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Tuberculosis (TB) and depression frequently co-occur, yet research has largely focused on prevalence rather than diagnostic or treatment methodologies. Given overlapping symptoms, robust research approaches are critical for improving detection and treatment strategies in persons with TB (PWTB). This protocol defines a scoping review that aims to map methodologies used to study depression in individuals with TB, identifying gaps in research design, diagnosis, and treatment that may hinder clinical and public health advancements. A search was conducted in MEDLINE, Embase, PsycINFO, Global Health, Cochrane Library, and Africa-Wide Information using controlled vocabulary related to TB and depression. Studies examining the TB-depression relationship will be included. We will use Covidence to facilitate screening, selection, and data extraction. We will extract data on study design, diagnostic tools, treatment interventions, and analytical approaches. Descriptive characteristics of included studies will be presented using figures and tables. Using the Reach-Effectiveness-Adoption-Implementation-Maintenance (RE-AIM) framework, we will evaluate reach by assessing the extent to which studies explore both directions of the TB-depression relationship and include diverse, high-risk populations. Effectiveness will be examined by categorizing study designs to assess methodological diversity and evaluating the diagnostic tools and treatment interventions used, along with their reported efficacy. Adoption will be analyzed by identifying where and by whom depression diagnosis and treatment methodologies have been implemented and whether research findings have influenced clinical guidelines or public health policies. Implementation will be assessed by identifying barriers and facilitators reported in qualitative studies or by researchers regarding the integration of depression care into TB treatment settings. Finally, maintenance will be determined by examining whether diagnostic and treatment methodologies were sustained within health systems, including long-term patient outcomes and the persistence of interventions beyond the research phase. By mapping existing methodologies and identifying research gaps, this review will provide valuable insights to guide future research study designs and improve diagnostic and treatment strategies for depression in PWTB.

The global type 2 diabetes mellitus (DM) epidemic threatens progress made in reducing tuberculosis (TB)-related mortality worldwide. Previous clinical studies have not fully evaluated potential confounding variables in addressing the impact of DM on TB treatment outcomes. The antidiabetic agent metformin regulates autophagy and may play a role as a host-directed therapeutic adjuvant to antitubercular treatment. We conducted a retrospective cohort study comprising patients aged ≥13 years undergoing treatment for culture-confirmed, drug-susceptible pulmonary TB. We assessed the effect of DM on mortality during TB treatment and 2-month TB sputum-culture conversion. We also evaluated the effect of metformin use on survival during TB treatment. Among 2416 patients undergoing TB treatment, after adjusting for age, sex, chronic kidney disease, cancer, hepatitis C, tobacco use, cavitary disease, and treatment adherence, patients with DM had 1.91 times higher odds (95% confidence interval [CI], 1.51-2.40) of death during TB treatment than patients without DM, and 1.72 (95% CI, 1.25-2.38) times higher odds of remaining culture-positive at 2 months. Metformin use in patients with DM was significantly associated with decreased mortality during TB treatment (hazard ratio, 0.56 [95% CI, .39-.82]), and metformin users had similar mortality as patients without DM. This study suggests that despite multiple potential confounding variables, DM poses an increased risk of adverse TB treatment outcomes. There was a significant association between metformin use and decreased mortality during TB treatment, suggesting a potential role for this agent as adjunctive, host-directed therapy.

Household contacts of patients with active pulmonary tuberculosis (TB) often have latent TB infection, and are at risk of progression to disease. We set out to investigate whether index TB case HIV status was linked to a higher probability of latent TB infection among household contacts. Data were collected prospectively from participants in the intervention arm of a household cluster-randomised trial in two South Africa provinces (Mangaung, Free State, and Capricorn, Limpopo). In intervention group households, TB contacts underwent HIV testing and tuberculin skin testing (TST). TST induration was estimated at two cut-offs (≥5mm, ≥10mm). Multilevel Bayesian regression models estimated posterior distributions of the percentage of household contacts with TST induration ≥5mm and ≥10mm by age group, and compared the odds of latent TB infection by key risk factors including HIV status index case age and study province. A total of 2,985 household contacts of 924 index cases were assessed, with most 2,725 (91.3%) undergoing TST. HIV prevalence in household contacts was 14% and 10% in Mangaung and Capricorn respectively. Overall, 16.8% (458/2,725) had TST induration of ≥5mm and 13.1% (359/2,725) ≥10mm. In Mangaung, children aged 0-4 years had a high TST positivity prevalence compared to their peers in Capricorn (22.0% vs. 7.6%, and 20.5% vs. 2.3%, using TST thresholds of ≥5mm and ≥10mm respectively). Compared to contacts from Capricorn, household contacts living in Mangaung were more likely to have TST induration ≥5mm (odds ratio [OR]: 3.08, 95% credibility interval [CI]: 2.13-4.58) and ≥10mm (OR: 4.52, 95% CI: 3.03-6.97). There was a 90% and 92% posterior probability that the odds of TST induration ≥5mm (OR: 0.79, 95% CI: 0.56-1.14) and ≥10mm (OR: 0.77, 95% CI: 0.53-1.10) respectively were lower in household contacts of HIV-positive compared to HIV-negative index cases. High TST induration positivity, especially among young children and people living in Mangaung indicates considerable TB transmission despite high antiretroviral therapy coverage. Household contact of HIV-positive index TB cases were less likely to have evidence of latent TB infection than contacts of HIV-negative index cases.

