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恶性疟原虫 HRP2 和 HRP3 序列变异与印度分离株:对疟疾快速诊断检测性能的影响。

Sequence variation in Plasmodium falciparum Histidine Rich Proteins 2 and 3 in Indian isolates: Implications for Malaria Rapid Diagnostic Test Performance.

机构信息

National Institute for Research in Tribal Health (NIRTH), Garha, Jabalpur, 482003, India.

Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia, 30329, USA.

出版信息

Sci Rep. 2017 May 2;7(1):1308. doi: 10.1038/s41598-017-01506-9.

DOI:10.1038/s41598-017-01506-9
PMID:28465622
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5430971/
Abstract

Commercial malaria rapid diagnostic tests (RDTs) detect P. falciparum histidine rich protein 2 (PfHRP2) and cross react with PfHRP3, a structural homologue. Here, we analysed natural variations in PfHRP2 and PfHRP3 sequences from Indian isolates and correlated these variations with RDT reactivity. A total 1392 P. falciparum positive samples collected from eight endemic states were PCR amplified for Pfhrp2 and Pfhrp3 genes and were sequenced. The deduced protein sequences were analysed for repeat variations and correlated with RDT reactivity. Out of 1392 PCR amplified samples, a single sample was Pfhrp2 negative and two samples were Pfhrp3 negative. Complete Pfhrp2 and Pfhrp3 sequences were obtained for 769 samples and 750 samples, respectively. A total of 16 distinct repeat motifs were observed for Pfhrp2 and 11 for Pfhrp3, including some new repeat types. No correlation was found between variations in the size of Pfhrp2 repeat types 2 and 7, nor between any combinations of repeat motifs, and performance of a commercial RDT at low parasite densities. The findings suggest that sequence diversity in Pfhrp2 and Pfhrp3 genes in Indian isolates is not likely to negatively influence performance of currently used PfHRP2 RDTs.

摘要

商业疟疾快速诊断检测(RDT)检测恶性疟原虫富含组氨酸蛋白 2(PfHRP2),并与 PfHRP3 发生交叉反应,PfHRP3 是一种结构同源物。在这里,我们分析了来自印度分离株的 PfHRP2 和 PfHRP3 序列的自然变异,并将这些变异与 RDT 反应性相关联。从 8 个流行地区采集了总共 1392 个疟原虫阳性样本,用于 Pfhrp2 和 Pfhrp3 基因的 PCR 扩增,并对这些基因进行了测序。对推导的蛋白质序列进行了重复变异分析,并与 RDT 反应性相关联。在 1392 个 PCR 扩增样本中,有一个样本 Pfhrp2 阴性,两个样本 Pfhrp3 阴性。获得了 769 个样本的完整 Pfhrp2 和 750 个样本的 Pfhrp3 序列。Pfhrp2 观察到了 16 个不同的重复基序,Pfhrp3 观察到了 11 个,包括一些新的重复类型。在 Pfhrp2 重复类型 2 和 7 的大小变化之间,以及在任何重复基序组合之间,都没有发现与商业 RDT 在低寄生虫密度下的性能之间存在相关性。研究结果表明,印度分离株中 Pfhrp2 和 Pfhrp3 基因的序列多样性不太可能对目前使用的 PfHRP2 RDT 的性能产生负面影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a66/5430971/5f63ed65a9a0/41598_2017_1506_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a66/5430971/2fb86ae4a837/41598_2017_1506_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a66/5430971/c965411f4185/41598_2017_1506_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a66/5430971/5f63ed65a9a0/41598_2017_1506_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a66/5430971/2fb86ae4a837/41598_2017_1506_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a66/5430971/c965411f4185/41598_2017_1506_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a66/5430971/5f63ed65a9a0/41598_2017_1506_Fig3_HTML.jpg

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