Efficacy of Artemether-Lumefantrine on various Plasmodium falciparum Kelch 13 and Pfmdr1 genes isolated in Ghana
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 therapeuti...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2020-11-01
|
| Series: | Parasite Epidemiology and Control |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405673120300593 |
| _version_ | 1818623397567922176 |
|---|---|
| author | Enoch Aninagyei Comfort Dede Tetteh Martin Oppong Alex Boye Desmond Omane Acheampong |
| author_facet | Enoch Aninagyei Comfort Dede Tetteh Martin Oppong Alex Boye Desmond Omane Acheampong |
| author_sort | Enoch Aninagyei |
| collection | DOAJ |
| description | 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 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. |
| first_indexed | 2024-12-16T18:40:25Z |
| format | Article |
| id | doaj.art-233ea70bfd21419fb3fa44154c27aa2a |
| institution | Directory Open Access Journal |
| issn | 2405-6731 |
| language | English |
| last_indexed | 2024-12-16T18:40:25Z |
| publishDate | 2020-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Parasite Epidemiology and Control |
| spelling | doaj.art-233ea70bfd21419fb3fa44154c27aa2a2022-12-21T22:21:03ZengElsevierParasite Epidemiology and Control2405-67312020-11-0111e00190Efficacy of Artemether-Lumefantrine on various Plasmodium falciparum Kelch 13 and Pfmdr1 genes isolated in GhanaEnoch Aninagyei0Comfort Dede Tetteh1Martin Oppong2Alex Boye3Desmond Omane Acheampong4University of Health and Allied Sciences, School of Basic and Biomedical Sciences, Department of Biomedical Sciences, PMB 31, Ho-Volta Region, Ghana; Corresponding authors.Ghana Health Service, Municipal Health Directorate, Ga West Municipal, Amasaman, GhanaGhana Health Service, Municipal Health Directorate, Ga West Municipal, Amasaman, GhanaUniversity of Cape Coast, School of Allied Health Sciences, Department of Medical Laboratory Science, Cape Coast, GhanaUniversity of Cape Coast, School of Allied Health Sciences, Department of Biomedical Sciences, Cape Coast, Ghana; Corresponding authors.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 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.http://www.sciencedirect.com/science/article/pii/S2405673120300593Artemether-LumefantrineParasite clearance characteristicsKelch 13 gene mutationsPfmdr1 genesGa West MunicipalGhana |
| spellingShingle | Enoch Aninagyei Comfort Dede Tetteh Martin Oppong Alex Boye Desmond Omane Acheampong Efficacy of Artemether-Lumefantrine on various Plasmodium falciparum Kelch 13 and Pfmdr1 genes isolated in Ghana Parasite Epidemiology and Control Artemether-Lumefantrine Parasite clearance characteristics Kelch 13 gene mutations Pfmdr1 genes Ga West Municipal Ghana |
| title | Efficacy of Artemether-Lumefantrine on various Plasmodium falciparum Kelch 13 and Pfmdr1 genes isolated in Ghana |
| title_full | Efficacy of Artemether-Lumefantrine on various Plasmodium falciparum Kelch 13 and Pfmdr1 genes isolated in Ghana |
| title_fullStr | Efficacy of Artemether-Lumefantrine on various Plasmodium falciparum Kelch 13 and Pfmdr1 genes isolated in Ghana |
| title_full_unstemmed | Efficacy of Artemether-Lumefantrine on various Plasmodium falciparum Kelch 13 and Pfmdr1 genes isolated in Ghana |
| title_short | Efficacy of Artemether-Lumefantrine on various Plasmodium falciparum Kelch 13 and Pfmdr1 genes isolated in Ghana |
| title_sort | efficacy of artemether lumefantrine on various plasmodium falciparum kelch 13 and pfmdr1 genes isolated in ghana |
| topic | Artemether-Lumefantrine Parasite clearance characteristics Kelch 13 gene mutations Pfmdr1 genes Ga West Municipal Ghana |
| url | http://www.sciencedirect.com/science/article/pii/S2405673120300593 |
| work_keys_str_mv | AT enochaninagyei efficacyofartemetherlumefantrineonvariousplasmodiumfalciparumkelch13andpfmdr1genesisolatedinghana AT comfortdedetetteh efficacyofartemetherlumefantrineonvariousplasmodiumfalciparumkelch13andpfmdr1genesisolatedinghana AT martinoppong efficacyofartemetherlumefantrineonvariousplasmodiumfalciparumkelch13andpfmdr1genesisolatedinghana AT alexboye efficacyofartemetherlumefantrineonvariousplasmodiumfalciparumkelch13andpfmdr1genesisolatedinghana AT desmondomaneacheampong efficacyofartemetherlumefantrineonvariousplasmodiumfalciparumkelch13andpfmdr1genesisolatedinghana |