growing political momentum to definitively address tuberculosis, could all make ending the pandemic within a generation more feasible than ever before. Moving forward with bold, comprehensive strategies Globally, the priority must be to deliver person-centred and family-centred services to all individuals with tuberculosis who present to care. This approach means ensuring that high-quality diagnostics, treatment, and prevention modalities are available to all, wherever they seek care. Improving quality of tuberculosis care in the private sector is crucial to end tuberculosis in high incidence countries such as India, the country with the highest tuberculosis burden. Modelling shows that optimising private sector engagement in India could avert 8 million deaths from tuberculosis between 2019 and 2045 (appendix p 3). In high drug-resistant tuberculosis burden countries, access to rapid drug susceptibility testing (DST) and second-line drugs is essential to success. In Moldova, where more than 25% of all tuberculosis cases are drug-resistant, improving access to DST and second-line drugs would reduce mortality from drug-resistant tuberculosis by 44% in the coming generation (appendix p 3). Secondly, tuberculosis programme budgets must increase to enable reaching these people and populations at high risk of tuberculosis. In Kenya, for example, where the proportions of HIV and tuberculosis coinfection are high, scaling up access to both antiretroviral therapy and tuberculosis preventive therapy can help save an additional 3 million lives over the next generation (appendix p 3). However, ultimately, the fight against tuberculosis will not be won unless countries also ensure that everyone, not just high-risk groups, can access essential health Key messages The Commission recommends five priority investments to achieve a tuberculosis-free world within a generation. These investments are designed to fulfil the mandate of the UN High Level Meeting on tuberculosis. In addition, they answer the question of how countries with high-burden tuberculosis and their development partners should target their future investments to ensure that ending tuberculosis is achievable. Invest first to ensure that high quality rapid diagnostics and treatment are provided to all individuals receiving care for tuberculosis, wherever they seek care This priority includes rapid drug susceptibility testing and second-line treatment for resistant forms of tuberculosis. Achieving universal, high-quality person-centred and family-centred care-including sustained improvement in the performance of private sector providers-usually should be the top policy and budget priority. Reach people and populations at high risk for tuberculosis (such as household and other close contacts of people with tuberculosis, and people with HIV) and bring them into care Active case-finding and treatment in high-risk populations demands adequate resources to reach and care for these populations. At the same time, reaching certain high-risk populations, such as people co-infec...

Background Routine services for tuberculosis (TB) are being disrupted by stringent lockdowns against the novel SARS-CoV-2 virus. We sought to estimate the potential long-term epidemiological impact of such disruptions on TB burden in high-burden countries, and how this negative impact could be mitigated. Methods We adapted mathematical models of TB transmission in three high-burden countries (India, Kenya and Ukraine) to incorporate lockdown-associated disruptions in the TB care cascade. The anticipated level of disruption reflected consensus from a rapid expert consultation. We modelled the impact of these disruptions on TB incidence and mortality over the next five years, and also considered potential interventions to curtail this impact. Findings Even temporary disruptions can cause long-term increases in TB incidence and mortality. If lockdown-related disruptions cause a temporary 50% reduction in TB transmission, we estimated that a 3-month suspension of TB services, followed by 10 months to restore to normal, would cause, over the next 5 years, an additional 1⋅19 million TB cases (Crl 1⋅06–1⋅33) and 361,000 TB deaths (CrI 333–394 thousand) in India, 24,700 (16,100–44,700) TB cases and 12,500 deaths (8.8–17.8 thousand) in Kenya, and 4,350 (826–6,540) cases and 1,340 deaths (815–1,980) in Ukraine. The principal driver of these adverse impacts is the accumulation of undetected TB during a lockdown. We demonstrate how long term increases in TB burden could be averted in the short term through supplementary “catch-up” TB case detection and treatment, once restrictions are eased. Interpretation Lockdown-related disruptions can cause long-lasting increases in TB burden, but these negative effects can be mitigated with rapid restoration of TB services, and targeted interventions that are implemented as soon as restrictions are lifted. Funding USAID and Stop TB Partnership

