Abstract
BackgroundSulphadoxine-pyrimethamine (SP), an antifolate, was replaced by artemether-lumefantrine as the first-line malaria drug treatment in Kenya in 2004 due to the wide spread of resistance. However, SP still remains the recommended drug for intermittent preventive treatment in pregnant women and infants (IPTP/I) owing to its safety profile. This study assessed the prevalence of mutations in dihydrofolate reductase (Pfdhfr) and dihydropteroate synthase (Pfdhps) genes associated with SP resistance in samples collected in Kenya between 2008 and 2012.MethodsField isolates collected from Kisumu, Kisii, Kericho and Malindi district hospitals were assessed for genetic polymorphism at various loci within Pfdhfr and Pfdhps genes by sequencing.ResultsAmong the Pfdhfr mutations, codons N51I, C59R, S108N showed highest prevalence in all the field sites at 95.5%, 84.1% and 98.6% respectively. Pfdhfr S108N prevalence was highest in Kisii at 100%. A temporal trend analysis showed steady prevalence of mutations over time except for codon Pfdhps 581 which showed an increase in mixed genotypes. Triple Pfdhfr N51I/C59R/S108N and double Pfdhps A437G/ K540E had high prevalence rates of 86.6% and 87.9% respectively. The Pfdhfr/Pfdhps quintuple, N51I/C59R/S108N/A437G/K540E mutant which has been shown to be the most clinically relevant marker for SP resistance was observed in 75.7% of the samples.ConclusionSP resistance is still persistently high in western Kenya, which is likely due to fixation of key mutations in the Pfdhfr and Pfdhps genes as well as drug pressure from other antifolate drugs being used for the treatment of malaria and other infections. In addition, there is emergence and increasing prevalence of new mutations in Kenyan parasite population. Since SP is used for IPTP/I, molecular surveillance and in vitro susceptibility assays must be sustained to provide information on the emergence and spread of SP resistance.
Highlights
Sulphadoxine-pyrimethamine (SP), an antifolate, was replaced by artemether-lumefantrine as the first-line malaria drug treatment in Kenya in 2004 due to the wide spread of resistance
This study presents the prevalence and trend of mutations in prevalence of mutations in dihydrofolate reductase (Pfdhfr) and P. falciparum dihydropteroate synthase (Pfdhps) genes in sample isolates collected from 4 different sites in Kenya between 2008 and 2012
Prevalence of SNPs in Pfdhfr and Pfdhps genes A total of 869 archival field isolates collected from Kisumu District Hospital (KDH), Kisii District Hospital (KSI), Kericho District Hospital (KCH) and Malindi District Hospital (MDH) between 2008 and 2012 were included in the study of which 822 were successfully sequenced
Summary
Sulphadoxine-pyrimethamine (SP), an antifolate, was replaced by artemether-lumefantrine as the first-line malaria drug treatment in Kenya in 2004 due to the wide spread of resistance. Sulphadoxine-pyrimethamine (SP) has been widely used as first-line treatment for uncomplicated falciparum malaria in many parts of the world including sub-Saharan Africa. It is used alone or in combination with other anti-malarials which has been effective until recently because of high levels of resistance [1,2]. SP is still used as intermittent preventive treatment of malaria in pregnancy (IPTp) in sub-Saharan Africa [4] It was recently recommended for use as intermittent preventive treatment of malaria in infants (IPTi) by the World Health Organization (WHO) in areas with low SP resistance [5]. There has been continued increase in SP resistance albeit being replaced as the first-line treatment [6], which is a major public health concern especially in sub-Saharan Africa [7]
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