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.

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.

Comparing the cost-effectiveness of two screening strategies for latent tuberculosis infection in Portugal.

INTRODUCTION AND OBJECTIVES: Screening for latent tuberculosis infection (LTBI) in close contacts of infectious TB cases might include Tuberculin Skin Test (TST) and Interferon-Gamma Release Assays (IGRA), in combination or as single-tests. In Portugal, the screening strategy changed from TST followed by IGRA to IGRA-only testing in 2016. Our objective was to compare the cost-effectiveness of two-step TST/IGRA with the current IGRA-only screening strategy in immunocompetent individuals exposed to individuals with respiratory TB. MATERIALS AND METHODS: We reviewed clinical records of individuals exposed to infectious TB cases diagnosed in 2015 and 2016, in two TB outpatient centers in the district of Porto. We estimated medical, non-medical and indirect costs for each screening strategy, taking into account costs of tests and health care personnel, travel distance from place of residence to screening site and employment status. We calculated the incremental cost-effectiveness ratio (ICER) as the cost difference between the two screening strategies with the difference number of LTBI diagnosis as a measure of cost-effectiveness, assuming that treating LTBI is a cost-effective intervention. We also calculated adjusted odds-ratios to test the association between diagnosis of LTBI and screening strategy and estimated the total cost for averting a potential TB case. RESULTS: We compared 499 contacts TST/IGRA screened with 547 IGRA-only. IGRA-only strategy yielded a higher screening effectiveness for diagnosing latent tuberculosis infection (aOR 2.12, 95%CI: 1.53 - 2.94). ICER was €106 per LTBI diagnosis, representing increased effectiveness with a slightly increased cost of IGRA-only screening strategy. CONCLUSIONS: Our data suggests that in Portugal LTBI screening with IGRA-only is more cost-effective than the two-step TST/IGRA testing strategy, preventing a higher number of cases of TB cases.

[Preventing TB among immigrants; aiming for an integrated approach to infectious diseases]. / Preventie van tbc bij migranten.

Tuberculosis (TB) still occurs frequently in the Netherlands among immigrants from countries where the disease is highly endemic, despite the mandatory TB screening upon settling in the Netherlands. The TB-ENDPoint study shows that immigrants from populations at risk for TB are prepared to be screened for latent TB infection (LTBI) and to complete preventative treatment. Cost-effectiveness analysis will have to determine whether and in which target groups screening can replace the present X-ray screening for TB. A targeted approach, in which LTBI screening is combined with screening for other infectious diseases such as hepatitis B and C and HIV, could favourably influence cost-effectiveness. Further research into implementation, involving all stakeholders, would be useful to optimize combined screening.

Cost-effectiveness of QuantiFERON-TB Gold In-Tube versus tuberculin skin test for diagnosis and treatment of Latent Tuberculosis Infection in primary health care workers in Brazil.

OBJECTIVES: The goal of this study was to perform a cost-effectiveness analysis from the public health system perspective, comparing five strategies for Latent Tuberculosis Infection (LTBI) diagnosis in primary health care workers in Brazil. DESIGN: Analytical model for decision making, characterized by cost-effectiveness analysis. SETTING: Primary Care Level, considering primary health care workers in Brazil. PARTICIPANTS: An analytical model for decision making, characterized by a tree of probabilities of events, was developed considering a hypothetical cohort of 10,000 primary health care workers, using the software TreeAge Pro™ 2013 to simulate the clinical and economic impacts of new diagnostic technology (QuantiFERON®-TB Gold in-Tube) versus the traditional tuberculin skin test. METHODS: This model simulated five diagnostic strategies for LTBI in primary health care workers (HCW) in Brazil: tuberculin skin testing using ≥5 mm cut-off, tuberculin skin testing ≥10 mm cut-off, QuantiFERON®-TB Gold in-Tube, tuberculin skin testing using ≥5 mm cut-off confirmed by QuantiFERON®-TB Gold In-Tube if TST positive, tuberculin skin testing using ≥10 mm cut-off confirmed by QuantiFERON®-TB Gold In-Tube if TST positive. PRIMARY AND SECONDARY OUTCOME MEASURES: The outcome measures are the number of individuals correctly classified by the test and the number of Tuberculosis cases avoided. RESULTS: The most cost-effective strategy was the tuberculin skin test considering ≥10mm cut-off. The isolated use of the QuantiFERON®-TB Gold In-Tube revealed the strategy of lower efficiency with incremental cost-effectiveness ratio (ICER) of US$ 146.05 for each HCW correctly classified by the test. CONCLUSIONS: The tuberculin skin test using ≥10 mm cut-off was the most cost-effective strategy in the diagnosis of Latent Tuberculosis Infection in primary health care works in Brazil.

