血清学诊断 HIV 感染者肺孢子菌肺炎：一项回顾性病例对照研究
Serum-based diagnosis of Pneumocystis pneumonia by detection of Pneumocystis jirovecii DNA and 1,3-β-D-glucan in HIV-infected patients: a retrospective case control study.
机构信息
Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Region Västra Götaland, Sahlgrenska University Hospital, Department of Infectious Diseases, Gothenburg, Sweden.
出版信息
BMC Infect Dis. 2019 Jul 23;19(1):658. doi: 10.1186/s12879-019-4289-4.
BACKGROUND
Pneumocystis jirovecii pneumonia (PCP) is one of the most common HIV-related opportunistic infections. The diagnosis of PCP is based on analyses from respiratory tract specimens which may require the invasive procedure of a diagnostic bronchoscopy. The objective of this study was to evaluate the diagnostic potential of Pneumocystis jirovecii PCR in serum combined with the 1,3-β-D-glucan (betaglucan) test for the diagnosis of PCP in HIV-infected patients.
METHODS
This was a retrospective case-control study including serum samples from 26 HIV-infected patients with PCP collected within 5 days prior to the start of PCP treatment, 21 HIV-infected control subjects matched by blood CD4 cell counts, and 18 blood donors. The serum samples were analyzed for Pneumocystis jirovecii PCR and betaglucan. The reference standard for PCP was based on previously described microbiological and clinical criteria.
RESULTS
All patients with PCP had detectabe Pneumocystis jirovecii DNA in serum yielding a sensitivity for the Pneumocystis jirovecii PCR assay in serum of 100%. All blood donors had negative Pneumocystis PCR in serum. The specificity when testing HIV-infected patients was 71%, but with a PCR Cycle threshold (Ct) value of 34 as cut-off the specificity was 90%. At a putative pretest probaility of 20%, the negative and positive predictive value for the Pneumocystis PCR assay in serum was 0.99 and 0.71, respectively. Betaglucan with cut-off level 200 pg/ml combined with a positive Pneumocystis jirovecii PCR result had sensitivity and specificity of 92 and 90%, respectively. The concentration of Pneumocystis jirovecii DNA in serum samples, expressed by the PCR Ct values, correlated inversely to the betaglucan levels in serum.
CONCLUSION
In this case-control study including 70% of all HIV-infected patients with PCP treated at Sahlgrenska University Hospital during a time period of 13 years, Pneumocystis PCR analysis on serum samples had a very high sensitivity and negative predictive value for the diagnosis of PCP in HIV-infected patients. A serum-based diagnostic procedure either based on Pneumocystis jirovecii PCR alone or in combination with betaglucan analysis may thus be feasible and would facilitate the care of HIV-infected patients with suspected PCP.
背景
肺孢子菌肺炎（PCP）是最常见的 HIV 相关机会性感染之一。PCP 的诊断基于呼吸道标本的分析，这可能需要诊断性支气管镜检查等有创程序。本研究的目的是评估血清中肺孢子菌 PCR 联合 1,3-β-D-葡聚糖（β-葡聚糖）检测对 HIV 感染患者 PCP 的诊断潜力。
方法
这是一项回顾性病例对照研究，纳入了 26 例在开始 PCP 治疗前 5 天内采集的血清样本，这些患者均患有 PCP，同时还纳入了 21 名按血液 CD4 细胞计数匹配的 HIV 感染对照受试者和 18 名献血者。对血清样本进行肺孢子菌 PCR 和β-葡聚糖分析。PCP 的参考标准基于先前描述的微生物学和临床标准。
结果
所有 PCP 患者的血清中均可检测到肺孢子菌 DNA，血清肺孢子菌 PCR 检测的敏感性为 100%。所有献血者的血清均为阴性 PCR。当检测 HIV 感染患者时，特异性为 71%，但当 PCR 循环阈值（Ct）值为 34 时，特异性为 90%。在假定的 20%的先验概率下，血清肺孢子菌 PCR 检测的阴性和阳性预测值分别为 0.99 和 0.71。以 200pg/ml 为截断值的β-葡聚糖联合阳性肺孢子菌 PCR 结果的敏感性和特异性分别为 92%和 90%。血清样本中肺孢子菌 DNA 的浓度（通过 PCR Ct 值表示）与血清中β-葡聚糖的水平呈反比。
结论
在这项包括了在 13 年期间在萨赫勒格兰纳大学医院接受治疗的 70%的所有 HIV 感染 PCP 患者的病例对照研究中，血清样本中的肺孢子菌 PCR 分析对 HIV 感染患者 PCP 的诊断具有很高的敏感性和阴性预测值。因此，基于血清的诊断程序，无论是基于单独的肺孢子菌 PCR 还是结合β-葡聚糖分析，都可能是可行的，并将有助于 HIV 感染疑似 PCP 患者的护理。
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