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| The New England journal of medicine. doi: 10.1056/NEJMoa1710775 |
| Single-Dose Tafenoquine to Prevent Relapse of Plasmodium vivax Malaria. |
| Lacerda MVG1, Llanos-Cuentas A2, Krudsood S3, Lon C4, Saunders DL5, Mohammed R6, Yilma D7, Batista Pereira D8, Espino FEJ9, Mia RZ10, Chuquiyauri R11, Val F12, Casapía M13, Monteiro WM14, Brito MAM15, Costa MRF16, Buathong N17, Noedl H18, Diro E19, Getie S20, Wubie KM21, Abdissa A22, Zeynudin A23, Abebe C24, Tada MS25, Brand F26, Beck HP27, Angus B28, Duparc S29, Kleim JP30, Kellam LM31, Rousell VM32, Jones SW33, Hardaker E34, Mohamed K35, Clover DD36, Fletcher K37, Breton JJ38, Ugwuegbulam CO39, Green JA40, Koh GCKW41 |
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1From Fundação de Medicina Tropical Dr Heitor Vieira Dourado, Manaus (M.V.G.L., F.V., W.M.M., M.A.M.B., M.R.F.C.), Fundação Oswaldo Cruz, Manguinhos, Rio de Janeiro (M.V.G.L.), and Centro de Pesquisa em Medicina Tropical Rondônia, Porto Velho (D.B.P., M.S.T.) - all in Brazil; Universidad Peruana Cayetano Heredia, Lima, Peru (A.L.-C., R.C., M.C.); Mahidol University (S.K.) and the Armed Forces Research Institute of Medical Sciences (C.L., D.L.S., N.B.), Bangkok, Thailand; the University of Gondar, Gondar (R.M., E.D., S.G., K.M.W.), and Jimma University, Jimma (D.Y., A.A., A.Z., C.A.) - both in Ethiopia; Research Institute for Tropical Medicine, Manila (F.E.J.E.), and Rio Tuba Nickel Foundation Hospital, Palawan (R.Z.M.) - both in the Philippines; Medical University of Vienna, Vienna (H.N.); Swiss Tropical and Public Health Institute and University of Basel, Basel (F.B., H.-P.B.), and Medicines for Malaria Venture, Geneva (S.D.) - both in Switzerland; Oxford University, Oxford (B.A.), and GlaxoSmithKline, Stockley Park West (J.-P.K., L.M.K., V.M.R., S.W.J., E.H., K.M., D.D.C., K.F., C.O.U., J.A.G., G.C.K.W.K.) - both in the United Kingdom; and GlaxoSmithKline, Collegeville, PA (J.J.B.).
2From Fundação de Medicina Tropical Dr Heitor Vieira Dourado, Manaus (M.V.G.L., F.V., W.M.M., M.A.M.B., M.R.F.C.), Fundação Oswaldo Cruz, Manguinhos, Rio de Janeiro (M.V.G.L.), and Centro de Pesquisa em Medicina Tropical Rondônia, Porto Velho (D.B.P., M.S.T.) - all in Brazil; Universidad Peruana Cayetano Heredia, Lima, Peru (A.L.-C., R.C., M.C.); Mahidol University (S.K.) and the Armed Forces Research Institute of Medical Sciences (C.L., D.L.S., N.B.), Bangkok, Thailand; the University of Gondar, Gondar (R.M., E.D., S.G., K.M.W.), and Jimma University, Jimma (D.Y., A.A., A.Z., C.A.) - both in Ethiopia; Research Institute for Tropical Medicine, Manila (F.E.J.E.), and Rio Tuba Nickel Foundation Hospital, Palawan (R.Z.M.) - both in the Philippines; Medical University of Vienna, Vienna (H.N.); Swiss Tropical and Public Health Institute and University of Basel, Basel (F.B., H.-P.B.), and Medicines for Malaria Venture, Geneva (S.D.) - both in Switzerland; Oxford University, Oxford (B.A.), and GlaxoSmithKline, Stockley Park West (J.-P.K., L.M.K., V.M.R., S.W.J., E.H., K.M., D.D.C., K.F., C.O.U., J.A.G., G.C.K.W.K.) - both in the United Kingdom; and GlaxoSmithKline, Collegeville, PA (J.J.B.). 3From Fundação de Medicina Tropical Dr Heitor Vieira Dourado, Manaus (M.V.G.L., F.V., W.M.M., M.A.M.B., M.R.F.C.), Fundação Oswaldo Cruz, Manguinhos, Rio de Janeiro (M.V.G.L.), and Centro de Pesquisa em Medicina Tropical Rondônia, Porto Velho (D.B.P., M.S.T.) - all in Brazil; Universidad Peruana Cayetano Heredia, Lima, Peru (A.L.-C., R.C., M.C.); Mahidol University (S.K.) and the Armed Forces Research Institute of Medical Sciences (C.L., D.L.S., N.B.), Bangkok, Thailand; the University of Gondar, Gondar (R.M., E.D., S.G., K.M.W.), and Jimma University, Jimma (D.Y., A.A., A.Z., C.A.) - both in Ethiopia; Research Institute for Tropical Medicine, Manila (F.E.J.E.), and Rio Tuba Nickel Foundation Hospital, Palawan (R.Z.M.) - both in the Philippines; Medical University of Vienna, Vienna (H.N.); Swiss Tropical and Public Health Institute and University of Basel, Basel (F.B., H.-P.B.), and Medicines for Malaria Venture, Geneva (S.D.) - both in Switzerland; Oxford University, Oxford (B.A.), and GlaxoSmithKline, Stockley Park West (J.-P.K., L.M.K., V.M.R., S.W.J., E.H., K.M., D.D.C., K.F., C.O.U., J.A.G., G.C.K.W.K.) - both in the United Kingdom; and GlaxoSmithKline, Collegeville, PA (J.J.B.). 4From Fundação de Medicina Tropical Dr Heitor Vieira Dourado, Manaus (M.V.G.L., F.V., W.M.M., M.A.M.B., M.R.F.C.), Fundação Oswaldo Cruz, Manguinhos, Rio de Janeiro (M.V.G.L.), and Centro de Pesquisa em Medicina Tropical Rondônia, Porto Velho (D.B.P., M.S.T.) - all in Brazil; Universidad Peruana Cayetano Heredia, Lima, Peru (A.L.-C., R.C., M.C.); Mahidol University (S.K.) and the Armed Forces Research Institute of Medical Sciences (C.L., D.L.S., N.B.), Bangkok, Thailand; the University of Gondar, Gondar (R.M., E.D., S.G., K.M.W.), and Jimma University, Jimma (D.Y., A.A., A.Z., C.A.) - both in Ethiopia; Research Institute for Tropical Medicine, Manila (F.E.J.E.), and Rio Tuba Nickel Foundation Hospital, Palawan (R.Z.M.) - both in the Philippines; Medical University of Vienna, Vienna (H.N.); Swiss Tropical and Public Health Institute and University of Basel, Basel (F.B., H.-P.B.), and Medicines for Malaria Venture, Geneva (S.D.) - both in Switzerland; Oxford University, Oxford (B.A.), and GlaxoSmithKline, Stockley Park West (J.-P.K., L.M.K., V.M.R., S.W.J., E.H., K.M., D.D.C., K.F., C.O.U., J.A.G., G.C.K.W.K.) - both in the United Kingdom; and GlaxoSmithKline, Collegeville, PA (J.J.B.). 5From Fundação de Medicina Tropical Dr Heitor Vieira Dourado, Manaus (M.V.G.L., F.V., W.M.M., M.A.M.B., M.R.F.C.), Fundação Oswaldo Cruz, Manguinhos, Rio de Janeiro (M.V.G.L.), and Centro de Pesquisa em Medicina Tropical Rondônia, Porto Velho (D.B.P., M.S.T.) - all in Brazil; Universidad Peruana Cayetano Heredia, Lima, Peru (A.L.-C., R.C., M.C.); Mahidol University (S.K.) and the Armed Forces Research Institute of Medical Sciences (C.L., D.L.S., N.B.), Bangkok, Thailand; the University of Gondar, Gondar (R.M., E.D., S.G., K.M.W.), and Jimma University, Jimma (D.Y., A.A., A.Z., C.A.) - both in Ethiopia; Research Institute for Tropical Medicine, Manila (F.E.J.E.), and Rio Tuba Nickel Foundation Hospital, Palawan (R.Z.M.) - both in the Philippines; Medical University of Vienna, Vienna (H.N.); Swiss Tropical and Public Health Institute and University of Basel, Basel (F.B., H.-P.B.), and Medicines for Malaria Venture, Geneva (S.D.) - both in Switzerland; Oxford University, Oxford (B.A.), and GlaxoSmithKline, Stockley Park West (J.