Cost-Effective Whole Transcriptome Sequencing Landscape and Diagnostic Potential Biomarkers in Active Tuberculosis.

Tuberculosis (TB) is a prevalent and severe infectious disease that poses a significant threat to human health. However, it is frequently disregarded as there are not enough quick and accurate ways to diagnose tuberculosis. Here, we develop a strategy for tuberculosis detection to address the challenges, including an experimental strategy, namely, Double Adapter Directional Capture sequencing (DADCSeq), an easily operated and low-cost whole transcriptome sequencing method, and a computational method to identify hub differentially expressed genes as well as the diagnosis of TB based on whole transcriptome data using DADCSeq on peripheral blood mononuclear cells (PBMCs) from active TB and latent TB or healthy control. Applying our approach to create a robust and stable TB multi-mRNA risk probability model (TBMMRP) that can accurately distinguish active and latent TB patients, including active TB and healthy controls in clinical cohorts, this diagnostic biomarker was successfully validated by several independent cross-platform cohorts with favorable performance in differentiating active TB from latent TB or active TB from healthy controls and further demonstrated superior or similar diagnostic accuracy compared to previous diagnostic markers. Overall, we develop a low-cost and effective strategy for tuberculosis diagnosis; as the clinical cohort increases, we can expand to different disease kinds and learn new features through our disease diagnosis strategy.

Latent tuberculosis prevalence, diagnosis and treatment in Multiple Sclerosis as a strategy for reducing infection reactivation during immunosuppressant therapy.

BACKGROUND: Tuberculosis is an infectious disease with a risk of reactivation in Multiple Sclerosis patients on immunosuppressant therapy. Diagnosis and treatment of Latent Tuberculosis Infection (LTBI) prevents the infection. OBJECTIVE: To diagnose and treat LTBI in Multiple Sclerosis (MS). METHODS: Cross-sectional study of the prevalence and treatment of LTBI in MS, between February 2021 and June 2023. LTBI was defined as an absence of symptoms, positive PPD or IGRA and normal chest X-ray. RESULTS: Of the 58 patients with MS, 17 (29.3 %) were diagnosed with LTBI, 15 with PPD > 5 mm and 2 with positive IGRA, 10 (58.8 %) female and 7 (41.1 %) male, mean age of 41.3 (SD ±13.4) years. All patients with LTBI were treated with immunomodulators or immunosuppressants: Fingolimod 5 (29.4 %), Natalizumab 5 (29.4 %), Cladribine 2 (11.8 %), Glatiramer 2 (11.8 %), Ocrelizumab 2 (11.8 %), and Interferon beta 1 (5.9 %). Steroids therapy for relapses, were used in 5/17 (93.8 %) with LTBI and 30/37 (81.1 %) without LTBI. To treat LTBI, 11 (64.7 %) received Isoniazid and 6 (35.3 %) Isoniazid plus Rifapentine. Hepatotoxicity occurred in 3 (17.6 %) with INH. There were no interruptions of ILTB treatment during the study. CONCLUSION: The prevalence of LTBI was found to be high and treatment proved safe.

Latent Tuberculosis Screening Among New Users of a Biologic or Targeted Synthetic Disease-Modifying Antirheumatic Drug: Gaps in Screening Overall and Among Janus Kinase Inhibitors.

