Background. There is substantial variation in the reported treatment outcomes for adult tuberculous meningitis (TBM). Data on survival and neurological disability by continent and HIV serostatus are scarce. Methods. We performed a systematic review and meta-analysis to characterize treatment outcomes for adult TBM. Following a systematic literature search (MEDLINE and EMBASE), studies underwent duplicate screening by independent reviewers in 2 stages to assess eligibility for inclusion. Two independent reviewers extracted data from included studies. We employed a random effects model for all meta-analyses. We evaluated heterogeneity by the I2 statistic. Results. We assessed 2197 records for eligibility; 39 primary research articles met our inclusion criteria, reporting on treatment outcomes for 5752 adults with TBM. The commonest reported outcome measure was 6-month mortality. Pooled 6-month mortality was 24% and showed significant heterogeneity (I2 > 95%; P <.01). Mortality ranged from 2% to 67% in Asian studies and from 23% to 80% in Sub-Saharan African studies. Mortality was significantly worse in HIV-positive adults at 57% (95% CI, 48%-67%), compared with 16% (95% CI, 10%-24%) in HIV-negative adults (P <.01). Physical disability was reported in 32% (95% CI, 22%-43%) of adult TBM survivors. There was considerable heterogeneity between studies in all meta-analyses, with I2 statistics consistently >50%. Conclusions. Mortality in adult TBM is high and varies considerably by continent and HIV status. The highest mortality is among HIV-positive adults in Sub-Saharan Africa. Standardized reporting of treatment outcomes will be essential to improve future data quality and increase potential for data sharing, meta-analyses, and facilitating multicenter tuberculosis research to improve outcomes.
Bibliographical noteFunding Information:
We thank clinical librarian Tom Roper (Brighton and Sussex University Hospitals NHS Trust) for his assistance with developing our search strategy. Financial support. This work was supported by the Fogarty International Center, National Institutes of Health, USA (R01NS086312, D43TW009345). Authors A.M.S., K.E., M.R., L.T., and D.R.B. are supported by the Fogarty International Center at the National Institutes of Health.
The Fogarty International Center of the National Institutes of Health provided funding fellowship support to the lead author of the study. The funders had no role in the study design, data collection, data analysis, data interpretation, or writing of the report. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.
© TheAuthor(s)2020.PublishedbyOxfordUniversityPressonbehalfofInfectiousDiseasesSociety of America. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
- Neurological sequelae
- Systematic review
- Tuberculous meningitis