RSS Feeds
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
- 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.
Abstract
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.
- Copyright ©2004 by the American College of Physicians
