Testing For Latent Tuberculosis Infection Research Articles

Antiviral immune response against HTLV-1 invalidates T-SPOT.TB® results in patients with HTLV-1-positive rheumatic diseases

BackgroundT-SPOT.TB®, one of the screening tests for latent tuberculosis infection (LTBI), yields invalid results in human T-cell leukemia virus type 1 (HTLV-1)-positive patients with rheumatoid arthritis. However, the detailed mechanisms behind this invalidation are unclear. Additionally, it remains unclear whether T-SPOT.TB® or QuantiFERON-TB (QFT) is more useful in HTLV-1-positive patients with rheumatic disease (RD).MethodAmong all of the HTLV-1-positive RD patients who visited our department between August 2012 and December 2022, 44 patients who were screened using T-SPOT.TB® were included in the analysis. QFT testing was performed in 33 of the 44 patients, and the results were compared with that of T-SPOT.TB®. Furthermore, we performed a culture experiment mimicking T-SPOT.TB® using peripheral blood mononuclear cells (PBMCs) obtained from HTLV-1-positive patients with RD. Additionally, T-cell subsets with autonomous product IFN-γ were analyzed using a flow cytometer.ResultsOf the included patients, 13 (29.5%) were invalid for T-SPOT.TB® because of the increased number of negative control spots. The median HTLV-1 proviral load in the invalid group was higher than that in the valid group (2.45 vs. 0.49 copies/100 PBMCs, respectively, p = 0.002). QFT was performed in all 33 patients, including 13 patients who were invalid in T-SPOT.TB®. The main source of IFN-γ production was CD8+ T-cells in the T-SPOT.TB® mimic experiment. Furthermore, Tax-expressing CD4+ T-cells and Tax-specific cytotoxic CD8+ T-cells were more frequently observed in patients with invalid results than in patients with valid results. CD4+ T-cell depletion in the T-SPOT.TB® mimic experiment reduced the population of IFN-γ producing CD8+ T cells.ConclusionT-SPOT.TB® may be invalidated by the interaction between Tax-expressing CD4+ T-cells and cytotoxic CD8+ T-cells. Moreover, HTLV-1-associated immune reactions due to contact between these cells may be unlikely to occur in QFT using whole blood. Therefore, our results reveal the superiority of QFT over T-SPOT.TB® as a screening test for LTBI in HTLV-1-positive patients with RD.

Performance of Current Diagnostic Tools in Detecting Latent Tuberculosis Among Healthcare Workers: A Systematic Review.

