WEB SEMINAR: Pediatric TB · 27-06-2008  · Web Seminar. Pediatric TB. Kim Connelly Smith, MD, MPH . June 27, 2008 . 1 . Childhood TuberculosisChildhood Tuberculosis . Kim Connelly

Web Seminar

Pediatric TB Kim Connelly Smith, MD, MPH

June 27, 2008

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Childhood TuberculosisChildhood Tuberculosis

Kim Connelly SmKim Connelly Smithith MD, MPHMD, MPH

OUTLOUTLINEINE ••Stages oStages off tuberculosistuberculosis ••DiDiagnosagnosttiicc chchallenallenggeses ••DiDiffefferenrenceces ofs of didiseasesease ooff pediatric TBpediatric TB

inin chchildrenildren anand adud adullttss ••New diagnoNew diagnosticstic testesttss && researresearchch ••5 clin5 clinical cases inical cases intterspersederspersed ••Time for questions atTime for questions at thethe endend

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Stages of TuberculosisStages of Tuberculosis

Exposure to Contagious Adult with

Pulmonary Disease

Latent TB Infection LTBI

Adult Active TB Disease

Child Active TB Disease

20 30%

5 10% Risk varies by age

5 50%

Household contacts

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Percent Risk of Disease by AgePercent Risk of Disease by Age

3030--50% lifetime50% lifetimeHIV Infected AdultsHIV Infected Adults++

55-10% lifetime risk10% lifetime riskHealthy AdultsHealthy Adults

16%16%1111 – 15 years*15 years*

2%2%66 – 10 years*10 years*

24%24%11 –– 5 years*5 years*

43%43%BirthBirth –– 1 year*1 year*

Risk of Active TBRisk of Active TBAge at InfectionAge at Infection

*Miller, Tuberculosis in Children Little Brown, Boston, 1963

+WHO, 2004

Risk of Progression to TB Disease by AgeRisk of Progression to TB Disease by Age

Age @ primary infectioAge @ primary infectionn Risk of DiseaseRisk of Disease �� BirthBirth-1212monthsmonths DiseaseDisease 50%50%

PulmoPulmonnary Disary Dis 3030-40%40% Miliary or TBMMiliary or TBM 1010--20%20%

�� 11-2 year2 yearss DiseaseDisease 2020--25%25% 75%75%PulmoPulmonnary Disary Dis

Miliary of TBMMiliary of TBM 22-5%5%

Marais BJ. Int J Tuberc Lung Dis 2004;8:392-402

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Daycare ExposureDaycare Exposure

Daycare ExposureDaycare Exposure

�� Index case, teacher assistant withIndex case, teacher assistant with AFB smear positive pulmonaryAFB smear positive pulmonary disease and cough for 6 weeksdisease and cough for 6 weeks

�� 135 children < 5 years of age, plus135 children < 5 years of age, plus adult staff members exposedadult staff members exposed

¾¾ Who is at risk?Who is at risk? ¾¾ Who needs TST?Who needs TST? ¾¾ Who needs CXR?Who needs CXR? ¾¾ Who needs treatment?Who needs treatment?

Smith, KC. Southern Medical Journal 93(9):877-880, 2000

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Daycare Exposure ManagementDaycare Exposure Management

��Who iWho iss at riat risskk?? •• ChildChildren aren anndd staffstaff

��Who needsWho needs TTSST?T? •• EveryoEveryonene wwiith sith signifgnifiiccant conant conttactact wwiith soth soururcece cacasese

��Who needsWho needs CCXXR?R? •• AlAll cl chhiilldredrenn lelessss thathann 55 yearsyears of age evenof age even ifif TST nTST neegatgatiiveve •• AnyAny coconnttaaccts wts wiithth popossiitivtivee TSTSTT ((>> 5mm)5mm)

��Who needsWho needs treatment?treatment? •• LTBI (poLTBI (possiittiivvee TST >5TST >5mm amm annd nord normmalal CXRCXR)) ININH for 9H for 9 monthsmonths •• ExpoExposedsed chchilildrdren leen lessss thathann 55 yearyears of age ns of age need Ieed INNH wiH windondoww

propprophylahylaxis forxis for 3 month3 monthss

�� FFoollollow uw upp?? •• RReepeat TSpeat TST 3 moT 3 months after exponths after exposuresure •• If negative anIf negative andd contactcontact brokbroken,en, stostopp IINNH prH prophyophylaxislaxis

