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      Cost-effectiveness of Latent Tuberculosis Infection Screening before Immigration to Low-Incidence Countries

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          Abstract

          Prospective migrants to countries where the incidence of tuberculosis (TB) is low (low-incidence countries) receive TB screening; however, screening for latent TB infection (LTBI) before immigration is rare. We evaluated the cost-effectiveness of mandated and sponsored preimmigration LTBI screening for migrants to low-incidence countries. We used discrete event simulation to model preimmigration LTBI screening coupled with postarrival follow-up and treatment for those who test positive. Preimmigration interferon-gamma release assay screening and postarrival rifampin treatment was preferred in deterministic analysis. We calculated cost per quality-adjusted life-year gained for migrants from countries with different TB incidences. Our analysis provides evidence of the cost-effectiveness of preimmigration LTBI screening for migrants to low-incidence countries. Coupled with research on sustainability, acceptability, and program implementation, these results can inform policy decisions.

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          Most cited references32

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          Systematic review: T-cell-based assays for the diagnosis of latent tuberculosis infection: an update.

          Interferon-gamma-release assays (IGRAs) are alternatives to the tuberculin skin test (TST). A recent meta-analysis showed that IGRAs have high specificity, even among populations that have received bacille Calmette-Guérin (BCG) vaccination. Sensitivity was suboptimal for TST and IGRAs. To incorporate newly reported evidence from 20 studies into an updated meta-analysis on the sensitivity and specificity of IGRAs. PubMed was searched through 31 March 2008, and citations of all original articles, guidelines, and reviews for studies published in English were reviewed. Studies that evaluated QuantiFERON-TB Gold, QuantiFERON-TB Gold In-Tube (both from Cellestis, Victoria, Australia), and T-SPOT.TB (Oxford Immunotec, Oxford, United Kingdom) or its precommercial ELISpot version, when data on the commercial version were lacking. For assessing sensitivity, the study sample had to have microbiologically confirmed active tuberculosis. For assessing specificity, the sample had to comprise healthy, low-risk individuals without known exposure to tuberculosis. Studies with fewer than 10 participants and those that included only immunocompromised participants were excluded. One reviewer abstracted data on participant characteristics, test characteristics, and test performance from 38 studies; these data were double-checked by a second reviewer. The original investigators were contacted for additional information when necessary. A fixed-effects meta-analysis with correction for overdispersion was done to pool data within prespecified subgroups. The pooled sensitivity was 78% (95% CI, 73% to 82%) for QuantiFERON-TB Gold, 70% (CI, 63% to 78%) for QuantiFERON-TB Gold In-Tube, and 90% (CI, 86% to 93%) for T-SPOT.TB. The pooled specificity for both QuantiFERON tests was 99% among non-BCG-vaccinated participants (CI, 98% to 100%) and 96% (CI, 94% to 98%) among BCG-vaccinated participants. The pooled specificity of T-SPOT.TB (including its precommercial ELISpot version) was 93% (CI, 86% to 100%). Tuberculin skin test results were heterogeneous, but specificity in non-BCG-vaccinated participants was consistently high (97% [CI, 95% to 99%]). Most studies were small and had limitations, including no gold standard for diagnosing latent tuberculosis and variable TST methods and cutoff values. Data on the specificity of the commercial T-SPOT.TB assay were limited. The IGRAs, especially QuantiFERON-TB Gold and QuantiFERON-TB Gold In-Tube, have excellent specificity that is unaffected by BCG vaccination. Tuberculin skin test specificity is high in non-BCG-vaccinated populations but low and variable in BCG-vaccinated populations. Sensitivity of IGRAs and TST is not consistent across tests and populations, but T-SPOT.TB appears to be more sensitive than both QuantiFERON tests and TST.
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            Meta-analysis: new tests for the diagnosis of latent tuberculosis infection: areas of uncertainty and recommendations for research.

