Drug-resistant tuberculosis: a priority pathogen for enhanced public health research and practice.

SummaryBackgroundGlobal evaluations of the progress towards the WHO End TB Strategy 2020 interim milestones on mortality (35% reduction) and incidence (20% reduction) have not been age specific. We aimed to assess global, regional, and national-level burdens of and trends in tuberculosis and its risk factors across five separate age groups, from 1990 to 2021, and to report on age-specific progress between 2015 and 2020.MethodsWe used the Global Burden of Diseases, Injuries, and Risk Factors Study 2021 (GBD 2021) analytical framework to compute age-specific tuberculosis mortality and incidence estimates for 204 countries and territories (1990–2021 inclusive). We quantified tuberculosis mortality among individuals without HIV co-infection using 22 603 site-years of vital registration data, 1718 site-years of verbal autopsy data, 825 site-years of sample-based vital registration data, 680 site-years of mortality surveillance data, and 9 site-years of minimally invasive tissue sample (MITS) diagnoses data as inputs into the Cause of Death Ensemble modelling platform. Age-specific HIV and tuberculosis deaths were established with a population attributable fraction approach. We analysed all available population-based data sources, including prevalence surveys, annual case notifications, tuberculin surveys, and tuberculosis mortality, in DisMod-MR 2.1 to produce internally consistent age-specific estimates of tuberculosis incidence, prevalence, and mortality. We also estimated age-specific tuberculosis mortality without HIV co-infection that is attributable to the independent and combined effects of three risk factors (smoking, alcohol use, and diabetes). As a secondary analysis, we examined the potential impact of the COVID-19 pandemic on tuberculosis mortality without HIV co-infection by comparing expected tuberculosis deaths, modelled with trends in tuberculosis deaths from 2015 to 2019 in vital registration data, with observed tuberculosis deaths in 2020 and 2021 for countries with available cause-specific mortality data.FindingsWe estimated 9·40 million (95% uncertainty interval [UI] 8·36 to 10·5) tuberculosis incident cases and 1·35 million (1·23 to 1·52) deaths due to tuberculosis in 2021. At the global level, the all-age tuberculosis incidence rate declined by 6·26% (5·27 to 7·25) between 2015 and 2020 (the WHO End TB strategy evaluation period). 15 of 204 countries achieved a 20% decrease in all-age tuberculosis incidence between 2015 and 2020, eight of which were in western sub-Saharan Africa. When stratified by age, global tuberculosis incidence rates decreased by 16·5% (14·8 to 18·4) in children younger than 5 years, 16·2% (14·2 to 17·9) in those aged 5–14 years, 6·29% (5·05 to 7·70) in those aged 15–49 years, 5·72% (4·02 to 7·39) in those aged 50–69 years, and 8·48% (6·74 to 10·4) in those aged 70 years and older, from 2015 to 2020. Global tuberculosis deaths decreased by 11·9% (5·77 to 17·0) from 2015 to 2020. 17 countries attained a 35% reduction in deaths due to tuberculosis between 2015 and 2020, most of which were in eastern Europe (six countries) and central Europe (four countries). There was variable progress by age: a 35·3% (26·7 to 41·7) decrease in tuberculosis deaths in children younger than 5 years, a 29·5% (25·5 to 34·1) decrease in those aged 5–14 years, a 15·2% (10·0 to 20·2) decrease in those aged 15–49 years, a 7·97% (0·472 to 14·1) decrease in those aged 50–69 years, and a 3·29% (–5·56 to 9·07) decrease in those aged 70 years and older. Removing the combined effects of the three attributable risk factors would have reduced the number of all-age tuberculosis deaths from 1·39 million (1·28 to 1·54) to 1·00 million (0·703 to 1·23) in 2020, representing a 36·5% (21·5 to 54·8) reduction in tuberculosis deaths compared to those observed in 2015. 41 countries were included in our analysis of the impact of the COVID-19 pandemic on tuberculosis deaths without HIV co-infection in 2020, and 20 countries were included in the analysis for 2021. In 2020, 50 900 (95% CI 49 700 to 52 400) deaths were expected across all ages, compared to an observed 45 500 deaths, corresponding to 5340 (4070 to 6920) fewer deaths; in 2021, 39 600 (38 300 to 41 100) deaths were expected across all ages compared to an observed 39 000 deaths, corresponding to 657 (–713 to 2180) fewer deaths.InterpretationDespite accelerated progress in reducing the global burden of tuberculosis in the past decade, the world did not attain the first interim milestones of the WHO End TB Strategy in 2020. The pace of decline has been unequal with respect to age, with older adults (ie, those aged >50 years) having the slowest progress. As countries refine their national tuberculosis programmes and recalibrate for achieving the 2035 targets, they could consider learning from the strategies of countries that achieved the 2020 milestones, as well as consider targeted interventions to improve outcomes in older age groups.FundingBill & Melinda Gates Foundation.

