Reduce Tuberculosis Incidence Research Articles

Verification of Sub-national Claim for ‘TB-free’ Status of Rajsamand District, Rajasthan, India-2020

Background: Tuberculosis (TB) caused by Mycobacterium tuberculosis is an opportunistic infection that affects the lungs in humans. Caseload of TB has been deemed it endemic in various regions of the world and India is on top of that list. The Government of India has set out a goal to eliminate tuberculosis in India by the year 2025 with the help of the National Strategic Plan (NSP) 2017–25. The objective of the index study was to verify the claim of Rajsamand district in Rajasthan, that it witnessed a >20% reduction in TB incidence between 2015 and 2020. Methodology: This was a mixed-methods study. Quantitative component (cross-sectional study): Secondary data review (review of records from Nikshay notification systems and National tuberculosis elimination program (NTEP) reports, utilization of drugs in the public sector, and drug sales in the private sector). Primary data collection through survey. Qualitative component: nominal group technique and key informant interviews. Result: Percentage decline of a ≥ 20% incidence in 2020 compared to baseline 2015 was not seen. The number needed to test (increased by 18.26% in 2020 as compared to the baseline of 2015. TB Score of Rajsamand district for the year 2020 was 68.34 out of 100. Conclusion: Rajsamand district’s claim of ≥20% reduction in TB incidence in the year 2020, was rejected.

Evaluating the significance of latent tuberculosis infection treatment in high‐incidence countries

Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) is a devastating and rapidly spreading disease. Despite years of scientific research and numerous efforts, it is still a major and resurgent health problem worldwide, with high mortality rates. Added to the concern is that TB persists as a latent infection, an occult face of TB, that becomes a potential reservoir for active tuberculosis. Since latent TB‐infected patients may eventually advance to the active form of TB, an accurate diagnosis and effective treatment of latent tuberculosis are essential for TB control. Latent tuberculosis infection (LTBI) treatment is a prominent component of TB control in low‐prevalence countries like the United States; however, its implication in high‐incidence countries like India is still challenging. Therefore, the present study aimed to evaluate the impact of implementing diagnosis and treatment of LTBI in high‐incidence countries using a mathematical model‐based approach. Through our model, we predicted the incidence rate based on the current treatment regimen in India for the year 2035, which is one of the milestones of WHO for a substantial reduction in TB incidence. We observed demographic variability in the effects of various parameters on the TB incidence rate. Finally, we formulated the putative treatment strategies to reduce the TB burden in high‐incidence scenarios. Further, we estimated the impact of these proposed treatment strategies on the drug‐resistant population in high‐incidence scenarios. The model predictions suggested molding the current treatment strategies and focused implementation of LTBI diagnosis and treatment in high‐incidence scenarios.

The Impact of Vaccination Programs on the Prevention of Infectious Disease Tuberculosis: A Case Study with Gasabo District in Rwanda

Introduction Tuberculosis (TB) remained a significant public health challenge globally, including in Gasabo District, Rwanda. Vaccination programs, particularly Bacille Calmette-Guérin (BCG) vaccination, played a crucial role in TB prevention. This study aimed to assess the impact of vaccination programs on TB prevention in Gasabo District, Rwanda, by analyzing vaccination coverage, TB incidence rates, demographic characteristics, and healthcare system factors.  Methods A retrospective cohort study design was employed, utilizing secondary data sources from healthcare facilities in Gasabo District. Data on vaccination coverage, TB incidence rates, demographic characteristics, and healthcare system factors were collected and analyzed. Statistical methods, including regression analysis and descriptive statistics, were used to assess the association between vaccination programs and TB prevention outcomes.  Findings The study found a significant association between BCG vaccination coverage and lower TB incidence rates in Gasabo District. Higher vaccination coverage was associated with reduced TB incidence rates, particularly among children. However, challenges such as incomplete vaccination data, potential confounding factors, and socio-economic disparities were identified. Despite these challenges, vaccination programs were found to be effective in reducing TB transmission and protecting vulnerable populations from TB infection.  Conclusion The findings highlighted the importance of vaccination programs in TB prevention efforts in Gasabo District, Rwanda. Strengthening vaccination coverage, enhancing healthcare system capacity, addressing socio-economic determinants, fostering collaborations, promoting research and innovation, and strengthening surveillance and monitoring systems are essential for optimizing TB prevention efforts. By implementing these recommendations, we can accelerate progress towards ending the TB epidemic and improving public health outcomes in Gasabo District and beyond.