-P.K., L.M.K., V.M.R., S.W.J., E.H., K.M., D.D.C., K.F., C.O.U., J.A.G., G.C.K.W.K.) - both in the United Kingdom; and GlaxoSmithKline, Collegeville, PA (J.J.B.). 6From Fundação de Medicina Tropical Dr Heitor Vieira Dourado, Manaus (M.V.G.L., F.V., W.M.M., M.A.M.B., M.R.F.C.), Fundação Oswaldo Cruz, Manguinhos, Rio de Janeiro (M.V.G.L.), and Centro de Pesquisa em Medicina Tropical Rondônia, Porto Velho (D.B.P., M.S.T.) - all in Brazil; Universidad Peruana Cayetano Heredia, Lima, Peru (A.L.-C., R.C., M.C.); Mahidol University (S.K.) and the Armed Forces Research Institute of Medical Sciences (C.L., D.L.S., N.B.), Bangkok, Thailand; the University of Gondar, Gondar (R.M., E.D., S.G., K.M.W.), and Jimma University, Jimma (D.Y., A.A., A.Z., C.A.) - both in Ethiopia; Research Institute for Tropical Medicine, Manila (F.E.J.E.), and Rio Tuba Nickel Foundation Hospital, Palawan (R.Z.M.) - both in the Philippines; Medical University of Vienna, Vienna (H.N.); Swiss Tropical and Public Health Institute and University of Basel, Basel (F.B., H.-P.B.), and Medicines for Malaria Venture, Geneva (S.D.) - both in Switzerland; Oxford University, Oxford (B.A.), and GlaxoSmithKline, Stockley Park West (J.-P.K., L.M.K., V.M.R., S.W.J., E.H., K.M., D.D.C., K.F., C.O.U., J.A.G., G.C.K.W.K.) - both in the United Kingdom; and GlaxoSmithKline, Collegeville, PA (J.J.B.). 7From Fundação de Medicina Tropical Dr Heitor Vieira Dourado, Manaus (M.V.G.L., F.V., W.M.M., M.A.M.B., M.R.F.C.), Fundação Oswaldo Cruz, Manguinhos, Rio de Janeiro (M.V.G.L.), and Centro de Pesquisa em Medicina Tropical Rondônia, Porto Velho (D.B.P., M.S.T.) - all in Brazil; Universidad Peruana Cayetano Heredia, Lima, Peru (A.L.-C., R.C., M.C.); Mahidol University (S.K.) and the Armed Forces Research Institute of Medical Sciences (C.L., D.L.S., N.B.), Bangkok, Thailand; the University of Gondar, Gondar (R.M., E.D., S.G., K.M.W.), and Jimma University, Jimma (D.Y., A.A., A.Z., C.A.) - both in Ethiopia; Research Institute for Tropical Medicine, Manila (F.E.J.E.), and Rio Tuba Nickel Foundation Hospital, Palawan (R.Z.M.) - both in the Philippines; Medical University of Vienna, Vienna (H.N.); Swiss Tropical and Public Health Institute and University of Basel, Basel (F.B., H.-P.B.), and Medicines for Malaria Venture, Geneva (S.D.) - both in Switzerland; Oxford University, Oxford (B.A.), and GlaxoSmithKline, Stockley Park West (J.-P.K., L.M.K., V.M.R., S.W.J., E.H., K.M., D.D.C., K.F., C.O.U., J.A.G., G.C.K.W.K.) - both in the United Kingdom; and GlaxoSmithKline, Collegeville, PA (J.J.B.). 8From Fundação de Medicina Tropical Dr Heitor Vieira Dourado, Manaus (M.V.G.L., F.V., W.M.M., M.A.M.B., M.R.F.C.), Fundação Oswaldo Cruz, Manguinhos, Rio de Janeiro (M.V.G.L.), and Centro de Pesquisa em Medicina Tropical Rondônia, Porto Velho (D.B.P., M.S.T.) - all in Brazil; Universidad Peruana Cayetano Heredia, Lima, Peru (A.L.-C., R.C., M.C.); Mahidol University (S.K.) and the Armed Forces Research Institute of Medical Sciences (C.L., D.L.S., N.B.), Bangkok, Thailand; the University of Gondar, Gondar (R.M., E.D., S.G., K.M.W.), and Jimma University, Jimma (D.Y., A.A., A.Z., C.A.) - both in Ethiopia; Research Institute for Tropical Medicine, Manila (F.E.J.E.), and Rio Tuba Nickel Foundation Hospital, Palawan (R.Z.M.) - both in the Philippines; Medical University of Vienna, Vienna (H.N.); Swiss Tropical and Public Health Institute and University of Basel, Basel (F.B., H.-P.B.), and Medicines for Malaria Venture, Geneva (S.D.) - both in Switzerland; Oxford University, Oxford (B.A.), and GlaxoSmithKline, Stockley Park West (J.-P.K., L.M.K., V.M.R., S.W.J., E.H., K.M., D.D.C., K.F., C.O.U., J.A.G., G.C.K.W.K.) - both in the United Kingdom; and GlaxoSmithKline, Collegeville, PA (J.J.B.). 9From Fundação de Medicina Tropical Dr Heitor Vieira Dourado, Manaus (M.V.G.L., F.V., W.M.M., M.A.M.B., M.R.F.C.), Fundação Oswaldo Cruz, Manguinhos, Rio de Janeiro (M.V.G.L.), and Centro de Pesquisa em Medicina Tropical Rondônia, Porto Velho (D.B.P., M.S.T.) - all in Brazil; Universidad Peruana Cayetano Heredia, Lima, Peru (A.L.-C., R.C., M.C.); Mahidol University (S.K.) and the Armed Forces Research Institute of Medical Sciences (C.L., D.L.S., N.B.), Bangkok, Thailand; the University of Gondar, Gondar (R.M., E.D., S.G., K.M.W.), and Jimma University, Jimma (D.Y., A.A., A.Z., C.A.) - both in Ethiopia; Research Institute for Tropical Medicine, Manila (F.E.J.E.), and Rio Tuba Nickel Foundation Hospital, Palawan (R.Z.M.) - both in the Philippines; Medical University of Vienna, Vienna (H.N.); Swiss Tropical and Public Health Institute and University of Basel, Basel (F.B., H.-P.B.), and Medicines for Malaria Venture, Geneva (S.D.) - both in Switzerland; Oxford University, Oxford (B.A.), and GlaxoSmithKline, Stockley Park West (J.-P.K., L.M.K., V.M.R., S.W.J., E.H., K.M., D.D.C., K.F., C.O.U., J.A.G., G.C.K.W.K.) - both in the United Kingdom; and GlaxoSmithKline, Collegeville, PA (J.J.B.). 10From Fundação de Medicina Tropical Dr Heitor Vieira Dourado, Manaus (M.V.G.L., F.V., W.M.M., M.A.M.B., M.R.F.C.), Fundação Oswaldo Cruz, Manguinhos, Rio de Janeiro (M.V.G.L.), and Centro de Pesquisa em Medicina Tropical Rondônia, Porto Velho (D.B.P., M.S.T.) - all in Brazil; Universidad Peruana Cayetano Heredia, Lima, Peru (A.L.-C., R.C., M.C.); Mahidol University (S.K.) and the Armed Forces Research Institute of Medical Sciences (C.L., D.L.S., N.B.), Bangkok, Thailand; the University of Gondar, Gondar (R.M., E.D., S.G., K.M.W.), and Jimma University, Jimma (D.Y., A.A., A.Z., C.A.) - both in Ethiopia; Research Institute for Tropical Medicine, Manila (F.E.J.E.), and Rio Tuba Nickel Foundation Hospital, Palawan (R.Z.M.) - both in the Philippines; Medical University of Vienna, Vienna (H.N.); Swiss Tropical and Public Health Institute and University of Basel, Basel (F.B., H.-P.B.), and Medicines for Malaria Venture, Geneva (S.D.) - both in Switzerland; Oxford University, Oxford (B.A.), and GlaxoSmithKline, Stockley Park West (J.-P.K., L.M.K., V.M.R., S.W.J., E.H., K.M., D.D.C., K.F., C.O.U., J.A.G., G.C.K.W.K.) - both in the United Kingdom; and GlaxoSmithKline, Collegeville, PA (J.J.B.). 11From Fundação de Medicina Tropical Dr Heitor Vieira Dourado, Manaus (M.V.G.L., F.V., W.M.M., M.A.M.B., M.R.F.C.), Fundação Oswaldo Cruz, Manguinhos, Rio de Janeiro (M.V.G.L.), and Centro de Pesquisa em Medicina Tropical Rondônia, Porto Velho (D.B.P., M.S.T.) - all in Brazil; Universidad Peruana Cayetano Heredia, Lima, Peru (A.L.