Post on 17-Dec-2015
What’s New in LTBI?What’s New in LTBI?
Mayo Clinic Center for TuberculosisMayo Clinic Center for TuberculosisWebinarWebinar
6 Mar 20146 Mar 2014
What’s New in LTBI?What’s New in LTBI?
Mayo Clinic Center for TuberculosisMayo Clinic Center for TuberculosisWebinarWebinar
6 Mar 20146 Mar 2014
Timothy R. Aksamit, MDTimothy R. Aksamit, MD
Associate Professor of MedicineAssociate Professor of MedicineMayo Clinic Mayo Clinic
College of MedicineCollege of Medicine
ConsultantConsultantPulmonary Disease and Critical Care MedicinePulmonary Disease and Critical Care Medicine
Department of Internal MedicineDepartment of Internal MedicineMayo ClinicMayo Clinic
Rochester, MinnesotaRochester, Minnesota
Timothy R. Aksamit, MDTimothy R. Aksamit, MD
Associate Professor of MedicineAssociate Professor of MedicineMayo Clinic Mayo Clinic
College of MedicineCollege of Medicine
ConsultantConsultantPulmonary Disease and Critical Care MedicinePulmonary Disease and Critical Care Medicine
Department of Internal MedicineDepartment of Internal MedicineMayo ClinicMayo Clinic
Rochester, MinnesotaRochester, Minnesota
What’s New in LTBI?What’s New in LTBI?What’s New in LTBI?What’s New in LTBI?
DISCLOSUREDISCLOSURE
Relevant Financial Relationship(s)Relevant Financial Relationship(s)NoneNone
DISCLOSUREDISCLOSURE
Relevant Financial Relationship(s)Relevant Financial Relationship(s)NoneNone
What’s New in LTBI?What’s New in LTBI?
ObjectivesObjectives
What’s New in LTBI?What’s New in LTBI?
ObjectivesObjectives
•Describe the use of Interferon Gamma Release Describe the use of Interferon Gamma Release Assays (IGRAs) for TB testing Assays (IGRAs) for TB testing in HCW in HCW
•Describe the use of shorter drug regimens for the Describe the use of shorter drug regimens for the treatment of Latent TB Infection (LTBI) treatment of Latent TB Infection (LTBI)
•Describe the public health perspective on the Describe the public health perspective on the advantages and limitations of using IGRAs and advantages and limitations of using IGRAs and short LTBI regimensshort LTBI regimens
•Describe the use of Interferon Gamma Release Describe the use of Interferon Gamma Release Assays (IGRAs) for TB testing Assays (IGRAs) for TB testing in HCW in HCW
•Describe the use of shorter drug regimens for the Describe the use of shorter drug regimens for the treatment of Latent TB Infection (LTBI) treatment of Latent TB Infection (LTBI)
•Describe the public health perspective on the Describe the public health perspective on the advantages and limitations of using IGRAs and advantages and limitations of using IGRAs and short LTBI regimensshort LTBI regimens
•BackgroundBackground
•Diagnostics – IGRADiagnostics – IGRA•HCWHCW
•TreatmentTreatment•RPT-INH 12 weeksRPT-INH 12 weeks
•SummarySummary
•BackgroundBackground
•Diagnostics – IGRADiagnostics – IGRA•HCWHCW
•TreatmentTreatment•RPT-INH 12 weeksRPT-INH 12 weeks
•SummarySummary
What’s New in LTBI?What’s New in LTBI?What’s New in LTBI?What’s New in LTBI?
•BackgroundBackground
•Diagnostics – IGRADiagnostics – IGRA•HCWHCW
•TreatmentTreatment•RPT-INH 12 weeksRPT-INH 12 weeks
•SummarySummary
•BackgroundBackground
•Diagnostics – IGRADiagnostics – IGRA•HCWHCW
•TreatmentTreatment•RPT-INH 12 weeksRPT-INH 12 weeks
•SummarySummary
What’s New in LTBI?What’s New in LTBI?What’s New in LTBI?What’s New in LTBI?
Latent TB Infection (LTBI)Latent TB Infection (LTBI)Latent TB Infection (LTBI)Latent TB Infection (LTBI)
LTBI is the presence of LTBI is the presence of M. tuberculosisM. tuberculosis organisms (tubercle bacilli) without symptoms organisms (tubercle bacilli) without symptoms or radiographic evidence of TB disease.or radiographic evidence of TB disease.
