However, point mutations in each of the genes, pfdhfr and pfdhps, cause conformational changes in the enzyme structures and result in prevention of adequate drug binding and parasite resistance to SP. Pyrimethamine and sulphadoxine inhibit the dihydrofolate reductase (PfDHFR) and dihydropteroate synthase (PfDHPS) activities of the folate biosynthesis pathway in the parasite. Įfficiency of SP for falciparum malaria treatment could be predicted by analysis of Plasmodium falciparum target genes. Additionally, SP is provided for chemoprophylaxis. In spite of these reports, people in several endemic areas still commonly use SP when they are suffering from malaria because of its effectiveness, fewer side effects, low cost, and the single oral dose treatment.
and in vitro resistance was confirmed by using field isolates obtained from 11 malaria-endemic provinces, including East Kalimantan Province. In vitro and in vivo SP resistance were found in four provinces: Central Java, East Timor, South Sulawesi, and Papua in 1991 by Tjitra et al. High rates of chloroquine resistance in falciparum and vivax malaria have been reported in Indonesia and sulphadoxine-pyrimethamine (SP) resistance in falciparum malaria was discovered in several endemic areas from 1981 to 1995. One of the major problems in Indonesia is parasite resistance to anti-malarial drugs. Malaria is one of the important public health problem in Indonesia, causing annual parasitic incidence of 1.85% and malarial outbreaks in several endemic areas leading 11 deaths in 2009. 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. The parasites acquiring five mutations in pfdhfr/ pfdhps haplotypes and four mutations with additional I588F did not respond adequately to SP treatment.
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). Two novel mutations of pfdhps gene, K540T and I588F, were determined in ten and five isolates, respectively. 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. Occasionally, a thick smear blood film for microscopy observation and blood spot on a filter paper for pfdhfr and pfdhps genotype analysis were collected.
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. MethodsĪfter obtaining informed consent, 61 uncomplicated falciparum malaria patients were recruited in Banjar district, South Kalimantan Province, Indonesia, from October 2009 to August 2010. However, pfdhfr, pfdhps genotypes and the correlations to SP treatment outcome in Indonesia has not yet been well analysed. Mutations in pfdhfr and pfdhps genes have been shown to associate with sulphadoxine-pyrimethamine (SP) resistance of Plasmodium falciparum parasites.
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