Prognostic models for 9-month mortality in tuberculous meningitis

Le Thi Phuong Thao, A. Dorothee Heemskerk, Ronald B. Geskus, Nguyen Thi Hoang Mai, Dang Thi Minh Ha, Tran Thi Hong Chau, Nguyen Hoan Phu, Nguyen Van Vinh Chau, Maxine Caws, Nguyen Huu Lan, Do Dang Anh Thu, Nguyen Thuy Thuong Thuong, Jeremy Day, Jeremy J. Farrar, M. Estee Torok, Nguyen Duc Bang, Guy E. Thwaites, Marcel Wolbers

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Abstract

Background. 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. Methods. 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 Webbased app (https://thaole.shinyapps.io/tbmapp/). Results. 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 HIVinfected 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. Conclusions. 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.

Original languageEnglish
Pages (from-to)523-532
Number of pages10
JournalClinical Infectious Diseases
Volume66
Issue number4
DOIs
Publication statusPublished - 15 Feb 2018
Externally publishedYes

Keywords

  • HIV
  • Mortality
  • Prognostic models
  • Tuberculous meningitis

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