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

Anna M. Stadelman; Jayne Ellis; Thomas H.A. Samuels; Ernest Mutengesa; Joanna Dobbin; Kenneth Ssebambulidde; Morris K. Rutakingirwa; Lillian Tugume; David R. Boulware; Daniel Grint; Fiona V. Cresswell

doi:10.1093/ofid/ofaa257

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

Anna M. Stadelman, Jayne Ellis, Thomas H.A. Samuels, Ernest Mutengesa, Joanna Dobbin, Kenneth Ssebambulidde, Morris K. Rutakingirwa, Lillian Tugume, David R. Boulware, Daniel Grint, Fiona V. Cresswell

Research output: Contribution to journal › Review article › peer-review

20 Scopus citations

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 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.

Original language	English (US)
Article number	ofaa257
Journal	Open Forum Infectious Diseases
Volume	7
Issue number	8
DOIs	https://doi.org/10.1093/ofid/ofaa257
State	Published - Aug 1 2020

Bibliographical note

Funding 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.

Funding Information:
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.

Publisher Copyright:
© 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.

Keywords

Meta-analysis
Mortality
Neurological sequelae
Systematic review
Tuberculous meningitis

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1093/ofid/ofaa257

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title = "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 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.",

keywords = "Meta-analysis, Mortality, Neurological sequelae, Systematic review, Tuberculous meningitis",

author = "Stadelman, {Anna M.} and Jayne Ellis and Samuels, {Thomas H.A.} and Ernest Mutengesa and Joanna Dobbin and Kenneth Ssebambulidde and Rutakingirwa, {Morris K.} and Lillian Tugume and Boulware, {David R.} and Daniel Grint and Cresswell, {Fiona V.}",

note = "Funding 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. Funding Information: 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. Publisher Copyright: {\textcopyright} 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.",

year = "2020",

month = aug,

day = "1",

doi = "10.1093/ofid/ofaa257",

language = "English (US)",

volume = "7",

journal = "Open Forum Infectious Diseases",

issn = "2328-8957",

publisher = "Oxford University Press",

number = "8",

}

TY - JOUR

T1 - Treatment outcomes in adult tuberculous meningitis

T2 - A systematic review and meta-analysis

AU - Stadelman, Anna M.

AU - Ellis, Jayne

AU - Samuels, Thomas H.A.

AU - Mutengesa, Ernest

AU - Dobbin, Joanna

AU - Ssebambulidde, Kenneth

AU - Rutakingirwa, Morris K.

AU - Tugume, Lillian

AU - Boulware, David R.

AU - Grint, Daniel

AU - Cresswell, Fiona V.

N1 - Funding 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. Funding Information: 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. Publisher Copyright: © 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.

PY - 2020/8/1

Y1 - 2020/8/1

N2 - 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.

AB - 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.

KW - Meta-analysis

KW - Mortality

KW - Neurological sequelae

KW - Systematic review

KW - Tuberculous meningitis

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U2 - 10.1093/ofid/ofaa257

DO - 10.1093/ofid/ofaa257

M3 - Review article

C2 - 32818138

AN - SCOPUS:85092089868

SN - 2328-8957

VL - 7

JO - Open Forum Infectious Diseases

JF - Open Forum Infectious Diseases

IS - 8

M1 - ofaa257

ER -

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

Abstract

Bibliographical note

Keywords

UN SDGs

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