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Diagnosi dell’infezione tubercolare
Dott.ssa Marialuisa Bocchino
Dipar4mento di Medicina Clinica e Chirurgia Università degli Studi di Napoli “Federico II”
PL Lin, J Immunol 2010
PJ Cardona, Arch Immunol Ther Exp 2010
Mod.E6
Mycobacterium, spp ESAT-6 CFP-10
M. tuberculosis M. bovis M. africanum M. kansasii M. marinum M. szulgai M. flavescens
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RD-‐1 related an-gens
QFT-‐IT procedure
TS-‐TB procedure
• Epidemiological seQng
• Test characteris4cs
• Technical laboratory exper4se • Clinical seQng
• Targeted popula4on
Low prevalence se6ngs: BeSer sensi4vity and specificity than TST BeSer correla4on with TB exposure Variable concordance with TST in close TB contacts Unknown predic4ve value High prevalence se6ngs: Reduced sensi4vity and specificity Reduced correla4on with TB exposure Good concordance with TST in TB close contacts Unknown predic4ve value Repeated infec-ons, exposure to NTM, effector T cells turnover, T reg cells turnover, host response, mycobacterial strains, technical exper-se, vaccine adop-on
Latent tuberculosis infec-on: IGRA performance
Menzies et al., Ann Intern Med 2008
hSp://www.bcgatlas.org
World Atlas of BCG Policies and Prac-ces
TST sensi4vity
R Diel, Chest 2010
QFT-‐IT sensi4vity
R Diel, Chest 2010
TS-‐TB sensi4vity
R Diel, Chest 2010
R Diel, Chest 2010
IGRA specificity
QFT-‐IT
TS-‐TB
The pooled rate of indeterminate results was low, 2.1% (95% CI, 0.02-‐0.023) for the QFT-‐IT and 3.8% (95% CI, 0.035-‐0.042) for the TS-‐TB, increasing to 4.4% (95% CI, 0.039-‐0.05) and 6.1% (95% CI, 0.052-‐0.071) respec4vely, among immunocompromised hosts.
R Diel, Chest 2010
M Bocchino, Expert Rev Mol Diagn 2009
RN van zyl Smit, PLoS ONE 2009
Boos-ng ü Only one study was performed in a high burden seQng ü Five studies used TS-‐TB, and 6 the QFT-‐IT ü Five studies concluded that boos4ng did not occur ü The effect appears to be more prevalent in individuals already IGRA-‐posi4ve ü The effect seems apparent ager the first 3 days and wanes ager 3 months ü Only a small percentage (2-‐12%) of IGRA-‐nega4ve individuals boost ager a TST ü IGRA tes4ng beSer to be performed before or within 72 hours of the TST
ü General recommenda4ons for use of IGRAs
ü Test selec4on
ü Situa4ons in which IGRA is preferred but a TST is acceptable
(homeless persons, drug-‐users, BCG vaccinated persons)
ü Situa4ons in which a TST is preferred but an IGRA is acceptable
(children aged <5 years)
ü Situa4ons in which either a TST or an IGRA may be used without preference
(close TB contacts, occupa4onal exposure)
ü Situa4ons in which tes4ng with both an IGRA and a TST may be considered
(high suspicion of false-‐nega4ve or false-‐posi4ve results, indeterminate, borderline or invalid results)
ü Medical management ager tes4ng
Updated Guidelines for Using Interferon Gamma Release Assays to Detect Mycobacterium tuberculosis Infec3on -‐-‐-‐ United States, 2010 Recommenda4ons and Reports June 25, 2010 / 59(RR05);1-‐25
Algorithm of all possible outcomes resul-ng from parallel IGRA and TST tes-ng
Lalvani A et al. BMB 2009
Areas for Addi-onal Research
Are IGRAs beSer at predic4ng subsequent ac4ve tuberculosis than TST?
Are persons with discordant TST and IGRA results at increased risk for ac4ve tuberculosis compared with persons with
concordant nega4ve results?Are higher IFN-‐γ responses associated with a greater risk for developing ac4ve tuberculosis?
Do IGRAs perform differently in children than in adults, in those with extrapulmonary versus pulmonary tuberculosis, in those
with HIV infec4on versus those without HIV infec4on, in those recently infected as compared with those infected years earlier,
and in those with latent infec4on as compared with those with ac4ve tuberculosis?
Why do simultaneously performed TST, QFT-‐GIT, QFT-‐G, and T-‐Spot results differ?
Can sensi4vity and specificity of IGRAs be improved by modifica4on in tes4ng methods, applica4on of different interpreta4on
criteria, or inclusion of addi4onal an4gens?
What is the best approach for determining cut points for IGRA interpreta4on, including situa4ons where Nil values are high or
Mitogen values are low?
To what extent does inclusion of a "borderline" interpreta4on improve IGRA accuracy? What causes varia4on in IGRA results
and to what extent?
What magnitude of change in IFN-‐γ response indicates new infec4on?
Ager exposure, how long does it take for an IGRA to become posi4ve?
What is the clinical significance of IGRA reversion?
What methods should be used to monitor IGRA quality?
Is there an associa4on between lymphocyte count and IFN-‐γ response (with or without HIV infec4on)?
What effect does treatment of M. tuberculosis infec4on have on IGRA results?
How do host and bacterial gene4c factors affect IGRA results?
