Variation in Plasmodium falciparum Histidine-Rich Protein 2 (Pfhrp2) and Plasmodium falciparum Histidine-Rich Protein 3 (Pfhrp3) Gene Deletions in Guyana and Suriname.
Variation in Plasmodium falciparum Histidine-Rich Protein 2 (Pfhrp2) and Plasmodium falciparum Histidine-Rich Protein 3 (Pfhrp3) Gene Deletions in Guyana and Suriname.
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DOI：
10.1371/journal.pone.0126805
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Udhayakumar V
中科院分区：
文献类型：
--
作者：
Akinyi Okoth S;Abdallah JF;Ceron N;Adhin MR;Chandrabose J;Krishnalall K;Huber CS;Goldman IF;Macedo de Oliveira A;Barnwell JW;Udhayakumar V
圭亚那和苏里南在减少疟疾负担方面取得了重要进展。虽然这两个国家都使用显微镜作为临床诊断的主要工具，但疟疾快速诊断测试在实验室支持可能有限或无法获得的内陆偏远地区是有用的。最近的报告表明，在南美洲的一些地区，由于出现了缺乏PfHRP2基因的恶性疟原虫，因此无法产生PfHRP2抗原，因此基于富组氨酸蛋白2 （PfHRP2）的恶性疟原虫特异性诊断检测可能会产生假阴性结果。在圭亚那和苏里南收集的寄生虫分离物中扩增Pfhrp2和pfhrp3基因，以确定是否存在这些基因缺失的循环分离物。监测Pfhrp3缺失，因为在基于pfhrp2的RDTs中使用的一些单克隆抗体与Pfhrp3蛋白交叉反应。我们发现来自圭亚那的97株符合纳入标准的分离株均为pfhrp2-和pfhrp3阳性。在苏里南（78例），14%的检测样本为pfhrp2阴性，4%为pfhrp3阴性。此外，对pfhrp2和pfhrp3近端的基因组区域的分析显示，基因组缺失延伸到侧翼基因。我们还研究了收集到的分离物的群体亚结构，以确定pfhrp2和pfhrp3缺失的寄生虫是否属于任何遗传亚型。聚类分析显示，两国分离的恶性疟原虫种群亚结构均不占优势，表明寄生虫种群间存在遗传混合。此外，来自苏里南的pfhrp2缺失寄生虫似乎没有共享单一的独特遗传背景。
Guyana and Suriname have made important progress in reducing the burden of malaria. While both countries use microscopy as the primary tool for clinical diagnosis, malaria rapid diagnostic tests (RDTs) are useful in remote areas of the interior where laboratory support may be limited or unavailable. Recent reports indicate that histidine-rich protein 2 (PfHRP2)-based diagnostic tests specific for detection of P. falciparum may provide false negative results in some parts of South America due to the emergence of P. falciparum parasites that lack the pfhrp2 gene, and thus produce no PfHRP2 antigen. Pfhrp2 and pfhrp3 genes were amplified in parasite isolates collected from Guyana and Suriname to determine if there were circulating isolates with deletions in these genes. Pfhrp3 deletions were monitored because some monoclonal antibodies utilized in PfHRP2-based RDTs cross-react with the PfHRP3 protein. We found that all 97 isolates from Guyana that met the inclusion criteria were both pfhrp2- and pfhrp3-positive. In Suriname (N = 78), 14% of the samples tested were pfhrp2-negative while 4% were pfhrp3-negative. Furthermore, analysis of the genomic region proximal to pfhrp2 and pfhrp3 revealed that genomic deletions extended to the flanking genes. We also investigated the population substructure of the isolates collected to determine if the parasites that had deletions of pfhrp2 and pfhrp3 belonged to any genetic subtypes. Cluster analysis revealed that there was no predominant P. falciparum population substructure among the isolates from either country, an indication of genetic admixture among the parasite populations. Furthermore, the pfhrp2-deleted parasites from Suriname did not appear to share a single, unique genetic background.
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