Interferon-gamma Release Assay Research Articles

Risk factors for tuberculosis among close IGRA-negative contacts of persons with infectious tuberculosis in Singapore

ObjectivesContacts of patients with infectious tuberculosis (TB) testing positive on interferon-gamma release assay (IGRA) are followed up to exclude active disease. However, identifying factors that predispose IGRA-negative contacts to TB could improve screening and follow-up strategies in a medium TB burden country such as Singapore. MethodsWe conducted a retrospective study of IGRA-negative contacts aged ≥2 years identified during contact investigation between January 2014 and December 2022. We examined the risk factors associated with developing active TB among contacts previously testing IGRA-negative, using univariate and multivariable logistic regression and odds ratios with 95% confidence intervals. ResultsOf 60,377 IGRA-negative contacts, 150 developed TB disease, and half were notified within 23 months of index patient diagnosis. IGRA-negative contacts of a smear-positive index patient were more likely to develop TB. Independent risk factors for TB were age >50 years, Malay ethnicity, having diabetes or end-stage renal failure, a “family” relationship with the index patient, or exposure in a dormitory or nursing home. ConclusionsIdentifying risk factors could help optimise follow-up strategies and preventive treatment in IGRA-negative individuals. The incidence rate of TB in this group was 150 per 100,000 population, substantially higher than in the community, with a median 92 weeks to develop disease. Findings suggest that follow-up should be extended to 24 months for contacts with these risk factors.

Risk Factors for Impaired Cellular or Humoral Immunity after Three Doses of SARS-CoV-2 Vaccine in Healthy and Immunocompromised Individuals.

Background: We aimed to identify the risk factors for impaired cellular and humoral immunity after three doses of the SARS-CoV-2 vaccine. Methods: Six months after the third vaccine dose, T-cell immunity was evaluated using interferon-gamma release assays (IGRAs) in 60 healthy and 139 immunocompromised (IC) individuals, including patients with hematologic malignancy (HM), solid malignancy (SM), rheumatic disease (RD), and kidney transplantation (KT). Neutralizing antibody titers were measured using the plaque reduction neutralization test (PRNT) and surrogate virus neutralization test (sVNT). Results: T-cell immunity results showed that the percentages of IGRA-positive results using wild-type/alpha spike protein (SP) and beta/gamma SP were 85% (51/60) and 75% (45/60), respectively, in healthy individuals and 45.6% (62/136) and 40.4% (55/136), respectively, in IC individuals. IC with SM or KT showed a high percentage of IGRA-negative results. The underlying disease poses a risk for impaired cellular immune response to wild-type SP. The risk was low when all doses were administered as mRNA vaccines. The risk factors for an impaired cellular immune response to beta/gamma SP were underlying disease and monocyte%. In the sVNT using wild-type SP, 12 of 191 (6.3%) individuals tested negative. In the PRNT of 46 random samples, 6 (13%) individuals tested negative for the wild-type virus, and 19 (41.3%) tested negative with omicrons. KT poses a risk for an impaired humoral immune response. Conclusions: Underlying disease poses a risk for impaired cellular immune response after the third dose of the SARS-CoV-2 vaccine; KT poses a risk for impaired humoral immune response, emphasizing the requirement of precautions in patients.

Evaluation of concordance of new QuantiFERON-TB Gold Plus platforms for Mycobacterium tuberculosis infection diagnosis in a prospective cohort of household contacts.

Tuberculosis is an airborne infectious disease caused by Mycobacterium tuberculosis that affects over 10 million people annually, with over 2 billion people carrying an asymptomatic tuberculosis infection (TBI) worldwide. Currently, TBI diagnosis includes tuberculin skin test and the blood-based interferon-gamma (IFN-γ) release assays, with Qiagen QuantiFERON-TB Gold Plus (QFT) being among those most widely utilized. We evaluated Qiagen's newer QFT platforms commercially available in a prospective cohort of tuberculosis contacts. A substantial agreement was obtained between the current QFT-enzyme-linked immunosorbent assay (ELISA) and the new QFT-chemiluminescence immunoassay (CLIA) platform, although QFT-CLIA provided higher concentrations of IFN-γ, leading to a 16.6% higher positivity rate. We highlight that both platforms may not be directly interchangeable and that further validation is required.

