Implementation of systematic screening for tuberculosis disease and tuberculosis preventive treatment among people living with HIV attending antiretroviral treatment clinics in Ghana: a national pilot study.

OBJECTIVES: To assess the yield and cost of implementing systematic screening for tuberculosis (TB) disease among people living with HIV (PLHIV) and initiation of TB preventive treatment (TPT) in Ghana. DESIGN: Prospective cohort study from August 2019 to December 2020. SETTING: One hospital from each of Ghana's regions (10 total). PARTICIPANTS: Any PLHIV already receiving or newly initiating antiretroviral treatment were eligible for inclusion. INTERVENTIONS: All participants received TB symptom screening and chest radiography. Those with symptoms and/or an abnormal chest X-ray provided a sputum sample for microbiological testing. All without TB disease were offered TPT. PRIMARY AND SECONDARY OUTCOME MEASURES: We estimated the proportion diagnosed with TB disease and proportion initiating TPT. We used logistic regression to identify factors associated with TB disease diagnosis. We used microcosting to estimate the health system cost per person screened (2020 US$). RESULTS: Of 12 916 PLHIV attending participating clinics, 2639 (20%) were enrolled in the study and screened for TB disease. Overall, 341/2639 (12.9%, 95% CI 11.7% to 14.3%) had TB symptoms and/or an abnormal chest X-ray; 50/2639 (1.9%; 95% CI 1.4% to 2.5%) were diagnosed with TB disease, 20% of which was subclinical. In multivariable analysis, only those newly initiating antiretroviral treatment were at increased odds of TB disease (adjusted OR 4.1, 95% CI 2.0 to 8.2). Among 2589 participants without TB, 2581/2589 (99.7%) initiated TPT. Overall, the average cost per person screened during the study was US$57.32. CONCLUSION: In Ghana, systematic TB disease screening among PLHIV was of high yield and modest cost when combined with TPT. Our findings support WHO recommendations for routine TB disease screening among PLHIV.

Prevalence of subclinical pulmonary tuberculosis in adults in community settings: an individual participant data meta-analysis.

BACKGROUND: Subclinical pulmonary tuberculosis, which presents without recognisable symptoms, is frequently detected in community screening. However, the disease category is poorly clinically defined. We explored the prevalence of subclinical pulmonary tuberculosis according to different case definitions. METHODS: We did a one-stage individual participant data meta-analysis of nationally representative surveys that were conducted in countries with high incidence of tuberculosis between 2007 and 2020, that reported the prevalence of pulmonary tuberculosis based on chest x-ray and symptom screening in participants aged 15 years and older. Screening and diagnostic criteria were standardised across the surveys, and tuberculosis was defined by positive Mycobacterium tuberculosis sputum culture. We estimated proportions of subclinical tuberculosis for three case definitions: no persistent cough (ie, duration ≥2 weeks), no cough at all, and no symptoms (ie, absence of cough, fever, chest pain, night sweats, and weight loss), both unadjusted and adjusted for false-negative chest x-rays and uninterpretable culture results. FINDINGS: We identified 34 surveys, of which 31 were eligible. Individual participant data were obtained and included for 12 surveys (620 682 participants) across eight countries in Africa and four in Asia. Data on 602 863 participants were analysed, of whom 1944 had tuberculosis. The unadjusted proportion of subclinical tuberculosis was 59·1% (n=1149/1944; 95% CI 55·8-62·3) for no persistent cough and 39·8% (773/1944; 36·6-43·0) for no cough of any duration. The adjusted proportions were 82·8% (95% CI 78·6-86·6) for no persistent cough and 62·5% (56·6-68·7) for no cough at all. In a subset of four surveys, the proportion of participants with tuberculosis but without any symptoms was 20·3% (n=111/547; 95% CI 15·5-25·1) before adjustment and 27·7% (95% CI 21·0-36·4) after adjustment. Tuberculosis without cough, irrespective of its duration, was more frequent among women (no persistent cough: adjusted odds ratio 0·79, 95% CI 0·63-0·97; no cough: adjusted odds ratio 0·76, 95% CI 0·62-0·93). Among participants with tuberculosis, 29·1% (95% CI 25·2-33·3) of those without persistent cough and 23·1% (18·8-27·4) of those without any cough had positive smear examinations. INTERPRETATION: The majority of people in the community who have pulmonary tuberculosis do not report cough, a quarter report no tuberculosis-suggestive symptoms at all, and a quarter of those not reporting any cough have positive sputum smears, suggesting infectiousness. In high-incidence settings, subclinical tuberculosis could contribute considerably to the tuberculosis burden and to Mycobacterium tuberculosis transmission. FUNDING: Mr Willem Bakhuys Roozeboom Foundation.

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.

Case finding of tuberculosis among mining communities in Ghana.

BACKGROUND: Data on active TB case finding activities among artisanal gold mining communities (AMC) is limited. The study assessed the yield of TB cases from the TB screening activities among AMC in Ghana, the factors associated with TB in these communities and the correlation between the screening methods and a diagnosis of TB. METHODS: We conducted secondary data analyses of NTP program data collected from TB case finding activities using symptom screening and mobile X-ray implemented in hard to reach AMC. Yield of TB cases, number needed to screen (NNS) and the number needed to test (NNT) to detect a TB case were assessed and logistic regression were conducted to assess factors associated with TB. The performance of screening methods chest X-ray and symptoms in the detection of TB cases was also evaluated. RESULTS: In total 10,441 people from 78 communities in 24 districts were screened, 55% were female and 60% (6,296) were in the aged 25 to 54 years. Ninety-five TB cases were identified, 910 TB cases per 100,000 population screened; 5.6% of the TB cases were rifampicin resistant. Being male (aOR 5.96, 95% CI 3.25-10.92, P < 0.001), a miner (aOR 2.70, 95% CI 1.47-4.96, P = 0.001) and age group 35 to 54 years (aOR 2.27, 95% CI 1.35-3.84, P = 0.002) were risk factors for TB. NNS and NNT were 110 and 24 respectively.; Cough of any duration had the strongest association with X-ray suggestive of TB with a correlation coefficient of 0.48. Cough was most sensitive for a diagnosis of TB; sensitivity of 86.3% (95% CI 79.4-93.2) followed by X-ray, sensitivity 81.1% (95% CI 71.7-88.4). The specificities of the symptoms and X-rays ranged from 80.2% (cough) to 97.3% (sputum). CONCLUSION: The high risk of TB in the artisanal mining communities and in miners in this study reinforces the need to target these populations with outreach programs particularly in hard to reach areas. The diagnostic value of cough highlights the usefulness of symptom screening in this population that may be harnessed even in the absence of X-ray to identify those suspected to have TB for further evaluation.