Interferon-gamma release assays and TB screening in high-income countries: A cost-effectiveness analysis

Respiratory Epidemiology and Clinical Research Unit, Montreal Chest Institute, McGill University, Montreal, Canada.
The International Journal of Tuberculosis and Lung Disease (Impact Factor: 2.32). 02/2007; 11(1):16-26.
Source: PubMed


Interferon-gamma release assays (IGRA) are now available alternatives to tuberculin skin testing (TST) for detection of latent tuberculosis infection (LTBI). We compared the cost-effectiveness of TST and IGRA in different populations and clinical situations, and with variation of a number of parameters.
Markov modelling was used to compare expected TB cases and costs over 20 years following screening for TB with different strategies among hypothetical cohorts of foreign-born entrants to Canada, or contacts of TB cases. The less expensive commercial IGRA, Quanti-FERON-TB Gold (QFT), was examined. Model inputs were derived from published literature.
For entering immigrants, screening with chest radiograph (CXR) would be the most and QFT the least cost-effective. Sequential screening with TST then QFT was more cost-effective than QFT alone in all scenarios, and more cost-effective than TST alone in selected subgroups. Among close and casual contacts, screening with TST or QFT would be cost saving; savings with TST would be greater than with QFT, except in contacts who were bacille Calmette-Guérin (BCG) vaccinated after infancy.
Screening for LTBI, with TST or QFT, is cost-effective only if the risk of disease is high. The most cost-effective use of QFT is to test TST-positive persons.

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    • "Indeed, our previous work shows that TSTC have a higher whole blood interferon-γ response at baseline than PTST- [15], so it is possible that an IGRA would have distinguished these two groups at baseline. However, the sensitivity [26,27] and cost-effectiveness [28] of IGRAs in TB-endemic settings is still a topic of debate. In addition, the risk score developed by Mandalakas et al. [11] can be used as a proxy for assessing infection, and the authors propose their risk score could be used in lieu of the TST or IGRA. "
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    ABSTRACT: Background Despite sustained exposure to a person with pulmonary tuberculosis (TB), some M. tuberculosis (Mtb) exposed individuals maintain a negative tuberculin skin test (TST). Our objective was to characterize these persistently negative TST (PTST-) individuals and compare them to TST converters (TSTC) and individuals who are TST positive at study enrollment. Methods During a TB household contact study in Kampala, Uganda, PTST-, TSTC, and TST + individuals were identified. PTST- individuals maintained a negative TST over a 2 year observation period despite prolonged exposure to an infectious tuberculosis (TB) case. Epidemiological and clinical characteristics were compared, a risk score developed by another group to capture risk for Mtb infection was computed, and an ordinal regression was performed. Results When analyzed independently, epidemiological risk factors increased in prevalence from PTST- to TSTC to TST+. An ordinal regression model suggested age (p < 0.01), number of windows (p < 0.01) and people (p = 0.07) in the home, and sleeping in the same room (p < 0.01) were associated with PTST- and TSTC. As these factors do not exist in isolation, we examined a risk score, which reflects an accumulation of risk factors. This compound exposure score did not differ significantly between PTST-, TSTC, and TST+, except for the 5–15 age group (p = 0.009). Conclusions Though many individual factors differed across all three groups, an exposure risk score reflecting a collection of risk factors did not differ for PTST-, TSTC and TST + young children and adults. This is the first study to rigorously characterize the epidemiologic risk profile of individuals with persistently negative TSTs despite close exposure to a person with TB. Additional studies are needed to characterize possible epidemiologic and host factors associated with this phenotype.
    Full-text · Article · Jun 2014 · BMC Infectious Diseases
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    • "On the other hand, using the TST + or QFT + decision rule could help clinicians who are worried about missing LTBI cases in high-risk groups, such as HIV/AIDS patients and young children. Such reasoning has been used to support cost-effectiveness analyses of the TST and QFT for diagnosis of LTBI [36]. The Bayesian approach we propose is an improvement over such approaches since it takes into account the joint uncertainty in the sensitivity and specificity parameters of both tests [37]. "
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    ABSTRACT: Background The absence of a gold standard, i.e., a diagnostic reference standard having perfect sensitivity and specificity, is a common problem in clinical practice and in diagnostic research studies. There is a need for methods to estimate the incremental value of a new, imperfect test in this context. Methods We use a Bayesian approach to estimate the probability of the unknown disease status via a latent class model and extend two commonly-used measures of incremental value based on predictive values [difference in the area under the ROC curve (AUC) and integrated discrimination improvement (IDI)] to the context where no gold standard exists. The methods are illustrated using simulated data and applied to the problem of estimating the incremental value of a novel interferon-gamma release assay (IGRA) over the tuberculin skin test (TST) for latent tuberculosis (TB) screening. We also show how to estimate the incremental value of IGRAs when decisions are based on observed test results rather than predictive values. Results We showed that the incremental value is greatest when both sensitivity and specificity of the new test are better and that conditional dependence between the tests reduces the incremental value. The incremental value of the IGRA depends on the sensitivity and specificity of the TST, as well as the prevalence of latent TB, and may thus vary in different populations. Conclusions Even in the absence of a gold standard, incremental value statistics may be estimated and can aid decisions about the practical value of a new diagnostic test.
    Full-text · Article · May 2014 · BMC Medical Research Methodology
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    • "Since the majority of asylum seekers are young adults the presence of LTBI among them would point to a recent contamination. Screening migrants for LTBI and treating those at risk of reactivation has been proven to be effective [4,5]. As most cases of active tuberculosis among asylum seekers occur within 5 years of entering Western countries and are due to the reactivation of a LTBI, screening and preventive treatment of LTBI, may be a complement to the screening for active tuberculosis in destination countries [6]. "
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    ABSTRACT: Background Screening and treatment of latent tuberculosis infection (LTBI) in asylum seekers (AS) may prevent future cases of tuberculosis. As the screening with Interferon Gamma Release Assay (IGRA) is costly, the objective of this study was to assess which factors were associated with LTBI and to define a score allowing the selection of AS with the highest risk of LTBI. Methods In across-sectional study, AS seekers recently arrived in Vaud County, after screening for tuberculosis at the border were offered screening for LTBI with T-SPOT.TB and questionnaire on potentially risk factors. The factors associated with LTBI were analyzed by univariate and multivariate regression. Results Among 393 adult AS, 98 (24.93%) had a positive IGRA response, five of them with active tuberculosis previously undetected. Six factors associated with LTBI were identified in multivariate analysis: origin, travel conditions, marital status, cough, age and prior TB exposure. Their combination leads to a robust LTBI predictive score. Conclusions The prevalence of LTBI and active tuberculosis in AS is high. A predictive score integrating six factors could identify the asylum seekers with the highest risk for LTBI.
    Full-text · Article · Nov 2012 · BMC Infectious Diseases
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