Deletion of Plasmodium falciparum Histidine-Rich Protein 2 (pfhrp2) and Histidine-Rich Protein 3 (pfhrp3) Genes in Colombian Parasites.

Deletion of Plasmodium falciparum Histidine-Rich Protein 2 (pfhrp2) and Histidine-Rich Protein 3 (pfhrp3) Genes in Colombian Parasites.
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DOI:
10.1371/journal.pone.0131576
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发表时间:
2015
期刊:
影响因子:
3.7
通讯作者:
Barnwell JW
Barnwell JW
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Murillo Solano C;Akinyi Okoth S;Abdallah JF;Pava Z;Dorado E;Incardona S;Huber CS;Macedo de Oliveira A;Bell D;Udhayakumar V;Barnwell JW

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许多研究分析了哥伦比亚疟疾快速诊断检测 (RDT) 的性能,性能差异归因于寄生虫水平、RDT 结果解释和/或 RDT 试剂盒的处理和储存等综合因素。然而,基于恶性疟原虫富含组氨酸蛋白 2 (PfHRP2) 的 RDT 结果观察到的一些不一致也可以通过在一些寄生虫分离株中删除编码蛋白质 pfhrp2 及其结构同源物 pfhrp3 的基因来解释。鉴于在邻近的秘鲁和巴西亚马逊地区已检测到 pfhrp2 和 pfhrp3 阴性恶性疟原虫分离株,我们假设哥伦比亚也可能存在 pfhrp2 和 pfhrp3 缺失的寄生虫。在这项研究中,我们测试了 1999 年至 2009 年间从哥伦比亚六个部门收集的 100 个历史样本中是否存在 pfhrp2、pfhrp3 及其侧翼基因。七个中性微卫星也被用来确定这些寄生虫的遗传背景。在 100 个寄生虫分离株中,总共有 18 个被发现删除了 pfhrp2,其中大多数(18 个中的 14 个)是从与秘鲁和巴西接壤的亚马逊部门收集的。从全国各地收集的 100 个样本中,有 52 个样本发现 pfhrp3 缺失。 pfhrp2 侧翼基因 PF3D7_0831900 和 PF3D7_0831700 分别在 100 个样本中的 22 个和 100 个样本中的 1 个中被删除。 pfhrp3 侧翼基因 PF3D7_1372100 和 PF3D7_1372400 在 100 个样本中的 55 个和 100 个样本中的 57 个中缺失。微卫星数据的结构分析表明,本研究中测试的哥伦比亚样本属于四个簇,并且它们主要根据地理区域进行分离。大多数 pfhrp2 删除的寄生虫被分配到单个簇并起源于亚马逊部门,尽管少数 pfhrp2 阴性寄生虫起源于其他三个簇。哥伦比亚亚马逊地区存在高比例的 pfhrp2 阴性分离株可能对该地区使用基于 PfHRP2 的 RDT 产生影响,并可能解释在进行基于 PfHRP2 的测试和测定时观察到的不一致情况。
A number of studies have analyzed the performance of malaria rapid diagnostic tests (RDTs) in Colombia with discrepancies in performance being attributed to a combination of factors such as parasite levels, interpretation of RDT results and/or the handling and storage of RDT kits. However, some of the inconsistencies observed with results from Plasmodium falciparum histidine-rich protein 2 (PfHRP2)-based RDTs could also be explained by the deletion of the gene that encodes the protein, pfhrp2, and its structural homolog, pfhrp3, in some parasite isolates. Given that pfhrp2- and pfhrp3-negative P. falciparum isolates have been detected in the neighboring Peruvian and Brazilian Amazon regions, we hypothesized that parasites with deletions of pfhrp2 and pfhrp3 may also be present in Colombia. In this study we tested 100 historical samples collected between 1999 and 2009 from six Departments in Colombia for the presence of pfhrp2, pfhrp3 and their flanking genes. Seven neutral microsatellites were also used to determine the genetic background of these parasites. In total 18 of 100 parasite isolates were found to have deleted pfhrp2, a majority of which (14 of 18) were collected from Amazonas Department, which borders Peru and Brazil. pfhrp3 deletions were found in 52 of the100 samples collected from all regions of the country. pfhrp2 flanking genes PF3D7_0831900 and PF3D7_0831700 were deleted in 22 of 100 and in 1 of 100 samples, respectively. pfhrp3 flanking genes PF3D7_1372100 and PF3D7_1372400 were missing in 55 of 100 and in 57 of 100 samples. Structure analysis of microsatellite data indicated that Colombian samples tested in this study belonged to four clusters and they segregated mostly based on their geographic region. Most of the pfhrp2-deleted parasites were assigned to a single cluster and originated from Amazonas Department although a few pfhrp2-negative parasites originated from the other three clusters. The presence of a high proportion of pfhrp2-negative isolates in the Colombian Amazon may have implications for the use of PfHRP2-based RDTs in the region and may explain inconsistencies observed when PfHRP2-based tests and assays are performed.
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