Testing for latent tuberculosis infection is essential for diagnosing Mycobacterium tuberculosis infections in asymptomatic individuals. Preventing the transition of latent to active tuberculosis is imperative, especially in high-risk populations such as healthcare workers. Interferon-gamma release assays (IGRAs) and the Mantoux/tuberculin skin test (TST) are two examples of diagnostic instruments utilized for detection. Systematic evaluations of the characteristics of widely available tests are very helpful for diagnosticians because these tests might not be easily accessible in situations with limited resources. This systematic review aims to evaluate and compare the diagnostic accuracy of tests for latent tuberculosis infectionin healthcare workers. The review, conducted from 2013 to 2024, aimed to identify studies on "Latent Tuberculosis," "Healthcare workers," "Diagnostic modalities," "TST," "Interferon-gamma release assays," and "IGRA." The review followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines and developed a data extraction toolkit. Three authors independently reviewed the literature, ensuring uniformity. Discrepancies were resolved through discussions and mediation until a consensus was reached. Statistical significance was defined as a p-value of 0.05 or lower. The review provides valuable insights into the diagnostic accuracy of these tests, particularly in high-risk populations. The TST had a sensitivity of 76.5% (confidence interval (CI) = 61.5-91.5%) and specificity of 77.2% (CI = 65-85%). Its positive predictive value (PPV) was 54.8% (CI = 45-65%), and the negative predictive value (NPV) was 88.5% (CI = 85-92%), with an odds ratio of 63.6 and an area under the curve (AUC) of 0.72. QuantiFERON-TB Gold In-Tube (QFT-GIT) showed a sensitivity of 68.35% (CI = 67.15-70.55%) and a specificity of 82.32% (CI = 72.32-97.47%). Its PPV was 56% (CI = 54-92%), and NPV was 92.7% (CI = 89-96%), with an odds ratio of 357.9 and an AUC of 0.767. QuantiFERON-TB Gold Plus (QFT-Plus) had a sensitivity of 85% (CI = 78.9-91.1%) and a specificity of 73.52% (CI = 35.71-93.75%). Its PPV was 59.2% (CI = 39.3-78.2%), and NPV was 95% (CI = 91.2-98%), with an odds ratio of 125.39 and an AUC of 0.89. T-SPOT.TB showed a sensitivity of 92% (CI = 87-97%) and a specificity of 95.7% (CI = 94-98%). Its PPV was 86.8% (CI = 85-95.8%), and NPV was 95.8% (CI = 92.5-96.7%), with an odds ratio of 1.03 and an AUC of 0.7. CLIA-IGRA had a sensitivity of 100% (CI = 99.9-100%) and a specificity of 95.57% (CI = 95.57-100%). Its PPV was 96.8% (CI = 96.8-100%), and NPV was 99.8% (CI = 99.8-100%), with an odds ratio of 1509 and an AUC of 0.97. HBHA-induced IGRA showed a sensitivity of 86.4% (CI = 71.1-97.3%) and a specificity of 82.5% (CI = 66.4-92.6%). Its PPV was 86.8% (CI = 66.7-95.3%), and NPV was 86.4% (CI = 57.8-95.7%), with an odds ratio of 6.18 and an AUC of 0.886. There are specific benefits and drawbacks of each diagnostic test for latent tuberculosis infection. With its exceptional sensitivity and specificity, the CLIA-IGRA test is a top choice for a precise diagnosis of tuberculosis. Practical factors such as availability and cost, however, might prevent its widespread usage. Both the QuantiFERON and TST are still useful tools, especially when used in certain populations or situations when their performance characteristics meet clinical requirements.

Mixed methods study on latent tuberculosis among agate stone workers and advocacy for testing silica dust exposed individuals in India

The 2021 tuberculosis (TB) preventive treatment guidelines in India included silicosis as a screening group, yet latent TB infection (LTBI) testing for silica-dust-exposed individuals is underemphasized. Focusing on an estimated 52 million silica-dust-exposed workers, particularly agate-stone workers in Khambhat, Gujarat, our study aims to estimate LTBI prevalence, identify predictors, and gather insights from TB and silicosis experts. Employing a sequential explanatory mixed-methods approach, a cross-sectional study involved 463 agate-stone workers aged ≥ 20 years in Khambhat, using IGRA kits for LTBI testing. In-depth interviews with experts complemented quantitative findings. Among agate-stone workers, 58% tested positive for LTBI, with predictors including longer exposure, type of work, and BCG vaccination. Our findings reveal a nearly double burden of LTBI compared to the general population, particularly in occupations with higher silica dust exposure. Experts advocate for including silica-dust-exposed individuals in high-risk groups for LTBI testing, exploring cost-effective alternatives like improved skin sensitivity tests, and shorter TB preventive treatment regimens to enhance compliance. Future research should explore upfront TB preventive treatment for silica-dust-exposed individuals with high LTBI prevalence and optimal exposure duration. This study underscores the urgent need for policy changes and innovative approaches to TB prevention among silica-dust-exposed populations, impacting global occupational health strategies.

Tuberculin skin test and Interferon-gamma release assay agreement, and associated factors with latent tuberculosis infection, in medical and nursing students in Bandung, Indonesia.

No gold standard diagnostic test exists for latent tuberculosis infection (LTBI). The intra-dermal tuberculin skin test (TST) has known limitations and Interferon-gamma release assays (IGRA) have been developed as an alternative. We aimed to assess agreement between IGRA and TST, and risk factors for test positivity, in Indonesian healthcare students. Medical and nursing students starting their clinical training were screened using IGRA and TST. Agreement between the two tests was measured using Cohen's Kappa coefficient. Logistic regression was used to identify factors associated with test positivity. Of 266 students, 43 (16.2%) were IGRA positive and 85 (31.9%) TST positive. Agreement between the two tests was 74.7% (kappa 0.33, 95% CI 0.21-0.45, P<0.0001). Students who had direct contact with family or friends with TB were less likely to be test positive using IGRA (AOR 0.18, 95% CI 0.05-0.64) and using TST (AOR 0.51, 95% CI 0.26-0.99). Test positivity for LTBI was lower when measured by IGRA than by TST, with poor agreement between the two tests. Known close TB contact was unexpectedly negatively associated with positivity by either test. Longitudinal studies may be required to help determine the best test for LTBI in healthcare students in Indonesia.