            Until recently, the tuberculin skin test was the only test for detecting latent tuberculosis (TB) infection, but 2 ex vivo interferon-gamma release assays (IGRAs) are now commercially licensed. To estimate sensitivity, specificity, and reproducibility of IGRAs (commercial or research versions of QuantiFERON [QFT] and Elispot) for diagnosing latent TB infection in healthy and immune-suppressed persons. The authors searched MEDLINE and reviewed citations of all original articles and reviews for studies published in English. Studies had evaluated IGRAs using Mycobacterium tuberculosis-specific antigens (RD1 antigens) and overnight (16- to 24-h) incubation times. Reference standards had to be clearly defined without knowledge of test results. DATA EXTRACTION AND QUALITY ASSESSMENT: Specific criteria for quality assessment were developed for sensitivity, specificity, and reproducibility. When newly diagnosed active TB was used as a surrogate for latent TB infection, sensitivity of all tests was suboptimal, although it was higher with Elispot. No test distinguishes active TB from latent TB. Sensitivity of the tuberculin skin test and IGRAs was similar in persons who were categorized into clinical gradients of exposure. Pooled specificity was 97.7% (95% CI, 96% to 99%) and 92.5% (CI, 86% to 99%) for QFT and for Elispot, respectively. Both assays were more specific than the tuberculin skin test in samples vaccinated with bacille Calmette-Guérin. Elispot was more sensitive than the tuberculin skin test in 3 studies of immune-compromised samples. Discordant tuberculin skin test and IGRA reactions were frequent and largely unexplained, although some may be related to varied definitions of positive test results. Reversion of IGRA results from positive to negative was common in 2 studies in which it was assessed. Most studies used cross-sectional designs with the inherent limitation of no gold standard for latent TB infection, and most involved small samples with a widely varying likelihood of true-positive and false-positive test results. There is insufficient evidence on IGRA performance in children, immune-compromised persons, and the elderly. New IGRAs show considerable promise and have excellent specificity. Additional studies are needed to better define their performance in high-risk populations and in serial testing. Longitudinal studies are needed to define the predictive value of IGRAs.
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              The cascade of care in diagnosis and treatment of latent tuberculosis infection: a systematic review and meta-analysis.

              WHO estimates that a third of the world's population has latent tuberculosis infection and that less than 5% of those infected are diagnosed and treated to prevent tuberculosis. We aimed to systematically review studies that report the steps from initial tuberculosis screening through to treatment for latent tuberculosis infection, which we call the latent tuberculosis cascade of care. We specifically aimed to assess the number of people lost at each stage of the cascade.
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                Author and article information

                Journal
                Emerg Infect Dis
                Emerging Infect. Dis
                EID
                Emerging Infectious Diseases
                Centers for Disease Control and Prevention
                1080-6040
                1080-6059
                April 2019
                : 25
                : 4
                : 661-671
                Affiliations
                [1]University of British Columbia, Vancouver, British Columbia, Canada (J.R. Campbell, J.C. Johnston, V.J. Cook, M. Sadatsafavi, R.K. Elwood, F. Marra);
                [2]British Columbia Centre for Disease Control, Vancouver (J.C. Johnston, V.J. Cook, R.K. Elwood)
                Author notes
                Address for correspondence: Fawziah Marra, University of British Columbia, 2405 Wesbrook Mall, Vancouver, BC V6T 1Z3, Canada; email: fawziah@ 123456mail.ubc.ca
                Article
                17-1630
                10.3201/eid2504.171630
                6433018
                30882302
                28b063c6-3207-412f-bbdc-798a3f418f3a
                History
                Categories
                Research
                Research
                Cost-effectiveness of Latent Tuberculosis Infection Screening before Immigration to Low-Incidence Countries

                Infectious disease & Microbiology
                tuberculosis,latent tuberculosis infection,tuberculosis and other mycobacteria,mass screening,cost–utility analysis,cost-effectiveness analysis,tuberculin test,interferon gamma release tests,migrants,immigration,canada,bacteria

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