Latent Tuberculosis Infection Testing Strategies for HIV-Positive Individuals in Hong Kong.

Importance: With immune recovery following early initiation of antiretroviral therapy (ART), the risk of tuberculosis (TB) reactivation among individuals with HIV could be reduced. The current strategy of annual latent TB infection (LTBI) testing should be revisited to increase cost-effectiveness and reduce the intensity of testing for individuals. Objective: To analyze the cost-effectiveness of LTBI testing strategies for individuals in Hong Kong with HIV who had negative LTBI test results at baseline. Design, Setting, and Participants: This decision analytical model study using a cost-effectiveness analysis included 3130 individuals with HIV in Hong Kong, China, which has an intermediate TB burden and a low incidence of HIV-TB coinfection. A system dynamics model of individuals with HIV attending a major HIV specialist clinic in Hong Kong was developed and parameterized by longitudinal clinical and LTBI testing records of patients during a 15-year period. The study population was stratified by age group, CD4 lymphocyte level, ART status, and right of abode. Alternative strategies for LTBI testing after a baseline test were compared with annual testing under different coverages of ART, LTBI testing, and LTBI treatment scenarios in the model. An annual discounting rate of 3.5% was used in cost-effectiveness analysis. Main Outcomes and Measures: Proportion of new TB cases averted above base case scenario, discounted quality-adjusted life-years gained (QALYG), incremental cost, and incremental cost-effectiveness ratios in 2017 to 2023. Results: A total of 3130 patients with HIV (2740 [87.5%] male and 2800 [89.5%] younger than 50 years at HIV diagnosis) with 16 630 person-years of follow-up data from 2002 to 2017 were analyzed. Of these, 94 patients (0.67 [95% CI, 0.51-0.91] per 100 person-years) developed TB. Model estimates of cumulative number of TB cases would reach 146 by 2023, with the annual number of new TB diagnoses ranging from 6 to 8. For patients who had negative LTBI test results at baseline, subsequent LTBI testing strategies were ranked by ascending effectiveness as follows: (1) no testing, (2) test by risk factors, (3) biennial testing for all, (4) up to 3 tests for all, and (5) annual testing for all. Applying a willingness-to-pay threshold of $50 000 per QALYG, none of the subsequent testing strategies were cost-effective. Test by risk factors and up to 3 tests for all were cost-effective only if the willingness-to-pay threshold was increased to $100 000 per QALYG and $200 000 per QALYG, respectively. More new TB cases would be averted by expanding LTBI testing and/or treatment coverage. Conclusions and Relevance: Changing the current testing strategy to less intense testing strategies is likely to be cost-effective in the presence of an increased coverage of baseline LTBI testing and/or treatment.

Interferon gamma release assays for Diagnostic Evaluation of Active tuberculosis (IDEA): test accuracy study and economic evaluation.