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TB Prevention After ExposureTB Prevention After Exposure �� HouseholHousehold cod contact wintact with contagith contagiousous

personperson ¾¾ TTeeeenn oorr adadulultt wwiitthh pupulmolmonnaryary TTBB didiseseasasee ¾¾ UUsuasuallylly >> 4 hours4 hours of coof contantacctt

�� IInnititiaial Tl TSSTT nneeggaattiiveve �� WiWindndow periow perioodd for TSTfor TST coconversinversionon (2(2-12 we12 weeekkss))

�� CXR andCXR and physiphysiccalal exam nexam normaormall �� INHINH pprropophyhylalaxxiis recommendeds recommended::

¾¾ FoForr cchihilldrdreenn << 4 yrs4 yrs of ageof age ¾¾ IImmummunosunosuppreppresssseedd patpatiienentsts ¾¾ PatienPatients ots on tun tumomor necror necrossis factois factorr-alalpphhaa

bloblocckerkerss ¾¾ May prMay preventevent prprogreogressssioion to dn to diiseaseasse de duuriringng

wiwindow pndow peeriodriod �� RepRepeat TSeat TST 2T 2-3 months after exposure3 months after exposure �� May stop INHMay stop INH iiff 22ndnd TSTST neT negatigative <5mve <5mmm

inin immuimmunoconocompetentmpetent patipatientsents

Preventable CasePreventable Case

With permission

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�� 15 mo old15 mo old

Pediatric TB Case a Missed OpportunityPediatric TB Case a Missed Opportunity

•• 10 days fussiness & decreased appetite10 days fussiness & decreased appetite •• 3 days in3 days inability tability too walk or sit upwalk or sit up •• CSF: 96 WBC (NL <7), 72%CSF: 96 WBC (NL <7), 72% LyLymphsmphs,,

198 Protein (NL <45)198 Protein (NL <45) •• Diagnosis: TB meningitisDiagnosis: TB meningitis

�� Family historyFamily history •• Mom with pulmMom with pulmonaryonary TBTB diadiaggnosednosed 55 momo

earlier onearlier on appropriappropriate treatate treatmmentent •• Dad diagnDad diagnoosed withsed with LTBI onLTBI on INHINH •• BBaaby initiaby initial Tl TSSTT 00mmmm @ 10 months of age@ 10 months of age ¾¾no CXRno CXR ¾¾no treatmno treatmentent ¾¾lostlost ttoo follow upfollow up

OutcomeOutcome Child treated withChild treated with RIPERIPE, completed 12 m, completed 12 moonthsnths��

�� Steroids for 1 mSteroids for 1 moonth with 2nth with 2-3 week taper t3 week taper too decrease CNS infladecrease CNS inflammationmmation Developed seizuDeveloped seizurres and hyes and hydrodrocceepphahalolousus rreequirquiringing��

VP shuntVP shunt �� Otherwise didOtherwise did well with nwell with noormal neurologicrmal neurologic

examinatiexaminatioonn and develand develoopmentpment �� Case potentially pCase potentially prreventable if treatedeventable if treated withwith

window prophylaxis when parent diagnosedwindow prophylaxis when parent diagnosed

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Differences InDifferences In Adult and Pediatric TBAdult and Pediatric TB

Reactivation DiseaseReactivation Disease OccursOccurs yeyearsars afafteterr��

prprimaimarry infy infeeccttioionn �� TypicalTypical of adultof adult

diseasedisease �� OccasiOccasionaonally seenlly seen inin

��

teensteens OftenOften cavitary diseasecavitary disease

�� High numHigh numbers ofbers of

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organiorganisms (AFB +)sms (AFB +) Usually symptomaticUsually symptomatic and contagiousand contagious

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Primary DiseasePrimary Disease