Cost-effectiveness of latent tuberculosis infection testing and treatment with 6-week regimen among key population in rural communities in China: a decision analysis study.

Several model studies suggested the implementation of latent tuberculosis infection (LTBI) testing and treatment could greatly reduce the incidence of tuberculosis (TB) and achieve the 2035 target of the "End TB" Strategy in China. The present study aimed to evaluate the cost-effectiveness of LTBI testing and TB preventive treatment among key population (≥ 50 years old) susceptible to TB at community level in China. A Markov model was developed to investigate the cost-effectiveness of LTBI testing using interferon gamma release assay (IGRA) and subsequent treatment with 6-month daily isoniazid regimen (6H) (as a standard regimen for comparison) or 6-week twice-weekly rifapentine and isoniazid regimen (6-week H2P2) in a cohort of 10,000 adults with an average initial age of 50 years. In the base-case analysis, LTBI testing and treatment with 6H was dominated (i.e., more expensive with a lower quality-adjusted life year (QALY)) by LTBI testing and treatment with 6-week H2P2. LTBI testing and treatment with 6-week H2P2 was more effective than no intervention at a cost of $20,943.81 per QALY gained, which was below the willingness-to-pay (WTP) threshold of $24,211.84 per QALY gained in China. The one-way sensitivity analysis showed the change of LTBI prevalence was the parameter that most influenced the results of the incremental cost-effectiveness ratios (ICERs). As estimated by a Markov model, LTBI testing and treatment with 6-week H2P2 was cost-saving compared with LTBI testing and treatment with 6H, and it was considered to be a cost-effective option for TB control in rural China.

Latent Tuberculosis Infection Testing Practices in a Large US Integrated Healthcare System.

Tuberculosis (TB) is a public health threat, with >80% of active TB in the United States occurring due to reactivation of latent TB infection (LTBI). We may be underscreening those with high risk for LTBI and overtesting those at lower risk. A better understanding of gaps in current LTBI testing practices in relation to LTBI test positivity is needed. This study, conducted between 1 January 2008 and 31 December 2019 at Kaiser Permanente Southern California, included individuals aged ≥18 years without a history of active TB. We examined factors associated with LTBI testing and LTBI positivity. Among 3 816 884 adults (52% female, 37% White, 37% Hispanic, mean age 43.5 years [standard deviation, 16.1]), 706 367 (19%) were tested for LTBI, among whom 60 393 (9%) had ≥1 positive result. Among 1 211 971 individuals who met ≥1 screening criteria for LTBI, 210 025 (17%) were tested for LTBI. Factors associated with higher adjusted odds of testing positive included male sex (1.32; 95% confidence interval, 1.30-1.35), Asian/Pacific Islander (2.78, 2.68-2.88), current smoking (1.24, 1.20-1.28), diabetes (1.13, 1.09-1.16), hepatitis B (1.45, 1.34-1.57), hepatitis C (1.54, 1.44-1.66), and birth in a country with an elevated TB rate (3.40, 3.31-3.49). Despite being risk factors for testing positive for LTBI, none of these factors were associated with higher odds of LTBI testing. Current LTBI testing practices may be missing individuals at high risk of LTBI. Additional work is needed to refine and implement screening guidelines that appropriately target testing for those at highest risk for LTBI.

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.

