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

OBJECTIVES: 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). METHODS: 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). RESULTS: 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). CONCLUSION: A multi-biomarker approach combining these cytokines demonstrates enhanced diagnostic accuracy for tuberculosis.

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

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Incidence of Tuberculosis Among Immigrants in Korea Who Participated in a Latent Tuberculosis Infection Screening Program.

BACKGROUND: With a rapid decrease in tuberculosis (TB) incidence, the significance of latent tuberculosis infection (LTBI) has been underscored in South Korea. Although South Korea does not have a high proportion of immigrants compared to other countries, there is a growing argument that it should actively embrace immigrants as a solution to address issues of low birth rates and population aging. This study aimed to assess TB incidence among immigrants who participated a pilot LTBI screening program in South Korea. METHODS: Records of immigrants participated in a pilot LTBI screening program in South Korea between 2018 and 2019 were linked with Korean National TB Surveillance System to determine TB development. Participants underwent interferon-gamma release assay (IGRA) and chest X-rays. Standardized incidence ratios (SIRs) stratified by age, country of origin's TB burden was calculated with a reference group of general South Korean population. RESULTS: Of a total of 9,517 participants, 14 TB cases were identified. Participants with positive IGRA results who did not initiate LTBI treatment showed TB incidence of 312.5 per 100,000 person-years, whereas those with negative results showed TB incidence of 34.4 per 100,000 person-years, resulting in an incidence rate ratio of 9.08 (95% confidence interval [CI], 2.50-32.99). SIR of TB among total participants including those with negative IGRA results was 2.60 (95% CI, 1.54-4.38; P < 0.001), whereas SIR among those with positive IGRA results was 5.86 (95% CI, 3.15-10.89; P < 0.001). In the calculation of SIR among participants with positive IGRA results, those aged under 35 from high TB-burden countries or intermediate TB-burden countries showed a high SIR (18.08; 95% CI, 2.55-128.37; P = 0.004), and 11.30 (95% CI, 2.82-45.16; P < 0.001), respectively). Contrary to previous reports that suggest the majority of elderly population with a positive IGRA result were due to remote infection and had a lower TB risk compared to younger ages, SIR among those aged 65 or over from intermediate TB-burden countries was 6.15 (95% CI, 0.87-43.69; P = 0.069), which was comparable to that in younger participants aged between 35 and 49 (SIR, 4.87; 95% CI, 1.22-19.49; P = 0.025) or those aged between 50 and 64 (SIR, 4.62; 95% CI, 1.73-12.31; P = 0.002). CONCLUSION: Young immigrants with positive IGRA results from countries with high or intermediate TB burden showed a relatively high TB risk compared to a general South Korea population. In addition, unexpected high TB risk was observed among elderly immigrants with positive IGRA results. In establishing future policies for LTBI in immigrants in South Korea, screenings should primarily focus on younger age group (who aged under 35). Additionally, further research is needed on the high TB risk observed in elderly immigrants.

Diagnostic approach of tuberculous lymphadenitis in a multicenter study.

INTRODUCTION: Tuberculous lymphadenitis (TBLN) is the most common infectious etiology of peripheral lymphadenopathy in adults, in Turkiye. This study aimed to identify the demographic, clinical, and laboratory variables that differentiate TBLN from non-tuberculous lymphadenitis (NTBLN), as well as the etiology of lymphadenopathy in adults. METHODOLOGY: Patients who were over 18 years old and were referred to the infectious disease outpatient clinics with complaints of swollen peripheral lymph nodes, and who underwent lymph node biopsy between 1 January 2010 and 1 March 2021, were included in this multicenter, nested case-control study. RESULTS: A total of 812 patients at 17 tertiary teaching and research hospitals in Turkiye were included in the study. TBLN was the most frequent diagnosis (53.69%). The proportion of patients diagnosed with TBLN was higher among females; and among those who had a higher erythrocyte sedimentation rate, positive purified protein derivative test, and positive interferon-gamma release test result (p < 0.05). However, TBLN was less frequent among patients with generalized lymphadenopathy, bilateral lymphadenopathy, axillary lymphadenopathy, inguinal lymphadenopathy, hepatomegaly, splenomegaly, leukocytosis, and moderately increased C reactive protein levels (p < 0.05). CONCLUSIONS: Identifying the variables that predict TBLN or discriminate TBLN from NTBLN will help clinicians establish optimal clinical strategies for the diagnosis of adult lymphadenopathy.

