Evidence map›Paper›PMID 41420179›Full record

ArticleMalaria journal2025

Comparative molecular surveillance of polymorphisms in chloroquine resistance transporter, multidrug resistance 1, and Kelch 13 genes associated with antimalarial drug resistance in Plasmodium falciparum isolates from Western Kenya.

Josephat Bungei, Collins Ouma, Daibin Zhong, Job Oyweri, Ming-Chieh Lee, Guofa Zhou, Harrysone Atieli, John Githure, Chloe Wang, Guiyun Yan

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In one paragraph

Article in Malaria journal, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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1citing papers in PubMed
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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

10 authors.

Josephat BungeiDepartment of Biomedical Sciences and Technology, Maseno University, Kisumu, Kenya. josephatbungei@gmail.com.
Collins OumaDepartment of Biomedical Sciences and Technology, Maseno University, Kisumu, Kenya.
Daibin ZhongDepartment of Population Health and Disease Prevention, University of California, Irvine, CA, USA.
Job OyweriDepartment of Biomedical Sciences and Technology, Maseno University, Kisumu, Kenya.
Ming-Chieh LeeDepartment of Population Health and Disease Prevention, University of California, Irvine, CA, USA.
Guofa ZhouDepartment of Population Health and Disease Prevention, University of California, Irvine, CA, USA.
Harrysone AtieliInternational Centers of Excellence for Malaria Research, Tom Mboya University, Homa Bay, Kenya.
John GithureInternational Centers of Excellence for Malaria Research, Tom Mboya University, Homa Bay, Kenya.
Chloe WangDepartment of Population Health and Disease Prevention, University of California, Irvine, CA, USA.
Guiyun YanDepartment of Population Health and Disease Prevention, University of California, Irvine, CA, USA.

Funding

Vector Biology of Invasive Anopheles stephensi in Rural to Urban Landscapes in EthiopiaU19AI129326 · NIAID · UNIVERSITY OF CALIFORNIA-IRVINE · PI Delenasaw Yewhalaw · 2017 to 2026
$19.9M
Research Training in Mosquito Genomics and Bioinformat*D43TW001505 · FIC · UNIVERSITY OF CALIFORNIA-IRVINE · PI Guiyun Yan · 2000 to 2026
$6.0M
FIC NIH HHS D43 TW001505NIAID NIH HHS U19 AI129326NIH HHS U19AI129326 and D43TW001505
6 · The paper itself

Abstract

backgroundMalaria treatment interventions play a central role in the prevention and control of Plasmodium falciparum infections worldwide. However, the emergence and spread of resistant P. falciparum parasites pose a serious public health challenge, as they reduce the effectiveness of antimalarial drugs and contribute to an increased global malaria burden. This study conducted a comparative molecular surveillance of antimalarial drug resistance in P. falciparum isolates from the Lake endemic and highland epidemic-prone regions of western Kenya.

methodsA cross-sectional study design was employed to screen patients presenting with malaria-associated symptoms among residents of the lake-endemic region of Nyando sub-County in Kisumu County and the highland epidemic-prone region of Marani sub-County in Kisii County. Single-nucleotide polymorphisms (SNPs) were genotyped in the chloroquine resistance transporter (Pfcrt), multidrug resistance 1 (Pfmdr1), and Kelch 13 (Pfk13) genes to identify validated molecular markers associated with resistance to chloroquine, artemisinin derivatives, and artemisinin partner drugs. A comparative analysis was conducted to assess mutation frequencies, genetic diversity, and selection pressure on molecular markers associated with antimalarial drug resistance between the Lake-endemic region and the highland epidemic-prone region.

resultsGenotyping of molecular markers detected M74I, N75E, and K76T mutations each at a frequency of 5.4% in Pfcrt, N146I (0.9%), Y184F (48.2%), and D1246Y (3.6%) in Pfmdr1, and S522C (0.9%), R561H (0.9%), and A675V (12.8%) in Pfk13. Comparative analysis revealed a significant prevalence of the Pfcrt M74I, N75E, and K76T alleles (11.5%) and the Pfk13 A675V allele (27.5%) in the Kisii region (p < 0.05). Pfcrt CVIET (5.4%), Pfmdr1 NFD (46.7%), and Pfk13 SRV (12.8%) were the dominant haplotypes. Additionally, a novel Pfmdr1 N146I mutation and rare Pfk13 S522C and R561H mutations were detected in the Kisumu region. Although the Kisii region presented greater genetic diversity of Pfk13, neutrality statistics, Tajima's D (-1.8474, p < 0.05), Fu's Fs (-3.835), and Fu and Li's F (-3.5041, p < 0.02), suggest significant population expansion in the Kisumu region, potentially driven by the emergence of the rare S522C and R561H alleles.

conclusionOur findings reveal the persistence of the Pfcrt CVIET haplotype and elevated Pfk13 A675V mutation in Kisii, with a moderate prevalence of Pfmdr1 Y184F mutation in both regions. Crucially, we detected emerging novel Pfmdr1 N146I and rare Pfk13 S522C and R561H mutations in Kisumu. Given that artemether-lumefantrine is Kenya's first-line treatment, continuous molecular surveillance is essential to elucidate the selection pressures driving the spread of resistant P. falciparum in western Kenya.

Indexed as

AntimalarialsATP-Binding Cassette, Sub-Family C ProteinsDrug ResistanceMembrane Transport ProteinsPlasmodium falciparumPolymorphism, Single NucleotideProtozoan ProteinsAdolescentAdultChildChild, PreschoolChloroquineCross-Sectional StudiesFemaleHumansKenyaAntimalarialsATP-Binding Cassette, Sub-Family C ProteinsChloroquineMdr1 protein, Plasmodium falciparumMembrane Transport ProteinsPfCRT protein, Plasmodium falciparumProtozoan ProteinsDrug resistanceGenotypesHaplotypesPfcrtPfk13Pfmdr1Plasmodium falciparumSelection pressure

Identifiers

PMID41420179
PMCPMC12751502

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