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.

Rapid antiretroviral therapy initiation in patients with advanced HIV disease: 6-month outcomes of an observational cohort evaluation in Lesotho.

For adults and adolescents, the World Health Organization defines advanced HIV disease (AHD) as a CD4 (cluster of differentiation 4) count of <200 cells/mm3 or a clinical stage 3 or 4 event. We describe clinical outcomes in a cohort of AHD patients at two regional hospitals in Lesotho. From November 2018-June 2019, we prospectively enrolled eligible patients (≥15 years) not on antiretroviral therapy (ART) presenting with WHO-defined AHD into a differentiated model of care for AHD (including rapid ART initiation) and followed them for six months. All patients received Tuberculosis (TB) symptom screening with further diagnostic testing; serum cryptococcal antigen (CrAg) screening was done for CD4 <100 cells/mm3 or WHO clinical stage 3 or 4. Medical record data were abstracted using visit checklist forms. Categorical and continuous variables were summarized using frequencies, percentages, and means, respectively. Kaplan-Meier was used to estimate survival. Of 537 HIV-positive patients screened, 150 (27.9%) had AHD of which 109 were enrolled. Mean age was 38 years and 62 (56.9%) were men. At initial clinic visit, 8 (7.3%) were already on treatment and 33% (36/109) had presumptive TB per symptom screening. Among 39/109 (40.2%) patients screened for CrAg at initial visit, five (12.8%) were CrAg-positive. Among 109 enrolled, 77 (70.6%) initiated ART at their initial clinic visit, while 32 delayed ART initiation (median delay: 14 days). Of the 109 participants enrolled, 76 (69.7%) completed the 6-month follow-up, 17 (15.6%) were lost to follow-up, 5 (4.6%) transferred to other health facilities and 11 (10.1%) died. The 6-month survival was 87.4%; among 74 patients with a viral load result, 6-month viral suppression (<1,000 copies/ml) was 85.1%. Our study found that even after the implementation of Test and Treat of ART in 2016 in Lesotho, over 25% of patients screened had AHD. Patients with AHD had a high prevalence of TB and CrAg positivity, underscoring the need to assess for AHD and rapidly initiate ART within a package of AHD care for optimal patient outcomes.

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.

Antituberculosis Drug Resistance Survey in Lesotho, 2008-2009: Lessons Learned.

SETTING: Drug resistance is an increasing threat to tuberculosis (TB) control worldwide. The World Health Organization advises monitoring for drug resistance, with either ongoing surveillance or periodic surveys. METHODS: The antituberculosis drug resistance survey was conducted in Lesotho in 2008-2009. Basic demographic and TB history information was collected from individuals with positive sputum smear results at 17 diagnostic facilities. Additional sputum sample was sent to the national TB reference laboratory for culture and drug susceptibility testing. RESULTS: Among 3441 eligible smear-positive persons, 1121 (32.6%) were not requested to submit sputum for culture. Among 2320 persons submitted sputum, 1164 (50.2%) were not asked for clinical information or did not have valid sputum samples for testing. In addition, 445/2320 (19.2%) were excluded from analysis because of other laboratory or data management reasons. Among 984/3441 (28.6%) persons who had data available for analysis, MDR-TB was present in 24/773 (3.1%) of new and 25/195 (12.8%) of retreatment TB cases. Logistical, operational and data management challenges affected survey results. CONCLUSION: MDR-TB is prevalent in Lesotho, but limitations reduced the reliability of our findings. Multiple lessons learned during this survey can be applied to improve the next drug resistance survey in Lesotho and other resource constrained countries may learn how to avoid these bottlenecks.

Preventing tuberculosis among HIV-infected pregnant women in Lesotho: the case for rolling out active case finding and isoniazid preventive therapy.

BACKGROUND: The Lesotho Ministry of Health issued guidelines on active case finding (ACF) for tuberculosis (TB) and isoniazid preventive therapy (IPT) in April 2011. ACF has been recommended in maternal and child health (MCH) settings globally, however, the feasibility of implementing IPT within MCH in countries with high concurrent HIV and TB epidemics is unknown. DESIGN/METHODS: The study evaluated the implementation of ACF and IPT guidelines in MCH settings in 2 health facilities in Lesotho. This descriptive prospective study analyzed data collected during routine services. Categorical data and continuous variables were summarized using descriptive statistics. The χ test or Wilcoxon rank-sum test was used to ascertain significant associations between categorical and continuous variables, respectively. RESULTS: Data from 160 HIV-positive and 640 HIV-negative women were reviewed. Within this study population, 99.8% of women were screened for TB, and 11.4% HIV-positive women compared with 2.3% HIV-negative women were reported to have symptoms of TB (P < 0.001). IPT was initiated in 124/158 (78.5%) HIV-positive pregnant women, 64.5% women completed a 6-month IPT regimen, 2 (1.6%) died of causes unrelated to IPT/TB, and 31.5% were lost to follow-up. Predictors of IPT initiation among HIV-positive women included gestational age at the first antenatal visit (unadjusted odds ratio, -0.93; 95% confidence interval: -0.88 to 0.98), and receipt of antiretroviral therapy for treatment rather than for prevention of mother-to-child transmission prophylaxis only (odds ratio, 4.59; 95% confidence interval: 1.32 to 15.93). CONCLUSIONS: Implementation of ACF and IPT is feasible within the MCH setting. Uptake of IPT during pregnancy among HIV-positive women was high, but with a high rate of loss to follow-up.