背景:缺乏金标准阻碍了结核性脑膜炎(TBM)的诊断。目前的微生物测试缺乏敏感性,临床诊断方法是主观的。因此,我们建立了一个诊断模型,可以在知道微生物测试结果之前使用。
方法:在越南进行的一项前瞻性观察性研究中,我们纳入了659名年龄[配方:见正文]岁的疑似脑部感染的个体。我们拟合了TBM状态的逻辑回归诊断模型,通过三个分枝杆菌测试的潜在类别模型估计未知值:Ziehl-Neelsen涂片,分枝杆菌培养,和GeneXpert.我们还重新评估了分枝杆菌测试性能,估计的个体分枝杆菌负荷,并量化验证试验阴性后TBM风险的降低。我们还拟合了一个简化模型,并开发了一个用于早期筛查的评分表。所有模型都进行了内部比较和验证。
结果:HIV参与者,miliaryTB,症状持续时间长,高脑脊液(CSF)淋巴细胞计数更可能患有TBM。HIV和更高的CSF蛋白与更高的分枝杆菌负荷相关。在简化模型中,HIV感染,临床症状持续时间长,神经外结核的临床或放射学证据与TBM相关,在基于Youden指数的切点上,全模型和简化模型诊断TBM的敏感性和特异性分别为86.0%和79.0%,分别为88.0%和75.0%。
结论:我们的诊断模型显示出可靠的性能,可作为临床医生检测TBM高危患者的决策助手。缺乏金标准阻碍了结核性脑膜炎的诊断。我们使用潜在类分析开发了一个诊断模型,结合验证性测试结果和危险因素。模型是准确的,校准良好,可以支持临床实践和研究。
BACKGROUND: Diagnosis of tuberculous meningitis (TBM) is hampered by the lack of a gold standard. Current microbiological tests lack sensitivity and clinical diagnostic approaches are subjective. We therefore built a diagnostic model that can be used before microbiological test results are known.
METHODS: We included 659 individuals aged [Formula: see text] years with suspected brain infections from a prospective observational study conducted in Vietnam. We fitted a logistic regression diagnostic model for TBM status, with unknown values estimated via a latent class model on three mycobacterial tests: Ziehl-Neelsen smear, Mycobacterial culture, and GeneXpert. We additionally re-evaluated mycobacterial test performance, estimated individual mycobacillary burden, and quantified the reduction in TBM risk after confirmatory tests were negative. We also fitted a simplified model and developed a scoring table for early screening. All models were compared and validated internally.
RESULTS: Participants with HIV, miliary TB, long symptom duration, and high cerebrospinal fluid (CSF) lymphocyte count were more likely to have TBM. HIV and higher CSF protein were associated with higher mycobacillary burden. In the simplified model, HIV infection, clinical symptoms with long duration, and clinical or radiological evidence of extra-neural TB were associated with TBM At the cutpoints based on Youden\'s Index, the sensitivity and specificity in diagnosing TBM for our full and simplified models were 86.0% and 79.0%, and 88.0% and 75.0% respectively.
CONCLUSIONS: Our diagnostic model shows reliable performance and can be developed as a decision assistant for clinicians to detect patients at high risk of TBM. Diagnosis of tuberculous meningitis is hampered by the lack of gold standard. We developed a diagnostic model using latent class analysis, combining confirmatory test results and risk factors. Models were accurate, well-calibrated, and can support both clinical practice and research.