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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?