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Tuberculosis (TB) and non-communicable diseases (NCD) share predisposing risk factors. TB-associated NCD might cluster within households affected with TB requiring shared prevention and care strategies. We conducted an individual participant data meta-analysis of national TB prevalence surveys to determine whether NCD cluster in members of households with TB. We identified eligible surveys that reported at least one NCD or NCD risk factor through the archive maintained by the World Health Organization and searching in Medline and Embase from 1 January 2000 to 10 August 2021, which was updated on 23 March 2023. We compared the prevalence of NCD and their risk factors between people who do not have TB living in households with at least one person with TB (members of households with TB), and members of households without TB. We included 16 surveys (n = 740,815) from Asia and Africa. In a multivariable model adjusted for age and gender, the odds of smoking was higher among members of households with TB (adjusted odds ratio (aOR) 1.23; 95% CI: 1.11-1.38), compared with members of households without TB. The analysis did not find a significant difference in the prevalence of alcohol drinking, diabetes, hypertension, or BMI between members of households with and without TB. Studies evaluating household-wide interventions for smoking to reduce its dual impact on TB and NCD may be warranted. Systematically screening for NCD using objective diagnostic methods is needed to understand the actual burden of NCD and inform comprehensive interventions.

Summary: Background: Non-communicable diseases (NCDs) and NCD risk factors, such as smoking, increase the risk for tuberculosis (TB). Data are scarce on the risk of prevalent TB associated with these factors in the context of population-wide systematic screening and on the association between NCDs and NCD risk factors with different manifestations of TB, where ∼50% being asymptomatic but bacteriologically positive (subclinical). We did an individual participant data (IPD) meta-analysis of national and sub-national TB prevalence surveys to synthesise the evidence on the risk of symptomatic and subclinical TB in people with NCDs or risk factors, which could help countries to plan screening activities. Methods: In this systematic review and IPD meta-analysis, we identified eligible prevalence surveys in low-income and middle-income countries that reported at least one NCD (e.g., diabetes) or NCD risk factor (e.g., smoking, alcohol use) through the archive maintained by the World Health Organization and by searching in Medline and Embase from January 1, 2000 to August 10, 2021. The search was updated on March 23, 2023. We performed a one-stage meta-analysis using multivariable multinomial models. We estimated the proportion of and the odds ratio for subclinical and symptomatic TB compared to people without TB for current smoking, alcohol use, and self-reported diabetes, adjusted for age and gender. Subclinical TB was defined as microbiologically confirmed TB without symptoms of current cough, fever, night sweats, or weight loss and symptomatic TB with at least one of these symptoms. We assessed heterogeneity using forest plots and I2 statistic. Missing variables were imputed through multi-level multiple imputation. This study is registered with PROSPERO (CRD42021272679). Findings: We obtained IPD from 16 national surveys out of 21 national and five sub-national surveys identified (five in Asia and 11 in Africa, N = 740,815). Across surveys, 15.1%–56.7% of TB were subclinical (median: 38.1%). In the multivariable model, current smoking was associated with both subclinical (OR 1.67, 95% CI 1.27–2.40) and symptomatic TB (OR 1.49, 95% CI 1.34–1.66). Self-reported diabetes was associated with symptomatic TB (OR 1.67, 95% CI 1.17–2.40) but not with subclinical TB (OR 0.92, 95% CI 0.55–1.55). For alcohol drinking ≥ twice per week vs no alcohol drinking, the estimates were imprecise (OR 1.59, 95% CI 0.70–3.62) for subclinical TB and OR 1.43, 95% CI 0.59–3.46 for symptomatic TB). For the association between current smoking and symptomatic TB, I2 was high (76.5% (95% CI 62.0–85.4), while the direction of the point estimates was consistent except for three surveys with wide CIs. Interpretation: Our findings suggest that current smokers are more likely to have both symptomatic and subclinical TB. These individuals can, therefore, be prioritised for intensified screening, such as the use of chest X-ray in the context of community-based screening. People with self-reported diabetes are also more likely to have symptomatic TB, but the association is unclear for subclinical TB. Funding: None.

Abstract 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.

