In vitro atovaquone/proguanil susceptibility and characterization of the cytochrome b gene of Plasmodium falciparum from different endemic regions of Thailand

Eighty three P. falciparum isolates collected during 1998 to 2005 from four different multidrug resistance areas of Thailand were determined for the in vitro atovaquone/proguanil susceptibilities using radioisotopic assay. Mutations in the cytb gene were determined by PCR-RFLP and sequence analysis.The mean atovaquone and proguanil IC50 was 3.4 nM and 36.5 μM, respectively. All 83 Thai isolates were atovaquone sensitive. None of the 83 isolates contained the mutations at codon 268 of the cytb gene. DNA sequencing of the cytb gene of 20 parasite isolates showed no other mutations.In agreement with a recent efficacy study of atovaquone/proguanil, the present information indicates that atovaquone/proguanil can be one of the drugs of choice for the treatment and prophylaxis of multidrug-resistant falciparum malaria in Thailand.Multidrug-resistant falciparum malaria is a major health problem along Thai-Myanmar and Thai-Cambodia borders. WHO has recommended artemisinin-based combination therapy as the first-line treatment for uncomplicated falciparum malaria in these multidrug resistance areas. In Thailand, a combination of artesunate and mefloquine has been used for more than 10 years. Recently, reduced efficacy of this combination has been reported from Thai-Cambodia border [1]. Effective chemoprophylaxis for malaria in these multidrug resistance areas is also needed especially for non-immune travelers. Thus the alternative drugs or drug combinations should be considered. Malarone？ is a fixed-dose combination of atovaquone and proguanil. It is highly effective for the treatment and prophylaxis of multidrug-resistant falciparum malaria [2,3]. Atovaquone exerts its action via inhibiting plasmodial mitochondria electron transport at the level of the cytochrome bc1 complex and collapsing mitochondrial membrane potential [4,5]. In addition, it inhibits dihydroorotate dehydrogenase (DHOD) enzyme which catalyses the reaction from dihydroorotate to orotate [6]. Therefore, atova