Interferon-gamma Release Assay Research Articles

Economic evaluation of diagnosis and treatment for latent tuberculosis infection among contacts of pulmonary tuberculosis patients in Thailand

Currently, interferon-gamma release assay (IGRA) is costly and not included as latent tuberculosis infection (LTBI) screening test strategy in Thailand’s Universal Coverage Scheme (UCS) benefit package. The objective of this study was to assess the cost-utility of LTBI screening strategies among tuberculosis (TB) contacts in Thailand. A hybrid decision tree and Markov model was developed to compare the lifetime costs and health outcomes of tuberculin skin test (TST) and IGRA, in comparison to no screening, based on a societal perspective. Health outcomes were the total number of TB cases averted and quality-adjusted life years (QALYs), with results presented as an incremental cost-effectiveness ratio (ICER). One-way and probabilistic sensitivity analyses were performed to explore uncertainties in all parameters. The ICER of TST compared with no screening was 27,645 baht per QALY gained, while that of IGRA compared to TST was 851,030 baht per QALY gained. In a cohort of 1000 TB contacts, both TST and IGRA strategies could avert 282 and 283 TB cases, respectively. At the Thai societal willingness-to-pay threshold of 160,000 baht per QALY gained, TST was deemed cost-effective, whereas IGRA would not be cost-effective, unless the cost of IGRA was reduced to 1,434 baht per test.

Overcoming the age-dependent SARS-CoV-2 vaccine response through hybrid immunity: analysis of humoral and cellular immunity with mass cytometry profiling

BackgroundAge-dependent immune responses to coronavirus disease 2019 (COVID-19) vaccinations and breakthrough infections (BIs) in young and middle-aged individuals are unclear.MethodsThis nationwide multicenter prospective cohort study analyzed immune responses in participants of the ChAdOx1 (ChAd)-ChAd-mRNA vaccine group using cytometry by time-of-flight, anti-spike protein antibody (Sab) and anti-nucleocapsid antibody (Nab) titers, plaque reduction neutralization tests (PRNTs), and interferon-gamma (IFN-γ) release assays at various time points.ResultsWe evaluated 347 participants with an average age of 38.9 ± 9.4 years (range: 21–63). There was a significant inverse correlation between age and Sab levels after the second dose (slope − 14.96, P = 0.032), and this was more pronounced after the third dose (slope − 208.9, P < 0.001). After BIs, older participants showed significantly higher Sab titers (slope 398.8, P = 0.001), reversing the age-related decline observed post-vaccination. This reversal was also observed in PRNTs against wild-type SARS-CoV-2 and the BA.1 and BA.5 variants. IFN-γ responses increased markedly after the third dose and Bis, but showed a weak positive correlation with age, without statistical significance. Immune cell profiling revealed an age-dependent decrease in the proportions of B-cell lineage cells. The proportions of naive CD4+ and CD8+ T cells were inversely correlated with age, whereas the proportions of mature T cell subsets with memory function, including memory CD4+ T, CD8+ TEM, CD8+ TEMRA, and TFH cells, increased with age.ConclusionsAge-dependent waning of the serologic response to COVID-19 vaccines occurred even in middle-aged individuals, but was reversed after BIs. IFN-γ responses were preserved, compensating for the decrease in naive T cell populations, with an increase in memory T cell populations.

Hybrid Immunity Protects against Antibody Fading after SARS-CoV-2mRNA Vaccination in Kidney Transplant Recipients, Dialysis Patients, and Medical Personnel: 9 Months Data from the Prospective, Observational Dia-Vacc Study.

(1) Background: Compared to medical personnel, SARS-CoV-2mRNA vaccination-related positive immunity rates, levels, and preservation over time in dialysis and kidney transplant patients are reduced. We hypothesized that COVID-19 pre-exposure influences both vaccination-dependent immunity development and preservation in a group-dependent manner. (2) Methods: We evaluated 2- and 9-month follow-up data in our observational Dia-Vacc study, exploring specific cellular (interferon-γ release assay = IGRA) and/or humoral immune responses (IgA/IgG/RBD antibodies) after two SARS-CoV-2mRNA vaccinations in 2630 participants, including medical personnel (301-MP), dialysis patients (1841-DP), and kidney transplant recipients (488-KTR). Study participants were also separated into COVID-19 pre-exposure (hybrid immunity) positive (n = 407) versus negative (n = 2223) groups. (3) Results: COVID-19 pre-exposure improved most vaccination-related positive immunity rates in KTR and DP at 2 months but not in MP, where rates reached almost 100% independent of hybrid immunity. In the COVID-19-negative study, patients' immunity faded between two and nine months, evaluated via the percentage of patients with an RBD antibody decrease >50%, and was markedly group- (MP-17.8%, DP-52.2%, and KTR-38.6%) and vaccine type-dependent. In contrast, in all patient groups with COVID-19, pre-exposure RBD antibody decreases of >50% were similarly rare (MP-4.3%, DP-7.2%, and KTR-0%) but still vaccine type-dependent, with numerically reduced numbers in mRNA-1273- versus BNT162b2mRNA-treated patients. Multivariable regression analysis of RBD antibody changes between two and nine months by interval scale categorization confirmed COVID-19 pre-exposure as a factor in inhibiting strong RBD Ab fading. COVID-19 pre-exposure in MP and DP also numerically reduced T-cell immunity fading. In DP, symptomatic (versus asymptomatic) COVID-19 pre-exposure was identified as a factor in reducing strong RBD Ab fading after vaccination. (4) Conclusions: After mRNA vaccination, immunity positivity rates in DP and KTR but not MP, as well as immunity preservation in MP/DP/KTR, are markedly improved via prior COVID-19 infection. In DP, prior symptomatic compared to asymptomatic COVID-19 disease was particularly effective in blocking immunity fading after mRNA vaccination.