Transmission of tuberculosis in rural Henan, China: a prospective population-based genomic spatial epidemiological study

ABSTRACT The incidence of tuberculosis (TB) has declined more slowly in rural than urban areas in China, and data on the patterns of transmission and the high-risk populations in rural areas remains scarce. We conducted a population-based study of culture-positive pulmonary TB patients diagnosed in rural Linzhou City, Henan Province from July 2018 to February 2023. Genomic clusters were defined based on whole-genome sequencing and risk factors for clustering were identified by logistic regression. Transmission events were inferred with phybreak and transmission links were sought through epidemiological investigation of clustered patients. Logistic regression was used to explore the relationship between genomic differences of patient isolates and geographical distances of patient residences. Spatial hotspots were defined using kernel density estimation. Of 455 culture-positive patients, 430 were included in the final analysis. Overall, 192 (44.7%,192/430) patients were grouped into 49 clusters. Clusters containing ≥5 patients accounted for 18.4% (9/49) of the clusters and clustering was highest in student patients. No super-spreaders were detected. Confirmed epidemiologic links were identified for only 18.2% of clustered patients. The clustering risk decreased rapidly with increasing distances between patient residences, but 77.6% of clustered patient pairs lived ≥5.0 km apart. Both the Central Subdistrict and Rencun Township were identified as hotspots for TB transmission. Recent transmission appears to be an important driver of the TB burden in Linzhou. The formulation of effective strategies to reduce TB incidence in rural areas will require further studies to identify high-risk populations and venues where local inhabitants congregate and transmit the infection.

The long-term effects of domestic and international tuberculosis service improvements on tuberculosis trends within the USA: a mathematical modelling study

For settings with low tuberculosis incidence, disease elimination is a long-term goal. We investigated pathways to tuberculosis pre-elimination (incidence <1·0 cases per 100 000 people) and elimination (incidence <0·1 cases per 100 000 people) in the USA, where incidence was estimated at 2·9 per 100 000 people in 2023. Using a mathematical modelling framework, we simulated how US tuberculosis incidence could be affected by changes in tuberculosis services in the countries of origin for future migrants to the USA, as well as changes in tuberculosis services inside the USA. To do so, we used a linked set of transmission dynamic models, calibrated to demographic and epidemiological data for each setting. We constructed intervention scenarios representing improvements in tuberculosis services internationally and within the USA, individually and in combination, plus a base-case scenario representing continuation of current services. We simulated health and economic outcomes until 2100, using a Bayesian approach to quantify uncertainty in these outcomes. Under the base-case scenario, US tuberculosis incidence was projected to decline to 1·8 cases per 100 000 (95% uncertainty interval [UI] 1·5-2·1) in the total population by 2050. Intervention scenarios produced substantial reductions in tuberculosis incidence, with the combination of all domestic and international interventions projected to achieve pre-elimination by 2033 (95% UI 2031-2037). Compared with the base-case scenario, this combination of interventions could avert 101 000 tuberculosis cases (95% UI 84 000-120 000) and 13 300 tuberculosis deaths (95% UI 10 500-16 300) in the USA from 2025 to 2050. Tuberculosis elimination was not projected before 2100. Strengthening tuberculosis services domestically, promoting the development of more effective technologies and interventions, and supporting tuberculosis programmes in countries with a high tuberculosis burden are key strategies for accelerating progress towards tuberculosis elimination in the USA. US Centers for Disease Control and Prevention.

Optimizing the cascade of prevention to protect people from tuberculosis: A potential game changer for reducing global tuberculosis incidence.