-C., R.C., M.C.); Mahidol University (S.K.) and the Armed Forces Research Institute of Medical Sciences (C.L., D.L.S., N.B.), Bangkok, Thailand; the University of Gondar, Gondar (R.M., E.D., S.G., K.M.W.), and Jimma University, Jimma (D.Y., A.A., A.Z., C.A.) - both in Ethiopia; Research Institute for Tropical Medicine, Manila (F.E.J.E.), and Rio Tuba Nickel Foundation Hospital, Palawan (R.Z.M.) - both in the Philippines; Medical University of Vienna, Vienna (H.N.); Swiss Tropical and Public Health Institute and University of Basel, Basel (F.B., H.-P.B.), and Medicines for Malaria Venture, Geneva (S.D.) - both in Switzerland; Oxford University, Oxford (B.A.), and GlaxoSmithKline, Stockley Park West (J.-P.K., L.M.K., V.M.R., S.W.J., E.H., K.M., D.D.C., K.F., C.O.U., J.A.G., G.C.K.W.K.) - both in the United Kingdom; and GlaxoSmithKline, Collegeville, PA (J.J.B.). 12From Fundação de Medicina Tropical Dr Heitor Vieira Dourado, Manaus (M.V.G.L., F.V., W.M.M., M.A.M.B., M.R.F.C.), Fundação Oswaldo Cruz, Manguinhos, Rio de Janeiro (M.V.G.L.), and Centro de Pesquisa em Medicina Tropical Rondônia, Porto Velho (D.B.P., M.S.T.) - all in Brazil; Universidad Peruana Cayetano Heredia, Lima, Peru (A.L.-C., R.C., M.C.); Mahidol University (S.K.) and the Armed Forces Research Institute of Medical Sciences (C.L., D.L.S., N.B.), Bangkok, Thailand; the University of Gondar, Gondar (R.M., E.D., S.G., K.M.W.), and Jimma University, Jimma (D.Y., A.A., A.Z., C.A.) - both in Ethiopia; Research Institute for Tropical Medicine, Manila (F.E.J.E.), and Rio Tuba Nickel Foundation Hospital, Palawan (R.Z.M.) - both in the Philippines; Medical University of Vienna, Vienna (H.N.); Swiss Tropical and Public Health Institute and University of Basel, Basel (F.B., H.-P.B.), and Medicines for Malaria Venture, Geneva (S.D.) - both in Switzerland; Oxford University, Oxford (B.A.), and GlaxoSmithKline, Stockley Park West (J.-P.K., L.M.K., V.M.R., S.W.J., E.H., K.M., D.D.C., K.F., C.O.U., J.A.G., G.C.K.W.K.) - both in the United Kingdom; and GlaxoSmithKline, Collegeville, PA (J.J.B.). 13From Fundação de Medicina Tropical Dr Heitor Vieira Dourado, Manaus (M.V.G.L., F.V., W.M.M., M.A.M.B., M.R.F.C.), Fundação Oswaldo Cruz, Manguinhos, Rio de Janeiro (M.V.G.L.), and Centro de Pesquisa em Medicina Tropical Rondônia, Porto Velho (D.B.P., M.S.T.) - all in Brazil; Universidad Peruana Cayetano Heredia, Lima, Peru (A.L.-C., R.C., M.C.); Mahidol University (S.K.) and the Armed Forces Research Institute of Medical Sciences (C.L., D.L.S., N.B.), Bangkok, Thailand; the University of Gondar, Gondar (R.M., E.D., S.G., K.M.W.), and Jimma University, Jimma (D.Y., A.A., A.Z., C.A.) - both in Ethiopia; Research Institute for Tropical Medicine, Manila (F.E.J.E.), and Rio Tuba Nickel Foundation Hospital, Palawan (R.Z.M.) - both in the Philippines; Medical University of Vienna, Vienna (H.N.); Swiss Tropical and Public Health Institute and University of Basel, Basel (F.B., H.-P.B.), and Medicines for Malaria Venture, Geneva (S.D.) - both in Switzerland; Oxford University, Oxford (B.A.), and GlaxoSmithKline, Stockley Park West (J.-P.K., L.M.K., V.M.R., S.W.J., E.H., K.M., D.D.C., K.F., C.O.U., J.A.G., G.C.K.W.K.) - both in the United Kingdom; and GlaxoSmithKline, Collegeville, PA (J.J.B.). 14From Fundação de Medicina Tropical Dr Heitor Vieira Dourado, Manaus (M.V.G.L., F.V., W.M.M., M.A.M.B., M.R.F.C.), Fundação Oswaldo Cruz, Manguinhos, Rio de Janeiro (M.V.G.L.), and Centro de Pesquisa em Medicina Tropical Rondônia, Porto Velho (D.B.P., M.S.T.) - all in Brazil; Universidad Peruana Cayetano Heredia, Lima, Peru (A.L.-C., R.C., M.C.); Mahidol University (S.K.) and the Armed Forces Research Institute of Medical Sciences (C.L., D.L.S., N.B.), Bangkok, Thailand; the University of Gondar, Gondar (R.M., E.D., S.G., K.M.W.), and Jimma University, Jimma (D.Y., A.A., A.Z., C.A.) - both in Ethiopia; Research Institute for Tropical Medicine, Manila (F.E.J.E.), and Rio Tuba Nickel Foundation Hospital, Palawan (R.Z.M.) - both in the Philippines; Medical University of Vienna, Vienna (H.N.); Swiss Tropical and Public Health Institute and University of Basel, Basel (F.B., H.-P.B.), and Medicines for Malaria Venture, Geneva (S.D.) - both in Switzerland; Oxford University, Oxford (B.A.), and GlaxoSmithKline, Stockley Park West (J.-P.K., L.M.K., V.M.R., S.W.J., E.H., K.M., D.D.C., K.F., C.O.U., J.A.G., G.C.K.W.K.) - both in the United Kingdom; and GlaxoSmithKline, Collegeville, PA (J.J.B.). 15From Fundação de Medicina Tropical Dr Heitor Vieira Dourado, Manaus (M.V.G.L., F.V., W.M.M., M.A.M.B., M.R.F.C.), Fundação Oswaldo Cruz, Manguinhos, Rio de Janeiro (M.V.G.L.), and Centro de Pesquisa em Medicina Tropical Rondônia, Porto Velho (D.B.P., M.S.T.) - all in Brazil; Universidad Peruana Cayetano Heredia, Lima, Peru (A.L.-C., R.C., M.C.); Mahidol University (S.K.) and the Armed Forces Research Institute of Medical Sciences (C.L., D.L.S., N.B.), Bangkok, Thailand; the University of Gondar, Gondar (R.M., E.D., S.G., K.M.W.), and Jimma University, Jimma (D.Y., A.A., A.Z., C.A.) - both in Ethiopia; Research Institute for Tropical Medicine, Manila (F.E.J.E.), and Rio Tuba Nickel Foundation Hospital, Palawan (R.Z.M.) - both in the Philippines; Medical University of Vienna, Vienna (H.N.); Swiss Tropical and Public Health Institute and University of Basel, Basel (F.B., H.-P.B.), and Medicines for Malaria Venture, Geneva (S.D.) - both in Switzerland; Oxford University, Oxford (B.A.), and GlaxoSmithKline, Stockley Park West (J.-P.K., L.M.K., V.M.R., S.W.J., E.H., K.M., D.D.C., K.F., C.O.U., J.A.G., G.C.K.W.K.) - both in the United Kingdom; and GlaxoSmithKline, Collegeville, PA (J.J.B.). 16From Fundação de Medicina Tropical Dr Heitor Vieira Dourado, Manaus (M.V.G.L., F.V., W.M.M., M.A.M.B., M.R.F.C.), Fundação Oswaldo Cruz, Manguinhos, Rio de Janeiro (M.V.G.L.), and Centro de Pesquisa em Medicina Tropical Rondônia, Porto Velho (D.B.P., M.S.T.) - all in Brazil; Universidad Peruana Cayetano Heredia, Lima, Peru (A.L.-C., R.C., M.C.); Mahidol University (S.K.) and the Armed Forces Research Institute of Medical Sciences (C.L., D.L.S., N.B.), Bangkok, Thailand; the University of Gondar, Gondar (R.M., E.D., S.G., K.M.W.), and Jimma University, Jimma (D.Y., A.A., A.Z., C.A.) - both in Ethiopia; Research Institute for Tropical Medicine, Manila (F.E.J.E.), and Rio Tuba Nickel Foundation Hospital, Palawan (R.Z.M.) - both in the Philippines; Medical University of Vienna, Vienna (H.N.); Swiss Tropical and Public Health Institute and University of Basel, Basel (F.B., H.