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Efficacy and safety of atovaquone/proguanil compared with mefloquine for treatment of acute Plasmodium falciparum malaria in Thailand.
Am J Trop Med Hyg. 1999 Apr; 60(4):526-32.AJ

Abstract

The increasing frequency of therapeutic failures in falciparum malaria underscores the need for novel, rapidly effective antimalarial drugs or drug combinations. Atovaquone and proguanil are blood schizonticides that demonstrate synergistic activity against multi-drug-resistant Plasmodium falciparum in vitro. In an open-label, randomized, controlled clinical trial conducted in Thailand, adult patients with acute P. falciparum malaria were randomly assigned to treatment with atovaquone and proguanil/hydrochloride (1,000 mg and 400 mg, respectively, administered orally at 24-hr intervals for three doses) or mefloquine (750 mg administered orally, followed 6 hr later by an additional 500-mg dose). 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 assessed by sequential clinical and laboratory assessments for 28 days. Atovaquone/proguanil was significantly more effective than mefloquine (cure rate 100% [79 of 79] vs. 86% [68 of 79]; P < 0.002). The atovaquone/proguanil and mefloquine treatments did not differ with respect to PCT (mean = 65 hr versus 74 hr) or FCT (mean = 59 hr versus 51 hr). Adverse events were generally typical of malaria symptoms and each occurred in < 10% of the patients in either group, with the exception of increased vomiting found in the atovaquone/proguanil group. Transient elevations of liver enzyme levels occurred more frequently in patients treated with atovaquone/proguanil than with mefloquine, but the differences were not significant and values returned to normal by day 28 in most patients. The combination of atovaquone and proguanil was well tolerated and more effective than mefloquine in the treatment of acute uncomplicated multidrug-resistant falciparum malaria in Thailand.

Authors+Show Affiliations

Hospital for Tropical Diseases, Mahidol University, Bangkok, Thailand.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Comparative Study
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10348224

Citation

Looareesuwan, S, et al. "Efficacy and Safety of Atovaquone/proguanil Compared With Mefloquine for Treatment of Acute Plasmodium Falciparum Malaria in Thailand." The American Journal of Tropical Medicine and Hygiene, vol. 60, no. 4, 1999, pp. 526-32.
Looareesuwan S, Wilairatana P, Chalermarut K, et al. Efficacy and safety of atovaquone/proguanil compared with mefloquine for treatment of acute Plasmodium falciparum malaria in Thailand. Am J Trop Med Hyg. 1999;60(4):526-32.
Looareesuwan, S., Wilairatana, P., Chalermarut, K., Rattanapong, Y., Canfield, C. J., & Hutchinson, D. B. (1999). Efficacy and safety of atovaquone/proguanil compared with mefloquine for treatment of acute Plasmodium falciparum malaria in Thailand. The American Journal of Tropical Medicine and Hygiene, 60(4), 526-32.
Looareesuwan S, et al. Efficacy and Safety of Atovaquone/proguanil Compared With Mefloquine for Treatment of Acute Plasmodium Falciparum Malaria in Thailand. Am J Trop Med Hyg. 1999;60(4):526-32. PubMed PMID: 10348224.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Efficacy and safety of atovaquone/proguanil compared with mefloquine for treatment of acute Plasmodium falciparum malaria in Thailand. AU - Looareesuwan,S, AU - Wilairatana,P, AU - Chalermarut,K, AU - Rattanapong,Y, AU - Canfield,C J, AU - Hutchinson,D B, PY - 1999/5/29/pubmed PY - 1999/5/29/medline PY - 1999/5/29/entrez SP - 526 EP - 32 JF - The American journal of tropical medicine and hygiene JO - Am J Trop Med Hyg VL - 60 IS - 4 N2 - The increasing frequency of therapeutic failures in falciparum malaria underscores the need for novel, rapidly effective antimalarial drugs or drug combinations. Atovaquone and proguanil are blood schizonticides that demonstrate synergistic activity against multi-drug-resistant Plasmodium falciparum in vitro. In an open-label, randomized, controlled clinical trial conducted in Thailand, adult patients with acute P. falciparum malaria were randomly assigned to treatment with atovaquone and proguanil/hydrochloride (1,000 mg and 400 mg, respectively, administered orally at 24-hr intervals for three doses) or mefloquine (750 mg administered orally, followed 6 hr later by an additional 500-mg dose). 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 assessed by sequential clinical and laboratory assessments for 28 days. Atovaquone/proguanil was significantly more effective than mefloquine (cure rate 100% [79 of 79] vs. 86% [68 of 79]; P < 0.002). The atovaquone/proguanil and mefloquine treatments did not differ with respect to PCT (mean = 65 hr versus 74 hr) or FCT (mean = 59 hr versus 51 hr). Adverse events were generally typical of malaria symptoms and each occurred in < 10% of the patients in either group, with the exception of increased vomiting found in the atovaquone/proguanil group. Transient elevations of liver enzyme levels occurred more frequently in patients treated with atovaquone/proguanil than with mefloquine, but the differences were not significant and values returned to normal by day 28 in most patients. The combination of atovaquone and proguanil was well tolerated and more effective than mefloquine in the treatment of acute uncomplicated multidrug-resistant falciparum malaria in Thailand. SN - 0002-9637 UR - https://www.unboundmedicine.com/medline/citation/10348224/Efficacy_and_safety_of_atovaquone/proguanil_compared_with_mefloquine_for_treatment_of_acute_Plasmodium_falciparum_malaria_in_Thailand_ L2 - https://ajtmh.org/doi/10.4269/ajtmh.1999.60.526 DB - PRIME DP - Unbound Medicine ER -