Long-term exposure to ambient fine particulate matter (PM2.5) and attributable pulmonary tuberculosis notifications in Ningxia Hui Autonomous Region, China: a health impact assessment.

INTRODUCTION: Long-term exposure to fine particulate matter (≤2.5 µm (PM2.5)) has been associated with pulmonary tuberculosis (TB) notifications or incidence in recent publications. Studies quantifying the relative contribution of long-term PM2.5 on TB notifications have not been documented. We sought to perform a health impact assessment to estimate the PM2.5- attributable TB notifications during 2007-2017 in Ningxia Hui Autonomous Region (NHAR), China. METHODS: PM2.5 attributable TB notifications were estimated at township level (n=358), stratified by age group and summed across NHAR. PM2.5-associated TB-notifications were estimated for total and anthropogenic PM2.5 mass and expressed as population attributable fractions (PAFs). The main analysis used effect and uncertainty estimates from our previous study in NHAR, defining a counterfactual of the lowest annual PM2.5 (30 µg/m3) level, above which we assumed excess TB notifications. Sensitivity analyses included counterfactuals based on the 5th (31 µg/m3) and 25th percentiles (38 µg/m3), and substituting effect estimates from a recent meta-analysis. We estimated the influence of PM2.5 concentrations, population growth and baseline TB-notification rates on PM2.5 attributable TB notifications. RESULTS: Over 2007-2017, annual PM2.5 had an estimated average PAF of 31.2% (95% CI 22.4% to 38.7%) of TB notifications while the anthropogenic PAF was 12.2% (95% CI 9.2% to 14.5%). With 31 and 38 µg/m3 as counterfactuals, the PAFs were 29.2% (95% CI 20.9% to 36.3%) and 15.4% (95% CI 10.9% to 19.6%), respectively. PAF estimates under other assumptions ranged between 6.5% (95% CI 2.9% to 9.6%) and 13.7% (95% CI 6.2% to 19.9%) for total PM2.5, and 2.6% (95% CI 1.2% to 3.8%) to 5.8% (95% CI 2.7% to 8.2%) for anthropogenic PM2.5. Relative to 2007, overall changes in PM2.5 attributable TB notifications were due to reduced TB-notification rates (-23.8%), followed by decreasing PM2.5 (-6.2%), and population growth (+4.9%). CONCLUSION: We have demonstrated how the potential impact of historical or hypothetical air pollution reduction scenarios on TB notifications can be estimated, using public domain, PM2.5 and population data. The method may be transferrable to other settings where comparable TB-notification data are available.

[Spatial-temporal distribution characteristics of etiologically positive pulmonary tuberculosis in Jiangsu Province from 2011 to 2021].

Objective: To analyze the spatial-temporal distribution of etiologically positive pulmonary tuberculosis (PTB) at the county (city, district) unit in Jiangsu Province from 2011 to 2021 to provide evidence for the implementation and adjustment of prevention and control strategies of PTB in Jiangsu Province. Methods: The registration data of etiologically positive PTB patients in Jiangsu Province from 2011 to 2021 were collected from the Tuberculosis Management Information System in the China Information System of Disease Control and Prevention. Data on the permanent population were from the statistical yearbook of each county (city, district) in Jiangsu Province. Geoda 1.18.0 software was used to analyze the global and local spatial autocorrelation and explore the spatial clustering. SaTScan 10.1 software was used to analyze the spatial-temporal clusters, and ArcGIS 10.7 software was used to visualize the spatial-temporal clusters. Results: A total of 128 240 etiological positive PTB cases were registered in Jiangsu Province from 2011 to 2021, with an average annual registration rate of 13.99/100 000. The registration rate showed an overall upward trend (trend χ2=63.49, P<0.001) after 2017, and the etiologically positive rate showed an overall upward trend (trend χ2=3 710.86, P<0.001). The annual Moran's I values ranged from 0.107 to 0.343, which showed a spatial clustering distribution. The results of local spatial autocorrelation analysis showed that there were "high-high" clustering areas in Jiangsu Province each year, showing a dynamic distribution, and most of the areas were distributed in the central and southern regions of Jiangsu Province, with the largest number (7) in 2015 and the smallest number (1) in 2011. A total of 4 spatial-temporal clustering areas were explored by spatial-temporal scanning analysis (all P<0.001), among which the first-level clustering area covered 3 counties (cities, districts), namely Changshu, Taicang, and Xiangcheng District of Suzhou, and the clustering time was from 2011 to 2015. The secondary clustering areas covered 24 counties (cities, districts), mainly covering Jiangsu's central and northern regions, such as Huai'an, Suqian, and Yancheng. The third-level clustering areas covered 26 counties (cities, districts); the fourth-level clustering area was the Gaochun District of Nanjing, with the clustering period from 2017 to 2021. Conclusions: From 2011 to 2021, the etiologically positive PTB registration rate at the county (city, district) level in Jiangsu Province had obvious spatial-temporal clustering characteristics. The clustering areas included the northern areas with relatively backward economies and the southern areas with better economic development. Multiple measures should be taken to prevent and control PTB according to the specific situation in different regions.

Cost-effectiveness of active tuberculosis screening among high-risk populations in low tuberculosis incidence countries: a systematic review, 2008 to 2023.

