Screening for Tuberculosis

Michael Gardam TB Clinic, Toronto Western Hospital

Annual risk is not constant

Risk of developing active disease

High Risk Period

Years after exposure

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)

No estimate 0-24 25-49 50-99 100-299 300 or more Estimated new TB cases (all forms) per 100 000 population

Risk factors for progression

Canadian Standards, 2008

nfection versus !isease

Latent Infection
Burden of organisms Symptoms Low

Active Disease
Low-High

None

None-florid Often infectious if pulmonary Often positive May be abnormal, Infiltrates, cavities 4 drugs pending sensitivities

Transmissibility Never infectious

Mantoux CXR

Usually positive 95% normal

Therapy

Optional preventative therapy

TB screening

Warning: skin testing can be confusing"

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

Purified Protein !eri&ati&e aka PP!, Tuberculin

!ifferent formulations used Contains appro*imatel$ +,, antigens Man$ antigens are shared bet%een different m$cobacteria
M tuberculosis comple* M bovis !CG strain of M bovis -n&ironmental m$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 %ith a killed &accine BCG &accination histor$ Pre&iousl$ positi&e but not 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

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 TB infection in health$ indi&iduals
!ecreased in immunocompromised

Sensiti&it$ closer to ;,< for acti&e disease 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,<6
#lder indi&iduals Ma*imal if inter&al bet%een 3 and 1 %eeks

Partiall$ corrected for b$ +7step testing but can ha&e continued boosting
BCG:3 $ear of age

(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

18mm

Iseman, 2000

Wh$ + step tests?

Perform a + step if'
@ou plan on testing the person again e5g5 at the time of first hire @ou %ant to increase the sensiti&it$ as much as possible

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 conBunction %ith epidemiolog$

e5g5, healthcare %orker in contact %ith acti&e case

Re&ersion
/p to >< of positi&e adults %ill become negati&e on repeat testing
More common in adults More common in those %ith moderate siCed induration More common in those %ith boosting
-speciall$ if boosted after 8 or more serial tests

'ninterpretable((try not to retest

Michael Gardam April 27,2005

Summar$
Reading and interpreting skin tests is not so simple5 This %as supposed to be fi*ed b$ nterferon Gamma Release (ssa$s

nterferon Gamma Release (ssa$s 4 GR(s6

DE7based tests

Gardam et.al. Lancet ID

nterferon7gamma release assa$s 4 GR(s6

FuantiE-R#D Gold
-) S(

T7Spot5TB
-) SP#T

(ntigens used in latest GR(s

T%o M. tuberculosis proteins are used in the assa$s'
-arl$ secreted antigenic target 4-S(T7A6 Culture filtrate protein 3, 4CEP73,6

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 Reasonably common M. szulgai in Canada M. flavescens

(d&antages of GR(s
More specific than the TST 4donGt 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$ donGt %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 setting of a positi&e GR( is unclear

!iscordant results
TST H, GR( I
Secondar$ to BCG or false negati&e GR(?

TST 7, GR( H
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&ed BCG 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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