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印度中部恰蒂斯加尔邦恶性疟原虫中与抗疟药耐药性相关突变的流行情况:从疟疾消除角度看

Prevalence of mutations linked to antimalarial resistance in Plasmodium falciparum from Chhattisgarh, Central India: A malaria elimination point of view.

作者信息

Patel Priyanka, Bharti Praveen K, Bansal Devendra, Ali Nazia A, Raman Rajive K, Mohapatra Pradyumna K, Sehgal Rakesh, Mahanta Jagadish, Sultan Ali A, Singh Neeru

机构信息

National Institute for Research in Tribal Health, Indian Council of Medical Research, Nagpur Road, Garha, Jabalpur, 482003, Madhya Pradesh, India.

Symbiosis School of Biomedical Sciences, Symbiosis International University, Lavale, Maharashtra, 412115, India.

出版信息

Sci Rep. 2017 Nov 30;7(1):16690. doi: 10.1038/s41598-017-16866-5.

Abstract

Antimalarial drug resistance is a major global challenge in malaria control and elimination. Mutations in six different genes of Plasmodium falciparum (crt, mdr1, dhfr, dhps, ATPase6 and K-13 propeller) that confer resistance to chloroquine, sulphadoxine-pyrimethamine and artemisinin-based combination therapy were analyzed in samples from Chhattisgarh. Seventy-eight percent of the samples were found to have a pfcrt mutation (53% double, 24% triple and 1% single mutant), and 59% of pfmdr1 genes were found to have an N86Y mutation. Double mutations were recorded in pfdhfr gene among 76% of the samples while only 6% of the samples harbored mutant genotypes in pfdhps. No mutation was found in the K-13 propeller gene, while only one sample showed a mutant genotype for the PfATPase6 gene. The Tajima test confirmed that there is no role of evolutionary natural selection in drug resistance, and gene pairwise linkage of disequilibrium showed significant intragenic association. The high level of pfcrt mutations suggests that parasite resistance to chloroquine is almost at a fixed level, whereas resistance to SP is evolving in the population and parasites remain sensitive to artemisinin derivatives. These findings provide potential information and understanding of the evolution and spread of different drug resistance alleles in Chhattisgarh.

摘要

抗疟药物耐药性是疟疾控制与消除工作中的一项重大全球挑战。对来自恰蒂斯加尔邦的样本分析了恶性疟原虫六个不同基因(crt、mdr1、dhfr、dhps、ATPase6和K-13螺旋桨)中的突变情况,这些突变赋予了对氯喹、磺胺多辛-乙胺嘧啶和青蒿素类联合疗法的耐药性。结果发现,78%的样本存在pfcrt突变(53%为双突变、24%为三突变、1%为单突变),59%的pfmdr1基因存在N86Y突变。76%的样本中pfdhfr基因出现双突变,而pfdhps中只有6%的样本含有突变基因型。K-13螺旋桨基因未发现突变,只有一个样本的PfATPase6基因呈现突变基因型。Tajima检验证实进化自然选择在耐药性中不起作用,基因成对不平衡连锁显示出显著的基因内关联。高水平的pfcrt突变表明寄生虫对氯喹的耐药性几乎处于固定水平,而对磺胺多辛-乙胺嘧啶的耐药性在种群中正在演变,寄生虫对青蒿素衍生物仍敏感。这些发现为恰蒂斯加尔邦不同耐药等位基因的进化和传播提供了潜在信息和认识。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f944/5709362/a8292b33a2cf/41598_2017_16866_Fig1_HTML.jpg

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