OBJECTIVE: We combined claims and electronic health record (EHR) data to provide contemporary and accurate estimates of latent tuberculosis (TB) screening among new users of a biologic or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD) and assess potential gaps in testing by drug type, patient characteristics, and practice. METHODS: Our denominator population was patients in the Rheumatology Informatics System for Effectiveness (RISE) registry and Medicare using a b/tsDMARD in 2018 without a claim or prescription in the year prior. TB screening was assessed in both Medicare and RISE 1 and 3 years before the medication start date. We calculated the proportion screened overall, by medication class, and by practice. We tested for demographic differences in screening using logistic regression. RESULTS: In the year before drug starts, 65.6% of patients had any TB screening; in a 3-year window, 72.9% had any TB screening. Rates of screening within 1 year by drug type were greater or equal to the overall screening rate for most drugs except for JAK inhibitors (JAKis) (46%) and interleukin-17 inhibitors (IL-17is) (11.5%). A lower proportion of Hispanic and Asian patients were screened compared with White patients. Practice screening rates ranged from 20.0% to 92.9% of patients within 1 year. CONCLUSION: We report higher screening rates than have previously been published because of combining claims and EHR data. However, important safety gaps remain, namely, reduced screening among new users of a JAKi or IL-17i and among Asian and Hispanic patients, as well as low-performing practices. Educational initiatives, team-based care delivery, task shifting, and technological interventions to address observed gaps in patient safety procedures are needed.

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.

PURPOSE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Cost-Effectiveness Analysis Comparing QuantiFERON-TB Gold Plus Test and Tuberculin Skin Test for the Diagnosis of Latent Tuberculosis Infection in Immunocompetent Subjects in Colombia.

OBJECTIVES: To determine the cost-effectiveness of the QuantiFERON-TB Gold Plus (QFT-Plus) test versus the tuberculin skin test in diagnosing latent tuberculosis infection in immunocompetent subjects in the context of the Colombian healthcare system. METHODS: A hypothetical cohort of 2000 immunocompetent adults vaccinated with Bacillus Calmette-Guérin at birth who are asymptomatic for tuberculosis disease was simulated and included in a decision tree over a horizon of <1 year. The direct healthcare costs related to tests, antituberculosis treatment, and medical care were considered, and diagnostic performance was used as a measure of effectiveness. The incremental cost-effectiveness ratio (ICER) was estimated, and univariate deterministic and probabilistic sensitivity analyses were carried out using 5000 simulations. The currency was the US dollar for the year 2022, with a cost-effectiveness threshold of $6666 USD (1 gross domestic product per capita for 2022). RESULTS: QFT-Plus was cost-effective with an ICER of $5687 USD for each correctly diagnosed case relative to a threshold of $6666 USD. In the deterministic analysis, QFT-Plus was cost-effective in half of the proposed scenarios. The variable that most affected the ICER was the prevalence of latent tuberculosis and test sensitivities. In the probabilistic analysis, QFT-Plus was cost-effective in 54.74% of the simulated scenarios, and tuberculin skin test was dominant in 13.84%. CONCLUSIONS: The study provides evidence of the cost-effectiveness of QFT-Plus compared with the tuberculin skin test in diagnosing latent tuberculosis infection in immunocompetent adults in the Colombian context.

Cost-effectiveness of expanded latent TB infection testing and treatment: Lynn City, Massachusetts, USA.

BACKGROUND: Between October 2016 and March 2019, Lynn Community Health Center in Massachusetts implemented a targeted latent TB infection testing and treatment (TTT) program, increasing testing from a baseline of 1,200 patients tested to an average of 3,531 patients tested, or 9% of the population per year.METHODS: We compared pre-implementation TTT, represented by the first two quarters of implementation data, to TTT, represented by 12 quarters of data. Time, diagnostic, and laboratory resources were estimated using micro-costing. Other cost and testing data were obtained from the electronic health record, pharmaceutical claims, and published reimbursement rates. A Markov cohort model estimated future health outcomes and cost-effectiveness from a societal perspective in 2020 US dollars. Monte Carlo simulation generated 95% uncertainty intervals.RESULTS: The TTT program exhibited extended dominance over baseline pre-intervention testing and had an incremental cost-effectiveness ratio (ICER) of US$52,603 (US$22,008â-"US$95,360). When compared to baseline pre-TTT testing, the TTT program averted an estimated additional 7.12 TB cases, 3.49 hospitalizations, and 0.16 deaths per lifetime cohort each year.CONCLUSIONS: TTT was more cost-effective than baseline pre-implementation testing. Lynn Community Health Centerâ-™s experience can help inform other clinics considering expanding latent TB infection testing.

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.

