Characterising progression and regression patterns across the spectrum of tuberculosis: a multistate modelling approach
Year: 2026
Type: article
Study design: Observational Study
Abstract: BACKGROUND: The conceptualisation of tuberculosis has undergone a paradigm shift from binary states to a spectrum, resulting in the International Consensus for Early TB (ICE-TB) framework. This study aimed to use data from a prospective, observational cohort study and multistate modelling to address the lack of contemporary data to quantify movement between ICE-TB states. METHODS: ERASE-TB was a prospective, observational cohort study evaluating novel diagnostic tests for earlier detection of tuberculosis. Household contacts aged at least 10 years in Zimbabwe, Tanzania, and Mozambique were followed up 6-monthly for 12-24 months with comprehensive tuberculosis investigations at each visit. Those not diagnosed with prevalent tuberculosis, with state classification from at least two timepoints were included. ICE-TB states were defined by use of symptomatology, interferon gamma release assays, chest radiographs, and sputum microbiology. A Markov multistate model based on ICE-TB was applied with one initial state (Mycobacterium tuberculosis non-infection), two intermediate states (M tuberculosis infection and non-infectious disease [asymptomatic-symptomatic]), and one absorbing state (infectious disease [asymptomatic-symptomatic]). Transition probabilities were predicted. FINDINGS: 1789 (84·8%) of 2109 recruited household contacts were included. At enrolment, most (1000 [55·9%]) did not have M tuberculosis infection; 674 (37·7%) had M tuberculosis infection, and 115 (6·5%) had non-infectious disease. 34 people developed infectious disease (23 asymptomatic, 11 symptomatic). In the multistate model, the transition probabilities of progressing from M tuberculosis non-infection to M tuberculosis infection and M tuberculosis infection to non-infectious disease were 13% and 3% by month 12. For those in non-infectious disease, the probabilities of regression and progression by month 12 were 85% and 13%, respectively. INTERPRETATION: This study applied the ICE-TB framework to describe movement between states by use of contemporary, granular, longitudinal data. Although most people remained static over time, the non-infectious state was more dynamic, with most people regressing over time. FUNDING: European and Developing Countries Clinical Trials Partnership.
Source: The Lancet Global Health
Authors: Leyla Larsson, Claire J Calderwood, Claire J Calderwood, Edson T Marambire, Rishi K Gupta, Denise Banze, Alfred Mfinanga, Mishelle Mugava, Etienne Leroy-Terquem, Joseph Jacob, Daisuke Yamada, Francisco Trinchan Fernandez, Patrick Lungu, Anita Mesic, Celso Khosa, Tina Minja, Junior Mutsvangwa, Michael Lauseker, Kathrin Held, Norbert Heinrich, Katharina Kranzer, Norbert Heinrich, Ursula Panzner, Christof Geldmacher, Kathrin Held, Andrea Rachow, Friedrich Riess, Tejaswi Appalarowthu, Deepika Zende, Anna-Lisa Behnke, Lilian Tina Minja, Nyanda Elias Ntinginya, Issa Sabi, Alfred Mfinanga, Harrieth Mwambola, Lwithio Sudi, Bariki Mtafya, Emanuel Sichone, Doreen Pamba, Abisai Kisinda, Peter Towo, Lilian Njovu, Alice Shoo, Willyhelmina Olomi, Celso Khosa, Denise Floripes Banze, Nelson Tembe, Nadia Sitoe, Carla Madeira, Candido Azize, Celina Nhamuave, Sidonia Nhacubangane, Jorge Ribeiro, Junior Mutsvangwa, Edson Marambire, Fungai Kavenga, Tsitsi Bandason, Kuda Mutasa, Martha Chipinduro, Sandra Rukobo, Mishelle Mugava, Beauty Makamure, Forget Makoga, Katharina Kranzer, Claire Calderwood, Claire Calderwood, Hazel Dockrell, Leyla Larsson, Anna Shepherd, Gunilla Källenius, Christopher Sundling, Lindsay Zurba
Institutions: Institut für Infektions- und Tropenmedizin, Ludwig-Maximilians-Universität München, London School of Hygiene & Tropical Medicine, Biomedical Research and Training Institute, University College London, Instituto Nacional de Saúde, National Institute for Medical Research, East, Central and Southern Africa Health Community, Médecins Sans Frontières, Médecins Sans Frontières, Instituut voor Tropische Geneeskunde, Liverpool School of Tropical Medicine, Institut für Medizinische Informationsverarbeitung, Biometrie und Epidemiologie, LMU Klinikum, Fraunhofer Institute for Translational Medicine and Pharmacology, German Center for Infection Research
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $6,680
Funders: Deutsches Zentrum für Infektionsforschung, Wellcome Trust, Astellas European Foundation, Chan Zuckerberg Initiative, National Institute for Health and Care Research, University College London, Fondation pour la Recherche Médicale, Astellas Pharma, Astellas Foundation for Research on Metabolic Disorders, BMA Foundation for Medical Research, European and Developing Countries Clinical Trials Partnership
Awards: PRecision biomArker Guided MAnagement of TuberculosIs Contacts (PRAGMATIC), Multimorbidity in TB-affected households: evaluation of disease clustering and the acceptability and yield of integrated health screening in southern Africa, Enhancing the characterisation of early respiratory disease to improve population health, G7063735130
OpenAlex ID: W7129060437