Phase IV Trial of Miltefosine in Adults and Children for Treatment of Visceral Leishmaniasis (Kala-Azar) in Bangladesh

Mahmudur Rahman Institute Of Epidemiology, Disease Control and Research, Dhaka, Bangladesh; Dhaka Medical College, Dhaka, Bangladesh; National Institute of Preventive and Social Medicine, Dhaka, Bangladesh; Rajshahi Medical College, Rajshahi, Bangladesh; Mymensingh Medical College, Mymensingh, Bangladesh; Directorate of Health Services, Dhaka, Bangladesh; World Health Organization Regional Office, Dhaka, Bangladesh; Department of Biological Anthropology, Cambridge University, Cambridge, United Kingdom; Fast-Track Drugs and Biologics LLC, North Bethesda, Potomac, Maryland; World Health Organization, Special Programme for Research and Training in Tropical Diseases, TDR-WHO, Geneva, Switzerland

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Be-Nazir Ahmed Institute Of Epidemiology, Disease Control and Research, Dhaka, Bangladesh; Dhaka Medical College, Dhaka, Bangladesh; National Institute of Preventive and Social Medicine, Dhaka, Bangladesh; Rajshahi Medical College, Rajshahi, Bangladesh; Mymensingh Medical College, Mymensingh, Bangladesh; Directorate of Health Services, Dhaka, Bangladesh; World Health Organization Regional Office, Dhaka, Bangladesh; Department of Biological Anthropology, Cambridge University, Cambridge, United Kingdom; Fast-Track Drugs and Biologics LLC, North Bethesda, Potomac, Maryland; World Health Organization, Special Programme for Research and Training in Tropical Diseases, TDR-WHO, Geneva, Switzerland

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M. Abul Faiz Institute Of Epidemiology, Disease Control and Research, Dhaka, Bangladesh; Dhaka Medical College, Dhaka, Bangladesh; National Institute of Preventive and Social Medicine, Dhaka, Bangladesh; Rajshahi Medical College, Rajshahi, Bangladesh; Mymensingh Medical College, Mymensingh, Bangladesh; Directorate of Health Services, Dhaka, Bangladesh; World Health Organization Regional Office, Dhaka, Bangladesh; Department of Biological Anthropology, Cambridge University, Cambridge, United Kingdom; Fast-Track Drugs and Biologics LLC, North Bethesda, Potomac, Maryland; World Health Organization, Special Programme for Research and Training in Tropical Diseases, TDR-WHO, Geneva, Switzerland

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M. Zafor Ullah Chowdhury Institute Of Epidemiology, Disease Control and Research, Dhaka, Bangladesh; Dhaka Medical College, Dhaka, Bangladesh; National Institute of Preventive and Social Medicine, Dhaka, Bangladesh; Rajshahi Medical College, Rajshahi, Bangladesh; Mymensingh Medical College, Mymensingh, Bangladesh; Directorate of Health Services, Dhaka, Bangladesh; World Health Organization Regional Office, Dhaka, Bangladesh; Department of Biological Anthropology, Cambridge University, Cambridge, United Kingdom; Fast-Track Drugs and Biologics LLC, North Bethesda, Potomac, Maryland; World Health Organization, Special Programme for Research and Training in Tropical Diseases, TDR-WHO, Geneva, Switzerland

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Quazi Tarikul Islam Institute Of Epidemiology, Disease Control and Research, Dhaka, Bangladesh; Dhaka Medical College, Dhaka, Bangladesh; National Institute of Preventive and Social Medicine, Dhaka, Bangladesh; Rajshahi Medical College, Rajshahi, Bangladesh; Mymensingh Medical College, Mymensingh, Bangladesh; Directorate of Health Services, Dhaka, Bangladesh; World Health Organization Regional Office, Dhaka, Bangladesh; Department of Biological Anthropology, Cambridge University, Cambridge, United Kingdom; Fast-Track Drugs and Biologics LLC, North Bethesda, Potomac, Maryland; World Health Organization, Special Programme for Research and Training in Tropical Diseases, TDR-WHO, Geneva, Switzerland

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Rahman Sayeedur Institute Of Epidemiology, Disease Control and Research, Dhaka, Bangladesh; Dhaka Medical College, Dhaka, Bangladesh; National Institute of Preventive and Social Medicine, Dhaka, Bangladesh; Rajshahi Medical College, Rajshahi, Bangladesh; Mymensingh Medical College, Mymensingh, Bangladesh; Directorate of Health Services, Dhaka, Bangladesh; World Health Organization Regional Office, Dhaka, Bangladesh; Department of Biological Anthropology, Cambridge University, Cambridge, United Kingdom; Fast-Track Drugs and Biologics LLC, North Bethesda, Potomac, Maryland; World Health Organization, Special Programme for Research and Training in Tropical Diseases, TDR-WHO, Geneva, Switzerland

