Whole blood mycobacterial growth assays for assessing human tuberculosis susceptibility: a systematic review and meta-analysis
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Published version
Author(s)
Bok, Jeroen
Hofland, Regina
Evans, Carlton
Type
Journal Article
Abstract
Background. Whole blood mycobacterial growth assays (WBMGA) quantify mycobacterial growth in fresh blood samples and may have potential for assessing tuberculosis vaccines and identifying individuals at risk of tuberculosis. We evaluated the evidence for the underlying assumption that in vitro WBMGA results can predict in vivo tuberculosis susceptibility. Methods. A systematic search was done for studies assessing associations between WBMGA results and tuberculosis susceptibility. Meta-analyses were performed for eligible studies by calculating population-weighted averages. Results. No studies directly assessed whether WBMGA results predicted tuberculosis susceptibility. 15 studies assessed associations between WBMGA results and proven correlates of tuberculosis susceptibility, which we divided in two categories. Firstly, WBMGA associations with factors known to reduce tuberculosis susceptibility was statistically significant in all 8 studies of: BCG vaccination; vitamin D supplementation; altitude; and HIV-negativity/therapy. Secondly, WBMGA associations with probable correlates of tuberculosis susceptibility was statistically significant in 3 studies of tuberculosis disease, in a parasitism study and in2 of the 5 studies of latent tuberculosis infection. Meta-analyses for associations between WBMGA results and BCG vaccination, tuberculosis infection, tuberculosis disease and HIV infection revealed consistent effects. There was considerable methodological heterogeneity. Conclusions. T he study results generally showed significant associations between WBMGA results and correlates of tuberculosis susceptibility. However, no study directly assessed whether WBMGA results predicted actual susceptibility to tuberculosis infection or disease. We recommend optimization and standardization of WBMGA methodology and prospective studies to determine whether WBMGA predict susceptibility to tuberculosis disease.
Date Issued
2021-05-11
Date Acceptance
2021-03-08
Citation
Frontiers in Immunology, 2021, 12
ISSN
1664-3224
Publisher
Frontiers Media
Journal / Book Title
Frontiers in Immunology
Volume
12
Copyright Statement
© 2021 Bok, Hofland and Evans. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
License URL
Sponsor
Sir Halley Stewart Trust
Wellcome Trust
Wellcome Trust
Wellcome Trust
Wellcome Trust
Medical Research Council (MRC)
Wellcome Trust
Wellcome Trust
Medical Research Council (MRC)
Grant Number
103548/103356
070005/Z/02/Z
076340/Z/05/Z
076078/Z/04/Z
100693/Z/12/Z
MR/K007467/1
097816/Z/11/A
105788/Z/14/Z
EP/V520354/1
Subjects
Science & Technology
Life Sciences & Biomedicine
Immunology
tuberculosis
mycobacterial growth assay
mycobacterial growth inhibition assay
MGIA
susceptibility
risk
INHIBITION
RESPONSES
IMMUNITY
MGIA
mycobacterial growth assay
mycobacterial growth inhibition assay
risk
susceptibility
tuberculosis
1107 Immunology
1108 Medical Microbiology
Publication Status
Published
Article Number
ARTN 641082