To describe the characteristics of people indicated for directly observed treatment (DOT) in Spain, and the factors associated with unsuccessful treatment.This was a multicentre observational study based on a prospective follow-up of patients over 18 years old diagnosed with TB between 2006 and 2019 from the registry of the Programa Integrado de Investigación en Tuberculosis (PII-TB). Sociodemographic and clinical variables were collected. Adjusted odds ratios (aORs) were calculated for the indication of DOT and for having an unsuccessful treatment.A total of 7,883 patients were included. The indication of DOT was associated with being homeless (aOR 5.93, 95% CI 3.03-11.59), inactivity status (aOR 2.55, 95% CI 2.02-3.23), alcohol consumption (aOR 1.94, 95% CI 1.51-2.48), parenteral drug use (aOR 1.77, 95% CI 1.06-2.95) and HIV diagnosis (aOR 1.96, 95% CI 1.16-3.29). Unsuccessful treatment was associated with having an HIV diagnosis (aPR 2.31, 95% CI 1.31-4.08), having a worse clinical and radiological evolution (clinical progression: APR 15.59, 95% CI 8.21-29.60; radiological progression: aPR 12.84, 95% CI 6.46-25.52), need for hospitalisation (aPR 1.73, 95% CI 1.10-2.73), unsatisfactory tolerability (aPR 2.82, 95% CI 1.49-5.29), the existence of difficulties in understanding the prescribed treatment (aPR 1.92, 95% CI 1.21-3.06), as well as worse treatment satisfaction (aPR 7.27, 95% CI 4.32-12.24).The prioritisation of vulnerable populations is a key aspect to carry out the new Global Plan to End TB 2023-2030. In these groups DOT indication should be increased to ensure adherence and patient follow-up and outcomes..

Background The lifetime risk of tuberculosis (TB) among individuals with latent Mycobacterium tuberculosis infection (LTBI) is commonly estimated as 5–10%, but is highly variable between individuals. Validated estimates of personalised risk are needed to facilitate precise targeting of preventative treatment. We aimed to characterise population-level TB risk among people tested for LTBI, and to develop and validate a prognostic model to estimate personalised risk of disease. Methods We pooled individual-level data from 18 systematically-identified cohort studies conducted in 20 countries with low TB transmission (annual incidence ≤20/100,000 persons). We estimated population-level incident TB risk using flexible parametric survival models with random effect intercepts by source study. We then developed and validated a flexible parametric survival prediction model for incident TB using the internal-external cross-validation framework, iteratively discarding one contributing dataset from model development and using it for validation. Findings In pooled data including 80,468 individuals tested for LTBI and 803 TB cases, 5-year cumulative risk of incident TB among people with untreated LTBI was 15.6% (95% CI 8.0–29.2) for child contacts, 4.8% (3.0–7.7) for adult contacts, 5.0% (1.6–14.5) for migrants, and 4.8% (1.5–14.3) for immunocompromised groups. We found highly variable estimates within risk groups, necessitating a personalised approach to risk-stratification. We thus developed a prognostic model that combines a quantitative measure of T cell sensitisation and clinical covariates. These covariates included age, history of TB exposure (household contact of smear-positive index case, other contact, migration from high TB burden country or no exposure), HIV status and receipt of a solid organ or haematological transplant. Validation of this model achieved a random-effects meta-analysis C-statistic of 0.88 (0.82–0.93) for incident TB over 2 years. Decision curve analysis revealed that applying the model improved clinical decision-making for targeting LTBI treatment. Interpretation TB incidence rates are heterogeneous among people identified as having LTBI by current standards, even after stratification by indication for screening. We present a freely available and directly data-driven personalised risk predictor for incident TB (www.periskope.org). PERISKOPE-TB will facilitate a programmatic paradigm shift by allowing a fully evidence-based and patient-centred approach to TB risk stratification in settings aiming towards pre-elimination globally.