The provision of tuberculosis preventive treatment is one of the critical interventions to reduce tuberculosis incidence and ultimately eliminate the disease, yet we still miss appropriate tools for an impactful intervention and treatment coverage remains low. We used recent data, epidemiological estimates, and research findings to analyze the challenges of each step of the cascade of tuberculosis prevention that currently delay the strategy implementation. We addressed research gaps and implementation bottlenecks that withhold key actions in tuberculosis case finding, testing for tuberculosis infection, provision of preventive treatment with safer, shorter regimens and supporting people to complete their treatment. Empowering communities to generate demand for preventive therapy and other prevention services in a holistic manner and providing adequate financial support to sustain implementation are essential requirements. The adoption of an effective, universal monitoring and evaluation system is a prerequisite to provide general and granular insight, and to steer progress of the tuberculosis infection strategy at global and local level.

Impact of COVID-19 pandemic responses on tuberculosis incidence: insights from Shantou, China

BackgroundVarious measures taken against the COVID-19 pandemic are not only effective in reducing the spread of the disease, but also lead to some unexpected results. This article regarded these measures as an intervention and explored their impact on the incidence of tuberculosis in Shantou, China.MethodsThe incidence rate and the surveillance data of tuberculosis from January 1st, 2018 to December 31st, 2021 were provided by the Shantou Tuberculosis Prevention and Control Institute. Data were divided into pre-pandemic period (January 1st, 2018 - December 31st, 2019) and pandemic periods (January 1st, 2020 - December 31st, 2021). The Interrupted Time Series (ITS) was used to analyze the trend of tuberculosis incidence prior to and during the COVID-19 epidemic.ResultsThe results showed that the incidence of tuberculosis cases in Shantou decreased significantly (p < 0.05) during the pandemic as compared to that prior to the pandemic. Among them, the 45–64 age group and the 65 + age group have statistically significant declines. When patients were stratified by occupation, the unemployed and those working in agriculture reduced the most.ConclusionsIn response to the pandemic, measures like lockdowns and quarantines seem to have reduced tuberculosis incidence. However, this does not imply a true decrease. Underlying causes for the reduced true incidence need further scrutiny. Findings offer a preliminary exploration of interventions designed for one disease but functioning as unexpected results for another.

Burden of COVID-19 pandemic on tuberculosis hospitalisation patterns at a tertiary care hospital in Rajasthan, India: a retrospective analysis

ObjectiveThis study aimed to investigate the burden of the COVID-19 pandemic on tuberculosis (TB) trends, patient demographics, disease types and hospitalisation duration within the Respiratory Medicine Department over three distinct...

Tuberculosis prevalence and rifampicin resistance among presumptive patients in Nasarawa State: A three-year retrospective study

Objective: To investigate the prevalence and rifampicin resistance of tuberculosis among presumptive patients in Nasarawa state, Nigeria. Methods: Patient data collected from January 2019 to December 2021 were retrospectively computed from the register at the tuberculosis laboratory of Dalhatu Araf Specialist Hospital, Lafia. A total of 91884 patient records were analyzed to determine tuberculosis prevalence, rifampicin resistance, and patients’ characteristics using Chi-squared test. Results: An overall prevalence of 8.0% was recorded among presumptive patients over the three-year period with a decreasing trend in prevalence from 10.0% (2019) to 6.5% (2021), though the number of samples progressively increased each year and more than doubled in 2021. Most of the patients tested for tuberculosis were females (52.6%) and were mostly older than 15 years (84.1%). Conversely, a higher resistance to rifampicin was observed among tuberculosis positive male patients (55.6%) than in females (44.4%). Similarly, tuberculosis positive patients older than 15 years (84.6%) showed greater resistance to rifampicin than those younger than 15 years (15.4%). Statistically, no relationship was established among age, sex, year of sampling and tuberculosis prevalence or rifampicin resistance rate. Conclusions: Despite the downward trends in tuberculosis prevalence and rifampicin resistance rate observed in this study, measures at maintaining the gains achieved in the fight against tuberculosis must remain paramount as the race towards reducing tuberculosis incidence and mortality by 2025 continues.