A costing framework to compare tuberculosis infection tests.

OBJECTIVE: To develop a framework to estimate the practical costs incurred from, and programmatic impact related to, tuberculosis (TB) infection testing-tuberculin skin tests (TST) versus interferon gamma release assay (IGRA)-in a densely populated high-burden TB area. METHODS: We developed a seven-step framework that can be tailored to individual TB programmes seeking to compare TB infection (TBI) diagnostics to inform decision-making. We present methodology to estimate (1) the prevalence of TBI, (2) true and false positives and negatives for each test, (3) the cost of test administration, (4) the cost of false negatives, (5) the cost of treating all that test positive, (6) the per-test cost incurred due to treatment and misdiagnosis and (7) the threshold at which laboratory infrastructure investments for IGRA are outweighed by system-wide savings incurred due to IGRA utilisation. We then applied this framework in a densely populated, peri-urban district in Lima, Peru with high rates of Bacillus Calmette-Guérin (BCG) vaccination. FINDINGS: The lower sensitivity of TST compared with IGRA is a major cost driver, leading to health system and societal costs due to misdiagnosis. Additionally, patient and staff productivity costs were greater for TST because it requires two patient visits compared with only one for IGRA testing. When the framework was applied to the Lima setting, we estimate that IGRA-associated benefits outweigh infrastructural costs after performing 672 tests. CONCLUSIONS: Given global shortages of TST and concerns about costs of IGRA testing and laboratory capacity building, this costing framework can provide public health officials and TB programmes guidance for decision-making about TBI testing locally. This framework was designed to be adaptable for use in different settings with available data. Diagnostics that increase accuracy or mitigate time to treatment should be thought of as an investment instead of an expenditure.

Assessment of the Cepheid 3-gene Host Response Fingerstick Blood Test (MTB-HR) on rapid diagnosis of tuberculosis.

ABSTRACTThe World Health Organization has identified high-priority target product profiles for new TB diagnostics which include rapid biomarker-based, non-sputum-based diagnostic testing, using an easily accessible sample. The Cepheid 3-gene Host Response Fingerstick Blood Prototype Test (MTB-HR) quantifies relative mRNA levels of a 3-gene signature (GBP5, DUSP3, and KLF2) from a whole-blood sample on the GeneXpert platform. The objective of the present study was to evaluate the performance of the MTB-HR to distinguish between active tuberculosis (ATB), latent Mycobacterium tuberculosis infection (LTBI), other pulmonary diseases, and healthy volunteers at a tertiary care centre. Among 653 participants enrolled in this study, 192 were diagnosed as having ATB, and the remaining 461 were classified as non-ATB, including 137 cases of LTBI, 224 cases of other pulmonary diseases, and 100 healthy volunteers. The corresponding AUCs of the MTB-HR in distinguishing untreated ATB from non-ATB, LTBI, other pulmonary diseases, and healthy volunteers were 0.814 (95% CI, 0.760-0.868, sensitivity 76.1%, specificity 71.6%), 0.739 (95% CI, 0.667-0.812, sensitivity 59.7%, specificity 78.1%), 0.825 (95% CI, 0.770-0.880, sensitivity 82.1%, specificity 65.6%), 0.892 (95% CI, 0.839-0.945, sensitivity 76.1%, specificity 88.0%), respectively. When only samples with TAT of less than 1 h were included, the AUC of the MTB-HR in distinguishing untreated ATB from non-ATB was largest, 0.920 (95% CI, 0.822-1.000, sensitivity 81.3%, specificity 87.7%). In conclusion, the MTB-HR assay shows potential as a rapid, blood-based screening and triage test for ATB, especially for untreated ATB, with the advantage of increased diagnostic yield since blood is more readily available.

A cost-effectiveness evaluation of latent tuberculosis infection screening of a migrant population in Malaysia.

