Impact of the COVID-19 pandemic on tuberculosis management in Spain.

BACKGROUND: The impact of COVID-19 on the diagnosis and management of tuberculosis (TB) patients is unknown. METHODS: Participating centres completed a structured web-based survey regarding changes to TB patient management during the COVID-19 pandemic. The study also included data from participating centres on patients aged ≥18 diagnosed with TB in 2 periods: March 15 to June 30, 2020 and March 15 to June 30, 2019. Clinical variables and information about patient household contacts were retrospectively collected. RESULTS: A total of 7 (70%) TB units reported changes in their usual TB team operations. Across both periods of study, 169 patients were diagnosed with active TB (90 in 2019, 79 in 2020). Patients diagnosed in 2020 showed more frequent bilateral lesions in chest X-ray than patients diagnosed in 2019 (P = 0.004). There was a higher percentage of latent TB infection and active TB among children in households of patients diagnosed in 2020, compared with 2019 (P = 0.001). CONCLUSIONS: The COVID-19 pandemic has caused substantial changes in TB care. TB patients diagnosed during the COVID-19 pandemic showed more extended pulmonary forms. The increase in latent TB infection and active TB in children of patient households could reflect increased household transmission due to anti-COVID-19 measures.

Diagnostic benefits of adding EspC, EspF and Rv2348-B to the QuantiFERON Gold In-tube antigen combination.

Interferon (IFN)-γ release assays (IGRAs) are used to diagnose latent tuberculosis (TB) infection (LTBI). To improve the accuracy of these tests, different approaches, such as alternative cytokine detection and using different antigens, are considered. Following this purpose, this study aims to evaluate the addition of EspC, EspF and Rv2348-B to those present in the QuantiFERON-TB Gold In-Tube (QFN-G-IT). We included 115 subjects: 74 active TB patients, 17 LTBI individuals and 24 healthy controls. Whole blood samples were collected in QFN-G-IT and in-house tubes containing different combinations of EspC, EspF and Rv2348-B, together with ESAT-6, CFP-10, and TB7.7. After overnight incubation at 37 ºC, plasma was harvested and IFN-γ quantified. IFN-γ levels in the QFN-G-IT and in-house tubes correlated very good (Spearman Rho(r) > 0.86). In-house antigen combinations distinguished healthy individuals from those with active TB and LTBI (specificities and sensitivities higher than 87.5% and 96.3%, respectively [AUC > 0.938]). Adding EspC, EspF and Rv2348-B, increased the sensitivity of the test, being the addition of EspC and Rv2348-B the combination that yielded a higher sensitivity with no specificity loss. Addition of these antigens could improve diagnosis in patients with impaired or immature immune response who are at high risk of developing TB.

Use of IP-10 detection in dried plasma spots for latent tuberculosis infection diagnosis in contacts via mail.

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.

Screening for active tuberculosis in high-risk groups.

OBJECTIVE: To evaluate an active case-finding strategy among drug users (DUs), economically disadvantaged individuals and recent immigrants from hyperendemic countries, a population at high risk of developing tuberculosis (TB). METHODS: Retrospective, observational study carried out by the Tuberculosis Unit of the City of Barcelona from September 2009 to December 2012. All participants underwent chest X-ray and were screened for symptoms. RESULTS: Of 5982 participants screened, 30 TB cases were detected (total prevalence 0.5%): 26 were pulmonary, 8 were smear-positive and 2 were resistant to multiple drugs. Directly observed treatment was advised for 19 patients (63%). TB prevalence in the recent immigrants group was significantly greater (1.77%) than in all other groups studied: economically disadvantaged individuals 0.30% (RR 5.9, 95%CI 2.30-15.14); DUs 0.62% (RR 2.05, 95%CI 0.91-4.64), non-recent immigrants 0.41% (RR 4.31, 95%CI 1.68-11.4); and all native-born individuals 0.41% (RR 4.33, 95%CI 1.71-10.92). The rate was much greater than the estimated prevalence for the general population of the city (∼20 cases/100,000 population). CONCLUSIONS: In high-risk groups, active case finding can be used as a public health intervention to detect a large number of TB cases.

Monitoring changes in anti-tuberculosis treatment: associated factors determined at the time of diagnosis.

