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-
1.
White NJ, 2008. The role of anti-malarial drugs in eliminating malaria. Malar J 7 (Suppl 1): S8.
-
2.
Arinaitwe E, Sandison TG, Wanzira H, Kakuru A, Homsy J, Kalamya J, Kamya MR, Vora N, Greenhouse B, Rosenthal PJ, Tappero J, Dorsey G, 2009. Artemether-lumefantrine versus dihydroartemisinin-piperaquine for falciparum malaria: a longitudinal, randomized trial in young Ugandan children. Clin Infect Dis 49: 1629–1637.
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Dorsey G, Staedke S, Clark TD, Njama-Meya D, Nzarubara B, Maiteki-Sebuguzi C, Dokomajilar C, Kamya MR, Rosenthal PJ, 2007. Combination therapy for uncomplicated falciparum malaria in Ugandan children: a randomized trial. JAMA 297: 2210–2219.
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Zongo I, Dorsey G, Rouamba N, Tinto H, Dokomajilar C, Guiguemde RT, Rosenthal PJ, Ouedraogo JB, 2007. Artemether-lumefantrine versus amodiaquine plus sulfadoxine-pyrimethamine for uncomplicated falciparum malaria in Burkina Faso: a randomised non-inferiority trial. Lancet 369: 491–498.
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Bousema JT, Schneider P, Gouagna LC, Drakeley CJ, Tostmann A, Houben R, Githure JI, Ord R, Sutherland CJ, Omar SA, Sauerwein RW, 2006. Moderate effect of artemisinin-based combination therapy on transmission of Plasmodium falciparum. J Infect Dis 193: 1151–1159.
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Okell LC, Drakeley CJ, Ghani AC, Bousema T, Sutherland CJ, 2008. Reduction of transmission from malaria patients by artemisinin combination therapies: a pooled analysis of six randomized trials. Malar J 7: 125.
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Bousema JT, Drakeley CJ, Mens PF, Arens T, Houben R, Omar SA, Gouagna LC, Schallig H, Sauerwein RW, 2008. Increased Plasmodium falciparum gametocyte production in mixed infections with P. malariae. Am J Trop Med Hyg 78: 442–448.
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Sutherland CJ, Ord R, Dunyo S, Jawara M, Drakeley CJ, Alexander N, Coleman R, Pinder M, Walraven G, Targett GA, 2005. Reduction of malaria transmission to Anopheles mosquitoes with a six-dose regimen of co-artemether. PLoS Med 2: e92.
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Yeka A, Dorsey G, Kamya MR, Talisuna A, Lugemwa M, Rwakimari JB, Staedke SG, Rosenthal PJ, Wabwire-Mangen F, Bukirwa H, 2008. Artemether-lumefantrine versus dihydroartemisinin-piperaquine for treating uncomplicated malaria: a randomized trial to guide policy in Uganda. PLoS ONE 3: e2390.
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Zongo I, Dorsey G, Rouamba N, Dokomajilar C, Sere Y, Rosenthal PJ, Ouedraogo JB, 2007. Randomized comparison of amodiaquine plus sulfadoxine-pyrimethamine, artemether-lumefantrine, and dihydroartemisinin-piperaquine for the treatment of uncomplicated Plasmodium falciparum malaria in Burkina Faso. Clin Infect Dis 45: 1453–1461.
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Anglaret X, Chene G, Attia A, Toure S, Lafont S, Combe P, Manlan K, N'Dri-Yoman T, Salamon R, 1999. Early chemoprophylaxis with trimethoprim-sulphamethoxazole for HIV-1-infected adults in Abidjan, Cote d'Ivoire: a randomised trial. Cotrimo-CI Study Group. Lancet 353: 1463–1468.
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The Effects of ACT Treatment and TS Prophylaxis on Plasmodium falciparum Gametocytemia in a Cohort of Young Ugandan Children
Abel Kakuru
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
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
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
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
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
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
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
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
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
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
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
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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EndNote
-
1.
White NJ, 2008. The role of anti-malarial drugs in eliminating malaria. Malar J 7 (Suppl 1): S8.
-
2.
Arinaitwe E, Sandison TG, Wanzira H, Kakuru A, Homsy J, Kalamya J, Kamya MR, Vora N, Greenhouse B, Rosenthal PJ, Tappero J, Dorsey G, 2009. Artemether-lumefantrine versus dihydroartemisinin-piperaquine for falciparum malaria: a longitudinal, randomized trial in young Ugandan children. Clin Infect Dis 49: 1629–1637.
-
3.
Dorsey G, Staedke S, Clark TD, Njama-Meya D, Nzarubara B, Maiteki-Sebuguzi C, Dokomajilar C, Kamya MR, Rosenthal PJ, 2007. Combination therapy for uncomplicated falciparum malaria in Ugandan children: a randomized trial. JAMA 297: 2210–2219.
-
4.
Kamya MR, Yeka A, Bukirwa H, Lugemwa M, Rwakimari JB, Staedke SG, Talisuna AO, Greenhouse B, Nosten F, Rosenthal PJ, Wabwire-Mangen F, Dorsey G, 2007. Artemether-lumefantrine versus dihydroartemisinin-piperaquine for treatment of malaria: a randomized trial. PLoS Clin Trials 2: e20.