A mathematical model based on ABC fractional order for TB transmission with treatment interruptions in case of Bule Hora town, Ethiopia

In this study, we introduce a novel fractional-order model enriched with the Atangana–Baleanu–Caputo derivative to explore the dynamics of TB transmission in developing nations, where tuberculosis (TB) remains a pressing public health concern requiring urgent attention. We outline the methodology employed, emphasizing key aspects such as solution existence, uniqueness, Hyers-Ulam stability, and numerical simulations. Equilibrium points of the system, including the Disease-Free Equilibrium (DFE) and the Endemic Equilibrium (EE), are revealed through adopted mathematical manipulations. Following rigorous numerical simulations employing the Euler approach and a meticulously crafted scheme, the study illustrates compartmental solutions across a spectrum of fractional orders. This approach provides a comprehensive understanding of the model’s behavior and its responsiveness to different parameter configurations. Remarkably, as the fractional order tends towards one, our findings align closely with those of traditional integer-order models, offering insightful parallels into the model’s dynamics. Additionally, our work emphasizes the pivotal role of vaccination as a preventive measure, elucidating its profound impact on reducing tuberculosis incidence within communities. The promotion of widespread access to TB vaccines emerges as a potent strategy in curtailing the disease’s prevalence, underscoring the significance of proactive vaccination initiatives. As conclusion, this study presents a comprehensive examination of TB dynamics through a fractional-order modeling approach. Our results pave the way for further exploration, including the investigation of alternative fractional-order derivatives and exploration of theoretical and numerical stability. These endeavors will enhance our understanding of TB dynamics and inform more effective strategies for disease control and prevention.

Spatially-targeted tuberculosis screening has limited impact beyond household contact tracing in Lima, Peru: A model-based analysis.

Mathematical models have suggested that spatially-targeted screening interventions for tuberculosis may efficiently accelerate disease control, but empirical data supporting these findings are limited. Previous models demonstrating substantial impacts of these interventions have typically simulated large-scale screening efforts and have not attempted to capture the spatial distribution of tuberculosis in households and communities at a high resolution. Here, we calibrate an individual-based model to the locations of case notifications in one district of Lima, Peru. We estimate the incremental efficiency and impact of a spatially-targeted interventions used in combination with household contact tracing (HHCT). Our analysis reveals that HHCT is relatively efficient with a median of 40 (Interquartile Range: 31.7 to 49.9) household contacts required to be screened to detect a single case of active tuberculosis. However, HHCT has limited population impact, producing a median incidence reduction of only 3.7% (Interquartile Range: 5.8% to 1.9%) over 5 years. In comparison, spatially targeted screening (which we modeled as active case finding within high tuberculosis prevalence areas 100 m2 grid cell) is far less efficient, requiring evaluation of ≈12 times the number of individuals as HHCT to find a single individual with active tuberculosis. Furthermore, the addition of the spatially targeted screening effort produced only modest additional reductions in tuberculosis incidence over the 5 year period (≈1.3%) in tuberculosis incidence. In summary, we found that HHCT is an efficient approach for tuberculosis case finding, but has limited population impact. Other screening approaches which target areas of high tuberculosis prevalence are less efficient, and may have limited impact unless very large numbers of individuals can be screened.

Comparative effectiveness of interventions for preventing tuberculosis: systematic review and network meta-analysis of interventional studies

Tuberculosis (TB) is the leading infectious cause of death globally. Several preventive measures are employed to prevent TB, yet there is a paucity of evidence on the effectiveness of these interventions. Therefore, this study aimed to identify the most effective interventions for reducing TB incidence. A systematic search was undertaken across five relevant databases including PubMed, SCOPUS, Web of Science, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from inception to February 22, 2023. Bayesian network meta-analysis (NMA) was conducted to compare the effectiveness of preventive interventions including preventive therapy, nutritional intervention, targeted screening, and vaccination in reducing TB incidence. Subgroup analysis was conducted to investigate the effectiveness of TB preventive treatments. Overall 82 articles were included in the NMA. Preventive therapy (OR=0.44, 95% CrI 0.36-0.52), BCG vaccination (OR=0.62, 95% CrI 0.39-0.98) and TB candidate vaccines (OR=0.67, 95% CrI 0.46-0.98) were more effective than placebo or no intervention. When all active interventions were considered, preventive therapy ranked as the best intervention. Of the preventive treatments, isoniazid (OR=0.46, 95% CrI 0.35-0.55), isoniazid plus rifampicin (OR=0.56, 95% CrI 0.32-0.97), isoniazid plus rifapentine (OR=0.49, 95% CrI 0.29-0.83), isoniazid plus ethambutol (OR=0.39, 95% CrI 0.15-0.99), isoniazid plus streptomycin (OR=0.12, 95% CrI 0.02-0.55), rifampicin (OR=0.41, 95% CrI 0.18-0.92), and rifampicin plus pyrazinamide (OR=0.51, 95% CrI 0.29-0.87) surpassed placebo/none. Our study suggested that when all available preventive interventions are considered, preventive therapy is likely the most effective intervention. Within TB preventive treatments, isoniazid plus streptomycin is likely ranked at the top. This comparative study provides important information for policymakers and stakeholders, enabling them to make informed decisions on preventive strategies, whilst considering local resources and capacity constraints. Curtin University strategic scholarship and Australian National Health and Medical Research Council, through an Emerging Leadership Investigator grant.