BackgroundIn countries with a low TB incidence (≤ 10 cases/100,000 population), active pulmonary tuberculosis (PTB) mostly affects vulnerable populations with limited access to healthcare. Thus, passive case-finding systems may not be successful in detecting and treating cases and preventing further transmission. Active and cost-effective search strategies can overcome this problem.AimWe aimed to review the evidence on the cost-effectiveness (C-E) of active PTB screening programmes among high-risk populations in low TB incidence countries.MethodsWe performed a systematic literature search covering 2008-2023 on PubMed, Embase, Center for Reviews and Dissemination, including Database of Abstracts of Reviews of Effects (DARE), National Health Services Economic Evaluation Database (NHS EED), Global Index Medicus and Cochrane Central Register of Controlled Trials (CENTRAL).ResultsWe retrieved 6,318 articles and included nine in this review. All included studies had an active case-finding approach and used chest X-ray, tuberculin skin test, interferon-gamma release assay and a symptoms questionnaire for screening. The results indicate that screening immigrants from countries with a TB incidence > 40 cases per 100,000 population and other vulnerable populations as individuals from isolated communities, people experiencing homelessness, those accessing drug treatment services and contacts, is cost-effective in low-incidence countries.ConclusionIn low-incidence countries, targeting high-risk groups is C-E. However, due to the data heterogenicity, we were unable to compare C-E. Harmonisation of the methods for C-E analysis is needed and would facilitate comparisons. To outline comprehensive screening and its subsequent C-E analysis, researchers should consider multiple factors influencing screening methods and outcomes.

Changes in tuberculosis burden and its associated risk factors in Guizhou Province of China during 2006-2020: an observational study.

BACKGROUND: Understanding the trends of tuberculosis (TB) burden and its risk factors at the provincial level in the context of global End TB targets is crucial to identify the progress and challenges in TB control. We aimed to estimate the burden of TB and risk factors for death from 2006 to 2020 for the first time in Guizhou Province, China. METHODS: Data were collected from the national TB surveillance system. Four indicators of TB burden and their corresponding age-standardized rates (ASRs), including incidence (ASIR), prevalence (ASPR), mortality (ASMR) and disability-adjusted life years (DALYs) (ASDR), were estimated and stratified by year, age, gender and prefecture. Temporal trends of ASRs were presented by locally weighted regression, and the annual percentage change was calculated. The correlation between gross domestic product (GDP) per capita and ASRs was evaluated by Pearson correlation analysis. The associated risk factors for death in PTB patients were determined using logistic regression models. RESULTS: A total of 557,476 pulmonary TB (PTB) cases and 11,234 deaths were reported, including 2233 (19.9%) TB specific deaths and 9001 (80.1%) deaths from other causes. The 15-year average incidence, prevalence and mortality rates were 94.6, 102.6 and 2.1 per 100,000 population, respectively. The average DALY rate was 0.60 per 1000 population. The ASIR and ASPR have shown downward trends since 2012, with the largest percentage decrease in 2020 (ASIR: -29.8%; ASPR: -30.5%). The number in TB specific deaths consistently decreased during the study period (P<0.001), while the increase in deaths from other causes drove the overall upward trend in ASMR and ASDR. Four ASRs remained high in males and 5 prefectures. GDP per capita was negatively associated with the ASIR, ASPR and ASDR (P<0.05). Among PTB patients, men, patients with no fixed job, those with a low GDP level, patients with increasing age, those previously treated, those with severe symptoms, those transferred in and those receiving directly observed treatment were more likely to suffer death. CONCLUSION: Guizhou has made progress in reducing PTB cases and TB specific deaths over the last 15 years. Targeted interventions are needed to address these risk factors for death in PTB patients and high-risk areas.

Financial burden of tuberculosis diagnosis and treatment for patients in Ethiopia: a systematic review and meta-analysis.

BACKGROUND: Despite the diagnosis and treatment of tuberculosis (TB) given free of charge in many high-burden countries, the costs that patients face in the cascade of care remain a major concern. Here, we aimed to investigate the financial burden of TB diagnosis and treatment for people with TB in Ethiopia. METHOD: For this systematic review and meta-analysis, we searched PubMed/MEDLINE, Embase, and Cochrane Center for Clinical Trials from December 1 2022 to 31 June 2023 for articles reporting the cost of diagnosis and treatment for patients regardless of their age with all forms of TB in Ethiopia. Major study outcomes were catastrophic costs, direct (out-of-pocket) pre-diagnosis, medical cost, and post-diagnosis costs, indirect (income loss) costs, coping costs, and total costs. We have used a threshold of 20% to define catastrophic costs. We used random-effects meta-analyses to calculate summary estimates of costs. R-studio software was used for analysis. The study is registered with PROSPERO: CRD42023387687. RESULT: Twelve studies, with a total of 4792 patients with TB, were included in our analysis. At the 20% threshold of total expenses, 51% of patients (2301 participants from 5 studies, 95% CI: 36-65%, I2 = 97%) faced catastrophic costs due to bacteriologically confirmed drug-sensitive pulmonary TB. Private facility diagnosis, drug-resistance TB, TB-HIV co-infection, hospitalization, and occupation were found to be associated with catastrophic costs. Reduction in the total cost spent by the patients was associated with digital adherence interventions, community-based direct observed therapy, short-course MDR-TB treatment regimens, and active case-finding. Pre-diagnosis costs had a positive correlation with diagnosis delays and the number of facilities visited until diagnosis. Post-diagnosis costs had a positive correlation with rural residence and inpatient treatments. CONCLUSION: Irrespective of a national policy of free TB service, more than half of TB patients are suffering catastrophic costs due to drug-sensitive pulmonary TB in Ethiopia and most of the patients spend a lot of money during the pre-diagnosis period and intensive phase, but declined drastically over time. Active case-finding, digital adherence interventions, community-based treatment, and comprehensive health insurance coverage have the potential to minimize the financial burden of TB diagnosis and treatment.