Suppression of host gene expression is associated with latent TB infection: a possible diagnostic biomarker

The World Health Organization End TB strategy aims for a 90% reduction of tuberculosis (TB) incidence by 2035. Systematic testing and treatment of latent TB infection (LTBI) among contacts of active TB patients is recommended as one of the ways to curtail TB incidence. However, there is a shortage of tools to accurately diagnose LTBI. We assessed the appropriateness of whole blood host transcriptomic markers (TM) to diagnose LTBI among household contacts of bacteriologically confirmed index cases compared to HIV negative healthy controls (HC). QuantiFERON-TB Gold Plus Interferon gamma release assay (IGRA) and reverse-transcriptase quantitative PCR were used to determine LTBI and quantify TM expression respectively. Association between TM expression and LTBI was evaluated by logistic regression modelling. A total of 100 participants, 49 TB exposed (TBEx) household contacts and 51 HC, were enrolled. Twenty-five (51%) TBEx individuals tested positive by IGRA, and were denoted as LTBI individuals, and 37 (72.5%) HC were IGRA-negative. Expression of 11 evaluated TM was significantly suppressed among LTBI compared to HC. Out of the 11 TM, ZNF296 and KLF2 expression were strongly associated with LTBI and successfully differentiated LTBI from HC. Paradoxically, 21 (49%) TBEx participants who tested IGRA negative exhibited the same pattern of suppressed TM expression as IGRA positive (LTBI-confirmed individuals). Results suggest that suppression of gene expression underlies LTBI and may be a more sensitive diagnostic biomarker than standard-of-care IGRA.

Is yearly interferon gamma release assay latent tuberculosis infection screening warranted among patients with rheumatological diseases on disease-modifying drugs in non-endemic settings?

Patients living with rheumatologic diseases on disease-modifying antirheumatic drugs (DMARD) are at an increased risk of developing tuberculosis (TB). Current guidelines recommend screening for latent tuberculosis infection (LTBI) before initiating DMARD. However, data is lacking on the value of yearly screening for LTBI. A retrospective chart review was conducted on adult patients (≥ 18 years) with rheumatologic disease on DMARD followed longitudinally in the outpatient rheumatology clinics between 2017-2021. Collected data included patient demographics, rheumatologic diagnosis, medications, TB-related risk factors, interferon gamma release assay (IGRA) results, LTBI diagnosis and treatment. Descriptive statistics were performed. Among 339 patients, 81 (23.9%) were male, 259 (76.4%) were white, and 93 (27.5%) were Latinx. Inflammatory arthritis (84.1%) was the most common rheumatic diagnosis. Common DMARD were JAK inhibitors (19.2%), TNF-alpha inhibitors (18.9%), and IL-17 A inhibitors (18.0%). Only 2 patients at baseline had positive IGRA, and both had a history of treated LTBI. Positive IGRA tests were recorded in 1 (0.7%), 3 (1.8%), 3 (1.3%), and 3 (1.1%) in the years 2018, 2019, 2020, and 2021, respectively. Four patients converted from negative to positive during serial yearly IGRA testing. After reviewing the IGRA test and TB risk factors, only one patient was considered newly diagnosed with LTBI, requiring 4 months of rifampin. In a non-endemic area, serial IGRA testing of low-risk patients on DMARD yielded very low rate of newly diagnosed LTBI. A targeted LTBI screening based on TB-related risk factors should be performed prior to IGRA testing rather than universal yearly screening in a non-endemic setting.

Conversion or reversion of interferon gamma release assays for Mycobacterium tuberculosis infection: a systematic review and meta-analysis.