Breaking the Chains of Tuberculosis: Quantifying the Effects of Literacy, Population Density, and Access to Improve Sanitation to Support Defense Health and Security in Indonesia

Background: Tuberculosis (TB) is a global health problem. It poses a significant burden worldwide, requiring urgent control measures and research for effective reduction especially in Indonesia.Objective: Investigating the effects of literacy, population density, and access to improved sanitation on TB incidence can provide insights into the relationship between these factors.Methods: This study was conducted in Jakarta, Indonesia from June to July 2023, using secondary data from 2005 to 2021. It employed a quantitative cross-sectional design to examine the relationship between variables. Data were collected from the ASEAN database and analyzed using descriptive and path analysis techniques to determine variable effects and significance. The study found that the incidence of tuberculosis in Indonesia initially decreased from 2005 to 2020 but significantly increased in 2021.Results: Population density, adult literacy rate, and access to improved sanitation all showed positive trends. Significant direct effects were observed among most variables, and indirect effects of population density on tuberculosis incidence were also identified through literacy and sanitation. The final model showed that higher population density correlated with increased access to sanitation and literacy rate, while access to improved sanitation was associated with reduced tuberculosis incidence. Overall, the model had a very good fit based on the indicators.Conclusion: Priority investments in sanitation infrastructure, especially in densely populated areas, along with improved access to sanitation facilities, combined with targeted health education campaigns and collaboration across defense, health, and education sectors, are recommended to enhance tuberculosis prevention and control

Nutritional supplementation to prevent tuberculosis incidence in household contacts of patients with pulmonary tuberculosis in India (RATIONS): a field-based, open-label, cluster-randomised, controlled trial

In India, tuberculosis and undernutrition are syndemics with a high burden of tuberculosis coexisting with a high burden of undernutrition in patients and in the population. The aim of this study was to determine the effect of nutritional supplementation on tuberculosis incidence in household contacts of adults with microbiologically confirmed pulmonary tuberculosis. In this field-based, open-label, cluster-randomised controlled trial, we enrolled household contacts of 2800 patients with microbiologically confirmed pulmonary tuberculosis across 28 tuberculosis units of the National Tuberculosis Elimination Programme in four districts of Jharkhand, India. The tuberculosis units were randomly allocated 1:1 by block randomisation to the control group or the intervention group, by a statistician using computer-generated random numbers. Although microbiologically confirmed pulmonary tuberculosis patients in both groups received food rations (1200 kcal, 52 grams of protein per day with micronutrients) for 6 months, only household contacts in the intervention group received monthly food rations and micronutrients (750 kcal, 23 grams of protein per day with micronutrients). After screening all household contacts for co-prevalent tuberculosis at baseline, all participants were followed up actively until July 31, 2022, for the primary outcome of incident tuberculosis (all forms). The ascertainment of the outcome was by independent medical staff in health services. We used Cox proportional hazards model and Poisson regression via the generalised estimating equation approach to estimate unadjusted hazard ratios, adjusted hazard ratios (aHRs), and incidence rate ratios (IRRs). This study is registered with CTRI-India, CTRI/2019/08/020490. Between Aug 16, 2019, and Jan 31, 2021, there were 10 345 household contacts, of whom 5328 (94·8%) of 5621 household contacts in the intervention group and 4283 (90·7%) of 4724 household contacts in the control group completed the primary outcome assessment. Almost two-thirds of the population belonged to Indigenous communities (eg, Santhals, Ho, Munda, Oraon, and Bhumij) and 34% (3543 of 10 345) had undernutrition. We detected 31 (0·3%) of 10 345 household contact patients with co-prevalent tuberculosis disease in both groups at baseline and 218 (2·1%) people were diagnosed with incident tuberculosis (all forms) over 21 869 person-years of follow-up, with 122 of 218 incident cases in the control group (2·6% [122 of 4712 contacts at risk], 95% CI 2·2-3·1; incidence rate 1·27 per 100 person-years) and 96 incident cases in the intervention group (1·7% [96 of 5602], 1·4-2·1; 0·78 per 100 person-years), of whom 152 (69·7%) of 218 were patients with microbiologically confirmed pulmonary tuberculosis. Tuberculosis incidence (all forms) in the intervention group had an adjusted IRR of 0·61 (95% CI 0·43-0·85; aHR 0·59 [0·42-0·83]), with an even greater decline in incidence of microbiologically confirmed pulmonary tuberculosis (0·52 [0·35-0·79]; 0·51 [0·34-0·78]). This translates into a relative reduction of tuberculosis incidence of 39% (all forms) to 48% (microbiologically confirmed pulmonary tuberculosis) in the intervention group. An estimated 30 households (111 household contacts) would need to be provided nutritional supplementation to prevent one incident tuberculosis. To our knowledge, this is the first randomised trial looking at the effect of nutritional support on tuberculosis incidence in household contacts, whereby the nutritional intervention was associated with substantial (39-48%) reduction in tuberculosis incidence in the household during 2 years of follow-up. This biosocial intervention can accelerate reduction in tuberculosis incidence in countries or communities with a tuberculosis and undernutrition syndemic. Indian Council of Medical Research-India TB Research Consortium.