Modelling of tuberculosis dynamics incorporating indirect transmission of contaminated environment and infectivity of smear-negative individuals: A case study for Xinjiang, China.

Xinjiang has been one of the high incidence areas of pulmonary tuberculosis (PTB) in China. Besides being infected by direct contacting with active PTB individuals (direct infection), the susceptible would be infected because of the exposure to the environment contaminated by Mycobacterium tuberculosis (indirect infection). Active PTB individuals include not only the smear-positive PTB (PTB+) but also the smear-negative PTB (PTB-) who are infectious due to their ability to release tiny Mycobacterium tuberculosis particles even in the absence of visible Mycobacterium tuberculosis in sputum. By taking account of direct/indirect infection and the difference between PTB+ and PTB- individuals in transmission capability, a periodic dynamical PTB transmission model is proposed. The model is fitted to the newly monthly PTB+ and PTB- cases in Xinjiang from 2008 to 2017 by Markov Chain Monte Carlo algorithm. Moreover, global sensitivity analysis is constructed to address the uncertainty of some key parameters by using Latin hypercube sampling and partial rank correlation coefficient methods. Basic reproduction number R0 for PTB transmission in Xinjiang is estimated to be 2.447 (95% CrI:(1.203, 3.844)), indicating that PTB has been prevalent in Xinjiang over the study period. Our results suggest that reducing the direct/indirect transmission rates, early screening, isolating and treating the latent, PTB+ and PTB- individuals, and enhancing the clearance of Mycobacterium tuberculosis in the environment could more effectively control PTB transmission in Xinjiang. The model fits the reported PTB data well and achieves acceptable prediction accuracy. We believe that our model can provide heuristic support for controlling PTB transmission in Xinjiang.

Cost-effectiveness analysis of adding tuberculosis household contact investigation on passive case-finding strategy in Southwestern Uganda.

INTRODUCTION: The standard passive case-finding strategy implemented by most developing countries is inadequate to detect new cases of Tuberculosis. A household contact investigation is an alternative approach. However, there is limited cost-effectiveness data to support planning and implementation in low and middle-income countries. The study aimed to evaluate the cost-effectiveness of adding household contact investigation (HCI) to the passive case-finding (PCF) strategy in the Tuberculosis control program in Southwestern Uganda. METHODS: We conducted an economic evaluation using a retrospective study approach and bottom-up costing (ingredients) techniques. It was a synthesis-based evaluation of existing data extracted from the District Health Information System (DHIS 2), TB registers, and a primary cost survey. The study compared two methods of Tuberculosis (TB) case finding (PCF and HCI) strategies. Regarding PCF, patients either self-reported their signs and symptoms or were prompted by healthcare workers. At the same time, HCI was done by home visiting and screening contacts of TB patients. Patients and household contacts presumed to have Tuberculosis were requested to produce samples for analysis. We applied a static decision-analytic modeling framework to examine both strategies' costs and effectiveness. The study relied on cost and probability estimates from National Tuberculosis (TB) program data, activity costs, and published literature. It was performed from the societal and provider perspectives over 1.5 years across 12 facilities in Ntungamo, Sheema, and Rwampara Districts. The primary effectiveness measure was the number of TB cases detected (yield) and the number needed to screen (NNS). The TB yield was calculated from the number of patients screened during the period under study. The incremental cost-effectiveness ratio (ICER) was expressed as cost in 2021 US$ per additional TB case detected. We did not apply a discount rate because of the short analytic time horizon. RESULTS: The unit costs of detecting a Tuberculosis case were US$ (United States dollar) 204.22 for PCF and US$ 315.07 for HCI. Patient and caregiver costs are five times more in PCF than in HCI [US$26.37 Vs. US$ 5.42]. The ICER was US$ 3,596.94 per additional TB case detected. The TB screening yields were 0.52% (1496/289140) for passive case finding and 5.8% (197/3414) for household contact investigation. Household contact investigation yield among children 0-14 Vs. 15+ years [6.2% Vs.5.4%] P = 0.04. The Yield among People living with HIV (PLHIV) Vs. HIV-negative [15.8% Vs.5.3%] P = 0.03 in HHCI. The PCF yield in men Vs. Women [1.12% Vs.0.28%] P<0.01. The NNS in PCF was 193 [95% CI: 186-294] and 17 [95% CI: 14-22] in HCI. CONCLUSION: Our baseline assumptions and the specific implementations of adding HCI to existing PCF programs in the context of rural African settings prove to be not cost-effective, rather than HCI as a strategy. HCI effectively identifies children and PLHIV with TB and should be prioritized. Meanwhile, the Passive case-finding strategy effectively finds men with TB and costs lower than household contact investigation.