Evaluation of SARS-CoV-2 interferon gamma release assay in BNT162b2 vaccinated healthcare workers.

To predict protective immunity to SARS-CoV-2, cellular immunity seems to be more sensitive than humoral immunity. Through an Interferon-Gamma (IFN-γ) Release Assay (IGRA), we show that, despite a marked decrease in total antibodies, 94.3% of 123 healthcare workers have a positive cellular response 6 months after inoculation with the 2nd dose of BNT162b2 vaccine. Despite the qualitative relationship found, we did not observe a quantitative correlation between IFN-γ and IgG levels against SARS-CoV-2. Using stimulated whole blood from a subset of participants, we confirmed the specific T-cell response to SARS-CoV-2 by dosing elevated levels of the IL-6, IL-10 and TNF-α. Through a 20-month follow-up, we found that none of the infected participants had severe COVID-19 and that the first positive cases were only 12 months after the 2nd dose inoculation. Future studies are needed to understand if IGRA-SARS-CoV-2 can be a powerful diagnostic tool to predict future COVID-19 severe disease, guiding vaccination policies.

Flow cytometry-based method using diversity of cytokine production differentiates between Mycobacterium tuberculosis infection and disease.

Authors present a pilot study of the development of innovative flow cytometry-based assay with a potential for use in tuberculosis diagnostics. Currently available tests do not provide robust discrimination between latent tuberculosis infection (TBI) and tuberculosis disease (TB). The desired application is to distinguish between the two conditions by evaluating the production of a combination of three cytokines: IL-2 (interleukin-2), IFNɣ (interferon gamma) and TNFɑ (tumor necrosis factor alpha) in CD4+ and CD8+ T cells. The study was conducted on 68 participants, divided into two arms according to age (paediatric and adults). Each arm was further split into three categories (non-infection (NI), TBI, TB) based on the immune reaction to Mycobacterium tuberculosis (M.tb) after a close contact with pulmonary TB. Each blood sample was stimulated with specific M.tb antigens present in QuantiFERON tubes (TB1 and TB2). We inferred TBI or TB based on the predominant cytokine response of the CD4+ and/or CD8+ T cells. Significant differences were detected between the NI, TBI and the TB groups in TB1 in the CD4+TNFɑ+parameter in children. Along with IL-2, TNFɑ seems to be the most promising diagnostic marker in both CD4+and CD8+ T cells. However, more detailed analyses on larger cohorts are needed to confirm the observed tendencies.

Impact of immune checkpoint inhibitors (ICIs) therapy on interferon-γ release assay (IGRA) and diagnostic value in non-small cell lung cancer (NSCLC) patients.

