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人群调查中恶性疟原虫分子诊断:陷阱与对策。

Plasmodium vivax molecular diagnostics in community surveys: pitfalls and solutions.

机构信息

Swiss Tropical and Public Health Institute, Socinstrasse 57, 4002, Basel, Switzerland.

University of Basel, Basel, Switzerland.

出版信息

Malar J. 2018 Jan 30;17(1):55. doi: 10.1186/s12936-018-2201-0.

DOI:10.1186/s12936-018-2201-0
PMID:29378609
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5789620/
Abstract

A distinctive feature of Plasmodium vivax infections is the overall low parasite density in peripheral blood. Thus, identifying asymptomatic infected individuals in endemic communities requires diagnostic tests with high sensitivity. The detection limits of molecular diagnostic tests are primarily defined by the volume of blood analysed and by the copy number of the amplified molecular marker serving as the template for amplification. By using mitochondrial DNA as the multi-copy template, the detection limit can be improved more than tenfold, compared to standard 18S rRNA targets, thereby allowing detection of lower parasite densities. In a very low transmission area in Brazil, application of a mitochondrial DNA-based assay increased prevalence from 4.9 to 6.5%. The usefulness of molecular tests in malaria epidemiological studies is widely recognized, especially when precise prevalence rates are desired. Of concern, however, is the challenge of demonstrating test accuracy and quality control for samples with very low parasite densities. In this case, chance effects in template distribution around the detection limit constrain reproducibility. Rigorous assessment of false positive and false negative test results is, therefore, required to prevent over- or under-estimation of parasite prevalence in epidemiological studies or when monitoring interventions.

摘要

间日疟原虫感染的一个显著特征是外周血中的寄生虫总密度较低。因此,在流行地区识别无症状感染者需要使用高灵敏度的诊断检测方法。分子诊断检测的检测限主要由分析的血液量和作为扩增模板的扩增分子标记的拷贝数决定。通过使用线粒体 DNA 作为多拷贝模板,与标准的 18S rRNA 靶标相比,检测限可以提高十倍以上,从而可以检测到更低的寄生虫密度。在巴西的一个低传播地区,应用基于线粒体 DNA 的检测方法将患病率从 4.9%提高到 6.5%。分子检测在疟疾流行病学研究中的应用已得到广泛认可,特别是在需要精确患病率时。然而,令人担忧的是,对于寄生虫密度非常低的样本,检测准确性和质量控制的证明存在挑战。在这种情况下,模板在检测限周围的分布中的偶然效应限制了可重复性。因此,需要严格评估假阳性和假阴性检测结果,以防止在流行病学研究或干预监测中对寄生虫患病率的过高或过低估计。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c846/5789620/157dc5c26283/12936_2018_2201_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c846/5789620/be72ee06968b/12936_2018_2201_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c846/5789620/01958ca918b1/12936_2018_2201_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c846/5789620/42c1fdb8d670/12936_2018_2201_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c846/5789620/d13e72d64f28/12936_2018_2201_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c846/5789620/157dc5c26283/12936_2018_2201_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c846/5789620/be72ee06968b/12936_2018_2201_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c846/5789620/01958ca918b1/12936_2018_2201_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c846/5789620/42c1fdb8d670/12936_2018_2201_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c846/5789620/d13e72d64f28/12936_2018_2201_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c846/5789620/157dc5c26283/12936_2018_2201_Fig5_HTML.jpg

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