Análisis espacio-temporal de la tuberculosis pulmonar para el periodo 2016-2020 en la Región Metropolitana, Chile / Spatio-temporal analysis of pulmonary tuberculosis in the Metropolitan Region of Chile since 2016 to 2020

INTRODUCCIÓN: El año 2020, la tuberculosis (TB) fue responsable por 9,9 millones de nuevos casos y 1,5 millones de muertes en el mundo. En Chile, se ha reportado aumento en las tasas de incidencia en los últimos años, con gran concentración de casos en la Región Metropolitana (RM). OBJETIVO: Evaluar la relación espacio-temporal de la TB pulmonar con variables socioeconómicas en la RM de Chile. MATERIAL Y MÉTODO: Estudio ecológico desarrollado entre los años 2016 y 2020. Los casos se obtuvieron desde el Ministerio de Salud (n = 4.370), describiéndose según: sexo, edad, año de confirmación diagnóstica, servicio de salud y comuna de residencia. Se utilizó análisis de componentes principales para la construcción de factores socioeconómicos comunales. La asociación entre factores y TB pulmonar se evaluó con un modelo binominal negativo multinivel. RESULTADOS: Se observó aumento en la tasa de incidencia (9,97 a 10,74 casos por 100 mil), disminución de la incidencia en personas ≥ 65 años (17,56 a 13,38) y en el promedio de edad (46,03 a 41,77 años). El factor caracterizado por mayor inmigración, hacinamiento y población urbana se asoció con mayores tasas de incidencia (RTI: 1,29; IC95: 1,23-134) y el factor con mayor escolaridad, menor pobreza y menor hacinamiento con menores tasas (RTI: 0,94; IC95: 0,89-0,98) en el periodo. CONCLUSIONES: La disminución en la edad de los casos junto a la concentración de casos en comunas urbanas y céntricas, asociadas con variables socioeconómicas desfavorables, confirman que la TB pulmonar continúa siendo un problema de relevancia a considerar.

BACKGROUND: In 2020, tuberculosis (TB) was responsible for 9.9 million new cases and 1.5 million deaths worldwide. In Chile, an increase in incidence rates has been reported in recent years, with a concentration of cases in the Metropolitan Region (MR). AIM: To evaluate the spatio-temporal relationship of pulmonary TB with socioeconomic variables in the MR of Chile. METHODS: Ecological study developed between 2016 and 2020. Cases were obtained from the Ministry of Health (n = 4,370) and described by: sex, age, year of confirmation, health service, and commune of residence. Principal component analysis was used to construct community socioeconomic factors, and the association between factors and pulmonary TB was evaluated with a multilevel negative binomial model. RESULTS: There was an increase in the incidence rate (9.97 to 10.74 cases per 100,000), a decrease in the incidence in people ≥ 65 years (17.56 to 13.38), and the average age (46.03 to 41.77 years). The factor characterized by greater immigration, overcrowding, and the urban population was associated with more elevated incidence rates (RTI: 1.29; IC95: 1.23-134), and the factor with higher education, less poverty, and less overcrowding with lower rates (RTI: 0.94; CI 95: 0.89-0.98) in the period. CONCLUSIONS: The decrease in the age of the cases together and the concentration of cases in urban and central communes, associated with unfavorable socioeconomic variables, confirm that pulmonary TB continues to be a relevant problem to consider.

The effect of diabetes mellitus on tuberculosis in eastern China: A decision-tree analysis based on a real-world study.

OBJECTIVES: The public health system faces major challenges due to the double burden of diabetes mellitus (DM) and tuberculosis (TB) in China. We aimed to investigate the prevalence and impact of diabetes on patients with TB. METHODS: Stratified cluster sampling was used to select 13 counties as study sites in the Zhejiang province. Patients who visited designated TB hospitals in these areas participated in this study between 1 January 2017 and 28 February 2019. Multiple logistic regression models were performed to investigate the association between DM and bacteriological and imaging results. A decision tree was used to predict the bacteriology and imaging results under the influence of DM. RESULTS: Of 5920 patients with newly diagnosed pulmonary tuberculosis, 643 (12.16%) had DM. Patients with pulmonary TB and DM were more likely to have pulmonary cavities (adjusted odds ratio [aOR], 2.81; 95% confidence intervals [95% CI]: 2.35-3.37) and higher rates of positive bacteriological tests (aOR, 2.32; 95% CI:1.87-2.87). Decision-tree analysis showed similar results. CONCLUSIONS: Concurrence of DM and pulmonary TB makes patients more likely to have positive bacteriological results and pulmonary cavities. Therefore, appropriate measures are necessary to promptly identify and manage patients with TB and DM.

Assessment of Family Tuberculosis Contact Screening Practice and its Associated Factors Among Pulmonary Tuberculosis Positive Patients in South Wollo Zone, Amhara Region, Ethiopia.

Objectives: The objective of this study was to assess the prevalence and the associated factors of family contact screening practice. Methods: An institution-based cross-sectional study was conducted among 403 randomly selected pulmonary tuberculosis index cases from 1st May to 30th June 2020. Data were collected through a face-to-face interviewer-administered questionnaire. Multivariable logistic regression was performed. Results: The prevalence of family contact screening was 55.3%, (CI: 60-50). Having family support for care and treatment (AOR = 2.21, 95% CI: 1.16-4.21), waiting time of less than 60 min (AOR = 2.03, 95% CI: 1.28-3.21), receiving health education on TB prevention and treatment (AOR = 1.86), 95% CI: 1.05-3.29), and having good knowledge about TB prevention (AOR = 2.76, 95% CI: 1.77-4.294) were factors associated with family TB contact screening practice. Conclusion: This study revealed that the prevalence of family contact screening was low as compared to national and global targets. Factors associated with family contact screening practice were: the presence of family support, shorter waiting time, health education offered by healthcare workers, and a good level of knowledge of the index cases.

Digital tool assessment for the community management of patients with pulmonary tuberculosis in Yiwu city, China: evidence from real world data in 2020.

