Revaccination with Bacille Calmette-Guérin (BCG) is associated with an increased risk of abscess and lymphadenopathy

The reported frequency and types of adverse events following initial vaccination and revaccination with Bacille Calmette-Guérin (BCG) varies worldwide. Using active surveillance in a randomised controlled trial of BCG vaccination (the BRACE trial), we determined the incidence and risk factors for the development of BCG injection site abscess and regional lymphadenopathy. Injection site abscess occurred in 3% of 1387 BCG-vaccinated participants; the majority (34/41, 83%) resolved without treatment. The rate was higher in BCG-revaccinated participants (OR 3.6, 95% CI 1.7–7.5), in whom abscess onset was also earlier (median 16 vs. 27 days, p = 0.008). No participant with an abscess had a positive interferon-gamma release assay. Regional lymphadenopathy occurred in 48/1387 (3%) of BCG-vaccinated participants, with a higher rate in revaccinated participants (OR 2.1, 95% CI 1.1–3.9). BCG-associated lymphadenopathy, but not injection site abscess, was influenced by age and sex. A previous positive tuberculin skin test was not associated with local reactions. The increased risk of injection site abscess or lymphadenopathy following BCG revaccination is relevant to BCG vaccination policy in an era when BCG is increasingly being considered for novel applications.

A pilot study for the evaluation of an interferon-gamma release assay (IGRA) to measure T-cell immune responses after SARS-CoV-2 infection or vaccination in a unique cloistered cohort

Background: Assessment of T-cell responses to SARS-CoV-2 antigens may be of value to determine long-lasting protection to breakthrough infections or reinfections. Interferon-gamma release assay is a validated method to test cellular immunity in mycobacterial infections and has been proposed for patients with SARS-CoV-2 infection or vaccination. Methods: Quantitative IgG to spike and qualitative IgG to nucleocapsid antigens were determined by chemiluminescence microparticle immunoassay using the Architect® platform (Abbott®), and interferon-gamma release assay against two Qiagen® proprietary mixes of SARS-CoV-2 spike protein (antigen-1 and antigen-2) were performed for a selected group of subjects. Results: A total of 121 subjects in a cloistered institution after a COVID-19 outbreak were studied. IgG-spike levels and interferon-gamma concentration were highest among subjects after two doses of vaccine, followed by patients with a longer history of past COVID-19 and no vaccination. Best cut-off for interferon-gamma assay was 25 IU/μL for all subgroups of individuals and the two sets of SARS-CoV-2 antigens studied. Conclusions: Testing T-cell response may be of clinical utility to determine immunity after exposure to SARS-CoV-2 antigens, with the interferon-gamma concentration of 25 IU/μL as the best cut-off either after infection or vaccination.

Tuberculose em Idade Pediátrica: Experiência de 12 Anos num Centro Terciário de Referência em Portugal

Introduction: The diagnosis of tuberculosis in children is a challenge namely because extrapulmonary tuberculosis and severe disease are more frequent in this age group. The aim of this study was to evaluate and reflect about severe tuberculosis in pediatric age, in a metropolitan area of Lisbon.Material and Methods: Descriptive study about patients under 18 years of age admitted with tuberculosis disease in a tertiary pediatric hospital, from 2008 to 2019 (12 years).Results: We report 145 patients, average of 12 cases/year, with an increase in the last three years. Median age of 12.9 years, 42.8% born in Portuguese-speaking African countries and 20% had a chronic disease. The diagnosis was pulmonary tuberculosis in 52.4% (n = 76) and extrapulmonary tuberculosis in 47.6%: lymphatic (n = 26), skeletal (n = 15), miliary (n = 8), meningeal (n = 7), peritoneal/ intestinal (n = 6), pleural (n = 4), renal (n = 1), cutaneous (n = 1), thoracic wall (n = 1) and salivary glands (n = 1). The tuberculin test was positive in 78/99 (78.8%) and Interferon Gamma Release Assay in 61/90 (67.8%). In 20.7% (n = 30) acid-fast bacilli were identified in gastric aspirate/sputum and the agent was identified in 59.3% (n = 86). Tuberculosis was resistant in 11% (n = 16). Patients with extrapulmonary tuberculosis were younger (p = 0.006) and had more prolonged therapy (p < 0.001). Therapy-related complications occurred in 11% (n = 16). One patient died (with terminal cancer).Conclusion: This study highlights the need for screening of tuberculosis in children from endemic countries, patients with immunosuppression and chronic disease.

Determinants of latent tuberculosis infection among nurses at public health centers in Indonesia

Background: The incidence of latent tuberculosis among healthcare workers, especially nurses, at public health centers in Indonesia has been increased. Therefore, factors related to the tuberculosis incidence need to be further investigated. Objective: This study aimed to identify the determinants of latent tuberculosis infection among nurses at public health centers in Indonesia. Methods: This non-experimental, cross-sectional study included 98 nurses. Data on the determinants of latent tuberculosis infection were collected using validated questionnaires, and the infection status was confirmed by Interferon Gamma Release Assay or IGRA test. Logistic regression was used for statistical analysis, with a significance level of p < 0.05. Results: Health facilities for tuberculosis transmission prevention were available in all public health centers (100%). Protocols for preventingtuberculosis transmission including occupational health and safety training (OR = 13.24, 95% CI [2.29–58.55]; p = 0.001), handwashing after contact with patients or specimens (OR = 20.55, 95% CI [4.23–99.93]; p = 0.000), and wearing of medical masks (OR = 9.56, 95% CI [1.99–45.69];p = 0.005) were found to be significant determinants of latent tuberculosis infection among nurses. Conclusion: The availability of protective equipment and implementation of health protocols among nurses at public health centers are the main determinants of latent tuberculosis infection. Hence, they should be maintained by all nurses to prevent the spread of tuberculosis. Funding: This study was funded by the Ministry of Research, Technology, and Higher Education (DRPM), Republic of Indonesia (Basic Research Grant, No 257-11/UN7.P4.3/PP/2019 in 2019).