To estimate the costs and benefits of screening for latent tuberculosis infection (LTBI) in a migrant population in Malaysia. An economic model was developed from a Malaysian healthcare perspective to compare QuantiFERON-TB Gold Plus (QuantiFERON) with the tuberculin skin test (TST). A decision tree was used to capture outcomes relating to LTBI screening followed by a Markov model that simulated the lifetime costs and benefits of the patient cohort. The Markov model did not capture the impact of secondary infections. The model included an R shiny interactive interface to allow adaptation to other scenarios and settings. QuantiFERON is both more effective and less costly than TST (dominant). Compared with QuantiFERON, the lifetime risk of developing active TB increases by approximately 40% for TST due to missed LTBI cases during screening (i.e. a higher number of false negative cases for TST). For a migrant population in Malaysia, QuantiFERON is cost-effective when compared with TST. Further research should consider targeted LTBI screening for migrants in Malaysia based on common risk factors.

Tuberculosis, focussed tools and the right schools: estimated impact and cost of a targeted student screening programme for tuberculosis infection.

BACKGROUND: The World Health Organization (WHO) recommends targeted screening for latent tuberculosis infection (LTBI) among high-risk populations. Recent studies that evaluate targeted school-based programmes in low burden settings are scarce. AIMS: To evaluate a school screening programme for recently arrived migrant students from moderate and high tuberculosis (TB) burden countries and estimate (1) the number of cases of active TB that were prevented and (2) the cost per case of active TB prevented. METHODS: Students were screened with tuberculin skin tests (TST) at schools with a high migrant population intake. Those with positive results were referred for specialist evaluation. Outcomes were retrospectively assessed using 5 years of prospectively collected data. Cost data were collected. Main outcomes measured were the number of children were diagnosed with LTBI who completed treatment, and programme costs. RESULTS: Of 4728 student screened, 295 (6.2%) were diagnosed with LTBI. Of these, 273 (92.5%) were offered preventive therapy, 242 (82.0%) commenced and 204 (69.2%) completed therapy. The number needed to screen (NNS) was 23 per completed course of preventive treatment for LTBI. Assuming a 10% lifetime risk of reactivation, the NNS was 386 per case of TB disease notification avoided. The cost of screening was A$23 932 per case of TB disease avoided. CONCLUSIONS: This TB strategy is supported by the high rate of TB infection in the student group, the treatment uptake and completion rates. Cost-benefit is linked with lifetime risk of TB reactivation. Targeted school screening programmes represent an important opportunity for TB control in low-burden settings.

A systematic review of cost-utility analyses of screening methods in latent tuberculosis infection in high-risk populations.

BACKGROUND: The World Health Organisation (WHO) recommends that testing and treatment for latent tuberculosis infection (LTBI) should be undertaken in high-risk groups using either interferon gamma release assays (IGRAs) or a tuberculin skin test (TST). As IGRAs are more expensive than TST, an assessment of the cost-effectiveness of IGRAs can guide decision makers on the most appropriate choice of test for different high-risk populations. This current review aimed to provide the most up to date evidence on the cost-effectiveness evidence on LTBI testing in high-risk groups-specifically evidence reporting the costs per QALY of different testing strategies. METHODS: A comprehensive search of databases including MEDLINE, EMBASE and NHS-EED was undertaken from 2011 up to March 2021. Studies were screened and extracted by two independent reviewers. The study quality was assessed using the Bias in Economic Evaluation Checklist (ECOBIAS). A narrative synthesis of the included studies was undertaken. RESULTS: Thirty-two studies reported in thirty-three documents were included in this review. Quality of included studies was generally high, although there was a weakness across all studies referencing sources correctly and/or justifying choices of parameter values chosen or assumptions where parameter values were not available. Inclusions of IGRAs in testing strategies was consistently found across studies to be cost-effective but this result was sensitive to underlying LTBI prevalence rates. CONCLUSION: While some concerns remain about uncertainty in parameter values used across included studies, the evidence base since 2010 has grown with modelling approaches addressing the weakness pointed out in previous reviews but still reaching the same conclusion that IGRAs are likely to be cost-effective in high-income countries for high-risk populations. Evidence is also required on the cost-effectiveness of different strategies in low to middle income countries and countries with high TB burden.

