The return of chloroquine-sensitive Plasmodium falciparum parasites in Jazan region, southwestern Saudi Arabia over a decade after the adoption of artemisinin-based combination therapy: analysis of genetic mutations in the pfcrt gene.

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

doi:10.1007/s00436-021-07323-4

Abstract

This study investigated the polymorphism in the P. falciparum chloroquine resistance transporter (pfcrt) gene 11years after chloroquine (CQ) cessation in Jazan region, southwestern Saudi Arabia. Two hundred and thirty-five P. falciparum isolates were amplified to detect mutations in the pfcrt gene. The pfcrt 76T molecular marker for CQ resistance was detected in 66.4% (156/235) of the isolates, while the K76 CQ-sensitive wild type was detected in 33.6%. The pfcrt 74I and pfcrt 75E point mutations were each found to be present in 56.2% of isolates, while only four isolates (1.7%) were found to carry the pfcrt 72S mutation. Moreover, four pfcrt haplotypes were identified as follows: the CVIET triple-allele (56.2%), SVMET double-allele (1.7%) and CVMNT single-allele (8.5%) mutant haplotypes and the CVMNK wild haplotype (33.6%). The analysis also revealed significant associations between the prevalence of mutant pfcrt alleles and haplotypes and the age group, governorate and nationality of the patients as well as the parasitaemia level (p < 0.05). The findings provide evidence of the potential re-emergence of CQ-susceptible P. falciparum strains in Jazan region over a decade after CQ discontinuation, with about one third of the isolates analysed carrying the pfcrt K76 CQ-sensitive wild allele and the CVMNK ancestral wild haplotype. Although the reintroduction of CQ cannot be recommended at present in Saudi Arabia, these findings support the rationale for a potential future role for CQ in malaria treatment. Therefore, continuous molecular and in vitro monitoring mutations of pfcrt polymorphism in Jazan region is highly recommended.

Highlights

Malaria, a mosquito-borne disease transmitted by the bite of the female Anopheles mosquito, is a leading cause of morbidity and mortality worldwide, especially in the tropics and subtropics
Given the ongoing challenges associated with the elimination of this serious disease, the current study investigated the frequency and distribution of pfcrt gene point mutations in P. falciparum isolates collected from Jazan region in southwestern Saudi Arabia, just over a decade after the cessation of CQ use and the adoption of ACT for the treatment of uncomplicated falciparum malaria
The current study provides important information on the status of CQ resistance in Jazan region, southwestern Saudi Arabia

Summary

Introduction

A mosquito-borne disease transmitted by the bite of the female Anopheles mosquito, is a leading cause of morbidity and mortality worldwide, especially in the tropics and subtropics. Antimalarial drug resistance has emerged as one of the most critical threats hampering the global efforts to control and eliminate malaria. In the late 1950s, CQ-resistant Plasmodium falciparum malaria emerged independently in Southeast Asia (Thai–Cambodian border) and in South America (Colombia) (Payne 1987). Resistant P. falciparum strains spread steadily across different countries throughout Southeast Asia and into India, as well as across South America in the 1960s and 1970s, and spread to Africa in the late 1970s with confirmed treatment failures reported in Kenya and Tanzania (Fogh et al 1979; Wellems and Plowe 2001). Despite the increasing spread of CQ resistance worldwide, CQ remained the first-line treatment for malaria until the 2000s

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