Background In the context of WHO's End TB strategy, there is a need to focus future control efforts on those interventions and innovations that would be most effective in accelerating declines in tuberculosis burden. Using a modelling approach to link the tuberculosis care cascade to transmission, we aimed to identify which improvements in the cascade would yield the greatest effect on incidence and mortality.Methods We engaged with national tuberculosis programmes in three country settings (India, Kenya, and Moldova) as illustrative examples of settings with a large private sector (India), a high HIV burden (Kenya), and a high burden of multidrug resistance (Moldova). We collated WHO country burden estimates, routine surveillance data, and tuberculosis prevalence surveys from 2011 (for India) and 2016 (for Kenya). Linking the tuberculosis care cascade to tuberculosis transmission using a mathematical model with Bayesian melding in each setting, we examined which cascade shortfalls would have the greatest effect on incidence and mortality, and how the cascade could be used to monitor future control efforts.Findings Modelling suggests that combined measures to strengthen the care cascade could reduce cumulative tuber culosis incidence by 38% (95% Bayesian credible intervals 27-43) in India, 31% (25-41) in Kenya, and 27% (17-41) in Moldova between 2018 and 2035. For both incidence and mortality, modelling suggests that the most important cascade losses are the proportion of patients visiting the private healthcare sector in India, missed diagnosis in health care settings in Kenya, and drug sensitivity testing in Moldova. In all settings, the most influential delay is the interval before a patient's first presentation for care. In future interventions, the proportion of individuals with tuberculosis who are on highquality treatment could offer a more robust monitoring tool than routine notifications of tuberculosis.Interpretation Linked to transmission, the care cascade can be valuable, not only for improving patient outcomes but also in identifying and monitoring programmatic priorities to reduce tuberculosis incidence and mortality.

Background: Routine services for tuberculosis (TB) are being disrupted by stringent lockdowns against the novel SARS-CoV-2 virus. We sought to estimate the potential long-term epidemiological impact of such disruptions on TB burden in high-burden countries, and how this negative impact could be mitigated. Methods: We adapted mathematical models of TB transmission in three high-burden countries (India, Kenya and Ukraine) to incorporate lockdown-associated disruptions in the TB care cascade. The anticipated level of disruption reflected consensus from a rapid expert consultation. We modelled the impact of these disruptions on TB incidence and mortality over the next five years, and also considered potential interventions to curtail this impact. Findings: Even temporary disruptions can cause long-term increases in TB incidence and mortality. If lockdown-related disruptions cause a temporary 50% reduction in TB transmission, we estimated that a 3-month suspension of TB services, followed by 10 months to restore to normal, would cause, over the next 5 years, an additional 1Á19 million TB cases (Crl 1Á06À1Á33) and 361,000 TB deaths (CrI 333À394 thousand) in India, 24,700 (16,100À44,700) TB cases and 12,500 deaths (8.8À17.8 thousand) in Kenya, and 4,350 (826À6,540) cases and 1,340 deaths (815À1,980) in Ukraine. The principal driver of these adverse impacts is the accumulation of undetected TB during a lockdown. We demonstrate how long term increases in TB burden could be averted in the short term through supplementary "catch-up" TB case detection and treatment, once restrictions are eased. Interpretation: Lockdown-related disruptions can cause long-lasting increases in TB burden, but these negative effects can be mitigated with rapid restoration of TB services, and targeted interventions that are implemented as soon as restrictions are lifted.

Despite high tuberculosis (TB) treatment success rate, treatment adherence is one of the major obstacles to tuberculosis control in Kenya. Our objective was to identify patient-related factors that were associated with time to TB treatment interruption and the geographic distribution of the risk of treatment interruption by county. Data of new and retreatment patients registered in TIBU, a Kenyan national case-based electronic data recording system, between 2013 and 2014 was obtained. Kaplan-Meier curves and log rank tests were used to assess the adherence patterns. Mixed-effects Cox proportional hazards modeling was used for multivariate analysis. Records from 90,170 patients were included in the study. The cumulative incidence of treatment interruption was 4.5% for new patients, and 8.5% for retreatment patients. The risk of treatment interruption was highest during the intensive phase of treatment. Having previously been lost to follow-up was the greatest independent risk factor for treatment interruption (HR: 4.79 [3.99, 5.75]), followed by being HIV-positive not on ART (HR: 1.96 [1.70, 2.26]) and TB relapse (HR: 1.70 [1.44, 2.00]). Male and underweight patients had high risks of treatment interruption (HR: 1.46 [1.35, 1.58]; 1.11 [1.03, 1.20], respectively). High rates of treatment interruption were observed in counties in the central part of Kenya while counties in the northeast had the lowest risk of treatment interruption. A better understanding of treatment interruption risk factors is necessary to improve adherence to treatment. Interventions should focus on patients during the intensive phase, patients who have previously been lost to follow-up, and promotion of integrated TB and HIV services among public and private facilities.