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TB: The Elispot In The Room Dr Jessica Potter TB Research Registrar Barts Health NHS Trust Overview Latent TB infection (LTBI) Tests for LTBI Interferon Gamma Release Assay (IGRA) IGRA: When to use it, when not to Questions Latent Tuberculosis Infection (LTBI) Asymptomatic/ dormant TB infection. An equilibrium between host and bacillus. Reservoir: 1/3 of the world’s population. ~10% of patients with LTBI go on to develop active disease. Natural History of Tuberculosis Break down of immune control Who’s at risk of LTBI becoming active disease? What is the point in diagnosing LTBI? LTBI is a reservoir of potential active infection LTBI treatment with 3 months of Rifampicin or 6 months of isoniazid reduces your risk of developing active TB in the future How can we test for LTBI? Tuberculin Skin Test - Measures the in-vivo immune response to TB. Type 4 delayed hypersensitivity reaction. T-cells, sensitised by prior infection with tubercle bacilli, NTM or by BCG vaccination are recruited to the skin site and release inflammatory cytokines. Maximum induration seen at 48-72 hours. TST – Pitfalls False positives due to: Previous BCG vaccination. Non-tuberculous mycobacteria Repeat testing Needle injury High dose >1 clinic visit. Operator dependent. 3 days for result. False negatives due to: Immunosuppression Under nutrition Disseminated TB Age – very young and old Malignancy Acute viral infection Sarcoidosis Inteferon Gamma Release Assay Interferon Gamma Release Assay - Measures the ex-vivo cellular immune response to TB RD1 region is different from BCG and codes for MTb specific antigens including ESAT-6 and CFP-10. Therefore IGRA can differentiate between TB infection and previous BCG vaccination. ESAT-6 and CFP-10 are also not found in the majority of NTM. Strong target of Th1 T-cells in M.Tb infection T-Spot vs ELISA In an ideal world we would have tests that: Differentiated between latent and active TB Is reliable in immunocompromised individuals. Predicts risk of disease progression. Allows monitoring of response to treatment So what can IGRA tests tell us? Can IGRA differentiate between latent and active TB infection? Sester M, Sotgiu G, Lange C, et al. Interferon-γ release assays for the diagnosis of active tuberculosis: a systematic review and meta-analysis. Eur Respir J 2011;37:100–11. Can IGRA be used to rule out active TB? Too many false negatives Sester M, Sotgiu G, Lange C, et al. Interferon-γ release assays for the diagnosis of active tuberculosis: a systematic review and metaanalysis. Eur Respir J 2011;37:100–11. Can IGRA be reliably used in immunocompromised individuals? • TB Elispot more sensitive than Quantiferon but still not 100% reliable. • NICE currently recommends a 2-stage approach with TST and IGRA in this group. NICE Recommendations & Guidance IGRA tests can differentiate between LTBI and previous BCG vaccination, TST does not. Testing for LTBI: CD4 < 200: TST + IGRA CD4 >200: IGRA Children <5: TST +/- IGRA New-entrants from high incidence countries 16-35: IGRA Contact screening: IGRA +/- TST Learning Points IGRA is NOT a diagnostic test for active IGRA can be used to test for LTBI in: TB. TB contacts who do not develop signs of active disease. New-entrants who do not have signs of active disease. Individuals who may require immunosuppressive treatment in the future including solid organ transplant recipients. Questions?