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脑脊液腺苷脱氨酶检测对结核性脑膜炎诊断的可疑价值。

The dubious value of cerebrospinal fluid adenosine deaminase measurement for the diagnosis of tuberculous meningitis.

作者信息

Ekermans Pieter, Dusé Adriano, George Jaya

机构信息

Department of Chemical Pathology, University of Witwatersrand and National Health Laboratory Service, Johannesburg, South Africa.

Department of Chemical Pathology and Department of Clinical Microbiology and Infectious Diseases, School of Pathology, Faculty of Health Sciences, University of Witwatersrand and National Health Laboratory Service, 7 York Road, Johannesburg, South Africa.

出版信息

BMC Infect Dis. 2017 Jan 31;17(1):104. doi: 10.1186/s12879-017-2221-3.

DOI:10.1186/s12879-017-2221-3
PMID:28143441
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5282858/
Abstract

BACKGROUND

The diagnosis of tuberculous meningitis (TBM) can be extremely difficult in the absence of culture confirmation. Cerebrospinal fluid (CSF) adenosine deaminase (ADA) can potentially assist in this regard, although its current value remains unclear. The literature on the usefulness of CSF ADA in TBM diagnosis is inconsistent, especially from an analytical point of view.

METHODS

A retrospective analysis of clinical and laboratory data relating to all CSF ADA requests during 2009 and 2010 in a South African quaternary healthcare setting was performed. A CSF ADA cut-off for TBM diagnosis was calculated using receiver operating characteristic curve analysis. The performance of CSF ADA in different infective and non-infective categories was assessed.

RESULTS

In total, 3548 CSF ADA requests were considered over the 2-year period. Of these, 1490 were for patients for whom both a CSF ADA and a mycobacterial culture were requested. The optimal cut-off was calculated at 2.0 U/L (AUC = 0.86; 95% CI = 0.82 - 0.89; p-value < 0.01; sensitivity of 85.9% (95% CI of 77.0 - 92.3) and specificity of 77.7% (95% CI of 75.4 - 79.8%); positive likelihood ratio = 3.85 and negative likelihood ratio = 0.18). At this cut-off 13 TBM cases were missed.

CONCLUSION

An optimal cut-off for routine use could not be established as too many TBM cases were missed. Specimen integrity, lack of ADA assay standardisation and overlap in performance of the assay in different diagnostic categories affect interpretation.

摘要

背景

在缺乏培养确诊的情况下,结核性脑膜炎(TBM)的诊断可能极其困难。脑脊液(CSF)腺苷脱氨酶(ADA)在这方面可能有辅助作用,但其目前的价值仍不明确。关于CSF ADA在TBM诊断中的有用性的文献并不一致,尤其是从分析的角度来看。

方法

对南非一家四级医疗机构2009年和2010年期间所有CSF ADA检测申请的临床和实验室数据进行回顾性分析。使用受试者工作特征曲线分析计算TBM诊断的CSF ADA临界值。评估CSF ADA在不同感染性和非感染性类别中的表现。

结果

在这两年期间,共考虑了3548份CSF ADA检测申请。其中,1490份是为同时申请了CSF ADA和分枝杆菌培养的患者。计算出的最佳临界值为2.0 U/L(曲线下面积 = 0.86;95%置信区间 = 0.82 - 0.89;p值 < 0.01;灵敏度为85.9%(95%置信区间为77.0 - 92.3),特异性为77.7%(95%置信区间为75.4 - 79.8%);阳性似然比 = 3.85,阴性似然比 = 0.18)。在此临界值下,漏诊了13例TBM病例。

结论

由于漏诊了太多TBM病例,无法确定常规使用的最佳临界值。样本完整性、ADA检测缺乏标准化以及该检测在不同诊断类别中的表现重叠影响了结果的解读。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cee/5282858/823a501a69db/12879_2017_2221_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cee/5282858/bb80bea88785/12879_2017_2221_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cee/5282858/c50b737fdfea/12879_2017_2221_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cee/5282858/0087ee28324f/12879_2017_2221_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cee/5282858/823a501a69db/12879_2017_2221_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cee/5282858/bb80bea88785/12879_2017_2221_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cee/5282858/c50b737fdfea/12879_2017_2221_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cee/5282858/0087ee28324f/12879_2017_2221_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cee/5282858/823a501a69db/12879_2017_2221_Fig4_HTML.jpg

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