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Molecular epidemiology of drug-resistant malaria in western Kenya highlands

DOI: 10.1186/1471-2334-8-105

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Abstract:

Using parasites from highland and lowland areas of western Kenya, we examined key mutations associated with Plasmodium falciparum resistance to sulfadoxine – pyrimethamine and chloroquine, including dihydrofolate reductase (pfdhfr) and dihydropteroate synthetase (pfdhps), chloroquine resistance transporter gene (pfcrt), and multi-drug resistance gene 1 (pfmdr1).We found that >70% of samples harbored 76T pfcrt mutations and over 80% of samples harbored quintuple mutations (51I/59R/108N pfdhfr and 437G/540E pfdhps) in both highland and lowland samples. Further, we did not detect significant difference in the frequencies of these mutations between symptomatic and asymptomatic malaria volunteers, and between highland and lowland samples.These findings suggest that drug resistance of malaria parasites in the highlands could be contributed by the mutations and their high frequencies as found in the lowland. The results are discussed in terms of the role of drug resistance as a driving force for malaria outbreaks in the highlands.Malaria is a major public health problem in sub-Saharan Africa and Plasmodium falciparum infection is a leading cause of morbidity and mortality inflicting a huge economic burden in countries where the disease is endemic [1]. It is estimated that death toll of malaria exceeds one million people each year, and the victims are primarily children under the age of five [2]. Until the early 1980s, the African highlands (generally referred to areas of >1,500 m above sea level) were either free of malaria or had very low incidences of the disease; however, since the late 1980s a series of malaria epidemics has occurred [3-9]. Among the many factors that may contribute to the highland malaria epidemics, resistance of the parasites to multiple antimalarials has not been extensively investigated. Resistance to antimalarial drugs is one of the major obstacles for effective malaria control. The first case of chloroquine (CQ) resistance in Kenya was reported i

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