Reduce Tuberculosis Incidence Research Articles

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 manupulations. 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.

Identification of additional ways to reduce the incidence of tuberculosis in HIV-infected patients. Retrospective Continuum Study.

Background: HIV infection was more often registered in the general population than in vulnerable groups according to official statistics from the Russian Federation in 2021.
 Aims: to determine the characteristic patient cohorts coinfected with tuberculosis (TB) and HIV in dynamic epidemiological environments, and propose additional organizational approaches for reducing TB incidence in patients with HIV.
 Materials and methods: we have investigated complete medical data for patients coinfected with TB and HIV in three Russian regions. Additionally, we analyzed the cohort of patients with TB, combined with HIV infection via sexual transmission. Furthermore, confidential interviews with patients coinfected with TB and HIV were undertaken. In particular, reasons for refusing clinical examination at a Russian Federal AIDS Center (RFAIDSC) were clarified.
 Results: among patients coinfected with TB and HIV, parenteral transmission remains the primary HIV infection route. At the same time, patients who become infected through sexual contact are also primarily socially disadvantaged, leading to the refusal of clinical examination and a consequent late detection of TB. On the other hand, patients report that due to unemployment, they do not have the financial means to travel to the regional RFAIDSC.
 More often, widespread, rapidly progressive MDR TB infections occurred among patients coinfected with TB and HIV, than for patients with TB but without HIV. Considering that every fourth TB patient in Russia has been diagnosed with HIV, and, at the same time, there are specific features regarding the development and course of TB, the generally accepted criteria for assessing the quality of TB without HIV care often become biased for coinfected patients. This can lead to unreasonably negative assessments of the antituberculosis system and its work.
 Conclusions: in view of the above, it is important to modify regulatory documents regarding informing patients about the importance of seeking timely medical help, solve the issue of travel for unemployed patients to medical examinations and in emergency cases. Additionally, it is important to introduce adjustments for the criteria in assessing the quality of patient TB care, thereby accounting for the pathogenesis of TB in patients with HIV coinfection.

Ending tuberculosis: the cost of missing the World Health Organization target in a low-incidence country.

BackgroundEnding tuberculosis (TB) is a global priority and targets for doing so are outlined in the World Health Organization (WHO) End TB Strategy. For low-incidence countries, eliminating TB requires high levels of wealth, low levels of income inequality and effective TB programmes and services that can meet the needs of people who have not benefited from these and are still at risk of TB. In Ireland, numerous reports have noted a need for more funding for TB prevention and control.AimThe aim of this research was to estimate the cost of not meeting the WHO End TB target of a 90% reduction in TB incidence in Ireland between 2015 and 2035.MethodsThe cost of projected TB cases between 2022 and 2035 is estimated based on trends in surveillance data for the period 2015 to 2019 and outcomes reported in the literature.ResultsBetween 2022 and 2035, it is projected that a failure to meet the WHO End TB Strategy target will result in an additional 989 cases of TB, 577.3 disability-adjusted life years and 35 deaths with TB in Ireland. The cost of this is estimated to be €70.779 million.ConclusionGiven the estimated cost, Ireland’s current prospects of eliminating TB and the tendency towards programmatic funding internationally, greater investment in TB prevention and control in Ireland is justifiable. A national elimination strategy with actions at the levels of the social determinants of health, the health system and the TB programme should be funded.