OBJECTIVES: To determine predictive factors for changes in standard anti-tuberculosis chemotherapy at the time of diagnosis. METHODS: A prospective study was performed among tuberculosis (TB) patients treated at specialised centres during 2008-2009. Treatment outcome was monitored per standard guidelines. Treatment was considered successful if the patient was cured or completed treatment. Factors associated with treatment modification were analysed at the bivariate and multivariate levels using logistic regression. RESULTS: A total of 427 patients were included in the study. The initial standard treatment regimen was retained for 249 patients (58.3%), extended to 9 months for 36 (8.4%) and changed for 142 (33.3%). Factors associated with a change of regimen at the multivariate level were female sex, age ≥ 50 years, human immunodeficiency virus infection, comorbidities, alcoholism, hospitalisation and culture-positive sputum. Drug resistance and toxicity were analysed independently. Treatment outcome was successful in 97.2% of cases without a regimen change and in 87.3% of those with a changed regimen (P < 0.001). CONCLUSION: Factors associated with changes in the initial anti-tuberculosis regimen should be considered for rigorous follow-up. Results obtained through individualised treatment provided by specialists were good despite the complexity of the cases treated.

Rifampicin plus isoniazid for the prevention of tuberculosis in an immigrant population.

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.

[Active tuberculosis case finding among immigrants in Barcelona]. / Búsqueda activa de tuberculosis en inmigrantes en Barcelona.

OBJECTIVE: To assess the prevalence of tuberculous infection and disease in recent economic immigrants in Barcelona. SUBJECTS AND METHOD: Examination and testing of immigrants. Tuberculin tests (TTs) were given and the presence of scars from tuberculosis vaccinations were noted. Thresholds of 5 and 15 mm were established for positivity in unvaccinated and vaccinated individuals, respectively. RESULTS: A total of 3651 persons were examined, but only 3151 completed the study. Eighteen were diagnosed with tuberculosis (571.2 per 100,000) and 50.6% were classified as positive TT reactors, 34.4% because of infection and 16.3% possibly because of tuberculosis vaccination. The percentage of reactors was significantly higher in the sample of economic immigrants than in the local population. Age, male sex, place of origin, greater poverty, and higher prevalence of disease in the country of origin were associated with tuberculous infection in the sample. DISCUSSION: Active case finding proved efficient. Interference from tuberculosis vaccination greatly affects the findings, depending on the positivity threshold that is established. We recommend that chest radiographs be used in addition to TTs. Immigration will change the nature of endemic tuberculosis in Spain, and strategies should be specifically designed to deal with the new challenges that will appear.

[A study of the tuberculous infection in adults]. / Estudio de la infección tuberculosa en adultos.

UNLABELLED: Tuberculous infection in adults is not a well known entity in our country, despite its epidemiological importance. We have designed an observational study in a homogeneous group of adult civil servants of Catalonia (n = 8,202) from 20 to 54 years old that were submitted to a health examination which included a tuberculin test, in order to study the tuberculous infection in these people and to evaluate the factors associated with this infection. RESULTS: The global prevalence of reactivity in tuberculin test was 22.36% and the prevalence of the tuberculous infection was 14.76%. The factors related to the tuberculous infection were the following: age, male sex, background of exposure to sources of contagion, and previous BCG vaccination. CONCLUSIONS: The prevalence of tuberculous infection in adults has declined, and is currently greater in men than women, among patients who recognize previous contact with a tuberculous patient, and among patients with previous BCG vaccination.

[Pulmonary symptomatic tuberculosis' diagnostic delay study]. / Estudio del retraso diagnóstico de la tuberculosis pulmonar sintomática.

OBJECTIVE: To study symptomatic pulmonary tuberculosis (PTB) diagnostic delay. PATIENTS AND METHODS: Prospective study of new symptomatic PTB cases (aged > or = 15 years) by structured interview with the patients and their families. The main variables analyzed were patient's delay (PD), doctor's delay (DD), diagnostic process delay (DPD), health care system delay (HCSD) and total delay between the onset of symptoms and start of treatment (TD). Univariate and multivariate statistical analyses were performed for each component of delay. RESULTS: Two hundred eighty-seven patients were studied. The mean delays in days standard deviations were TD 81.8 77.3; PD 43.3 55.7; DD 28.4 59.6; DPD 10.0 17.7, and HCSD 38.5 62.5. CONCLUSIONS: Patients are responsible for 50% of excess delay in diagnosing symptomatic PTB. Patients in the health care system experienced diagnostic delays over 60 days in 18.5% of cases, doctors being responsible for 75% of the diagnostic delay attributable to the system.