Utility of a novel lipoarabinomannan assay for the diagnosis of tuberculous meningitis in a resource-poor high-HIV prevalence setting.
Utility of a novel lipoarabinomannan assay for the diagnosis of tuberculous meningitis in a resource-poor high-HIV prevalence setting.
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DOI：
10.1186/1743-8454-6-13
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发表时间：
2009-11-02
影响因子：
--
通讯作者：
Dheda K
中科院分区：
文献类型：
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作者：
Patel VB;Bhigjee AI;Paruk HF;Singh R;Meldau R;Connolly C;Ndung'u T;Dheda K
在非洲，结核性脑膜炎(TBM)是艾滋病毒阳性患者的一种重要机会性感染。目前用于TBM的诊断工具表现不佳。特别是，结核病的快速诊断具有挑战性，因为涂片显微镜的产量很低，而且聚合酶链式反应在资源匮乏的环境中并不广泛使用。我们使用存档的脑脊液样本，评估了一种新的标准化的脂阿拉伯甘露聚糖(LAM)抗原检测方法在50名非洲TBM嫌疑人中的表现结果，其中68%是HIV阳性。在50名参与者中，14名患者为确诊患者，23名患者为可能患者，13名患者为非TBM患者。非结核病组有5例HIV阳性患者失访，不能明确排除合并结核分枝杆菌感染。检测的敏感性和特异性分别为：LAM法、法和涂片镜检分别为0%和100%、93%和77%。在这项初步的概念验证研究中，LAM抗原检测可以实现对TBM的快速诊断。尽管特异性不是最优的，但由于研究设计中固有的分类偏差，由于缺乏临床随访，不可能排除推定的非TBM病例中的TBM，因此这里提供的估计可能不可靠。由于在很大程度上无法获得PCR，LAM检测很可能被证明是在HIV高发环境下快速诊断TBM的有用的辅助手段。这些初步结果证明了进一步研究的合理性，现在需要进行前瞻性研究，以确定这项技术在诊断TBM中的位置。
In Africa, tuberculous meningitis (TBM) is an important opportunistic infection in HIV-positive patients. Current diagnostic tools for TBM perform sub-optimally. In particular, the rapid diagnosis of TBM is challenging because smear microscopy has a low yield and PCR is not widely available in resource-poor settings. We evaluated the performance outcome of a novel standardized lipoarabinomannan (LAM) antigen-detection assay, using archived cerebrospinal fluid samples, in 50 African TBM suspects of whom 68% were HIV-positive. Of the 50 participants 14, 23 and 13 patients had definite, probable and non-TBM, respectively. In the non-TB group there were 5 HIV positive patients who were lost to follow-up and in whom concomitant infection with Mycobacterium tuberculosis could not be definitively excluded. The test sensitivities and specificities were as follows: LAM assay 64% and 69% (cut-point 0.22), smear microscopy 0% and 100% and PCR 93% and 77%, respectively. In this preliminary proof-of-concept study, a rapid diagnosis of TBM could be achieved using LAM antigen detection. Although specificity was sub-optimal, the estimates provided here may be unreliable because of a classification bias inherent in the study design where it was not possible to exclude TBM in the presumed non-TBM cases owing to a lack of clinical follow-up. As PCR is largely unavailable, the LAM assay may well prove to be a useful adjunct for the rapid diagnosis of TBM in high HIV-incidence settings. These preliminary results justify further enquiry and prospective studies are now required to definitively establish the place of this technology for the diagnosis of TBM.