Features of detection of latent tuberculosis infection in patients with inflammatory intestinal diseases

A quarter of the world’s population has latent tuberculosis infection (LTBI). Systemic immunosuppression is a risk factor for the reactivation of LTBI and the development of active tuberculosis, and such reactivation is associated with a substantial risk of morbidity and mortality. Despite the growing global prevalence of inflammatory bowel diseases (IBD) and the use of immunosuppressive therapies, current recommendations for LTBI testing and treatment in IBD patients lack a systematic approach due to a lack of evidence. Currently, the main challenge in accurately diagnosing inflammatory bowel diseases (IBD) is the high prevalence of conditions that lead to intestinal lesions mimicking IBD.

Randomized Controlled Trial of Clinical Guidelines Versus Interactive Decision-Support for Improving Medical Trainees' Confidence with Latent Tuberculosis Care.

In order to eliminate tuberculosis (TB) in the USA, primary care providers must take on an expanded role in the diagnosis and management of latent tuberculosis infection (LTBI). Clinical practice guidelines and recommendations exist for LTBI management, but there is a need for innovative tools to improve medical students' and residents' knowledge of evidence-based practices for LTBI testing and treatment. To assess the impact of LTBI-ASSIST, a free online decision support aid, as a novel educational tool and mechanism of delivering clinical practice guidelines for medical trainees. A single site, randomized controlled trial of trainees delivered by electronic survey. Medical students and Internal Medicine residents at the Johns Hopkins University School of Medicine. Participants were randomized in 1:1 ratio to receive the US clinical practice guidelines and recommendations for Latent TB management (control arm) or the guidelines plus an introduction to LTBI-ASSIST (LTBI-ASSIST arm) as they completed a case-based knowledge assessment and reported confidence with domains of LTBI care. (1) Proportion of questions answered correctly on a case-based knowledge assessment; (2) change in reported confidence with domains of LTBI care. One hundred and thirty participants completed the knowledge assessment. Those randomized to receive the LTBI-ASSIST Tool performed better on the case-based knowledge assessment with a mean score of 75.9% (95% CI: 70.6-81.1), compared to 57.4% (52.8-62.0) in the group that received the guidelines only (p <0.001). Similarly, the LTBI-ASSIST group reported a higher change in confidence (measured as post-assessment confidence minus pre-assessment confidence), compared to the control group, in six of the seven domains of LTBI care. LTBI-ASSIST can be an effective supplement to existing guidelines in educating medical trainees and helping providers find evidence-based, guideline-supported answers for questions encountered in clinical practice. NIH Clinical Trial Registry No. NCT05772065.

Screening for tuberculosis infection and effectiveness of preventive treatment among people with HIV in low-incidence settings.

To determine the yield of screening for latent tuberculosis infection (LTBI) among people with HIV (PWH) in low tuberculosis (TB) incidence countries (<10 TB cases per 100 000 persons). A systematic review and meta-analysis were performed to assess prevalence and predictive factors of LTBI, rate of TB progression, effect of TB preventive treatment (TPT), and numbers needed to screen (NNS). PubMed and Cochrane Library were searched for studies reporting primary data, excluding studies on active or paediatric TB. We extracted LTBI cases, odds ratios, and TB incidences; pooled estimates using a random-effects model; and used the Newcastle-Ottawa scale for bias. In 51 studies with 65 930 PWH, 12% [95% confidence interval (CI) 10-14] had a positive LTBI test, which was strongly associated with origin from a TB-endemic country [odds ratio (OR) 4.7] and exposure to TB (OR 2.9). Without TPT (10 629 PWH), TB incidence was 28/1000 person-years (PY; 95% CI 12-45) for LTBI-test positive versus 4/1000 PY (95% CI 0-7) for LTBI-test-negative individuals. Among 625 PWH (1644 PY) receiving TPT, 15 developed TB (6/1000 PY). An estimated 20 LTBI-positive individuals would need TPT to prevent one case of TB, and numbers NNS to detect LTBI or prevent active TB varied according to a-priori risk of LTBI. The relatively high prevalence of LTBI among PWH and the strong correlation with origin from a TB-endemic country support risk-stratified LTBI screening strategies for PWH in low-incidence countries and treating those who test positive.