Interferon-gamma release assays (IGRA) are widely used for diagnosis of latent tuberculosis infection. However, with repeat testing, IGRA transformation (conversion or reversion) may be detected and is challenging to interpret. We reviewed the frequency of and risk factors for IGRA transformation. We screened public databases for studies of human participants that reported the frequency of IGRA transformation. We extracted study and subject characteristics, details of IGRA testing and results. We calculated the pooled frequency of IGRA transformation (and transient transformation) and examined associated risk factors. The pooled frequency of IGRA conversion or reversion from 244 studies was estimated at 7.3% (95% CI 6.1-8.5%) or 22.8% (20.1-25.7%), respectively. Transient conversion or reversion were estimated at 46.0% (35.7-56.4%) or 19.6% (9.2-31.7%) of conversion or reversion events respectively. Indeterminate results seldom reverted to positive (1.2% [0.1-3.5%]). IGRA results in the borderline positive or negative range were associated with increased risk of conversion or reversion (pooled OR: conversion, 4.15 [3.00-5.30]; reversion, 4.06 [3.07-5.06]). BCG vaccination was associated with decreased risk of conversion (0.70, 0.56-0.84), cigarette smoking with decreased risk of reversion (0.44, 0.06-0.82), and female sex with decreased risk of either conversion or reversion (conversion, 0.66 [0.58-0.75]; reversion, 0.46 [0.31-0.61]). IGRA conversion is less common than reversion, and frequently transient. Research is needed to determine whether individuals with reversion would benefit from tuberculosis preventive treatment. Re-testing of people with indeterminate results is probably not indicated, since indeterminate results seldom revert to positive.

Examining Diagnostic Efficacy: GeneXpert Versus Traditional Staining Techniques With Culture in the Diagnosis of Tuberculosis.

Introduction The tuberculosis (TB) diagnosis involves various methods, such as microscopic examination, culture-based methods, molecular techniques, chest X-rays, serological tests, and interferon-gamma release assays. These methods help identify and confirm TB and its resistance to rifampicin, balancing speed and accuracy for prompt treatment initiation and effective disease management. Aims and objectives To assess the diagnostic accuracy of GeneXpert, Ziehl-Neelsen staining, and fluorescence staining compared to culture media in TB-suspected patients. Materials and methods We analysed 416 patient samples for TB over one year using GeneXpert, Ziehl-Neelsen staining, fluorescence staining, andLöwenstein-Jensen (LJ) medium. Only samples with a suspicion of TB were included in the study. The samples received without clinical history and requests for all four tests were excluded. Results A total of 416 patient samples were categorised into pulmonary and extrapulmonary samples. GeneXpert detected 62 positive cases for TB, out of which 53 were rifampicin-sensitive, seven were rifampicin-indeterminate, and two were rifampicin-resistant. The indeterminate samples were further evaluated using the line probe assay (LPA), of which six were rifampicin-sensitive, and one was rifampicin-resistant. Fluorescent staining detected 44 cases, Ziehl-Neelsen staining detected 40 cases, and LJ culture medium detected 65 cases. Conclusion GeneXpert is superior to staining methods for detecting TB. GeneXpert, combined with microscopyand culture, can enhance TB and multi-drug resistant tuberculosis (MDR-TB) detection and aid in early treatment initiation.

Evaluating the role of Mycobacterium tuberculosis PCR in ruling out active tuberculosis

Laboratory algorithms using Acid-Fast Bacilli staining and Mycobacterium tuberculosis (Mtb) polymerase chain reaction (PCR) are often used to remove isolation precautions. A retrospective case review of 52 patients with culture-confirmed pulmonary Mtb revealed 4 subjects with negative sputum Acid-Fast Bacilli smears and negative Mtb PCRs. All had significant risk factors for Mtb and had a positive interferon-gamma release assay. A negative PCR test result does not exclude an Mtb diagnosis.

Retrospective analysis of the clinical utility of multi-cytokine profiles in smear-negative pulmonary tuberculosis.

