Antimalarial drug resistance is a substantial impediment to malaria control. The spread of resistance has been described using genetic markers which are important epidemiological tools. We carried out a temporal analysis of changes in allele frequencies of 12 drug resistance markers over two decades of changing antimalarial drug policy in Kenya. We did not detect any of the validated <i>kelch 13 (k13</i>) artemisinin resistance markers, nonetheless, a single <i>k13 allele</i>, K189T, was maintained at a stable high frequency (>10%) over time. There was a distinct shift from <i>chloroquine resistant transporter (crt</i>)-76, <i>multi-drug resistant gene 1</i> (<i>mdr1</i>)-86 and <i>mdr1</i>-1246 chloroquine (CQ) resistance alleles to a 99% prevalence of CQ sensitive alleles in the population, following the withdrawal of CQ from routine use. In contrast, the <i>dihydropteroate synthetase (dhps</i>) double mutant (437G and 540E) associated with sulfadoxine-pyrimethamine (SP) resistance was maintained at a high frequency (>75%), after a change from SP to artemisinin combination therapies (ACTs). The novel <i>cysteine desulfurase (nfs</i>) K65 allele, implicated in resistance to lumefantrine in a West African study, showed a gradual significant decline in allele frequency pre- and post-ACT introduction (from 38% to 20%), suggesting evidence of directional selection in Kenya, potentially not due to lumefantrine. The high frequency of CQ-sensitive parasites circulating in the population suggests that the re-introduction of CQ in combination therapy for the treatment of malaria can be considered in the future. However, the risk of a re-emergence of CQ resistant parasites circulating below detectable levels or being reintroduced from other regions remains.
Antimicrobial agents and chemotherapy
KEMRI-Wellcome Trust Research Programme, CGMRC, Kenya.