Prevalence of tuberculosis skin test positivity among healthcare workers: results of an observational study

Prevalence of latent tuberculosis infection in transplant candidates: A systematic review and meta-analysis

Latent Tuberculosis in Healthcare Workers: Time to Act

Increased prevalence of latent tuberculosis infection (LTBI) has been observed among high-risk populations such as healthcare workers (HCWs). The results may depend on the method of LTBI assessment, interferon-gamma release assay (IGRA) and/or tuberculin skin test (TST). Here, we investigated the prevalence and risk factors for LTBI assessed by both IGRAs and TST in HCWs living in Morocco, a country with intermediate tuberculosis (TB) endemicity and high BCG vaccination coverage. HCWs were recruited in two Moroccan hospitals, Rabat and Meknes. All the participants underwent testing for LTBI by both IGRA (QuantiFERON-TB Gold In-Tube, QFT-GIT) and TST. Different combinations of IGRA and TST results defined the LTBI status. Risk factors associated with LTBI were investigated using a mixed-effect logistic regression model. The prevalence of LTBI among 631 HCWs (age range 18–60 years) varied from 40.7% (95%CI 36.9–44.5%) with QFT-GIT to 52% (95%CI 48.2–56.0%) with TST using a 10 mm cut-off. The highest agreement between QFT-GIT and TST (κ = 0.50; 95%CI 0.43–0.56) was observed with the 10 mm cut-off for a positive TST. For a definition of LTBI status using a double positive result for both QFT-GIT and TST, significant associations were found with the following risk factors: being male (OR = 2.21; 95%CI 1.40–3.49; p = 0.0007), belonging to age groups 35–44 years (OR = 2.43; 95%CI 1.45–4.06; p = 0.0007) and even more 45–60 years (OR = 4.81; 95%CI 2.72–8.52; p = 7.10−8), having a family history of TB (OR = 6.62; 95%CI 2.59–16.94; p = 8.10−5), and working at a pulmonology unit (OR = 3.64; 95%CI 1.44–9.23; p = 0.006). Smoking was associated with LTBI status when defined by a positive QFT-GIT result (OR = 1.89; 95%CI 1.12–3.21; p = 0.02). A high prevalence of LTBI was observed among HCWs in two Moroccan hospitals. Male gender, increased age, family history of TB, and working at a pulmonology unit were consistent risk factors associated with LTBI.

Latent tuberculosis infection among adults attending HIV services at an urban tertiary hospital in Malawi.

Healthcare workers (HCWs) represent a significant demographic for screening latent tuberculosis infection (LTBI) due to their potential exposure to infectious patients. Tests based on immunology detection, such as the tuberculin skin test (TST) and the interferon-gamma release assay (IGRA), have been pivotal in diagnosing LTBI. The objective of this study was to evaluate the efficacy of the IGRA test in detecting LTBI compared to the TST among HCWs in an infectious disease hospital. In a cross-sectional study conducted in August 2019 at the Sulianti Saroso Infectious Disease Hospital, we examined 84 HCWs selected through consecutive sampling. Participants were assessed using questionnaires, and the IGRA and TST tests were performed. The findings revealed that 42 (50%) HCWs tested positive for LTBI based on the IGRA test. Most were female, aged 36-45 years, had direct exposure to TB patients, and had been in the healthcare profession for over a decade. The concordance between the TST and IGRA test, as indicated by a κ value, was 0.234. Furthermore, a significant correlation was observed between the incidence of LTBI and the duration of the healthcare profession (p=0.016). In conclusion, our research suggests that both TST and IGRA tests can effectively detect LTBI. The IGRA test had a higher positivity rate among HCWs with over ten years of service.