Economic Evaluation of Screening Strategy for Latent Tuberculosis Infection (LTBI) in Contacts of Tuberculosis Patients: Systematic Review and Quality Assessment.

A tuberculin skin test (TST) or interferon-gamma release assay (IGRA) can be used to screen for latent tuberculosis infection (LTBI). Due to its low cost, TST has been used particularly in underdeveloped countries. The limitations of TST were poor specificity in populations with a high prevalence of Bacille Calmette-Guérin (BCG) vaccination and variability of test readers. IGRA is used as an alternative to TST in settings where higher costs can be supported. The lack of studies conducted in high TB incidence countries since previous review, and using relevant assessment tools of the quality appraisal make the need for updated studies and a more comprehensive systematic review. This study aimed to conduct a systematic review of published economic evaluations of screening strategies for LTBI in contacts of TB patients, assess the quality of these studies, and compare the assessment results related to a country's income level in order to provide information to other countries. The databases were searched in January 2022 including MEDLINE and Scopus. Two independent reviewers evaluated the included studies based on eligibility criteria, data extraction, and quality assessment. Eleven economic evaluations of LTBI diagnostic tests in TB contacts were included. Most studies were conducted in high-income countries (91%) and used cost-effectiveness analysis methods (73%). The quality assessment of reporting and data sources was appropriate, ranging from 71% to 89%. Interventions varied from study to study. The outcomes were cost per life years gained (27%), cost per quality-adjusted life year gained (27%), cost per TB case prevented (36%), and cost per close contact case (10%). In high-income countries which were not countries with high TB burden, the use of IGRA alone for screening TB contacts was cost-effective, whereas TST was cost-effective in only two studies. In comparison to TST, IGRA could reduce false-positive results, resulting in fewer patients undergoing TB treatment and preventive treatment.

GeneXpert or chest-X-ray or tuberculin skin testing for household contact assessment (GXT): protocol for a cluster-randomized trial.

BACKGROUND: The World Health Organization recommends tuberculosis (TB) preventive treatment (TPT) for all people living with HIV (PLH) and household contacts (HHC) of index TB patients. Tests for TB infection (TBI) or to rule out TB disease (TBD) are preferred, but if not available, this should not be a barrier if access to these tests is limited for high-risk people, such as PLH and HHC under 5 years old. There is equipoise on the need for these tests in different risk populations, especially HHC aged over 5. METHODS: This superiority cluster-randomized multicenter trial with three arms of equal size compares, in Benin and Brazil, three strategies for HHC investigation aged 0-50: (i) tuberculin skin testing (TST) or interferon gamma release assay (IGRA) for TBI and if positive, chest X-Ray (CXR) to rule out TBD in persons with positive TST or IGRA; (ii) same as (i) but GeneXpert (GX) replaces CXR; and (iii) no TBI testing. CXR for all; if CXR is normal, TPT is recommended. All strategies start with symptom screening. Clusters are defined as HHC members of the same index patients with newly diagnosed pulmonary TBD. The main outcome is the proportion of HHC that are TPT eligible who start TPT within 3 months of the index TB patient starting TBD treatment. Societal costs, incidence of severe adverse events, and prevalence of TBD are among secondary outcomes. Stratified analyses by age (under versus over 5) and by index patient microbiological status will be conducted. All participants provide signed informed consent. The study was approved by the Research Ethic Board of the Research Institute of the McGill University Health Centre, the Brazilian National Ethical Board CONEP, and the "Comité Local d'Éthique Pour la Recherche Biomédicale (CLERB) de l'Université de Parakou," Benin. Findings will be submitted for publication in major medical journals and presented in conferences, to WHO and National and municipal TB programs of the involved countries. DISCUSSION: This randomized trial is meant to provide high-quality evidence to inform WHO recommendations on investigation of household contacts, as currently these are based on very low-quality evidence. TRIAL REGISTRATION: ClinicalTrials.gov NCT04528823.

