Importance of kelch 13 C580Y mutation in the studies of artemisinin resistance in Plasmodium falciparum in Greater Mekong Subregion

Zaw, Myo Thura; Wang, Qisheng; Emran, Nor Amalina

doi:10.1016/j.jmii.2019.07.006

“…In 2005, the WHO recommended using artemisinin-based combination therapies (ACT) as first- and second-line treatments for uncomplicated P. falciparum malaria 9 . Unfortunately, since then, studies have reported that delayed parasite clearance and ACT treatment failure due to artemisinin resistance is widespread in the Greater Mekong Subregion of Southeast Asia 10 , 11 .…”

Section: Introductionmentioning

confidence: 99%

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

Al-Mekhlafi

¹

,

Madkhali

²

,

Atroosh

³

et al. 2022

Sci Rep

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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.

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“…In 2005, the WHO recommended using artemisinin-based combination therapies (ACT) as rst-and second-line treatments for uncomplicated P. falciparum malaria 9 . Unfortunately, since then, studies have reported that delayed parasite clearance and ACT treatment failure due to artemisinin resistance is widespread in the Greater Mekong Subregion of Southeast Asia 10,11 .…”

Section: Introductionmentioning

confidence: 99%

Polymorphism Analysis of pfmdr1 Gene in Plasmodium falciparum Isolates 11 Years Post-adoption of Artemisinin-based Combination Therapy in Saudi Arabia

Al-Mekhlafi¹,

Madkhali²,

Atroosh³

et al. 2021

Preprint

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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.

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“…The objective of this study is to verify the possible utility of the KASP technique in the analysis of resistance to antimalarial drugs. To validate the method, three SNPs involved in most of the resistance of the most widespread treatments have been selected: i) SNP C580Y of the gene that codes for the Kelch13 protein (Gene PF3D7_1343700) that is present in 80% of cases of resistance to artemisinin treatments [12]; ii) SNP Y86N of the Pfmdr1 gene (gene PF3D7_0523000) that is involved in resistance to different drugs such as quinine, chloroquine, me oquine, halofantrine, amodiaquine and lumefantrine; the latter frequently used in combination with artemisinin, and where a natural selection of this SNP has been observed after treatment [13,14,15]; and iii) SNP M133I of the Pfcytb gene (gene MAL MYTH 3) that is related to resistance to atovaquone [16] and menoctone [17], being the most frequent mutation in in vitro tests.…”

Section: Introductionmentioning

confidence: 99%

KASP: a genotyping method to rapid identification of resistance in Plasmodium falciparum

Alvarez-Fernandez

¹

,

Bernal

²

,

Villajos

³

et al. 2020

Preprint

0

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Background The emergence and spread of antimalarial resistance continues to hinder malaria control. Plasmodium falciparum, the species that causes most human malaria cases and most deaths, has shown resistance to almost all known antimalarials. This antimalarial resistance arises from the development and subsequent expansion of Single Nucleotide Polymorfisms (SNPs) in specific parasite genes. A quick and cheap tool for the detection of drug resistance can be crucial and very useful for use in hospitals and in malaria control programs. It has been demonstrated in different contexts that genotyping by Kompetitive Allele Specific PCR (KASP), is a simple, fast and economical method that allows a high-precision biallelic characterization of SNPs, hence its possible utility in the study of resistance in P. falciparum. Methods Three SNPs involved in most cases of resistance to the most widespread antimalarial treatments have been analyzed by PCR plus sequencing and by KASP (C580Y of the Kelch13 gene, Y86N of the Pfmdr1 gene and M133I of the Pfcytb gene). A total of 113 P. falciparum positive samples and 24 negative samples, previously analyzed by PCR and sequencing, were selected for this assay. Likewise, the samples were genotyped for the MSP-1 and MSP-2 genes, and the Multiplicity of Infection (MOI) and parasitaemia were measured to observe their possible influence on the KASP method. Results The KASP results showed the same expected mutations and wild type genotypes as the reference method, with few exceptions that correlated with very low parasitaemia samples. In addition, two cases of heterozygotes that had not been detected by sequencing were found. No correlation was found between the MOI or parasitaemia and the KASP values of the sample. The reproducibility of the technique shows no oscillations between repetitions in any of the three SNPs analyzed. Conclusions The KASP assays developed in our study were efficient and versatile for the determination of the Plasmodium genotypes related to resistance. The method is simple, fast, reproducible with low cost in personnel, material and equipment and scalable, being able to core KASP arrays, including numerous SNPs, to complete the main pattern of mutations associated to P. falciparum resistance.

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Importance of kelch 13 C580Y mutation in the studies of artemisinin resistance in Plasmodium falciparum in Greater Mekong Subregion

Cited by 14 publications

References 22 publications

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

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

Polymorphism Analysis of pfmdr1 Gene in Plasmodium falciparum Isolates 11 Years Post-adoption of Artemisinin-based Combination Therapy in Saudi Arabia

KASP: a genotyping method to rapid identification of resistance in Plasmodium falciparum

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