Weinreich Felix, Hahn Andreas, Eberhardt Kirsten Alexandra, Kann Simone, Köller Thomas, Warnke Philipp, Dupke Susann, Dekker Denise, May Jürgen, Frickmann Hagen, Loderstädt Ulrike
Department of Microbiology and Hospital Hygiene, Bundeswehr Hospital Hamburg, 20359 Hamburg, Germany.
Institute for Medical Microbiology, Virology and Hygiene, University Medicine Rostock, 18057 Rostock, Germany.
Diagnostics (Basel). 2022 Apr 16;12(4):1007. doi: 10.3390/diagnostics12041007.
Prior to the implementation of new diagnostic techniques, a thorough evaluation is mandatory in order to ensure diagnostic reliability. If positive samples are scarcely available, however, such evaluations can be difficult to perform. Here, we evaluated four SeeGene Allplex real-time PCR assays amplifying a total of 28 bacteria, microsporidal and parasitic nucleic acid sequence targets in human stool samples in a multicentric approach. In the assessments with strongly positive samples, sensitivity values ranging between 13% and 100% were recorded for bacteria, between 0% and 100% for protozoa and between 7% and 100% for helminths and microsporidia; for the weakly positive samples, the recorded sensitivity values for bacteria ranged from 0% to 100%; for protozoa, from 0% to 40%; and for helminths and microsporidia, from 0% to 53%. For bacteria, the recorded specificity was in the range between 87% and 100%, while a specificity of 100% was recorded for all assessed PCRs targeting parasites and microsporidia. The intra- and inter-assay variations were generally low. Specifically for some helminth species, the sensitivity could be drastically increased by applying manual nucleic acid extraction instead of the manufacturer-recommended automatic procedure, while such effects were less obvious for the bacteria and protozoa. In summary, the testing with the chosen positive control samples showed varying degrees of discordance between the evaluated Allplex assays and the applied in-house reference assays associated with higher cycle threshold values in the Allplex assays, suggesting that samples with very low pathogen densities might be missed. As the targeted species can occur as harmless colonizers in the gut of individuals in high-endemicity settings as well, future studies should aim at assessing the clinical relevance of the latter hint.
在实施新的诊断技术之前,必须进行全面评估以确保诊断的可靠性。然而,如果难以获得阳性样本,此类评估可能难以进行。在此,我们采用多中心方法,对四种SeeGene Allplex实时PCR检测方法进行了评估,这些方法可扩增人粪便样本中总共28种细菌、微孢子虫和寄生虫的核酸序列靶点。在对强阳性样本的评估中,细菌的灵敏度值在13%至100%之间,原生动物在0%至100%之间,蠕虫和微孢子虫在7%至100%之间;对于弱阳性样本,细菌的记录灵敏度值在0%至100%之间;原生动物在0%至40%之间;蠕虫和微孢子虫在0%至53%之间。对于细菌,记录的特异性在87%至100%之间,而针对所有评估的寄生虫和微孢子虫的PCR检测记录的特异性为100%。批内和批间变异通常较低。具体而言,对于某些蠕虫种类,采用手动核酸提取而非制造商推荐的自动程序可大幅提高灵敏度,而对细菌和原生动物的此类影响则不太明显。总之,使用选定的阳性对照样本进行检测显示,评估的Allplex检测方法与应用的内部参考检测方法之间存在不同程度的不一致,且Allplex检测方法中的循环阈值较高,这表明病原体密度极低的样本可能会被漏检。由于在高流行地区个体的肠道中,目标物种也可能作为无害的定植菌出现,未来的研究应旨在评估后一种情况的临床相关性。