Background Tuberculosis (TB) remains a leading cause of mortality, particularly among people with HIV (PWH). In South Africa, the targeted universal TB testing (TUTT) strategy was introduced to shift from symptom-based to symptom-agnostic screening to improve early case detection in PWH. However, limited research has explored provider perceptions of the TUTT strategy. We explored healthcare professionals’ perceptions of the introduction, feasibility, challenges, and potential solutions for implementing TUTT. Methods We conducted a qualitative study using in-depth interviews with 11 purposively selected healthcare professionals (nurses, program managers, and doctors) involved in integrated TB/HIV care in KwaZulu-Natal Province, South Africa. Interviews were audio-recorded, transcribed, and analysed through inductive thematic analysis. Results Four thematic categories with eight overarching themes were identified. TUTT introduction was characterised by largely informal communication, which contributed to variable understanding, while structured dissemination and mentorship supported clearer uptake. TUTT feasibility was shaped by facility capacity, with adequate staffing, diagnostic resources, and workflow organisation enabling smoother integration, whereas under-resourced facilities struggled. Implementation challenges included sputum collection difficulties, especially among asymptomatic PWH, staff shortages, heavy workloads, and fragmented TB/HIV data systems. Proposed solutions centred on expanding access through alternative triage tools such as mobile digital chest X-rays, point-of-care tests, community-based testing, and strengthening provider training, role clarity, and patient education. Conclusion TUTT is perceived as a valuable strategy to improve TB detection in PWH, but its success hinges on addressing operational, infrastructural, and patient engagement barriers. Strengthening resources, integrating data systems, and adopting locally tailored, patient-centred approaches are essential to bridge the gap between policy and practice, thereby optimizing TUTT.

Timely descriptions of HIV service characteristics and their evolution over time across diverse settings are important for monitoring the scale-up of evidence-based program strategies, understanding the implementation landscape, and examining service delivery factors that influence HIV care outcomes. The International epidemiology Databases to Evaluate AIDS (IeDEA) consortium undertakes periodic cross-sectional surveys on service availability and care at participating HIV treatment sites to characterize trends and inform the scientific agenda for HIV care and implementation science communities. IeDEA's 2020 general site assessment survey was developed through a consultative, 18-month process that engaged diverse researchers in identifying content from previous surveys that should be retained for longitudinal analyses and in developing expanded and new content to address gaps in the literature. An iterative review process was undertaken to standardize the format of new survey questions and align them with best practices in survey design and measurement and lessons learned through prior IeDEA site assessment surveys. The survey questionnaire developed through this process included eight content domains covered in prior surveys (patient population, staffing and community linkages, HIV testing and diagnosis, new patient care, treatment monitoring and retention, routine HIV care and screening, pharmacy, record-keeping and patient tracing), along with expanded content related to antiretroviral therapy (differentiated service delivery and roll-out of dolutegravir-based regimens); mental health and substance use disorders; care for pregnant/postpartum women and HIV-exposed infants; tuberculosis preventive therapy; and pediatric/adolescent tuberculosis care; and new content related to Kaposi's sarcoma diagnostics, the impact of COVID-19 on service delivery, and structural barriers to HIV care. The survey was distributed to 238 HIV treatment sites in late 2020, with a 95% response rate. IeDEA's approach for site survey development has broad relevance for HIV research networks and other priority health conditions.

