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Abstract
Atovaquone and proguanil hydrochloride are blood schizonticides that demonstrate in
vitro synergy against drug-resistant strains of Plasmodium falciparum. When coadministered, they may therefore be effective for the treatment of malaria
in regions where there is known or suspected drug resistance. In an open-label, randomized,
parallelgroup, clinical trial conducted in Zambia, 163 patients (age range, 14 to
54 years) with acute P falciparum malaria were randomly assigned to receive treatment with atovaquone and proguanil
hydrochloride (1000 and 400 mg, respectively, administered orally at 24-hour intervals
for 3 doses; n = 82) or pyrimethamine/sulfadoxine (75/1500 mg administered orally
as a single dose; n = 81). Efficacy was assessed by cure rate (the percentage of patients
in whom parasitemia was eliminated and did not recur during 28 days of follow-up),
parasite clearance time (PCT), and fever clearance time (FCT). Safety was determined
by sequential clinical and laboratory assess ments over 28 days. Cure rates did not
differ significantly between patients treated with atovaquone and proguanil (100%)
and those treated with pyrimethamine/ sulfadoxine (98.8%). Patients in the atovaquone
and proguanil group had a significantly shorter FCT than patients in the pyrimethamine/sulfadoxine
group (mean, 30.4 vs 44.9 hours; P < 0.05) but a longer PCT (mean, 64.0 vs 51.4 hours; P < 0.05). Both treatments were well tolerated; adverse events and laboratory abnormalities
were typical of those normally observed in patients with malaria. In this study, the
combination of atovaquone and proguanil was equally effective and as well tolerated
as pyrimethamine/sulfadoxine for the treatment of acute, uncomplicated, drugresistant
falciparum malaria in Zambia.
Key words
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Article info
Publication history
Accepted:
March 2,
1999
Identification
Copyright
© 1999 Published by Elsevier Inc.