Lessons Learned from Implementation of an Interferon Gamma Release Assay to Screen for Latent Tuberculosis Infection in a Large Multicenter Observational Cohort Study in Brazil

The IGRA has emerged as a useful tool for identifying persons with LTBI. Although the implementation of IGRAs is of utmost importance, to our knowledge there is scarce information on the identification of logistical and technical challenges for systematic screening for LTBI on a large scale.

Targeting screening and treatment for latent tuberculosis infection towards asylum seekers from high-incidence countries – a model-based cost-effectiveness analysis

Background Enhancing tuberculosis (TB) prevention and care in a post-COVID-19-pandemic phase will be essential to ensure progress towards global TB elimination. In low-burden countries, asylum seekers constitute an important high-risk group. TB frequently arises post-immigration due to the reactivation of latent TB infection (LTBI). Upon-entry screening for LTBI and TB preventive treatment (TPT) are considered worthwhile if targeted to asylum seekers from high-incidence countries who usually present with higher rates of LTBI. However, there is insufficient knowledge about optimal incidence thresholds above which introduction could be cost-effective. We aimed to estimate, among asylum seekers in Germany, the health impact and costs of upon-entry LTBI screening/TPT introduced at different thresholds of country-of-origin TB incidence. Methods We sampled hypothetical cohorts of 30–45 thousand asylum seekers aged 15 to 34 years expected to arrive in Germany in 2022 from cohorts of first-time applicants observed in 2017–2019. We modelled LTBI prevalence as a function of country-of-origin TB incidence fitted to data from observational studies. We then used a probabilistic decision-analytic model to estimate health-system costs and quality-adjusted life years (QALYs) under interferon gamma release assay (IGRA)-based screening for LTBI and rifampicin-based TPT (daily, 4 months). Incremental cost-effectiveness ratios (ICERs) were calculated for scenarios of introducing LTBI screening/TPT at different incidence thresholds. Results We estimated that among 15- to 34-year-old asylum seekers arriving in Germany in 2022, 17.5% (95% uncertainty interval: 14.2–21.6%) will be latently infected. Introducing LTBI screening/TPT above 250 per 100,000 country-of-origin TB incidence would gain 7.3 (2.7–14.8) QALYs at a cost of €51,000 (€18,000–€114,100) per QALY. Lowering the threshold to ≥200 would cost an incremental €53,300 (€19,100–€122,500) per additional QALY gained relative to the ≥250 threshold scenario; ICERs for the ≥150 and ≥ 100 thresholds were €55,900 (€20,200–€128,200) and €62,000 (€23,200–€142,000), respectively, using the next higher threshold as a reference, and considerably higher at thresholds below 100. Conclusions LTBI screening and TPT among 15- to 34-year-old asylum seekers arriving in Germany could produce health benefits at reasonable additional cost (with respect to international benchmarks) if introduced at incidence thresholds ≥100. Empirical trials are needed to investigate the feasibility and effectiveness of this approach.

Decreased annual risk of tuberculosis infection in South Korean healthcare workers using interferon-gamma release assay between 1986 and 2005

Background Tuberculosis (TB) has been a major public health problem in South Korea. Although TB notification rate in Korea is gradually decreasing, still highest among the member countries of the Organization for Economic Cooperation and Development. To effectively control TB, understanding the TB epidemiology such as prevalence of latent tuberculosis infection (LTBI) and annual risk of TB infection (ARI) are important. This study aimed to identify the prevalence of LTBI and ARI among South Korean health care workers (HCWs) based on their interferon-gamma release assays (IGRA). Methods This was single center, cross-sectional retrospective study in a tertiary hospital in South Korea. We performed IGRA in HCWs between May 2017 and March 2018. We estimated ARI based on IGRA results. Logistic regression model was used to identify factors affecting IGRA positivity. Results A total of 3233 HCWs were analyzed. Median age of participants was 38.0 and female was predominant (72.6%). Overall positive rate of IGRA was 24.1% and IGRA positive rates age-group wise were 6.6%, 14.4%, 34.3%, and around 50% in the age groups 20s, 30s, 40s, and 50s and 60s, respectively. The ARIs was 0.26–1.35% between 1986 and 2005; rate of TB infection has gradually decreased in the last two decades. Multivariable analysis indicated that older age, healed TB lesion in x-ray, and male gender were risk factors for IGRA positivity, whereas working in high-risk TB departments was not. Conclusions Results showed that ARI in South Korean HCWs gradually decreased over two decades, although LTBI remained prevalent. Our results suggest that the LTBI test result of HCWs might be greatly affected by age, rather than occupational exposure, in intermediate TB burden countries. Thus, careful interpretation considering the age structure is required.