�� Typical of childhood TTypical of childhood TBB �� Usually not cavitaryUsually not cavitary �� Most common xMost common x--ray: pulmoray: pulmonnararyy

infiltrate with or without hilarinfiltrate with or without hilar adenopathyadenopathy �� Low numbers of organismsLow numbers of organisms ¾¾AFB smears negatiAFB smears negative inve in 95% of cases95% of cases ¾¾Culture nCulture neegative igative inn 60% of cases60% of cases

�� Not contNot contagiagioous in childus in children < 12 yren < 12 yrrss �� Often asymptomOften asymptomatic (50%)atic (50%)

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Adult TAdult TBB DiseaseDisease

Pulmonary Extrapulmonary

85% Pulmonary

15% Extrapulmonary

CDC

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Adult Extrapulmonary TB Disease (15%)Adult Extrapulmonary TB Disease (15%)

Lymphatic Pleural GU Other Bone/Joint Miliary Meningeal

23% Pleural

25% Lymphatic

16% GU

13% Other

10% Bone/Joint

9% Miliary

4% Meningeal

CDC

Pediatric TB DiseasePediatric TB Disease

Pulmonary Extrapulmonary75%

Pulmonary

25% Extrapulmonary

CDC

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Extrapulmonary TB DiseaseExtrapulmonary TB Disease in Children (25%)in Children (25%)

Lymphatic Bone/Joint Other Miliary Pleural Meningeal

6% Pleural

67% Lymphatic

5% Other

4% Bone/Joint

5% Miliary

14% Meningeal

CDC

*Feigin & Cherry, Text of Pedi ID

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Unique Challenges of TB in ChildrenUnique Challenges of TB in Children �� More difficultMore difficult

diagnosisdiagnosis �� Nonspecific signsNonspecific signs

and symptomsand symptoms �� Fewer mycobacteriaFewer mycobacteria �� Fewer positiveFewer positive

bacteriologic testsbacteriologic tests �� Increases risk ofIncreases risk of

progression to activeprogression to active diseasedisease

�� Higher risk ofHigher risk of extrapulmonary andextrapulmonary and TB meningitisTB meningitis

LymphadenopathyLymphadenopathy

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Clinical CaseClinical Case Cervical LymphadenopathyCervical Lymphadenopathy

�� 8 yr old8 yr old with cewith cervicrvicalal lymphadenopathylymphadenopathy

�� HistoryHistory:: ¾¾ LANLAN forfor 3 m3 moontnthshs ¾¾ PMHxPMHx: Healt: Healthhyy

¾¾ BCG vacciBCG vaccinene at biat birthrth ¾¾ TB skinTB skin test 15 mmtest 15 mm

�� Physical ExPhysical Exam:am: ¾¾ 3 cm a3 cm annteterior cerior cervical LANrvical LAN ¾¾ 1.5 cm1.5 cm susupraclavpraclaviicucularlar

llyymphadenopathymphadenopathy �� CXR:CXR: ¾¾ HiHilar Llar LAAN,N, no inno inffiltiltratrateess

�� Is this TBIs this TB disease?disease? �� WWhhaatt eellssee cocoululd id itt bebe??

Hilar & Cervical LymphadenopathyHilar & Cervical Lymphadenopathy

��DiDifferefferentiantiall DxDx ¾¾ TuberculosisTuberculosis ¾¾NonNon TB mTB myycobacteriacobacteria

(NTM)(NTM) ¾¾ Lymphoma/LeukemiaLymphoma/Leukemia ¾¾HIVHIV ¾¾OtherOther caucausseses

�� Diagnostic testsDiagnostic tests ¾¾BiBiopsy (Fopsy (FNA or surgicalNA or surgical

for culture and path)for culture and path) ¾¾ InterferonInterferon γγ BBlloodood ttestest

fofor TB infectior TB infectionn

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ResultsResults

�� FineFine neeneedle aspirate of nodle aspirate of node:de: ¾¾ Pathology: lymphoma,Pathology: lymphoma, no TBno TB by cby cuulture orlture or microscopymicroscopy

�� InterferonInterferon γγ BlBlood test food test foorr TTBB ¾¾ PoPosisititiveve ¾¾ DDiiagnagnooststicic for latfor latentent TTBB ininffeectction or diseaseion or disease

�� Diagnoses:Diagnoses: ¾¾ LTBI (TB lLTBI (TB lyymphmph node dnode diiseasesease ususualualllyy lloocalicalized)zed)

