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Abstract Background In household contact investigations of tuberculosis (TB), a second tuberculin skin test (TST) obtained several weeks after a first negative result consistently identifies individuals that undergo TST conversion. It remains unclear whether this delay in M. tuberculosis infection is related to differences in the infectious exposure, TST boosting, partial host resistance, or some other factor. Methods We conducted a household contact study Vitória, Brazil. Between 2008 and 2013, we identified culture-positive pulmonary TB patients and evaluated their household contacts with both a TST and interferon gamma release assay (IGRA), and identified TST converters at 8–12 weeks post study enrollment. Contacts were classified as TST-positive (≥10 mm) at baseline, TST converters, or persistently TST-negative. We compared TST converters to TST-positive and to TST-negative contacts separately, using generalized estimating equations. Results We enrolled 160 index patients and 838 contacts; 523 (62.4%) were TST+, 62 (7.4%) TST converters, and 253 (30.2%) TST−. TST converters were frequently IGRA− at 8–12 weeks. In adjusted analyses, characteristics distinguishing TST converters from TST+ contacts (no contact with another TB patient and residence ownership) were different than those differentiating them from TST− contacts (stronger cough in index patient and contact BCG scar). Conclusions The individual risk and timing of M. tuberculosis infection within households is variable and dependent on index patient, contact and environmental factors within the household, and the surrounding community. Our findings suggest a threshold effect in the risk of infection in humans.

BACKGROUND:Mycobacterium tuberculosis cultures of cough-generated aerosols from patients with pulmonary tuberculosis (TB) are a quantitative method to measure infectiousness and to predict secondary outcomes in exposed contacts. However, their reproducibility has not been established. OBJECTIVE:To evaluate the predictive value of colony-forming units (CFU) of M. tuberculosis in cough aerosols on secondary infection and disease in household contacts in Brazil. METHODS:Adult sputum smear+ and culture+ pulmonary TB cases underwent a standard evaluation and were categorized according to aerosol CFU. We evaluated household contacts for infection at baseline and at 8 weeks with TST and IGRA, and secondary disease. RESULTS:We enrolled 48 index TB cases; 40% had negative aerosols, 27% low aerosols (

Abstract Background Addiction medicine consultation and medications for opioid use disorder are shown to improve outcomes for patients hospitalized with infective endocarditis associated with injection drug use. Existing studies describe settings where addiction medicine consultation and initiation of medications for opioid use disorder are not commonplace, and rates of antibiotic therapy completion are infrequently reported. This retrospective study sought to quantify antibiotic completion outcomes in a setting where these interventions are routinely implemented. Methods Medical records of patients hospitalized with a diagnosis of bacteremia or infective endocarditis at an urban hospital between October 1, 2015 and December 31, 2017 were screened for active injection drug use within 6 months of hospitalization and infective endocarditis. Demographic and clinical parameters, receipt of antibiotics and medications for opioid use disorder, and details of re-hospitalizations within 1 year of discharge were recorded. Results Of 567 subjects screened for inclusion, 47 had infective endocarditis and active injection drug use. Addiction medicine consultation was completed for 41 patients (87.2%) and 23 (48.9%) received medications for opioid use disorder for the entire index admission. Forty-three patients (91.5%) survived to discharge, of which 28 (59.6%) completed antibiotic therapy. Twenty-nine survivors (67.4%) were re-hospitalized within 1 year due to infectious complications of injection drug use. Conclusions Among patients admitted to a center with routine addiction medicine consultation and initiation of medications for opioid use disorder, early truncation of antibiotic therapy and re-hospitalization were commonly observed.

Summary: Background: Evidence on the comparative performance of purified protein derivative tuberculin skin tests (TST) and interferon-gamma release assays (IGRA) for predicting incident active tuberculosis (TB) remains conflicting. We conducted an individual participant data meta-analysis to directly compare the predictive performance for incident TB disease between TST and IGRA to inform policy. Methods: We searched Medline and Embase from 1 January 2002 to 4 September 2020, and studies that were included in previous systematic reviews. We included prospective longitudinal studies in which participants received both TST and IGRA and estimated performance as hazard ratios (HR) for the development of all diagnoses of TB in participants with dichotomised positive test results compared to negative results, using different thresholds of positivity for TST. Secondary analyses included an evaluation of the impact of background TB incidence. We also estimated the sensitivity and specificity for predicting TB. We explored heterogeneity through pre-defined sub-group analyses (e.g. country-level TB incidence). Publication bias was assessed using funnel plots and Egger's test. This review is registered with PROSPERO, CRD42020205667. Findings: We obtained data from 13 studies out of 40 that were considered eligible (N = 32,034 participants: 36% from countries with TB incidence rate ≥100 per 100,000 population). All reported data on TST and QuantiFERON Gold in-Tube (QFT-GIT). The point estimate for the TST was highest with higher cut-offs for positivity and particularly when stratified by bacillus Calmette–Guérin vaccine (BCG) status (15 mm if BCG vaccinated and 5 mm if not [TST5/15 mm]) at 2.88 (95% CI 1.69–4.90). The pooled HR for QFT-GIT was higher than for TST at 4.15 (95% CI 1.97–8.75). The difference was large in countries with TB incidence rate

Abstract Objective Mycobacterium tuberculosis infection leads to latent or active tuberculosis (TB). Increased uptake on 18F-fluoro-2-deoxy-glucose-positron emission tomography/computed tomography (FDG-PET/CT) has been reported in the lungs and lymph nodes of individuals with recent infection and active TB, but not in individuals without known recent exposure or suggestive symptoms. We describe five patients with lung nodules not suspected to be due to TB in whom abnormalities on FDG-PET/CT scans ultimately were attributed to TB infection. Results Patient records were searched using the words “positron emission tomography/computed tomography” and 24 codes for TB between 2004 and 2013. Patients with a diagnosis of TB and a PET/CT scan were included. Clinical and radiographic data were retrieved. PET/CT images were reviewed by an experienced radiologist. FDG-PET/CT scans revealed elevated FDG-uptake in lungs of five patients subsequently diagnosed with active (n = 3) or clinically inactive (n = 2) tuberculosis. Uptake magnitude was unrelated to disease activity. These findings suggest that tuberculosis latency may include periods of percolating inflammation of uncertain relationship to future disease risk.

This study developed a clinical score based on clinical and radiographic data for the diagnosis of smear-negative pulmonary tuberculosis (SNPT). SNPT was defined as a positive culture in Ogawa in a patient with two negative sputum smears. Data from patients admitted to the emergency ward with respiratory symptoms and negative acid-fast bacilli (AFB) smears was analyzed by means of logistic regression to develop the predictive score.Two hundred and sixty two patients were included. Twenty patients had SNPT. The variables included in the final model were hemoptysis, weight loss, age > 45 years old, productive cough, upper-lobe infiltrate, and miliary infiltrate. With those, a score was constructed. The score values ranged from -2 to 6. The area under the curve for the ROC curve was 0.83 (95% CI 0.74-0.90). A score of value 0 or less was associated with a sensitivity of 93% and a score of more than 4 points was associated with a specificity of 92% for SNPT. Fifty-two point twenty-nine percent of patients had scores of less than one or more than four, what provided strong evidence against and in favor, respectively, for the diagnosis of SNPT. The score developed is a cheap and useful clinical tool for the diagnosis of SNPT and can be used to help therapeutic decisions in patients with suspicion of having SNPT.