To evaluate cytokine profiles and interferon-gamma release assay (IGRA) for their diagnostic capabilities in the differentiation of tuberculosis (TB) from non-TB conditions, as well as smear-negative pulmonary tuberculosis (SNPT) from smear-positive pulmonary tuberculosis (SPPT). A total of 125 participants were included, 77 of whom had TB and 48 who didn't, and demographic, clinical, and laboratory data were collected, including cytokine levels and IGRA results. The TB patients were further divided into 2 subgroups: SNPT (n=42) and SPPT (n=35). Compared to non-TB, the TB group had lower BMI, higher WBC, neutrophils, monocytes, ESR and CRP (p<0.05). TB patients showed higher IL-2, IL-6, IFN-γ, IL-8 (p<0.001) and higher IGRA positivity (88.3% versus [vs.] 29.2%, p<0.001). Between SNPT and SPPT, moderate effect sizes were observed for IFN-α, IL-2, IL-10, IL-8 (Cohen's d 0.59-0.76), with lower IGRA positivity in SNPT (81.0% vs. 97.1%, p=0.015). ROC analysis indicated IFN-α, IL-2, IL-10, IL-8 had moderate accuracy for SNPT diagnosis (AUCs 0.668-0.734), and combining these improved accuracy (AUC 0.759, 80% sensitivity, 64.2% specificity). A multi-biomarker approach combining these cytokines demonstrates enhanced diagnostic accuracy for tuberculosis.

Overlooked, dismissed, and downplayed: reversion of Mycobacterium tuberculosis immunoreactivity.

Tuberculosis (TB) is caused by Mycobacterium tuberculosis (Mtb). Following infection, immune responses to Mtb antigens can be measured using the tuberculin skin test or an interferon-γ release assay. The gain of Mtb immunoreactivity, a change from a negative to a positive tuberculin skin test or interferon-γ release assay result, is called conversion and has long been used as a measure of Mtb exposure. However, the loss of immunoreactivity (reversion; a positive followed by a negative result) has often been overlooked. Instead, in clinical and epidemiological circles, Mtb immunoreactivity is commonly considered to persist lifelong and confer a lifetime of disease risk. We present a critical review, describing the evidence for reversion from cohort studies, ecological studies and studies of TB progression risk. We outline the inconsistent reasons why reversion has been dismissed from common understanding and present evidence demonstrating that, just as conversion predominantly indicates prior exposure to Mtb antigens, so its opposite, reversion, suggests the reduction or absence of exposure (endogenous or exogenous). Mtb immunoreactivity is dynamic in both individuals and populations and this is why it is useful for stratifying short-term TB progression risk. The neglect of reversion has shaped TB research and policy at all levels, influencing clinical management and skewing Mtb infection risk estimation and transmission modelling, leading to an underestimation of the contribution of re-exposure to the burden of TB, a serious oversight for an infectious disease. More than a century after it was first demonstrated, it is time to incorporate reversion into our understanding of the natural history of TB.

Not Your Usual Exposure: Tuberculosis Contact Investigation Related to Contaminated Bone Allograft

Background: Mycobacterium tuberculosis transmission through contaminated bone allograft product is unusual and was first described in 2021 with a second outbreak in 2023. In July 2023, Michigan Medicine conducted contact tracing for healthcare personnel (HCP), patients, and visitors following exposure to an immunocompromised patient with surgical site infection and subsequent widely disseminated tuberculosis (bacteremia, pulmonary, lymphadenopathy) following spinal fusion with bone allograft in April 2023. The patient was in the emergency department, operating room (OR), and inpatient units for 9 days prior to initiation of Airborne Precautions (AP). Methods: Michigan Medicine is a 1,107 bed academic hospital. HCP are screened for tuberculosis with interferon-gamma release assay (IGRA) testing upon hire and following tuberculosis exposure. Exposure testing includes baseline IGRA testing and follow-up testing at 10-12 weeks post exposure. Exposure criteria for this investigation was defined as sharing room airspace with the tuberculosis patient prior to initiation of airborne precautions or Central Sterile Processing Department (CSPD) staff involved with instrument decontamination without the use of a respirator. Of note, universal masking with surgical masks was not required during this time for staff and patients/visitors, with the exception of CSPD and OR staff. Contact tracing was performed by Infection Prevention and Occupational Health Services managed all test results and conversions. Results: 176 employees from perioperative care areas (n=30), CSPD (n=7), OR (n=9) and inpatient units (n=130) were IGRA tested. Five employee conversions were identified: one surgeon, one circulating OR nurse, two CSPD decontamination staff, and one respiratory therapist. At time of detection, none of the conversions had evidence of active tuberculosis. Additionally, 46 patients and visitors were tested with zero conversions. HCP compliance with IGRA testing was initially 15% before engagement from hospital and unit leadership and human resources. With intervention, employee compliance reached 100%. Conclusion: Despite standard use of surgical masks for OR and CSPD staff, aerosolization of infected bone graft material played an important role in tuberculosis transmission during surgery and instrument cleaning. Respiratory therapy practices in the ICU setting likely also increased risk for pulmonary tuberculosis transmission. Achieving 100% HCP compliance for baseline and follow-up IGRA testing is challenging and requires engagement of both unit and hospital leadership and human resources to ensure all HCP are tested.

