World Health Organization, 2005. World Malaria Report 2005. Available at: http://rbm.who.int/wmr2005/html/1-1.htm. Accessed April 10, 2007.
Chanda P, Masiye F, Chitah BM, Sipilanyambe N, Hawela M, Banda P, Okorosobo T, 2007. A cost-effectiveness analysis of artemether lumefantrine for the treatment of uncomplicated malaria in Zambia. Malar J 6: 21.
Novartis, 2007. Patients benefit from artemether/lumefantrine community development. Proceedings of the American Society of Tropical Medicine and Hygiene 56th Annual Meeting, November 4–8, 2007, Philadelphia, PA.
Kimani D, 2007. New Drug Brings Down Cost of Treating Malaria. Global Business Coalition on HIV/AIDS, Tuberculosis and Malaria. Available at: http://www.businessfightsaids.org. Accessed April 20, 2007.
Ogutu BR, Apollo OJ, McKinney D, Okoth W, Siangla J, Dubovsky F, Tucker K, Waitumbi JN, Diggs C, Wittes J, Malkin E, Leach A, Soisson LA, Milman JB, Otieno L, Holland CA, Polhemus M, Remich SA, Ockenhouse CF, Cohen J, Ballou WR, Martin SK, Angov E, Stewart VA, Lyon JA, Heppner DG, Withers MRMSP-1 Malaria Vaccine Working Group, 2009. Blood stage malaria vaccine eliciting high antigen-specific antibody concentrations confers no protection to young children in Western Kenya. PLoS One 4: e4708.
Bloland PB, Boriga DA, Ruebush TK, McCormick JB, Roberts JM, Oloo AJ, Hawley W, Lal A, Nahlen B, Campbell CC, 1999. Longitudinal cohort study of the epidemiology of malaria infections in an area of intense malaria transmission II. Descriptive epidemiology of malaria infection and disease among children. Am J Trop Med Hyg 60: 641–648.
Ndenga B, Githeko A, Omukunda E, Munyekenye G, Atieli H, Wamai P, Mbogo C, Minakawa N, Zhou G, Yan G, 2006. Population dynamics of malaria vectors in western Kenya highlands. J Med Entomol 43: 200–206.
Githeko AK, Ayisi JM, Odada PK, Atieli FK, Ndenga BA, Githure JI, Yan G, 2006. Topography and malaria transmission heterogeneity in western Kenya highlands: prospects for focal vector control. Malar J 5: 107.
Kifude CM, Polhemus ME, Heppner DG, Withers MR, Ogutu BR, Waitumbi JN, 2007. Hb Kenya among Luo adults and young children in malaria holoendemic western Kenya: screened by high performance liquid chromatography and confirmed by polymerase chain reaction. Hemoglobin 31: 401–408.
May J, Evans JA, Timmann C, Ehmen C, Busch W, Thye T, Agbenyega T, Horstmann RD, 2007. Hemoglobin variants and disease manifestations in severe falciparum malaria. J Am Med Assoc 297: 2220–2226.
Ruwende C, Khoo SC, Snow RW, Yates SN, Kwiatkowski D, Gupta S, Warn P, Allsopp CE, Gilbert SC, Peschu N, Newbold CI, Greenwood BM, Marsh K, Hill VS, 1995. Natural selection of hemi- and heterozygotes for G6PD deficiency in Africa by resistance to severe malaria. Nature 20: 246–249.
Wambua S, Mwangi TW, Kortok M, Uyoga SM, Macharia AW, Mwacharo JK, Weatherall DJ, Snow RW, Marsh K, Williams TN, 2006. The effect of alpha+-thalassaemia on the incidence of malaria and other diseases in children living on the coast of Kenya. PLoS Med 3: e158.
Williams TN, Wambua S, Uyoga S, Macharia A, Mwacharo JK, Newton CR, Maitland K, 2005. Both heterozygous and homozygous alpha+ thalassemias protect against severe and fatal Plasmodium falciparum malaria on the coast of Kenya. Blood 106: 368–371.
Liu YT, Old JM, Miles K, Fisher CA, Weatherall DJ, Clegg JB, 2000. Rapid detection of alpha-thalassaemia deletions and alpha-globin gene triplication by multiplex polymerase chain reactions. Br J Haematol 108: 295–299.
Waitumbi JN, Kifude CM, Polhemus ME, Heppner DG, Withers MR, Ogutu BR, 2007. Hb G-Philadelphia or Stanleyville II? When the phenotype and genotype do not agree. Eur J Haematol 79: 177–178.
