OBJECTIVE To describe the characteristics of people indicated for directly observed treatment (DOT) in Spain, and the factors associated with unsuccessful treatment. METHODS 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. RESULTS 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). CONCLUSION 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.
OBJECTIVES: To compare the tolerance, adherence and effectiveness of two approaches for the treatment of latent tuberculosis infection (LTBI): 6 months of isoniazid (6H) vs. 3 months of isoniazid ...plus rifampicin (3RH).POPULATION: Immigrants with LTBI.METHODS: Participants were
enrolled in a controlled, randomised clinical trial in Barcelona, Spain, from April 2001 to April 2005. Monthly follow-up was done to assess tolerance, side effects and adherence. Effectiveness was evaluated at 5 years.RESULTS: In the 590 subjects enrolled, the rate of adherence was greater
in the 3RH than in the 6H arm (72% vs. 52.4%, P = 0.001). No differences between study arms were observed with respect to hepatotoxicity or side effects. Variables associated with non-adherence were diagnosis by screening (OR 1.88, 95%CI 1.26-2.82, P = 0.001), illegal immigration
status (OR 1.48, 95%CI 1.01-2.15, P = 0.03), unemployment (OR 1.91, 95%CI 1.28-2.85, P = 0.0008), illiteracy (OR 1.73, 95%CI 1.04-2.88, P = 0.02), lack of family support (OR 3.7, 95%CI 2.54-5.4, P = 0.001) and the 6-month treatment regimen
(OR 2.45, 95%CI 1.68-3.57, P = 0.0001). None of the patients who completed either treatment developed tuberculosis.CONCLUSIONS: The 3RH regimen facilitates adherence to LTBI treatment and offers a safe, well-tolerated and effective alternative.
Summary Objective Performance of IFN-γ 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-γ 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-γ levels. Correlation between the three assays was good ( κ = 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-γ T-cell based assays in combination with an additional IP-10 assay detection could be useful for diagnosing active TB and LTBI in children.
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%).
The aim of the present study was to compare the performance of the interferon (IFN)-γ tests (QuantiFERON®-TB Gold In-Tube (QFT-G-IT) and T-SPOT®.TB) with the tuberculin skin test (TST) in diagnosing ...tuberculosis (TB) infection in children, and to analyse discordant results. This was a prospective study including 98 children from contact-tracing studies and 68 children with TST indurations ≥ 5 mm recruited during public health screenings. Positive IFN-γ tests results were associated with risk of exposure (p<0.0001). T-SPOT.TB was positive in 11 (78.6%) out of 14 cases with active TB and QFT-G-IT in nine (64.3%) out of 14 cases. Sensitised T-cells against Mycobacterium avium were detected in six out of 12 children not vaccinated with bacille Calmette-Guérin (BCG), a TST induration 5-9 mm in diameter and both IFN-γ tests negative. In concordant IFN-γ tests results, a positive correlation was found (p = 0.0001) between the number of responding cells and the amount of IFN-γ released. However, in discordant IFN-γ tests results this correlation was negative (p = 0.371): an increase in the number of spot-forming cells correlated with a decrease in the amount of IFN-γ released. The use of IFN-γ tests is helpful for the diagnosis of TB infection, avoiding cross-reactions with BCG immunisation and nontuberculous mycobacterial infections. The analysis of highly discordant results requires further investigation to elucidate possible clinical implications.
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 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 an ...in vitro T-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 with Mycobacterium avium sensitin (having cross-reaction with Mycobacterium intracellulare and Mycobacterium scrofulaceum) and the presence of reactive T-cells was determined by an ex vivo ELISPOT. From the 21 patients, in 10 cases (47.6%), we obtained a positive ELISPOT result after stimulation with M. avium sensitin, 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 gamma-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.
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 multi-variate 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.
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