Antifolate Resistance Mutation and Proguanil Susceptibility among Plasmodium Falciparum Isolates in Thai-Cambodia Border

Abstract

Malaria is still one of the major public health problems in Thailand. Malaria parasite, Plasmodium falciparum, has been found to resist to most available antimalarial drugs. Although the ACTs base combination is still effective against falciparum infection, few resistant cases were reported.  Malarone, a combination of atovaquone and proguanil, had been introduced for prophylaxis and treatment in Trat and Chanthaburi Provinces, 2009 – 2011, to prolong the life span of the ACTs base combination therapy. The purpose of this study is to assess the point mutation of in vitro susceptibility and dhfr gene against proguanil before and after the administration of Malarone. A total of 37 blood samples collected from patients attending malaria clinic at Trat and Chanthaburi Province during 1993 to 2011 were analysed. The results revealed four mutations at 51^N/I, 59^C/R, 108^S/NT and 164^I/L residues in the dhfr gene. All samples had at least three point mutations and moderately resistant against proguanil with MIC ranging from 10^-5- 5x10^-5 M. These mutations were also maintained in falciparum samples collected from the same areas prior to and during Malarone usage. The number and position of point mutations were correlated with proguanil susceptibility. Although the proguanil alone should not be recommended for falciparum malaria prophylaxis and treatment in this region, proguanil and atovaquone combination, with their synergistic effects, may effective against falciparum treatment.