World Health Organization, 2003. Assessment and Monitoring Antimalarial Drug Efficacy for the Treatment of Uncomplicated Falciparum Malaria. Available at: http://www.who.int/malaria/docs/ProtocolWHO.pdf. Accessed April 10, 2007.
Andersen P, Borgan O, Gill RD, Keiding N, 1993. Statistical Models Based on Counting Processes, 1st ed. New York, NY: Springer-Verlag.
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 18: e20.
Kokwaro G, Mwai L, Nzila A, 2007. Artemether/lumefantrine in the treatment of uncomplicated falciparum malaria. Expert Opin Pharmacother 8: 75–94.
Bukirwa H, Yeka A, Kamya MR, Talisuna A, Banek K, Bakyaita N, Rwakimari JB, Rosenthal PJ, Wabwire-Mangen F, Dorsey G, Staedke SG, 2006. Artemisinin combination therapies for treatment of uncomplicated malaria in Uganda. PLoS Clin Trials 1: e7.
van den Broek I, Kitz C, Attas SA, Libama F, Balasegaram M, Guthmann JP, 2006. Efficacy of three artemisinin combination therapies for the treatment of uncomplicated Plasmodium falciparum malaria in the Republic of Congo. Malar J 5: 113.
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 randomized non-inferiority trial. Lancet 369: 491–498.
Falade CO, Makanga M, Premji Z, Ortmann CE, Stockmeyer M, de Palacios PI, 2005. Efficacy and safety of artemether-lumefantrine (Coartem) tablets (six-dose regimen) in African infants and children with acute, uncomplicated falciparum malaria. Trans R Soc Trop Med Hyg 99: 459–467.
Makanga M, Premji Z, Falade C, Karbwang J, Mueller EA, Andriano K, Hunt P, de Palacios PI, 2006. Efficacy and safety of the six-dose regimen of artemether-lumefantrine in pediatrics with uncomplicated Plasmodium falciparum malaria: a pooled analysis of individual patient data. Am J Trop Med Hyg 74: 991–998.
Bhatt KM, Samia BM, Bhatt SM, Wasunna KM, 2006. Efficacy and safety of an artesunate/mefloquine combination, (artequin) in the treatment of uncomplicated P. falciparum malaria in Kenya. East Afr Med J 83: 236–242.
Terlouw DJ, Aidoo MA, Udhayakumar V, Kolczak MS, Oloo AJ, Kager PA, Lal A, Nahlen B, ter Kuile FO, 2002. Increased efficacy of sulfadoxine-pyrimethamine in the treatment of uncomplicated falciparum malaria among children with sickle cell trait in western Kenya. J Infect Dis 186: 1661–1668.
Nzila AM, Nduati E, Mberu EK, Hopkins SC, Monks SA, Winstanley PA, Watkins WM, 2000. Molecular evidence of greater selective pressure for drug resistance exerted by the long-acting antifolate Pyrimethamine/Sulfadoxine compared with the shorter-acting chlorproguanil/dapsone on Kenyan Plasmodium falciparum. J Infect Dis 181: 2023–2028.
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From April 2005 to April 2006, a phase 2 malaria vaccine trial in Kenya enrolled 400 children aged 12–47 months. Each received mixed supervised and unsupervised artemether-lumefantrine for uncomplicated malaria, using a standard six-dose regimen, by weight. Children were followed for detection of parasitemia and clinical malaria. A median of two negative malaria blood films occurred during every recurrent parasitemia (RP) episode, suggesting reinfection over late recrudescence. Median time to RP after starting artemether-lumefantrine was 37 days (36–38). Of 2,020 evaluable artemether-lumefantrine treatments, there were no RPs in 99% by day 14, 71% by day 28, and 41% by day 42. By World Health Organization standards, 71% of treatment courses had adequate responses. Although recrudescence in some cannot be ruled out, our cohort had a shorter median time to RP compared with other artemether-lumefantrine treatment studies. This underscores patient counseling on completing all treatment doses for optimal protection from RP.
Financial support: This study was funded by the US Department of Defense Global Emerging Infections Surveillance and Response System (GEIS), the Malaria Vaccine Initiative at Program for Appropriate Technology in Health (PATH), the US Agency for International Development, and the Military Infectious Diseases Research Program.
Ethical review: Study subjects were recruited, screened, and enrolled under a phase II malaria vaccine protocol approved by the Kenyan Medical Research Institute, the Western Institutional Review Board, and the US Army Surgeon General's Institutional Review Board. The trial was registered as NCT 0023990. A subsequent amendment to provide additional data analysis was approved by the Walter Reed Army Institute of Research Human Use Review Committee and the Uniformed Services University of the Health Sciences Institutional Review Board.
