IGRAs: Should they replace the TST in the identification of latent tuberculosis?
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IGRAs: Should they replace the TST in the identification of latent tuberculosis?. Objectives • Describe how interferon-gamma release assays (IGRAs) work. • List three advantages and disadvantages of IGRA in comparison to tuberculin skin testing (TST).

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IGRAs: Should they replace the TST in the identification of latent tuberculosis?

  • Objectives

    • • Describe how interferon-gamma release assays (IGRAs) work.

  • • List three advantages and disadvantages of IGRA in comparison to tuberculin skin testing (TST).

  • • Identify populations where IGRA testing may be of benefit in the management of latent tuberculosis infection.

  • AllenKraut, MD, frcpc

  • Medical Director, Occupational Health WRHA WRHA T8 Forum April 12.2012

    • Conflict of Interest

      • • Received Quantiferon TB Gold in Tube Tubes from Cellestis as part of a research study.


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    • New Technologies - Blood tests

      • • Interferon Gamma Release Assays (IGRAs)

        • • White blood cells in people infected with TB release Gamma interferon

      • •  Detect specific Mycobacterium TB proteins

        • • Less likely to give false positive results

    • • Can not differentiate latent and active disease

    • Some issues with TST

      • •  Difficulty reading test.

      • • 6mm inter reader variability

      • •  Not specific for Mycobacterium Tuberculosis

        • • False +ve with BCG or Atypical Mycobacterium

    • •  Requires two visits days apart for reading

    • • Subject to boosting

    • •  Definition of positive test depends on circumstances

    • Interferon Gamma Release Assays (IGRAs)

      • • Quantiferon-TB Gold In-Tube Assay

        • •  ESAT-6, CFP - 10, TB7.7

        • •  Measure IFN- Gamma ELISA

      • • T-spot.TB Assay

        • •   ESAT-6, CFP - 10

        • • Count spots which are related to the number of cells releasing Gamma Interferon.


    K latent tuberculosis?

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    Blood needs to be

    C

    processed within 8

    hours. Can be

    O KKCSSt

    extended to 32 hours

    by adding a specific reagent

    -

    T-spot.TB assay

    TspotTB

    • PY*      .-

      • Rl • i ■

    IGRAs

    • IGRAs in HCP

      • • Significant discordance is found between TST and IGRA positivity rates in healthcare workers (HCWs),

        • • TST+/IGRA- - BCG vaccinations.

    • •  IGRAs seem to correlate with markers of exposure in HCWs

    • • Serial testing results limited

      • • CCDRVol36 June 2010

    • Advantages

      • •   More specific for Mycobacterium TB.

        • " Atypical mycobacteria

          • • M. koniosii. M siulgoi. and M matmum

      • •   Single patient encounter

    • •   Objective criteria for positive response Disadvantages

      • •   Requires blood draw

      • •   Requires sophisticated equipment

      • •   Elements of processing time sensitive

      • •   Results may not be readily available

      • •   ? Immunosuppressed -Tspot.TB may be better

      • •   Higher direct costs, but may have lower costs if include all required follow up and treatment

    • 6,530 healthcare workers (HCWs) screened for latent tuberculosis infection

      • AS 10 I It U > .crcou-d »iiMJI'l <;i f

    • 25 fold increase in conversion rate using QFT vs TST Direct costs

      • • QFTTB Gold in Tube $436,096

    • • TST $78,360. Indirect costs

      • • confirmatory TSTs, additional chest radiographs, extra nurse assessments, and examinations.

  • Total costs $521,890

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      • Inlrctun Control and Hoipi|alCp«l«niiiloa 2010:11.HIS !>8S


    IGRA result latent tuberculosis?

    ♦ve

    -ve

    TST result

    «ve

    LTBI

    low risk don't treat. High risk treat.

    -ve

    High Risk Treat Low risk ??

    No LTBI

    • IGRA performance in contacts and outbreak investigations

    • •  IGRAs correlate well with surrogate markers of exposure

      • in contact and outbreak settings, but not necessarily better than TST in all populations.

  • •  Correlation between IGRA results and surrogate markers of

    • exposure is better than TST in low incidence settings where BCG has been commonly used; this is not evident in high incidence countries.

  • •  Discordance between TST and IGRAs are almost always

    • found. Concordance levels seem to vary when IGRA and TST cut-off points are changed

    • Are IGRA results constant?

      • • Reversion rates are higher when baseline IFN-y levels are just above the cut-off point and when baseline results are discordant (i.e. TST-/IGRA+).

      • • Reversion rates low when baseline IFN-y levels are high and when baseline results are concordantly positive (TST+/IGRA+).

    • CTS recommendations

      • • Immunocompromised •TSTfirst test

        • • If TST -ve IGRA can be used and if +ve consider treatment

        • • Degree of benefit unknown in TST-ve IGRA+ve.

        • • T Spot .TB may be better in an immunosuppressed population

    • CTS recommendations

      • • IGRAs should not be used in the diagnosis of active TB in adults may be a supplemental aide in dx in children.

      • • Contacts-

        • • IGRAs can be used to confirm +ve TSTS

      • • IGRAS or TSTs can be used to identify +vesforTXforLTBI

    • International Guidelines

  • Clin Microbiol Infect 2011; 17: 806-814

    • •   33 guidelines and position papers from 25 countries and two supranational organizations.

    • •   The results show considerable diversity in the recommendations on IGRAs

      • •   (i) two-step approach of tuberculin skin test (TST) first, followed by IGRA either when

        • •   the TST is negative (to increase sensitivity, mainly in immunocompromised individuals).

        • •   or when the TST is positive (to increase specificity, mainly In BCG vaccinated individuals);

      • •   (ii) Either TST or IGRA, but not both;

      • •   (iii) IGRA and TST together (to increase sensitivity),

      • •   (iv) IGRA only, replacing the TST.

    • •   Overall, the use of IGRAs is increasingly recommended,


  • Clin Microbiol Infect 2011; 17:806-814

    • •  Most of the current guidelines do not use objective. transparent methods to grade evidence and recommendations, and

    • •  Do not disclose conflicts of interests

    • •  future IGRA guidelines must aim to be transparent, evidence-basea. periodically updated, and free of financial conflicts and industry involvement.

  • Conclusions

    • IGRAs will help identify who needs treatment for LTBI

    • Exact role need to be determined

      • • Very helpful in low risk TST +ve BCG population

    • •  ? immunosuppressed population

  • •  Useful for population that is hard to follow Definition of positive reaction may have to vary depending on situation of testing


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