BACKGROUND: Tuberculosis (TB), a highly contagious respiratory disease, presents a significant global health threat, with a notable increase in incidence reported by the WHO in 2022. Particularly, the interplay between TB and non-small cell lung cancer (NSCLC) gains attention, especially considering the rising use of immune checkpoint inhibitors (ICIs) in cancer treatment. This interplay may influence TB diagnostics and reactivation, warranting a closer examination. METHODS: A retrospective analysis was conducted on clinical data of NSCLC patients with positive T-SPOT results before undergoing anti-tumor treatment at Zhongshan Hospital (Xiamen), Fudan University, from January 1, 2021 to December 31, 2022. We assessed the incidence of tuberculosis reactivation and treatment outcomes among these patients. Moreover, we compared the differences in tuberculosis activity between the ICIs and non-ICIs treatment groups. Additionally, we observed the changes in T-SPOT spot count before and after immunotherapy, analyzing their association with tuberculosis activity and prognosis. RESULTS: A total of 40 NSCLC patients with positive T-SPOT results before treatment were included in the study, with 26 patients in the ICIs treatment group and 14 patients in the non-ICIs treatment group. The study found no significant differences between the two groups in terms of gender, age, stage, histological type, performance status, driver gene expression, and distant metastasis. With a median follow-up time of 10.0 (6.0-14.5) months, three cases (11.5%) in the ICIs treatment group developed tuberculosis activity, diagnosed at 2, 3, and 12 months after ICIs treatment initiation. Conversely, no tuberculosis activity was observed in the non-ICIs treatment group, and the difference between the two groups was not significant (P = 0.186). Among the 32 patients who received ICIs treatment, spot count dynamics were diverse: four cases (12.5%) showed an increase, 12 cases (37.5%) had no change, and 16 cases (50.0%) had a decrease. During the follow-up, the progression rate (PD) was 50.0%, 75.0%, and 62.5% in the three groups, respectively (P = 0.527). Similarly, the mortality rate was 0%, 25.0%, and 25.0%, respectively (P = 0.106). Interestingly, among the patients with decreased spot counts, three cases (18.75%) were diagnosed with active pulmonary tuberculosis. CONCLUSIONS: For NSCLC patients with a positive T-SPOT response undergoing ICIs treatment, our study observed indications of active tuberculosis. The varied T-SPOT spot count changes post-ICIs treatment suggest a complex interaction, potentially linking T-SPOT spot count reduction to tuberculosis reactivation risk. These preliminary findings underscore the importance of further research to more accurately assess T-SPOT's diagnostic utility in this context.

Screening for latent tuberculosis in migrants-status quo and future challenges.

OBJECTIVES: To review the evidence that migrants from tuberculosis (TB) high-incidence countries migrating to TB low-incidence countries significantly contribute to active TB cases in the counties of destination, primarily through reactivation of latent TB. METHODS: This is a narrative review. The different screening programs in the countries of destination are reviewed either based on screening and preventive treatment of latent TB pre or more commonly - post arrival. RESULTS: Screening can be performed using interferon-gamma release assays (IGRA) or tuberculin skin tests (TST). Preventive treatment of latent TB is using either monotherapy with isoniazid, or in combination with rifampicin or rifapentine. We discuss the ethical issues of preventive treatment in asymptomatic individuals and how these are addressed in different screening programs. CONCLUSION: Screening migrants from TB high endemic countries to TB low endemic countries is beneficial. There is a lack of standardization and agreement on screening protocols, follow up and treatment.

Impact of annual TB screening on stone quarry workers in high-incidence Portuguese municipalities.

The Portuguese municipalities of Penafiel and Marco de Canaveses are high TB incidence areas, where stone quarry workers represent a vulnerable population.To assess the annual rate of TB infection (ARI) in stone quarry workers and to compare it with the TB notification rate in the general community.An annual TB infection screening strategy using interferon-gamma release assay (IGRA) was implemented in 2018 for workers from high-risk stone quarries. A prospective cohort was enrolled and workers screened in periods of 2 years were included. IGRA-positive workers were referred for preventive treatment. ARI was calculated as the proportion of workers with IGRA conversion.Of the 232 IGRA-negative workers in 2018, 20 tested positive in 2019 (8.6% ARI). Of 171 IGRA-negative workers in 2019, eight tested positive in 2021 (4.7% in 2 years). Two of the 150 IGRA-negative workers in 2021 tested positive in 2022 (1.3% ARI). ARI decreased by 84.9% between 2019 and 2022. In the two municipalities, the TB notification rate declined 23.9% between 2018 and 2021.A more pronounced reduction in ARI was observed among stone quarry workers regularly screened for TB infection compared to the notification rate among the general population in high-incidence municipalities. A screening strategy for high-risk populations, together with enforced community measures, could foster risk reduction in the community..

