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Evaluating latent tuberculosis infection diagnostics using latent class analysis
  1. Jason E Stout1,
  2. Yanjue Wu2,
  3. Christine S Ho3,
  4. April C Pettit4,
  5. Pei-Jean Feng3,
  6. Dolly J Katz3,
  7. Smita Ghosh3,
  8. Thara Venkatappa3,
  9. Ruiyan Luo5
  10. on behalf of the Tuberculosis Epidemiologic Studies Consortium
    1. 1 Division of Infectious Diseases and International Health, Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA
    2. 2 Northrop Grumman, McLean, Virginia, USA
    3. 3 Division of Tuberculosis Elimination, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
    4. 4 Division of Infectious Diseases, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
    5. 5 Department of Epidemiology and Biostatistics, Georgia State University, School of Public Health, Atlanta, Georgia, USA
    1. Correspondence to Dr Jason E Stout, Division of Infectious Diseases and International Health, Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA; stout002{at}mc.duke.edu

    Abstract

    Background Lack of a gold standard for latent TB infection has precluded direct measurement of test characteristics of the tuberculin skin test and interferon-γ release assays (QuantiFERON Gold In-Tube and T-SPOT.TB).

    Objective We estimated test sensitivity/specificity and latent TB infection prevalence in a prospective, US-based cohort of 10 740 participants at high risk for latent infection.

    Methods Bayesian latent class analysis was used to estimate test sensitivity/specificity and latent TB infection prevalence among subgroups based on age, foreign birth outside the USA and HIV infection.

    Results Latent TB infection prevalence varied from 4.0% among foreign-born, HIV-seronegative persons aged <5 years to 34.0% among foreign-born, HIV-seronegative persons aged ≥5 years. Test sensitivity ranged from 45.8% for the T-SPOT.TB among foreign-born, HIV-seropositive persons aged ≥5 years to 80.7% for the tuberculin skin test among foreign-born, HIV-seronegative persons aged ≥5 years. The skin test was less specific than either interferon-γ release assay, particularly among foreign-born populations (eg, the skin test had 70.0% specificity among foreign-born, HIV-seronegative persons aged ≥5 years vs 98.5% and 99.3% specificity for the QuantiFERON and T-SPOT.TB, respectively). The tuberculin skin test’s positive predictive value ranged from 10.0% among foreign-born children aged <5 years to 69.2% among foreign-born, HIV-seropositive persons aged ≥5 years; the positive predictive values of the QuantiFERON (41.4%) and T-SPOT.TB (77.5%) were also low among US-born, HIV-seropositive persons aged ≥5 years.

    Conclusions These data reinforce guidelines preferring interferon-γ release assays for foreign-born populations and recommending against screening populations at low risk for latent TB infection.

    Trial registration number NCT01622140.

    • tuberculosis
    • clinical epidemiology
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    Footnotes

    • Contributors JES designed the study, performed the analysis, drafted the manuscript and approved the final version. YW, CSH, ACP, P-JF, DJK and SG participated in study design and analysis, revised the manuscript for critically important content and approved the final version. TV participated in study design, revised the manuscript for critically important content and approved the final version. RL participated in the analysis, revised the manuscript for critically important content and approved the final version.

    • Funding The study was funded by a contract with the Centers for Disease Control and Prevention. Support for the analysis was also provided by a voucher from Duke Research Computing. References in this manuscript to any specific commercial products, process, service, manufacturer or company does not constitute its endorsement or recommendation by the US Government or the Centers for Disease Control and Prevention.

    • Disclaimer The findings and conclusions are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention.

    • Competing interests None declared.

    • Patient consent Not required.

    • Ethics approval The study was approved by the Centers for Disease Control and Prevention Institutional Review Board (IRB) and by IRBs at those sites that did not defer to the CDC IRB.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Collaborators California Department of Public Health (Richmond): Jennifer Flood, Lisa Pascopella (includes San Francisco Department of Public Health: Julie Higashi; County of San Diego Health and Human Services Agency: Marisa Moore (CDC); and University of California San Diego Antiviral Research Center: Richard Garfein and Constance Benson); Denver (CO) Health and Hospital Authority: Robert Belknap and Randall Reves; Duke University (Durham, North Carolina): Jason Stout (includes Carolinas Medical Center (Charlotte, North Carolina): Amina Ahmed; Vanderbilt University Medical Center (Nashville, Tennessee): Timothy Sterling and April Pettit; Wake County Human Services (Raleigh, North Carolina): Jason Stout); Emory University (Atlanta): Henry M. Blumberg (includes DeKalb County Board of Health: Alawode Oladele); University of Florida (Gainesville): Michael Lauzardo and Marie Nancy Séraphin; Hawaii Department of Health (Honolulu): Richard Brostrom; Maricopa County Department of Public Health (Phoenix, Arizona): Renuka Khurana; Maryland Department of Health (Baltimore): Wendy Cronin and Susan Dorman; Public Health—Seattle and King County: Masahiro Narita and David Horne; University of North Texas Health Science Center (Fort Worth): Thaddeus Miller.

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