Summary: Background: Effectiveness of health programmes can be undermined when the implementation misaligns with local beliefs and behaviours. To design context-driven implementation strategies, we explored beliefs and behaviours regarding chronic respiratory disease (CRD) in diverse low-resource settings. Methods: This observational mixed-method study was conducted in Africa (Uganda), Asia (Kyrgyzstan and Vietnam) and Europe (rural Greece and a Roma camp). We systematically mapped beliefs and behaviours using the SETTING-tool. Multiple qualitative methods among purposively selected community members, health-care professionals, and key informants were triangulated with a quantitative survey among a representative group of community members and health-care professionals. We used thematic analysis and descriptive statistics. Findings: We included qualitative data from 340 informants (77 interviews, 45 focus group discussions, 83 observations of community members’ households and health-care professionals’ consultations) and quantitative data from 1037 community members and 204 health-care professionals. We identified three key themes across the settings; namely, (1) perceived CRD identity (community members in all settings except the rural Greek strongly attributed long-lasting respiratory symptoms to infection, predominantly tuberculosis); (2) beliefs about causes (682 [65·8%] of 1037 community members strongly agreed that tobacco smoking causes symptoms, this number was 198 [19·1%] for household air pollution; typical perceived causes ranged from witchcraft [Uganda] to a hot–cold disbalance [Vietnam]); and (3) norms and social structures (eg, real men smoke [Kyrgyzstan and Vietnam]). Interpretation: When designing context-driven implementation strategies for CRD-related interventions across these global settings, three consistent themes should be addressed, each with common and context-specific beliefs and behaviours. Context-driven strategies can reduce the risk of implementation failure, thereby optimising resource use to benefit health outcomes. Funding: European Commission Horizon 2020. Translations: For the Greek, Russian and Vietnamese translations of the abstract see Supplementary Materials section.

Background Uganda introduced Xpert® MTB/RIF assay into its TB diagnostic algorithm in January 2012. In July 2018, this assay was replaced with Xpert® MTB/RIF Ultra assay. We set out to compare the tests done and tuberculosis cases detected by Xpert® MTB/RIF and Xpert® MTB/RIF Ultra assay in Uganda. Methods This was a before and after study, with the tests done and TB cases detected between Jan-June 2019 when using Xpert® MTB/RIF Ultra assay compared to those done between Jan-June 2018 while using Xpert® MTB/RIF assay. This data was analyzed using Stata version 13, it was summarized into measures of central tendency and the comparison between Xpert® MTB/RIF Ultra and Xpert® MTB/RIF was explored using a two-sided T-test which was considered significant if p Results One hundred and twelve (112) GeneXpert sites out of a possible 239 were included in the study. 128,476 (M: 1147.11, SD: 842.88) tests were performed with Xpert® MTB/RIF Ultra assay, with 9693 drug-susceptible TB (DS-TB) cases detected (M: 86.54, SD: 62.12) and 144 (M: 1.28, SD: 3.42) Rifampicin Resistant TB cases (RR-TB). Whilst 107, 890 (M: 963.30, SD: 842.88) tests were performed with Xpert® MTB/RIF assay between, 8807 (M: 78.63, SD: 53.29) DS-TB cases were detected, and 147 (M: 1.31, SD: 2.39) RR-TB cases. The Number Need to Test (NNT) to get one TB case was 12 for Xpert® MTB/RIF and 13 for Xpert ®MTB/RIF Ultra. On comparing the two assays in terms of test performance (p = 0.75) and case detection both susceptible TB (p = 0.31) and RR-TB (p = 0.95) were not found statistically significant. Conclusions This study found no significant difference in test performance and overall detection of DS-TB and RR-TB when using Xpert® MTB/RIF Ultra and Xpert® MTB/RIF assays. The health systems approach should be used to elucidate all the probable potential of Xpert® MTB/RIF Ultra.

