Treatment Outcomes in Adult Tuberculous Meningitis: A Systematic Review and Meta-analysis

Abstract

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 I ² 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 (I ² > 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 I ² 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.

Keywords: meta-analysis; mortality; neurological sequelae; systematic review; tuberculous meningitis.

Figure 1.

Flow diagram of the study selection process.

Figure 2.

Tuberculous meningitis mortality by country. Pooled mortality for tuberculous meningitis by country. Mortality for countries with only 1 study reflect the reported mortality for that 1 study.

Figure 3.

Tuberculous meningitis mortality by outcome reporting time point. Forest plots depicting mortality due to tuberculous meningitis at 3, 6, and 12 months. One study was excluded because the outcome time point was not reported.

Figure 4.

Tuberculous meningitis mortality by HIV status. Forest plot depicting mortality due to tuberculous meningitis stratified by HIV status. HIV status explains a significant amount of the heterogeneity in tuberculous meningitis mortality (P < .01).