Effect of a latent tuberculosis infection programme for healthcare workers in a country with an intermediate tuberculosis burden

Management of latent tuberculosis infection (LTBI) among healthcare workers (HCWs) is crucial for the prevention of nosocomial tuberculosis (TB) transmission. We aimed to determine the effect of an LTBI programme for HCWs in a tertiary care hospital in a country with an intermediate TB burden. In 2013, baseline LTBI screening was implemented for newly hired doctors and nurses, along with annual screening of HCWs in high-risk departments. HCWs with LTBI were also provided with treatment. Since 2017, all HCWs without an LTBI test result have been tested for LTBI. We assessed the annual incidence of active TB among HCWs between 2013 and 2020. Additionally, we evaluated the incidence of active TB among HCWs employed at the hospital in 2020, with a specific focus on those who had undergone LTBI tests between 2013 and 2018, considering their LTBI test results and treatment status. The incidence of active TB among HCWs significantly decreased between 2013 and 2020. The average risk reduction for pulmonary TB was 10.2% per year (95% CI, 1.0-19.0; P=0.034). Among HCWs employed at the hospital in 2020, 4354 individuals underwent LTBI tests between 2013 and 2018. Of them, 927 (21.3%) tested positive. Nine (1.5%) of 588 without LTBI treatment developed active TB. Among the 1285 HCWs who underwent follow-up testing, 62 (4.8%) converted, and one (4.3%) of the 23 without treatment developed active TB. None of those who received treatment were diagnosed with active TB. The LTBI programme significantly reduced the incidence of active TB in HCWs. LTBI screening and treatment should be implemented, particularly in countries with a high or intermediate TB burden.

Using Electronic Health Record Data to Measure the Latent Tuberculosis Infection Care Cascade in Safety-Net Primary Care Clinics

Prevention of tuberculosis disease through diagnosis and treatment of latent tuberculosis infection is critical for achieving tuberculosis elimination in the U.S. Diagnosis and treatment of latent tuberculosis infection in safety-net primary care settings that serve patients at risk for tuberculosis may increase uptake of this prevention effort and accelerate progress toward elimination. Optimizing tuberculosis prevention in these settings requires measuring the latent tuberculosis infection care cascade (testing, diagnosis, and treatment) and identifying gaps to develop solutions to overcome barriers. We used electronic health record data to describe the latent tuberculosis infection care cascade and identify gaps among a network of safety-net primary care clinics. Electronic health record data for patients seen in the OCHIN Clinical Network, the largest network of safety-net clinics in the U.S., between 2012 and 2019 were extracted. electronic health record data were used to measure the latent tuberculosis infection care cascade: patients who met tuberculosis screening criteria on the basis of current recommendations were tested for tuberculosis infection, diagnosed with latent tuberculosis infection, and prescribed treatment for latent tuberculosis infection. Outcomes were stratified by diagnostic test and treatment regimen. Among 1.9 million patients in the analytic cohort, 43.5% met tuberculosis screening criteria, but only 21.4% were tested for latent tuberculosis infection; less than half (40.4%) were tested using an interferon-gamma release assay. Among those with a valid result, 10.5% were diagnosed with latent tuberculosis infection, 29.1% of those were prescribed latent tuberculosis infection treatment, and only 33.6% were prescribed a recommended rifamycin-based regimen. Electronic health record data can be used to measure the latent tuberculosis infection care cascade. A large proportion of patients in this safety-net clinical network are at high risk for tuberculosis infection. Addressing identified gaps in latent tuberculosis infection testing and treatment may have a direct impact on improving tuberculosis prevention in primary care clinics and accelerate progress toward elimination.

