1. Diagnosi
dell’infezione
tubercolare
Dott.ssa Marialuisa Bocchino
Dipar4mento
di
Medicina
Clinica
e
Chirurgia
Università
degli
Studi
di
Napoli
“Federico
II”
11. Mycobacterium, spp
ESAT-6 CFP-10
M. tuberculosis
M. bovis
M. africanum
M. kansasii
M. marinum
M. szulgai
M. flavescens
+
+
+
+
+
+
+
+
+
+
+
+
+
+
RD-‐1
related
an-gens
15.
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
23. 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
25. 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
26.
27.
28.
29.
30.
31.
32.
33.
34. 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
35. Algorithm
of
all
possible
outcomes
resul-ng
from
parallel
IGRA
and
TST
tes-ng
Lalvani
A
et
al.
BMB
2009
36. 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?