Anti-tumor necrosis factor-a (anti-TNF-a) drugs are widely used for the management of patients who suffer from Crohn’s disease (CD) and ulcerative colitis (UC). Screening for latent tuberculosis infection (LTBI) and hepatitis B virus (HBV) is mandatory prior to commencing therapy with anti-TNF-a drugs, due to an increased reactivation risk for these diseases. Unfortunately, in the case of LTBI, a consensus has not been reached, highlighted by the heterogeneity of current guidelines, regarding the use of the tuberculin skin test (TST) or an interferon-gamma release assay (IGRA) as parts of the initial screening strategy [1, 2]. Historically, the diagnosis of LTBI has been dependent on the TST whose mechanism relies on a delayed-type T cell mediated hypersensitivity reaction to purified protein derivative (PPD). Regrettably, the TST has well-known limitations including potential sources for false positive results, due to the non-specific nature of PPD leading to cross-reactivity with non-tuberculosis mycobacterium and individuals who have received bacillus Calmette-Guerin vaccination. Moreover, there is intrinsic test subjectivity due to induration interpretation; furthermore, two healthcare visits are required. Alternatively, the IGRAs, which measure the release of interferon-gamma post antigen exposure, have recently gained popularity as an alternative for LTBI diagnosis as their antigens are more specific for Mycobacterium tuberculosis. Nonetheless, IGRA testing is more expensive and requires appropriate infrastructure, potentially limiting its universal implementation. In this issue, van der Have et al. [3] describe a costeffectiveness analysis in patients with CD of screening strategies for LTBI and HBV: (1) traditional LTBI screening (TST and chest X-ray) versus additional IGRA testing; and (2) HBV screening versus no HBV screening. Neither extensive LTBI screening (traditional testing plus IGRA) nor HBV screening were cost-effective. Nevertheless, if LTBI prevalence was[12 % or the TST false positivity rate [20 %, cost-effectiveness of extensive testing was achieved, emphasizing the importance of the varying global prevalence of LTBI and the sensitivity and specificity of LTBI diagnostic tests. Similarly, if HBV reactivity or HBVrelated mortality were[37 and[62 %, respectively, HBV screening was cost-effective, leading the authors to conclude that although extensive LTBI screening and HBV screening are effective, their implementation should be targeted towards high-risk populations. An interesting aspect to this study was how the authors calculated probabilities for the LTBI-component of the model, which appear to be largely derived from a recent meta-analysis which analyzed TST and IGRA performance in patients with inflammatory bowel disease (IBD) [4]. Concerning the perceived false-positivity rate of TST, it appears the authors based this off an estimate of discordance between TST?/IGRAresults, which is simply the discrepancy between these two tests in a patient. IGRAs are not commonly regarded as the ‘gold standard’ in LTBI diagnostics; therefore, the discordance is potentially an inaccurate quantification of false positivity. Moreover, it was unclear how the authors established the advantage that additional IGRA testing would have over traditional LTBI screening. It appears that they may have estimated this from the alternate discordant scenario TST-/IGRA?, which would lend itself to the same limitations as the false positivity risk. N. Shahidi B. Bressler (&) Division of Gastroenterology, Department of Medicine, University of British Columbia, 770-1190 Hornby Street, Vancouver, BC V6Z 2K5, Canada e-mail: brian_bressler@hotmail.com

This study established the diagnosis and risk factors of latent tuberculosis infection (LTBI) among health-care workers in an endemic population using Tuberculin skin test (TST) and Quantiferon TB-gold. A total of 609 Healthcare workers from tuberculosis treatment facilities in Akwa Ibom State, Nigeria were studied. The Interferon-gamma release assay was performed using 3ml of whole blood by ELISA according to the manufacturer’s instruction (Cellestis Ltd., Carnegie, Australia) after which 0.1 ml of 5 tuberculin units of Purified Protein Derivative (PPD) was administered intra-dermally to each subject. TST results were read after 72 hours by measuring the size of indurations in millimetres. Data were analysed using SPSS version 17 (SPSS Inc., Chicago, Illinois). At the threshold of 10 mm, the prevalence of LTBI by TST was 45.8% and 24.8% at the IGRA diagnostic value of ≥ 0.351 IU. Laboratory staff and ward orderlies as well as being in service for >10 years, were more significantly associated with LTBI. A moderate agreement of 76.7%, k = 0.51 was obtained between TST at 10 mm, and QFT. Neither previous exposure to TST nor BCG vaccination affected the prevalence of LTBI in the study population. The difference of 54% prevalence of LTBI between TST and QFT may be due to non-tuberculous mycobacterium (NTM) since TST is non-specific. This may have grave implications of drug toxicity and development of resistance to anti-TB drug among individuals harbouring NTM, but receiving anti-TB medication. The 76.7% agreement between the two tests is an indication that the 10 mm cut-off induration for TST is still relevant in the diagnosis of LTBI.