-P.B.), and Medicines for Malaria Venture, Geneva (S.D.) - both in Switzerland; Oxford University, Oxford (B.A.), and GlaxoSmithKline, Stockley Park West (J.-P.K., L.M.K., V.M.R., S.W.J., E.H., K.M., D.D.C., K.F., C.O.U., J.A.G., G.C.K.W.K.) - both in the United Kingdom; and GlaxoSmithKline, Collegeville, PA (J.J.B.). 17From Fundação de Medicina Tropical Dr Heitor Vieira Dourado, Manaus (M.V.G.L., F.V., W.M.M., M.A.M.B., M.R.F.C.), Fundação Oswaldo Cruz, Manguinhos, Rio de Janeiro (M.V.G.L.), and Centro de Pesquisa em Medicina Tropical Rondônia, Porto Velho (D.B.P., M.S.T.) - all in Brazil; Universidad Peruana Cayetano Heredia, Lima, Peru (A.L.-C., R.C., M.C.); Mahidol University (S.K.) and the Armed Forces Research Institute of Medical Sciences (C.L., D.L.S., N.B.), Bangkok, Thailand; the University of Gondar, Gondar (R.M., E.D., S.G., K.M.W.), and Jimma University, Jimma (D.Y., A.A., A.Z., C.A.) - both in Ethiopia; Research Institute for Tropical Medicine, Manila (F.E.J.E.), and Rio Tuba Nickel Foundation Hospital, Palawan (R.Z.M.) - both in the Philippines; Medical University of Vienna, Vienna (H.N.); Swiss Tropical and Public Health Institute and University of Basel, Basel (F.B., H.-P.B.), and Medicines for Malaria Venture, Geneva (S.D.) - both in Switzerland; Oxford University, Oxford (B.A.), and GlaxoSmithKline, Stockley Park West (J.-P.K., L.M.K., V.M.R., S.W.J., E.H., K.M., D.D.C., K.F., C.O.U., J.A.G., G.C.K.W.K.) - both in the United Kingdom; and GlaxoSmithKline, Collegeville, PA (J.J.B.). 18From Fundação de Medicina Tropical Dr Heitor Vieira Dourado, Manaus (M.V.G.L., F.V., W.M.M., M.A.M.B., M.R.F.C.), Fundação Oswaldo Cruz, Manguinhos, Rio de Janeiro (M.V.G.L.), and Centro de Pesquisa em Medicina Tropical Rondônia, Porto Velho (D.B.P., M.S.T.) - all in Brazil; Universidad Peruana Cayetano Heredia, Lima, Peru (A.L.-C., R.C., M.C.); Mahidol University (S.K.) and the Armed Forces Research Institute of Medical Sciences (C.L., D.L.S., N.B.), Bangkok, Thailand; the University of Gondar, Gondar (R.M., E.D., S.G., K.M.W.), and Jimma University, Jimma (D.Y., A.A., A.Z., C.A.) - both in Ethiopia; Research Institute for Tropical Medicine, Manila (F.E.J.E.), and Rio Tuba Nickel Foundation Hospital, Palawan (R.Z.M.) - both in the Philippines; Medical University of Vienna, Vienna (H.N.); Swiss Tropical and Public Health Institute and University of Basel, Basel (F.B., H.-P.B.), and Medicines for Malaria Venture, Geneva (S.D.) - both in Switzerland; Oxford University, Oxford (B.A.), and GlaxoSmithKline, Stockley Park West (J.-P.K., L.M.K., V.M.R., S.W.J., E.H., K.M., D.D.C., K.F., C.O.U., J.A.G., G.C.K.W.K.) - both in the United Kingdom; and GlaxoSmithKline, Collegeville, PA (J.J.B.). 19From Fundação de Medicina Tropical Dr Heitor Vieira Dourado, Manaus (M.V.G.L., F.V., W.M.M., M.A.M.B., M.R.F.C.), Fundação Oswaldo Cruz, Manguinhos, Rio de Janeiro (M.V.G.L.), and Centro de Pesquisa em Medicina Tropical Rondônia, Porto Velho (D.B.P., M.S.T.) - all in Brazil; Universidad Peruana Cayetano Heredia, Lima, Peru (A.L.-C., R.C., M.C.); Mahidol University (S.K.) and the Armed Forces Research Institute of Medical Sciences (C.L., D.L.S., N.B.), Bangkok, Thailand; the University of Gondar, Gondar (R.M., E.D., S.G., K.M.W.), and Jimma University, Jimma (D.Y., A.A., A.Z., C.A.) - both in Ethiopia; Research Institute for Tropical Medicine, Manila (F.E.J.E.), and Rio Tuba Nickel Foundation Hospital, Palawan (R.Z.M.) - both in the Philippines; Medical University of Vienna, Vienna (H.N.); Swiss Tropical and Public Health Institute and University of Basel, Basel (F.B., H.-P.B.), and Medicines for Malaria Venture, Geneva (S.D.) - both in Switzerland; Oxford University, Oxford (B.A.), and GlaxoSmithKline, Stockley Park West (J.-P.K., L.M.K., V.M.R., S.W.J., E.H., K.M., D.D.C., K.F., C.O.U., J.A.G., G.C.K.W.K.) - both in the United Kingdom; and GlaxoSmithKline, Collegeville, PA (J.J.B.). 20From Fundação de Medicina Tropical Dr Heitor Vieira Dourado, Manaus (M.V.G.L., F.V., W.M.M., M.A.M.B., M.R.F.C.), Fundação Oswaldo Cruz, Manguinhos, Rio de Janeiro (M.V.G.L.), and Centro de Pesquisa em Medicina Tropical Rondônia, Porto Velho (D.B.P., M.S.T.) - all in Brazil; Universidad Peruana Cayetano Heredia, Lima, Peru (A.L.-C., R.C., M.C.); Mahidol University (S.K.) and the Armed Forces Research Institute of Medical Sciences (C.L., D.L.S., N.B.), Bangkok, Thailand; the University of Gondar, Gondar (R.M., E.D., S.G., K.M.W.), and Jimma University, Jimma (D.Y., A.A., A.Z., C.A.) - both in Ethiopia; Research Institute for Tropical Medicine, Manila (F.E.J.E.), and Rio Tuba Nickel Foundation Hospital, Palawan (R.Z.M.) - both in the Philippines; Medical University of Vienna, Vienna (H.N.); Swiss Tropical and Public Health Institute and University of Basel, Basel (F.B., H.-P.B.), and Medicines for Malaria Venture, Geneva (S.D.) - both in Switzerland; Oxford University, Oxford (B.A.), and GlaxoSmithKline, Stockley Park West (J.-P.K., L.M.K., V.M.R., S.W.J., E.H., K.M., D.D.C., K.F., C.O.U., J.A.G., G.C.K.W.K.) - both in the United Kingdom; and GlaxoSmithKline, Collegeville, PA (J.J.B.). 21From Fundação de Medicina Tropical Dr Heitor Vieira Dourado, Manaus (M.V.G.L., F.V., W.M.M., M.A.M.B., M.R.F.C.), Fundação Oswaldo Cruz, Manguinhos, Rio de Janeiro (M.V.G.L.), and Centro de Pesquisa em Medicina Tropical Rondônia, Porto Velho (D.B.P., M.S.T.) - all in Brazil; Universidad Peruana Cayetano Heredia, Lima, Peru (A.L.-C., R.C., M.C.); Mahidol University (S.K.) and the Armed Forces Research Institute of Medical Sciences (C.L., D.L.S., N.B.), Bangkok, Thailand; the University of Gondar, Gondar (R.M., E.D., S.G., K.M.W.), and Jimma University, Jimma (D.Y., A.A., A.Z., C.A.) - both in Ethiopia; Research Institute for Tropical Medicine, Manila (F.E.J.E.), and Rio Tuba Nickel Foundation Hospital, Palawan (R.Z.M.) - both in the Philippines; Medical University of Vienna, Vienna (H.N.); Swiss Tropical and Public Health Institute and University of Basel, Basel (F.B., H.-P.B.), and Medicines for Malaria Venture, Geneva (S.D.) - both in Switzerland; Oxford University, Oxford (B.A.), and GlaxoSmithKline, Stockley Park West (J.-P.K., L.M.K., V.M.R., S.W.J., E.H., K.M., D.D.C., K.F., C.O.U., J.A.G., G.C.K.W.K.) - both in the United Kingdom; and GlaxoSmithKline, Collegeville, PA (J.J.B.). 22From Fundação de Medicina Tropical Dr Heitor Vieira Dourado, Manaus (M.V.G.L., F.V., W.M.M., M.A.M.B., M.R.F.C.), Fundação Oswaldo Cruz, Manguinhos, Rio de Janeiro (M.V.G.L.), and Centro de Pesquisa em Medicina Tropical Rondônia, Porto Velho (D.B.P., M.S.T.) - all in Brazil; Universidad Peruana Cayetano Heredia, Lima, Peru (A.L.