학술논문
Increased sensitivity of malaria parasites to common antimalaria drugs after the introduction of artemether-lumefantrine: Implication of policy change and implementation of more effective drugs in fight against malaria.
Document Type
article
Author
Winnie Okore; Collins Ouma; Raphael O Okoth; Redemptah Yeda; Luicer O Ingasia; Edwin W Mwakio; Douglas O Ochora; Duncan M Wakoli; Joseph G Amwoma; Gladys C Chemwor; Jackline A Juma; Charles O Okudo; Agnes C Cheruiyot; Benjamin H Opot; Dennis Juma; Timothy E Egbo; Ben Andagalu; Amanda Roth; Edwin Kamau; Hoseah M Akala
Source
PLoS ONE, Vol 19, Iss 6, p e0298585 (2024)
Subject
Language
English
ISSN
1932-6203
Abstract
Single nucleotide polymorphisms (SNPs) in the Plasmodium falciparum multi-drug resistance protein 1 (Pfmrp1) gene have previously been reported to confer resistance to Artemisinin-based Combination Therapies (ACTs) in Southeast Asia. A total of 300 samples collected from six sites between 2008 and 2019 under an ongoing malaria drug sensitivity patterns in Kenya study were evaluated for the presence of SNPs at Pfmrp1 gene codons: H191Y, S437A, I876V, and F1390I using the Agena MassARRAY® platform. Each isolate was further tested against artemisinin (ART), lumefantrine (LU), amodiaquine (AQ), mefloquine (MQ), quinine (QN), and chloroquine (CQ) using malaria the SYBR Green I-based method to determine their in vitro drug sensitivity. Of the samples genotyped, polymorphism at Pfmrp1 codon I876V was the most frequent, with 59.3% (163/275) mutants, followed by F1390I, 7.2% (20/278), H191Y, 4.0% (6/151), and S437A, 3.3% (9/274). A significant decrease in median 50% inhibition concentrations (IC50s) and interquartile range (IQR) was noted; AQ from 2.996 ng/ml [IQR = 2.604-4.747, n = 51] in 2008 to 1.495 ng/ml [IQR = 0.7134-3.318, n = 40] (P