Background: High-quality medication compliance is critical for the cure of pulmonary tuberculosis (PTB); however, the implementation of directly observed treatment (DOT) under direct interview still faces huge difficulties. Assessment of the effect of digital tool during community management has not been performed in eastern China. Methods: All drug-sensitive PTB cases notified in Yiwu city from June to December 2020 were divided into the routine group and digital tool group based on patients' willingness. The variables influencing the on-time completion level of home visits, medication adherence and treatment outcomes were estimated. Results: A total of 599 eligible patients were enrolled, with 268 participating in the routine group and 331 using a digital tool. Most participants were men (n = 357, 59.6%), and nearly all were new cases (n = 563, 94.0%). Participants' mean age was 44.22 ± 20.32 years. There were significant differences in age, diagnostic type, and source of patients between the two groups. During the study period, the digital tool group had a higher on-time completion rate of home visits (91.5% vs. 82.5%) and medication adherence rate (94.3% vs. 89.6%) than the routine group, whereas there was no significant difference in the treatment success rate between the two groups (91.2% vs. 86.8%). Multivariate logistic regression analysis demonstrated that the digital tool group showed a more positive function in the on-time completion status of home visits, with an adjusted odds ratio of 0.41 (95% confidence interval: 0.25-0.70). Conclusion: Digital tools can be employed to improve the on-time completion rate of home visits in Yiwu city. Further large-scale studies that use digital tools for community management are warranted.

A temporal analysis on patient and health service delays in pulmonary tuberculosis in Portugal: inter and intra­regional differences and in(equalities) between gender and age.

BACKGROUND: Tuberculosis (TB) diagnosis and treatment delays increase the period of infectiousness, making TB control difficult and increasing the fatality rates. This study aimed to determine the evolution of health care service delay (time between the patient's first contact with the health service and the diagnosis/start of treatment) and patient delay (time between onset symptoms date and the date of first contact with health services) for Pulmonary Tuberculosis (PTB) in Portugal between 2008 and 2017 across different regions, age groups and gender. METHODS: An exploratory analysis was performed, trends of both delays were studied, and 36 months forecasts were generated. We used the permutation test to test differences between groups and the Seasonal and Trend decomposition using Loess (STL) method and Autoregressive Integrated Moving Average (ARIMA) models for forecasting for both Health and Patient delays. We used data from notified PTB cases in mainland Portugal between 2008 and 2017, provided by the national surveillance system. RESULTS: Health delays remained relatively constant while patient delays increased. Females had significantly higher health delays in some regions. Individuals older than 64 had higher health delays than younger individuals, while patient delay for working-age individuals between 15 and 64 years old, presents higher patient delay. CONCLUSIONS: Forecasts presage that the upward trend of the delays is unlikely to fall in the coming years. It is important to understand the evolution of the delays and predict how these will evolve. Our understanding of the delays behaviours will contribute to better health policies and resources allocation.

Symptom- and chest-radiography screening for active pulmonary tuberculosis in HIV-negative adults and adults with unknown HIV status.

BACKGROUND: Systematic screening in high-burden settings is recommended as a strategy for early detection of pulmonary tuberculosis disease, reducing mortality, morbidity and transmission, and improving equity in access to care. Questioning for symptoms and chest radiography (CXR) have historically been the most widely available tools to screen for tuberculosis disease. Their accuracy is important for the design of tuberculosis screening programmes and determines, in combination with the accuracy of confirmatory diagnostic tests, the yield of a screening programme and the burden on individuals and the health service. OBJECTIVES: To assess the sensitivity and specificity of questioning for the presence of one or more tuberculosis symptoms or symptom combinations, CXR, and combinations of these as screening tools for detecting bacteriologically confirmed pulmonary tuberculosis disease in HIV-negative adults and adults with unknown HIV status who are considered eligible for systematic screening for tuberculosis disease. Second, to investigate sources of heterogeneity, especially in relation to regional, epidemiological, and demographic characteristics of the study populations. SEARCH METHODS: We searched the MEDLINE, Embase, LILACS, and HTA (Health Technology Assessment) databases using pre-specified search terms and consulted experts for unpublished reports, for the period 1992 to 2018. The search date was 10 December 2018. This search was repeated on 2 July 2021. SELECTION CRITERIA: Studies were eligible if participants were screened for tuberculosis disease using symptom questions, or abnormalities on CXR, or both, and were offered confirmatory testing with a reference standard. We included studies if diagnostic two-by-two tables could be generated for one or more index tests, even if not all participants were subjected to a microbacteriological reference standard. We excluded studies evaluating self-reporting of symptoms. DATA COLLECTION AND ANALYSIS: We categorized symptom and CXR index tests according to commonly used definitions. We assessed the methodological quality of included studies using the QUADAS-2 instrument. We examined the forest plots and receiver operating characteristic plots visually for heterogeneity. We estimated summary sensitivities and specificities (and 95% confidence intervals (CI)) for each index test using bivariate random-effects methods. We analyzed potential sources of heterogeneity in a hierarchical mixed-model. MAIN RESULTS: The electronic database search identified 9473 titles and abstracts. Through expert consultation, we identified 31 reports on national tuberculosis prevalence surveys as eligible (of which eight were already captured in the search of the electronic databases), and we identified 957 potentially relevant articles through reference checking. After removal of duplicates, we assessed 10,415 titles and abstracts, of which we identified 430 (4%) for full text review, whereafter we excluded 364 articles. In total, 66 articles provided data on 59 studies. We assessed the 2 July 2021 search results; seven studies were potentially eligible but would make no material difference to the review findings or grading of the evidence, and were not added in this edition of the review. We judged most studies at high risk of bias in one or more domains, most commonly because of incorporation bias and verification bias. We judged applicability concerns low in more than 80% of studies in all three domains. The three most common symptom index tests, cough for two or more weeks (41 studies), any cough (21 studies), and any tuberculosis symptom (29 studies), showed a summary sensitivity of 42.1% (95% CI 36.6% to 47.7%), 51.3% (95% CI 42.8% to 59.7%), and 70.6% (95% CI 61.7% to 78.2%, all very low-certainty evidence), and a specificity of 94.4% (95% CI 92.6% to 95.8%, high-certainty evidence), 87.6% (95% CI 81.6% to 91.8%, low-certainty evidence), and 65.1% (95% CI 53.3% to 75.4%, low-certainty evidence), respectively. The data on symptom index tests were more heterogenous than those for CXR. The studies on any tuberculosis symptom were the most heterogeneous, but had the lowest number of variables explaining this variation. Symptom index tests also showed regional variation. The summary sensitivity of any CXR abnormality (23 studies) was 94.7% (95% CI 92.2% to 96.4%, very low-certainty evidence) and 84.8% (95% CI 76.7% to 90.4%, low-certainty evidence) for CXR abnormalities suggestive of tuberculosis (19 studies), and specificity was 89.1% (95% CI 85.6% to 91.8%, low-certainty evidence) and 95.6% (95% CI 92.6% to 97.4%, high-certainty evidence), respectively. Sensitivity was more heterogenous than specificity, and could be explained by regional variation. The addition of cough for two or more weeks, whether to any (pulmonary) CXR abnormality or to CXR abnormalities suggestive of tuberculosis, resulted in a summary sensitivity and specificity of 99.2% (95% CI 96.8% to 99.8%) and 84.9% (95% CI 81.2% to 88.1%) (15 studies; certainty of evidence not assessed). AUTHORS' CONCLUSIONS: The summary estimates of the symptom and CXR index tests may inform the choice of screening and diagnostic algorithms in any given setting or country where screening for tuberculosis is being implemented. The high sensitivity of CXR index tests, with or without symptom questions in parallel, suggests a high yield of persons with tuberculosis disease. However, additional considerations will determine the design of screening and diagnostic algorithms, such as the availability and accessibility of CXR facilities or the resources to fund them, and the need for more or fewer diagnostic tests to confirm the diagnosis (depending on screening test specificity), which also has resource implications. These review findings should be interpreted with caution due to methodological limitations in the included studies and regional variation in sensitivity and specificity. The sensitivity and specificity of an index test in a specific setting cannot be predicted with great precision due to heterogeneity. This should be borne in mind when planning for and implementing tuberculosis screening programmes.

