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Efficacy of Artemether-Lumefantrine on various Plasmodium falciparum Kelch 13 and Pfmdr1 genes isolated in Ghana

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dc.contributor.author Aninagyei, Enoch
dc.contributor.author Tetteh, Comfort Dede
dc.contributor.author Oppong, Martin
dc.contributor.author Boye, Alex
dc.contributor.author Acheampong, Desmond Omane
dc.date.accessioned 2023-09-29T15:06:24Z
dc.date.available 2023-09-29T15:06:24Z
dc.date.issued 2020-10-23
dc.identifier.uri http://hdl.handle.net/123456789/8724
dc.description.abstract Introduction: 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 uncompli- cated malaria patients were recruited with prior consent. The patients were treated orally with A-L according to national treatment guidelines. Baseline parasitaemia was determined be- fore 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 en_US
dc.language.iso en en_US
dc.publisher University of Cape Coast en_US
dc.subject Artemether-Lumefantrine en_US
dc.subject Parasite clearance characteristics en_US
dc.subject Kelch 13 gene mutations en_US
dc.subject Pfmdr1 genes en_US
dc.subject Ga West Municipal en_US
dc.subject Ghana en_US
dc.title Efficacy of Artemether-Lumefantrine on various Plasmodium falciparum Kelch 13 and Pfmdr1 genes isolated in Ghana en_US
dc.type Article en_US


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