BACKGROUND: Interferon gamma release assays (IGRAs) are blood tests recommended for the diagnosis of tuberculosis (TB) infection. There is currently uncertainty about the role and clinical utility of IGRAs in the diagnostic workup of suspected active TB in routine NHS clinical practice. OBJECTIVES: To compare the diagnostic accuracy and cost-effectiveness of T-SPOT.TB® (Oxford Immunotec, Abingdon, UK) and QuantiFERON® TB GOLD In-Tube (Cellestis, Carnegie, VIC, Australia) for diagnosis of suspected active TB and to estimate the diagnostic accuracy of second-generation IGRAs. DESIGN: Prospective within-patient comparative diagnostic accuracy study. SETTING: Secondary care. PARTICIPANTS: Adults (aged ≥ 16 years) presenting as inpatients or outpatients at 12 NHS hospital trusts in London, Slough, Oxford, Leicester and Birmingham with suspected active TB. INTERVENTIONS: The index tests [T-SPOT.TB and QuantiFERON GOLD In-Tube (QFT-GIT)] and new enzyme-linked immunospot assays utilising novel Mycobacterium tuberculosis antigens (Rv3615c, Rv2654, Rv3879c and Rv3873) were verified against a composite reference standard applied by a panel of clinical experts blinded to IGRA results. MAIN OUTCOME MEASURES: Sensitivity, specificity, predictive values and likelihood ratios were calculated to determine diagnostic accuracy. A decision tree model was developed to calculate the incremental costs and incremental health utilities [quality-adjusted life-years (QALYs)] of changing from current practice to using an IGRA as an initial rule-out test. RESULTS: A total of 363 patients had active TB (culture-confirmed and highly probable TB cases), 439 had no active TB and 43 had an indeterminate final diagnosis. Comparing T-SPOT.TB and QFT-GIT, the sensitivities [95% confidence interval (CI)] were 82.3% (95% CI 77.7% to 85.9%) and 67.3% (95% CI 62.1% to 72.2%), respectively, whereas specificities were 82.6% (95% CI 78.6% to 86.1%) and 80.4% (95% CI 76.1% to 84.1%), respectively. T-SPOT.TB was more sensitive than QFT-GIT (relative sensitivity 1.22, 95% CI 1.14 to 1.31; p < 0.001), but the specificities were similar (relative specificity 1.02, 95% CI 0.97 to 1.08; p = 0.3). For both IGRAs the sensitivity was lower and the specificity was higher for human immunodeficiency virus (HIV)-positive than for HIV-negative patients. The most promising novel antigen was Rv3615c. The added value of Rv3615c to T-SPOT.TB was a 9% (95% CI 5% to 12%) relative increase in sensitivity at the expense of specificity, which had a relative decrease of 7% (95% CI 4% to 10%). The use of current IGRA tests for ruling out active TB is unlikely to be considered cost-effective if a QALY was valued at £20,000 or £30,000. For T-SPOT.TB, the probability of being cost-effective for a willingness to pay of £20,000/QALY was 26% and 21%, when patients with indeterminate test results were excluded or included, respectively. In comparison, the QFT-GIT probabilities were 8% and 6%. Although the use of IGRAs is cost saving, the health detriment is large owing to delay in diagnosing active TB, leading to prolonged illness. There was substantial between-patient variation in the tests used in the diagnostic pathway. LIMITATIONS: The recruitment target for the HIV co-infected population was not achieved. CONCLUSIONS: Although T-SPOT.TB was more sensitive than QFT-GIT for the diagnosis of active TB, the tests are insufficiently sensitive for ruling out active TB in routine clinical practice in the UK. Novel assays offer some promise. FUTURE WORK: The novel assays require evaluation in distinct clinical settings and in immunosuppressed patient groups. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and the NIHR Health Protection Research Unit in Respiratory Infections, Imperial College London, London, UK.

Tuberculosis (TB) is one of the world's most important infectious diseases. In 2014, 1.5 million deaths were caused by the disease ­ about one death every 25 seconds. Traditional diagnosis of TB is based partly on the tuberculin skin test. Blood tests such as QuantiFERON GOLD In-Tube (QFT-GIT; Cellestis, Carnegie, VIC, Australia) and T-SPOT.TB^® (Oxford Immunotec, Abingdon, UK) are now available. However, these two tests are not used as part of current NHS practice because of the lack of evidence about how well the tests perform when diagnosing symptomatic (active) TB in routine clinical practice. The purpose of our study was to compare the ability of QFT-GIT and T-SPOT.TB to differentiate people with active TB from those without active TB in a population suspected of the disease. We also assessed new blood tests that are currently being developed for diagnosis of active TB. We recruited 1074 patients with suspected TB from 14 NHS hospitals in London, Slough, Oxford, Leicester and Birmingham into our study. We found that T-SPOT.TB correctly detected more people with active TB than QFT-GIT; T-SPOT.TB would miss about 18 people out of every 100, whereas QFT-GIT would miss about 33 people out of every 100 with active TB. For this reason, neither test is good enough for routine clinical use because the number of people with active TB who are incorrectly diagnosed as not having active TB is unacceptably high. In addition, neither test is good value for money. However, we did find that some of the newer blood tests performed better than T-SPOT.TB and their usefulness should be further investigated.

Outlook for tuberculosis elimination in California: An individual-based stochastic model.