The aim of this study was to test the use of IP-10 detection in dried plasma from contact studies individuals (contacts of smear positive patients), by comparing it with IP-10 and IFN-γ detection in direct plasma, to establish IP-10 detection in DPS as a useful assay for LTBI diagnosis. Whole blood samples were collected from 80 subjects: 12 with active tuberculosis (TB), and 68 from contact studies. The amount of IFN-γ produced by sensitized T cells was determined in direct plasma by QuantiFERON Gold In-Tube test. IP-10 levels were determined in direct and dried plasma by an in-house ELISA. For dried plasma IP-10 determination, two 25 µl plasma drops were dried in Whatman903 filter paper and sent by mail to the laboratory. Regarding TB patients, 100.0%, 91.7% and 75.0% were positive for IFN-γ detection and IP-10 detection in direct and dried plasma, respectively. In contacts, 69.1%, 60.3% and 48.5% had positive results after IFN-γ and IP-10 in direct and dried plasma, respectively. The agreement among in vitro tests was substantial and IP-10 levels in direct and dried plasma were strongly correlated (r = 0.897). In conclusion, IP-10 detection in dried plasma is a simple and safe method that would help improve LTBI management.

The emergence of drug-resistant tuberculosis (TB) is a challenge to TB control in Europe. We evaluated second-line drug susceptibility testing in Mycobacterium tuberculosis isolates from patients with multidrug-resistant, pre-extensively drug-resistant (pre-XDR-TB) and XDR-TB at 23 TBNET sites in 16 European countries. Over 30% of bacilli from patients with pre-XDR-TB showed resistance to any fluoroquinolone and almost 70% to any second-line injectable drug. Respectively >90% and >80% of the XDR-TB strains tested showed phenotypic resistance to pyrazinamide and ethambutol. Resistance to prothionamide/ethionamide was high in bacilli from pre-XDR-TB patients (43%) and XDR-TB patients (49%).

Objective: Performance of IFN-gamma assays in children is compromised. Therefore, we investigated the utility of IP-10 for the detection of active tuberculosis (TB) and latent tuberculosis infection (LTBI) diagnosis in children; comparing its positivity with QuantiFERON-TB Gold In-Tube (QFN-G-IT) and T-SPOT. TB.Methods: We studied 230 children from three groups: active TB, screening (healthy children without known exposure to active TB patient screened at school or by their paediatrician) and contact-tracing studies. IFN-gamma release was determined by QFN-G-IT and T-SPOT. TB. IP-10 was detected in QFN-G-IT supernatants by ELISA.Results: When combining QFN-G-IT and IP-10 assays, positive results improved significantly from 38.3% in QFN-G-IT and 33.9% in IP-10 to 41.3%. Age and type of contact were significant risk factors associated with positive QFN-G-IT and IP-10 results. IP-10 levels after antigen-specific stimulation were significantly higher in comparison to IFN-gamma levels. Correlation between the three assays was good (k = 0.717-0.783).Conclusions: IP-10 cytokine is expressed in response to TB specific-antigens used in QFN-G-IT. In conclusion, the use of IFN-gamma T-cell based assays in combination with an additional IP-10 assay detection could be useful for diagnosing active TB and LTBI in children. (C) 2014 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

OBJECTIVE: To determine the risk of latent tuberculous infection (LTBI) among contacts of smokers with tuberculosis (TB).METHODS: A study was conducted to determine the prevalence of LTBI among contacts of TB cases aged >14 years in Catalonia, Spain. A survey was carried out for each TB case and their contacts. LTBI was diagnosed using the tuberculin skin test (>= 5 mm). The risk of LTBI associated with smoking was determined by multivariate logistic regression analysis, with adjusted odds ratio (aOR) and their 95% confidence intervals (CI).RESULTS: The smoking prevalence among TB cases was 40.7% (439/1079). The prevalence of LTBI among their contacts was 29.7% (2281/7673). It was higher among contacts of smoking index cases (35.3%) than among those of non-smokers (25.7%). Smoking was independently associated with an increased risk of LTBI among contacts (aOR 1.5, 95 %CI 1.3-1.7), and was estimated to be responsible for 12.8% of infections.CONCLUSIONS: Index case smoking increases the risk of LTBI and should be systematically investigated. A reduction in smoking could lower the risk of infection substantially.