Introduction: East Africa countries (Tanzania, Kenya, and Uganda) are among tuberculosis high burdened countries globally. As we race to accelerate progress towards a world free of tuberculosis by 2035, gaps related to screening and diagnosis in the cascade care need to be addressed. Methods: We conducted a three-year (2015–2017) retrospective study using routine program data in 21 health facilities from East Africa. Data abstraction were done at tuberculosis clinics, outpatient departments (OPD), human immunodeficiency virus (HIV) and diabetic clinics, and then complemented with structured interviews with healthcare providers to identify possible gaps related to integration, screening, and diagnosis of tuberculosis. Data were analyzed using STATA™ Version 14.1. Results: We extracted information from 49,454 presumptive TB patients who were registered in the 21 facilities between January 2015 and December 2017. A total of 9,565 tuberculosis cases were notified; 46.5% (4,450) were bacteriologically confirmed and 31.5% (3,013) were HIV-infected. Prevalence of tuberculosis among presumptive pulmonary tuberculosis cases was 17.4%. The outcomes observed were as follows: 79.8% (7,646) cured or completed treatment, 6.6% (634) died, 13.3% (1,270) lost to follow-up or undocumented and 0.4% (34) treatment failure. In all countries, tuberculosis screening was largely integrated at OPD and HIV clinics. High patient load, weak laboratory specimen referral system, shortage of trained personnel, and frequent interruption of laboratory supplies were the major cited challenges in screening and diagnosis of tuberculosis. Conclusion: Screening and diagnostic activities were frequently affected by scarcity of human and financial resources. Tuberculosis screening was mainly integrated at OPD and HIV clinics, with less emphasis on the other health facility clinics. Closing gaps related to TB case finding and diagnosis in developing countries requires sustainable investment for both human and financial resources and strengthen the integration of TB activities within the health system.

Abstract Background Low-resource settings are disproportionally burdened by chronic lung disease due to early childhood disadvantages and indoor/outdoor air pollution. However, data on the socioeconomic impact of respiratory diseases in these settings are largely lacking. Therefore, we aimed to estimate the chronic lung disease-related socioeconomic burden in diverse low-resource settings across the globe. To inform governmental and health policy, we focused on work productivity and activity impairment and its modifiable clinical and environmental risk factors. Methods We performed a cross-sectional, observational FRESH AIR study in Uganda, Vietnam, Kyrgyzstan, and Greece. We assessed the chronic lung disease-related socioeconomic burden using validated questionnaires among spirometry-diagnosed COPD and/or asthma patients (total N = 1040). Predictors for a higher burden were studied using multivariable linear regression models including demographics (e.g. age, gender), health parameters (breathlessness, comorbidities), and risk factors for chronic lung disease (smoking, solid fuel use). We applied identical models per country, which we subsequently meta-analyzed. Results Employed patients reported a median [IQR] overall work impairment due to chronic lung disease of 30% [1.8–51.7] and decreased productivity (presenteeism) of 20.0% [0.0–40.0]. Remarkably, work time missed (absenteeism) was 0.0% [0.0–16.7]. The total population reported 40.0% [20.0–60.0] impairment in daily activities. Breathlessness severity (MRC-scale) (B = 8.92, 95%CI = 7.47–10.36), smoking (B = 5.97, 95%CI = 1.73–10.22), and solid fuel use (B = 3.94, 95%CI = 0.56–7.31) were potentially modifiable risk factors for impairment. Conclusions In low-resource settings, chronic lung disease-related absenteeism is relatively low compared to the substantial presenteeism and activity impairment. Possibly, given the lack of social security systems, relatively few people take days off work at the expense of decreased productivity. Breathlessness (MRC-score), smoking, and solid fuel use are potentially modifiable predictors for higher impairment. Results warrant increased awareness, preventive actions and clinical management of lung diseases in low-resource settings from health policymakers and healthcare workers.

Effectiveness of health interventions can be substantially impaired by implementation failure. Context-driven implementation strategies are critical for successful implementation. However, there is no practical, evidence-based guidance on how to map the context in order to design context-driven strategies. Therefore, this practice paper describes the development and validation of a systematic context-mapping tool. The tool was cocreated with local end-users through a multistage approach. As proof of concept, the tool was used to map beliefs and behaviour related to chronic respiratory disease within the FRESH AIR project in Uganda, Kyrgyzstan, Vietnam and Greece. Feasibility and acceptability were evaluated using the modified Conceptual Framework for Implementation Fidelity. Effectiveness was assessed by the degree to which context-driven adjustments were made to implementation strategies of FRESH AIR health interventions. The resulting Setting-Exploration-Treasure-Trail-to-Inform-implementatioN-strateGies (SETTING-tool) consisted of six steps: (1) Coset study priorities with local stakeholders, (2) Combine a qualitative rapid assessment with a quantitative survey (a mixed-method design), (3) Use context-sensitive materials, (4) Collect data involving community researchers, (5) Analyse pragmatically and/or in-depth to ensure timely communication of findings and (6) Continuously disseminate findings to relevant stakeholders. Use of the tool proved highly feasible, acceptable and effective in each setting. To conclude, the SETTING-tool is validated to systematically map local contexts for (lung) health interventions in diverse low-resource settings. It can support policy-makers, non-governmental organisations and health workers in the design of context-driven implementation strategies. This can reduce the risk of implementation failure and the waste of resource potential. Ultimately, this could improve health outcomes.

