Mefloquine compared with doxycycline for the prophylaxis of malaria in Indonesian soldiers. A randomized, double-blind, placebo-controlled trial.
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.


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


METHODS
Northeastern Irian Jaya, Indonesia.


METHODS
204 Indonesian soldiers.


METHODS
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.


METHODS
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.
Ohrt
C
C
Department of Clinical Pharmacology, Walter Reed Army Institute of Research, Washington, DC 20307-5100, USA.
Richie
T L
TL
Widjaja
H
H
Shanks
G D
GD
Fitriadi
J
J
Fryauff
D J
DJ
Handschin
J
J
Tang
D
D
Sandjaja
B
B
Tjitra
E
E
Hadiarso
L
L
Watt
G
G
Wignall
F S
FS
D000328:Adult; D000962:Antimalarials / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004318:Doxycycline / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004349:Drug Packaging; D005500:Follow-Up Studies; D006801:Humans; D007214:Indonesia; D008288:Malaria / Q000517:prevention & control*; D008297:Male; D015767:Mefloquine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D010349:Patient Compliance; D010919:Placebos
D000962:Antimalarials; D010919:Placebos; D004318:Doxycycline; D015767:Mefloquine