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印度东北部国际边界地区无并发症恶性疟原虫疟疾病例 PfMDR1 多态性的时空分布。

Spatio-temporal distribution of PfMDR1 polymorphism among uncomplicated Plasmodium falciparum malaria cases along international border of north east India.

机构信息

National Institute of Malaria Research, Indian Council of Medical Research, Sector - 8, Dwarka, New Delhi, India.

National Institute of Malaria Research, Indian Council of Medical Research, Sector - 8, Dwarka, New Delhi, India.

出版信息

Infect Genet Evol. 2018 Sep;63:285-290. doi: 10.1016/j.meegid.2018.05.025. Epub 2018 May 26.

DOI:10.1016/j.meegid.2018.05.025
PMID:29842979
Abstract

PfMDR1 single nucleotide polymorphisms (SNP) are good correlate markers for antimalarial drug resistance worldwide. Present study is a comprehensive view of screening of PfMDR1 polymorphism to antimalarials practiced with geography and time. Study sites Mizoram, Tripura, Meghalaya chosen are at multivariate drug pressure due to cross border migration and transmission. Mizoram is gateway to south east Asia through Myanmar whereas Tripura, Meghalaya share porous border with Bangladesh. Baseline finger pricked blood stained filter paper for confirmed uncomplicated Plasmodium falciparum infected patients (year 2015) were obtained from National Institute of Malaria Research, New Delhi, India. PfMDR1 polymorphism for codon N86Y, Y184F, D1246Y was determined by PCR-RFLP, further confirmed by sequencing. There observed marked predominance of Plasmodium isolates with PfMDR1 wild type alleles for all codons under study i.e. 86, 184, 1246. Spatially, Plasmodium isolates from Mizoram were most diverse with co-existence of PfMDR1 genotype with NYD, YYD, NFD haplotypes, followed by Tripura. Isolates from Meghalaya were of all NYD haplotype. Reports, referring to screening of PfMDR1 SNPs to CQ/SP/AS-SP across India, were archived. Temporal study show distinct rise in proportion of PfMDR1 wild type N86 allele since introduction of Artemether-Lumefantrine as first line antimalarial. Hence spatio-temporal screening of Plasmodium population with PfMDR1 single nucleotide polymorphism accounts for its association with antimalarial susceptibility and validate PfMDR1 SNPs as antimalarial drug resistant marker.

摘要

PfMDR1 单核苷酸多态性 (SNP) 是全球抗疟药物耐药性的良好相关标志物。本研究全面观察了 PfMDR1 多态性与地理位置和时间的抗疟药物筛选。选择的研究地点米佐拉姆邦、特里普拉邦和梅加拉亚邦由于跨境移民和传播而处于多种药物压力之下。米佐拉姆邦是通过缅甸进入东南亚的门户,而特里普拉邦和梅加拉亚邦与孟加拉国的边界则是多孔的。从印度新德里国家疟疾研究所获得了确诊为无并发症恶性疟原虫感染患者的基线指尖刺破血斑滤纸(2015 年)。通过 PCR-RFLP 确定 PfMDR1 密码子 N86Y、Y184F 和 D1246Y 的多态性,进一步通过测序确认。在所研究的所有密码子中,观察到 PfMDR1 野生型等位基因的疟原虫分离株明显占主导地位,即 86、184、1246。从空间上看,米佐拉姆邦的疟原虫分离株最为多样化,存在 PfMDR1 基因型与 NYD、YYD、NFD 单倍型共存,其次是特里普拉邦。梅加拉亚邦的分离株均为 NYD 单倍型。有关印度各地针对 CQ/SP/AS-SP 筛查 PfMDR1 SNPs 的报告已被存档。时间研究表明,自从青蒿琥酯-咯萘啶作为一线抗疟药物引入以来,PfMDR1 野生型 N86 等位基因的比例明显上升。因此,对疟原虫种群进行 PfMDR1 单核苷酸多态性的时空筛选,可证明其与抗疟药物敏感性有关,并验证 PfMDR1 SNPs 作为抗疟药物耐药性的标志物。

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