Relationship between biologic modifying agents and development of latent tuberculosis in pediatrics.

INTRODUCTION: Biologic modifying agents are associated with an increased risk for infection with mycobacteria. The aim of this study is to document patients who received different biologic modifying therapies in our pediatric rheumatology department and the possibility of development of tuberculosis (TB). METHODOLOGY: This retrospective study was conducted in Ankara City Hospital. Pediatric patients who were treated with biologic modifying agents between 2010-2020 were documented. Development of TB and the risk factors were assessed in this patient group. RESULTS: There were 72 patients who were treated with different biologic modifying agents. Tuberculin skin test (TST) was positive in 7 (9.7%) patients during follow up. Three patients whose TST was positive had received canakinumab, 2 received etanercept, 1 received adalimumab and 1 received anakinra. Median duration of therapy was 43.5 (16.5-168) months for these patients and the duration was longer than patients who did not develop latent tuberculosis (p = 0.04). Patients who developed latent TB under treatment were significantly older than the patients who did not (p = 0.01). CONCLUSIONS: According to our findings, 9.7% of pediatric patients who received biologic modifying agent therapy developed latent TB. Patients who developed latent TB were older, and the duration of treatment was longer than patients who did not develop latent TB. Although not statistically significant, canakinumab, which is known as an agent less likely to cause TST conversion, was in fact the most common agent that caused TST conversion.

Cost-effectiveness of interferon-γ release assay for screening of latent tuberculosis infection in individuals with schizophrenia.

Schizophrenia is recognized as a significant risk factor for tuberculosis (TB). This study aimed to evaluate the effectiveness and cost-effectiveness of interferon-γ release assay (IGRA) with preventive treatment for screening of latent tuberculosis infection (LTBI) in individuals with schizophrenia. A state transition model was developed from a healthcare payer perspective on a lifetime horizon. Ten strategies were compared by combining two different tests for LTBI, i.e. IGRA and tuberculin skin test (TST), and five different preventive treatments, i.e. 9-month isoniazid (9H), 3-month isoniazid and rifapentine (3HP) by directly observed therapy, 3HP by self-administered therapy, 3-month isoniazid and rifampin (3RH), and 4-month rifampin (4R). The main outcomes were costs, quality-adjusted life-years (QALYs), life expectancy life-years (LYs), incremental cost-effectiveness ratios, drug-sensitive tuberculosis (DS-TB) cases, and TB-related deaths. For both bacillus Calmette-Guérin (BCG)-vaccinated and non-BCG-vaccinated individuals, IGRA with 4R was the most cost-effective and TST with 3RH was the least effective. Among schizophrenic individuals in Japan, IGRA with 4R saved US$17.8 million, increased 58,981 QALYs and 935 LYs, and prevented 222 DS-TB cases and 75 TB-related deaths compared with TST with 3RH. In individuals with schizophrenia, IGRA with 4R is recommended for LTBI screening with preventive treatment to reduce costs, morbidity, and mortality from TB.

Incidence, risk factors for active tuberculosis infection and changes of IGRA in patients with Takayasu arteritis: a prospective cohort study.

There is limited evidence to support the association between tuberculosis (TB) and the occurrence of Takayasu arteritis (TAK). To investigate the incidence of active TB (ATB) in TAK and explore the impact of anti-rheumatic therapy on the occurrence of ATB or reactivation of Latent TB infection (LTBI) and their effect on interferon-γ release assay (IGRA) results, we conducted a prospective study based on the Chinese Registry for Systemic Vasculitis cohort. The standard incidence ratio (SIR) was calculated and stratified by age. Kaplan-Meier analysis was used to determine the effect of variables on ATB or LTBI reactivation in patients with TAK. Data from 825 patients with TAK in the registry were analysed. During a median follow-up of 5 years, 5 patients developed ATB with a crude incidence of 154 (95%CI:57-381) person-years/100,000. The SIR was 5.59 (95%CI:1.81-13.04). Glucocorticoids and conventional disease-modifying anti-rheumatic drugs (cDMARDs) did not increase the risk of ATB or LTBI reactivation (P > 0.05). However, the use of tumour necrosis factor inhibitor (TNFi) increased the risk of ATB in patients with LTBI (P < 0.001). Furthermore, the value of the IGRA assay decreased after treatment (P < 0.05). In conclusion, the incidence of TB infection is markedly increased in patients with TAK and patients with TAK are at high risk of developing ATB. Treatment with glucocorticoids and cDMARDs does not significantly increase the risk for ATB in patients with TAK. Moreover, IGRA may have limited effectiveness in monitoring ATB infection or LTBI reactivation in patients with TAK.

