Abstract
Tuberculous meningitis (TBM) is the most severe form of extrapulmonary tuberculosis. We developed and validated prognostic models for 9-month mortality in adults with TBM, with or without human immunodeficiency virus (HIV) infection. We included 1699 subjects from 4 randomized clinical trials and 1 prospective observational study conducted at 2 major referral hospitals in Southern Vietnam from 2001-2015. Modeling was based on multivariable Cox proportional hazards regression. The final prognostic models were validated internally and temporally and were displayed using nomograms and a Web-based app (https://thaole.shinyapps.io/tbmapp/). 951 HIV-uninfected and 748 HIV-infected subjects with TBM were included; 219 of 951 (23.0%) and 384 of 748 (51.3%) died during 9-month follow-up. Common predictors for increased mortality in both populations were higher Medical Research Council (MRC) disease severity grade and lower cerebrospinal fluid lymphocyte cell count. In HIV-uninfected subjects, older age, previous tuberculosis, not receiving adjunctive dexamethasone, and focal neurological signs were additional risk factors; in HIV-infected subjects, lower weight, lower peripheral blood CD4 cell count, and abnormal plasma sodium were additional risk factors. The areas under the receiver operating characteristic curves (AUCs) for the final prognostic models were 0.77 (HIV-uninfected population) and 0.78 (HIV-infected population), demonstrating better discrimination than the MRC grade (AUC, 0.66 and 0.70) or Glasgow Coma Scale score (AUC, 0.68 and 0.71) alone. The developed models showed good performance and could be used in clinical practice to assist physicians in identifying patients with TBM at high risk of death and with increased need of supportive care.
Highlights
Tuberculous meningitis (TBM) accounted for around 1-5% of the 10.4 million new tuberculosis cases in 2015 and is the most severe manifestation of the disease, killing or disabling around half of all sufferers [1]
TBM is especially common in children and those infected with human immunodeficiency virus (HIV), in whom outcomes are poor [2]
Compared with HIV-uninfected subjects, those infected with HIV tended to be younger, were more frequently male (85.6% male vs. 62.3% male) and diagnosed with Medical Research Council (MRC) grade III (25.6% vs. 18.5%)
Summary
Tuberculous meningitis (TBM) accounted for around 1-5% of the 10.4 million new tuberculosis cases in 2015 and is the most severe manifestation of the disease, killing or disabling around half of all sufferers [1]. The primary objective of this study was to develop and validate novel robust prognostic models for 9month mortality in adult TBM patients with and without HIV co-infection. The models were based on a large dataset of 1699 subjects (951 HIV-uninfected, 748 HIV-infected) enrolled in four randomized controlled trials and one prospective cohort study conducted in Vietnam. We developed and validated prognostic models for 9-month mortality in HIV-uninfected and HIVinfected adults with TBM. The areas under the receiver operating characteristic curves (AUCs) for the final prognostic models were 0.77 (HIV-uninfected population) and 0.78 (HIV-infected population), demonstrating markedly better discrimination than the MRC grade (AUC 0.66 and 0.70) or the Glasgow Coma Score (AUC 0.68 and 0.71) alone.
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