The aim of the present study was to determine the role of previous non-tuberculous mycobacteria sensitisation in children as a factor of discordant results between tuberculin skin test (TST) and anin vitroT-cell based assay (T-SPOT.TB; Oxford Immunotec, Oxford, UK).We enrolled 21 non-bacille Calmette-Guérin-vaccinated paediatric patients for suspicious of latent tuberculosis infection (LTBI). These patients yielded a positive TST and a negative T-SPOT.TB. Cells were stimulated withMycobacterium aviumsensitin (having cross-reaction withMycobacterium intracellulareandMycobacterium scrofulaceum) and the presence of reactive T-cells was determined by anex vivoELISPOT.From the 21 patients, in 10 cases (47.6%), we obtained a positive ELISPOT result after stimulation withM. aviumsensitin, in six (28.6%) cases, the result was negative and in the remaining five (23.8%) cases, the result was indeterminate.In conclusion, previous non-tuberculous mycobacteria sensitisation induces false-positive results in the TST for diagnosing LTBI and the use of γ-interferon tests could avoid unnecessary chemoprophylaxis treatment among a child population.

During a 2-year period (2003-2004), tuberculosis (TB) transmission in Barcelona and the factors related to transmission among the Spanish- and foreign-born populations were studied by molecular epidemiology. Data were obtained from TB cases and Conventional Contact Tracing registries and genotyping was performed using restriction fragment length polymorphism (RFLP)-IS6110 and MIRU12 as a secondary typing method. Of the 892 TB cases reported, 583 (65.3%) corresponded to Spanish-born and 309 (34.6%) to foreign-born. Six hundred and eighty-seven cases (77%) were confirmed by culture. RFLP typing of 463/687 (67.4%) isolates was performed, revealing 280 (60.5%) unique and 183 (39.5%) shared patterns, which were grouped into 65 clusters. Spanish-born individuals were significantly more clustered than foreign-born individuals (44.6% vs. 28.8%; p 0.016). Clustering in foreign-born individuals was associated with HIV (p 0.051, odds ratio = 3.1, 95% confidence interval 1-10.9) and alcohol abuse (p 0.022), whereas, in the Spanish-born individuals, clustering was associated with age in the range 21-50 years, (p 0.024). Of the total clusters, 36/65 (55.3%) included only Spanish-born patients, whereas 22/65 (33.8%) included individuals from both populations. In mixed clusters, the index case was Spanish-born in 53% and foreign-born in 47%. Among the foreign-born, 2.8% were ill on arrival, 30% developed TB within the first year and 50.3% developed TB within the first 2 years; 58.3% were from South America. In conclusion, half of the foreign-born TB patients developed the disease during the first 2 years after arrival, which, in most cases, was the result of endogenous reactivation. Recent TB transmission among Spanish-born and foreign-born populations, as well as bidirectional transmission between communities, contributed significantly to the burden of TB in Barcelona, suggesting the need to improve Public Health interventions in both populations.

Background: The homeless are at very high risk of suffering tuberculosis (TB). The aims of this study were to determine the prevalence and risk factors for tuberculosis infection and disease among the homeless in Barcelona and to evaluate the roles of case finding and contact investigation. Methods: Observational prevalence study carried out between 1997 and 1998. Participants: 447 homeless patients (394 men and 53 women) were evaluated before admission to shelters and free-meal services. At the same time, 48 co-residents with smear-positive TB patients in 2 long-term shelters were evaluated too. A chest X-ray and Tuberculin Skin Test were performed on all subjects. Sputum smears were processed by the Ziehl–Neelsen and Löwenstein–Jensen procedures in patients with radiographic findings consistent with pulmonary TB. Results: Of the 447 homeless examined, 335 (75%) were infected with Mycobacterium tuberculosis. Active pulmonary TB was diagnosed in five persons (1.11%), and 62 (13.8%) had radiographic evidence of inactive pulmonary TB. Tuberculosis infection was associated with age and smoking, but not with sex or alcohol abuse. No significant differences in infection rates were found between the main group and 48 homeless co-residents of smear-positive subjects. Only 16.9% of the homeless with active TB in Barcelona in the same period were diagnosed through active case-finding, the remainder being mainly detected in hospitals (69.8%) and other several centres (13.3%). Conclusions: Homeless individuals have a very high risk of TB infection and disease and contact investigation requires specific methods for them. Programmes of screening and supervised treatment should be ensured in this group.