BackgroundTuberculosis (TB) is the 9th leading cause of death from a single infectious agent. Patients live in a complex health care system with both formal and informal providers, and it is important that a TB diagnosis is not missed at the first interaction with the health care system. In this study, we highlight the health seeking behavior of patients and missed opportunities for early TB diagnosis for which interventions could be instituted to ensure early TB diagnosis and prompt TB treatment initiation.MethodsThis study was nested in a cross-sectional study that assessed the accuracy of different Xpert MTB/Rif implementation strategies in programmatic settings at the referral hospitals in Uganda. We documented the symptom profile of presumptive TB patients and assessed the health seeking behavior of those with chronic cough by calculating proportion of patients that visited each type of health facility and further calculated the odds of being TB positive given the type of health facility initially visited for consultation.ResultsA total of 1,863 presumptive TB patients were enrolled of which 979 (54.5%) were male, and 1795 (99.9%) had chronic cough. A total of 1352 (75.4%) had previously sought care for chronic cough, with 805 (59.6%) seeking care from a public health facility followed by private health facility (289; 21.4%). Up to 182 (13.5%) patients visited a drug store for chronic cough. Patients whose first contact was a private health facility were more likely to have a positive GeneXpert test (adjOR 1.4, 95% CI: 1.0-1.9; p = 0.047).ConclusionsChronic cough is a main symptom for many of the presumptive TB patients presenting at referral hospitals, with several patients having to visit the health system more than once before a TB diagnosis is made. This suggests the need for patients to be thoroughly evaluated at first interface with the health care system to ensure prompt diagnosis and treatment initiation. Improved TB diagnosis possibly with the GeneXpert test, at first contact with the health care system has potential to increase TB case finding and break the transmission cycle in the community.

Diagnosis of smear-negative tuberculosis (TB), which is frequently seen in HIV-infected patients, is a challenge without conventional culture methods. Since 2007, the WHO (World Health Organization) has endorsed new or improved tests for increased and rapid diagnosis of TB. This study was undertaken in an effort to evaluate the accuracy of two rapid culture methods: the Microscopic Observation Drug Susceptibility assay (MODS) and Nitrate Reductase Assay (NRA), and the molecular based test Xpert ® MTB/Rif (Xpert), for diagnosis of smear-negative TB in HIV patients using the mycobacteria growth indicator tube (MGIT) in the BACTECTM MGITTM 960 system as the reference test. 430 smear-negative patients with presumptive TB were enrolled in a cross-sectional study at a tertiary care facility in Uganda. Their sputum was tested on MODS, NRA, Xpert and MGIT. Of the 430 patients, 373 had complete results to compute test accuracy. Mycobacterium tuberculosis (MTB) was detected in 43 patients by MGIT. The sensitivity and specificity were 24.4% and 98.1% for MODS, 41.5% and 92% for NRA, 48.8% and 95.1% for Xpert, respectively. The low sensitivity of the tests implies that additional diagnostics such as chest X-ray and conventional liquid culture methods might still be needed to detect TB in smear-negative HIV patients. The high specificity of the tests is useful to confirm TB in HIV patients with symptoms suggestive of TB.

INTRODUCTION: diagnostic guidelines for Tuberculosis (TB) in HIV infected patients previously relied on microscopy where the value of initial antibiotic treatment for exclusion of pulmonary TB (PTB) was limited. New guidelines rely on the Xpert MTB Rif test (Xpert). However, the value of the antibiotic treatment remains unclear particularly in individuals who are smear-negative and Xpert-negative-given Xpert has only moderate sensitivity for smear-negative PTB. We assessed an algorithm involving initial treatment with antibiotics prior empiric TB treatment in HIV patients with presumptive PTB who were both smear and Xpert negative.