Polymorphism analysis of pfmdr1 gene in Plasmodium falciparum isolates 11\xa0years post-adoption of artemisinin-based combination therapy in Saudi Arabia

Hesham M Al-Mekhlafi,Aymen M Madkhali,Yee-Ling Lau,Khalid Y Ghailan,Talal H Alharazi,Abdullah A Mobarki,Hassan A Hamali,Ahmad Hassn Ghzwani,Zaki M Eisa,Wahib M Atroosh,Ahmed A Abdulhaq,Khalid Ammash Zain

doi:10.1038/s41598-021-04450-x

Abstract

A total of 227 Plasmodium falciparum isolates from Jazan region, southwestern Saudi Arabia were amplified for the P. falciparum multi-drug resistance 1 (pfmdr1) gene to detect point mutations 11 years after the introduction of artemisinin-based combination therapy (ACT) in Saudi Arabia. The pfmdr1 86Y mutation was found in 11.5% (26/227) of the isolates while the N86 wild allele was detected in 88.5%. Moreover, 184F point mutations dominated (86.3%) the instances of pfmdr1 polymorphism while no mutation was observed at codons 1034, 1042 and 1246. Three pfmdr1 haplotypes were identified, NFSND (74.9%), NYSND (13.7%) and YFSND (11.4%). Associations of the prevalence of 86Y mutation and YFSND haplotype with participants’ nationality, residency and parasitaemia level were found to be significant (P < 0.05). The findings revealed significant decline in the prevalence of the pfmdr1 86Y mutation in P. falciparum isolates from Jazan region over a decade after the implementation of ACT treatment. Moreover, the high prevalence of the NFSND haplotype might be indicative of the potential emergence of CQ-sensitive but artemether-lumefantrine-resistant P. falciparum strains since the adoption of ACT. Therefore, continuous monitoring of the molecular markers of antimalarial drug resistance in Jazan region is highly recommended.

Highlights

A total of 227 Plasmodium falciparum isolates from Jazan region, southwestern Saudi Arabia were amplified for the P. falciparum multi-drug resistance 1 gene to detect point mutations 11 years after the introduction of artemisinin-based combination therapy (ACT) in Saudi Arabia
The prevalence of the pfmdr1 86Y mutation found by the current study is far lower than that reported by the only two studies available from Saudi Arabia, which were conducted in Jazan region in 2010 and 2 01226,27
The current study demonstrated that three pfmdr[1] haplotypes are circulating in Jazan region, with the single-mutant NFSND (74.9%) dominant followed by the wild NYSND (13.7%), and the double-mutant YFSND (11.4%) haplotypes

Summary

Introduction

A total of 227 Plasmodium falciparum isolates from Jazan region, southwestern Saudi Arabia were amplified for the P. falciparum multi-drug resistance 1 (pfmdr1) gene to detect point mutations 11 years after the introduction of artemisinin-based combination therapy (ACT) in Saudi Arabia. The findings revealed significant decline in the prevalence of the pfmdr1 86Y mutation in P. falciparum isolates from Jazan region over a decade after the implementation of ACT treatment. Previous studies have concluded that, for these five SNPS, substitution of asparagine by tyrosine at codon 86 (N86Y), which is the most prevalent mutation in Asian and African parasites, enhances parasite resistance to CQ and AQ but at the same time increases susceptibility to a wide range of first-line antimalarial drugs including LMF, MFQ and dihydroartemisinin (DHA)[13,15]. Prevalence rates of up to 100% of the P. falciparum chloroquine resistance transporter (pfcrt) 76 T point mutation (the primary driver of CQ resistance) were r eported[25,26]

Objectives

Methods

Results

Discussion

Conclusion