ANDAND ¾¾ LymphomaLymphoma

�� Treatment:Treatment: ¾¾ CChhemoemoththeerarappyy ffoor lyr lympmphhoomama AANNDD ¾¾ INH daiINH daillyy for 9 mofor 9 montnthshs forfor LTBILTBI

¾¾ consiconsidder proler prolongedonged treatmtreatmentent duriduringng iimmunosuppresmmunosuppresiionon

Diagnosis for TB in ChildrenDiagnosis for TB in Children �� GoGold Standardld Standard –

PoPossiittiiveve TTB CB Cuullttururee OR,OR, Clinical DiagnClinical Diagnoosis:sis: �� AbnormalAbnormal CXR,CXR, lablabooratratoory,ry,

or phor physical examinysical examinationation consistent with TBconsistent with TB ANDAND 1 or more of the following:1 or more of the following: ¾¾ PoPositive tubsitive tubeercrculin skinulin skin testtest ¾¾ ContagiContagioouuss aduladultt sosoururccee

casecase identifiedidentified ¾¾ CClinlinicaicall coucourrsese conconssististeenntt

with TB diseasewith TB disease ¾¾ ImprovemeImprovemennt ot onn TBTB therapytherapy

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AFB smeAFB smeaars and Cultrs and Cultures inures in ChildreChildren and Infan and Infantsnts

¾¾AFB smeAFB smeaar usualr usualllyy negativenegative ¾¾ In 95% of patients <In 95% of patients <112 years of age2 years of age

¾¾Low yLow yiieelld od onn TBTB culturculturee ¾¾ OnlOnlyy 40% p40% poosisititive ive inn cchhilildrendren

11-12 yrs o12 yrs off age withage with pulmpulm TBTB

¾¾Obtaining cultObtaining cultureuress fromfrom chchildrildren with pulmonen with pulmonarary TBy TB ¾¾ Early moEarly morninrningg gastrigastric aspic aspirates (x3)rates (x3) ¾¾ BronchoBroncho alvealveolaolarr lalavage (BAL)vage (BAL) ¾¾ Sputum iSputum inn chchiillddren >5yrs sometiren >5yrs sometimesmes

Teens siTeens simimillarar to adulto adults its iff ccaviavitatary TBry TB¾¾

¾¾ InfantsInfants with pulwith pulmmonary TBonary TB ¾¾ 6060-7700% cul% culttures posures pos ¾¾ AdulAdult source case it source case immportantportant

Diagnosis is Difficult in ChildrenDiagnosis is Difficult in Children & Most are Not Contagious& Most are Not Contagious

�� Usually recent infection/primaryUsually recent infection/primary diseadiseassee

�� Low TB organism colony countLow TB organism colony count �� Poor tussive forcePoor tussive force �� Poor sputum productionPoor sputum production �� Half with disease have noHalf with disease have no

symsymppttoomsms �� Teens mTeens may have adult likeay have adult like

ddiisseeasase ane and may bd may bee ccoonnttagagiouiouss

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Congenital TB CaseCongenital TB Case

•• Pneumonia diagnPneumonia diagnoosed atsed at 34 wks of pregnancy34 wks of pregnancy �� MotherMother

•• TST 0mm, nTST 0mm, noo knknowown expn expoossuurere •• Treated withTreated with aziazithromycinthromycin & pneumoni& pneumoniaa

resolresolvveded

�� BabyBaby •• Became ill a fewBecame ill a few weeks after birthweeks after birth •• Developed extensive pneumDeveloped extensive pneumooniania •• ProgProgressed tressed too respirespirratory failatory failureure •• RequiredRequired ECMOECMO •• AFB smear pAFB smear poosisititive fromve from tracheal aspiratetracheal aspirate

grew MTB, pan susceptiblegrew MTB, pan susceptible

Video ClipVideo Clip

�� 10 minut10 minute video of family ane video of family and MDd MD interviewsinterviews ProducedProduced in 2003 bin 2003 byy lloocalcal CBS affiliate forCBS affiliate for��

ChildrenChildren’’s Mirs Miraacle Netwocle Networrk Tk Teeletholethonn fofor fundr fund

