- 1. ImmunologiaTB/HIV AndreaGori UOMala/eInfe23ve
AOSanGerardo,Monza UniversitMilano-Bicocca [email protected]
Milano,21-22Marzo2014 !
2. InterferonGammaReleaseAssay(IGRA)tes;ng 3.
Clinicalu;lityofinterferongammarelease assays(IGRAs) 4.
Biologicalphenomenaofmother-newbornimmune
interac;onwhichcantheore;callyaectnewborn
immuneresponsestomicrobialan;gens 5.
Sensi;vityofIGRAsinHIV-infectedindividuals
withconrmedac;vetuberculosis 6.
Propor;onofindeterminateIGRAresultsin
HIV-infectedpersonsscreenedforLTBI 7.
ImpactofCD4+cellcountonthepropor;onof posi;veIGRAresults 8.
ImpactofCD4+cellcountonthepropor;onof indeterminateIGRAresults 9.
IGRAtestfortheDiagnosisofLTBIinHIV- InfectedIndividuals -
CurrentevidencesuggeststhatIGRAperformsimilarlytotheTST
atiden3fyingHIV+individualswhocouldbenetfromLTBI treatment -
Importantques3onsremainunanswereddespitethesubstan3al
bodyofliteratureonIGRAs: -
HIV+individualswithanega3veIGRAresultmayhavealowriskof
progressiontoac3veTB -
IGRAs(par3cularlyTSPOT)maybemoresensi3vethanTSTinHIV-
infectedindividualsandlessaectedbyadvancedimmunosuppression -
ClinicalTrialsareneededtomoredeni3velydeterminewhetherIGRAs
couldimprovetheiden3ca3onofpeoplelivingwithHIV -
Un3lsuchdataareavailable,thedecisiontouseIGRAorTST(orboth)
willdependonna3onalguidelinesaswellasresourceandogis3c
considera3ons. 10. -
Thediagnos3cvalueofinterferon-releaseassays(IGRAs)for
ac3vetuberculosisinlow-andmiddle-incomecountriesis unclear -
TherewasnoconsistentevidencethateitherIGRAwasmore
sensi3vethanthetuberculinskintestforac3vetuberculosis diagnosis -
Conclusions:neitherthetuberculinskintestnorIGRAshave
valueforac3vetuberculosisdiagnosis,especiallyinthe
contextofHIVcoinfec3on Interferon-ReleaseAssaysforAc;vePulmonary
TuberculosisDiagnosis 11. Comparisonofsensi;vityofT-SPOTVSQFT-GIT
amongpersonswithsuspectedac;vetuberculosis 12.
Sensi;vityofQFT-GITandT-SPOTinHIV-andHIV
+personswithconrmedac;vetuberculosis 13.
Sensi;vitydierencebetweenIGRAandTST
Plotsdisplay%dierences(IGRAsensi3vityTSTsensi3vity)forconrmedac3ve
pulmonarytuberculosis 14. Interferon-ReleaseAssaysforAc;ve
PulmonaryTuberculosisDiagnosis -
AsinthecaseoftheTST,thedatasuggestnoroleforusing
IGRAsforac3vetuberculosisdiagnosisforadultslivinginlow-
andmiddle-incomecountries -
Thesedatashouldnothelpinformevidence-basedpolicieson
theroleofIGRAsinac3vetuberculosisdiagnosis -
Indeed,aWHOExpertGroupconsideringthisevidencerecently
recommendedthatIGRAsshouldnotbeusedasareplacement
forconven3onalmicrobiologicaldiagnosisofpulmonaryand extrapulmonary
15. - Tuberculosisisuniqueamongthemajorinfec3ousdiseasesin
thatitlacksaccuraterapidpoint-of-carediagnos3ctests -
Failuretocontrolthespreadoftuberculosisislargelyduetoour
inabilitytodetectandtreatallinfec3ouscasesofpulmonary
tuberculosisina3melyfashion,allowingcon3nued
Mycobacteriumtuberculosistransmissionwithincommuni3es 16.
AnalysisofMtb-specicTcellresponsesinthe valida;oncohort 17.
Quan;ta;veandqualita;veanalysisofMtb- specicTcellresponses
Latentinfec3on Ac3vedisease 18.
Func;onalproleofMtb-specicCD4+Tcells
onthebasisofIFN-,IL-2orTNF-produc;on 19.
PercentagesofCFP-10orESAT-6specic
single-posi;veTNF-producingCD4+Tcells 20.
ProleofMtb-specicCD4+Tcellsduring
untreatedTBdiseaseandthenaZerTBtreatment 21.
M.tuberculosisspecicCD4+Tcellresponses
andlatentinfec;onorac;vedisease -
Rapiddiagnosisofac3veMycobacteriumtuberculosis(Mtb)
infec3onremainsaclinicalandlaboratorychallenge -
WehaveanalyzedthecytokineproleIFN-,TNF-andIL-2
ofMtb-specicTcellsbypolychroma3cowcytometry -
Substan3alincreaseinthepropor3onofsingle-posi3veTNF-
Mtb-specicCD4+Tcellsinsubjectswithac3vedisease,
andthisparameterwasthestrongestpredictorofdiagnosis
ofac3vediseaseversuslatentinfec3on -
Therefore,thepropor3onofsingle-posi3veTNF-Mtb-
specicCD4+Tcellsisanewtoolfortherapiddiagnosisof
ac3vetuberculosisdisease 22. DivisionofOnco-Haemathology,SanGerardo
Hospital,UniversityMilano-Bicocca Monza,Italy LuisaVerga
FaustoRossini PietroPioltelli EnricoPogliani
DivisionofDivisionofPathology,SanGerardo Hospital,
UniversityMilan-Bicocca Monza,Italy AmbrogioBrenna SerenaCu`n
GiorgioCatore` DivisionofMicrobiologyandVirologyLaboratories,
SanGerardoHospital,Monza,Italy SergioMalandrin AnnalisaCavallero
HaemathologyandTransfusionCenter,San GerardoHospital,Monza,Italy
PaoloPerseghin AriannaIncontri ChairofImmunology,
UniversityofMilan,Milan,Italy DariaTrabaaoni MarinaSaresella
MaraBiasin Mario(Mago)Clerici DepartmentofInfec;ousDiseases,
L.SaccoHospital,UniversityofMilan Milan,Italy, FabioFranze`
FabioZanini StefanoRusconi StefaniaPiconi GiulianoRizzardini
ClinicofInfec;ousDiseases,SanPaoloHospital, UniversityofMilan
Milan,Italy GiuliaMarche` CamillaTinca; AntonelladArminioMonforte
DivisionediMala`eInfe`ve A.O.SanGerardo Monza GiuseppeLapadula
SilviaCostarelli AlessandraBandera MariannaRossi NicolaSquillace
AlessandroSoria AntonioMuscatello Sebas;anoLeone
GuglielmoMigliorino 23. BACKUPSLIDES 24.
InterferonGammaReleaseAssay(IGRA)tes;ng 25. summary curves from the
HSROC model contain a summary operating point (red square)
representing summarized sensitivity and specificity point estimates
for individual study estimates (open circles). The 95% confidence
region is delineated by the area in the orange dashed line.
