In 2021, there were ∼1.4 million and 187 000 TB deaths in the HIV-negative population and PLHIV, respectively [1]. The estimated number of global TB deaths had fallen by 30% and 69% during the two decades preceding 2019 in the HIV-negative population and PLHIV, respectively [1, 6]. For PLHIV, this progress primarily related to massive distribution of ART and implementation of HIV preventive measures, along with intensified screening for TB among PLHIV [25, 26]. Between 2019 and 2021, the estimated number of TB deaths rose from 1.4 to 1.6 million (the same number of deaths recorded in 2017) [1]. The End TB Strategy set the target of a 35% reduction in TB mortality between 2015 and 2020 in 2021, only a 5.9% decline has been achieved. Among the HIV-negative population, men, women and children (15 years old) accounted for 54%, 32% and 14%, respectively, of the estimated global TB deaths in 2021 [1]. In the HIV-negative population, estimated TB mortality in men was highest in those aged ⩾35 years. In contrast, estimated TB mortality among HIV-negative women is highest between the age groups ranging from birth to 24 years [1]. This proportion of childhood deaths is higher than the 11% of estimated cases accounted for by children, indicating difficulties in TB diagnosis and treatment in children that result in disproportionate mortality rates [1]. The South-East Asian and African regions account for 82% of the total estimated TB mortality among the HIV-negative population and 86% of estimated TB deaths among PLHIV [1]. However, it is important to note that nearly all TB mortality estimates in the African region rely heavily upon TB incidence estimates, which may be subject to underdiagnosis, case underreporting and other biases. MDR-TB Drug resistance is a major threat to TB care and control. TB that does not respond to both rifampicin and isoniazid is referred to as MDR-TB TB that does not respond to rifampicin is referred to as RR-TB. Globally, there were an estimated 450 000 incident cases of MDR/RR-TB in 2021 [1]. That is 13% less than 2015, but 3.1% more than 2020 [1]. This represents 3.6% of estimated new TB cases, whereas the proportion among previously treated TB cases was 18%. In addition to person-to-person transmission, TB drug resistance is the result of poor TB management [27–29]. Inappropriate treatment regimens, reduced drug quality (due to low-storage conditions) and poor treatment adherence can result in selection and spread of resistant M. tuberculosis mutants, leading to an increase in drug resistance [28]. The WHO European region has the highest estimated proportion of MDR/RR-TB among new and previously treated TB cases (26% and 57%, respectively) [1]. TB treatment coverage and outcomes With treatment, most people who develop TB can be cured. The End TB Strategy target is minimal treatment coverage of 90% by 2025 [4]. WHO treatment coverage is approximated as the number of people reported with TB divided by estimated incidence this will therefore exclude all unreported cases on treatment and include all reported cases off treatment. Over the last few years, the global treatment coverage (for both DR-TB and drug-susceptible TB) has shifted considerably, from 72% in 2019, to 59% in 2020, and 61% in 2021. For MDR/RR-TB the coverage levels are much lower, with an estimated one in three people developing MDR/ RR-TB on treatment [1]. Approximately 70% of the gap in estimated incidence and treatment 22 https://doi.org/10.1183/2312508X.10023922 ERS MONOGRAPH |THE CHALLENGE OF TB IN THE 21ST CENTURY