Authors' addresses: Joseph V. Woodring, Walter Reed Army Institute of Research, Silver Spring, MD, E-mail: joseph.woodring@us.army.mil. Bernhards Ogutu and John Waitumbi, United States Army Medical Research Unit-Kenya/Kenya Medical Research Institute, United States Army Medical Research Unit-Kenya, Kisumu, Kenya, E-mails: bogutu@wrp-ksm.org and jwaitumbi@wrp-ksm.org. David Schnabel, United States Army Medical Research Unit-Kenya, United States Army Medical Research Unit-Kenya, Nairobi, Kenya, E-mail: dschnabel@wrp-nbo.org. Cara H. Olsen, Uniformed Services University of the Health Sciences, Preventive Medicine and Biometrics, Bethesda, MD, E-mail: colsen@usuhs.mil. Douglas Walsh, United States Army Medical Research Unit-Kenya, United States Army Medical Research Unit-Kenya, Kisian, Kenya, E-mail: douglas.walsh@afrims.org. Gray Heppner and Mark Polhemus, Walter Reed Army Institute of Research, Malaria Vaccine Development, Silver Spring, MD, E-mails: donald.heppner@us.army.mil and mark.polhemus@conus.army.mil.
World Health Organization, 2005. World Malaria Report 2005. Available at: http://rbm.who.int/wmr2005/html/1-1.htm. Accessed April 10, 2007.
Chanda P, Masiye F, Chitah BM, Sipilanyambe N, Hawela M, Banda P, Okorosobo T, 2007. A cost-effectiveness analysis of artemether lumefantrine for the treatment of uncomplicated malaria in Zambia. Malar J 6: 21.
Novartis, 2007. Patients benefit from artemether/lumefantrine community development. Proceedings of the American Society of Tropical Medicine and Hygiene 56th Annual Meeting, November 4–8, 2007, Philadelphia, PA.
Kimani D, 2007. New Drug Brings Down Cost of Treating Malaria. Global Business Coalition on HIV/AIDS, Tuberculosis and Malaria. Available at: http://www.businessfightsaids.org. Accessed April 20, 2007.
Ogutu BR, Apollo OJ, McKinney D, Okoth W, Siangla J, Dubovsky F, Tucker K, Waitumbi JN, Diggs C, Wittes J, Malkin E, Leach A, Soisson LA, Milman JB, Otieno L, Holland CA, Polhemus M, Remich SA, Ockenhouse CF, Cohen J, Ballou WR, Martin SK, Angov E, Stewart VA, Lyon JA, Heppner DG, Withers MRMSP-1 Malaria Vaccine Working Group, 2009. Blood stage malaria vaccine eliciting high antigen-specific antibody concentrations confers no protection to young children in Western Kenya. PLoS One 4: e4708.
Bloland PB, Boriga DA, Ruebush TK, McCormick JB, Roberts JM, Oloo AJ, Hawley W, Lal A, Nahlen B, Campbell CC, 1999. Longitudinal cohort study of the epidemiology of malaria infections in an area of intense malaria transmission II. Descriptive epidemiology of malaria infection and disease among children. Am J Trop Med Hyg 60: 641–648.
Ndenga B, Githeko A, Omukunda E, Munyekenye G, Atieli H, Wamai P, Mbogo C, Minakawa N, Zhou G, Yan G, 2006. Population dynamics of malaria vectors in western Kenya highlands. J Med Entomol 43: 200–206.
Githeko AK, Ayisi JM, Odada PK, Atieli FK, Ndenga BA, Githure JI, Yan G, 2006. Topography and malaria transmission heterogeneity in western Kenya highlands: prospects for focal vector control. Malar J 5: 107.
Kifude CM, Polhemus ME, Heppner DG, Withers MR, Ogutu BR, Waitumbi JN, 2007. Hb Kenya among Luo adults and young children in malaria holoendemic western Kenya: screened by high performance liquid chromatography and confirmed by polymerase chain reaction. Hemoglobin 31: 401–408.
May J, Evans JA, Timmann C, Ehmen C, Busch W, Thye T, Agbenyega T, Horstmann RD, 2007. Hemoglobin variants and disease manifestations in severe falciparum malaria. J Am Med Assoc 297: 2220–2226.
Ruwende C, Khoo SC, Snow RW, Yates SN, Kwiatkowski D, Gupta S, Warn P, Allsopp CE, Gilbert SC, Peschu N, Newbold CI, Greenwood BM, Marsh K, Hill VS, 1995. Natural selection of hemi- and heterozygotes for G6PD deficiency in Africa by resistance to severe malaria. Nature 20: 246–249.