Although there is ample evidence that smoking increases the risk of tuberculosis (TB), the magnitude of impact on TB risk among HIV-infected persons is poorly described. Given that a high proportion of patients with TB are co-infected with HIV in South Africa, the risks arising from the intersection of smoking, TB, and HIV/AIDS have key relevance for tobacco control policies. To evaluate the association of pulmonary tuberculosis (PTB) with current tobacco smoking among men with HIV in South Africa. Case-control study of antiretroviral therapy naïve men with confirmed HIV-infection in Johannesburg. Cases had laboratory-confirmed PTB and controls had no evidence of active TB. Participants were interviewed to collect detailed smoking histories. We enrolled 146 men diagnosed with PTB and 133 controls. Overall, 33% of participants were currently smoking, defined as smoking a cigarette within 2 months (34% cases vs. 32% controls, p = 0.27). Median CD4 count was lower (60 vs. 81 cells/mm3, P = 0.03) and median viral load was higher (173 vs. 67 copies/ul per thousand, P<0.001) among cases versus controls. In adjusted analyses, current smoking tripled the odds of PTB (aOR 3.2; 95%CI: 1.3-7.9, P = 0.01) and former smoking nearly doubled the odds of PTB (aOR 1.8; 95%CI 0.8-4.4, P = 0.18) compared to never smoking. Males with HIV that smoke are at greater odds for developing PTB than non-smokers. Extensive smoking cessation programs are needed to reduce odds of TB and promote health among adults living with HIV.

The importance of high-incidence \"hotspots\" to population-level tuberculosis (TB) incidence remains poorly understood. TB incidence varies widely across countries, but within smaller geographic areas (e.g., cities), TB transmission may be more homogeneous than other infectious diseases. We constructed a steady-state compartmental model of TB in Rio de Janeiro, replicating nine epidemiological variables (e.g., TB incidence) within 1 % of their observed values. We estimated the proportion of TB transmission originating from a high-incidence hotspot (6.0% of the city's population, 16.5% of TB incidence) and the relative impact of TB control measures targeting the hotspot vs. the general community. If each case of active TB in the hotspot caused 0.5 secondary transmissions in the general community for each within-hotspot transmission, the 6.0% of people living in the hotspot accounted for 35.3% of city-wide TB transmission. Reducing the TB transmission rate (i.e., number of secondary infections per infectious case) in the hotspot to that in the general community reduced city-wide TB incidence by 9.8% in year 5, and 29.7% in year 50—an effect similar to halving time to diagnosis for the remaining 94% of the community. The importance of the hotspot to city-wide TB control depended strongly on the extent of TB transmission from the hotspot to the general community. High-incidence hotspots may play an important role in propagating TB epidemics. Achieving TB control targets in a hotspot containing 6% of a city's population can have similar impact on citywide TB incidence as achieving the same targets throughout the remaining community.

The goal of this study was to perform a cost-effectiveness analysis from the public health system perspective, comparing five strategies for Latent Tuberculosis Infection (LTBI) diagnosis in primary health care workers in Brazil. Analytical model for decision making, characterized by cost-effectiveness analysis. Primary Care Level, considering primary health care workers in Brazil. An analytical model for decision making, characterized by a tree of probabilities of events, was developed considering a hypothetical cohort of 10,000 primary health care workers, using the software TreeAge Pro™ 2013 to simulate the clinical and economic impacts of new diagnostic technology (QuantiFERON®-TB Gold in-Tube) versus the traditional tuberculin skin test. This model simulated five diagnostic strategies for LTBI in primary health care workers (HCW) in Brazil: tuberculin skin testing using ≥5 mm cut-off, tuberculin skin testing ≥10 mm cut-off, QuantiFERON®-TB Gold in-Tube, tuberculin skin testing using ≥5 mm cut-off confirmed by QuantiFERON®-TB Gold In-Tube if TST positive, tuberculin skin testing using ≥10 mm cut-off confirmed by QuantiFERON®-TB Gold In-Tube if TST positive. The outcome measures are the number of individuals correctly classified by the test and the number of Tuberculosis cases avoided. The most cost-effective strategy was the tuberculin skin test considering ≥10mm cut-off. The isolated use of the QuantiFERON®-TB Gold In-Tube revealed the strategy of lower efficiency with incremental cost-effectiveness ratio (ICER) of US$ 146.05 for each HCW correctly classified by the test. The tuberculin skin test using ≥10 mm cut-off was the most cost-effective strategy in the diagnosis of Latent Tuberculosis Infection in primary health care works in Brazil.

