Presence of P lasmodium falciparum strains with artemisinin-resistant K13 mutation C469Y in Busia County, Western Kenya

Abstract Malaria remains a key health and economic problem, particularly in sub-Saharan Africa. The emergence of artemisinin drug resistance (ART-R) parasite strains poses a serious threat to the control and elimination of this scourge. This is because artemisinin-based combination therapies (ACTs)...

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Main Authors: Mark Makau, Bernard N. Kanoi, Calvin Mgawe, Michael Maina, Mimie Bitshi, Edwin K. Too, Taeko K. Naruse, Hussein M. Abkallo, Harrison Waweru, Ferdinand Adung’o, Osamu Kaneko, Jesse Gitaka
Format: Article
Language:English
Published: BMC 2024-10-01
Series:Tropical Medicine and Health
Online Access:https://doi.org/10.1186/s41182-024-00640-1
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author Mark Makau
Bernard N. Kanoi
Calvin Mgawe
Michael Maina
Mimie Bitshi
Edwin K. Too
Taeko K. Naruse
Hussein M. Abkallo
Harrison Waweru
Ferdinand Adung’o
Osamu Kaneko
Jesse Gitaka
author_facet Mark Makau
Bernard N. Kanoi
Calvin Mgawe
Michael Maina
Mimie Bitshi
Edwin K. Too
Taeko K. Naruse
Hussein M. Abkallo
Harrison Waweru
Ferdinand Adung’o
Osamu Kaneko
Jesse Gitaka
author_sort Mark Makau
collection DOAJ
description Abstract Malaria remains a key health and economic problem, particularly in sub-Saharan Africa. The emergence of artemisinin drug resistance (ART-R) parasite strains poses a serious threat to the control and elimination of this scourge. This is because artemisinin-based combination therapies (ACTs) remain the first-line treatment in the majority of malaria-endemic regions in Sub-Saharan Africa. Certain single-nucleotide polymorphisms in the propeller domains of Plasmodium falciparum Kelch 13 protein (K13) have been associated with delayed parasite clearance in vivo and in vitro. These mutations serve as vital molecular markers for tracking the emergence and dispersion of resistance. Recently, there have been increasing reports of the emergence and spread of P. falciparum ART-R parasites in the Eastern Africa region. This necessitates continued surveillance to best inform mitigation efforts. This study investigated the presence of all reported mutations of K13 propeller domains in the parasite population in Busia County, Kenya, a known malaria-endemic region. Two hundred twenty-six participants with microscopically confirmed uncomplicated malaria were recruited for this study. They were treated with artemether–lumefantrine under observation for the first dose, and microscopic examination was repeated 1 day later after ensuring the participants had taken the second and third doses. P. falciparum DNA from all samples underwent targeted amplification of the K13 gene using a semi-nested PCR approach, followed by Sanger sequencing. The recently validated ART-R K13 mutation C469Y was identified in three samples. These three samples were among 63 samples with a low reduction in parasitemia on day 1, suggesting day 1 parasitemia reduction rate is a useful parameter to enrich the ART-R parasites for further analysis. Our findings highlight the need for continuous surveillance of ART-R in western Kenya and the region to determine the spread of ART-R and inform containment.