The impact of HIV and tuberculosis interventions on South African adult tuberculosis trends, 1990-2019: a mathematical modeling analysis

ObjectivesTo quantify the South African adult tuberculosis (TB) incidence and mortality attributable to HIV between 1990 and 2019 and to estimate the reduction in TB incidence due to directly observed therapy, antiretroviral therapy (ART), isoniazid preventive therapy, increased TB screening, and Xpert MTB/RIF. MethodsWe developed a dynamic TB transmission model for South Africa. A Bayesian approach was used to calibrate the model to South African-specific data sources. Counterfactual scenarios were simulated to estimate TB incidence and mortality attributable to HIV and the impact of interventions on TB incidence. ResultsBetween 1990 and 2019, 8.8 million (95% confidence interval [CI] 8.3-9.3 million) individuals developed TB, and 2.1 million (95% CI 2.0-2.2 million) died from TB. A total of 55% and 69% of TB cases and mortality were due to HIV, respectively. Overall, TB screening and ART substantially reduced TB incidence by 28.2% (95% CI 26.4-29.8%) and 20.0% (95% CI 19.2-20.7%), respectively, in 2019; other interventions had minor impacts. ConclusionHIV has dramatically increased TB incidence and mortality in South Africa. The provision of ART and intensification of TB screening explained most recent declines in TB incidence.

Population benefits of addressing programmatic and social determinants of gender disparities in tuberculosis in Viet Nam: A modelling study.

High prevalence of infectious tuberculosis among men suggests potential population-wide benefits from addressing programmatic and social determinants of gender disparities. Utilising a sex-stratified compartmental transmission model calibrated to tuberculosis burden estimates for Viet Nam, we modelled interventions to increase active case finding, to reduce tobacco smoking, and to reduce alcohol consumption by 2025 in line with national and global targets. For each intervention, we examined scenarios differentially targeting men and women and evaluated impact on tuberculosis morbidity and mortality in men, women, and children in 2035. Active case finding interventions targeting men projected greater reductions in tuberculosis incidence in men, women, and children (16.2%, uncertainty interval, UI, 11.4-23.0%, 11.8%, UI 8.0-18.6%, and 21.5%, UI 16.9-28.5%, respectively) than those targeting women (5.2%, UI 3.8-7.1%, 5.4%, UI 3.9-7.3%, and 8.6%, UI 6.9-10.7%, respectively). Projected reductions in tuberculosis incidence for interventions to reduce male tobacco smoking and alcohol consumption were greatest for men (17.4%, UI 11.8-24.7%, and 11.0%, UI 5.4-19.4%, respectively), but still substantial for women (6.9%, UI 3.8-12.5%, and 4.4%, UI 1.9-10.6%, respectively) and children (12.7%, UI 8.4-19.0%, and 8.0%, UI 3.9-15.0%, respectively). Comparable interventions targeting women projected limited impact, with declines of 0.3% (UI 0.2%-0.3%) and 0.1% (UI 0.0%-0.1%), respectively. Addressing programmatic and social determinants of men's tuberculosis burden has population-wide benefits. Future interventions to increase active case finding, to reduce tobacco smoking, and to reduce harmful alcohol consumption, whilst not ignoring women, should focus on men to most effectively reduce tuberculosis morbidity and mortality in men, women, and children.

Vigilância da Tuberculose nos Profissionais de Saúde como contributo na erradicação de uma Pandemia

Introduction/Framework Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis. Despite the available treatment, it’s an important driver of global morbidity and mortality. It reaches mainly the lungs but can reach any organ. The main route of infection is inhalation of aerosolized particles or contaminated micro-droplets. Global efforts for early diagnosis and adequate treatment have made it possible to remove Tuberculosis from the worldwide ten leading causes of death in 2019. The worldwide incidence is around ten million, probably underestimated. Tuberculosis represents an often-overlooked pandemic, which remains an important cause of death from an infectious disease whose, in contrast to other infections, incidence has recently risen as occupational disease. Methodology It’s a narrative review of the national and international guidelines about Tuberculosis in healthcare workers, with an adaptation to the Portuguese reality using estimations from countries with a similar disease incidence. Contents The World Health Organization argues that the benefit of screening and treating Latent Tuberculosis Infection outweighs the individual risks and therefore should be performed whenever possible. Following these guidelines, the Portuguese health council (Direção-Geral da Saúde) determined that health institutions, within the scope of health surveillance of their workers, must adopt procedures that allow for the early detection of Tuberculosis and Latent Tuberculosis Infection. Thus, the Occupational Medicine Services are responsible for assessing and manage the professional exposure to this biological agent. The End TB Strategy program aspires to the worldwide eradication of Tuberculosis by 2035, aiming to reduce Tuberculosis incidence and mortality by 80 and 95%, respectively, as well as universal access to proper treatment. Discussion and Conclusions The authors argue that the institutional contribution with the reinforcement of hospital infection control measures, the implementation of regular occupational Tuberculosis surveillance programs and the containment of the disease, through timely screening after unprotected exposure, are essentials measures for the achievement of the ambitious outlined goals. Regardless of their job model, these programs should be applied to all workers, contributing to the maintenance of their health, the main Occupational Medicine’s goal. Finally, the authors share ten common questions from daily basis clinical practice and present methodological suggestions. KEY-WORDS: Labor Health Surveillance; Healthcare workers; Prevention of Occupational Diseases; Screening; Tuberculosis; Latent Tuberculosis Infection.