-C., R.C., M.C.); Mahidol University (S.K.) and the Armed Forces Research Institute of Medical Sciences (C.L., D.L.S., N.B.), Bangkok, Thailand; the University of Gondar, Gondar (R.M., E.D., S.G., K.M.W.), and Jimma University, Jimma (D.Y., A.A., A.Z., C.A.) - both in Ethiopia; Research Institute for Tropical Medicine, Manila (F.E.J.E.), and Rio Tuba Nickel Foundation Hospital, Palawan (R.Z.M.) - both in the Philippines; Medical University of Vienna, Vienna (H.N.); Swiss Tropical and Public Health Institute and University of Basel, Basel (F.B., H.-P.B.), and Medicines for Malaria Venture, Geneva (S.D.) - both in Switzerland; Oxford University, Oxford (B.A.), and GlaxoSmithKline, Stockley Park West (J.-P.K., L.M.K., V.M.R., S.W.J., E.H., K.M., D.D.C., K.F., C.O.U., J.A.G., G.C.K.W.K.) - both in the United Kingdom; and GlaxoSmithKline, Collegeville, PA (J.J.B.). 23From Fundação de Medicina Tropical Dr Heitor Vieira Dourado, Manaus (M.V.G.L., F.V., W.M.M., M.A.M.B., M.R.F.C.), Fundação Oswaldo Cruz, Manguinhos, Rio de Janeiro (M.V.G.L.), and Centro de Pesquisa em Medicina Tropical Rondônia, Porto Velho (D.B.P., M.S.T.) - all in Brazil; Universidad Peruana Cayetano Heredia, Lima, Peru (A.L.-C., R.C., M.C.); Mahidol University (S.K.) and the Armed Forces Research Institute of Medical Sciences (C.L., D.L.S., N.B.), Bangkok, Thailand; the University of Gondar, Gondar (R.M., E.D., S.G., K.M.W.), and Jimma University, Jimma (D.Y., A.A., A.Z., C.A.) - both in Ethiopia; Research Institute for Tropical Medicine, Manila (F.E.J.E.), and Rio Tuba Nickel Foundation Hospital, Palawan (R.Z.M.) - both in the Philippines; Medical University of Vienna, Vienna (H.N.); Swiss Tropical and Public Health Institute and University of Basel, Basel (F.B., H.-P.B.), and Medicines for Malaria Venture, Geneva (S.D.) - both in Switzerland; Oxford University, Oxford (B.A.), and GlaxoSmithKline, Stockley Park West (J.-P.K., L.M.K., V.M.R., S.W.J., E.H., K.M., D.D.C., K.F., C.O.U., J.A.G., G.C.K.W.K.) - both in the United Kingdom; and GlaxoSmithKline, Collegeville, PA (J.J.B.). 24From Fundação de Medicina Tropical Dr Heitor Vieira Dourado, Manaus (M.V.G.L., F.V., W.M.M., M.A.M.B., M.R.F.C.), Fundação Oswaldo Cruz, Manguinhos, Rio de Janeiro (M.V.G.L.), and Centro de Pesquisa em Medicina Tropical Rondônia, Porto Velho (D.B.P., M.S.T.) - all in Brazil; Universidad Peruana Cayetano Heredia, Lima, Peru (A.L.-C., R.C., M.C.); Mahidol University (S.K.) and the Armed Forces Research Institute of Medical Sciences (C.L., D.L.S., N.B.), Bangkok, Thailand; the University of Gondar, Gondar (R.M., E.D., S.G., K.M.W.), and Jimma University, Jimma (D.Y., A.A., A.Z., C.A.) - both in Ethiopia; Research Institute for Tropical Medicine, Manila (F.E.J.E.), and Rio Tuba Nickel Foundation Hospital, Palawan (R.Z.M.) - both in the Philippines; Medical University of Vienna, Vienna (H.N.); Swiss Tropical and Public Health Institute and University of Basel, Basel (F.B., H.-P.B.), and Medicines for Malaria Venture, Geneva (S.D.) - both in Switzerland; Oxford University, Oxford (B.A.), and GlaxoSmithKline, Stockley Park West (J.-P.K., L.M.K., V.M.R., S.W.J., E.H., K.M., D.D.C., K.F., C.O.U., J.A.G., G.C.K.W.K.) - both in the United Kingdom; and GlaxoSmithKline, Collegeville, PA (J.J.B.). 25From Fundação de Medicina Tropical Dr Heitor Vieira Dourado, Manaus (M.V.G.L., F.V., W.M.M., M.A.M.B., M.R.F.C.), Fundação Oswaldo Cruz, Manguinhos, Rio de Janeiro (M.V.G.L.), and Centro de Pesquisa em Medicina Tropical Rondônia, Porto Velho (D.B.P., M.S.T.) - all in Brazil; Universidad Peruana Cayetano Heredia, Lima, Peru (A.L.-C., R.C., M.C.); Mahidol University (S.K.) and the Armed Forces Research Institute of Medical Sciences (C.L., D.L.S., N.B.), Bangkok, Thailand; the University of Gondar, Gondar (R.M., E.D., S.G., K.M.W.), and Jimma University, Jimma (D.Y., A.A., A.Z., C.A.) - both in Ethiopia; Research Institute for Tropical Medicine, Manila (F.E.J.E.), and Rio Tuba Nickel Foundation Hospital, Palawan (R.Z.M.) - both in the Philippines; Medical University of Vienna, Vienna (H.N.); Swiss Tropical and Public Health Institute and University of Basel, Basel (F.B., H.-P.B.), and Medicines for Malaria Venture, Geneva (S.D.) - both in Switzerland; Oxford University, Oxford (B.A.), and GlaxoSmithKline, Stockley Park West (J.-P.K., L.M.K., V.M.R., S.W.J., E.H., K.M., D.D.C., K.F., C.O.U., J.A.G., G.C.K.W.K.) - both in the United Kingdom; and GlaxoSmithKline, Collegeville, PA (J.J.B.). 26From Fundação de Medicina Tropical Dr Heitor Vieira Dourado, Manaus (M.V.G.L., F.V., W.M.M., M.A.M.B., M.R.F.C.), Fundação Oswaldo Cruz, Manguinhos, Rio de Janeiro (M.V.G.L.), and Centro de Pesquisa em Medicina Tropical Rondônia, Porto Velho (D.B.P., M.S.T.) - all in Brazil; Universidad Peruana Cayetano Heredia, Lima, Peru (A.L.-C., R.C., M.C.); Mahidol University (S.K.) and the Armed Forces Research Institute of Medical Sciences (C.L., D.L.S., N.B.), Bangkok, Thailand; the University of Gondar, Gondar (R.M., E.D., S.G., K.M.W.), and Jimma University, Jimma (D.Y., A.A., A.Z., C.A.) - both in Ethiopia; Research Institute for Tropical Medicine, Manila (F.E.J.E.), and Rio Tuba Nickel Foundation Hospital, Palawan (R.Z.M.) - both in the Philippines; Medical University of Vienna, Vienna (H.N.); Swiss Tropical and Public Health Institute and University of Basel, Basel (F.B., H.-P.B.), and Medicines for Malaria Venture, Geneva (S.D.) - both in Switzerland; Oxford University, Oxford (B.A.), and GlaxoSmithKline, Stockley Park West (J.-P.K., L.M.K., V.M.R., S.W.J., E.H., K.M., D.D.C., K.F., C.O.U., J.A.G., G.C.K.W.K.) - both in the United Kingdom; and GlaxoSmithKline, Collegeville, PA (J.J.B.). 27From Fundação de Medicina Tropical Dr Heitor Vieira Dourado, Manaus (M.V.G.L., F.V., W.M.M., M.A.M.B., M.R.F.C.), Fundação Oswaldo Cruz, Manguinhos, Rio de Janeiro (M.V.G.L.), and Centro de Pesquisa em Medicina Tropical Rondônia, Porto Velho (D.B.P., M.S.T.) - all in Brazil; Universidad Peruana Cayetano Heredia, Lima, Peru (A.L.-C., R.C., M.C.); Mahidol University (S.K.) and the Armed Forces Research Institute of Medical Sciences (C.L., D.L.S., N.B.), Bangkok, Thailand; the University of Gondar, Gondar (R.M., E.D., S.G., K.M.W.), and Jimma University, Jimma (D.Y., A.A., A.Z., C.A.) - both in Ethiopia; Research Institute for Tropical Medicine, Manila (F.E.J.E.), and Rio Tuba Nickel Foundation Hospital, Palawan (R.Z.M.) - both in the Philippines; Medical University of Vienna, Vienna (H.N.); Swiss Tropical and Public Health Institute and University of Basel, Basel (F.B., H.