Expansion of tumor-infiltrating lymphocytes in non-small cell lung cancer: Clinical potential and efficacy in EGFR mutation subsets

Our study aimed to expand tumor-infiltrating lymphocytes (TILs) from primary non-small cell lung cancers (NSCLCs) and evaluate their reactivity against tumor cells. We expanded TILs from 103 primary NSCLCs using histopathological analysis, flow cytometry, IFN-γ release assays, cell-mediated cytotoxicity assays, and in vivo efficacy tests. TIL expansion was observed in all cases, regardless of EGFR mutation status. There was also an increase in the median CD4+/CD8+ ratio during expansion. In post-rapid expansion protocol (REP) TILs, 13 out of 16 cases, including all three cases with EGFR mutations, exhibited a two-fold or greater increase in IFN-γ secretion. The cytotoxicity assay revealed enhanced tumor cell death in three of the seven cases, two of which had EGFR mutations. In vivo functional testing in a patient-derived xenograft model showed a reduction in tumor volume. The anti-tumor activity of post-REP TILs underscores their potential as a therapeutic option for advanced NSCLC, irrespective of mutation status.

Exploring the limits of interferon-γ releasing assay screening in large-scale populations

Exploring the limits of interferon-γ releasing assay screening in large-scale populations

Application of Interferon-γ Release Assay in the Assessment of T-Cell Immunity to SARS-CoV-2 Antigens in the Cohort of Pediatric Patients with Juvenile Idiopathic Arthritis.

Background: an accurate assessment of the immunity against SARS-CoV-2 can facilitate a better understanding and management of not only the recent coronavirus but similar pathogens as well. Objective: the aim of this study was to evaluate T-cell immunity with reference to antibody titers in a group of pediatric patients with autoimmune arthritides utilizing the widely known Interferon-γ Release Assay (IGRA). Materials and Methods: This study was conducted in the cohort of 55 children suffering from Juvenile Idiopathic Arthritis (JIA). This research analyzed the SARS-CoV-2 T-cell response measured by a specific quantitative IGRA, followed by a serological ELISA test measuring the presence and quantity of IgG, IgM, and IgA antibodies in serum. Results: The cellular response to SARS-CoV-2 measured by the IGRA test significantly correlated with the antibody titers, IgA (p < 0.00003, R = 0.537), IgG (p < 0.0001, R = 0.668), and IgG nucleocapsid protein (NCP) (p < 0.003, R = 0.0399), with no correlation with IgM levels. The antibody levels in patients receiving biological agents were significantly lower compared to the rest of the cohort (p = 0.0369), while traditional disease-modifying antirheumatic drugs had no such effect. Limitations: the main limitation of the research is the small sample size, mostly due to the specific cohort of patients and the lack of a healthy control. Conclusions: IGRA appears to be a viable tool in the accurate evaluation of T-cell responses to SARS-CoV-2, and serodiagnostics alone is not always sufficient in the assessment of immune responses.

The Effect of Exposure to SARS-CoV-2 Vaccination and Infection on Humoral and Cellular Immunity in a Cohort of Patients with Immune-Mediated Diseases: A Pilot Study.