Latent tuberculosis infection testing in a large integrated healthcare system

PurposeTuberculosis (TB) is a public health threat with >80% of active TB in the United States occurring due to reactivation of latent tuberculosis infection (LTBI). We may be under-screening those with high risk for LTBI and over-testing those at lower risk. A better understanding of gaps in current LTBI testing practices, particularly as it relates to LTBI test positivity, is needed. MethodsThis study, conducted between 01/01/2008 and 12/31/2019 at Kaiser Permanente Southern California, included individuals aged ≥18years without history of active TB. We examined factors associated with LTBI testing and LTBI positivity. ResultsAmong 3,816,884 adults (52% female, 37% White, mean age 43.5years [SD 16.1]), 706,367 (19%) were tested for LTBI, among whom 60,393 (9%) had ≥1 positive result. Among 1,211,971 individuals meeting ≥1 screening criteria for LTBI, 210,025 (17%) were tested for LTBI. Factors associated with higher odds of testing positive included male sex (OR:1.32, 95% CI:1.30–1.35), Asian/Pacific Islanders (2.78, 2.68–2.88), current smoking (1.24, 1.20–1.28), diabetes (1.13, 1.09–1.16), hepatitis B (1.45, 1.34–1.57), hepatitis C (1.54, 1.44–1.66), and birth in a TB endemic country (3.40, 3.31–3.49). Despite being risk factors for testing positive for LTBI, none of these factors were associated with higher odds of LTBI testing (Fig. 1). ConclusionsWe identified a mismatch between populations tested for LTBI and populations testing positive. Current LTBI testing practices may be missing individuals at high risk of LTBI. Additional work is needed to develop and implement screening guidelines that appropriately target testing for those at highest risk for LTBI.

Tabby2: a user-friendly web tool for forecasting state-level TB outcomes in the United States

BackgroundIn the United States, the tuberculosis (TB) disease burden and associated factors vary substantially across states. While public health agencies must choose how to deploy resources to combat TB and latent tuberculosis infection (LTBI), state-level modeling analyses to inform policy decisions have not been widely available.MethodsWe developed a mathematical model of TB epidemiology linked to a web-based user interface — Tabby2. The model is calibrated to epidemiological and demographic data for the United States, each U.S. state, and the District of Columbia. Users can simulate pre-defined scenarios describing approaches to TB prevention and treatment or create their own intervention scenarios. Location-specific results for epidemiological outcomes, service utilization, costs, and cost-effectiveness are reported as downloadable tables and customizable visualizations. To demonstrate the tool’s functionality, we projected trends in TB outcomes without additional intervention for all 50 states and the District of Columbia. We further undertook a case study of expanded treatment of LTBI among non-U.S.–born individuals in Massachusetts, covering 10% of the target population annually over 2025-2029.ResultsBetween 2022 and 2050, TB incidence rates were projected to decline in all states and the District of Columbia. Incidence projections for the year 2050 ranged from 0.03 to 3.8 cases (median 0.95) per 100,000 persons. By 2050, we project that majority (> 50%) of TB will be diagnosed among non-U.S.–born persons in 46 states and the District of Columbia; per state percentages range from 17.4% to 96.7% (median 83.0%). In Massachusetts, expanded testing and treatment for LTBI in this population was projected to reduce cumulative TB cases between 2025 and 2050 by 6.3% and TB-related deaths by 8.4%, relative to base case projections. This intervention had an incremental cost-effectiveness ratio of $180,951 (2020 USD) per quality-adjusted life year gained from the societal perspective.ConclusionsTabby2 allows users to estimate the costs, impact, and cost-effectiveness of different TB prevention approaches for multiple geographic areas in the United States. Expanded testing and treatment for LTBI could accelerate declines in TB incidence in the United States, as demonstrated in the Massachusetts case study.

Latent Tuberculosis Screening Cascade for Non-US-Born Persons in a Large Health System.

Review of electronic health records revealed substantial drop-off at each stage of the latent tuberculosis infection (LTBI) care cascade among non-US-born persons in an academic primary care system. Of 5148 persons eligible for LTBI screening, 1012 (20%) had an LTBI test, and 140 (48%) of 296 LTBI-positive persons received LTBI treatment.

Tuberculosis related barriers and facilitators among immigrants in Atlantic Canada: A qualitative study.

