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在加尔各答市实施基于青蒿素的联合疗法10年后,与抗疟药物耐药性相关的标记基因多态性的流行情况。

Prevalence of polymorphisms in marker genes associated with antimalarial drug resistance in following 10 years of artemisinin-based combination therapy implementation in urban Kolkata.

作者信息

Acharya Alisha, Naskar Arindam, Chaudhury Abhijit, Sardar Ashif Ali, Samanta Anwesha, Guha Subhasish Kamal, Maji Ardhendu Kumar, Bera Dilip Kumar, Saha Pabitra

机构信息

Department of Microbiology, Kolkata, West Bengal, India.

Department of Tropical Medicine, Kolkata, West Bengal, India.

出版信息

Trop Parasitol. 2024 Jan-Jun;14(1):23-29. doi: 10.4103/tp.tp_43_23. Epub 2024 Feb 15.

Abstract

CONTEXT

Resistance to antimalarial drugs is one of the major challenges for malaria elimination. In India, artemisinin combination therapy (artesunate-sulfadoxin pyrimethamine) was introduced in place of chloroquine (CQ) for the treatment of uncomplicated falciparum malaria in 2010. Periodical monitoring of polymorphisms in antimalarial drug resistance marker genes will be useful for assessing drug pressure, mapping and monitoring of drug resistance status; and will be helpful for searching alternative treatments.

OBJECTIVES

This study was conducted to study the polymorphisms in antimalarial drug resistance marker genes among clinical isolates collected from Kolkata after 10 years of artemisinin-based combination therapie (ACT) implementation.

MATERIALS AND METHODS

Blood samples were collected from mono-infected patients and polymorphisms in CQ resistance transporter , multidrug resistance , dihydrofolate reductase , dihydropteroate synthetase , and propeller genes were analysed by polymerase chain reaction and DNA sequencing.

RESULTS

In gene, C72S, and K76T mutation was recorded in 100% isolates and no mutations was detected in any of the targeted codons of gene. A double mutant haplotype SVMNT and wildtype haplotype NYD in were prevalent in 100% of study isolates. Triple mutant haplotype ANRNI-SGKAA was recorded. No polymorphism in gene was documented in any of the isolates.

CONCLUSIONS

Observed wild codon N86 along with Y184 and D1246 of gene might be an indication of the reappearance of CQ sensitivity. The absence of quadruple and quintuple haplotypes in gene along with the wild haplotype of pfK13 is evidence of ACT effectivity. Hence, similar studies with large sample size are highly suggested for monitoring the drug resistance status of .

摘要

背景

抗疟药物耐药性是疟疾消除面临的主要挑战之一。在印度,2010年引入了青蒿素联合疗法(青蒿琥酯 - 磺胺多辛 - 乙胺嘧啶)来替代氯喹(CQ)治疗非复杂性恶性疟。定期监测抗疟药物耐药性标记基因的多态性,对于评估药物压力、绘制和监测耐药性状况以及寻找替代治疗方法将是有用的。

目的

本研究旨在研究在基于青蒿素的联合疗法(ACT)实施10年后,从加尔各答收集的临床分离株中抗疟药物耐药性标记基因的多态性。

材料与方法

从单一感染患者采集血样,通过聚合酶链反应和DNA测序分析CQ耐药转运蛋白、多药耐药、二氢叶酸还原酶、二氢蝶酸合酶和螺旋桨基因的多态性。

结果

在基因中,100%的分离株记录到C72S和K76T突变,在基因的任何目标密码子中均未检测到突变。基因中的双突变单倍型SVMNT和野生型单倍型NYD在100%的研究分离株中普遍存在。记录到三突变单倍型ANRNI - SGKAA。在任何分离株中均未记录到基因的多态性。

结论

观察到的野生密码子N86以及基因的Y184和D1246可能表明CQ敏感性的重现。基因中四重和五重单倍型的缺失以及pfK13的野生单倍型是ACT有效性的证据。因此,强烈建议进行类似的大样本研究以监测的耐药性状况。

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