Digital health use in latent tuberculosis infection care: A systematic review.

PURPOSE: With one-quarter of the world's population estimated to have latent tuberculosis infection (LTBI), it is important that the drop-outs from the LTBI cascade of care are minimized. Digital health technology could play an important role in case detection and treatment adherence. This study aims to evaluate the use and impact of digital health technology in LTBI care. METHODS: A systematic literature search was conducted on six electronic databases from database inception until May 31st 2021. Studies that reported on the clinical use or economic analysis of digital health technology for LTBI care were included. Two investigators independently evaluated, extracted relevant studies, and assessed the risk of bias of using the Cochrane tools. The studies were synthesized qualitatively. RESULTS: Fifteen articles describing 14 studies were included. Voice and/or textual reminders and synchronous video call to improve LTBI treatment adherence were the most commonly examined digital health interventions. Other interventions examined the use of mobile phones to improve the number of patients who returned for tuberculin skin test follow-up measurement (screening retention) and eLearning videos to enhance health literacy in LTBI care. The economic analysis supported the use of textual reminders in LTBI treatment as a cost-effective option for widescale implantation. CONCLUSIONS: Despite limited evidence on the effects of digital health technologies in LTBI, available studies suggest they are at least equivalent to current practice. This means digital health can potentially supplement current practice, to constantly monitor and engage with people undergoing LTBI screening or treatment, as an initiative to ensure the provision of continuous and optimal care to all LTBI-affected individuals.

Cost-effectiveness of testing for latent tuberculosis infection in people with HIV.

OBJECTIVE: The aim of this study was to estimate the cost-effectiveness of screening strategies for predicting LTBI that progresses to active tuberculosis (TB) in people with HIV. DESIGN: We developed a decision-analytical model that constituted a decision tree covering diagnosis of LTBI and a Markov model covering progression to active TB. The model represents the lifetime experience following testing for LTBI, and discounting costs, and benefits at 3.5% per annum in line with UK standards. We undertook probabilistic and one-way sensitivity analyses. SETTING: UK National Health Service and Personal Social Service perspective in a primary care setting. PARTICIPANTS: Hypothetical cohort of adults recently diagnosed with HIV. INTERVENTIONS: Interferon-gamma release assays and tuberculin skin test. MAIN OUTCOME MEASURE: Cost per quality-adjusted life year (QALY). RESULTS: All strategies except T-SPOT.TB were cost-effective at identifying LTBI, with the QFT-GIT-negative followed by TST5mm strategy being the most costly and effective. Results indicated that there was little preference between strategies at a willingness-to-pay threshold of £20 000. At thresholds above £40 000 per QALY, there was a clear preference for the QFT-GIT-negative followed by TST5mm, with a probability of 0.41 of being cost-effective. Results showed that specificity for QFT-GIT and TST5mm were the main drivers of the economic model. CONCLUSION: Screening for LTBI has important public health and clinical benefits. Most of the strategies are cost-effective. These results should be interpreted with caution because of the paucity of studies included in the meta-analysis of test accuracy studies. Additional high-quality primary studies are needed to have a definitive answer about, which strategy is the most effective.

The Health and Economic Benefits of Tests That Predict Future Progression to Tuberculosis Disease.

BACKGROUND: Effective targeting of latent tuberculosis infection (LTBI) treatment requires identifying those most likely to progress to tuberculosis (TB). We estimated the potential health and economic benefits of diagnostics with improved discrimination for LTBI that will progress to TB. METHODS: A base case scenario represented current LTBI testing and treatment services in the United States in 2020, with diagnosis via. interferon-gamma release assay (IGRA). Alternative scenarios represented tests with higher positive predictive value (PPV) for future TB but similar price to IGRA, and scenarios that additionally assumed higher treatment initiation and completion. We predicted outcomes using multiple transmission-dynamic models calibrated to different geographic areas and estimated costs from a societal perspective. RESULTS: In 2020, 2.1% (range across model results: 1.1%-3.4%) of individuals with LTBI were predicted to develop TB in their remaining lifetime. For IGRA, we estimated the PPV for future TB as 1.3% (0.6%-1.8%). Relative to IGRA, we estimated a test with 10% PPV would reduce treatment volume by 87% (82%-94%), reduce incremental costs by 30% (15%-52%), and increase quality-adjusted life years by 3% (2%-6%). Cost reductions and health improvements were substantially larger for scenarios in which higher PPV for future TB was associated with greater initiation and completion of treatment. CONCLUSIONS: We estimated that tests with better predictive performance would substantially reduce the number of individuals treated to prevent TB but would have a modest impact on incremental costs and health impact of TB prevention services, unless accompanied by greater treatment acceptance and completion.

