Men, women and children of all ages are susceptible to TB. However, in 2021, men accounted for the majority (56.5%) of TB cases, and in 2019, the age-standardised mortality rate was twice as large for HIV-negative men as for HIV-negative women in 107 countries [7]. Women and children (aged 15 years) accounted for 32.5% and 11% of TB cases, respectively [1]. The greater proportion of TB amongst men is consistent with the larger male/female ratios reported in national TB surveys. This could be related to differences in human biology, diagnostics, reporting or access to and use of TB services [1, 9–11]. However, more deaths and incident cases occur among HIV-positive women than HIV-positive men [7]. A likely explanation is the larger contribution of unsafe sex and partner violence in high HIV-endemic countries [7]. Among men, global estimated TB incidence is highest within the 25–54 years age group. Among adult women, those of reproductive age (aged 15–34 years) are most affected by TB [1]. A recent systematic review estimated a TB infection prevalence during pregnancy of 30–34% in high-burden settings [12]. Pregnancy has also been shown to increase the risk of TB infection or progression to TB [12, 13]. TB during pregnancy is associated with an increased risk of adverse outcomes for both mother and child [14]. Early diagnosis and treatment are essential to reducing TB-related maternal and neonatal mortality [15]. TB incidence estimates include both new TB episodes and episodes of relapse after treatment both are referred to as incident TB cases. New and relapse patients accounted for 96% of all TB notifications in 2021. There are large differences between the yearly incidence estimates and the number of new and relapse case notifications (figure 2a) these differences reflect the proportion of people missed by the healthcare system, as well as under-notification of diagnosed patients and those commencing TB treatment. Four countries (India, Indonesia, the Philippines and Pakistan) accounted for over half of the gap between case notifications and estimated TB incidence [1]. The global proportion of new and relapse TB patients who were diagnosed with PTB and EPTB was 83% and 17%, respectively, in 2021. Approximately 5.3 million people worldwide were diagnosed with PTB in 2021, of which 3.34 million (63%) were bacteriologically confirmed. This was a significant rise on the almost-steady 57% of diagnosed PTB cases with bacteriological confirmation in 2010–2020 [1, 16, 17]. These proportions were largest in the American region (79%) and lowest in the Western Pacific region (56%). There is considerable 250 300 200 100 125 150 75 50 30 0 2021 2020 2019 2018 2017 2010 2011 2012 2013 2014 2015 2016 Year African South-East Asian Global Eastern Mediterranean Western Pacific European Americas FIGURE 1 Incidence rate per 100 000 population during 2010–2021 in each of the WHO regions. Data from [8]. 20 https://doi.org/10.1183/2312508X.10023922 ERS MONOGRAPH |THE CHALLENGE OF TB IN THE 21ST CENTURY Rate per 100 000 population, log scale