Accuracy of molecular biology techniques for the diagnosis of Strongyloides stercoralis infection—A systematic review and meta-analysis

BackgroundStrongyloides stercoralis infection is a neglected tropical disease which can lead to severe symptoms and even death in immunosuppressed people. Unfortunately, its diagnosis is hampered by the lack of a gold standard, as the sensitivity of traditional parasitological tests (including microscopic examination of stool samples and coproculture) is low. Hence, alternative diagnostic methods, such as molecular biology techniques (mostly polymerase chain reaction, PCR) have been implemented. However, there are discrepancies in the reported accuracy of PCR.MethodologyA systematic review with meta-analysis was conducted in order to evaluate the accuracy of PCR for the diagnosis of S. stercoralis infection. The protocol was registered with PROSPERO International Prospective Register of Systematic Reviews (record: CRD42016054298). Fourteen studies, 12 of which evaluating real-time PCR, were included in the analysis. The specificity of the techniques resulted high (ranging from 93 to 95%, according to the reference test(s) used). When all molecular techniques were compared to parasitological methods, the sensitivity of PCR was assessed at 71.8% (95% CI 52.2–85.5), that decreased to 61.8% (95% CI 42.0–78.4) when serology was added among the reference tests. Similarly, sensitivity of real-time PCR resulted 64.4% (95% CI 46.2–77.7) when compared to parasitological methods only, 56.5% (95% CI 39.2–72.4) including serology.ConclusionsPCR might not be suitable for screening purpose, whereas it might have a role as a confirmatory test.

背景：粪类圆线虫（Strongyloides stercoralis）感染是一种被忽视的热带病，免疫功能低下人群感染后可出现严重症状甚至死亡。遗憾的是，目前该病的诊断缺乏金标准：传统寄生虫学检测方法（包括粪便样本镜检与粪便培养）的灵敏度较低，严重制约了临床诊断工作。为此，学界已将聚合酶链反应（polymerase chain reaction, PCR）等分子生物学技术作为替代诊断手段，但现有报道的PCR诊断准确性存在较大差异。
方法：本研究开展了一项联合元分析（meta-analysis）的系统评价，以评估PCR诊断粪类圆线虫感染的准确性。研究方案已在PROSPERO国际系统评价前瞻性注册库完成注册（记录号：CRD42016054298）。最终纳入14项相关研究，其中12项针对实时PCR（real-time PCR）展开评估。分析结果显示，此类检测技术的特异性较高（依据所采用的参照检测方案，特异性范围为93%~95%）。当仅将寄生虫学方法作为参照检测时，所有分子生物学检测方法的综合灵敏度为71.8%（95%置信区间（confidence interval, CI）：52.2~85.5）；若将血清学检测纳入参照检测范畴，则灵敏度降至61.8%（95% CI：42.0~78.4）。类似地，仅以寄生虫学方法为参照时，实时PCR的综合灵敏度为64.4%（95% CI：46.2~77.7），纳入血清学参照后则降至56.5%（95% CI：39.2~72.4）。
结论：PCR或不适用于粪类圆线虫感染的筛查工作，但可作为确认试验发挥辅助诊断价值。