The need to prioritise childhood tuberculosis case detection

The WHO's new End TB Strategy 2016–2035 has evolved from previous global strategies to respond to old and new challenges and take advantage of new opportunities. It frames the global fight against TB as a development, social justice and human rights issue, while re-emphasizing the public health and clinical fundaments of TB care and prevention. In this commentary, we outline how TB prevention, care and control will both benefit from and contribute to the achievement of the new Sustainable Development Goals that were recently adopted at the United Nations.

World Tuberculosis Day 2022: aligning COVID-19 and tuberculosis innovations to save lives and to end tuberculosis

Detection of isoniazid, fluoroquinolone, ethionamide, amikacin, kanamycin, and capreomycin resistance by the Xpert MTB/XDR assay: a cross-sectional multicentre diagnostic accuracy study

BackgroundTuberculosis (TB) is the largest cause of mortality due to a single infectious agent. There were ∼9.6 million cases of TB and ∼1.5 million TB deaths in 2014, of which...

Ending tuberculosis in the sustainable development era in China: what are the health system challenges? A mixed-methods study

Tuberculosis in South Asia: A regional analysis of burden, progress, and future projections using the global burden of disease (1990–2021)

The magnitude of TB disease, including drug resistance, is huge and alarming in India, being the highest-burden country. The steps taken during the initial decades after getting independence in 1947 were slower and not very effective which is reflected in the timeline depicting changes (from NTP to RNTCP and then NTEP) in India’s TB control policies. India has been proactive for the last couple of years with strong scientific, political and financial support in its battle against TB with the ‘WHO End TB Strategy’. To achieve an ambitious goal of eliminating TB by 2025, the program has adopted a multifaceted approach that includes early detection of DSTB and DRTB cases with the genexpert diagnostics, use of potent regimen and preventive care of household contacts. However, a simultaneous multi-dimensional uplift of socioeconomic, educational, nutritional status, personal health and hygiene etc., of the community is not to be ignored. A vignette case of TB with multiple complicating events during management is included to highlight the problem of managing difficult-to-treat TB cases. The role of multidisciplinary specialist expert committee support to deal with adverse drug reactions (ADR) due to newer anti-TB (Bedaquiline, delamanid/pretomanid), use of repurposed antibiotics and efficacious management of comorbidities is also being recognized to strengthen the program. Potent new anti-TB drugs to shorten the duration of treatment, quick diagnostics tools, and effective preventive vaccine with a strong infrastructure laboratory network are the urgent needs of the day

SummaryBackgroundThe economic burden on households affected by tuberculosis through costs to patients can be catastrophic. WHO's End TB Strategy recognises and aims to eliminate these potentially devastating economic effects. We assessed whether aggressive expansion of tuberculosis services might reduce catastrophic costs.MethodsWe estimated the reduction in tuberculosis-related catastrophic costs with an aggressive expansion of tuberculosis services in India and South Africa from 2016 to 2035, in line with the End TB Strategy. Using modelled incidence and mortality for tuberculosis and patient-incurred cost estimates, we investigated three intervention scenarios: improved treatment of drug-sensitive tuberculosis; improved treatment of multidrug-resistant tuberculosis; and expansion of access to tuberculosis care through intensified case finding (South Africa only). We defined tuberculosis-related catastrophic costs as the sum of direct medical, direct non-medical, and indirect costs to patients exceeding 20% of total annual household income. Intervention effects were quantified as changes in the number of households incurring catastrophic costs and were assessed by quintiles of household income.FindingsIn India and South Africa, improvements in treatment for drug-sensitive and multidrug-resistant tuberculosis could reduce the number of households incurring tuberculosis-related catastrophic costs by 6–19%. The benefits would be greatest for the poorest households. In South Africa, expanded access to care could decrease household tuberculosis-related catastrophic costs by 5–20%, but gains would be seen largely after 5–10 years.InterpretationAggressive expansion of tuberculosis services in India and South Africa could lessen, although not eliminate, the catastrophic financial burden on affected households.FundingBill & Melinda Gates Foundation.