BACKGROUNDInterferon gamma release assays (IGRA) is highly specific for Mycobacterium tuberculosis and is the preferred test in BCG-vaccinated individuals. The few studies that have screened health care workers (HCWs) in Saudi Arabia for latent tuberculosis infection (LTBI) using IGRA have varied in agreement with the traditional tuberculin skin test (TST).OBJECTIVEAssess the prevalence of LTBI among HCWs working in the Hajj pilgrimage using IGRA and TST and measuring their agreement.DESIGNCross-sectional prospective.SETTINGMultiple non-tertiary care hospitals.PATIENTS AND METHODSHCWs who worked during the Hajj pilgrimage in Saudi Arabia in December 2015. Data was collected by standardized questionnaire. Samples were drawn and analyzed by standard methods.MAIN OUTCOME MEASURESThe prevalence of LTBI among HCW and the agreement by kappa statistic between QFT-GIT and TST.SAMPLE SIZE520 subjects.RESULTSThe sample included 30.7% nurses and 19.2% physicians. The majority were BCG vaccinated (98.5%). There were a total of 56 positive by QFT-GIT and the LTBI rate was 10.8%. In 50 QFT positive/476 TST negative the LTBI rate was 10.5% in discordant tests, and in 6 QFT positive/44 TST positive it was 13.6% in concordant tests. The overall agreement between both tests was poor—83% and kappa was 0.02. LTBI prevalence was associated with longer employment (13.1 [9.2] years). The QFT-GIT positive test was significantly higher in physicians (P=.02) and in HCWs working in chest hospitals 16/76 (21.05%) (P=.001).CONCLUSIONAgreement between the tests was poor. QFT-GIT detected LTBI when TST was negative in HCWs who had a history of close contact with TB patients.LIMITATIONSA second step TST was not feasible within 2–3 weeks.

Tuberculosis remains a significant global health concern, and healthcare workers (HCWs) face a high risk of acquiring latent tuberculosis infection (LTBI) through occupational exposure. In the Latin American and Caribbean (LAC) region, where the burden of tuberculosis is substantial, understanding the prevalence of LTBI among HCWs is crucial for effective infection control measures. Therefore, we conducted a systematic review and meta-analysis to estimate the prevalence of LTBI among HCWs in LAC countries. Our search included MEDLINE, Scopus, EMBASE, Web of Science, and Google Scholar databases, focusing on relevant English-language records. We looked for observational studies from inception until December 2023. Our analysis included 38 studies representing 15,236 HCWs and 6,728 LTBI cases. These studies spanned the period from 1994 to 2023 and were conducted in Brazil, Peru, Cuba, Colombia, Trinidad and Tobago, Mexico, and Chile. The mean prevalence of LTBI among HCWs was 35.32% (range 17.86-56.00%) for interferon-gamma release assay (IGRA) and 43.67% (range 6.68-70.29%) for tuberculin skin test (TST). The pooled prevalence of LTBI among HCWs was 34.5% (95% CI 25.4-44.1%) for IGRA and 43.0% (95% CI 35.5-50.7%) for TST. When considering both IGRA and TST tests, the overall prevalence of LTBI among HCWs was 40.98% (95% CI 34.77-47.33%). LTBI was associated with longer lengths of employment and exposure to patients, family members, or any person with TB. Additionally, older HCWs faced a higher risk of LTBI. Specific professional roles (such as nurses, nurse technicians, or physicians), smoking, and deficient TB infection control measures increased the likelihood of LTBI. However, information regarding gender and BCG vaccination status showed discordance among studies. Our findings underscore a substantial burden of LTBI among HCWs in LAC countries. Implementing adequate infection control measures is essential to prevent and control transmission within healthcare settings.