RATIONALE: As part of the End TB Strategy, the World Health Organization calls for low-tuberculosis (TB) incidence settings to achieve pre-elimination (<10 cases per million) and elimination (<1 case per million) by 2035 and 2050, respectively. These targets require testing and treatment for latent tuberculosis infection (LTBI). OBJECTIVES: To estimate the ability and costs of testing and treatment for LTBI to reach pre-elimination and elimination targets in California. METHODS: We created an individual-based epidemic model of TB, calibrated to historical cases. We evaluated the effects of increased testing (QuantiFERON-TB Gold) and treatment (three months of isoniazid and rifapentine). We analyzed four test and treat targeting strategies: (1) individuals with medical risk factors (MRF), (2) non-USB, (3) both non-USB and MRF, and (4) all Californians. For each strategy, we estimated the effects of increasing test and treat by a factor of 2, 4, or 10 from the base case. We estimated the number of TB cases occurring and prevented, and net and incremental costs from 2017 to 2065 in 2015 U.S. dollars. Efficacy, costs, adverse events, and treatment dropout were estimated from published data. We estimated the cost per case averted and per quality-adjusted life year (QALY) gained. MEASUREMENTS AND MAIN RESULTS: In the base case, 106,000 TB cases are predicted to 2065. Pre-elimination was achieved by 2065 in three scenarios: a 10-fold increase in the non-USB and persons with MRF (by 2052), and 4- or 10-fold increase in all Californians (by 2058 and 2035, respectively). TB elimination was not achieved by any intervention scenario. The most aggressive strategy, 10-fold in all Californians, achieved a case rate of 8 (95% UI 4-16) per million by 2050. Of scenarios that reached pre-elimination, the incremental net cost was $20 billion (non-USB and MRF) to $48 billion. These had an incremental cost per QALY of $657,000 to $3.1 million. A more efficient but somewhat less effective single-lifetime test strategy reached as low as $80,000 per QALY. CONCLUSIONS: Substantial gains can be made in TB control in coming years by scaling-up current testing and treatment in non-USB and those with medical risks.

Cost-effectiveness assessment of three components of the bovine tuberculosis surveillance system by intradermal tuberculin testing in French cattle farms by a scenario tree approach.

In most officially bovine tuberculosis (bTB)-free countries, bTB has not been fully eradicated. Costly and time-consuming surveillance and control measures are therefore still in place to control this infection. An officially bTB-free status, both at the national and at the herd level, influences whether and when animals can be sold. Thus, this infection is still an economic issue, justifying measures towards its eradication. An evaluation of the cost-effectiveness of such measures would be highly useful, especially to optimise the costs of control measures and their adaptation to a local epidemiological context. We evaluated the cost-effectiveness of three mandatory surveillance protocols currently used in France by herd type (type of production, size, and turnover of the herd) under French field conditions. The first protocol ("strict") implies the direct slaughter and post-mortem analyses of any intradermal cervical tuberculin test (ICT) reactor, and negative results to a second intradermal cervical comparative tuberculin test (ICCT) to regain bTB-free status of the herd. In the second protocol ("compliant quick-path") bTB-free status can be regain if post-mortem analyses of reactors to the first ICT are negative. In the third protocol ("compliant slow-path"), ICCT-reactive animals are tested using the interferon gamma assay; the results of this test influence the path of further investigation. We built scenario trees for each of these protocols at the animal level. They allowed us to estimate herd sensitivity and the total cost of each protocol by herd type. The protocols could be ordered by decreasing herd sensitivity and cost, regardless of the herd type, as follows: strict protocol, compliant quick-path protocol, and compliant slow-path protocol. We calculated a cost-effectiveness index to evaluate the cost-effectiveness of each protocol. The strict protocol was never the most cost-effective, regardless of herd type, due to higher costs relative to the other protocols, despite better herd sensitivity. We found the compliant quick-path to be the most cost-effective protocol for big beef, big dairy, and mixed herds. The compliant slow-path was the most cost-effective for small-scale beef and dairy herds. All differences were significant. This comparison of the cost-effectiveness of the protocols by herd type could help authorities to choose the most suitable protocol in the investigation of suspected cases, depending on the herd type, but could be improved by accounting for important sociological data, such as the acceptability of the protocols.

A screening strategy for latent tuberculosis in healthcare workers: Cost-effectiveness and budget impact of universal versus targeted screening.