-P.B.), and Medicines for Malaria Venture, Geneva (S.D.) - both in Switzerland; Oxford University, Oxford (B.A.), and GlaxoSmithKline, Stockley Park West (J.-P.K., L.M.K., V.M.R., S.W.J., E.H., K.M., D.D.C., K.F., C.O.U., J.A.G., G.C.K.W.K.) - both in the United Kingdom; and GlaxoSmithKline, Collegeville, PA (J.J.B.). 28From Fundação de Medicina Tropical Dr Heitor Vieira Dourado, Manaus (M.V.G.L., F.V., W.M.M., M.A.M.B., M.R.F.C.), Fundação Oswaldo Cruz, Manguinhos, Rio de Janeiro (M.V.G.L.), and Centro de Pesquisa em Medicina Tropical Rondônia, Porto Velho (D.B.P., M.S.T.) - all in Brazil; Universidad Peruana Cayetano Heredia, Lima, Peru (A.L.-C., R.C., M.C.); Mahidol University (S.K.) and the Armed Forces Research Institute of Medical Sciences (C.L., D.L.S., N.B.), Bangkok, Thailand; the University of Gondar, Gondar (R.M., E.D., S.G., K.M.W.), and Jimma University, Jimma (D.Y., A.A., A.Z., C.A.) - both in Ethiopia; Research Institute for Tropical Medicine, Manila (F.E.J.E.), and Rio Tuba Nickel Foundation Hospital, Palawan (R.Z.M.) - both in the Philippines; Medical University of Vienna, Vienna (H.N.); Swiss Tropical and Public Health Institute and University of Basel, Basel (F.B., H.-P.B.), and Medicines for Malaria Venture, Geneva (S.D.) - both in Switzerland; Oxford University, Oxford (B.A.), and GlaxoSmithKline, Stockley Park West (J.-P.K., L.M.K., V.M.R., S.W.J., E.H., K.M., D.D.C., K.F., C.O.U., J.A.G., G.C.K.W.K.) - both in the United Kingdom; and GlaxoSmithKline, Collegeville, PA (J.J.B.). 29From Fundação de Medicina Tropical Dr Heitor Vieira Dourado, Manaus (M.V.G.L., F.V., W.M.M., M.A.M.B., M.R.F.C.), Fundação Oswaldo Cruz, Manguinhos, Rio de Janeiro (M.V.G.L.), and Centro de Pesquisa em Medicina Tropical Rondônia, Porto Velho (D.B.P., M.S.T.) - all in Brazil; Universidad Peruana Cayetano Heredia, Lima, Peru (A.L.-C., R.C., M.C.); Mahidol University (S.K.) and the Armed Forces Research Institute of Medical Sciences (C.L., D.L.S., N.B.), Bangkok, Thailand; the University of Gondar, Gondar (R.M., E.D., S.G., K.M.W.), and Jimma University, Jimma (D.Y., A.A., A.Z., C.A.) - both in Ethiopia; Research Institute for Tropical Medicine, Manila (F.E.J.E.), and Rio Tuba Nickel Foundation Hospital, Palawan (R.Z.M.) - both in the Philippines; Medical University of Vienna, Vienna (H.N.); Swiss Tropical and Public Health Institute and University of Basel, Basel (F.B., H.-P.B.), and Medicines for Malaria Venture, Geneva (S.D.) - both in Switzerland; Oxford University, Oxford (B.A.), and GlaxoSmithKline, Stockley Park West (J.-P.K., L.M.K., V.M.R., S.W.J., E.H., K.M., D.D.C., K.F., C.O.U., J.A.G., G.C.K.W.K.) - both in the United Kingdom; and GlaxoSmithKline, Collegeville, PA (J.J.B.). 30From Fundação de Medicina Tropical Dr Heitor Vieira Dourado, Manaus (M.V.G.L., F.V., W.M.M., M.A.M.B., M.R.F.C.), Fundação Oswaldo Cruz, Manguinhos, Rio de Janeiro (M.V.G.L.), and Centro de Pesquisa em Medicina Tropical Rondônia, Porto Velho (D.B.P., M.S.T.) - all in Brazil; Universidad Peruana Cayetano Heredia, Lima, Peru (A.L.-C., R.C., M.C.); Mahidol University (S.K.) and the Armed Forces Research Institute of Medical Sciences (C.L., D.L.S., N.B.), Bangkok, Thailand; the University of Gondar, Gondar (R.M., E.D., S.G., K.M.W.), and Jimma University, Jimma (D.Y., A.A., A.Z., C.A.) - both in Ethiopia; Research Institute for Tropical Medicine, Manila (F.E.J.E.), and Rio Tuba Nickel Foundation Hospital, Palawan (R.Z.M.) - both in the Philippines; Medical University of Vienna, Vienna (H.N.); Swiss Tropical and Public Health Institute and University of Basel, Basel (F.B., H.-P.B.), and Medicines for Malaria Venture, Geneva (S.D.) - both in Switzerland; Oxford University, Oxford (B.A.), and GlaxoSmithKline, Stockley Park West (J.-P.K., L.M.K., V.M.R., S.W.J., E.H., K.M., D.D.C., K.F., C.O.U., J.A.G., G.C.K.W.K.) - both in the United Kingdom; and GlaxoSmithKline, Collegeville, PA (J.J.B.). 31From Fundação de Medicina Tropical Dr Heitor Vieira Dourado, Manaus (M.V.G.L., F.V., W.M.M., M.A.M.B., M.R.F.C.), Fundação Oswaldo Cruz, Manguinhos, Rio de Janeiro (M.V.G.L.), and Centro de Pesquisa em Medicina Tropical Rondônia, Porto Velho (D.B.P., M.S.T.) - all in Brazil; Universidad Peruana Cayetano Heredia, Lima, Peru (A.L.-C., R.C., M.C.); Mahidol University (S.K.) and the Armed Forces Research Institute of Medical Sciences (C.L., D.L.S., N.B.), Bangkok, Thailand; the University of Gondar, Gondar (R.M., E.D., S.G., K.M.W.), and Jimma University, Jimma (D.Y., A.A., A.Z., C.A.) - both in Ethiopia; Research Institute for Tropical Medicine, Manila (F.E.J.E.), and Rio Tuba Nickel Foundation Hospital, Palawan (R.Z.M.) - both in the Philippines; Medical University of Vienna, Vienna (H.N.); Swiss Tropical and Public Health Institute and University of Basel, Basel (F.B., H.-P.B.), and Medicines for Malaria Venture, Geneva (S.D.) - both in Switzerland; Oxford University, Oxford (B.A.), and GlaxoSmithKline, Stockley Park West (J.-P.K., L.M.K., V.M.R., S.W.J., E.H., K.M., D.D.C., K.F., C.O.U., J.A.G., G.C.K.W.K.) - both in the United Kingdom; and GlaxoSmithKline, Collegeville, PA (J.J.B.). 32From Fundação de Medicina Tropical Dr Heitor Vieira Dourado, Manaus (M.V.G.L., F.V., W.M.M., M.A.M.B., M.R.F.C.), Fundação Oswaldo Cruz, Manguinhos, Rio de Janeiro (M.V.G.L.), and Centro de Pesquisa em Medicina Tropical Rondônia, Porto Velho (D.B.P., M.S.T.) - all in Brazil; Universidad Peruana Cayetano Heredia, Lima, Peru (A.L.-C., R.C., M.C.); Mahidol University (S.K.) and the Armed Forces Research Institute of Medical Sciences (C.L., D.L.S., N.B.), Bangkok, Thailand; the University of Gondar, Gondar (R.M., E.D., S.G., K.M.W.), and Jimma University, Jimma (D.Y., A.A., A.Z., C.A.) - both in Ethiopia; Research Institute for Tropical Medicine, Manila (F.E.J.E.), and Rio Tuba Nickel Foundation Hospital, Palawan (R.Z.M.) - both in the Philippines; Medical University of Vienna, Vienna (H.N.); Swiss Tropical and Public Health Institute and University of Basel, Basel (F.B., H.-P.B.), and Medicines for Malaria Venture, Geneva (S.D.) - both in Switzerland; Oxford University, Oxford (B.A.), and GlaxoSmithKline, Stockley Park West (J.-P.K., L.M.K., V.M.R., S.W.J., E.H., K.M., D.D.C., K.F., C.O.U., J.A.G., G.C.K.W.K.) - both in the United Kingdom; and GlaxoSmithKline, Collegeville, PA (J.J.B.). 