Prevention of latent tuberculosis infection (LTBI) in healthcare workers (HCWs) to ensure the "Right to Occupational Safety" is a special challenge globally, as HCWs have a higher risk of acquiring the infection in hospital settings because of frequent close exposure to patients suffering from tuberculosis (TB). Aretrospective study was performed with the aim of assessing the prevalence of LTBI related to demographical and occupational risk factors among HCWs employed in a large hospital in Italy. The study involved 1461 HCWs screened for LTBI by Mantoux tuberculin skin test (TST) and then confirmed with Interferon Gamma Release Assay (IGRA) test in case of positivity. Immunosuppressed and BGC-vaccinated workers were tested directly with IGRA. LTBI was diagnosed in 4.1% of the HCWs and the prevalence resulted lower than other studies conducted in low TB incidence countries. The variables significantly linked with higher frequency of the infection were: age ≥40 years (OR = 3.14; 95% CI: 1.13-8.74; p < 0.05), length of service ≥15 years (OR = 4.11; 95% CI: 1.48-11.43; p < 0.05) and not being trained on TB prevention (OR = 3.46; 95% CI: 1.85-6.46; p < 0.05). Not trained HCWs presented a higher risk of LTBI also after adjustment for age and length of service, compared to trained HCWs. screening of HCWs for LTBI should be always considered in routinely occupational surveillance in order to early diagnose the infection and prevent its progression. Safety policies in hospital settings centered on workers' training on TB prevention is crucial to minimize LTBI occurrence in HCWs.

Introduction: Anti-tumour necrosis factor (anti-TNF) therapy is associated with the risk of reactivation of Tuberculosis (TB). There is a wide variation in screening practices for latent TB infection (LTBI) prior to anti-TNF therapy, and low prevalence areas lack robust screening process. Objective: To evaluate a risk stratification strategy followed by Interferon gamma release assay (IGRA) testing for LTBI in patients prior to anti-TNF therapy in a low TB prevalence area in UK. Method: Standardised risk assessment questionnaire was used to screen 352 patients for LTBI prior to anti-TNF therapy over a 5 year period (61% had rheumatoid arthritis, 71% were on Adalimumab, F:M=1.4:1, mean age 52 (±14.4) yrs). 9Low risk9 group started anti-TNF with no further testing and were not offered chemoprophylaxis. 9At risk9 group was assessed and QuantiFERON- TB Gold In-Tube (QFT-GIT) was performed. All patients were followed up for development of active TB. Results: The study population was mainly White British (93.8%). Nine (2.6%) were diagnosed with LTBI; only one was from a high risk ethnicity. Five of them completed prophylaxis and started anti-TNF treatment. Four declined TB prophylaxis and did not wish to proceed to anti-TNF therapy. None of the 9at risk9 groups (either IGRA negative or following TB chemoprophylaxis) developed active TB. Similarly, 9low risk9 group remained disease free (average length of follow up, 30 months, SD 15.3). Conclusion: In a low TB prevalence area, initial risk assessment followed by IGRA testing seems to be effective in preventing development of active TB in patients starting anti-TNF therapy.

Introduction: Clinical training may expose medical and nursing students to workplace hazards comparable to those encountered by healthcare workers (HCWs). This study was designed to investigate the prevalence of latent tuberculosis infection (LTBI) and associated risk factors among medical and nursing students. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria, a systematic review was conducted utilising four electronic databases to appraise and synthesise the literature on LTBI which used the tuberculin skin test (TST) and the blood interferon-gamma release assay (IGRA). Results: Original articles published in the English language between 2010 and 2020 were included, yielding 14 relevant articles. The average prevalence of LTBI in high-burden countries was 38.2% for TST and 20.6% for the IGRA test. According to TST and IGRA findings, the average prevalence of LTBI in nations with an intermediate burden was 16.7% and 4.7 %, respectively. The average prevalence was 2.8% and 1.1% from the TST and IGRA tests for low-burden countries, respectively. A greater risk of LTBI was shown to be related with an increase in age among postgraduate medical school students, a history of Bacillus Calmette-Guerin (BCG) vaccination, origin from high-risk tuberculosis (TB) countries, increased hours of hospital exposure, a history of contact with TB cases, a high body mass index, older age group students, and a lower TB knowledge score. Conclusion: The available evidence from this review emphasised the importance of developing and implementing efficient and cost-effective TB infection-control programmes, particularly in high-burden countries and amongst students at risk.