OBJECTIVE: To evaluate the clinical, cost-efficiency, and budgetary implications of universal versus targeted latent tuberculosis infection (LTBI) screening strategies among healthcare workers (HCWs) in an intermediate tuberculosis (TB)-burden country. DESIGN: Pragmatic cost-effectiveness and budget impact analysis using decision-analytic modeling. SETTING: A tertiary-care hospital in Singapore. METHODS: We compared 7 potentially implementable LTBI screening programs including universal and targeted strategies with different screening frequencies. Feasible targeting methods included stratification by country of origin (a proxy for risk of prior TB exposure) and by high-risk occupation. The clinical and financial consequences of each strategy were estimated relative to "no screening" (current practice) and compared to locally appropriate cost-effectiveness thresholds. All analyses were conducted from the hospital's perspective over a 3-year time horizon, based on the typical hospital planning period. Parameter uncertainties were accounted for using sensitivity analyses. RESULTS: In our model, relative to current practice, screening new international hires and triennial screening of existing high-risk workers is most cost-effective (US$58 per quality adjusted life year [QALY]) and decreases active TB cases from 19 to 14. Screening all new hires combined with triennial universal screening, with or without annual high-risk screening or annual universal screening, reduced active TB to a range of 19 to 6 cases, but these strategies are less cost-effective and require substantially higher expenditures. CONCLUSIONS: Targeted LTBI screening for HCWs can be highly cost-effective for hospitals in settings similar to Singapore. More inclusive screening strategies (including regular universal screening) can yield better outcomes but are less efficient and may even be unaffordable.

Interferon-gamma release assay for tuberculosis screening of solid-organ transplant recipients is cost-effective.

OBJECTIVES: Tuberculosis (TB) is a serious infectious disease with high mortality for solid-organ transplantation. Preventive therapy of latent tuberculosis infection (LTBI) has been considered to reduce TB risk and improve outcomes of transplantation. The aim of this study was to evaluate the cost-effectiveness of the interferon-gamma release assays (IGRAs); QuantiFERON®-TB Gold in-Tube (QFT) and T-SPOT®.TB (TSPOT)), for kidney, liver and lung transplant recipients in low TB incidence countries. METHODS: Decision trees and Markov models were developed for four strategies; QFT, TSPOT, the tuberculin skin test (TST) and no screening. Targeted populations were hypothetical cohorts of kidney, liver and lung transplant recipients aged 40 years using a societal perspective on a lifetime horizon. Per-person costs, effectiveness and incremental cost effectiveness ratios were calculated and compared. RESULTS: QFT was the most cost-effective (Kidney; US$ 5679, 3.026 QALYs, Liver; US$ 5914, 2.365 QALYs, Lung; US$ 6092, 3.761 QALYs). No screening was the least effective. Cost-effectiveness was not sensitive to BCG vaccination rate, and the costs of screening tests and treatment. CONCLUSIONS: TB screening using IGRA with individualized TB risk assessment and follow-up monitoring of drug toxicity during LTBI treatment is recommended for solid organ transplantation, on the basis of the benefits and cost-effectiveness.

Two interferon gamma release assays for predicting active tuberculosis: the UK PREDICT TB prognostic test study.