��

raisingraising TelethonTelethon no longer atno longer at ChildrenChildren’’s Memorials Memorial

��

HermannHermann Please excuse thePlease excuse the phonephone nunumbers anmbers andd advertisements which we could nadvertisements which we could noott ededitit

�� PhysicianPhysicianss:: •• OkanOkan EElidelidemmirir, Pediatr, Pediatriic Pulmonarc Pulmonaryy •• Amir KhaAmir Khann,, NeonatologyNeonatology •• KKiim Smitm Smithh,, PPediatediatric Tric TB,B, GenGeneraleral PediatPediatrics Hospitrics Hospitalalistist

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OutcomeOutcome �� MotherMother

•• Repeat TST after bRepeat TST after baaby dby diagnosed,iagnosed, 15mm15mm •• CCXXRR nornormmaall,, no otno otheherr sosoururccee iiddeennttiiffiieedd •• UterineUterine bibiopsopsyy shshowedowed granulomas consistentgranulomas consistent

with active TBwith active TB •• Treated for extraTreated for extra ppuulmonary,lmonary, uteriuterinne TBe TB

�� BabyBaby •• Treated 12 mTreated 12 moonths for miliary and TBnths for miliary and TB

meningitismeningitis •• RequiredRequired home oxygenhome oxygen and NG tube feedingsand NG tube feedings

fofor 8 mor 8 monthsnths •• Healed with complete recovery and nHealed with complete recovery and noo sequellasequella

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Congenital TuberculosisCongenital Tuberculosis

�� ExtExtrremely raemely rare, less thare, less thann 300 ca300 casesses

��

published in world literature*published in world literature* HigheHigherr riskrisk if mif moother has untreatedther has untreated primary or disseminatprimary or disseminated disease duringed disease during

��

pregnancypregnancy Most common TMost common TB sourcB source for infants ise for infants is rreespspiriratoratory transy transmmississiion fron froomm aduadulltt

��

household contacthousehold contact WindWindow pow prropophylaxihylaxiss or sepaor separation fration frromom cacase rese recommended for expcommended for expoosesedd infinfaantsnts

*Weisoly DL, Khan AM, Elidemir O, Smith KC: Pediatric Pulmonology 37(5):470-473, 2004.

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InterferonInterferon--γγ Release Assays (IGRA)Release Assays (IGRA) Blood test for TBBlood test for TB

��MTB speMTB speccific antigens:ific antigens: ¾¾ GenGenees in regis in region of differenon of differencce (RD1) one (RD1) on MTBMTB genomegenome

¾¾ CuCultltuurree filtfiltrraattee pprrootteeiinn 1010 ((CCFFPP-10)10) ¾¾ EarlyEarly secretorysecretory antiantigen targetgen target 6 (ESAT6 (ESAT-6)6)

�� Stimulate TStimulate T-Cell production of IFCell production of IFNN-γγ ��Diagnosis LTBI &/or diseaseDiagnosis LTBI &/or disease ��Does not cross reacDoes not cross react with BGC vaccinet with BGC vaccine

or most other myor most other mycobacteriacobacteria ��RequiresRequires:: ¾¾ ssiinngglele medmediicacal visl visiitt ¾¾ bblloooodd ccoollelleccttioionn ¾¾ llaboratory equiaboratory equipment andpment and personnelpersonnel

��Results in 24 hrsResults in 24 hrs �� LittleLittle publispublished dhed daata in cta in chhildreildrenn

Commercial TestsCommercial Tests QuantaFERONQuantaFERON--TB GoldTB Gold

Company: Cellestis,Company: Cellestis, AustraliaAustralia

FDA approvedFDA approved Available in manyAvailable in many

countries and somecountries and some labs in USlabs in US

�� Method:Method: ¾¾ Whole bloodWhole blood ¾¾ Incubated with MTBIncubated with MTB

antigensantigens (ESAT(ESAT-6 & CFP6 & CFP-10)10)

¾¾ TT-Cells produce IFNCells produce IFN- γγ ¾¾ SupernateSupernate removedremoved ¾¾ IFNIFN- γγ measured bymeasured by

ELISA readerELISA reader

TT--Spot TB or ELISPOTSpot TB or ELISPOT Company: OxfordCompany: Oxford ImmunotecImmunotec,,