Tuberculosis (TB) is a disease caused by the bacterium Mycobacterium tuberculosis and affects approximately one-quarter of the world's population. Immigrant populations in Canada are disproportionately affected by TB. Canada's immigration medical examinations include screening for active TB but not latent TB infection (LTBI). In LTBI, the bacterium remains dormant within the host but can reactivate and cause disease. Once active, TB can be transmitted to close contacts sharing confined spaces leading to the possibility of outbreaks in the broader community. This study aimed to 1) assess the current TB knowledge, perceived risk, and risk behaviors of immigrants in Atlantic Canada as well as 2) identify barriers and facilitators to testing and treatment of TB among this population. Three focus group discussions were conducted with a total of 14 non-Canadian born residents of New Brunswick aged 19 years and older. Data were analyzed using inductive thematic analysis. Four themes were identified from the data relating to barriers to testing and treatment of LTBI: 1) Need for education, 2) stigma, 3) fear of testing, treatment, and healthcare system, and 4) complacency. Results included reasons individuals would not receive TB testing, treatment, or seek help, as well as facilitators to testing and treatment. These findings may inform the implemention of an LTBI screening program in Atlantic Canada and more broadly across the country.

Understanding the Decline of Incident, Active Tuberculosis in People With Human Immunodeficiency Virus in Switzerland.

People with human immunodeficiency virus type 1 (HIV-1) (PWH) are frequently coinfected with Mycobacterium tuberculosis (MTB) and at risk for progressing from asymptomatic latent TB infection (LTBI) to active tuberculosis (TB). LTBI testing and preventive treatment (TB specific prevention) are recommended, but its efficacy in low transmission settings is unclear. We included PWH enrolled from 1988 to 2022 in the Swiss HIV Cohort study (SHCS). The outcome, incident TB, was defined as TB ≥6 months after SHCS inclusion. We assessed its risk factors using a time-updated hazard regression, modeled the potential impact of modifiable factors on TB incidence, performed mediation analysis to assess underlying causes of time trends, and evaluated preventive measures. In 21 528 PWH, LTBI prevalence declined from 15.1% in 2001% to 4.6% in 2021. Incident TB declined from 90.8 cases/1000 person-years in 1989 to 0.1 in 2021. A positive LTBI test showed a higher risk for incident TB (hazard ratio [HR] 9.8, 5.8-16.5) but only 10.5% of PWH with incident TB were tested positive. Preventive treatment reduced the risk in LTBI test positive PWH for active TB (relative risk reduction, 28.1%, absolute risk reduction 0.9%). On population level, the increase of CD4 T-cells and reduction of HIV viral load were the main driver of TB decrease. TB specific prevention is effective in selected patient groups. On a population level, control of HIV-1 remains the most important factor for incident TB reduction. Accurate identification of PWH at highest risk for TB is an unmet clinical need.

Examining Test Cutoffs to Optimize Diagnosis of Latent Tuberculosis Infection in People Born Outside the United States.

Rationale: Detection of latent tuberculosis infection (LTBI) in persons born in high tuberculosis (TB) incidence countries living in low TB incidence countries is key to TB elimination in low-incidence countries. Optimizing LTBI tests is critical to targeting treatment. Objectives: To compare the sensitivity and specificity of tuberculin skin test (TST) and two interferon-γ release assays at different cutoffs and of a single test versus dual testing. Methods: We examined a subset (N = 14,167) of a prospective cohort of people in the United States tested for LTBI. We included non-U.S.-born, human immunodeficiency virus-seronegative people ages 5 years and older with valid TST, QuantiFERON-TB Gold-in-Tube (QFT), and T-SPOT.TB (TSPOT) results. The sensitivity/specificity of different test cutoffs and test combinations, obtained from a Bayesian latent class model, were used to construct receiver operating characteristic (ROC) curves and assess the area under the curve (AUC) for each test. The sensitivity/specificity of dual testing was calculated. Results: The AUC of the TST ROC curve was 0.81 (95% credible interval (CrI), 0.78-0.86), with sensitivity/specificity at cutoffs of 5, 10, and 15 mm of 86.5%/61.6%, 81.7%/71.3%, and 55.6%/88.0%, respectively. The AUC of the QFT ROC curve was 0.89 (95% CrI, 0.86-0.93), with sensitivity/specificity at cutoffs of 0.35, 0.7, and 1.0 IU/mL of 77.7%/98.3%, 66.9%/99.1%, and 61.5%/99.4%. The AUC of the TSPOT ROC curve was 0.92 (95% CrI, 0.88-0.96) with sensitivity/specificity for five, six, seven, and eight spots of 79.2%/96.7%, 76.8%/97.7%, 74.0%/98.6%, and 71.8%/99.5%. Sensitivity/specificity of TST-QFT, TST-TSPOT, and QFT-TSPOT at standard cutoffs were 73.1%/99.4%, 64.8%/99.8%, and 65.3%/100%. Conclusion: Interferon-γ release assays have a better predictive ability than TST in people at high risk of LTBI.

