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The effect of new Mycobacterium tuberculosis infection on the sensitivity of prognostic TB signatures

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BACKGROUND: Tests that identify individuals at greatest risk of TB will allow more efficient targeting of preventive therapy. The WHO target product profile for such tests defines optimal sensitivity of 90% and minimum sensitivity of 75% for predicting incident TB. The CORTIS (Correlate of Risk Targeted Intervention Study) evaluated a blood transcriptomic signature (RISK11) for predicting incident TB in a high transmission setting. RISK11 is able to predict TB disease progression but optimal prognostic performance was limited to a 6-month horizon.

METHODS: Using a mathematical model, we estimated how subsequent Mycobacterium tuberculosis (MTB) infection may have contributed to the decline in sensitivity of RISK11. We calculated the effect at different RISK11 thresholds (60% and 26%) and for different assumptions about the risk of MTB infection.

RESULTS: Modelled sensitivity over 15 months, excluding new infection, was 28.7% (95% CI 12.3–74.1) compared to 25.0% (95% CI 12.7–45.9) observed in the trial. Modelled sensitivity exceeded the minimum criteria (>75%) over a 9-month horizon at the 60% threshold and over 12 months at the 26% threshold.

CONCLUSIONS: The effect of new infection on prognostic signature performance is likely to be small. Signatures such as RISK11 may be most useful in individuals, such as household contacts, where probable time of infection is known.

Keywords: biomarkers; modelling; preventive therapy; tuberculosis

Document Type: Research Article

Affiliations: 1: TB Modelling Group, TB Centre, Centre for Mathematical Modelling of Infectious Diseases, Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK 2: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA 3: South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, Division of Immunology, Department of Pathology, University of Cape Town, Observatory, South Africa

Publication date: December 1, 2021

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  • The International Journal of Tuberculosis and Lung Disease (IJTLD) is for clinical research and epidemiological studies on lung health, including articles on TB, TB-HIV and respiratory diseases such as COVID-19, asthma, COPD, child lung health and the hazards of tobacco and air pollution. Individuals and institutes can subscribe to the IJTLD online or in print – simply email us at [email protected] for details.

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