Wambua S, Mwangi TW, Kortok M, Uyoga SM, Macharia AW, Mwacharo JK, Weatherall DJ, Snow RW, Marsh K, Williams TN, 2006. The effect of alpha+-thalassaemia on the incidence of malaria and other diseases in children living on the coast of Kenya. PLoS Med 3: e158.
Williams TN, Wambua S, Uyoga S, Macharia A, Mwacharo JK, Newton CR, Maitland K, 2005. Both heterozygous and homozygous alpha+ thalassemias protect against severe and fatal Plasmodium falciparum malaria on the coast of Kenya. Blood 106: 368–371.
Liu YT, Old JM, Miles K, Fisher CA, Weatherall DJ, Clegg JB, 2000. Rapid detection of alpha-thalassaemia deletions and alpha-globin gene triplication by multiplex polymerase chain reactions. Br J Haematol 108: 295–299.
Waitumbi JN, Kifude CM, Polhemus ME, Heppner DG, Withers MR, Ogutu BR, 2007. Hb G-Philadelphia or Stanleyville II? When the phenotype and genotype do not agree. Eur J Haematol 79: 177–178.
World Health Organization, 2003. Assessment and Monitoring Antimalarial Drug Efficacy for the Treatment of Uncomplicated Falciparum Malaria. Available at: http://www.who.int/malaria/docs/ProtocolWHO.pdf. Accessed April 10, 2007.
Andersen P, Borgan O, Gill RD, Keiding N, 1993. Statistical Models Based on Counting Processes, 1st ed. New York, NY: Springer-Verlag.
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 18: e20.
Kokwaro G, Mwai L, Nzila A, 2007. Artemether/lumefantrine in the treatment of uncomplicated falciparum malaria. Expert Opin Pharmacother 8: 75–94.
Bukirwa H, Yeka A, Kamya MR, Talisuna A, Banek K, Bakyaita N, Rwakimari JB, Rosenthal PJ, Wabwire-Mangen F, Dorsey G, Staedke SG, 2006. Artemisinin combination therapies for treatment of uncomplicated malaria in Uganda. PLoS Clin Trials 1: e7.
van den Broek I, Kitz C, Attas SA, Libama F, Balasegaram M, Guthmann JP, 2006. Efficacy of three artemisinin combination therapies for the treatment of uncomplicated Plasmodium falciparum malaria in the Republic of Congo. Malar J 5: 113.
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 randomized non-inferiority trial. Lancet 369: 491–498.
Falade CO, Makanga M, Premji Z, Ortmann CE, Stockmeyer M, de Palacios PI, 2005. Efficacy and safety of artemether-lumefantrine (Coartem) tablets (six-dose regimen) in African infants and children with acute, uncomplicated falciparum malaria. Trans R Soc Trop Med Hyg 99: 459–467.
Makanga M, Premji Z, Falade C, Karbwang J, Mueller EA, Andriano K, Hunt P, de Palacios PI, 2006. Efficacy and safety of the six-dose regimen of artemether-lumefantrine in pediatrics with uncomplicated Plasmodium falciparum malaria: a pooled analysis of individual patient data. Am J Trop Med Hyg 74: 991–998.
Bhatt KM, Samia BM, Bhatt SM, Wasunna KM, 2006. Efficacy and safety of an artesunate/mefloquine combination, (artequin) in the treatment of uncomplicated P. falciparum malaria in Kenya. East Afr Med J 83: 236–242.
Terlouw DJ, Aidoo MA, Udhayakumar V, Kolczak MS, Oloo AJ, Kager PA, Lal A, Nahlen B, ter Kuile FO, 2002. Increased efficacy of sulfadoxine-pyrimethamine in the treatment of uncomplicated falciparum malaria among children with sickle cell trait in western Kenya. J Infect Dis 186: 1661–1668.
Nzila AM, Nduati E, Mberu EK, Hopkins SC, Monks SA, Winstanley PA, Watkins WM, 2000. Molecular evidence of greater selective pressure for drug resistance exerted by the long-acting antifolate Pyrimethamine/Sulfadoxine compared with the shorter-acting chlorproguanil/dapsone on Kenyan Plasmodium falciparum. J Infect Dis 181: 2023–2028.
Past two years | Past Year | Past 30 Days | |
---|---|---|---|
Abstract Views | 1534 | 1453 | 19 |
Full Text Views | 293 | 6 | 0 |
PDF Downloads | 83 | 11 | 0 |