The genetic diversity and drug resistance of plasmodium falciparum population in Sai Yok District, Kanchanaburi

Abstract

The population structure of the causative agents of human malaria, Plasmodium sp., especially P. falciparum, depends on the local epidemiological and demographic situations. Examples include the incidence of malaria, the vector transmission intensity and migration of inhabitants. This study revealed changes in population structure of parasite in Kanchanaburi between 2004 and 2007 using 12 microsatellite loci. It was found that migrations of people between the Thai-Myanmar borders in the last two years had an effect on P. falciparum population dynamics in this area. Furthermore, the changes in population structure were also observed by using four microsatellite loci within and flanking the pfmdr1 gene previously proposed to be responsible for mefloquine resistance. The declining trend in the proportion of mefloquine resistance in this area since 2005 implies that the combining artesunate and mefloquine may help reduce mefloquine resistance in this area. It also implies that mefloquine-artesunate combination can continue to be the first-line drug regimen for uncomplicated malaria. The parasite structures in other six malaria endemic provinces of Thailand were analyzed. The analysis showed that P. falciparum shows a variation of genetically structured populations across local areas of Thailand. The analysis also showed that although Thailand is considered a low transmission area, a relatively high level of genetic diversity and the lack of linkage disequilibrium were found in five of the seven study areas. The two exceptions were Yala and Kanchanaburi. In Yala province, a clonal population structure was revealed, while some linkage disequilibrium and high genetic diversity was observed in Kanchanaburi. This finding could help in understanding the special dynamics of parasite populations in areas with different pattern of drug use. A comparison of the genetic structure of P. falciparum populations in Thailand with those in the French Guyana, Congo and Cameroon revealed a significant genetic differentiation between them, except the two African countries, whilst the genetic variability of P. falciparum amongst countries showed overlapping distributions. No obvious relationship was found between the pfmdr1 gene sequence, the microsatellite genotype and mefloquine response level of sampling parasite from Kanchanaburi populations collected at different time periods. The result suggested that this set of microsatellite loci was not informative enough to distinguish individual parasite possessed different response to mefloquine.