Clinical efficacy of artemisinin-lumefantrine and status of antifolate drug resistance markers in western Kenya

Abstract

Background: The development of Plasmodium falciparum resistance to sulfadoxine-pyrimethamine (SP) necessitated its replacement with artemether-lumefantrine (AL) in Kenya. However, the delayed parasite clearance following treatment with artemisinin derivatives has now spread in the Greater Mekong Sub region and may emerge or spread to other malaria endemic regions. Since parasites resistance to drugs is correlated with specific gene mutations, molecular markers associated with antimalarial drugs offer a powerful tool to monitor the emergence and spread of resistance. In this study, we assessed the clinical efficacy of AL following its adoption and the current levels of antifolate drug resistant markers after its ban in Kenyan health facilities. Methods: We conducted a therapeutic efficacy study between May and November 2015 in Chulaimbo sub-County, Kisumu, Kenya. A total of 76 patients ≥6 and ≤60 months of age with confirmed Plasmodium falciparum mono-infection were enrolled, treated with AL and followed up for a period of 28 days. Study endpoints were adequate clinical and parasitological response (ACPR) on the 28 day and known SP molecular markers of resistance were also determined. Results: The study showed that 97% of the participants had cleared parasitemia within 48 hours with an adequate clinical and parasitological response (ACPR) of 100% clearance on day 3. On Pfdhfr/Pfdhps mutants, N51I was identified in the P. falciparum isolates with a prevalence of 94% while C59R and S108N had 92% each. The prevalence of mutation at Pfdhps codons A437G and K540E stood at 94% and 91% respectively. Conclusion: AL was found to be highly efficacious since no plasmodium falciparum parasites were observed after day 3 making it a drug of choice in Kenya. Evidence of quintuple mutations frequency is high in the study population threatening the future use of SP.