Recent Developments in Tuberculous Meningitis Pathogenesis and Diagnostics.
Recent Developments in Tuberculous Meningitis Pathogenesis and Diagnostics.
复制标题
DOI：
10.12688/wellcomeopenres.15506.1
复制
发表时间：
2019-01-01
影响因子：
--
通讯作者：
Thuong, Nguyen Thuy Thuong
中科院分区：
文献类型：
--
作者：
Cresswell, Fiona V;Davis, Angharad G;Thuong, Nguyen Thuy Thuong
结核性脑膜炎（TBM）的发病机制尚不清楚，但当代分子生物学技术使我们对TBM的认识有所提高。例如，中性粒细胞似乎在TBM的免疫发病机制中起着重要作用，炎症的缺乏或过度都可能对TBM有害。此外，hiv相关免疫抑制的严重程度是炎症反应的重要决定因素；晚期免疫抑制患者（CD4+ t细胞计数150个/ μ l）。宿主遗传学也可能影响LT4AH基因型预测越南成年TBM患者炎症表型、类固醇反应性和生存率的结果。在印度尼西亚，脑脊液色氨酸水平是生存的一个预测因子，提示色氨酸代谢可能在TBM发病机制中起重要作用。这些不同的反应意味着我们必须考虑在TBM中采用“一刀切”的抗细菌或免疫调节治疗方法是否真的是最好的方法。当然，为了进行适当的治疗，必须对TBM进行早期和快速的诊断。诊断一直是一项挑战，但结核病诊断领域正在发展，使用GeneXpert MTB/Rif Ultra，现在可以在不到两小时的时间内达到至少70%的灵敏度。此外，先进的分子技术，如CRISPR-MTB和下一代宏基因组测序，可能为TBM诊断带来希望。基于宿主的生物标志物和特征在儿童和成人TBM中作为辅助生物标志物正在进一步评估，即使有改进的分子测定，病例仍然遗漏。更好地掌握宿主和病原体的行为可能导致改进诊断、靶向免疫治疗以及可能基于生物标志物的患者特异性治疗方案。
The pathogenesis of Tuberculous meningitis (TBM) is poorly understood, but contemporary molecular biology technologies have allowed for recent improvements in our understanding of TBM. For instance, neutrophils appear to play a significant role in the immunopathogenesis of TBM, and either a paucity or an excess of inflammation can be detrimental in TBM. Further, severity of HIV-associated immunosuppression is an important determinant of inflammatory response; patients with the advanced immunosuppression (CD4+ T-cell count of 150 cells/muL. Host genetics may also influence outcomes with LT4AH genotype predicting inflammatory phenotype, steroid responsiveness and survival in Vietnamese adults with TBM. Whist in Indonesia, CSF tryptophan level was a predictor of survival, suggesting tryptophan metabolism may be important in TBM pathogenesis. These varying responses mean that we must consider whether a "one-size-fits-all" approach to anti-bacillary or immunomodulatory treatment in TBM is truly the best way forward. Of course, to allow for proper treatment, early and rapid diagnosis of TBM must occur. Diagnosis has always been a challenge but the field of TB diagnosis is evolving, with sensitivities of at least 70% now possible in less than two hours with GeneXpert MTB/Rif Ultra. In addition, advanced molecular techniques such as CRISPR-MTB and metagenomic next generation sequencing may hold promise for TBM diagnosis. Host-based biomarkers and signatures are being further evaluated in childhood and adult TBM as adjunctive biomarkers as even with improved molecular assays, cases are still missed. A better grasp of host and pathogen behaviour may lead to improved diagnostics, targeted immunotherapy, and possibly biomarker-based, patient-specific treatment regimens.