Estimating the global burden of viable Mycobacterium tuberculosis infection: A mathematical modelling study

BACKGROUND: Estimating the proportion of individuals currently infected with Mycobacterium tuberculosis (Mtb) is key for informing global health policies. Although a substantial portion of the global population exhibit tuberculous immunoreactivity, not all have a viable Mtb infection. Moreover, individuals with recent infections are at a higher risk of developing tuberculosis (TB). Here, we present estimates of the global burden of viable Mtb infection, using new insights into the natural history of TB. METHODS AND FINDINGS: We constructed country-specific trends in annual risk of infection considering estimates of TB burden, immunoreactivity reversion, and age-specific mixing. We applied these trends to a deterministic mathematical model incorporating reinfection and self-clearance to estimate recent (within 2 years) and total viable Mtb infections. Empirical data on self-clearance are limited, so rates were informed by modelling estimates. In 2022, we estimated that 133.7 million people (95% uncertainty interval [UI]: 104.0, 171.1) had a recent Mtb infection, representing 1.7% (95% UI: 1.3, 2.2) of the global population. In total, 288.9 million people (95% UI: 242.2, 342.7)-or 3.7% (95% UI: 3.1, 4.3) globally-were estimated to harbour a viable Mtb infection. Among those recently infected, 12.0% (95% UI: 11.4, 12.7) were children under 15 years of age. Most recent infections were found in the World Health Organization regions of South-East Asia (49.0%; 95% UI: 37.2, 62.4), the Western Pacific (19.7%; 95% UI: 12.6, 30.5), and Africa (17.9%; 95% UI: 12.9, 24.1). India, Indonesia, and China had the highest burden, with 39.1 million (95% UI: 18.0, 73.6), 12.0 million (95% UI: 5.8, 22.9), and 11.2 million (95% UI: 5.0, 25.5) people, respectively, recently infected with Mtb. Sensitivity analyses of varying self-clearance scenarios showed significant changes in global estimates of viable Mtb infection, particularly in total burden, with lower self-clearance rates. Overall uncertainty in the estimates was considerable, reflecting limitations in the underlying data informing key model parameters. CONCLUSIONS: Our findings offer global burden estimates of viable Mtb infection and reveal a sizable population recently infected with Mtb and at high risk of progression to disease. New diagnostic tools that can detect individuals with viable Mtb-particularly those who would benefit from TB preventive therapy-are urgently needed.