BACKGROUND: Despite a recent decline in the annual incidence of tuberculosis (TB) in the UK, rates remain higher than in most Western European countries. The detection and treatment of latent TB infection (LTBI) is an essential component of the UK TB control programme. OBJECTIVES: To assess the prognostic value and cost-effectiveness of the current two interferon gamma release assays (IGRAs) compared with the standard tuberculin skin test (TST) for predicting active TB among untreated individuals at increased risk of TB: (1) contacts of active TB cases and (2) new entrants to the UK from high-TB-burden countries. DESIGN: A prospective cohort study and economic analysis. PARTICIPANTS AND SETTING: Participants were recruited in TB clinics, general practices and community settings. Contacts of active TB cases and migrants who were born in high-TB-burden countries arriving in the UK were eligible to take part if they were aged ≥ 16 years. MAIN OUTCOME MEASURES: Outcomes include incidence rate ratios comparing the incidence of active TB in those participants with a positive test result and those with a negative test result for each assay, and combination of tests and the cost per quality-adjusted life-year (QALY) for each screening strategy. RESULTS: A total of 10,045 participants were recruited between May 2010 and July 2015. Among 9610 evaluable participants, 97 (1.0%) developed active TB. For the primary analysis, all test data were available for 6380 participants, with 77 participants developing active TB. A positive result for TSTa (positive if induration is ≥ 5 mm) was a significantly poorer predictor of progression to active TB than a positive result for any of the other tests. Compared with TSTb [positive if induration is ≥ 6 mm without prior bacillus Calmette-Guérin (BCG) alone, T-SPOT®.TB (Oxford Immunotec Ltd, Oxford, UK), TSTa + T-SPOT.TB, TSTa + IGRA and the three combination strategies including TSTb were significantly superior predictors of progression. Compared with the T-SPOT.TB test alone, TSTa + T-SPOT.TB, TSTb + QuantiFERON® TB Gold In-Tube (QFT-GIT; QIAGEN GmbH, Hilden, Germany) and TSTb + IGRA were significantly superior predictors of progression and, compared with QFT-GIT alone, T-SPOT.TB, TSTa + T-SPOT.TB, TSTa + QFT-GIT, TSTa + IGRA, TSTb + T-SPOT.TB, TSTb + QFT-GIT and TSTb + IGRA were significantly superior predictors of progression. When evaluating the negative predictive performance of tests and strategies, negative results for TSTa + QFT-GIT were significantly poorer predictors of non-progression than negative results for TSTa, T-SPOT.TB and TSTa + IGRA. The most cost-effective LTBI testing strategies are the dual-testing strategies. The cost and QALY differences between the LTBI testing strategies were small; in particular, QFT-GIT, TSTb + T-SPOT.TB and TSTb + QFT-GIT had very similar incremental net benefit estimates. CONCLUSION: This study found modest differences between tests, or combinations of tests, in identifying individuals who would go on to develop active TB. However, a two-step approach that combined TSTb with an IGRA was the most cost-effective testing option. IMPLICATIONS FOR PRACTICE AND FUTURE RESEARCH: The two-step TSTb strategy, which stratified the TST by prior BCG vaccination followed by an IGRA, was the most cost-effective approach. The limited ability of current tests to predict who will progress limits the clinical utility of tests. The implications of these results for the NHS England/Public Health England national TB screening programme for migrants should be investigated. STUDY REGISTRATION: This study is registered as NCT01162265. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Cost-effectiveness of contact screening strategies for tuberculosis among high-school adolescents in South Korea.

BACKGROUND: Effective latent tuberculous infection (LTBI) control among adolescents is a critical component of tuberculosis (TB) elimination in Korea. OBJECTIVE: To compare the cost-effectiveness of the following contact screening strategies for LTBI among high-school adolescents after TB outbreaks: QuantiFERON®-TB Gold In-Tube (QFT-GIT), the tuberculin skin test (TST), or TST/QFT-GIT (two-step strategy). METHOD: The costs of post-TB outbreak screening strategies were calculated using a mixed (top-down and bottom-up) cost analysis method and expressed in 2015 US dollars. Cost-effectiveness was evaluated using a decision analysis model from the health system perspective, comparing cumulative health care costs and the total number of TB cases averted. RESULTS: In a hypothetical cohort of 1000 students, screening using the TST-alone strategy averted 1.6 TB cases at a total cost of US$52 566. The QFT-GIT-alone strategy helped avert 2.0 TB cases, but was associated with a much higher total cost (US$108 435), resulting in an incremental cost-effectiveness ratio of US$140 933/TB case averted. The two-step TST/QFT-GIT strategy was worse than the TST-alone strategy, averting 1.3 TB cases at US$75 267. CONCLUSION: The TST-alone strategy was the most cost-effective; the QFT-GIT-alone strategy averted the greatest number of TB cases but incurred the highest cost in contact investigation for school TB outbreaks.

The effectiveness and cost-effectiveness of screening for latent tuberculosis among migrants in the EU/EEA: a systematic review.

BackgroundMigrants account for a large and growing proportion of tuberculosis (TB) cases in low-incidence countries in the European Union/European Economic Area (EU/EEA) which are primarily due to reactivation of latent TB infection (LTBI). Addressing LTBI among migrants will be critical to achieve TB elimination. Methods: We conducted a systematic review to determine effectiveness (performance of diagnostic tests, efficacy of treatment, uptake and completion of screening and treatment) and a second systematic review on cost-effectiveness of LTBI screening programmes for migrants living in the EU/EEA. Results: We identified seven systematic reviews and 16 individual studies that addressed our aims. Tuberculin skin tests and interferon gamma release assays had high sensitivity (79%) but when positive, both tests poorly predicted the development of active TB (incidence rate ratio: 2.07 and 2.40, respectively). Different LTBI treatment regimens had low to moderate efficacy but were equivalent in preventing active TB. Rifampicin-based regimens may be preferred because of lower hepatotoxicity (risk ratio = 0.15) and higher completion rates (82% vs 69%) compared with isoniazid. Only 14.3% of migrants eligible for screening completed treatment because of losses along all steps of the LTBI care cascade. Limited economic analyses suggest that the most cost-effective approach may be targeting young migrants from high TB incidence countries. Discussion: The effectiveness of LTBI programmes is limited by the large pool of migrants with LTBI, poorly predictive tests, long treatments and a weak care cascade. Targeted LTBI programmes that ensure high screening uptake and treatment completion will have greatest individual and public health benefit.