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M. Ridwanur Rahman Institute Of Epidemiology, Disease Control and Research, Dhaka, Bangladesh; Dhaka Medical College, Dhaka, Bangladesh; National Institute of Preventive and Social Medicine, Dhaka, Bangladesh; Rajshahi Medical College, Rajshahi, Bangladesh; Mymensingh Medical College, Mymensingh, Bangladesh; Directorate of Health Services, Dhaka, Bangladesh; World Health Organization Regional Office, Dhaka, Bangladesh; Department of Biological Anthropology, Cambridge University, Cambridge, United Kingdom; Fast-Track Drugs and Biologics LLC, North Bethesda, Potomac, Maryland; World Health Organization, Special Programme for Research and Training in Tropical Diseases, TDR-WHO, Geneva, Switzerland

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Moazzem Hossain Institute Of Epidemiology, Disease Control and Research, Dhaka, Bangladesh; Dhaka Medical College, Dhaka, Bangladesh; National Institute of Preventive and Social Medicine, Dhaka, Bangladesh; Rajshahi Medical College, Rajshahi, Bangladesh; Mymensingh Medical College, Mymensingh, Bangladesh; Directorate of Health Services, Dhaka, Bangladesh; World Health Organization Regional Office, Dhaka, Bangladesh; Department of Biological Anthropology, Cambridge University, Cambridge, United Kingdom; Fast-Track Drugs and Biologics LLC, North Bethesda, Potomac, Maryland; World Health Organization, Special Programme for Research and Training in Tropical Diseases, TDR-WHO, Geneva, Switzerland

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Abdul Mannan Bangali Institute Of Epidemiology, Disease Control and Research, Dhaka, Bangladesh; Dhaka Medical College, Dhaka, Bangladesh; National Institute of Preventive and Social Medicine, Dhaka, Bangladesh; Rajshahi Medical College, Rajshahi, Bangladesh; Mymensingh Medical College, Mymensingh, Bangladesh; Directorate of Health Services, Dhaka, Bangladesh; World Health Organization Regional Office, Dhaka, Bangladesh; Department of Biological Anthropology, Cambridge University, Cambridge, United Kingdom; Fast-Track Drugs and Biologics LLC, North Bethesda, Potomac, Maryland; World Health Organization, Special Programme for Research and Training in Tropical Diseases, TDR-WHO, Geneva, Switzerland

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Ziauddin Ahmad Institute Of Epidemiology, Disease Control and Research, Dhaka, Bangladesh; Dhaka Medical College, Dhaka, Bangladesh; National Institute of Preventive and Social Medicine, Dhaka, Bangladesh; Rajshahi Medical College, Rajshahi, Bangladesh; Mymensingh Medical College, Mymensingh, Bangladesh; Directorate of Health Services, Dhaka, Bangladesh; World Health Organization Regional Office, Dhaka, Bangladesh; Department of Biological Anthropology, Cambridge University, Cambridge, United Kingdom; Fast-Track Drugs and Biologics LLC, North Bethesda, Potomac, Maryland; World Health Organization, Special Programme for Research and Training in Tropical Diseases, TDR-WHO, Geneva, Switzerland

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M. Nazrul Islam Institute Of Epidemiology, Disease Control and Research, Dhaka, Bangladesh; Dhaka Medical College, Dhaka, Bangladesh; National Institute of Preventive and Social Medicine, Dhaka, Bangladesh; Rajshahi Medical College, Rajshahi, Bangladesh; Mymensingh Medical College, Mymensingh, Bangladesh; Directorate of Health Services, Dhaka, Bangladesh; World Health Organization Regional Office, Dhaka, Bangladesh; Department of Biological Anthropology, Cambridge University, Cambridge, United Kingdom; Fast-Track Drugs and Biologics LLC, North Bethesda, Potomac, Maryland; World Health Organization, Special Programme for Research and Training in Tropical Diseases, TDR-WHO, Geneva, Switzerland

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C. G. Nicholas Mascie-Taylor Institute Of Epidemiology, Disease Control and Research, Dhaka, Bangladesh; Dhaka Medical College, Dhaka, Bangladesh; National Institute of Preventive and Social Medicine, Dhaka, Bangladesh; Rajshahi Medical College, Rajshahi, Bangladesh; Mymensingh Medical College, Mymensingh, Bangladesh; Directorate of Health Services, Dhaka, Bangladesh; World Health Organization Regional Office, Dhaka, Bangladesh; Department of Biological Anthropology, Cambridge University, Cambridge, United Kingdom; Fast-Track Drugs and Biologics LLC, North Bethesda, Potomac, Maryland; World Health Organization, Special Programme for Research and Training in Tropical Diseases, TDR-WHO, Geneva, Switzerland

