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 Plasmodium 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 P. falciparum crt (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 N86Y mutant allele (the mutant nucleotide is underlined). Likewise, most isolates harbored the wild-type Pfmdr-1 D1246 allele (79.8%), with only 12 (6.38%) specimens with the D1246Y mutant allele and 26 (13.8%) with mixed alleles. All the samples had a single copy of the Pfmdr-1 gene (mean of 0.907 ؎ 0.141 copies). None of the sequenced parasites had mutations in 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.A ntimalarial drug resistance has hampered progress in malaria control and has led to several changes in drug policies over time. To minimize the potential emergence of drug resistance, the World Health Organization (WHO) recommends the use of artemisinin-based combination therapy (ACT), which consists of an artemisinin derivative coformulated with another class of antimalarial (1). In Kenya, the use of chloroquine (CQ) as the first line of malaria treatment was discontinued in the late 1990s due to a high percentage of treatment failures. CQ was replaced by sulfadoxinepyrimethamine (SP) as the first line of treatment, with amodiaquine (AQ) as a second choice. However, the use of SP was shortlived, as the majority of circulating parasites rapidly developed resistance to SP (reviewed in reference 2). Therefore, in April 2004, the ACT artemether-lumefantrine (AL; Coartem) was recommended as the first-line therapy for the treatment of uncomplicated Plasmodium falciparum malaria in Kenya, although this was not fully implemented until late 2006, when the country was finally able to undertake delivery of large quantities of the drug. Thus, between 2004 and 2006, AQ was briefly used as the first-line treatment for malaria in Kenya. Dihydroartemisinin-piperaquine (DHAP) is the current second-line antimalarial drug treatment, while artesu...

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 the 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 I51R59N108: I164 genotype and the double-mutant Pfdhps S436 G437E540: A581A613 genotype was high. Two triple-mutant Pfdhps genotypes, S436 G437E540G581: A613 and H436G437E540: A581A613, were found, with the latter thus far being uniquely found in western Kenya. The prevalence of the S436 G437E540G581: A613 genotype was low. However, a steady increase in the prevalence of the Pfdhps triple-mutant H436G437E540: A581A613 genotype has been observed since its appearance in early 2000. Isolates with these genotypes 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 prevalence of the H436G437E540: A581A613 triple mutant may be increasing in this population and could compromise the efficacy of SP for intermittent preventive treatment in pregnant women if it increases the resistance threshold further.