Practical considerations for a TB controlled human infection model (TB-CHIM); the case for TB-CHIM in Africa, a systematic review of the literature and report of 2 workshop discussions in UK and Malawi
File(s)
Author(s)
Type
Journal Article
Abstract
<ns4:p>
<ns4:bold>Background:</ns4:bold>
Tuberculosis (TB) remains a major challenge in many domains including diagnosis, pathogenesis, prevention, treatment, drug resistance and long-term protection of the public health by vaccination. A controlled human infection model (CHIM) could potentially facilitate breakthroughs in each of these domains but has so far been considered impossible owing to technical and safety concerns.
</ns4:p>
<ns4:p>
<ns4:bold>Methods:</ns4:bold>
A systematic review of mycobacterial human challenge studies was carried out to evaluate progress to date, best possible ways forward and challenges to be overcome. We searched MEDLINE (1946 to current) and CINAHL (1984 to current) databases; and Google Scholar to search citations in selected manuscripts. The final search was conducted 3
<ns4:sup>rd</ns4:sup>
February 2022. Inclusion criteria: adults ≥18 years old; administration of live mycobacteria; and interventional trials or cohort studies with immune and/or microbiological endpoints. Exclusion criteria: animal studies; studies with no primary data; no administration of live mycobacteria; retrospective cohort studies; case-series; and case-reports. Relevant tools (Cochrane Collaboration for RCTs and Newcastle-Ottawa Scale for non-randomised studies) were used to assess risk of bias and present a narrative synthesis of our findings.
</ns4:p>
<ns4:p>
<ns4:bold>Results:</ns4:bold>
The search identified 1,388 titles for review; of these 90 were reviewed for inclusion; and 27 were included. Of these, 15 were randomised controlled trials and 12 were prospective cohort studies. We focussed on administration route, challenge agent and dose administered for data extraction. Overall, BCG studies including fluorescent BCG show the most immediate utility, and genetically modified
<ns4:italic>Mycobacteria tuberculosis</ns4:italic>
is the most tantalising prospect of discovery breakthrough.
</ns4:p>
<ns4:p>
<ns4:bold>Conclusions:</ns4:bold>
The TB-CHIM development group met in 2019 and 2022 to consider the results of the systematic review, to hear presentations from many of the senior authors whose work had been reviewed and to consider best ways forward. This paper reports both the systematic review and the deliberations.
</ns4:p>
<ns4:p>
<ns4:bold>Registration:</ns4:bold>
PROSPERO (
<ns4:ext-link xmlns:ns5="http://www.w3.org/1999/xlink" ext-link-type="uri" ns5:href="https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022302785">CRD42022302785</ns4:ext-link>
; 21 January 2022).
</ns4:p>
<ns4:bold>Background:</ns4:bold>
Tuberculosis (TB) remains a major challenge in many domains including diagnosis, pathogenesis, prevention, treatment, drug resistance and long-term protection of the public health by vaccination. A controlled human infection model (CHIM) could potentially facilitate breakthroughs in each of these domains but has so far been considered impossible owing to technical and safety concerns.
</ns4:p>
<ns4:p>
<ns4:bold>Methods:</ns4:bold>
A systematic review of mycobacterial human challenge studies was carried out to evaluate progress to date, best possible ways forward and challenges to be overcome. We searched MEDLINE (1946 to current) and CINAHL (1984 to current) databases; and Google Scholar to search citations in selected manuscripts. The final search was conducted 3
<ns4:sup>rd</ns4:sup>
February 2022. Inclusion criteria: adults ≥18 years old; administration of live mycobacteria; and interventional trials or cohort studies with immune and/or microbiological endpoints. Exclusion criteria: animal studies; studies with no primary data; no administration of live mycobacteria; retrospective cohort studies; case-series; and case-reports. Relevant tools (Cochrane Collaboration for RCTs and Newcastle-Ottawa Scale for non-randomised studies) were used to assess risk of bias and present a narrative synthesis of our findings.
</ns4:p>
<ns4:p>
<ns4:bold>Results:</ns4:bold>
The search identified 1,388 titles for review; of these 90 were reviewed for inclusion; and 27 were included. Of these, 15 were randomised controlled trials and 12 were prospective cohort studies. We focussed on administration route, challenge agent and dose administered for data extraction. Overall, BCG studies including fluorescent BCG show the most immediate utility, and genetically modified
<ns4:italic>Mycobacteria tuberculosis</ns4:italic>
is the most tantalising prospect of discovery breakthrough.
</ns4:p>
<ns4:p>
<ns4:bold>Conclusions:</ns4:bold>
The TB-CHIM development group met in 2019 and 2022 to consider the results of the systematic review, to hear presentations from many of the senior authors whose work had been reviewed and to consider best ways forward. This paper reports both the systematic review and the deliberations.
</ns4:p>
<ns4:p>
<ns4:bold>Registration:</ns4:bold>
PROSPERO (
<ns4:ext-link xmlns:ns5="http://www.w3.org/1999/xlink" ext-link-type="uri" ns5:href="https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022302785">CRD42022302785</ns4:ext-link>
; 21 January 2022).
</ns4:p>
Date Issued
2023-02-10
Citation
Wellcome Open Research, 8, pp.71-71
Publisher
F1000 Research Ltd
Start Page
71
End Page
71
Journal / Book Title
Wellcome Open Research
Volume
8
Copyright Statement
© 2023 McCarthy J. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
License URL
Identifier
10.12688/wellcomeopenres.18767.1
Publication Status
Published online
Date Publish Online
2023-02-10