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spelling doaj-art-60e9f5ea585b49fca76c334fb91eebb22025-08-20T01:50:39ZengBMCTropical Medicine and Health1349-41472024-10-015211810.1186/s41182-024-00640-1Presence of P lasmodium falciparum strains with artemisinin-resistant K13 mutation C469Y in Busia County, Western KenyaMark Makau0Bernard N. Kanoi1Calvin Mgawe2Michael Maina3Mimie Bitshi4Edwin K. Too5Taeko K. Naruse6Hussein M. Abkallo7Harrison Waweru8Ferdinand Adung’o9Osamu Kaneko10Jesse Gitaka11Centre for Malaria Elimination, Institute of Tropical Medicine, Mount Kenya UniversityCentre for Malaria Elimination, Institute of Tropical Medicine, Mount Kenya UniversityCentre for Malaria Elimination, Institute of Tropical Medicine, Mount Kenya UniversityCentre for Malaria Elimination, Institute of Tropical Medicine, Mount Kenya UniversityDepartment of Protozoology, Institute of Tropical Medicine (NEKKEN), Nagasaki UniversityDepartment of Protozoology, Institute of Tropical Medicine (NEKKEN), Nagasaki UniversityDepartment of Protozoology, Institute of Tropical Medicine (NEKKEN), Nagasaki UniversityAnimal and Human Health Program, International Livestock Research Institute (ILRI)Centre for Malaria Elimination, Institute of Tropical Medicine, Mount Kenya UniversityCentre for Infectious and Parasitic Diseases Control Research, Kenya Medical Research InstituteDepartment of Protozoology, Institute of Tropical Medicine (NEKKEN), Nagasaki UniversityCentre for Malaria Elimination, Institute of Tropical Medicine, Mount Kenya UniversityAbstract Malaria remains a key health and economic problem, particularly in sub-Saharan Africa. The emergence of artemisinin drug resistance (ART-R) parasite strains poses a serious threat to the control and elimination of this scourge. This is because artemisinin-based combination therapies (ACTs) remain the first-line treatment in the majority of malaria-endemic regions in Sub-Saharan Africa. Certain single-nucleotide polymorphisms in the propeller domains of Plasmodium falciparum Kelch 13 protein (K13) have been associated with delayed parasite clearance in vivo and in vitro. These mutations serve as vital molecular markers for tracking the emergence and dispersion of resistance. Recently, there have been increasing reports of the emergence and spread of P. falciparum ART-R parasites in the Eastern Africa region. This necessitates continued surveillance to best inform mitigation efforts. This study investigated the presence of all reported mutations of K13 propeller domains in the parasite population in Busia County, Kenya, a known malaria-endemic region. Two hundred twenty-six participants with microscopically confirmed uncomplicated malaria were recruited for this study. They were treated with artemether–lumefantrine under observation for the first dose, and microscopic examination was repeated 1 day later after ensuring the participants had taken the second and third doses. P. falciparum DNA from all samples underwent targeted amplification of the K13 gene using a semi-nested PCR approach, followed by Sanger sequencing. The recently validated ART-R K13 mutation C469Y was identified in three samples. These three samples were among 63 samples with a low reduction in parasitemia on day 1, suggesting day 1 parasitemia reduction rate is a useful parameter to enrich the ART-R parasites for further analysis. Our findings highlight the need for continuous surveillance of ART-R in western Kenya and the region to determine the spread of ART-R and inform containment.https://doi.org/10.1186/s41182-024-00640-1
spellingShingle Mark Makau
Bernard N. Kanoi
Calvin Mgawe
Michael Maina
Mimie Bitshi
Edwin K. Too
Taeko K. Naruse
Hussein M. Abkallo
Harrison Waweru
Ferdinand Adung’o
Osamu Kaneko
Jesse Gitaka
Presence of P lasmodium falciparum strains with artemisinin-resistant K13 mutation C469Y in Busia County, Western Kenya
Tropical Medicine and Health
title Presence of P lasmodium falciparum strains with artemisinin-resistant K13 mutation C469Y in Busia County, Western Kenya
title_full Presence of P lasmodium falciparum strains with artemisinin-resistant K13 mutation C469Y in Busia County, Western Kenya
title_fullStr Presence of P lasmodium falciparum strains with artemisinin-resistant K13 mutation C469Y in Busia County, Western Kenya
title_full_unstemmed Presence of P lasmodium falciparum strains with artemisinin-resistant K13 mutation C469Y in Busia County, Western Kenya
title_short Presence of P lasmodium falciparum strains with artemisinin-resistant K13 mutation C469Y in Busia County, Western Kenya
title_sort presence of p lasmodium falciparum strains with artemisinin resistant k13 mutation c469y in busia county western kenya
url https://doi.org/10.1186/s41182-024-00640-1
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