Disseminated tuberculosis after anti-TNF alpha treatment: Do not blindly trust the IGRA test.

INTRODUCTION: Interferon gamma release assay (IGRA) is used to detect latent tuberculosis prior to biological treatments in the context of suspected inflammatory rheumatism. METHODS: We report the case of a 50-year-old woman with negative IGRA test before adalimumab introduction for presumed axial spondyloarthritis. RESULTS: The worsening of symptoms under treatment led to further investigations and the diagnostic of disseminated tuberculosis (TB) was later established with miliary and multiple bone locations such as spondylitis and sacroilitis. The patient's history revealed past exposure to tuberculosis. This observation illustrates the limitations of IGRA in such situation due to its variable performance for active TB diagnosis. CONCLUSION: Misdiagnosis is frequent in bone tuberculosis due to non-specific signs. We draw the attention to the importance of a global risk assessment prior to the introduction of biological treatment for suspected chronic inflammatory rheumatism and recall the risk factors for false-negative IGRA. An extended treatment course may be necessary after exposure to anti-TNF-alpha.

Interferon-Gamma-Release assay and absolute CD8 lymphocyte count for acquired immunosuppression monitoring in critically ill patients.

Guided biomarker-personalized immunotherapy is advancing rapidly as a means to rejuvenate immune function in injured patients who are the most immunosuppressed. A recent study introduced a fully automated interferon-γ release assay (IGRA) for monitoring the functionality of T lymphocytes in patients with septic shock. While a significant decrease in IFN-γ release capacity was observed, a significant correlation with CD8 lymphocyte absolute count was also reported, raising the question of whether ex-vivo IFN-γ production would be only a surrogate marker for lymphocyte count or if these two parameters conveyed distinct and complementary information. In a large cohort of more than 353 critically ill patients following various injuries (sepsis, trauma, major surgery), the primary objective of the present study was to simultaneously evaluate the association between ex vivo IFN-γ release and CD8 cell count with regard to adverse outcome. Our findings provide a clear-cut result, as they distinctly demonstrate that IGRA offers higher-quality information than CD8 count in terms of an independent association with the occurrence of an adverse outcome. These results strengthen the case for incorporating IGRA into the array of biomarkers of interest for defining endotypes in sepsis. This holds especially true given that fully automated tests are now readily available and could be used in routine clinical practice.

Tuberculosis and childhood cancer - A review of literature.

