Association of diabetes, smoking, and alcohol use with subclinical-to-symptomatic spectrum of tuberculosis in 16 countries: an individual participant data meta-analysis of national tuberculosis prevalence surveys

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

Tobacco smoking clusters in households affected by tuberculosis in an individual participant data meta-analysis of national tuberculosis prevalence surveys: Time for household-wide interventions?

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

Association of diabetes, smoking, and alcohol use with subclinical-to-symptomatic spectrum of tuberculosis in 16 countries: an individual participant data meta-analysis of national tuberculosis prevalence surveys

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

National tuberculosis prevalence surveys in Africa, 2008–2016: an overview of results and lessons learned

Objective and methods: Worldwide, tuberculosis (TB) is the leading cause of death from a single infectious agent. In many countries, national TB prevalence surveys are the only way to reliably measure the burden of TB disease and can also provide other evidence to inform national efforts to improve TB detection and treatment. Our objective was to synthesise the results and lessons learned from national surveys completed in Africa between 2008 and 2016, to complement a previous review for Asia. Results: Twelve surveys completed in Africa were identified: Ethiopia (2010–2011), Gambia (2011–2013), Ghana (2013), Kenya (2015–2016), Malawi (2013–2014), Nigeria (2012), Rwanda (2012), Sudan (2013–2014), Tanzania (2011–2012), Uganda (2014–2015), Zambia (2013–2014) and Zimbabwe (2014). The eligible population in all surveys was people aged ≥15 years who met residency criteria. In total 588 105 individuals participated, equivalent to 82% (range 57–96%) of those eligible. The prevalence of bacteriologically confirmed pulmonary TB disease in those ≥15 years varied from 119 (95% CI 79–160) per 100 000 population in Rwanda and 638 (95% CI 502–774) per 100 000 population in Zambia. The male:female ratio was 2.0 overall, ranging from 1.2 (Ethiopia) to 4.1 (Uganda). Prevalence per 100 000 population generally increased with age, but the absolute number of cases was usually highest among those aged 35–44 years. Of identified TB cases, 44% (95% CI 40–49) did not report TB symptoms during screening and were only identified as eligible for diagnostic testing due to an abnormal chest X-ray. The overall ratio of prevalence to case notifications was 2.5 (95% CI 1.8–3.2) and was consistently higher for men than women. Many participants who did report TB symptoms had not sought care; those that had were more likely to seek care in a public health facility. HIV prevalence was systematically lower among prevalent cases than officially notified TB patients with an overall ratio of 0.5 (95% CI 0.3–0.7). The two main study limitations were that none of the surveys included people <15 years, and 5 of 12 surveys did not have data on HIV status. Conclusions: National TB prevalence surveys implemented in Africa between 2010 and 2016 have contributed substantial new evidence about the burden of TB disease, its distribution by age and sex, and gaps in TB detection and treatment. Policies and practices to improve access to health services and reduce under-reporting of detected TB cases are needed, especially among men. All surveys provide a valuable baseline for future assessment of trends in TB disease burden

Association between current smoking of people with TB and the same in their household members.

Association between current smoking of people with TB and the same in their household members.</p

Association between alcohol drinking of people with TB and the same in their household members.

Association between alcohol drinking of people with TB and the same in their household members.</p

Sensitivity analysis- prevalence of NCD/NCD risk factors in members of households with TB compared to those without TB.

Sensitivity analysis- prevalence of NCD/NCD risk factors in members of households with TB compared to those without TB.</p

Sensitivity analysis-impact of misclassification of diabetes on its association with members of households with TB.

Sensitivity analysis-impact of misclassification of diabetes on its association with members of households with TB.</p

Alcohol drinking twice per week or more in members of households with TB compared to those without TB.

Alcohol drinking twice per week or more in members of households with TB compared to those without TB.</p

PRISMA-IPD checklist of items to include when reporting a systematic review and meta-analysis of individual participant data (IPD).

PRISMA-IPD checklist of items to include when reporting a systematic review and meta-analysis of individual participant data (IPD).</p