Malaria control is hindered by the evolution and spread of resistance to antimalarials, necessitating multiple changes to drug policies over time. A comprehensive antimalarial drug resistance surveillance program is vital for detecting the potential emergence of resistance to antimalarials including current artemisinin-based combination therapies.An antimalarial drug resistance surveillance study involving 203 P. falciparum malaria-positive children was conducted in western Kenya between 2010 and 2013. Specimens from enrolled children were analyzed in vitro for sensitivity to chloroquine (CQ), amodiaquine (AQ), mefloquine (MQ), lumefantrine and artemisinin derivatives (artesunate and dihydroartemisinin), and for drug resistance allele polymorphisms in Pfcrt, Pfmdr-1 and the K13 propeller domain (K13).We observed a significant increase in the proportion of samples with the Pfcrt wild type (CVMNK) genotype, from 61.2% in 2010 to 93.0% in 2013 (p < 0.0001) and higher proportions of parasites with elevated sensitivity to CQ in vitro. The majority of isolates harbored the wild type N allele in Pfmdr-1 codon 86 (93.5 %), with only 7 (3.50%) samples with the mutant N86Y allele. Likewise, most isolates harbored the wild-type Pfmdr-1 D1246 allele (79.8%) with only 12 (6.38%) specimens with the mutant D1246Y allele and 26 (13.8%) with mixed alleles. All the samples had a single copy of the Pfmdr-1 gene (mean= 0.907+/-0.141). None of the sequenced parasites had mutations in the K13.Our results suggest that artemisinin is likely to remain highly efficacious and that CQ sensitivity appears to be on the rise in western Kenya.

The molecular basis of sulfadoxine-pyrimethamine (SP) resistance lies in a combination of single-nucleotide polymorphisms (SNPs) in two genes coding for Plasmodium falciparum dihydrofolate reductase (Pfdhfr) and P. falciparum dihydropteroate synthase (Pfdhps), targeted by pyrimethamine and sulfadoxine, respectively. The continued use of SP for intermittent preventive treatment in pregnant women in many African countries, despite SP's discontinuation as a first-line antimalarial treatment option, due to high levels of drug resistance, may further increase the prevalence of SP-resistant parasites and/or lead to selection of new mutations. An antimalarial drug resistance surveillance study was conducted in western Kenya between 2010 and 2013. A total of 203 clinical samples from children with uncomplicated malaria were genotyped for SNPs associated with SP resistance. The prevalence of the triple mutant Pfdhfr C50 I51R59N: 108I164 and the double mutant Pfdhps S436 G437E540: A581A613 genotypes was high. Two triple mutant Pfdhps genotypes were found: S436 G437E540G: 581A613 and H: 436 G437E540: A581A613, with the latter, thus far, uniquely found in western Kenya. The prevalence of the S436 G: 437 E: 540 G: 581A613 genotype was low. However, a steady increase in the triple Pfdhps H: 436 G: 437 E: 540A581A613 genotype was observed since its appearance in early 2000. These isolates shared substantial microsatellite haplotypes with the most common double mutant allele suggesting that this triple mutant allele may have evolved locally. Overall, these findings show that the triple H: 436 G437E540: A581A613 mutant may be increasing in this population and could compromise the efficacy of SP for IPTp if it increases the resistant threshold further.