Alert sign and symptoms for the early diagnosis of pulmonary tuberculosis: analysis of patients followed by a tertiary pediatric hospital

BackgroundIntercepting earlier suspected TB (Tuberculosis) cases clinically is necessary to reduce TB incidence, so we described signs and symptoms of retrospective cases of pulmonary TB and tried to evaluate which could be early warning signs.MethodsWe conducted a retrospective descriptive study of pulmonary TB cases in children in years 2005–2017; in years 2018–2020 we conducted a cohort prospective study enrolling patients < 18 years accessed to Emergency Department (ED) with signs/symptoms suggestive of pulmonary TB.ResultsIn the retrospective analysis, 226 patients with pulmonary TB were studied. The most frequently described items were contact history (53.5%) and having parents from countries at risk (60.2%). Cough was referred in 49.5% of patients at onset, fever in 46%; these symptoms were persistent (lasting ≥ 10 days) in about 20%. Lymphadenopathy is described in 15.9%. The prospective study enrolled 85 patients of whom 14 (16.5%) were confirmed to be TB patients and 71 (83.5%) were non-TB cases. Lymphadenopathy and contact history were the most correlated variables. Fever and cough lasting ≥ 10 days were less frequently described in TB cases compared to non-TB patients (p < 0.05).ConclusionsIn low TB endemic countries, pulmonary TB at onset is characterized by different symptoms, i.e. persistent fever and cough are less described, while more relevant are contact history and lymphadenopathy. It was not possible to create a score because signs/symptoms usually suggestive of pulmonary TB (considered in the questionnaire) were not significant risk factors in our reality, a low TB country.

Exploration of 4-aminopyrrolo[2,3-d]pyrimidine as antitubercular agents.

Tuberculosis (TB) is one of the leading causes of death worldwide. Developing new anti-TB compounds using cost-effective processes is critical to reduce TB incidence and accomplish the End TB Strategy milestone. Herein, we describe the synthesis and structure–activity relationships of a library of thirty 7H-Pyrrolo[2,3-d]pyrimidine derivatives providing insights into the contributions of different aromatic, aryl and alkyl substitution at the C-4 position of the 7-deazapurine ring. The minimum inhibitory concentration (MIC) of the compounds against the green fluorescent protein (GFP) reporter strain of Mycobacterium tuberculosis was assayed using the standard broth microdilution method, and cell toxicity was determined using the MTT assay. Sixteen compounds displayed in vitro activity against the GFP reporter strain of Mycobacterium tuberculosis with MIC90 values of 0.488–62.5 µM. This study highlights the most potent derivative, N-(4-phenoxy phenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine with a MIC90 value of 0.488 µM and was non-cytotoxic to the Vero cell line. Moreover, all the potent compounds from this series have a ClogP value less than 4 and molecular weight < 400; thus, likely to maintain drug-likeness during lead optimisation.Graphical abstract Supplementary InformationThe online version contains supplementary material available at 10.1007/s11030-022-10453-1.