LSTM Home > LSTM Research > LSTM Online Archive

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

Gordon, Stephen ORCID:, Sichone, Simon, Chirwa, Anthony E., Hazenberg, Phoebe, Kafuko, Zacharia, Ferreira, Daniela ORCID:, Flynn, Joanne, Fortune, Sarah, Balasingam, Shobana, Biagini, Giancarlo ORCID:, McShane, Helen, Mwandumba, Henry ORCID:, Jambo, Kondwani ORCID:, Dedha, Keertan, Raj Sharma, Nimisha, Robertson, Brian D., Walker, Naomi ORCID: and Morton, Ben ORCID: (2023) '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, p. 71.

9ac806b2-2a95-449d-8d2d-42524c33c015_18767_-_ben_morton_(2).pdf - Published Version
Available under License Creative Commons Attribution.

Download (1MB) | Preview


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 3rd 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.

Item Type: Article
Subjects: WA Public Health > WA 20.5 Research (General)
WF Respiratory System > WF 20 Research (General)
WF Respiratory System > Tuberculosis > WF 200 Tuberculosis (General)
Faculty: Department: Biological Sciences > Department of Tropical Disease Biology
Clinical Sciences & International Health > Clinical Sciences Department
Digital Object Identifer (DOI):
Depositing User: Rachel Dominguez
Date Deposited: 21 Feb 2023 15:29
Last Modified: 18 May 2023 10:22


View details

Actions (login required)

Edit Item Edit Item