-piperaquine (DP) for all treatments of uncomplicated malaria (N = 4,380) as well as TS prophylaxis for different durations. The risks of gametocytemia detected by microscopy in the 28 days after antimalarial therapy were compared using multivariate analyses. The risk of gametocyte detection was significantly higher in patients treated with DP compared with AL (adjusted relative risk = 1.85, P < 0.001) and among children prescribed TS prophylaxis (adjusted relative risk = 1.76, P < 0.001). The risk of gametocytemia and its potential for increasing transmission should be considered when evaluating different ACTs and TS prophylaxis for malaria control.

Author Notes

* Address correspondence to Abel Kakuru, Infectious Diseases Research Collaboration, PO Box 749, Tororo, Kampala 256, Uganda. E-mail: abelkakuru@gmail.com

Financial support: Participants in this study were enrolled in programs supported by the US President's Emergency Plan for AIDS Relief and Cooperative Agreement No. U62P024421 from the Centers for Disease Control and Prevention (CDC); National Center for HIV, Viral Hepatitis, STD, and TB Prevention (NCHHSTP); and Global AIDS Program (GAP). P.J. is supported by National Institutes of Health T32 Training Grant 2 T32 AI 60530-6 and a Burroughs Wellcome Fund/American Society of Tropical Medicine and Hygiene Postdoctoral Fellowship. Funding was also provided by the Doris Duke Charitable Foundation (G.D. is a recipient of the Clinical Scientist Development Award).

Authors' addresses: Abel Kakuru, Emmanuel Arinaitwe, Humphrey Wanzira, Mary Muhindo, Victor Bigira, and Emmanuel Osilo, Infectious Diseases Research Collaboration, Kampala, Uganda, E-mails: abelkakuru@gmail.com, emmy3md@yahoo.com, wanzirah@yahoo.com, marymkakuru@gmail.com, vbigira@gmail.com, and goodbeads@yahoo.co.uk. Prasanna Jagannathan and Grant Dorsey, Department of Medicine, San Francisco General Hospital, University of California, San Francisco, CA, E-mails: jagannathanp@medsfgh.ucsf.edu and gdorsey@medsfgh.ucsf.edu. Jaco Homsy, Institute for Global Health, University of California, San Francisco, CA, E-mail: jhomsy@psg.ucsf.edu. Moses R. Kamya, Department of Medicine, Makerere University College of Health Sciences, Kampala, Uganda, E-mail: mkamya@infocom.co.ug. Jordan W. Tappero, Global AIDS Program, Centers for Disease Control and Prevention, Atlanta, GA, E-mail: jwt0@cdc.gov.

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