Genotypic and spatial analysis of transmission dynamics of tuberculosis in Shanghai, China: a 10-year prospective population-based surveillance study

With improved tuberculosis (TB) control programs, the incidence of TB in China declined dramatically over the past few decades, but recently the rate of decrease has slowed, especially in large cities such as Shanghai. To help formulate strategies to further reduce TB incidence, we performed a 10-year study in Songjiang, a district of Shanghai, to delineate the characteristics, transmission patterns, and dynamic changes of the local TB burden. We conducted a population-based study of culture-positive pulmonary TB patients diagnosed in Songjiang during 2011-2020. Genomic clusters were defined with a threshold distance of 12-single-nucleotide-polymorphisms based on whole-genome sequencing, and risk factors for clustering were identified by logistic regression. Transmission inference was performed using phybreak. The distances between the residences of patients were compared to the genomic distances of their isolates. Spatial patient hotspots were defined with kernel density estimation. Of 2212 enrolled patients, 74.7% (1652/2212) were internal migrants. The clustering rate (25.2%, 558/2212) and spatial concentrations of clustered and unclustered patients were unchanged over the study period. Migrants had significantly higher TB rates but less clustering than residents. Clustering was highest in male migrants, younger patients and both residents and migrants employed in physical labor. Only 22.1% of transmission events occurred between residents and migrants, with residents more likely to transmit to migrants. The clustering risk decreased rapidly with increasing distances between patient residences, but more than half of clustered patient pairs lived ≥5km apart. Epidemiologic links were identified for only 15.6% of clustered patients, mostly in close contacts. Although some of the TB in Songjiang's migrant population is caused by strains brought by infected migrants, local, recent transmission is an important driver of the TB burden. These results suggest that further reductions in TB incidence require novel strategies to detect TB early and interrupt urban transmission. Shanghai Municipal Science and Technology Major Project (ZD2021CY001), National Natural Science Foundation of China (82272376), National Research Council of Science and Technology Major Project of China (2017ZX10201302-006).

The path to tuberculosis elimination: a renewed vision.

