Efficacy and safety of atovaquone/proguanil as suppressive prophylaxis for Plasmodium falciparum malaria.
Currently recommended prophylactic regimens for Plasmodium falciparum malaria are associated with a high incidence of adverse events and/or suboptimal efficacy. In a double-blind, placebo-controlled, randomized clinical trial in western Kenya, adult volunteers received a treatment course of atovaquone/proguanil hydrochloride (250 mg/100 mg per tablet) to eliminate preexisting infection. Immediately thereafter, subjects were randomized to one of the three prophylactic regimens to receive one atovaquone/proguanil tablet daily (n = 68), two atovaquone/proguanil tablets daily (n = 65), or placebo (n = 65) for 10 weeks. The study endpoint for any subject was the development of parasitemia, evident on blood smear, during prophylaxis. Of the evaluable subjects, all in the low-dose (54 of 54) and high-dose (54 of 54) atovaquone/proguanil groups remained malaria-free during the 10-week prophylaxis period, in contrast to only 48% (26 of 54) in the placebo group (P < .001). Both atovaquone/proguanil prophylactic regimens were as well tolerated as placebo. Thus, atovaquone/proguanil appears to be highly efficacious and safe as prophylaxis for P. falciparum malaria.
U.S. Army Medical Research Unit, Nairobi, Kenya.
G D
GD
Shanks
D M
DM
Gordon
F W
FW
Klotz
G M
GM
Aleman
A J
AJ
Oloo
D
D
Sadie
T R
TR
Scott
D000293:Adolescent; D000328:Adult; D000368:Aged; D000962:Antimalarials / Q000009:adverse effects / Q000627:therapeutic use*; D053626:Atovaquone; D004311:Double-Blind Method; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D019353:Endemic Diseases; D005260:Female; D006801:Humans; D007630:Kenya / Q000453:epidemiology; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000453:epidemiology / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D009285:Naphthoquinones / Q000009:adverse effects / Q000627:therapeutic use*; D018512:Parasitemia / Q000517:prevention & control; D002727:Proguanil / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
D000962:Antimalarials; D009285:Naphthoquinones; D002727:Proguanil; D053626:Atovaquone