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. Funding: None.

Risk for development of active tuberculosis in patients with chronic airway disease-a systematic review of evidence.

Reports suggest an increased risk of tuberculosis (TB) in people with chronic airway diseases (CADs) such as chronic obstructive pulmonary disease (COPD), but evidence has not been systematically reviewed. We performed a systematic review by searching MEDLINE and Embase for studies published from 1 January 1993 to 15 January 2021 reporting the association between the incident risk of TB in people with CADs (asthma, COPD and bronchiectasis). Two reviewers independently assessed the quality of individual studies. We included nine studies, with two from low-income high TB burden countries. Three cohort studies reported a statistically significant independent association between COPD and the risk of TB in high-income countries (n=711 389). Hazard ratios for incident TB ranged from 1.44 to 3.14 adjusted for multiple confounders including age, sex and comorbidity. There was large between-study heterogeneity (I2=97.0%) across studies. The direction of effect on the TB risk from asthma was inconsistent. Chronic bronchitis or bronchiectasis studies were limited. The small number of available studies demonstrated an increased risk of TB in people with COPD; however, the magnitude of the increase varies by setting and population. Data in high TB burden countries and for other CADs are limited.

Sensitivity and specificity of WHO's recommended four-symptom screening rule for tuberculosis in people living with HIV: a systematic review and meta-analysis.

BACKGROUND: Since 2011, WHO recommends a four-symptom screening rule to exclude active tuberculosis in people living with HIV before starting tuberculosis preventive treatment (ie, absence of current cough, weight loss, night sweats, or fever). We assessed the sensitivity and specificity of the screening rule among people living with HIV based on antiretroviral therapy (ART) status and the added contribution of chest radiography. METHODS: We did a systematic review and meta-analysis. We searched PubMed, Embase, and the Cochrane Library from Jan 1, 2011, to March 12, 2018, for studies published after the WHO issued recommendations on the use of the four-symptom screening rule. We also searched abstracts from relevant international conferences. We included studies that collected sputum or any specimens (eg, urine, blood, or fine-needle aspirates from lymph nodes) from people with HIV regardless of signs or symptoms. Case-control studies were excluded because they are prone to bias. Active tuberculosis was diagnosed with bacteriological confirmation by culture or Xpert MTB/RIF of any specimens. Two investigators extracted the data, including age, sex, and ART status. We calculated sensitivity, specificity, and 95% CI. When at least four studies were available, we estimated pooled sensitivity and specificity using random and effects bivariate models; otherwise we used univariate random-effects models. FINDINGS: Of 4615 records identified by the search, 21 were included in the review (involving 15 427 people including 1559 with active tuberculosis). 18 eligible studies were included in the final meta-analysis. Seven studies provided data on people receiving ART. The pooled sensitivity of the four-symptom screening rule was lower for 4640 people on ART (51·0%, 95% CI 28·4-73·2) than for 8664 who were ART-naive (89·4%, 83·0-93·5). Pooled specificity for those on ART was 70·7% (95% CI 47·8-86·4) and for ART-naive people was 28·1% (18·6-40·1). On the basis of data from 646 individuals in two studies, the addition of any abnormal chest radiographic findings in people on ART improved sensitivity from 52·2% (95% CI 38·0-66·0) to 84·6% (69·7-92·9) but decreased specificity from 55·5% (95% CI 51·8-59·2) to 29·8% (26·3-33·6). INTERPRETATION: Our review suggested a lower sensitivity of the WHO four-symptom screening rule among people with HIV who are on ART than in those who are ART naive. The addition of chest radiography could improve the screening rule in people living with HIV who are on ART, provided it does not pose a barrier to preventive treatment. FUNDING: None.

National policies on the management of latent tuberculosis infection: review of 98 countries.

OBJECTIVE: To review policies on management of latent tuberculosis infection in countries with low and high burdens of tuberculosis. METHODS: We divided countries reporting data to the World Health Organization (WHO) Global Tuberculosis Programme into low and high tuberculosis burden, based on WHO criteria. We identified national policy documents on management of latent tuberculosis through online searches, government websites, WHO country offices and personal communication with programme managers. We made a descriptive analysis with a focus on policy gaps and deviations from WHO policy recommendations. FINDINGS: We obtained documents from 68 of 113 low-burden countries and 30 of 35 countries with the highest burdens of tuberculosis or human immunodeficiency virus (HIV)-associated tuberculosis. Screening and treatment of latent tuberculosis infection in people living with HIV was recommended in guidelines of 29 (96.7%) high-burden and 54 (79.7%) low-burden countries. Screening for children aged < 5 years with household tuberculosis contact was the policy of 25 (83.3%) high- and 28 (41.2%) low-burden countries. In most high-burden countries the recommendation was symptom screening alone before treatment, whereas in all low-burden countries it was testing before treatment. Some low-burden countries' policies did not comply with WHO recommendations: nine (13.2%) recommended tuberculosis preventive treatment for travellers to high-burden countries and 10 (14.7%) for patients undergoing abdominal surgery. CONCLUSION: Lack of solid evidence on certain aspects of management of latent tuberculosis infection results in national policies which vary considerably. This highlights a need to advance research and develop clear, implementable and evidence-based WHO policies.