Prevalence, acceptability, and cost of routine screening for pulmonary tuberculosis among pregnant women in Cotonou, Benin.

OBJECTIVES: We sought to evaluate the yield, cost, feasibility, and acceptability of routine tuberculosis (TB) screening of pregnant women in Cotonou, Benin. DESIGN: Mixed-methods, cross-sectional study with a cost assessment. SETTING: Eight participating health facilities in Cotonou, Benin. PARTICIPANTS: Consecutive pregnant women presenting for antenatal care at any participating site who were not in labor or currently being treated for TB from April 2017 to April 2018. INTERVENTIONS: Screening for the presence of TB symptoms by midwives and Xpert MTB/RIF for those with cough for at least two weeks. Semi-structured interviews with 14 midwives and 16 pregnant women about experiences with TB screening. PRIMARY AND SECONDARY OUTCOME MEASURES: Proportion of pregnant women with cough of at least two weeks and/or microbiologically confirmed TB. The cost per pregnant woman screened and per TB case diagnosed in 2019 USD from the health system perspective. RESULTS: Out of 4,070 pregnant women enrolled in the study, 94 (2.3%) had a cough for at least two weeks at the time of screening. The average (standard deviation) age of symptomatic women was 26 ± 5 years and 5 (5.3%) had HIV. Among the 94 symptomatic women, 2 (2.3%) had microbiologically confirmed TB for a TB prevalence of 49 per 100,000 (95% CI: 6 to 177 per 100,000) among pregnant women enrolled in the study. The average cost to screen one pregnant woman for TB was $1.12 USD and the cost per TB case diagnosed was $2271 USD. Thematic analysis suggested knowledge of TB complications in pregnancy was low, but that routine TB screening was acceptable to both midwives and pregnant women. CONCLUSION: Enhanced screening for TB among pregnant women is feasible, acceptable, and inexpensive per woman screened, however in this setting has suboptimal yield even if it can contribute to enhance TB case finding.

The circuits of healthcare: Understanding healthcare seeking behaviour-A qualitative study with tuberculosis patients in Lisbon, Portugal.

BACKGROUND: Understanding health delivery service from a patient´s perspective, including factors influencing healthcare seeking behaviour, is crucial when treating diseases, particularly infectious ones, like tuberculosis. This study aims to trace and contextualise the trajectories patients pursued towards diagnosis and treatment, while discussing key factors associated with treatment delays. Tuberculosis patients' pathways may serve as indicator of the difficulties the more vulnerable sections of society experience in obtaining adequate care. METHODS: We conducted 27 semi-structured interviews with tuberculosis patients attending a treatment centre in a suburban area of Lisbon. We invited nationals and migrant patients in active treatment to participate by sharing their illness experiences since the onset of symptoms until the present. The Health Belief Model was used as a reference framework to consolidate the qualitative findings. RESULTS: By inductive analysis of all interviews, we categorised participants' healthcare seeking behaviour into 4 main types, related to the time participants took to actively search for healthcare (patient delay) and time the health system spent to diagnose and initiate treatment (health system delay). Each type of healthcare seeking behaviour identified (inhibited, timely, prolonged, and absent) expressed a mindset influencing the way participants sought healthcare. The emergency room was the main entry point where diagnostic care cascade was initiated. Primary Health Care was underused by participants. CONCLUSIONS: The findings support that healthcare seeking behaviour is not homogeneous and influences diagnostic delays. If diagnostic delays are to be reduced, the identification of behavioural patterns should be considered when designing measures to improve health services' delivery. Healthcare professionals should be sensitised and perform continuous capacity development training to deal with patients´ needs. Inhibited and prolonged healthcare seeking behaviour contributes significantly to diagnostic delays. These behaviours should be detected and reverted. Timely responses, from patients and the healthcare system, should be promoted.