Tuberculosis and malignancy are major public health problems in developing countries like India and causes significant morbidity and mortality. Mycobacterium tuberculosis is an aerobic acid-fast bacilli which is an important pathogen especially complicating clinical status of paediatric oncology patients and treatment of infection with this bacilli is challenging in this subpopulation of patients because of ongoing immunosuppression and relative lack of published guidelines. Atypical presentations of tuberculosis in children also complicate the diagnosis and management. All the more, in tuberculosis endemic area lung cancer may be mistakenly diagnosed as tuberculosis or vice versa and this wrong diagnosis increases the burden on country's health status. It is noted that tuberculosis prevalence is high in children with haematological malignancy and head and neck tumours compared to other solid organ tumours. Moreover, it is found that morbidity and mortality from tuberculosis is more in children from WHO listed high TB burden countries who undergo hematopoietic stem cell and solid organ transplantation. Use of immune checkpoint inhibitors as novel therapy in treatment of childhood malignancies has led to modification of the body's immunological response and has resulted in increased latent tuberculosis infection reactivation as one immune-related infectious consequence. Latent TB infection screening is important concept in management of paediatric oncology patients. Currently, the tests employed as screening diagnostics for LTBI are interferon-gamma release assay (IGRA) blood test and the tuberculin skin test (TST). Various regimens have been suggested for the treatment of LTBI. But, after a positive IGRA or TST and prior to latent TB treatment, active tuberculosis should be ruled out by detailed history taking, examination and appropriate investigations so as to minimize the risk of drug resistance with anti-tuberculosis monotherapy used in LTBI treatment. To add on to literature, Non tuberculous mycobacteria are universally present environmental organisms. However, in immunocompromised children especially in subpopulation of malignancy, NTM is known to cause infections which needs protocol based management. Also importance has to given to implementation of adequate preventive and corrective measures to prevent such opportunistic infection in paediatric oncology subpopulation. In this review, we provide an overview of tuberculosis in paediatric oncology patients and summarize the expansive body of literature on the tuberculosis mimicking carcinoma, tuberculosis burden in transplantation patients and those receiving immune check point inhibitors, latent TB infection screening and management, and NTM infection in children with malignancy.

A five-year analysis of latent tuberculosis infection in Queensland, 2016-2020.

Background Australia is aiming to reach tuberculosis pre-elimination targets by 2035. As a low-incidence setting, control efforts will increasingly rely on the management of latent tuberculosis infection (LTBI). We undertook this descriptive analysis to assess the recent trends of LTBI testing in Queensland. Methods Our objective was to describe the features of LTBI testing in Queensland, and to estimate the range of possible annual notifications were it to be made a notifiable condition. We collated both state-wide and region-specific data on tuberculin skin testing (TST) and interferon gamma release assays (IGRA) conducted in Queensland during the five-year period 1 January 2016 - 31 December 2020. We used reports on Medicare-funded TST and IGRA testing in Queensland, as well as tuberculosis notification data, to understand the representativeness of our data and to derive state-wide estimates. Results We analysed 3,899 public TST, 5,463 private TST, 37,802 public pathology IGRA, and 31,656 private pathology IGRA results. The median age of people tested was 31 years; 57% of those tested were female. From our data sources, an annual average of 1,067 positive IGRA and 354 positive TST results occurred in Queensland. Building on this minimum value, we estimate possible latent tuberculosis notifications in Queensland could range from 2,901 to 6,995 per annum. Private laboratory TSTs are estimated to contribute the lowest number of potential notifications (range: 170-340), followed by private laboratory IGRA testing (range: 354-922), public laboratory IGRA testing (range: 706-1,138), and public setting TSTs (range: 1,671-4,595). Conclusion If LTBI were to be made notifiable, these estimates would place it among the ten most notified conditions in Queensland. This has implications for potential surveillance methods and goals, and their associated system and resource requirements.

HBHA-IGRA and cytotoxic mediators release assays for the diagnosis of cervical tuberculous lymphadenitis.

IMPORTANCE: Cervical tuberculous lymphadenitis (CTL), the most frequent extrapulmonary form of tuberculosis, is currently a major health problem in Tunisia and in several regions around the world. CTL diagnosis is challenging mainly due to the paucibacillary nature of the disease and the potential misdiagnosis as cervical non-tuberculous lymphadenitis. This study demonstrates the added value of the heparin-binding hemagglutinin-interferon-gamma release assay as an immunoassay in the context of CTL.

Accuracy of QuantiFERON in active tuberculosis suspects with comorbidities and nontuberculous mycobacterial infection in Northern California.

