Treatment outcomes in adult tuberculous meningitis: a systematic review and meta-analysis

Abstract

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 two 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 2,197 records for eligibility; 39 primary research articles met our inclusion criteria reporting on treatment outcomes for 5,752 adults with TBM. The commonest reported outcome measure was six-month mortality. Pooled six-month mortality was 24% and showed significant heterogeneity (I2 >95%; p<0·01). 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<0·01). 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 amongst 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 multi-center tuberculosis research to improve outcomes.