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Mefloquine Compared with Doxycycline for the Prophylaxis of Malaria in Indonesian Soldiers: A Randomized, Double-Blind, Placebo-Controlled Trial

Colin Ohrt, MD; Thomas L. Richie, MD, PhD; Hendra Widjaja, MD; G. Dennis Shanks, MD; Januar Fitriadi, MD; David J. Fryauff, ScD; Jurg Handschin, PhD; Douglas Tang, PhD; Bernardus Sandjaja, MD; Emiliana Tjitra, MD, MSc; Lukas Hadiarso, MD; George Watt, MD, DTM&H; and F. Stephen Wignall, MD
[+] Article, Author, and Disclosure Information

For author affiliations and current author addresses, see end of text. Disclaimer: The views expressed here are those of the authors and not necessarily those of the U.S. Army, the U.S. Navy, the U.S. Department of Defense, or the Indonesian Army. Acknowledgments: The authors thank many officials of the Indonesian Army, Provincial Health Service, Ministry of Health, for assistance; the staff of Pfizer Indonesia for providing the weekly blister packs of doxycyline; and the commanders and soldiers of battalions 143 and 731 for their support and cooperation. They also thank the field workers-Syaiful Umawan, Dewa Putu Budi Wilantara, Frans Subawa, Imanuddin, Jumiati, Khamdi, I. Nyoman Bonder, I. Gusti Nyoman Parwata, Ujang Jaenuddin, and Nursiin-who were key to the success of this study. Grant Support: In part by F. Hoffmann-La Roche, Basel, Switzerland; U.S. Army Medical Research and Material Command; and U.S. Naval Medical Research and Development Command. Doxycycline and doxycycline placebo were provided free of charge by Pfizer Indonesia; mefloquine hydrochloride was provided free of charge by F. Hoffmann-La Roche, Nutley, New Jersey; and mefloquine placebo was provided by F. Hoffmann-La Roche, Basel, Switzerland. Requests for Reprints: Colin Ohrt, MD, Department of Clinical Pharmacology, Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Washington, DC 20307-5100. Current Author Addresses: Dr. Ohrt: Department of Clinical Pharmacology, Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Washington, DC 20307-5100.

Copyright ©2004 by the American College of Physicians

Ann Intern Med. 1997;126(12):963-972. doi:10.7326/0003-4819-126-12-199706150-00006
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Background: Mefloquine and doxycycline are the two drugs recommended for prophylaxis of malaria for visitors to areas where Plasmodium falciparum is resistant to chloroquine.

Objective: To compare the efficacy and tolerability of mefloquine with those of doxycycline as prophylaxis for malaria.

Design: Randomized, double-blind, placebo-controlled field trial of chemoprophylaxis of malaria.

Setting: Northeastern Irian Jaya, Indonesia.

Participants: 204 Indonesian soldiers.

Intervention: After radical curative treatment, participants were randomly assigned to receive 100 mg of doxycycline per day and mefloquine placebo; 250 mg of mefloquine per week (preceded by a loading dose of 250 mg/d for 3 days) and doxycycline placebo; or placebos for both drugs. Prophylaxis lasted approximately 13 weeks.

Measurements: The primary end point for efficacy was the first occurrence of malaria, as documented by a positive malaria smear. Malaria smears were obtained weekly and when patients had symptoms suggesting malaria. Reported symptoms were recorded daily, and an exit study questionnaire was conducted.

Results: In the placebo group, 53 of 69 soldiers developed malaria (9.1 person-years), resulting in an attack rate of 5.8 cases per person-year (95% CI, 4.3 to 7.7 cases per person-year). Plasmodium falciparum accounted for 57% of cases, and P. vivax accounted for 43% of cases. No malaria occurred in the 68 soldiers (16.9 person-years) in the mefloquine group; thus, the protective efficacy of mefloquine was 100% (CI, 96% to 100%). In the doxycycline group, P. falciparum malaria occurred in 1 of 67 soldiers (16.0 person-years), yielding a protective efficacy of 99% (CI, 94% to 100%). Both drugs were very well tolerated.

Conclusions: Mefloquine and doxycycline were both highly efficacious and well tolerated as prophylaxis of malaria in Indonesian soldiers.


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Figure 1.
Kaplan-Meier plot (survival curve) of estimated cumulative probability of remaining free of malaria in 69 placebo recipients.Plasmodium falciparumP. vivax

Plots are for all cases of malaria (53 cases), cases of malaria caused by (30 cases), and cases of malaria caused by (23 cases). The species-specific curves consider the other species as censored (removed) at the time of occurrence of malaria. The mefloquine and doxycycline groups were excluded from this plot for clarity. Short vertical bars represent the four participants who dropped out of the study; numbers in parentheses are the numbers of participants at risk.

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