Abstract:
Artemether-Lumefantrine (A-L) remains the drug of choice for the treatment of
uncomplicated malaria in Ghana. However, the pharmaco-activity of A-L has not been assessed
on various Plasmodium falciparum Kelch 13 and Pfmdr1 genes. Therefore, this study sought to
determine the therapeutic efficacy of A-L on P. falciparum parasites isolated from Ghana.
Methods: The clinical study was done in Ga West Municipality, Ghana, where 78 uncomplicated
malaria patients were recruited with prior consent. The patients were treated orally
with A-L according to national treatment guidelines. Baseline parasitaemia was determined before
treatment and 8-hourly parasitaemia posttreatment were determined till initial clearance
of parasitaemia and at days 7, 14, 21, and 28. Kelch 13 and Pfmdr1 genes were genotyped by
sequencing using baseline samples. Parasite clearance characteristics were determined using
Parasite Clearance Estimator beta 0.9 application.
Results: Five Kelch 13 (F446I, S466N, R539I, A578S, and A676S) and three Pfmdr1 mutations (N86Y,
Y184F and D1246Y) were identified in 78 infected samples. About 8% of the samples contained
two Pfmdr1 double mutations (N86Y & D1246Y and Y184F & N86Y). Additionally, three samples
(3.8%) were found to contain both Kelch 13 mutations and Pfmdr1 wild type genes. In all patients,
parasitaemia persisted within the first 24 h of A-L therapy. However, at hour 40, only two patients
were parasitaemic while all patients were aparasitaemic at hour 48. The genotypic profiles of the
two persistent parasites at hour 40 were F446I and D1246Y, and R539I, Y184F, and N86Y. The
slope half-life of the former was 6.4 h while the latter was 6.9 h and their respective PCT99
were 47.9 h and 49.2 h as well as a clearance rate constants of 0.109 and 0.092 respectively.
Conclusion: This study reports the effectiveness of A-L on various P. falciparum mutant alleles.
However, continuous surveillance of Kelch 13 mutations and Pfmdr1 gene in Ghana and regular
assessment of the therapeutic efficacy of A-L and other artemisinin derivatives is recommended.