Frequent detection of IFN-gamma -producing memory effector and effector T cells in patients with progressive multifocal leukoencephalopathy.

Progressive Multifocal Leukoencephalopathy (PML) is a rare and deadly demyelinating disease caused by JC virus (JCV) replication in the central nervous system. PML occurs exclusively in patients with severe underlying immune deficiencies, including AIDS and hematological malignancies. PML has also emerged as a significant threat to patients on potent new immunosuppressive biologics, including natalizumab in multiple sclerosis. Here, we developed an IFN-γ release assay (IGRA) that mainly detects JCV-specific effector memory T cells and effectors T cells in the blood. This assay was frequently positive in patients with active PML (with a positive JCV PCR in CSF) of various underlying immunosuppression causes (84% sensitivity). Only 3% of healthy donors had a positive response (97% specificity). The frequency of positivity also increased in multiple sclerosis patients according to the time on natalizumab (up to 36% in patients treated for more than 48 months, who are considered at a higher risk of PML). The results show this assay's frequent or increased positivity in patients with PML or an increased risk of PML, respectively. The assay may help to stratify the risk of PML.

Systemic and ocular outcomes in TB-immunoreactive patients receiving immunomodulatory therapy for non-infectious uveitis: a case-control study

BackgroundTuberculosis (TB)-immunoreactivity, measured in vivo (tuberculin skin test (TST)) or in vitro (interferon gamma release assay (IGRA)), can be found in latent, active or even following clearance of TB infection....

How useful is chest x-ray in addition to routine QuantiFERON® in the detection of latent tuberculosis prior to biologics?

Screening for latent tuberculosis (TB) infection is recommended prior to commencing some biologics with QuantiFERON®/interferon gamma-releasing assay (IGRA) and chest x-ray (CXR) recommended on the BAD biologics checklist. QuantiFERON® is highly sensitive while CXR is poorly sensitive and poorly specific. In our cohort of 995 patients, 2.3% had a positive IGRA and 8.3% had any abnormality on CXR with just 0.8% suggestive of TB. Patients were just as likely to have an abnormal CXR if they had a positive or negative IGRA (p=0.927). We suggest that routine screening with IGRA alone is sufficient in the dermatology population particularly in the setting of a low TB incidence country such as the United Kingdom.

Identification of cytokine signatures in HIV‑infected individuals with and without Mycobacterium tuberculosis co‑infection.

Individuals with human immunodeficiency virus (HIV) infection are susceptible to immune system dysregulation, particularly during co-infection with Mycobacterium tuberculosis (MTB). Although there is an association between cytokine profiles and HIV-MTB co-infection, little is known about the cytokine-related host immune response mechanism to HIV-MTB co-infection. Therefore, the present study aimed to analyze expression of cytokines IL-17A, IFN-γ, TNF, IL-2, IL-10, IL-6 and IL-4 in individuals with HIV-MTB co-infection. A total of 30 patients with HIV and 40 with HIV-MTB co-infection were recruited into the present study, including those with active (A) (n=19) and latent (L)TB (n=21). HIV infection status was established based on national HIV guideline (Pedoman Nasional Pelayanan Kedokteran Tatalaksana HIV). ATB was confirmed using a positive acid-fast bacillus staining and culture of sputum; LTB status was established using IFN-γ release assay. Furthermore, the levels of cytokines IL-17A, IFN-γ, TNF, IL-10, IL-6, IL-4 and IL-2 were measured using flow cytometric bead array and CD4 cell count was performed by PIMA™ CD4 assay. IFN-γ, TNF, IL-10, IL-6 and IL-2 were able to significantly differentiate patients with HIV-ATB from those with HIV-LTB. Furthermore, in the patient subgroup with CD4 count <350 cells/µl, IFN-γ, IL-10 and IL-6 were able to differentiate between patients with HIV-ATB and HIV alone, as well as between patients with HIV-ATB and HIV-LTB. Based on these findings, the cytokine profiles are likely to be distinct between individuals with HIV infection with A- and LTB. Furthermore, the expression of CD4-positive T cells may influence the immune response in the body under HIV-MTB co-infection.

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