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Background  Mutations in  pfdhfr  and  pfdhps  genes have been shown to associate with sulphadoxine-pyrimethamine (SP) resistance of  Plasmodium falciparum  parasites. However,  pfdhfr ,  pfdhps  genotypes and the correlations to SP treatment outcome in Indonesia has not yet been well analysed.    Methods  After obtaining informed consent, 61 uncomplicated falciparum malaria patients were recruited in Banjar district, South Kalimantan Province, Indonesia, from October 2009 to August 2010. They were treated by a single oral dose of SP and its effects on clinical and parasitological status were followed until day 28 after treatment. Occasionally, a thick smear blood film for microscopy observation and blood spot on a filter paper for  pfdhfr  and  pfdhps  genotype analysis were collected.    Results   Pfdhfr  and  pfdhps  genotypes from 24  P. falciparum -infected patients consisting of adequate clinical parasitological response (ACPR) (n = 6; 25.0%) and early treatment failure (ETF) (n = 10; 41.7%) or late parasitological failure (LPF) (n = 8; 33.3%) were obtained by sequencing. Two novel mutations of  pfdhps  gene, K540T and I588F, were determined in ten and five isolates, respectively. These mutations were present in the  pfdhfr / pfdhps  combined haplotypes of AN RN I/S GTG A (n = 6), AN RNL /S GTG A (n = 4), and AN RN I/S GE AA(588 F ) (n = 5), (mutation codons are bold typed); these haplotypes were mostly belonging to parasitological failure (ETF or LPF). The parasites acquiring five mutations in  pfdhfr / pfdhps  haplotypes and four mutations with additional I588F did not respond adequately to SP treatment.    Conclusion  Many of  Plasmodium falciparum  infected patients in Banjar district, South Kalimantan, Indonesia did not respond adequately to SP treatment and these low ineffectiveness of SP in this area was associated with two novel mutations of  pfdhps,  K540T and I588F.

malaria journal

Two novel mutations of pfdhps K540T and I588F, affecting sulphadoxine-pyrimethamine-resistant response in uncomplicated falciparum malaria at Banjar district, South Kalimantan Province, Indonesia