Tuberculosis (TB) elimination and pre-elimination, with thresholds of 1 and 10 incident cases per million population, respectively, were considered achievable for low TB incidence countries in the 1990s, when they were conceived. However, it has since become clear that, even in low TB incidence settings with effective programmes and sufficient resources, achieving pre-elimination in the next decade will require a dramatic acceleration of efforts. In this review, we describe the history of the TB elimination concept and existing country experiences, as well as the interventions available to accelerate the progress towards this threshold. We then propose a framework for near-term progress towards the more aspirational goal of TB pre-elimination. This framework consists of five stages (high incidence, moderate incidence, low incidence, nearing pre-elimination and pre-elimination) that are benchmarked to specific levels of TB incidence in each country. Using this framework, countries can set 5-year targets of achieving certain reductions in TB incidence and/or reaching the next stage, through the use of strategies tailored to both local epidemiology and available organisation and infrastructure. TB elimination remains as an aspirational goal in all stages, but certain activities can be prioritised in the short term to make more rapid progress, ensure local-level buy-in and increase accountability. As TB pre-elimination is approached, certain ethical and social concerns are likely to rise in importance; these concerns are also discussed. Our aim in setting this framework is to guide clinicians, public health experts and decision makers in taking actionable next steps in the trajectory towards TB pre-elimination and elimination.

Undiagnosed Pulmonary Tuberculosis (TB) and Coronavirus Disease 2019 (COVID-19) in Adults Dying at Home in a High-TB-Burden Setting, Before and During Pandemic COVID-19: An Autopsy Study.

Missing or undiagnosed patients with tuberculosis (TB) or coronavirus disease 2019 (COVID-19) are of concern. Identifying both infections in patients with no diagnosis prior to death contributes to understanding the burden of disease. To confirm reports of global reduction in TB incidence, a 2012 autopsy study of adults dying at home of natural causes in a high-TB-burden setting was repeated, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) assessments after the first COVID-19 surge in South Africa. Adult decedents who died at home with insufficient information to determine cause of death, no recent hospitalization, and no current antemortem TB or COVID-19 diagnosis were identified between March 2019 and October 2020 with a 4-month halt during lockdown. A standardized verbal autopsy followed by minimally invasive needle autopsy (MIA) was performed. Biopsies were taken for histopathology from liver, bilateral brain and lung; bronchoalveolar lavage fluid was collected for Xpert (MTB/RIF) and mycobacterial culture, and blood for human immunodeficiency virus (HIV) polymerase chain reaction (PCR) testing. After the start of the COVID-19 pandemic, a nasopharyngeal swab and lung tissue were subjected to SARS-CoV-2 PCR testing. Sixty-six MIAs were completed in 25 men and 41 women (median age, 60 years); 68.2% had antemortem respiratory symptoms and 30.3% were people with HIV. Overall, TB was diagnosed in 11 of 66 (16.7%) decedents, and 14 of 41 (34.1%) in the COVID-19 pandemic were SARS-CoV-2 positive. Undiagnosed TB in adults dying at home has decreased but remains unacceptably high. Forty percent of decedents had undiagnosed COVID-19, suggesting that estimates of excess deaths may underestimate the impact of SARS-CoV-2 on mortality.

Evaluation of Clinical and Economic Efficiency and Impact of Mass Fluorography Screening on Tuberculosis Epidemiological Rates in Four Federal Districts of the Russian Federation with Different Levels of Population Coverage with Mass Fluorography Screening

The objective: to evaluate the clinical and economic efficiency and impact of mass fluorography screening of the population on tuberculosis mortality and rates of timely tuberculosis detection in four federal districts of the Russian Federation with different levels of tuberculosis detection and coverage of the population with fluorography mass screening.Subjects and Methods. Analytical materials of the Federal Center for Monitoring of Tuberculosis Transmission Control in the Russian Federation posted on official websites were used. The rates were analyzed by applied statistics methods. All statistical calculations were performed with 0.95 significance.Results. A correlation analysis was performed between the coverage, effectiveness of tuberculosis detection by mass fluorography screening of the population and main rates reflecting the epidemic situation and timeliness of tuberculosis detection in the Russian Federation and its four federal districts. There was no correlation between the detection effectiveness and main markers of timeliness of tuberculosis detection. It was found out that against the background of increased costs for mass fluorography screening, its implementation did not provide significant positive results in reducing tuberculosis incidence and mortality which indicated their low clinical and economic efficiency.

Contextualizing and optimizing novel strategies to improve the latent TB continuum of care: Insights from people living with HIV and health care providers in Brazil.