A high index of suspicion is needed to initiate appropriate testing for tuberculosis due to its protean symptoms, yet health-care providers in low-incidence settings are becoming less familiar with the disease as rates decline. We aimed to estimate delays in tuberculosis diagnosis and treatment at the US national level between 2008 and 2016. In this retrospective observational cohort study, we repurposed private insurance claims data provided by Aetna (Connecticut, USA), to measure health-care delays in tuberculosis diagnosis in the USA in 2008–16. Active tuberculosis was determined by diagnosis codes and the filling of anti-tuberculosis treatment prescriptions. Health-care delays were defined as the duration between the first health-care visit for a tuberculosis symptom and the initiation of anti-tuberculosis treatment. We assessed if delays varied over time, and by patient and system variables, using multivariable regression. We estimated household tuberculosis transmission and respiratory complications after treatment initiation. We confirmed 738 active tuberculosis cases (incidence 1·45 per 100 000 person-years) with a median health-care delay of 24 days (IQR 10–45). Multivariable regression analysis showed that longer delays were associated with older age (8·4% per 10 year increase [95% CI 4·0 to 13·1]; p<0·0086) and non-HIV immunosuppression (19·2% [15·1 to 60·0]; p=0·0432). Presenting with three or more symptoms was associated with a shorter delay (−22·5% [–39·1 to −2·0]; p=0·0415), relative to presenting with one symptom, as did use of chest imaging (−24·9% [–37·9 to −8·9]; p<0·0098), tuberculosis nucleic acid amplification tests (−19·2% [–32·7 to −3·1]; p=0·0241), and care by a tuberculosis specialist provider (−17·2% [–33·1 to −22·3]; p<0·0087). Longer delays were associated with an increased rate of respiratory complications even after controlling for patient characteristics, and an increased rate of secondary tuberculosis among dependents. In the USA, the median health-care delay for privately insured patients with tuberculosis exceeds WHO-recommended levels of 21 days (3 weeks). The results suggest the need for health-care provider education on best practices in tuberculosis diagnosis, including the use of molecular tests and the maintenance of a high index of suspicion for the disease. US National Institutes of Health.

Mobile phone-based messaging support and biomarker feedback independently show evidence of increasing an individual's likelihood of quitting smoking. However, the combination of these two strategies to facilitate smoking cessation has not been adequately explored. We conducted a randomized controlled trial in Baltimore, Maryland, to assess the efficacy of COach2Quit, a smartphone application that provides exhaled carbon monoxide readings with message support. The primary outcome was self-reported and biochemically verified smoking cessation at 30-day follow-up. Secondary outcomes were reduction in smoking, motivation to quit, and engagement and satisfaction with COach2Quit. An intention-to-treat analysis was conducted. Adult smokers were randomized 1:1 to receive brief advice and COach2Quit (intervention, n = 50) or brief advice only (control, n = 52). Thirteen participants were lost to follow-up. At 30-day follow-up, one participant in each arm quit smoking. Median change in carbon monoxide levels (in parts per million (ppm)) (intervention: -3.0 [interquartile range (IQR) -12.0, 2.0]; control: -2.5 [IQR -9.0, 2.0]) and median change in number of cigarettes smoked per day (intervention: -5.5 [IQR -14.0, -1.0]; control: -6.0 [IQR -10.0, -2.0]) was similar between study arms. There was no significant difference in mean percent change in the Reasons for Quitting scale score (intervention: 6.3 [95% confidence interval = -2.2% to 14.8%]; control: -3.6 [95% confidence interval = -9.2% to 2.1%]). A majority (n = 32, 91%) of participants liked having COach2Quit to help them quit smoking. There were no significant differences in smoking cessation, smoking reduction, and motivation to quit between study arms. However, high satisfaction with the COach2Quit application indicates its feasibility and acceptability as a smoking cessation tool. Smoking is the leading preventable cause of morbidity and mortality in the United States. Although counseling and pharmacotherapy are efficacious for smoking cessation, they are not easily accessible or desirable to all smokers, highlighting the need for identifying other interventions. There is evidence for the efficacy of mobile phone-based messaging support for smoking cessation. However, there is limited research on the efficacy of biomarker feedback, much less interventions that combine these two approaches. This research contributes to filling this gap and identifying novel interventions to facilitate smoking cessation.