Latent tuberculosis infection (LTBI) management is crucial to WHO's End TB Strategy. Indian guidelines recommend treating under-five children with household TB contacts after ruling out active TB, regardless of TBI testing. However, the precise LTBI burden among children in high TB burden settings like India is unknown. A community-based study in Mumbai's urban slums screened and managed under-five children at LTBI risk to understand its epidemiology and inform TB control interventions. Total 369 eligible under-five children were enrolled for the study. LTBI screening was done using Tuberculin skin test and Interferon gamma release assay. Active TB was ruled out before initiation of TB preventive therapy among LTBI positives. Statistical tests like chi-square, logistic regression analysis and Hosmer-Lemeshow test were used. Overall, LTBI prevalence among under-five children was 12.4% by IGRA and 21.4% by TST. Undernourished children had significantly lower LTBI positivity by IGRA (p = 0.027), while those with household contacts, longer contact duration and drug-resistant tuberculosis (DR-TB) exhibited proportionally greater IGRA positivity (p = <0.001). The study found a lower LTBI prevalence among under-five children compared to adults, with key risk factors being HHC, DR-TB contact, and prolonged exposure. These findings suggest the need to revise or revisit the TPT framework for this age group in India, particularly by implementing a test-and-treat approach.

The global tuberculosis epidemic and progress in care, prevention, and research: an overview in year 3 of the End TB era

Strengthening public health for a Healthy China

BackgroundAlthough MDR-TB is recognized as a significant threat, systematic descriptions of its long-term (>30 years) global spatiotemporal evolution patterns are still limited.ObjectivesThis study conducted a 46-year spatiotemporal analysis of global MDR-TB (1990–2035) to provide key evidence for evaluating and refining the WHO End TB Strategy.MethodsWe used Global Burden of Disease data to identify identified temporal inflection points in ASIR, ASDR, and DALYs using Joinpoint regression. Spatial clustering was quantified using Moran’s I and Getis-Ord hotspot analysis. A Bayesian age-period-cohort model projected MDR-TB incidence from 2022 to 2035.ResultsThe male-to-female ratio was approximately 1.5:1. Incidence was highest at 30–60 years, deaths at 60+, DALYs peak at 45–60; children under 14 years of age significantly affected. ASIR rose from 0.97/100 k (1990) to 6.39/100 k (2000), then declined (APC: −3.15%) post-2005 to 5.62/100 k (2021); males exhibited a sharper increase (+2.39%) and slower decline (−0.71%). ASDR peaked at 2.12/100 k (2002; males 27% higher). DALYs peaked at 89.05/100 k (2003). Sub-Saharan Africa is hyperendemic (Moran’s I = 12.38, p < 0.001; Somalia: 57.25/100 k), with high-high clusters in Africa/Kyrgyzstan. Projections: Global ASIR declines modestly (−1.62% by 2035), but 480,000 cases expected due to population growth; female incidence drops 7.27% (2025+), male trends stable.ConclusionMDR-TB has proven more challenging than anticipated, with persistent hotspots in sub-Saharan Africa and a disproportionate impact on males, the older adults, and children. Despite a marginal decline in ASIR to 5.46 per 100,000, the absolute number of cases is projected to rise to 480,000 by 2035 due to sustained population growth and aging. This will seriously hinder the WHO End TB Strategy. Addressing MDR-TB should prioritize key populations and regions, targeted resources, tailored interventions, sustained investment in diagnostics and treatment, and stronger government support for patient care.

SUMMARYBACKGROUND:Programmatic management of TB infection is a critical component of the WHO End TB Strategy. Interferon-gamma release assays (IGRAs) overcome some limitations of the tuberculin skin test, but implementation of IGRA testing in low-resource settings is challenging.METHODS:In this feasibility study, we evaluated performance of a novel digital lateral-flow assay, the QIAreach® QuantiFERON® TB (QIAreach-QFT) test, against the QuantiFERON®-TB Gold Plus (QFT-Plus) assay. A population with a mix of risk factors for TB infection (111 donors) were sampled over multiple days. A total of 207 individual blood samples were tested according to the manufacturer’s instructions.RESULTS:The overall percentage agreement was 95.6% (two-sided 95% CI 91.8–98), with a positive percentage agreement (i.e., sensitivity) of 100% (95% CI 94.7–100) and a negative percentage agreement (i.e., specificity) of 95.6% (95% CI 90.6–98.4). All QFT-Plus positive specimens with TB1-Nil and TB2-Nil values less than 1 IU/ml tested positive on QIAreach-QFT.CONCLUSIONS:QIAreach QFT is a deployable, accurate testing solution for decentralised testing. It has the potential to overcome key hurdles for TB infection screening in high-burden settings thus helping to achieve the WHO End TB programme goals.