Social inequalities associated with the onset of tuberculosis in disease-prone territories in a city from northeastern Brazil.

INTRODUCTION: Tuberculosis remains a major health problem worldwide, killing thousand adults and children every year mainly in developing countries as Brazil. The disease is socially determined, caused mainly by inequalities as overcrowding, bad conditions of housing, unemployment, and limited access to health care. The aim of this study was to identify the social inequalities associated with the onset of tuberculosis in disease-prone territories in a city from the Northeast. METHODOLOGY: This was an ecological study, which has gathered patients diagnosed with tuberculosis through secondary data source in a city from the northeast of Brazil. The GAMLSS statistical model has been applied considering as response variable the count of Tuberculosis cases and the independent variable, the social conditions. The double Poisson distribution was considered in the analysis. The best model fitted was selected according the Akaike information criterion value. For all tests, the p value < 0.05 was considered as statistically significant. RESULTS: 460 patients with diagnosis of tuberculosis were identified, which represents an incidence of 36.3 cases/100,000 in males and 20.7 cases/100,000 in females. Regarding social inequality associated with tuberculosis, income (households with per capita income between 1/8 and 3 minimum wages), gender and age (Proportion of males under 15 years of age) were associated with the disease. CONCLUSIONS: The findings evidenced the social determinants associated with tuberculosis, with a greater occurrence of the disease in areas with mostly male children and low-income families, these issues must be managed within and beyond the health sector, which is mandatory for the Tuberculosis elimination.

Impact of socio-economic factors on Tuberculosis treatment outcomes in north-eastern Uganda: a mixed methods study.

BACKGROUND: Tuberculosis (TB) is a major public health problem and at 48%, Karamoja in North-Eastern Uganda has the lowest treatment success rate nationally. Addressing the social determinants of TB is crucial to ending TB. This study sought to understand the extent and ways in which socio-economic factors affect TB treatment outcomes in Karamoja. METHODS: We conducted a convergent parallel mixed methods study in 10 TB Diagnostic and Treatment Units. The study enrolled former TB patients diagnosed with drug-susceptible TB between April 2018 and March 2019. Unit TB and laboratory registers were reviewed to identify pre-treatment losses to follow-up. Four focus group discussions with former TB patients and 18 key informant interviews with healthcare workers were conducted. Principle component analysis was used to generate wealth quintiles that were compared to treatment outcomes using the proportion test. The association between sociodemographic characteristics and TB treatment outcomes was evaluated using the chi-square test and multiple logistic regression. RESULTS: A total of 313 participants were randomly selected from 1184 former TB patients recorded in the unit TB registers. Of these, 264 were contacted in the community and consented to join the study: 57% were male and 156 (59.1%) participants had unsuccessful treatment outcomes. The wealthiest quintile had a 58% reduction in the risk of having an unsuccessful treatment outcome (adj OR = 0.42, 95% CI 0.18-0.99, p = 0.047). People who were employed in the informal sector (adj OR = 4.71, 95% CI 1.18-18.89, p = 0.029) and children under the age of 15 years who were not in school or employed (adj OR = 2.71, 95% CI 1.11-6.62, p = 0.029) had significantly higher odds of unsuccessful treatment outcome. Analysis of the pre-treatment loss to follow-up showed that 17.2% of patients with pulmonary bacteriologically confirmed TB did not initiate treatment with a higher proportion among females (21.7%) than males (13.5%). Inadequate food, belonging to migratory communities, stigma, lack of social protection, drug stock-outs and transport challenges affected TB treatment outcomes. CONCLUSIONS: This study confirmed that low socio-economic status is associated with poor TB treatment outcomes emphasizing the need for multi- and cross-sectoral approaches and socio-economic enablers to optimise TB care.

Combined assessment of tuberculosis case notification rate and infection control at health facilities of Dale districts, Sidama Zone, Southern Ethiopia.

BACKGROUND: Mycobacterium tuberculosis (TB) is the deadliest disease that claims millions of deaths globally. Ethiopia is among the countries heavily hit by the disaster. Despite the effective directly observed treatment and TB infection control (TBIC) measures provided by the world health organization (WHO), the rate of new cases increased daily throughout the country. Healthcare workers (HCWs) are at highest risk serving without having the necessary facility in place while overcrowding of patients exacerbated TB transmission. The study aimed to assess TBIC implementation and analyze case notification rate (CNR) of smear-positive pulmonary TB in the selected health facilities at Dale district, Sidama Zone, Southern Ethiopia. METHODS: Seven health care facilities have been visited in the study area and smear-positive pulmonary TB notification rate was determined retrospectively during the years 2012 to 2014. Data on smear positive test results and demographic characteristics were collected from the TB unit registries. A structured questionnaire, facility survey, and observation checklists were used to assess the presence of TBIC plans at the health care facilities. RESULTS: The overall case notification rate of smear-positive pulmonary tuberculosis was 5.3% among all 7696 TB suspected patients. The odds of being diagnosed with smear-positive TB were 24% more in males than in females (adj OR = 1.24, 95% CI: (1.22, 1.55). Moreover, in the study area, only 28% of the facilities have been practiced TB infection control and 71% of the facilities assigned a focal person for the TBIC plan. The implementation of environmental control measures in the facilities was ranged between 16-83%. N95 particulate respirators were found only in 14% of the facilities. CONCLUSION: TB CNR in Dale district was low. Moreover, implementations of TBIC in Dale district health facilities were poor when the survey was done. Hence, urgent measures should be taken to reverse the burden of TB.

