Transcript Slide 1
IGRAs: Should they replace the TST in the identification of latent tuber Objectives • Describe how interferon-gamma release assays (IGRAs) work. • List three advantages and disadvantages of IGRA in comparison to • Identify populations where IGRA testing may be of benefit in the m 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. 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 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 • 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. ■ i • [:i,i | v, .o' <«0 NO0J!*»" ndulemi nale" »0 35 lll'mi ami lK1 o( Nil Any MO <0 35iU'.tiIo-<2SSoINi iOi 58 0 <0 35 IU rvi o- <25S d Ni <05 >B0 Any Arty SJVSSJff*"* T-spot.TB assay TspotTB K A *-!.-*...*..•«•• ------_. Y Q-- • n«-*i«*.«. Blood needs to be C processed within 8 hours. Can be extended to 32 hours by adding a specific reagent O KKCSSt - PY* .- Rl • i ■ IGRAs IGRAs in HCP Advantages • More specific for Mycobacterium TB. • Significant discordance is found between TST and IGRA positivity rates in h " Atypical mycobacteria • M. koniosii. M siulgoi. and M matmum • TST+/IGRA- - BCG vaccinations. • Single patient encounter • Objective criteria for positive response Disadvantages • Requires blood draw • IGRAs seem to correlate with markers of exposure in HCWs • Serial testing results limited • Requires sophisticated equipment • Elements of processing time sensitive • CCDRVol36 June 2010 • 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 :»^r-~u>cb>Qn <-ii • TST $78,360. Indirect costs IIM h(«of> F"«>n»cl • confirmatory TSTs, additional chest radiographs, extra nurse assessment I 13 (idiimcti liw folk ixctoimoithfji i-tun (Kc»cfliJi iKriiuinolpio'tivcJ I lciicd«ilh ISI I (Ncjjlivcl ll'.i.mvcl IDfdncK Inlrctun Control and Hoipi|alCp«l«niiiloa 2010:11.HIS !>8S Total costs $521,890 IGRA performance in contacts and outbreak investigatio Are IGRA results constant? • IGRAs correlate well with surrogate markers of exposure in contact and outbreak settings, but not necessarily better than TST in all populations. • Reversion rates are higher when baseline IFN-y levels are just above the cut-off point and when baseline results are discordant • Correlation between IGRA results and surrogate markers of • Reversion rates low when baseline IFN-y levels are high and when baseline results are concordantly positive (TST+/IGRA+). exposure is better than TST in low incidence settings where BCG has been commonly used; this is not evident in h • Discordance between TST and IGRAs are almost always found. Concordance levels seem to vary when IGRA and TST cut-off points are changed CTS recommendations CTS recommendations • Immunocompromised •TSTfirst • IGRAs should not be used in the diagnosis of active TB in adults may be a supplemental aidetest in dx in children. • If TST -ve IGRA can be used and if +ve consider treatment • Contacts• IGRAs can be used to confirm +ve TSTS • IGRAS or TSTs can be used to identify +vesforTXforLTBI • Degree of benefit unknown in TST-ve IGRA+ve. • T Spot .TB may be better in an immunosuppressed population International Guidelines Clin Microbiol Infect 2011; 17: 806-814 IGRA result • 33 guidelines and position papers from 25 countries and two supranational organizations. • The results show considerable diversity in the recommendations on IGRAs ♦ve -ve • (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); TST result «ve LTBI low risk don't treat. High risk treat. • (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, -ve High Risk Treat Low risk ?? No LTBI International Guidelines Clin Microbiol Infect 2011; 17:806-814 Conclusions IGRAs will help identify • Most of the current guidelines do not use objective. transparent methods to grade evidence and recommendations, and who needs treatment for LTBI • Do not disclose conflicts of interests • Exact role need to be determined future IGRA guidelines must aim to be transparent, evidence-basea. periodically updated, and free of financial conflicts and industry involvement. • Very helpful in low risk TST +ve BCG population • ? immunosuppressed population • Useful for population that is hard to follow Definition of positive reaction m