Genetic diversity of Plasmodium falciparum histidine-rich protein 2 (PfHRP2) and its effect on the performance of PfHRP2-based rapid diagnostic tests

Genetic diversity of Plasmodium falciparum histidine-rich protein 2 (PfHRP2) and its effect on the performance of PfHRP2-based rapid diagnostic tests
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DOI:
10.1086/432010
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发表时间:
2005-09-01
影响因子:
6.4
通讯作者:
Cheng, Q
Cheng, Q
中科院分区:
医学2区
文献类型:
--
作者:
Baker, J;McCarthy, J;Cheng, Q

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抗疟药成本的上升增加了对疟疾准确诊断的需求。快速诊断测试为改善疟疾诊断提供了巨大潜力,特别是在偏远地区。许多RDT是基于检测恶性疟原虫富组氨酸蛋白(PfHRP)2,但现场试验的报告质疑其灵敏度和可靠性。我们假设基于PfHRP 2的RDT结果的变异性与靶抗原的变异性有关。我们通过检查PfHRP2的遗传多样性来验证这一假设,PfHRP2包括许多氨基酸重复序列,来自19个国家的75个恶性疟原虫株系和分离株,并使用2个基于PfHRP2的RDT检测寄生虫亚群。我们观察到PfHRP2序列的广泛多样性,无论是在国内和国家之间。Logistic回归分析表明,2种重复类型可预测RDT检测灵敏度(准确率为87.5%),预测表明亚太地区只有84%的恶性疟原虫可能在密度下被检测到
Rising costs of antimalarial agents are increasing the demand for accurate diagnosis of malaria. Rapid diagnostic tests (RDTs) offer great potential to improve the diagnosis of malaria, particularly in remote areas. Many RDTs are based on the detection of Plasmodium falciparum histidine-rich protein (PfHRP) 2, but reports from field tests have questioned their sensitivity and reliability. We hypothesize that the variability in the results of PfHRP2-based RDTs is related to the variability in the target antigen. We tested this hypothesis by examining the genetic diversity of PfHRP2, which includes numerous amino acid repeats, in 75 P. falciparum lines and isolates originating from 19 countries and testing a subset of parasites by use of 2 PfHRP2-based RDTs. We observed extensive diversity in PfHRP2 sequences, both within and between countries. Logistic regression analysis indicated that 2 types of repeats were predictive of RDT detection sensitivity (87.5% accuracy), with predictions suggesting that only 84% of P. falciparum parasites in the Asia-Pacific region are likely to be detected at densities