Tuberculosis (TB) causes 1 in 3 deaths among people living with HIV (PLHIV). Diagnosing and treating latent tuberculosis infection (LTBI) is critical to reducing TB incidence and mortality. Blood-based screening tests (e.g., QuantiFERON-TB Gold Plus (QFT+)) and shorter-course TB preventive therapy (TPT) regimens such as 3HP (3 months weekly isoniazid-rifapentine) hold significant promise to improve TB outcomes. We qualitatively explored barriers and solutions to optimizing QFT+ and 3HP among PLHIV in three cities in Brazil. We conducted 110 in-depth interviews with PLHIV, health care providers (HCP) and key informants (KI). Content analysis was conducted including the use of case summaries and comparison of themes across populations and contexts. LTBI screening and treatment practices were dependent on HCP's perceptions of whether they were critical to improving TB outcomes. Many HCP lacked a strong understanding of LTBI and perceived the current TPT regimen as complicated. HCP reported that LTBI screening and treatment were constrained by clinic staffing challenges. While PLHIV generally expressed willingness to consider any test or treatment that doctors recommended, they indicated HCP rarely discussed LTBI and TPT. TB testing and treatment requests were constrained by structural factors including financial and food insecurity, difficulties leaving work for appointments, stigma and family responsibilities. QFT+ and 3HP were viewed by all participants as tools that could significantly improve the LTBI cascade by avoiding complexities of TB skin tests and longer LTBI treatment courses. QFT+ and 3HP were perceived to have challenges, including the potential to increase workload on over-burdened health systems if not implemented alongside improved supply chains, staffing, and training, and follow-up initiatives. Multi-level interventions that increase understanding of the importance of LTBI and TPT among HCP, improve patient-provider communication, and streamline clinic-level operations related to QFT+ and 3HP are needed to optimize their impact among PLHIV and reduce TB mortality.

Progress towards the 2020 milestones of the end TB strategy in Cambodia: estimates of age and sex specific TB incidence and mortality from the Global Burden of Disease Study 2019

BackgroundCambodia was recently removed from the World Health Organization’s (WHO’s) top 30 high tuberculosis (TB) burden countries. However, Cambodia’s TB burden remains substantial, and the country is on the WHO’s new global TB watchlist. We aimed to examine the levels and trends in the fatal and non-fatal TB burden in Cambodia from 1990 to 2019, assessing progress towards the WHO End TB interim milestones, which aim to reduce TB incidence rate by 20% and TB deaths by 35% from 2015 to 2020.MethodsWe leveraged the Global Burden of Disease 2019 (GBD 2019) analytical framework to compute age- and sex-specific TB mortality and incidence by HIV status in Cambodia. We enumerated TB mortality utilizing a Bayesian hierarchical Cause of Death Ensemble modeling platform. We analyzed all available data sources, including prevalence surveys, population-based tuberculin surveys, and TB cause-specific mortality, to produce internally consistent estimates of incidence and mortality using a compartmental meta-regression tool (DisMod-MR 2.1). We further estimated the fraction of tuberculosis mortality among individuals without HIV coinfection attributable to the independent effects of alcohol use, smoking, and diabetes.ResultsIn 2019, there were 6500 (95% uncertainty interval 4830–8680) deaths due to all-form TB and 50.0 (43.8–57.8) thousand all-form TB incident cases in Cambodia. The corresponding age-standardized rates were 53.3 (39.9–69.4) per 100,000 population for mortality and 330.5 (289.0–378.6) per 100,000 population for incidence. From 2015 to 2019, the number of all-form TB deaths decreased by 11.8% (2.3–21.1), while the age-standardized all-form TB incidence rate decreased by 11.1% (6.3–15.6). Among individuals without HIV coinfection in 2019, alcohol use accounted for 28.1% (18.2–37.9) of TB deaths, smoking accounted for 27.0% (20.2–33.3), and diabetes accounted for 12.5% (7.1–19.0). Removing the combined effects of these risk factors would reduce all-form TB deaths by 54.2% (44.2–62.2).DiscussionDespite significant progress in reducing TB morbidity and mortality since 1990, Cambodia is not on track to achieve the 2020 WHO End TB interim milestones. Existing programs in Cambodia can benefit from liaising with risk factor control initiatives to accelerate progress toward eliminating TB in Cambodia.