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EFFICACY OF ATOVAQUONE-PROGUANIL FOR TREATMENT OF ACUTE MULTIDRUG-RESISTANT PLASMODIUM FALCIPARUM MALARIA IN THAILAND

SRIVICHA KRUDSOOD, SAMIR N. PATEL, NOPADDON TANGPUKDEE, WIPA THANACHARTWET, WATTANA LEOWATTANA, KARNCHANA PORNPININWORAKIJ, ANDREA K. BOGGILD, SORNCHAI LOOAREESUWAN, AND KEVIN C. KAIN^*

A combination of atovaquone-proguanil (Malarone^®; GlaxoSmithKline, Research Triangle Park, NC) was previously shown to be highly effective in the treatment of uncomplicated Plasmodium falciparum malaria. However, there are only limited recent efficacy data, particularly from regions of multidrug resistance. In this study, we examined the efficacy of atovaquone-proguanil for the treatment of uncomplicated P. falciparum malaria on the Thailand-Myanmar border. Patients were given directly observed atovaquone-proguanil (1,000 mg/400 mg) once a day for three days and followed-up for four weeks in a non-transmission area. Of 140 eligible patients enrolled in this open-label study, 97.8% (95% confidence interval = 95.4–100%) responded to therapy and remained clear of parasitemia at follow-up. Mean parasite clearance time was 41.9 hours and mean fever clearance time was 37.1 hours. On the basis of genotyping, three cases of treatment failure were identified (1 RIII and 2 RI). These data indicate that atovaquone-proguanil remains highly efficacious for the treatment of multidrug-resistant P. falciparum malaria in Thailand.

Received October 11, 2006. Accepted for publication January 1, 2007.

Financial support: This study was supported by a Canada Institutes of Health Research (CIHR) Team Grant in Malaria (Kevin C. Kain), operating grant MT-13721 (Kevin C. Kain), Genome Canada through the Ontario Genomics Institute (Kevin C. Kain), Physicians’ Services Incorporated (Kevin C. Kain), and CIHR Canada Research Chair (Kevin C. Kain).

Disclosure: The authors have no conflict of interest with respect to this study.

^* Address correspondence to Kevin C. Kain, Tropical Disease Unit, University Health Network–Toronto General Hospital, EN-13-214, 200 Elizabeth Street, Toronto, Ontario, Canada M5G 2C4. E-mail: kevin.kain{at}uhn.on.ca

These authors contributed equally to this report.

Authors’ addresses: Srivicha Krudsood, Nopaddon Tangpukdee, Wipa Thanachartwet, Wattana Leowattana, Karnchana Pornpininworakij, and Sornchai Looareesuwan, Hospital for Tropical Diseases, Mahidol University, Bangkok 10400, Thailand. Samir N. Patel, Andrea K. Boggild, and Kevin C. Kain, Tropical Disease Unit, University Health Network–Toronto General Hospital, EN-13-214, 200 Elizabeth Street, Toronto, Ontario, Canada M5G 2C4, Telephone: 416-340-3535, Fax: 416–595–5826, E-mail: kevin.kain{at}uhn.on.ca.