Latent Tuberculosis Infection Treatment Practices in Two Large Integrated Health Systems in California, 2009-2018.

Treatment of latent tuberculosis infection (LTBI) is highly effective at preventing active tuberculosis (TB) disease. Understanding LTBI treatment practices in US health system settings is critical to identify opportunities to improve treatment prescription, initiation, and completion, and thus to prevent TB disease. We assessed LTBI treatment practices among a cohort of adults after their first positive LTBI test (tuberculin skin test [TST] or interferon gamma release assay [IGRA]) between 2009 and 2018 at 2 large integrated health systems in California. We described the prescription, initiation, and completion of LTBI treatment (isoniazid [INH], rifampin, and rifamycin-INH short-course combinations) by demographic and clinical characteristics. We used multivariable robust Poisson regression to examine factors that were independently associated with treatment prescription and completion. Among 79 302 individuals with a positive LTBI test, 33.0% were prescribed LTBI treatment, 28.3% initiated treatment, and 18.5% completed treatment. Most individuals were prescribed INH (82.0%), but treatment completion was higher among those prescribed rifamycin-INH short-course combinations (69.6% for INH + rifapentine and 70.3% for INH + rifampin) compared with those prescribed INH (56.3%) or rifampin (56.6%). In adjusted analyses, treatment prescription and completion were associated with older age, female sex, more comorbidities, immunosuppression, not being born in a high-TB incidence country, and testing positive with IGRA vs TST. LTBI treatment is underutilized, requiring tailored interventions to support treatment prescription and completion for patients with LTBI.

The latent tuberculosis infection cascade of care during the COVID-19 pandemic response in a Mid-Sized US city

BackgroundThe COVID-19 pandemic response may unintentionally disrupt multiple public health services, including tuberculosis control programs. We aimed to assess differences in the cascade of care for latent tuberculosis infection (LTBI) in a Midwest U.S. city during the COVID-19 pandemic response. MethodsWe conducted a retrospective cohort study of adult patients who presented for LTBI evaluation at the Hamilton County Public Health Tuberculosis Clinic in Ohio between 2019 and 2020. The pre-COVID-19 response period was defined as 01/2019 to 02/2020, and the COVID-19 pandemic response period (first wave) was defined as 04/2020 to 12/2020. We reviewed electronic medical records to extract sociodemographic information, medical history, follow-up and treatment data to define steps within the LTBI cascade of care. Logistic regressions were used to assess factors associated with LTBI treatment acceptance and completion, adjusted by potential confounders and COVID-19 period. ResultsData from 312 patients were included. There was a significant decrease in the number of monthly LTBI referrals (median, 18 vs. 8, p = 0.02) and LTBI evaluations (median, 17.5 vs. 7, p < 0.01) during the first wave of COVID-19. The proportion for whom immigration was listed as the indication for LTBI testing also declined (30% vs. 9%; p < 0.01) during COVID-19. More LTBI diagnoses were based on interferon-gamma release assay (IGRA; 30% vs. 49%; p < 0.01) during the COVID-19 response period. The proportion of people in the clinic for whom treatment for LTBI was recommended was similar before and during COVID-19 (76% vs. 81%, p = 0.41), as was LTBI treatment acceptance rates (56% vs. 64%, p = 0.28), and completion rates (65% vs. 63%, p = 0.85). In multivariate analysis, LTBI treatment acceptance was associated with Hispanic ethnicity, younger age, male sex, IGRA being used for diagnosis, and non-healthcare occupation, independent of COVID-19 period. LTBI treatment completion was associated with taking a rifamycin-containing regimen, independent of COVID-19 period. ConclusionWe observed a significant decline in the number of monthly LTBI referrals and evaluations during the first wave of COVID-19, revealing an unintended negative impact of the COVID-19 response in our region. However, LTBI treatment acceptance and completion rates were not affected during COVID-19.