RANDOMIZED, CONTROLLED, DOUBLE-BLIND TRIAL OF DAILY ORAL AZITHROMYCIN IN ADULTS FOR THE PROPHYLAXIS OF PLASMODIUM VIVAX MALARIA IN WESTERN THAILAND

D. GRAY HEPPNER JR. Department of Immunology and Medicine, United States Army Medical Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; Walter Reed Army Institute of Research, Silver Spring, Maryland; Kwai River Christian Hospital, Sangkhlaburi, Kanchanaburi Province, Thailand; Research Division, Thai Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; United States Army Medical Materiel Development Activity, Fort Detrick, Frederick, Maryland

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DOUGLAS S. WALSH Department of Immunology and Medicine, United States Army Medical Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; Walter Reed Army Institute of Research, Silver Spring, Maryland; Kwai River Christian Hospital, Sangkhlaburi, Kanchanaburi Province, Thailand; Research Division, Thai Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; United States Army Medical Materiel Development Activity, Fort Detrick, Frederick, Maryland

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NICHAPAT UTHAIMONGKOL Department of Immunology and Medicine, United States Army Medical Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; Walter Reed Army Institute of Research, Silver Spring, Maryland; Kwai River Christian Hospital, Sangkhlaburi, Kanchanaburi Province, Thailand; Research Division, Thai Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; United States Army Medical Materiel Development Activity, Fort Detrick, Frederick, Maryland

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DOUGLAS B. TANG Department of Immunology and Medicine, United States Army Medical Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; Walter Reed Army Institute of Research, Silver Spring, Maryland; Kwai River Christian Hospital, Sangkhlaburi, Kanchanaburi Province, Thailand; Research Division, Thai Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; United States Army Medical Materiel Development Activity, Fort Detrick, Frederick, Maryland

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SOMCHIT TULYAYON Department of Immunology and Medicine, United States Army Medical Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; Walter Reed Army Institute of Research, Silver Spring, Maryland; Kwai River Christian Hospital, Sangkhlaburi, Kanchanaburi Province, Thailand; Research Division, Thai Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; United States Army Medical Materiel Development Activity, Fort Detrick, Frederick, Maryland

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BARNYEN PERMPANICH Department of Immunology and Medicine, United States Army Medical Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; Walter Reed Army Institute of Research, Silver Spring, Maryland; Kwai River Christian Hospital, Sangkhlaburi, Kanchanaburi Province, Thailand; Research Division, Thai Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; United States Army Medical Materiel Development Activity, Fort Detrick, Frederick, Maryland

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THEERA WIMONWATTRAWATEE Department of Immunology and Medicine, United States Army Medical Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; Walter Reed Army Institute of Research, Silver Spring, Maryland; Kwai River Christian Hospital, Sangkhlaburi, Kanchanaburi Province, Thailand; Research Division, Thai Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; United States Army Medical Materiel Development Activity, Fort Detrick, Frederick, Maryland

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NIPHON CHUANAK Department of Immunology and Medicine, United States Army Medical Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; Walter Reed Army Institute of Research, Silver Spring, Maryland; Kwai River Christian Hospital, Sangkhlaburi, Kanchanaburi Province, Thailand; Research Division, Thai Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; United States Army Medical Materiel Development Activity, Fort Detrick, Frederick, Maryland

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ANINTITA LAOBOONCHAI Department of Immunology and Medicine, United States Army Medical Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; Walter Reed Army Institute of Research, Silver Spring, Maryland; Kwai River Christian Hospital, Sangkhlaburi, Kanchanaburi Province, Thailand; Research Division, Thai Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; United States Army Medical Materiel Development Activity, Fort Detrick, Frederick, Maryland

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PRASIT SOOKTO Department of Immunology and Medicine, United States Army Medical Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; Walter Reed Army Institute of Research, Silver Spring, Maryland; Kwai River Christian Hospital, Sangkhlaburi, Kanchanaburi Province, Thailand; Research Division, Thai Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; United States Army Medical Materiel Development Activity, Fort Detrick, Frederick, Maryland

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THOMAS G. BREWER Department of Immunology and Medicine, United States Army Medical Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; Walter Reed Army Institute of Research, Silver Spring, Maryland; Kwai River Christian Hospital, Sangkhlaburi, Kanchanaburi Province, Thailand; Research Division, Thai Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; United States Army Medical Materiel Development Activity, Fort Detrick, Frederick, Maryland