Cost-effectiveness analysis of strategies using new immunological diagnostic tests of latent tuberculosis infection before TNF-blockers therapy.

Several tests have been proposed to detect latent tuberculosis (LTB). OBJECTIVE: To evaluate the cost-effectiveness of different interferon-gamma release assays based strategies used to screen LTB before tumour necrosis factor (TNF) blockers initiation. METHODS: Consecutive patients with rheumatoid arthritis, spondyloarthritis or Crohn's disease for whom TNF-blockers were considered, were recruited in 15 tertiary care centres. All were screened for LTB with tuberculin skin test (TST), QuantiFERON TB Gold® in tube (QFT) and T-SPOT.TB® (TSpot) on the same day. Cost-minimization and cost-effectiveness analysis, testing 8 screening test combinations, were conducted. Effectiveness was defined as the percentage of LTB treatment avoided and compared with TST alone. Cost were elicited in the payer perspective, included all the costs related to the screening procedure. RESULTS: No tuberculosis reactivation was observed after TNF-blocker initiation. TST followed by QFT if TST was positive was found as the best screening strategy, i.e. the less costly (-54€ compared to reference) and most effective (effectiveness 0.93), resulting in an incremental cost-effectiveness ratio of -192€ per treatment avoided. A probabilistic sensitivity analysis confirmed this result in 72.3% of simulations. CONCLUSION: TST followed by QFT if TST was positive is the most cost-effective strategy in screening for LTB in patients before starting anti-TNF therapy. TRIALREGNO: NCT00811343.

Sequential strategy for the LTBI screening of newly-arrived immigrants in vulnerable social situations. / Estrategia secuencial para el cribado de la ITBL en inmigrantes recién llegados en situación social vulnerable.

INTRODUCTION: Some studies indicate high prevalences of latent tuberculosis infection (LTBI) in the immigrant population, which is relevant because 5-10% of cases will develop active tuberculosis. The objective of this study is to describe the results of a sequential strategy in the newly-arrived immigrant population for the diagnosis of LTBI using the tuberculin skin test (TST) and IGRAs. METHODS: A retrospective descriptive study was carried out with immigrants between 6 and 35years of age from shelters, referred to an international health unit between July 2013 and June 2016. The TST was performed and when it was ≥5mm, IGRAs were conducted. LTBI was defined as an IGRA ≥0.35IU/ml and normal chest X-ray. RESULTS: Of the 184 cases, 138 (75.0%) were men, 23.0 years of age. The most common geographical areas were: 63 (34.2%) from Asia, 42 (22.8%) from Eastern Europe and 41 (22.3%) from sub-Saharan Africa. The TST was ≥10mm in 79 cases (42.9%). The prevalence of LTBI using the sequential strategy was 33/184 (17.9%). Cohen's Kappa index (between TST≥10mm and IGRAs) was 0.226. CONCLUSION: Basing LTBI screening on the TST alone could give rise to an overestimation. Some studies show that sequential screening would be the most cost-effective; this seems most evident in BCG-vaccinated populations.

Cost-effectiveness of Testing and Treatment for Latent Tuberculosis Infection in Residents Born Outside the United States With and Without Medical Comorbidities in a Simulation Model.

