Status of Artemisinin Resistance-Conferring Plasmodium Falciparum Malaria Kelch-13 R561H Polymorphism in Mutasa District, Zimbabwe

Abstract

Malaria is a major public health problem, with 228 million cases and 405,000 deaths in 2018. Mutations in the PfKelch13 propeller domain constitute the molecular basis of artemisinin resistance. These mutations are suspected to reduce function of the drug target, PfKelch13, rendering the parasite resistant. The aim of the current study was to determine prevalence of artemisinin resistance-conferring P. falciparum Kelch 13 R561H mutant parasites and their relation to ACT treatment failure in Mutasa District from April 2021- June 2021. An unmatched case-control study was conducted in Mutasa District clinics (St Peters, Chinaka and Chisuko). Participants with a malaria RDT positive test result was enrolled after consenting. A Dried Blood spot sample was collected and transported to Africa University Laboratories for genotyping of the Kelch13 R561H mutations in P. falciparum parasites. ACT drugs were bought in Mutasa communities and Mozambique boader with Zimbabwe and were tested using the Guo et al. (2016) Dipstick test for detecting fake/ substandard ACT drugs. A total of 82 participants were enrolled with 32 cases and 50 controls. 87 DBS from the lab repository collected in 2003 when ACT were also genotyped. A Bivariate analysis of the risk factors for suspected malaria treatment failure was done. The risk factors analysed comprised ACT readily available(p=0.523), test for malaria before getting ACT(p=0.403), patient received health education regarding ACT adherence(p=0.536), Completed ACT course(p=0.411), community campaigns on ACT use(p=0.240), experienced side effects after taking ACT(p=0.418), received counselling on ACT use(p=0.614) and ever bought ACT from vendors(p=0.912). All these risk factors were not associated with suspected malaria treatment failure. Laboratory genotyping of the K13 R561H markers, 4.3% of the analysed samples were K13R561H mutant type parasites while 42.0% were K13R561H wild type. ACT drug quality test showed that 7.1% of the ACTs bought along the border were fake or false. The suspected malaria treatment failure was attributed to the presence of the K13R561H mutations. Fake/ falsified antimalarial ACT drugs were observed in Mutasa District. None of the suspected malaria treated failure risk factors were associated with malaria treatment failures in Mutasa District possibly due to small sample size achieved in current study. The newly lab developed assay K13R561H SNP assay can be used for monitoring ACT drug resistance and inform policy, subject to further field validations.