-
5.
Faye B, Offianan AT, Ndiaye JL, Tine RC, Toure W, Djoman K, Sylla K, Ndiaye PS, Penali L, Gaye O, 2010. Efficacy and tolerability of artesunate-amodiaquine (Camoquin plus) versus artemether-lumefantrine (Coartem) against uncomplicated Plasmodium falciparum malaria: multisite trial in Senegal and Ivory Coast. Trop Med Int Health 15: 608–613.
-
6.
Zongo I, Dorsey G, Rouamba N, Tinto H, Dokomajilar C, Guiguemde RT, Rosenthal PJ, Ouedraogo JB, 2007. Artemether-lumefantrine versus amodiaquine plus sulfadoxine-pyrimethamine for uncomplicated falciparum malaria in Burkina Faso: a randomised non-inferiority trial. Lancet 369: 491–498.
-
7.
Bousema JT, Schneider P, Gouagna LC, Drakeley CJ, Tostmann A, Houben R, Githure JI, Ord R, Sutherland CJ, Omar SA, Sauerwein RW, 2006. Moderate effect of artemisinin-based combination therapy on transmission of Plasmodium falciparum. J Infect Dis 193: 1151–1159.
-
8.
Okell LC, Drakeley CJ, Ghani AC, Bousema T, Sutherland CJ, 2008. Reduction of transmission from malaria patients by artemisinin combination therapies: a pooled analysis of six randomized trials. Malar J 7: 125.
-
9.
Bousema JT, Drakeley CJ, Mens PF, Arens T, Houben R, Omar SA, Gouagna LC, Schallig H, Sauerwein RW, 2008. Increased Plasmodium falciparum gametocyte production in mixed infections with P. malariae. Am J Trop Med Hyg 78: 442–448.
-
10.
Sutherland CJ, Ord R, Dunyo S, Jawara M, Drakeley CJ, Alexander N, Coleman R, Pinder M, Walraven G, Targett GA, 2005. Reduction of malaria transmission to Anopheles mosquitoes with a six-dose regimen of co-artemether. PLoS Med 2: e92.
-
11.
Yeka A, Dorsey G, Kamya MR, Talisuna A, Lugemwa M, Rwakimari JB, Staedke SG, Rosenthal PJ, Wabwire-Mangen F, Bukirwa H, 2008. Artemether-lumefantrine versus dihydroartemisinin-piperaquine for treating uncomplicated malaria: a randomized trial to guide policy in Uganda. PLoS ONE 3: e2390.
-
12.
Zongo I, Dorsey G, Rouamba N, Dokomajilar C, Sere Y, Rosenthal PJ, Ouedraogo JB, 2007. Randomized comparison of amodiaquine plus sulfadoxine-pyrimethamine, artemether-lumefantrine, and dihydroartemisinin-piperaquine for the treatment of uncomplicated Plasmodium falciparum malaria in Burkina Faso. Clin Infect Dis 45: 1453–1461.
-
13.
Mens PF, Sawa P, van Amsterdam SM, Versteeg I, Omar SA, Schallig HD, Kager PA, 2008. A randomized trial to monitor the efficacy and effectiveness by QT-NASBA of artemether-lumefantrine versus dihydroartemisinin-piperaquine for treatment and transmission control of uncomplicated Plasmodium falciparum malaria in western Kenya. Malar J 7: 237.
-
14.
Nambozi M, Van Geertruyden JP, Hachizovu S, Chaponda M, Mukwamataba D, Mulenga M, Ubben D, D'Alessandro U, 2011. Safety and efficacy of dihydroartemisinin-piperaquine versus artemether-lumefantrine in the treatment of uncomplicated Plasmodium falciparum malaria in Zambian children. Malar J 10: 50.
-
15.
Bassat Q, Mulenga M, Tinto H, Piola P, Borrmann S, Menendez C, Nambozi M, Valea I, Nabasumba C, Sasi P, Bacchieri A, Corsi M, Ubben D, Talisuna A, D'Alessandro U, 2009. Dihydroartemisinin-piperaquine and artemether-lumefantrine for treating uncomplicated malaria in African children: a randomised, non-inferiority trial. PLoS ONE 4: e7871.
-
16.
Four Artemisinin-Based Combinations (4ABC) Study Group, 2011. A head-to-head comparison of four artemisinin-based combinations for treating uncomplicated malaria in African children: a randomized trial. PLoS Med 8: e1001119.
-
17.
Anglaret X, Chene G, Attia A, Toure S, Lafont S, Combe P, Manlan K, N'Dri-Yoman T, Salamon R, 1999. Early chemoprophylaxis with trimethoprim-sulphamethoxazole for HIV-1-infected adults in Abidjan, Cote d'Ivoire: a randomised trial. Cotrimo-CI Study Group. Lancet 353: 1463–1468.
-
18.
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.
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19.
Nunn AJ, Mwaba P, Chintu C, Mwinga A, Darbyshire JH, Zumla A, 2008. Role of co-trimoxazole prophylaxis in reducing mortality in HIV infected adults being treated for tuberculosis: randomised clinical trial. BMJ 337: a257.
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