United KingdomUnited Kingdom FDA pendingFDA pending Available in Europe & CanadaAvailable in Europe & Canada

�� Method:Method: ¾¾ TT-cellscells ¾¾ Incubated with MTBIncubated with MTB

antigensantigens (ESAT(ESAT-6 & CFP6 & CFP-10)10)

¾¾ TT-Cells produce INFCells produce INF- γγ ¾¾ IFNIFN- γγ binds to antibodybinds to antibody

in wellsin wells ¾¾ Spots develop and areSpots develop and are

counted manually or bycounted manually or by readerreader

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TT--Spot or ELISPOT ResultsSpot or ELISPOT Results

Positive TPositive T--SpotSpot Negative TNegative T--SpotSpot

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Sensitivity and Specificity of IGRASensitivity and Specificity of IGRA

QuantaFERONQuantaFERON-TB GoldTB Gold Sensitivity* (95%CI)Sensitivity* (95%CI)

Mori (04)Mori (04) 89 (8289 (82-94)94) Ravn (05)Ravn (05) 85 (7285 (72-94)94) Kang (05)Kang (05) 80 (6780 (67-90)90) PaiPai (05)(05) 75 (6475 (64-85)85)

Specificity+ (95%CI)Specificity+ (95%CI) Mori (04)Mori (04) 98 (9598 (95-99)99) Ravn (05)Ravn (05) 97 (8797 (87-100)100) Kang (05)Kang (05) 96 (9096 (90-99)99)

GolettiGoletti (05)(05) 90 (6890 (68-99)99)

TT-Spot TB or ELISPOTSpot TB or ELISPOT Sensitivity* (95%CI)Sensitivity* (95%CI)

LalvniLalvni (01a)(01a) 96 (8596 (85-99)99) LalvniLalvni (01b) 80 (66(01b) 80 (66-90)90) PathanPathan (01)(01) 92 (7492 (74-99)99) Chapman (02) 92 (81Chapman (02) 92 (81-98)98) Liebeschuetz(04) 83 (75Liebeschuetz(04) 83 (75-89)89) Meier (05)Meier (05) 97 (9097 (90-100)100)

Specificity+ (95%CI)Specificity+ (95%CI) LalvniLalvni (01a)(01a) 91 (8091 (80-98)98) PathanPathan (01)(01) 100(89100(89-100)100) Meier (05)Meier (05) 92 (6292 (62-100)100)

Pai, Expert Rev Mol Diagn. 6(3):413-422 (2006)

*Sensitivity in pts with active TB, Cx = Gold standard +Specificity in healthy low risk patients without TB

MetaMeta--analysanalysis of 58 IGRA Studiesis of 58 IGRA Studies Summary of findingsSummary of findings

�� SensitSensitivivityity similar fosimilar for TST and IGRA bloor TST and IGRA blood testsd tests ¾¾ IGRA testIGRA tests & TSTs & TST 7070-88%88%

�� IGRA testIGRA tests shs show eow exxcellentcellent SpecificitySpecificity ¾¾ IGRA testIGRA testss 9292-97%97% ¾¾ TST (due to BCGTST (due to BCG & NTM cros& NTM cross reactis reactionon)) 66%66%

�� PediatricPediatric data insudata insufficientfficient ¾¾ TB diagnTB diagnoosis msis moore difficure difficultlt inin childchildrenren

¾¾ No Gold standard for LTBINo Gold standard for LTBI ¾¾Not enNot enouough published datagh published data

Menzies, D, et al. Ann Intern Med 2007;146:340 354

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Sensitivity of TSTSensitivity of TST vsvs ELISPOTELISPOT 693 Children Exposed to Active TB in Gambia693 Children Exposed to Active TB in Gambia

413 Both Negative

165 Both Positive

TST

5560

ELISPOT

Hill, PC, et al. Pediatrics 2006;117;1542 1548.