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PHILIP MCDANIEL Department of Immunology and Medicine, United States Army Medical Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; Walter Reed Army Institute of Research, Silver Spring, Maryland; Kwai River Christian Hospital, Sangkhlaburi, Kanchanaburi Province, Thailand; Research Division, Thai Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; United States Army Medical Materiel Development Activity, Fort Detrick, Frederick, Maryland

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CHIRAPA EAMSILA Department of Immunology and Medicine, United States Army Medical Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; Walter Reed Army Institute of Research, Silver Spring, Maryland; Kwai River Christian Hospital, Sangkhlaburi, Kanchanaburi Province, Thailand; Research Division, Thai Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; United States Army Medical Materiel Development Activity, Fort Detrick, Frederick, Maryland

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KOSOL YONGVANITCHIT Department of Immunology and Medicine, United States Army Medical Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; Walter Reed Army Institute of Research, Silver Spring, Maryland; Kwai River Christian Hospital, Sangkhlaburi, Kanchanaburi Province, Thailand; Research Division, Thai Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; United States Army Medical Materiel Development Activity, Fort Detrick, Frederick, Maryland

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KATHLEEN UHL Department of Immunology and Medicine, United States Army Medical Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; Walter Reed Army Institute of Research, Silver Spring, Maryland; Kwai River Christian Hospital, Sangkhlaburi, Kanchanaburi Province, Thailand; Research Division, Thai Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; United States Army Medical Materiel Development Activity, Fort Detrick, Frederick, Maryland

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DENNIS E. KYLE Department of Immunology and Medicine, United States Army Medical Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; Walter Reed Army Institute of Research, Silver Spring, Maryland; Kwai River Christian Hospital, Sangkhlaburi, Kanchanaburi Province, Thailand; Research Division, Thai Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; United States Army Medical Materiel Development Activity, Fort Detrick, Frederick, Maryland

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LISA W. KEEP Department of Immunology and Medicine, United States Army Medical Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; Walter Reed Army Institute of Research, Silver Spring, Maryland; Kwai River Christian Hospital, Sangkhlaburi, Kanchanaburi Province, Thailand; Research Division, Thai Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; United States Army Medical Materiel Development Activity, Fort Detrick, Frederick, Maryland

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ROBERT E. MILLER Department of Immunology and Medicine, United States Army Medical Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; Walter Reed Army Institute of Research, Silver Spring, Maryland; Kwai River Christian Hospital, Sangkhlaburi, Kanchanaburi Province, Thailand; Research Division, Thai Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; United States Army Medical Materiel Development Activity, Fort Detrick, Frederick, Maryland

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CHANSUDA WONGSRICHANALAI Department of Immunology and Medicine, United States Army Medical Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; Walter Reed Army Institute of Research, Silver Spring, Maryland; Kwai River Christian Hospital, Sangkhlaburi, Kanchanaburi Province, Thailand; Research Division, Thai Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; United States Army Medical Materiel Development Activity, Fort Detrick, Frederick, Maryland

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We assessed the prophylactic efficacy of azithromycin (250 mg/day) against malaria in 276 adults in western Thailand in a randomized, double-blind, placebo-controlled trial. After antimalarial suppressive treatment, volunteers were randomized in a 2:1 ratio to either the azithromycin or placebo, respectively. Study medication was given for an average of 74 days. The azithromycin group (n = 179) had five endpoint parasitemias (1 Plasmodium vivax and 4 P. falciparum), and the placebo group (n = 97) had 28 endpoint parasitemias (21 P. vivax, 5 P. falciparum, and 2 mixed infections). Adverse events and compliance and withdrawal rates were similar in both groups. The protective efficacy (PE) of azithromycin was 98% for P. vivax (95% confidence interval [CI] = 88–100%). There were too few cases to reliably estimate the efficacy of azithromycin for P. falciparum (PE =71%, 95% C =−14–94%). We conclude that daily azithromycin was safe, well-tolerated, and had a high efficacy for the prevention of P. vivax malaria.

Author Notes

Reprint requests: D. Gray Heppner Jr., Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910.
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