33From Fundação de Medicina Tropical Dr Heitor Vieira Dourado, Manaus (M.V.G.L., F.V., W.M.M., M.A.M.B., M.R.F.C.), Fundação Oswaldo Cruz, Manguinhos, Rio de Janeiro (M.V.G.L.), and Centro de Pesquisa em Medicina Tropical Rondônia, Porto Velho (D.B.P., M.S.T.) - all in Brazil; Universidad Peruana Cayetano Heredia, Lima, Peru (A.L.-C., R.C., M.C.); Mahidol University (S.K.) and the Armed Forces Research Institute of Medical Sciences (C.L., D.L.S., N.B.), Bangkok, Thailand; the University of Gondar, Gondar (R.M., E.D., S.G., K.M.W.), and Jimma University, Jimma (D.Y., A.A., A.Z., C.A.) - both in Ethiopia; Research Institute for Tropical Medicine, Manila (F.E.J.E.), and Rio Tuba Nickel Foundation Hospital, Palawan (R.Z.M.) - both in the Philippines; Medical University of Vienna, Vienna (H.N.); Swiss Tropical and Public Health Institute and University of Basel, Basel (F.B., H.-P.B.), and Medicines for Malaria Venture, Geneva (S.D.) - both in Switzerland; Oxford University, Oxford (B.A.), and GlaxoSmithKline, Stockley Park West (J.-P.K., L.M.K., V.M.R., S.W.J., E.H., K.M., D.D.C., K.F., C.O.U., J.A.G., G.C.K.W.K.) - both in the United Kingdom; and GlaxoSmithKline, Collegeville, PA (J.J.B.). 34From Fundação de Medicina Tropical Dr Heitor Vieira Dourado, Manaus (M.V.G.L., F.V., W.M.M., M.A.M.B., M.R.F.C.), Fundação Oswaldo Cruz, Manguinhos, Rio de Janeiro (M.V.G.L.), and Centro de Pesquisa em Medicina Tropical Rondônia, Porto Velho (D.B.P., M.S.T.) - all in Brazil; Universidad Peruana Cayetano Heredia, Lima, Peru (A.L.-C., R.C., M.C.); Mahidol University (S.K.) and the Armed Forces Research Institute of Medical Sciences (C.L., D.L.S., N.B.), Bangkok, Thailand; the University of Gondar, Gondar (R.M., E.D., S.G., K.M.W.), and Jimma University, Jimma (D.Y., A.A., A.Z., C.A.) - both in Ethiopia; Research Institute for Tropical Medicine, Manila (F.E.J.E.), and Rio Tuba Nickel Foundation Hospital, Palawan (R.Z.M.) - both in the Philippines; Medical University of Vienna, Vienna (H.N.); Swiss Tropical and Public Health Institute and University of Basel, Basel (F.B., H.-P.B.), and Medicines for Malaria Venture, Geneva (S.D.) - both in Switzerland; Oxford University, Oxford (B.A.), and GlaxoSmithKline, Stockley Park West (J.-P.K., L.M.K., V.M.R., S.W.J., E.H., K.M., D.D.C., K.F., C.O.U., J.A.G., G.C.K.W.K.) - both in the United Kingdom; and GlaxoSmithKline, Collegeville, PA (J.J.B.). 35From Fundação de Medicina Tropical Dr Heitor Vieira Dourado, Manaus (M.V.G.L., F.V., W.M.M., M.A.M.B., M.R.F.C.), Fundação Oswaldo Cruz, Manguinhos, Rio de Janeiro (M.V.G.L.), and Centro de Pesquisa em Medicina Tropical Rondônia, Porto Velho (D.B.P., M.S.T.) - all in Brazil; Universidad Peruana Cayetano Heredia, Lima, Peru (A.L.-C., R.C., M.C.); Mahidol University (S.K.) and the Armed Forces Research Institute of Medical Sciences (C.L., D.L.S., N.B.), Bangkok, Thailand; the University of Gondar, Gondar (R.M., E.D., S.G., K.M.W.), and Jimma University, Jimma (D.Y., A.A., A.Z., C.A.) - both in Ethiopia; Research Institute for Tropical Medicine, Manila (F.E.J.E.), and Rio Tuba Nickel Foundation Hospital, Palawan (R.Z.M.) - both in the Philippines; Medical University of Vienna, Vienna (H.N.); Swiss Tropical and Public Health Institute and University of Basel, Basel (F.B., H.-P.B.), and Medicines for Malaria Venture, Geneva (S.D.) - both in Switzerland; Oxford University, Oxford (B.A.), and GlaxoSmithKline, Stockley Park West (J.-P.K., L.M.K., V.M.R., S.W.J., E.H., K.M., D.D.C., K.F., C.O.U., J.A.G., G.C.K.W.K.) - both in the United Kingdom; and GlaxoSmithKline, Collegeville, PA (J.J.B.). 36From Fundação de Medicina Tropical Dr Heitor Vieira Dourado, Manaus (M.V.G.L., F.V., W.M.M., M.A.M.B., M.R.F.C.), Fundação Oswaldo Cruz, Manguinhos, Rio de Janeiro (M.V.G.L.), and Centro de Pesquisa em Medicina Tropical Rondônia, Porto Velho (D.B.P., M.S.T.) - all in Brazil; Universidad Peruana Cayetano Heredia, Lima, Peru (A.L.-C., R.C., M.C.); Mahidol University (S.K.) and the Armed Forces Research Institute of Medical Sciences (C.L., D.L.S., N.B.), Bangkok, Thailand; the University of Gondar, Gondar (R.M., E.D., S.G., K.M.W.), and Jimma University, Jimma (D.Y., A.A., A.Z., C.A.) - both in Ethiopia; Research Institute for Tropical Medicine, Manila (F.E.J.E.), and Rio Tuba Nickel Foundation Hospital, Palawan (R.Z.M.) - both in the Philippines; Medical University of Vienna, Vienna (H.N.); Swiss Tropical and Public Health Institute and University of Basel, Basel (F.B., H.-P.B.), and Medicines for Malaria Venture, Geneva (S.D.) - both in Switzerland; Oxford University, Oxford (B.A.), and GlaxoSmithKline, Stockley Park West (J.-P.K., L.M.K., V.M.R., S.W.J., E.H., K.M., D.D.C., K.F., C.O.U., J.A.G., G.C.K.W.K.) - both in the United Kingdom; and GlaxoSmithKline, Collegeville, PA (J.J.B.). 37From Fundação de Medicina Tropical Dr Heitor Vieira Dourado, Manaus (M.V.G.L., F.V., W.M.M., M.A.M.B., M.R.F.C.), Fundação Oswaldo Cruz, Manguinhos, Rio de Janeiro (M.V.G.L.), and Centro de Pesquisa em Medicina Tropical Rondônia, Porto Velho (D.B.P., M.S.T.) - all in Brazil; Universidad Peruana Cayetano Heredia, Lima, Peru (A.L.-C., R.C., M.C.); Mahidol University (S.K.) and the Armed Forces Research Institute of Medical Sciences (C.L., D.L.S., N.B.), Bangkok, Thailand; the University of Gondar, Gondar (R.M., E.D., S.G., K.M.W.), and Jimma University, Jimma (D.Y., A.A., A.Z., C.A.) - both in Ethiopia; Research Institute for Tropical Medicine, Manila (F.E.J.E.), and Rio Tuba Nickel Foundation Hospital, Palawan (R.Z.M.) - both in the Philippines; Medical University of Vienna, Vienna (H.N.); Swiss Tropical and Public Health Institute and University of Basel, Basel (F.B., H.-P.B.), and Medicines for Malaria Venture, Geneva (S.D.) - both in Switzerland; Oxford University, Oxford (B.A.), and GlaxoSmithKline, Stockley Park West (J.-P.K., L.M.K., V.M.R., S.W.J., E.H., K.M., D.D.C., K.F., C.O.U., J.A.G., G.C.K.W.K.) - both in the United Kingdom; and GlaxoSmithKline, Collegeville, PA (J.J.B.). 38From Fundação de Medicina Tropical Dr Heitor Vieira Dourado, Manaus (M.V.G.L., F.V., W.M.M., M.A.M.B., M.R.F.C.), Fundação Oswaldo Cruz, Manguinhos, Rio de Janeiro (M.V.G.L.), and Centro de Pesquisa em Medicina Tropical Rondônia, Porto Velho (D.B.P., M.S.T.) - all in Brazil; Universidad Peruana Cayetano Heredia, Lima, Peru (A.L.-C., R.C., M.C.); Mahidol University (S.K.) and the Armed Forces Research Institute of Medical Sciences (C.L., D.L.S., N.B.), Bangkok, Thailand; the University of Gondar, Gondar (R.M., E.D., S.G., K.M.W.), and Jimma University, Jimma (D.Y., A.A., A.Z., C.A.) - both in Ethiopia; Research Institute for Tropical Medicine, Manila (F.E.J.E.), and Rio Tuba Nickel Foundation Hospital, Palawan (R.Z.M.) - both in the Philippines; Medical University of Vienna, Vienna (H.N.); Swiss Tropical and Public Health Institute and University of Basel, Basel (F.B., H.