Post on 03-Jun-2018
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Screening for
Tuberculosis
Screening for
Tuberculosis
Michael Gardam
TB Clinic,
Toronto Western Hospital
Annual risk is not constant
Riskofdevelopingactivedisease
Years after exposure
High Risk PeriodHigh Risk Period
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Risk factors for infection
Exposure Risk factors
Born in high-risk country
Occupation (e.g.healthcare worker)
Serious travel to high-risk country
Close contact of known active case
Age
Immunosuppression (HIV)
Estimated new TB cases (all
forms) per 100 000 population
No estimate
0-24
50-99
300 or more
25-49
100-299
Risk factors for progression
Canadian Standards, 2008
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nfection versus !isease
Latent Infection Active Disease
Burden oforganisms
Low Low-High
Symptoms None None-florid
Transmissibility Never infectious Often infectious ifpulmonary
Mantoux Usually positive Often positive
CXR 95% normal May be abnormal,Infiltrates, cavities
Therapy Optional preventativetherapy
4 drugs pendingsensitivities
TB screening
Warning: skin testing can be confusing"
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Screening guidance
#nl$ screen if $ou plan on doing something%ith the results
f looking for infection or disease, onl$ screen
those that ha&e a reason to be infected
Screening lo% pre&alence populations %ill result in
a high proportion of false positi&e results
Screening modalities
Chest radiograph screening detects'
(cti&e pulmonar$ disease
Those at high risk of de&eloping acti&e disease
Will miss most people with latent infection
Tuberculin skins testing and Interferon
Gamma Release Assays (IGRAs detect'
)atent infection
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Purified Protein !eri&ati&e
aka PP!, Tuberculin
!ifferent formulations used Contains appro*imatel$ + antigens
Man$ antigens are shared bet%een differentm$cobacteria
M tuberculosis comple*
M bovis
!CG strain of M bovis
-n&ironmental m$cobacteria
Contraindications
Se&ere reactions in
the past
Pre&ious documented
positi&e
-*tensi&e skin disease
Recent significant
&iral illness
"ot Contraindications
Pregnanc$
Recent &accination %itha killed &accine
BCG &accination histor$
Pre&iousl$ positi&e butnot documented
Children
Ho% to read a test
Measure induration using the pen techni.ue
n Canada' trans&erse diameter
n the /S, a&erage of the longitudinal and
trans&erse diameters
0 1mm is positi&e if'
2no%n recent contact
Significantl$ immunocompromise
Has fibronodular disease on their chest film
0 3 mm is positi&e for e&er$bod$ else
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Tuberculin skin test measurement
nterobser&er &ariabilit$ 4+51 mm6 ntra7obser&er &ariabilit$ 43587359 mm6
Biologic &ariabilit$ 4:8mm6
A change in up to #mm between tests can
$ust be due to %ariability&
Sensiti&it$ and specificit$
Sensiti&it$ cited as 9;< for latent TBinfection in health$ indi&iduals
!ecreased in immunocompromised
Sensiti&it$ closer to ;< for acti&edisease
Specificit$ influenced b$ BCG&accination, other m$cobacterial
e*posure
Boosting
#ccurs %ith remote BCG, at$pical
m$cobacteria, M. tuberculosis e*posure
Common 4178
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(ge at BCG &accination
and positi&e TSTs
nfanc$' no difference in positi&it$ bet%een&accinated and un&accinated after 1 $ears
Primar$ school' 317+1< remain positi&e after
3 $ears
nduration = 3>mm unlikel$ to be BCG
Iseman, 2000
18mm
Wh$ + step tests?
Perform a + step if'
@ou plan on testing the person again e5g5 atthe time of first hire
@ou %ant to increase the sensiti&it$ as muchas possible
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Con&ersion
!ifferent definitions'A mm' more sensiti&e, less specific
Ma$ be difficult to interpret gi&en &ariabilit$
3 mm' more specific, less sensiti&e
Best interpreted in conunction %ithepidemiolog$
e5g5, healthcare %orker in contact %ith acti&e case
Michael Gardam April 27,2005
Re&ersion
/p to >< of positi&e adults %ill becomenegati&e on repeat testing
More common in adults
More common in those %ith moderate siedinduration
More common in those %ith boosting -speciall$ if boosted after 8 or more serial tests
'ninterpretabletry not to retest
Summar$
Reading and interpreting skin tests is not so
simple5
This %as supposed to be fi*ed b$ nterferon
Gamma Release (ssa$s
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nterferon Gamma Release (ssa$s
4GR(s6
DE7based tests
Gardam et.al. Lancet ID
nterferon7gamma release assa$s
4GR(s6
FuantiE-R#D Gold
-)S(
T7Spot5TB
-)SP#T
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(ntigens used in latest GR(s
T%o M. tuberculosis proteins are used in theassa$s'
-arl$ secreted antigenic target 4-S(T7A6
Culture filtrate protein 3 4CEP736
Compare %ith =+ antigens in Tuberculin
Specific antigens for TB?
-S(T7A and CEP73 are also found in'
M. leprae
Wild t$pe M. bovis 4not the BCG strains6
M. marinum
M. kansasii
M. szulgai
M. flavescens
Reasonably common
in Canada
(d&antages of GR(s
More specific than the TST 4dont react to BCG
and most other non7TB m$cobacteria6
#nl$ 3 &isit re.uired
Do boosting phenomenon T7Spot5TB is more sensiti&e than the TST in
immunocompromised
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Hemodial$sis patients
Passalent et. al., CJASN 2006
!isad&antages
Same general issues as the TST in
immunocompromised i5e5 the$ dont %ork as
%ell
-*pensi&e, often patients must pa$ for them
)imited a&ailabilit$
Ha&e same issues %ith re&ersion as the TST
The risk of de&eloping acti&e TB in the settingof a positi&e GR( is unclear
!iscordant results
TST , GR( I
Secondar$ to BCG or false negati&e GR(?
TST 7, GR(
Poor sensiti&it$ of the TST or false positi&e GR(?
)ou cannot tell with certainty
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!iscordant results in lo% risk, BCG
&accinated population
!iscordant results in moderate or high
risk, BCG &accinated populations
GR( Summar$
(t present, the role for GR(s is relati&el$limited
testing lo% risk populations %ho ha&e recei&edBCG
mmunocompromised populations 4T7Spot5TB6
TST is generall$ the preferred test in Canada
Conclusions
Chest radiograph screening is best as an initial
assessment for pulmonar$ TB
TSTs and GR(s are best for detecting latent
infections
nterpreting TSTs is complicated
GR(s ha&e some ad&antages but are not
panaceas
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