Immunization against COVID-19 is needed in patients with immune-mediated inflammatory diseases (IMIDs). However, data on long-term immunity kinetics remain scarce. This study aimed to compare the humoral and cellular response to COVID-19 in patients with immune-mediated inflammatory diseases (IMIDs) compared to healthy controls. We compared the humoral and cellular response to SARS-Cov-2 elicited by vaccination and/or infection in a prospective cohort of 20 IMID patients compared with a group of 21 healthcare workers (HCWs). We assessed immunity before and after the third and fourth dose of BNT162b2 or after COVID-19 infection using quantitative IgG anti-SARS-CoV-2 Spike antibody (anti-S-IgG), neutralization assay, and specific interferon-gamma (IFN-g) release assay (IGRA). The responses were compared with those of healthy controls. The two groups were similar in age and total exposure, becoming infected for the first time, mainly after the third dose. Neutralizing antibodies and IGRA were negative in 9.5% of IMID patients but not in any HCWs. No significant difference was found between neutralization titers to BA.1 in the IMID and the HCW groups. The study highlights the SARS-CoV-2 immunological responses in healthy controls and IMID patients, suggesting that the combined stimuli of vaccination and infection in IMID patients could promote a more profound immunological response.

Surveillance of close contacts of patients with infectious tuberculosis: a prospective cohort study

BackgroundA long-term follow-up of close contacts to monitor their infection status is essential to formulate a promising screening strategy. The study aimed to assess the dynamics of tuberculosis (TB) infection using Interferon-γ release assay (IGRA) and determine risk factors associated with TB infection.MethodsDefinite TB patients were interviewed and their household contacts were screened for TB infection by IGRA during 12-month longitudinal investigation.ResultsWe included in our analyses 184 household contacts of 92 index TB patients. 87 individuals (47.3%) in contact group progressed to TB infection, of whom 86 developed into IGRA positive within 24 weeks. Close contacts with a higher age and comorbidities are easier to exhibit TB infection. Analysis showed that risk factors for becoming IGRA-positive individuals included residence, older age, comorbidities, BCG scar and high bacterial load. Contacts with BCG scar had a lower IGRA-positive rate.ConclusionIGRA conversion generally occurs within 24 weeks after exposure. The TB transmission happens since subclinical TB stage and the presence of BCG scar is an independent protective factor reducing risk of TB infection among close contacts. Repeated IGRA tests are sensible to conducted among close contacts at 24 weeks after exposure to identify the IGRA-positive individuals.

Comparison of Lateral-flow Nanoparticle Fluorescence Assay and ELISA Method for Interferon-y Release Assay Test

The detection of latent tuberculosis (TB) infection to prevent progression to active TB disease is an essential part of the WHO's end-TB strategy. Diagnosis of latent TB infection is based on detecting immune responses to Mycobacterium tuberculosis antigens. Interferon Gamma Release Assays (IGRA) are superior to Tuberculin Skin Tests (TST) for detecting latent infection; however, the performance of IGRA is limited in resource-limited settings. This study evaluated the sensitivity, specificity, and agreement of the lateral-flow nanoparticle fluorescence assay (QIAreach QFT) compared with the ELISA method (QFT-Plus) as a reference test. This cross-sectional study was carried out in the laboratory department of Siloam Hospitals in Lippo Village, Banten, Indonesia, between January and June 2023. A total of 60 samples consisting of both males and females of all age groups were tested for QFT-Plus and were involved in the study using consecutive samples. Sensitivity, specificity, Negative Predictive Value (NPV), and Positive Predictive Value (PPV) of QIAreach QFT were 100% (95% CI 86.28-100), 70.96% (95% CI 51.96-85.78), 100%, (95% CI 84.56-100) and 73.53% (95% CI 55.64-87.12), respectively. The agreement calculation using Cohen's kappa coefficient, excluding indeterminate data, showed a kappa value 0.68 (95% CI 0.507-0.864). QIAreach QFT, with its superiority, could support the expansion of IGRA testing, particularly in remote areas, thereby helping the eradication attempt of TB infection.