-P.B.), and Medicines for Malaria Venture, Geneva (S.D.) - both in Switzerland; Oxford University, Oxford (B.A.), and GlaxoSmithKline, Stockley Park West (J.-P.K., L.M.K., V.M.R., S.W.J., E.H., K.M., D.D.C., K.F., C.O.U., J.A.G., G.C.K.W.K.) - both in the United Kingdom; and GlaxoSmithKline, Collegeville, PA (J.J.B.). 39From Fundação de Medicina Tropical Dr Heitor Vieira Dourado, Manaus (M.V.G.L., F.V., W.M.M., M.A.M.B., M.R.F.C.), Fundação Oswaldo Cruz, Manguinhos, Rio de Janeiro (M.V.G.L.), and Centro de Pesquisa em Medicina Tropical Rondônia, Porto Velho (D.B.P., M.S.T.) - all in Brazil; Universidad Peruana Cayetano Heredia, Lima, Peru (A.L.-C., R.C., M.C.); Mahidol University (S.K.) and the Armed Forces Research Institute of Medical Sciences (C.L., D.L.S., N.B.), Bangkok, Thailand; the University of Gondar, Gondar (R.M., E.D., S.G., K.M.W.), and Jimma University, Jimma (D.Y., A.A., A.Z., C.A.) - both in Ethiopia; Research Institute for Tropical Medicine, Manila (F.E.J.E.), and Rio Tuba Nickel Foundation Hospital, Palawan (R.Z.M.) - both in the Philippines; Medical University of Vienna, Vienna (H.N.); Swiss Tropical and Public Health Institute and University of Basel, Basel (F.B., H.-P.B.), and Medicines for Malaria Venture, Geneva (S.D.) - both in Switzerland; Oxford University, Oxford (B.A.), and GlaxoSmithKline, Stockley Park West (J.-P.K., L.M.K., V.M.R., S.W.J., E.H., K.M., D.D.C., K.F., C.O.U., J.A.G., G.C.K.W.K.) - both in the United Kingdom; and GlaxoSmithKline, Collegeville, PA (J.J.B.). 40From Fundação de Medicina Tropical Dr Heitor Vieira Dourado, Manaus (M.V.G.L., F.V., W.M.M., M.A.M.B., M.R.F.C.), Fundação Oswaldo Cruz, Manguinhos, Rio de Janeiro (M.V.G.L.), and Centro de Pesquisa em Medicina Tropical Rondônia, Porto Velho (D.B.P., M.S.T.) - all in Brazil; Universidad Peruana Cayetano Heredia, Lima, Peru (A.L.-C., R.C., M.C.); Mahidol University (S.K.) and the Armed Forces Research Institute of Medical Sciences (C.L., D.L.S., N.B.), Bangkok, Thailand; the University of Gondar, Gondar (R.M., E.D., S.G., K.M.W.), and Jimma University, Jimma (D.Y., A.A., A.Z., C.A.) - both in Ethiopia; Research Institute for Tropical Medicine, Manila (F.E.J.E.), and Rio Tuba Nickel Foundation Hospital, Palawan (R.Z.M.) - both in the Philippines; Medical University of Vienna, Vienna (H.N.); Swiss Tropical and Public Health Institute and University of Basel, Basel (F.B., H.-P.B.), and Medicines for Malaria Venture, Geneva (S.D.) - both in Switzerland; Oxford University, Oxford (B.A.), and GlaxoSmithKline, Stockley Park West (J.-P.K., L.M.K., V.M.R., S.W.J., E.H., K.M., D.D.C., K.F., C.O.U., J.A.G., G.C.K.W.K.) - both in the United Kingdom; and GlaxoSmithKline, Collegeville, PA (J.J.B.). 41From Fundação de Medicina Tropical Dr Heitor Vieira Dourado, Manaus (M.V.G.L., F.V., W.M.M., M.A.M.B., M.R.F.C.), Fundação Oswaldo Cruz, Manguinhos, Rio de Janeiro (M.V.G.L.), and Centro de Pesquisa em Medicina Tropical Rondônia, Porto Velho (D.B.P., M.S.T.) - all in Brazil; Universidad Peruana Cayetano Heredia, Lima, Peru (A.L.-C., R.C., M.C.); Mahidol University (S.K.) and the Armed Forces Research Institute of Medical Sciences (C.L., D.L.S., N.B.), Bangkok, Thailand; the University of Gondar, Gondar (R.M., E.D., S.G., K.M.W.), and Jimma University, Jimma (D.Y., A.A., A.Z., C.A.) - both in Ethiopia; Research Institute for Tropical Medicine, Manila (F.E.J.E.), and Rio Tuba Nickel Foundation Hospital, Palawan (R.Z.M.) - both in the Philippines; Medical University of Vienna, Vienna (H.N.); Swiss Tropical and Public Health Institute and University of Basel, Basel (F.B., H.-P.B.), and Medicines for Malaria Venture, Geneva (S.D.) - both in Switzerland; Oxford University, Oxford (B.A.), and GlaxoSmithKline, Stockley Park West (J.-P.K., L.M.K., V.M.R., S.W.J., E.H., K.M., D.D.C., K.F., C.O.U., J.A.G., G.C.K.W.K.) - both in the United Kingdom; and GlaxoSmithKline, Collegeville, PA (J.J.B.). |
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Abstract BACKGROUND: Treatment of Plasmodium vivax malaria requires the clearing of asexual parasites, but relapse can be prevented only if dormant hypnozoites are cleared from the liver (a treatment termed "radical cure"). Tafenoquine is a single-dose 8-aminoquinoline that has recently been registered for the radical cure of P. vivax. METHODS: This multicenter, double-blind, double-dummy, parallel group, randomized, placebo-controlled trial was conducted in Ethiopia, Peru, Brazil, Cambodia, Thailand, and the Philippines. We enrolled 522 patients with microscopically confirmed P. vivax infection (>100 to <100,000 parasites per microliter) and normal glucose-6-phosphate dehydrogenase (G6PD) activity (with normal activity defined as ≥70% of the median value determined at each trial site among 36 healthy male volunteers who were otherwise not involved in the trial). All patients received a 3-day course of chloroquine (total dose of 1500 mg). In addition, patients were assigned to receive a single 300-mg dose of tafenoquine on day 1 or 2 (260 patients), placebo (133 patients), or a 15-mg dose of primaquine once daily for 14 days (129 patients). The primary outcome was the Kaplan-Meier estimated percentage of patients who were free from recurrence at 6 months, defined as P. vivax clearance without recurrent parasitemia. RESULTS: In the intention-to-treat population, the percentage of patients who were free from recurrence at 6 months was 62.4% in the tafenoquine group (95% confidence interval [CI], 54.9 to 69.0), 27.7% in the placebo group (95% CI, 19.6 to 36.6), and 69.6% in the primaquine group (95% CI, 60.2 to 77.1). The hazard ratio for the risk of recurrence was 0.30 (95% CI, 0.22 to 0.40) with tafenoquine as compared with placebo (P<0.001) and 0.26 (95% CI, 0.18 to 0.39) with primaquine as compared with placebo (P<0.001). Tafenoquine was associated with asymptomatic declines in hemoglobin levels, which resolved without intervention. CONCLUSIONS: Single-dose tafenoquine resulted in a significantly lower risk of P. vivax recurrence than placebo in patients with phenotypically normal G6PD activity. (Funded by GlaxoSmithKline and Medicines for Malaria Venture; DETECTIVE ClinicalTrials.gov number, NCT01376167 .). |
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Publikations ID: 30650322 Quelle: öffnen |
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