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Jonathan Berman Institute Of Epidemiology, Disease Control and Research, Dhaka, Bangladesh; Dhaka Medical College, Dhaka, Bangladesh; National Institute of Preventive and Social Medicine, Dhaka, Bangladesh; Rajshahi Medical College, Rajshahi, Bangladesh; Mymensingh Medical College, Mymensingh, Bangladesh; Directorate of Health Services, Dhaka, Bangladesh; World Health Organization Regional Office, Dhaka, Bangladesh; Department of Biological Anthropology, Cambridge University, Cambridge, United Kingdom; Fast-Track Drugs and Biologics LLC, North Bethesda, Potomac, Maryland; World Health Organization, Special Programme for Research and Training in Tropical Diseases, TDR-WHO, Geneva, Switzerland

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Byron Arana Institute Of Epidemiology, Disease Control and Research, Dhaka, Bangladesh; Dhaka Medical College, Dhaka, Bangladesh; National Institute of Preventive and Social Medicine, Dhaka, Bangladesh; Rajshahi Medical College, Rajshahi, Bangladesh; Mymensingh Medical College, Mymensingh, Bangladesh; Directorate of Health Services, Dhaka, Bangladesh; World Health Organization Regional Office, Dhaka, Bangladesh; Department of Biological Anthropology, Cambridge University, Cambridge, United Kingdom; Fast-Track Drugs and Biologics LLC, North Bethesda, Potomac, Maryland; World Health Organization, Special Programme for Research and Training in Tropical Diseases, TDR-WHO, Geneva, Switzerland

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Miltefosine (target dose of 2.5 mg/kg/day for 28 days) is the recommended treatment for visceral leishmaniasis (kala-azar) in Bangladesh on the basis of data from India. We evaluated miltefosine in a phase IV trial of 977 patients in Bangladesh. At the six-month final follow up, 701 were cured. 24 showed initial treatment failure, and 95 showed treatment failure at 6 months, although 73 of the 95 showed treatment failure solely by the criterion of low hemoglobin values. One hundred twenty-one patients were not assessable. With the conservative assumption that all low hemoglobin values represented treatment failure, the final per protocol cure rate was 85%. Of 13 severe adverse events, 6 led to treatment discontinuation and 7 resulted in deaths, but only 1 death (associated with diarrhea) could be attributed to drug. Nearly all non-serious adverse events were gastrointestinal: vomiting in 25% of patients and diarrhea in 8% of patients. Oral miltefosine is an attractive alternative to intramuscular antimony and intravenous amphotericin B for treatment of kala-azar in Bangladesh.

Author Notes

*Address correspondence to Byron Arana, TDR/WHO, Geneva, Switzerland. E-mail: aranab@who.int

Financial support: The study was funded by the Special Program for Research and Training in Tropical Diseases (TDR-WHO), by a grant to Mahmudur Rahman.

Authors' addresses: Mahmudur Rahman and Be-Nazir Ahmed, Institute Of Epidemiology, Disease Control and Research, Dhaka, Bangladesh, E-mail: mrahman@citechco.net. M. Abul Faiz, Dhaka Medical College, Dhaka, Bangladesh. M. Zafor Ullah Chowdhury, National Institute of Preventive and Social Medicine, Dhaka, Bangladesh. Quazi Tarikul Islam, Rajshahi Medical College, Rajshahi, Bangladesh. Rahman Sayeedur, Mymensingh Medical College, Mymensingh, Bangladesh. M. Ridwanur Rahman and M. Nazrul Islam, Dhaka Medical College, Dhaka, Bangladesh. Moazzem Hossain, Directorate of Health Services, Dhaka, Bangladesh. Abdul Mannan Bangali and Ziauddin Ahmad, World Health Organization Regional Office, Dhaka, Bangladesh. C. G. Nicholas Mascie-Taylor, Department of Biological Anthropology, Cambridge University, Cambridge CB2 1QH, United Kingdom. Jonathan Berman, Fast-Track Drugs and Biologics LLC, North Bethesda, Potomac, MD, E-mail: jbe9320457@aol.com. Byron Arana, World Health Organization, Special Programme for Research and Training in Tropical Diseases, TDR-WHO, Geneva, Switzerland, E-mail: aranab@who.int.

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