Artemether-Lumefantrine Plasmodium Falciparum clearance and associated factors among uncomplicated Malaria patients in Adjumani District, Uganda

Abstract

The development of artemisinin resistance threatens the efforts to global malaria control. Artemisinin resistance has been reported in Northern Uganda and some African countries. Considering both host and parasite genetic factors to adequately understand and monitor the emerging threat and the spread of artemisinin resistance is vital. This longitudinal study recruited 100 symptomatic malaria patients aged five and above; who had P. falciparum infection and were prescribed artemether-lumefantrine. Microscopy and qPCR were used to determine day 0 and day 3 parasitemia. 80 Parasite DNA were sequenced for mutation in the K13-propeller gene using Sanger sequencing. The prevalence of human CYP2B6*6 allele was determined by Restricted Fragment Length Polymorphism using the patient's DNA (100). Sequence data was analysed by MEGA11 and processed in Excel and STATA15 with the rest, a Mann-Whitney U test was used to compare parasite clearance. 63% of patients had detectable parasites by qPCR and 24% by microscopy at day 3. Polymorphism in the P. falciparum K13-propeller gene was detected in 15 of the 80 samples sequenced. The K13 mutations found were C469Y (12.5%, 10/80), A675V (2.5%, 2/80), A569S (1.25%, 1/80), A578S (1.25%, 1/80), and F491S (1.25%, 1/80), C469Y demonstrated low parasite clearance (P=0.03). Genotype frequency for human CYP2B6*6 was 43% GG, 17% TT and 40% GT. GT patients showed reduced parasite clearance compared to GG and TT (P=0.02). Conclusion and Recommendation: There is an increase in the prevalence of Day 3 Plasmodium falciparum in AL-treated patients. Parasite K13 mutations, candidates of artemisinin resistance, were detected in parasites isolated from the patients. There is interindividual variability in the patient CYP2B6*6 gene. Parasite K13 mutation and patients' CYP2B6*6 variability affect parasite clearance. There is a need to re-evaluate the efficacy of artemisinin agents in malaria treatment in the country, considering both host and parasite factors, and alternative treatment approaches should be intensified.