Accelerated Bacille Calmette-Guérin reactions: More than meets the eye

An accelerated local injection site reaction following Bacille Calmette-Guérin (BCG) vaccination has been associated with underlying active tuberculosis (TB) in high TB-prevalence settings. The clinical significance of this accelerated BCG reaction in individuals without TB symptoms, particularly in low TB-prevalence countries, is unclear.Using safety surveillance data and baseline interferon-gamma release assays (IGRA) within an international randomised trial of BCG vaccination in healthcare workers (the BRACE trial), we aimed to determine the incidence, and investigate for clinical implications, of an accelerated BCG reaction in asymptomatic adults in low and high TB-prevalence settings.An accelerated BCG reaction occurred in 755/1984 (38 %) of BCG-vaccinees. Although more frequently painful, tender, erythematous and/or swollen within the first fourteen days of vaccination, compared with non-accelerated reactions, the majority of injection site reactions were mild and did not meet criteria for an adverse event.Prior mycobacterial exposure, through prior BCG vaccination (OR 2.46, 95%CI 1.93–3.13, p < 0.001) or latent TB infection (OR 4.17, 95%CI 1.16–14.93, p = 0.03), and female sex (OR 1.27, 95%CI 1.03–1.57, p = 0.02), were key determinants for the occurrence of an accelerated BCG reaction.The development of an accelerated local reaction to BCG vaccination in an individual without prior history of BCG vaccination, should prompt consideration of further investigations for potential underlying TB infection.

A Mycobacterium bovis outbreak among exhibition animals at a zoo in the Republic of Korea: the first contact investigation of zoonotic tuberculosis.

Between July 2, 2021, and September 20, 2022, a Mycobacterium bovis outbreak occurred among exhibition animals at a zoo in the Republic of Korea. This study was conducted to assess the likelihood of M. bovis transmission to human contacts through a contact investigation and to implement preventive treatment for latent tuberculosis infection (LTBI). In this descriptive study, the Korea Disease Control and Prevention Agency conducted a contact investigation, which included interviews, interferon-gamma release assay (IGRA) tests, and chest X-rays. Contacts underwent IGRA testing on 2 occasions: initial testing of 29 contacts (15 in the first cluster of infection and 14 in the second cluster) and follow-up testing of the 15 contacts in the first cluster. The study included 29 participants, 18 of whom were male (62.1%) and 11 female (37.9%). The mean participant age was 37.3 years (standard deviation, 9.6 years). In the initial IGRA tests, 6 of the 29 participants tested positive, indicating a prevalence of 20.7%. Following prolonged exposure, 1 additional positive case was detected in follow-up testing, raising the prevalence of LTBI to 24.1%. None of the contacts had active tuberculosis. Among the 7 individuals with positive results, 2 (28.6%) underwent treatment for LTBI. This study faced challenges in confirming the transmission of M. bovis infection from infected animals to humans in the Republic of Korea. Nevertheless, adopting a One Health approach necessitates the implementation of surveillance systems and infection control protocols, particularly for occupational groups at high risk of exposure.

Effect of Smoking on Longitudinal Interferon-ϒ Release Assay Results among Close Contacts of People with Pulmonary Tuberculosis.

Diagnosis of M. tuberculosis (Mtb) infection in close contacts is critical for TB control. Smoking is a risk factor for Mtb infection and TB disease but its effect on longitudinal interferon-gamma release assay (IGRA) results remains unknown. We conducted a multi-site prospective study in Brazil between 2015-2019, among close contacts of adults with culture-confirmed pulmonary TB. IGRA was performed at baseline, month 6 if negative at baseline, and month 24-30 after enrollment. IGRA results were categorized as IGRA-positive (maintained from baseline to last visit), IGRA-conversion (from negative to positive at any time), IGRA-reversion (from positive to negative at any time), and IGRA-negative (maintained from baseline to last visit). Associations between IGRA results and smoking status at baseline (current/former vs never) in contacts were evaluated using propensity score-adjusted logistic regression models. Estimated propensity score was used as a covariate in models, which regressed the outcome (IGRA-positive, IGRA-conversion, IGRA-reversion) on smoking status. Of 430 close contacts, 89 (21%) were IGRA-positive, 30 (7%) were converters, 30 (7%) were reverters and 22 were indeterminate. Smoking frequency was 26 (29%) among IGRA-positive contacts, 7 (23%) in converters, and 3 (10%) in reverters. Smoking in contacts was associated with lower odds of IGRA-reversion (adjusted odds ratio = 0.16; 95% confidence interval = [0.03-0.70]). We did not detect associations between smoking and IGRA-positive or IGRA-conversion. Our findings highlight the importance of smoking on longitudinal IGRA results. This has implications for clinical care and clinical trials in which IGRA status is monitored or used as an outcome.