Prevalence of Latent Tuberculosis Infection Among Healthy Young Children and Adolescents and a Two-step Approach for the Diagnosis of Tuberculosis Infection in Chengdu, China.

BACKGROUND: China has a high burden of tuberculosis and latent tuberculosis infection (LTBI). The aim of this study was to estimate the prevalence of LTBI among healthy young children and adolescents and test a 2-step approach to explore the threshold for the diagnosis of tuberculosis infection in Chengdu, China. METHODS: Healthy preschool children and school-going children in Chengdu, Sichuan Province, were screened for LTBI using the tuberculin skin test (TST). Preschool children with TST ≥ 5 mm also underwent interferon-γ release assay (IGRA) to explore the threshold of this 2-step approach. RESULTS: In total, 5667 healthy young children and adolescents completed TST test between July 2020 and January 2021 and were included in the present analysis. The age of the participants ranged from 2.4 to 18 years (median 7.25 ± 4.514 years), of which 2093 (36.9%) were younger than 5 years. The overall prevalence of LTBI was 6.37% and 6.64% in children younger than 5 years old. Fourteen of the 341 preschool children with TST ≥5 mm were interferon-γ release assay positive, of which 4 showed a TST result of 5-10 mm, and 6 preschool children received preventive treatment for LTBI. CONCLUSIONS: Healthy young children and adolescents should also be considered as important target populations for LTBI screening. TST can be recommended for first-line screening as part of a 2-step approach for LTBI screening using a positive threshold of 5 mm.

Prevalence of latent tuberculosis infection among participants of the national LTBI screening program in South Korea - A problem of low coverage rate with current LTBI strategy.

Background: The Government of South Korea launched a national preemptive latent tuberculosis infection (LTBI) screening program in 2016, including more than 1. 6 million population in congregate settings. The objective of this study was to analyze LTBI prevalence and its risk factors in each setting. Additionally, the proportion of LTBI pool covered by the current national LTBI strategy was investigated. Methods: Database for results of interferon gamma release assay (IGRA), X-ray, and baseline demographic information was linked with National Health Information Database, national tuberculosis (TB) surveillance database, and national contact investigation database. Participants were categorized into three groups: Group A, workers of postpartum care centers, social welfare facilities and educational institutions; Group B, first year students in high school and out-of-school youths; and Group C, inmates of correctional facilities. Relative risks of LTBI by sex, age, place of living, income level, and comorbidities were calculated. Results: A total of 444,394 participants in Group A, 272,224 participants in Group B, and 11,511 participants in Group C who participated in the national LTBI screening program between 2017 and 2018 were included, with LTBI prevalence of 20.7, 2.0, and 33.2%, respectively. Age was the single most important risk factor in Group A and Group C. Low-income level was another risk factor commonly identified in all groups. Among participants with positive IGRA results, 2.7, 4.4, and 3.3% in Groups A, B and C, respectively, had past TB exposure history since 2013. Current LTBI guideline targeting high or moderate TB risk disease covered 6.5, 0.6, and 1.1% of participants with positive IGRA results in Groups A, B and C, respectively. Conclusion: Only a small proportion of participants with positive IGRA results could be covered by the current LTBI strategy. Expansion of LTBI strategy by identifying further high-TB risk group in the general population is required.