The QuantiFERON-TB Gold (QFT) is routinely utilized in North American health systems to detect a cellular immune response to Mycobacterium tuberculosis antigens in symptomatic and asymptomatic patients. The sensitivity of QFT in tuberculosis (TB) patients with comorbidities is not well established and the specificity of QFT in patients with nontuberculous mycobacteria (NTM) infections is incompletely understood. Between 2012 and 2023, all patients with culture-positive TB and patients with NTM infection per the expert diagnostic guidelines or biopsy-proven NTM infection who had a concurrent QFT test were included in this study. The sensitivity and specificity of QFT were measured in TB and NTM patients, respectively. In 109 patients with active TB, the overall sensitivity of QFT was 78.0% (85/109; 95% CI: 70.1, 85.7). The sensitivity was 86.0% (49/57; 95% CI: 76.6, 94.8) and 69.2% (36/52; 95% CI: 56.7, 81.8) in immunocompetent and immunocompromised patients, respectively. The overall specificity of QFT in 88 patients with NTM infection was 76.1% (67/88; 95% CI: 67.2, 85.0). After the exclusion of 17 NTM patients with risk factors for latent TB infection, the specificity was 94.4% (67/71; 95% CI: 89.1, 99.7). Two patients had NTM species known to cross-react with QFT. In two NTM patients infected with species (Mycobacterium intracellulare subsp. intracellulare and Mycobacterium intracellulare subsp. chimaera) not known to cross-react, whole genome sequencing did not detect ESAT-6 or CFP-10. In Northern California, the QFT assay demonstrated moderately low to moderately high sensitivity in TB patients and very high specificity in NTM patients, thus ruling out concerns for cross-reactivity with NTM.

Impact of Human Immunodeficiency Virus and Peripartum Period on Mycobacterium tuberculosis Infection Detection.

BACKGROUND: Pregnancy and human immunodeficiency virus (HIV) may influence tuberculosis infection detection using interferon (IFN)-γ release assay (QFT-Plus; Qiagen) and tuberculin skin test (TST). METHODS: Participants in Western Kenya underwent QFT-Plus and TST in pregnancy, 6 weeks postpartum (6wkPP) and 12 months postpartum (12moPP). RESULTS: 400 participants (200 with HIV [WHIV], 200 HIV-negative) enrolled during pregnancy (median 28 weeks' gestation [interquartile range, 24-30]). QFT-Plus positivity prevalence was higher than TST in pregnancy (32.5% vs 11.6%) and through 12moPP (6wkPP, 30.9% for QFT-Plus vs 18.0% for TST; 12moPP, 29.5% vs 17.1%; all P < .001), driven primarily by QFT-Plus-positive/TST-negative discordance among HIV-negative women. Tuberculosis infection test conversion incidence was 28.4/100 person-years (PY) and higher in WHIV than HIV-negative women (35.5 vs 20.9/100 PY; hazard ratio, 1.73 [95% confidence interval, 1.04-2.88]), mostly owing to early postpartum TST conversion among WHIV. Among QFT-Plus-positive participants in pregnancy, Mycobacterium tuberculosis  (Mtb)-specific IFN-γ responses were dynamic through 12moPP and lower among WHIV than HIV-negative women with tuberculosis infection at all time points. CONCLUSIONS: QFT-Plus had higher diagnostic yield than TST in peripartum women. Peripartum QFT-Plus positivity was stable and less influenced by HIV than TST. Mtb-specific IFN-γ responses were dynamic and lower among WHIV. Tuberculosis infection test conversion incidence was high between pregnancy and early postpartum, potentially owing to postpartum immune recovery.

Uniting for Ukraine Tuberculosis Screening Experience, San Francisco, California, USA.

Ukraine surveillance data suggest high tuberculosis (TB) incidence, including multidrug resistance. Of 299 newcomers from Ukraine screened in San Francisco, California, USA, by using an interferon-γ-release-assay (IGRA) and chest radiograph, 7.4% were IGRA positive and 1 had laboratory-confirmed pansusceptible TB. Screening with IGRA and chest radiograph can help characterize TB risk.