Importance: Testing for and treating latent tuberculosis infection (LTBI) is among the main strategies to achieve TB elimination in the United States. The best approach to testing among non-US born residents, particularly those with comorbid conditions, is uncertain. Objective: To estimate health outcomes, costs, and cost-effectiveness of LTBI testing and treatment among non-US born residents with and without medical comorbidities. Design, Setting, and Participants: Decision analytic tree and Markov cohort simulation model among non-US born residents with no comorbidities, with diabetes, with HIV infection, or with end-stage renal disease (ESRD) using a health care sector perspective with 3% annual discounting. Strategies compared included no testing, tuberculin skin test (TST), interferon gamma release assay (IGRA), confirm positive (initial TST, IGRA only for TST-positive results; both tests positive indicates LTBI), and confirm negative (initial IGRA, then TST for IGRA-negative; any test positive indicates LTBI). All strategies were coupled to treatment with 3 months of self-administered rifapentine and isoniazid. Main Outcomes and Measures: Number needed to test and treat to prevent 1 case of TB reactivation, discounted quality-adjusted life-years (QALYs), discounted lifetime medical costs, and incremental cost-effectiveness ratios (ICERs). Results: Improving health outcomes increased costs, with choice of test dependent on willingness to pay. Strategies ranked by ascending costs and benefits: no testing, confirm positive, TST, IGRA, and confirm negative. The ICERs varied by non-US born patient risk group: patients with no comorbidities, IGRA was likely cost-effective at $83 000/QALY; patients with diabetes, both confirm positive ($53 000/QALY) and IGRA ($120 000/QALY) were likely cost-effective; patients with HIV, confirm negative was clearly preferred ($63 000/QALY); and patients with ESRD, no testing was cost-effective. Increased LTBI prevalence and reduced return for TST reading improved IGRA's relative performance. In 10 000 probabilistic simulations among non-US born patients with no comorbidities, with diabetes, and with HIV, some form of testing was virtually always cost-effective. These simulations highlight the uncertainty of test choice for non-US born patients with no comorbidities and non-US born patients with diabetes, but strategies including IGRA were preferred in over 60% of simulations for all non-US born populations except those with ESRD. Conclusions and Relevance: Testing for and treating LTBI among non-US born residents with and without selected comorbidities is likely cost-effective except among those with ESRD in whom competing risks of death limit benefits. Strategies including IGRA fell below a $100 000/QALY willingness-to-pay threshold for non-US born patients with no comorbidities, patients with diabetes, and patients with HIV.

Methodological considerations for economic modelling of latent tuberculous infection screening in migrants.

Tuberculosis (TB) in migrants from endemic to low-incidence countries results mainly from the reactivation of latent tuberculous infection (LTBI). LTBI screening policies for migrants vary greatly between countries, and the evidence on the cost-effectiveness of the different approaches is weak and heterogeneous. The aim of this review was to assess the methodology used in published economic evaluations of LTBI screening among migrants to identify critical methodological options that must be considered when using modelling to determine value for money from different economic perspectives. Three electronic databases were searched and 10 articles were included. There was considerable variation across this small number of studies with regard to economic perspective, main outcomes, modelling technique, screening options and target populations considered, as well as in parameterisation of the epidemiological situation, test accuracy, efficacy, safety and programme performance. Only one study adopted a societal perspective; others adopted a health care or wider government perspective. Parameters representing the cascade of screening and treating LTBI varied widely, with some studies using highly aspirational scenarios. This review emphasises the need for a more harmonised approach for economic analysis, and better transparency in how policy options and economic perspectives influence methodological choices. Variability is justifiable for some parameters. However, sufficient data are available to standardise others. A societal perspective is ideal, but can be challenging due to limited data. Assumptions about programme performance should be based on empirical data or at least realistic assumptions. Results should be interpreted within specific contexts and policy options, with cautious generalisations.

Taking Costs and Diagnostic Test Accuracy into Account When Designing Prevalence Studies: An Application to Childhood Tuberculosis Prevalence.

BACKGROUND: When planning a study to estimate disease prevalence to a pre-specified precision, it is of interest to minimize total testing cost. This is particularly challenging in the absence of a perfect reference test for the disease because different combinations of imperfect tests need to be considered. We illustrate the problem and a solution by designing a study to estimate the prevalence of childhood tuberculosis in a hospital setting. METHODS: All possible combinations of 3 commonly used tuberculosis tests, including chest X-ray, tuberculin skin test, and a sputum-based test, either culture or Xpert, are considered. For each of the 11 possible test combinations, 3 Bayesian sample size criteria, including average coverage criterion, average length criterion and modified worst outcome criterion, are used to determine the required sample size and total testing cost, taking into consideration prior knowledge about the accuracy of the tests. RESULTS: In some cases, the required sample sizes and total testing costs were both reduced when more tests were used, whereas, in other examples, lower costs are achieved with fewer tests. CONCLUSION: Total testing cost should be formally considered when designing a prevalence study.