TST positive 32.5%

ELISPOT positive 32.3%

83% agreement Between tests

Houston Pediatric THouston Pediatric T--Spot TB StudySpot TB Study Comparing TST, TComparing TST, T--Spot and Clinical DxSpot and Clinical Dx

�� TotalTotal 254 patients •• 212 ch212 childrenildren

254 patients

�� LTBILTBI 126126 �� TB diseaseTB disease 3232

•• 19 cul19 culttureure ppoositisitiveve

�� NegativNegative conte controlsrols 8787 �� ExExclcludeduded 99

•• due tdue too inconcluinconclusive labsive lab or missing clinical dataor missing clinical data

�� DisDiscordanccordance he hiighgh 64%64% •• MoreMore TST positTST positiiveve aammongong BCBCG vaccinaG vaccinatedted

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Houston Pediatric THouston Pediatric T--Spot TB StudySpot TB Study

NANAAllAll16%16%Percent TSTPercent TST -

AllAllNANA84%84% SensitivitySensitivity

Percent TST +Percent TST +

9%9%94%94% ““SpecificitySpecificity””

11%11%Percent TPercent T-SpotSpot -

91%91%6%6%89%89% SensitivitySensitivity

Percent TPercent T-Spot+Spot+

454588881919Total numberTotal number 152 (table)152 (table)

ContactsContacts with +TST,with +TST,

no BCGno BCG

ControlsControls No Exp Risk,No Exp Risk,

-TSTTST

Cases withCases with Culture +Culture +

MTBMTB GoldGold

StandardStandard

Flores, Jaime, et al. Poster presentation at International Union Against TB and Lung Disease Meeting, Feb, 2007

Summary InterferonSummary Interferon--γγ teststests �� Variable sensitVariable sensitivivityity

•• False negaFalse negativestives similar to TSTsimilar to TST (5(5-10%)10%) ¾¾ sseennssititivitivity imy impprroovveedd witwithh bbootthh tetessttss

•• IGRA SenIGRA Senssitivitivitityy maymay bebe hhiighgherer tthhanan TSTTST inin ¾¾ Very youngVery young ¾¾ DiDissemisseminated TBnated TB didiseasesease ¾¾ ImmunosuppresseImmunosuppressedd

�� HigHighhly sly sppecificecific •• DoesDoes notnot ccrrossoss reacreact with BCt with BCG vaccineG vaccine •• Or most other mycobacOr most other mycobactteriaeria

�� Single viSingle visisit requit requirreded �� Results inResults in 24 h24 hooursurs �� Helpful inHelpful in BCG vaccinated adBCG vaccinated adultsults �� More expensive than TSTMore expensive than TST

•• But may preventBut may prevent unneunnecessary xcessary x-rraays/mediys/medical vical visisits ats anndd treatmentreatment it inn adadulultsts wiwitthh BCGBCG hihistostorryy

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Pediatric TB CasePediatric TB Case

�� 12 mo12 month old boy came in with:nth old boy came in with: ¾¾10 day10 dayss fever (102fever (102--105)105) ¾¾4 days of vomiting4 days of vomiting and irritabilityand irritability ¾¾Chronic OM with PE tChronic OM with PE tuubes since 9bes since 9

mosmos of age, no ear discharge atof age, no ear discharge at presentationpresentation ¾¾Admitted to hospital for vomiting &Admitted to hospital for vomiting &

treated with IV cephalosporintreated with IV cephalosporin

Case Presentation, ContCase Presentation, Cont •• Transferred to MedicTransferred to Medicaal Centl Center for master for mastoiditisoiditis ¾¾RoutineRoutine ccuulturelture of middof middle earle ear neganegative at 2 daystive at 2 days

•• Lumbar puLumbar puncture anncture and CSF on day 2d CSF on day 2 ¾¾WBCWBC 360, dif 25360, dif 25 PP, 67, 67 LL, 8, 8 MM

¾¾ProProtteieinn 210 (normal 15210 (normal 15-45)45) ¾¾RoutineRoutine CxCx negative atnegative at 2 days2 days

•• Tuberculin skin test 0mmTuberculin skin test 0mm •• CXRCXR – normnormalal iinniittiiaalllly they thenn mimililiary patterary patternn •• No risk, traNo risk, travvel or knownel or known exposureexposure to TBto TB •• Brain MRIBrain MRI ¾¾MMuultltiple eniple enhanhancciningg nnoodulesdules ¾¾enhancemeenhancemennt of brain stem and basal gangliont of brain stem and basal ganglion ¾¾RightRight ototomastomastooiditiditisis

