variation among countries, following a general trend of lower rates of bacterial confirmation in low-income countries and higher rates in high-income countries, where there is increased access to and quality of diagnostic tests. In recent years, evidence has emerged of a new stage in the natural history of TB, called subclinical TB (defined in Box 1) [19–21]. Recent estimates show that ∼50% of individuals with bacteriological confirmation do not report TB-compatible symptoms [22, 23]. It remains uncertain how much subclinical TB cases contribute to global transmission and what implications this will have for TB prevention and treatment strategies [22, 24]. Mortality The WHO TB mortality estimates are produced using different sources, including vital registration data and mortality surveys when available, or by multiplying incidence estimates by case fatality rates (CFRs) (mostly in low- and middle-income countries). For PLHIV, the WHO mortality estimates are calculated using treatment-adjusted CFRs. Higher CFRs are applied to undiagnosed (and thus untreated) TB patients. BOX 1 Terminology definitions of TB and Mycobacterium tuberculosis infection, as defined by the latest WHO guidelines [18], and subclinical TB, as defined by the Stop TB Partnership [19] TB Clinical disease state resulting from M. tuberculosis infection it is associated with symptoms and can be clinically diagnosed or bacteriologically confirmed. TBI State of persistent immune response to stimulation of M. tuberculosis antigens with no evidence of clinical manifestation of TB disease. Subclinical TB State of persistent immune response to stimulation of M. tuberculosis antigens with no evidence of clinical manifestation of TB disease. A positive result to TST or IGRA is frequently used as a proxy of TBI. b) 7.5 7.0 6.5 6.0 5.5 2015 2017 2016 2018 2019 2020 2021 Year a) 15 10 5 2000 2010 2005 2015 2020 Year FIGURE 2 Trends in estimated case incidence (blue) and case notifications (black) of people newly diagnosed with TB in a) 2000–2021 and b) 2015–2021. The blue area represents the 95% uncertainty interval. The red area represents the period after the onset of the COVID-19 pandemic. Reproduced and modified from [8] with permission. https://doi.org/10.1183/2312508X.10023922 21 EPIDEMIOLOGY |R. VERSTRAETEN ET AL. Case notifications (millions)b) Case notifications (millions)a)