Patient delay and associated factors among tuberculosis patients in Gamo zone public health facilities, Southern Ethiopia: An institution-based cross-sectional study.

BACKGROUND: Delayed tuberculosis diagnosis and treatment increase morbidity, mortality, expenditure, and transmission in the community. Early diagnosis and initiation of treatment are essential for effective TB control. Therefore, the main objective of this study was to assess the magnitude and factors associated with patient delay among tuberculosis patients in Gamo Zone, Southern Ethiopia. METHODS: A cross-sectional study was conducted in Gamo Zone, Southern Ethiopia from February to April 2019. Fifteen health facilities of the study area were selected randomly and 255 TB patients who were ≥18 years of age were included. Data were collected using a questionnaire through face-to-face interviews and analyzed using SPSS version 20.0. Patient delay was analyzed using the median as the cut-off value. Multivariable logistic regression analysis was fitted to identify factors associated with patient delay. A p-value of ≤ 0.05 with 95% CI was considered to declare a statistically significant association. RESULTS: The median (inter-quartile range) of the patient delay was 30 (15-60) days. About 56.9% of patients had prolonged patients' delay. Patient whose first contact were informal provider (adjusted odds ratio [AOR]: 2.24; 95% confidence interval [CI] 1.29, 3.86), presenting with weight loss (AOR: 2.53; 95%CI: 1.35, 4.74) and fatigue (AOR: 2.38; 95%CI: 1.36, 4.17) and body mass index (BMI) categories of underweight (AOR: 1.74; 95%CI: 1.01, 3.00) were independently associated with increased odds of patient delay. However, having good knowledge about TB (AOR: 0.44; 95% CI: 0.26, 0.76) significantly reduce patients' delay. CONCLUSION: In this study, a significant proportion of patients experienced more than the acceptable level for the patient delay. Knowledge about TB, the first action to illness, presenting symptoms, and BMI status were identified factors associated with patient delay. Hence, raising public awareness, regular training, and re-training of private and public healthcare providers, involving informal providers, and maintenance of a high index of suspicion for tuberculosis in the vulnerable population could reduce long delays in the management of TB.

Understanding health care-seeking behaviour of the tribal population in India among those with presumptive TB symptoms.

BACKGROUND AND OBJECTIVES: Understanding the drivers for care-seeking among those who present with symptoms of TB is crucial for early diagnosis of TB and prompt treatment, which will in turn halt further TB transmission. While TB is a challenge among the tribal population, little is known about the care-seeking behaviour and the factors influencing care-seeking behaviour among the tribal population across India. METHODOLOGY: This community-based descriptive study was carried out in 17 states of India across 6 zones, covering 88 villages from tribal districts with over 70% tribal population. The sample population included individuals ≥15 years old who were screened through an interview for symptoms suggestive of pulmonary TB (PTB), currently and/or previously on anti-TB treatment. Those with symptoms were then assessed on their health-seeking behavior using a semi-structured interview schedule. RESULTS: Among 74532 eligible participants screened for symptoms suggestive of TB, 2675 (3.6%) were found to be presumptive TB cases. Of them, 659 (24.6%) sought care for their symptoms. While 48.2% sought care after a week, 19.3% sought care after one month or more, with no significant difference in the first point of care; 46.9% approaching a private and 46.7% a public facility. The significant factors influencing care-seeking behaviour were knowledge on TB (OR: 4.64 (3.70-5.83), p < 0.001), age<35 years (OR: 1.60 (1.28-2.00), p < 0.001), co-morbidities like asthma (OR: 1.80 (1.38-2.35), p < 0.001) and blood pressure (OR: 2.59 (1.75-3.85), p < 0.001), symptoms such as blood in sputum (OR: 1.69 (1.32-2.16), p < 0.001), shortness of breath (OR: 1.43 (1.19-1.72), p < 0.001) and weight loss (OR: 1.59 (1.33-1.89), p < 0.001). The cough was the most often reported symptom overall. There were gender differences in symptoms that prompted care-seeking: Males were more likely to seek care for weight loss (OR: 1.78 (1.42-2.23), p<0.001), blood in the sputum (OR: 1.69 (1.25-2.28), p<0.001), shortness of breath (OR: 1.49 (1.18-1.88), p<0.001) and fever (OR: 1.32 (1.05-1.65), p = 0.018). Females were more likely to seek care for blood in sputum (OR: 1.68 (1.10-2.58), p = 0.018) and shortness of breath (OR = 1.35, (1.01-1.82), p = 0.048). The cough did not feature as a significant symptom that prompted care-seeking. CONCLUSION: Delayed healthcare-seeking behaviour among those with symptoms presumptive of TB in the tribal population is a major concern. Findings point to differences across gender about symptoms that prompt care-seeking in this population. Gender-sensitive interventions with health system strengthening are urgently needed to facilitate early diagnosis and treatment among this population.