Background Emerging artemisinin resistance threatens the effort to eliminate malaria; artemisinin resistance investigation emphasizes parasites’ genetic modification as the leading cause of treatment failure. But CYP2B6*6 is vital in determining Artemisinin pharmacokinetics hence treatment outcome. Interindividual variability may mediate variable responses to artemisinin therapy among malaria patients.

Methods We recruited 100 symptomatic malaria patients aged five and above; who had P. falciparum infection and prescribed Artemether-Lumefantrine. We established their parasite load change during a 3-day treatment using the quantitative Polymerase Chain Reaction (qPCR) technique. We determined the prevalence of CYP2B6*6 Single Nucleotide Polymorphism among the patients and assessed the relationship with parasitological outcome.

Results 63% of patients had detectable parasites by qPCR, 54% had slow parasite load reduction, and 24% had parasite fold reduction of <100, while 5% of the individuals had > 10000 parasites/µL at day 3. Genotype frequency for CYP2B6*6 was 43% GG, 17%TT and 40% GT. Heterozygosity was associated with slow parasite clearance; P=0.02. The majority of the males were heterozygous.

Conclusion Most patients had delayed parasite reduction after Artemether-Lumefantrine therapy; this is more prevalent among CYP2B6*6 heterozygous individuals. Delayed parasite load reduction could be due to the slow activation of artemisinin to its active metabolite by CYP2B6*6 heterozygous patients. Such patients will have subtherapeutic levels of the active drug, unable to clear the parasite in the required treatment duration at the recommended dosage of artemisinin. The difference in treatment outcomes between different genotypes indicated that host genetic variability could determine treatment outcomes or confer selection pressure against artemisinin and the partner drug.

Funding: EDCTP2 under Pfkelch13 emergence (TMA2019CDF-2662) through MSc Scholarship.