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
Wellcome Open Research, vol. 8, pp. 71
Abstract
Background: 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. Methods: 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 rd 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. Results: 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 Mycobacteria tuberculosis is the most tantalising prospect of discovery breakthrough. Conclusions: 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. Registration: PROSPERO ( CRD42022302785 ; 21 January 2022).
Authors 18
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University of Liverpool · Liverpool School of Tropical Medicine · Malawi-Liverpool-Wellcome Trust Clinical Research Programme · Leiden University Medical Center · University of Edinburgh
Affiliation as printed
Blantyre Malawi Liverpool Wellcome Trust Clinical Research Programme
Liverpool L3 5QA Liverpool School of Tropical Medicine
. Meta Roestenberg, Leiden University Medical Center, Leiden, The Netherlands
. University of Edinburgh, Edinburgh, UK
Liverpool School of Tropical Medicine, Liverpool, L3 5QA, UK
Malawi Liverpool Wellcome Trust Clinical Research Programme, Blantyre, Malawi
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Malawi-Liverpool-Wellcome Trust Clinical Research Programme · University of Edinburgh
Affiliation as printed
Blantyre Malawi Liverpool Wellcome Trust Clinical Research Programme
. University of Edinburgh, Edinburgh, UK
Malawi Liverpool Wellcome Trust Clinical Research Programme, Blantyre, Malawi
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Malawi-Liverpool-Wellcome Trust Clinical Research Programme · University of Edinburgh
Affiliation as printed
Blantyre Malawi Liverpool Wellcome Trust Clinical Research Programme
. University of Edinburgh, Edinburgh, UK
Malawi Liverpool Wellcome Trust Clinical Research Programme, Blantyre, Malawi
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University of Liverpool · Liverpool School of Tropical Medicine · Leiden University Medical Center
Affiliation as printed
Liverpool L3 5QA Liverpool School of Tropical Medicine
. Meta Roestenberg, Leiden University Medical Center, Leiden, The Netherlands
Liverpool School of Tropical Medicine, Liverpool, L3 5QA, UK
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Affiliation as printed
1Day Africa Lusaka Province 1Day Sooner
1Day Africa, 1Day Sooner, Lusaka Province, Zambia
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University of Liverpool · Liverpool School of Tropical Medicine · Leiden University Medical Center · University of Oxford
Affiliation as printed
Liverpool L3 5QA Liverpool School of Tropical Medicine
Oxford Vaccine Group Oxford University of Oxford
. Meta Roestenberg, Leiden University Medical Center, Leiden, The Netherlands
Liverpool School of Tropical Medicine, Liverpool, L3 5QA, UK
Oxford Vaccine Group, University of Oxford, Oxford, UK
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Affiliation as printed
Centre for Vaccine Research Pittsburgh Pennsylvania University of Pittsburgh
Centre for Vaccine Research, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
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Affiliation as printed
Harvard T.H. Chan School of Public Health Boston Massachusetts Harvard University
Harvard T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts, USA
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Affiliation as printed
London Wellcome Trust
Wellcome Trust, London, UK
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University of Liverpool · Liverpool School of Tropical Medicine · Leiden University Medical Center
Affiliation as printed
Liverpool L3 5QA Liverpool School of Tropical Medicine
. Meta Roestenberg, Leiden University Medical Center, Leiden, The Netherlands
Liverpool School of Tropical Medicine, Liverpool, L3 5QA, UK
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University of Oxford · Jenner Institute
Affiliation as printed
Oxford The Jenner Institute, University of Oxford
The Jenner Institute, University of Oxford, Oxford, UK
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University of Liverpool · Liverpool School of Tropical Medicine · Malawi-Liverpool-Wellcome Trust Clinical Research Programme · Leiden University Medical Center · University of Edinburgh
Affiliation as printed
Blantyre Malawi Liverpool Wellcome Trust Clinical Research Programme
Liverpool L3 5QA Liverpool School of Tropical Medicine
. Meta Roestenberg, Leiden University Medical Center, Leiden, The Netherlands
. University of Edinburgh, Edinburgh, UK
Liverpool School of Tropical Medicine, Liverpool, L3 5QA, UK
Malawi Liverpool Wellcome Trust Clinical Research Programme, Blantyre, Malawi
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University of Liverpool · Liverpool School of Tropical Medicine · Malawi-Liverpool-Wellcome Trust Clinical Research Programme · Leiden University Medical Center · University of Edinburgh
Affiliation as printed
Blantyre Malawi Liverpool Wellcome Trust Clinical Research Programme
Liverpool L3 5QA Liverpool School of Tropical Medicine
. Meta Roestenberg, Leiden University Medical Center, Leiden, The Netherlands
. University of Edinburgh, Edinburgh, UK
Liverpool School of Tropical Medicine, Liverpool, L3 5QA, UK
Malawi Liverpool Wellcome Trust Clinical Research Programme, Blantyre, Malawi
-
Affiliation as printed
Cape Town University of Cape Town
University of Cape Town, Cape Town, South Africa
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Affiliation as printed
London Wellcome Trust
Wellcome Trust, London, UK
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Affiliation as printed
London Imperial College London
Imperial College London, London, UK
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University of Liverpool · Liverpool School of Tropical Medicine · Leiden University Medical Center
Affiliation as printed
Liverpool L3 5QA Liverpool School of Tropical Medicine
. Meta Roestenberg, Leiden University Medical Center, Leiden, The Netherlands
Liverpool School of Tropical Medicine, Liverpool, L3 5QA, UK
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University of Liverpool · Liverpool School of Tropical Medicine · Leiden University Medical Center
Affiliation as printed
Liverpool L3 5QA Liverpool School of Tropical Medicine
. Meta Roestenberg, Leiden University Medical Center, Leiden, The Netherlands
Liverpool School of Tropical Medicine, Liverpool, L3 5QA, UK
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