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OutcomeOutcome �� TB treatmentTB treatment stastarrted for suspected TBted for suspected TB

meningitismeningitis ¾¾ INH, RifampinINH, Rifampin (12(12 months), PZA, EMBmonths), PZA, EMB && SterSteroidsoids

�� Mother wiMother with + TST,th + TST, nnoormalrmal CXR,CXR, nnoo ssoourceurce case identcase identiifiedfied

�� Middle eMiddle eaar fluid andr fluid and CSF later grew MTBCSF later grew MTB ¾¾ GrewGrew > 1 month after prese> 1 month after presenntationtation ¾¾ PaPansnsusceptiusceptibleble

�� ComplicatComplications & ouions & outcome:tcome: ¾¾ HydrocephaHydrocephalloous &us & VVPP sshhununtt ¾¾ VeryVery mildmild hemipareshemiparesiiss ¾¾ CCoogngnititivivelyely doindoing wg wellell

�� Note: from researcNote: from researchh studstudyy ¾¾ InteInterferorferonn γγ blood testblood test positive forpositive for TBTB

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Disney World 2006

With permission

Tuberculosis MeningitisTuberculosis Meningitis

�� Higher risk inHigher risk in ininfantfantss �� Gradual onset over days or 1Gradual onset over days or 1-2 weeks compared2 weeks compared

to bacterial meningto bacterial meningitisitis �� Cerebral Spinal Fluid (CSF)Cerebral Spinal Fluid (CSF) ¾¾Normal to moderately highNormal to moderately high WBC (20WBC (20’’ss-100100’’s),s),

lymphlymphoocytic pcytic prredominanceedominance ¾¾Very higVery highh proteiprotein, usually >100n, usually >100-300300

�� MRIMRI ¾¾BrainBrain stestemm & basal& basal gaganglion enhancementnglion enhancement ¾¾Sometimes no findings on MRISometimes no findings on MRI

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Tuberculosis Meningitis, contTuberculosis Meningitis, cont

�� Possible complicationsPossible complications ¾¾ HydrocephaHydrocephalloousus ¾¾ Stroke/iStroke/innffararctscts ¾¾ CCoogngnititivive impaire impairmenmentt ¾¾ Normal outcome possible ifNormal outcome possible if trtreatedeated in early stages (50%in early stages (50%

in my experience)in my experience)

�� TreatmentTreatment ¾¾ 4 T4 TB medsB meds ununttil susceptil susceptibiibilliittiies knes knowown, INn, INH/H/Rif fRif foor 12r 12

monthsmonths ¾¾ steroids (1steroids (1-2 months) to decrea2 months) to decreasese inflammatioinflammationn aanndd

scarscar formationformation ¾¾ SymptomsSymptoms ofteoftenn getget wwoorse berse beforefore better,better, manmanyy treatreat it inn

hospihospittalal forfor fifirstrst montmonthh

New Research on Horizon for TBNew Research on Horizon for TB

�� Improved diagnImproved diagnoostic testsstic tests ¾¾ For LTBIFor LTBI ¾¾ For aFor acctive dtive diiseasesease ¾¾ Head toHead to heahead QFT /d QFT / TT-SpSpotot //

TST sTST sttudiudieess

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¾¾ More pediatric dataMore pediatric data

New drugs for TBNew drugs for TB treatmenttreatment

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��

Shorter treatmentsShorter treatments New TB vaccines inNew TB vaccines in

��

international clinical tinternational clinical trrialsials Rapid tests for drugRapid tests for drug

markers)markers) resistanceresistance (genetic(genetic

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THANKSTHANKS

�� Heartland National TB CenterHeartland National TB Center �� Research collaborators:Research collaborators:

•• Drs. JeffDrs. Jeffrey Starey Starrke & Edke & Edward Gward Grraviaviss,ss, BaBaylor Cylor Coollege ofllege of MeMedicine, Houston, TXdicine, Houston, TX

�� Funding:Funding: •• OxfOxfoordrd ImmunotecImmunotec, Inc, UK, Inc, UK

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QuestionsQuestions

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