Background Congenital tuberculosis (TB) is uncommon and difficult to detect in neonates due to its nonspecific symptoms. We conducted a contact investigation of infants and healthcare workers (HCWs) exposed to a neonate with congenital TB in a neonatal ICU (NICU) in Korea. Methods A premature infant born was admitted to NICU on September 16, 2022. On October 24, the infant's mother was diagnosed with miliary TB, and infant’s sputum AFB stain showed 4 positive results. All NICU infants and HCWs during the same period were screened for active pulmonary TB using chest radiography (CXR) immediately. Exposed infants were evaluated with a TST and CXR three months after exposure. Interferon-Gamma Release Assay (IGRA) testing was performed on those with a positive TST or abnormal CXR finding. Prophylactic rifampin was provided to the exposed infants for 3 months, as index had isoniazid-resistant M. tuberculosis infection. Exposed HCWs underwent IGRA testing immediately after exposure (1st IGRA) and at 8 to 10 weeks post-exposure (2nd IGRA), and CXR was performed 6 months after exposure. Results Five out of 82 exposed infants had positive TST (≥ 10 mm) results, while all 31 infants who underwent IGRA testing had negative results. All five with positive TST had received BCG vaccination a median 105 days before. Of the 119 exposed HCWs, three had a conversion; two had negative results (on annual IGRA testing performed according to the national TB prevention Act) before exposure and positive at 1st IGRA test, and one had negative 1st IGRA test then positive 2nd IGRA test. None had active TB during 6-month follow-up. Conclusion We found that 6% of exposed infants had positive TST results and 0% had positive IGRA, while 2.5% of exposed HCWs had conversion. Considering the possibility of false positive TST results due to prior BCG vaccination, the chance of transmission to the infants would be 0%; otherwise, it would be 6.1%. Disclosures All Authors: No reported disclosures

Introduction Prior to immunosuppression, rheumatology patients are routinely screened for latent tuberculosis (TB) infection using interferon-gamma release assays (IGRAs). Variability in the management of latent and indeterminate IGRA results across institutionslimited long-term outcome data. A retrospective study was conducted at Tawam Hospital, United Arab Emirates, to investigate the incidence and management protocols associated with positive and indeterminate IGRAresults, as well as TBinfection, among patients with rheumatic conditions. Methods A single-center retrospective observational study was performed at Tawam Hospital, Abu Dhabi, UAE. Ethical approval for this study was obtained from the Tawam Human Research Ethics Committee. Laboratory records and the hospital's electronic medical system were used to obtain information about IGRA results over a 12-year period (April 2010-April 2022). The hospital's electronic medical system was used to obtain patient information and subsequent management approaches of positive and indeterminate IGRAs.Moreover, long-term follow-up data were collected to determine the risk of TB reactivation in the cohort. Results We found a total of 1,012 positive and 223 indeterminate IGRA test results within the 12-year period. Within the rheumatology department, 123 positive and 39 indeterminate IGRA results were identified. In the indeterminate IGRA group, the majority were women (n = 24, 61.5%) and UAE nationals (n = 22, 56.4%), and their mean age was 38.6 years. Systemic lupus erythematosus was the most prevalent rheumatologic condition (n = 21, 53.8%). Thirteen (33.3%) were on disease-modifying anti-rheumatic drugs (DMARDs) and 26 (66.7%) were on corticosteroids during IGRA testing. A total of eight patients (20.5%) received anti-TB medications. In the positive IGRA group, the mean age was 55.7 years and the female-to-male ratio was 3:1. The most common rheumatologic condition was rheumatoid arthritis (n = 69, 56%). Sixty-five (52.8%) patients were on conventional DMARDs, 43 (34.9%) were on corticosteroids during IGRA testing, and 74 (60%) received anti-TB medications. Two cases (1.6%) of active TB infections were detected among patients with positive IGRA tests, both of whom were receiving anti-tumor necrosis factor alpha inhibitor treatment in combination with methotrexate. No cases of active TB infection were observed in the indeterminate IGRA group. Conclusion Long-term data on the risk of TB activation in positive and indeterminate IGRA results for rheumatological conditions are low. It is recommended to reassess the choice of using anti-TNF-α, with a positive IGRA result if no other feasible alternatives can be offered. Our findings stress the importance of age, underlying diseases, and immunosuppressive treatments in interpreting IGRA results and guiding patient management. A large multicenter study is needed to understand the differences and outcomes of such patients in TB endemic and nonendemic geographical areas.

CD14++CD16- classical monocyte subset secreting IL-1ß and IL-10 is associated with 'Tuberculosis Resisters' phenotype.