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

Abstract

This study investigated the polymorphism in the P. falciparum chloroquine resistance transporter (pfcrt) gene 11 years after chloroquine (CQ) cessation in Jazan region, southwestern Saudi Arabia. Two hundred and thirty-ve P. falciparum isolates were ampli ed 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 identi ed: the CVIET triple-allele (56.2%), SVMET doubleallele (1.7%), and CVMNT single-allele (8.5%) mutant haplotypes, and the CVMNK wild haplotype (33.6%). The analysis also revealed signi cant 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 ndings 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 ndings 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.

Molecular surveillance of anti-malarial drug resistance genes in Plasmodium falciparum isolates in Odisha, India

“…In contrast, a high prevalence of Pfcrt K76 T (67.5%) and Pfmdr 1 N86 Y (80%) was observed in another study conducted before CQ withdrawal from the state during 2008–2010 [ 17 ]. The result obtained is similar to the observations made in Malawi, Tanzania, Mozambique, Northern Uganda, Saudi Arabia [ 23 – 27 ], but in contrast to southern Benin [ 28 ] and in other parts of India reported recently [ 29 – 32 ]. The present study, although limited to a small number of samples, indicates not only the presence of three types haplotypes (CVMNK: wild type, CV IET mutant type: believed to be of Southeast Asian origin, CVMN T mutant type: believed to be of African Origin) but also inform the high genetic diversity present in field isolates of P. falciparum for CQ drug-resistant genes in Odisha, India.…”

Molecular surveillance of antimalarial drug resistance genes in Plasmodium falciparum isolates in Odisha, India: A decade after CQ withdrawal

“…Interestingly high rates of wild alleles of Pfcrt (K76, 98%) and Pfmdr1 (N86 and Y184, 97%) observed in this study compared to our earlier study conducted before CQ withdrawal during 2008-2010 [15] provides evidence of the return of CQ-susceptible P. falciparum strains in Odisha. The results obtained is similar to the observations made in Malawi, Tanzania, Mozambique, Northern Uganda, Saudi Arabia [37,38,39,40,41] but in contrast to southern Benin [30]. Further DNA sequence polymorphism study that not only informs distribution of different haplotypes, but also the evolutionary potentiality of mutation in the drug-resistant genes that can directly translate to molecular epidemiology of human diseases like malaria.…”

The Effect of Artemisinin-Based Drugs vs Non-artemisinin-based Drugs on Gametophyte Carrying in the Body After the Treatment of Uncomplicated Falciparum Malaria: A Systematic Review and Meta-analysis

“…Also, a study found that the initial response of C-SP was significantly better than that of AL ( Mayxay et al, 2003 ). However, due to the emergence of recurrent resistance to Plasmodium falciparum, some areas had to stop using chloroquine and sulfadiazine as antimalarial drugs ( Mekonnen et al, 2014 ; Madkhali et al, 2021 ).…”