Implications of subclinical tuberculosis for vaccine trial design and global effect

Gavin J Churchyard; Rein M G J Houben; Katherine Fielding; Andrew L Fiore-Gartland; Hanif Esmail; Alison D Grant; Molebogeng X Rangaka; Marcel Behr; Alberto L Garcia-Basteiro; Emily B Wong; Mark Hatherill; Vidya Mave; Alemnew F Dagnew; Alexander C Schmidt; Willem A Hanekom; Frank Cobelens; Richard G White

doi:10.1016/S2666-5247(24)00127-7

Implications of subclinical tuberculosis for vaccine trial design and global effect

Lancet Microbe. 2024 Oct;5(10):100895. doi: 10.1016/S2666-5247(24)00127-7. Epub 2024 Jul 1.

Authors

Gavin J Churchyard¹, Rein M G J Houben², Katherine Fielding³, Andrew L Fiore-Gartland⁴, Hanif Esmail⁵, Alison D Grant⁶, Molebogeng X Rangaka⁷, Marcel Behr⁸, Alberto L Garcia-Basteiro⁹, Emily B Wong¹⁰, Mark Hatherill¹¹, Vidya Mave¹², Alemnew F Dagnew¹³, Alexander C Schmidt¹³, Willem A Hanekom¹⁴, Frank Cobelens¹⁵, Richard G White²

Affiliations

¹ Aurum Institute NPC, Houghton, Parktown, South Africa; Department of Medicine, Vanderbilt University, Nashville, TN, USA; School of Public Health, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa. Electronic address: gchurchyard@auruminstitute.org.
² Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK; TB Modelling Group, TB Centre, London School of Hygiene & Tropical Medicine, London, UK.
³ Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK.
⁴ University of Washington, Seattle, WA, USA.
⁵ MRC Clinical Trials Unit, University College London, London, UK; WHO Collaborating Centre for TB Research and Innovation, Institute for Global Health, University College London, London, UK.
⁶ TB Centre, London School of Hygiene & Tropical Medicine, London, UK; Department of Clinical Research, London School of Hygiene & Tropical Medicine, London, UK; Africa Health Research Institute, KwaZulu-Natal, Durban, South Africa.
⁷ MRC Clinical Trials Unit, University College London, London, UK; CIDRI-AFRICA, School of Public Health, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
⁸ McGill International TB Centre, McGill University, Montreal, QC, Canada.
⁹ ISGlobal, Hospital Clínic - Universitat de Barcelona, Barcelona, Spain; Centro de Investigação em Saúde de Manhiça (CISM), Maputo, Mozambique; Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFECT), Barcelona, Spain.
¹⁰ Africa Health Research Institute, KwaZulu-Natal, Durban, South Africa; Division of Infectious Diseases, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
¹¹ South African Tuberculosis Vaccine Initiative, Department of Pathology and Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
¹² Byramjee-Jeejeebhoy Government Medical College, Johns Hopkins University Clinical Research Site, Pune, India.
¹³ Gates Medical Research Institute, Cambridge, MA, USA.
¹⁴ Division of Infection and Immunity, University College London, London, UK; Africa Health Research Institute, KwaZulu-Natal, Durban, South Africa.
¹⁵ Department of Global Health and Amsterdam Institute for Global Health and Development, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Netherlands.

Abstract

Tuberculosis is a leading cause of death from an infectious agent globally. Infectious subclinical tuberculosis accounts for almost half of all tuberculosis cases in national tuberculosis prevalence surveys, and possibly contributes to transmission and might be associated with morbidity. Modelling studies suggest that new tuberculosis vaccines could have substantial health and economic effects, partly based on the assumptions made regarding subclinical tuberculosis. Evaluating the efficacy of prevention of disease tuberculosis vaccines intended for preventing both clinical and subclinical tuberculosis is a priority. Incorporation of subclinical tuberculosis as a composite endpoint in tuberculosis vaccine trials can help to reduce the sample size and duration of follow-up and to evaluate the efficacy of tuberculosis vaccines in preventing clinical and subclinical tuberculosis. Several design options with various benefits, limitations, and ethical considerations are possible in this regard, which would allow for the generation of the evidence needed to estimate the positive global effects of tuberculosis vaccine trials, in addition to informing policy and vaccination strategies.

Publication types

Review

MeSH terms

Clinical Trials as Topic*
Global Health
Humans
Mycobacterium tuberculosis / immunology
Research Design
Tuberculosis Vaccines* / administration & dosage
Tuberculosis Vaccines* / therapeutic use
Tuberculosis* / epidemiology
Tuberculosis* / immunology
Tuberculosis* / prevention & control
Vaccination

Substances

Tuberculosis Vaccines

Grants and funding

UM1 AI154463/AI/NIAID NIH HHS/United States