No GOLD STANDARDNo GOLD STANDARD
LTBI is the presence of LTBI is the presence of M. tuberculosisM. tuberculosis organisms (tubercle bacilli) without symptoms organisms (tubercle bacilli) without symptoms or radiographic evidence of TB disease.or radiographic evidence of TB disease.
No GOLD STANDARDNo GOLD STANDARD
Latent TB Infection (LTBI)Latent TB Infection (LTBI)Latent TB Infection (LTBI)Latent TB Infection (LTBI)
ERJ 33: 956, 2009ERJ 33: 956, 2009ERJ 33: 956, 2009ERJ 33: 956, 2009
Latent TB Infection (LTBI)Latent TB Infection (LTBI)Latent TB Infection (LTBI)Latent TB Infection (LTBI)
LTBI is the presence of LTBI is the presence of M. tuberculosisM. tuberculosis organisms (tubercle bacilli) organisms (tubercle bacilli) without symptoms or radiographic evidence of TB disease.without symptoms or radiographic evidence of TB disease.
No GOLD STANDARD – Natural history is uncertainNo GOLD STANDARD – Natural history is uncertain
“ “LTBI” = Persistent adaptive M.LTBI” = Persistent adaptive M. Tb Tb immune response immune response
LTBI is the presence of LTBI is the presence of M. tuberculosisM. tuberculosis organisms (tubercle bacilli) organisms (tubercle bacilli) without symptoms or radiographic evidence of TB disease.without symptoms or radiographic evidence of TB disease.
No GOLD STANDARD – Natural history is uncertainNo GOLD STANDARD – Natural history is uncertain
“ “LTBI” = Persistent adaptive M.LTBI” = Persistent adaptive M. Tb Tb immune response immune response
????
Testing for Testing for TB Disease and InfectionTB Disease and Infection
Testing for Testing for TB Disease and InfectionTB Disease and Infection
TB TB DISEASEDISEASEPulm and Pulm and
XPXP
TB TB DISEASEDISEASEPulm and Pulm and
XPXP
TB INFECTION (LTBI)TB INFECTION (LTBI)TB INFECTION (LTBI)TB INFECTION (LTBI)
TerminologyTerminologyTerminologyTerminology
• ““Treatment of latent TB infection”Treatment of latent TB infection” replaces the terms replaces the terms “preventive therapy” and “chemoprophylaxis“preventive therapy” and “chemoprophylaxis”” to to promote greater understanding of the concept for promote greater understanding of the concept for both patients and providers.both patients and providers.
• Targeted tuberculin testingTargeted tuberculin testing is used to focus program is used to focus program activities and provider practices on groups at the activities and provider practices on groups at the highest risk for TB.highest risk for TB.
• ““Treatment of latent TB infection”Treatment of latent TB infection” replaces the terms replaces the terms “preventive therapy” and “chemoprophylaxis“preventive therapy” and “chemoprophylaxis”” to to promote greater understanding of the concept for promote greater understanding of the concept for both patients and providers.both patients and providers.
• Targeted tuberculin testingTargeted tuberculin testing is used to focus program is used to focus program activities and provider practices on groups at the activities and provider practices on groups at the highest risk for TB.highest risk for TB.
Targeted Tuberculin TestingTargeted Tuberculin TestingTargeted Tuberculin TestingTargeted Tuberculin Testing
• Detects persons with LTBI who would benefit from Detects persons with LTBI who would benefit from treatmenttreatment
• De-emphasizes testing of groups that are not at De-emphasizes testing of groups that are not at high risk for TBhigh risk for TB
• Can help reduce the waste of resources and Can help reduce the waste of resources and prevent inappropriate treatmentprevent inappropriate treatment
• Detects persons with LTBI who would benefit from Detects persons with LTBI who would benefit from treatmenttreatment
• De-emphasizes testing of groups that are not at De-emphasizes testing of groups that are not at high risk for TBhigh risk for TB
• Can help reduce the waste of resources and Can help reduce the waste of resources and prevent inappropriate treatmentprevent inappropriate treatment
•BackgroundBackground
•Diagnostics – IGRADiagnostics – IGRA•HCWHCW
•TreatmentTreatment•RPT-INH 12 weeksRPT-INH 12 weeks
•SummarySummary
•BackgroundBackground
•Diagnostics – IGRADiagnostics – IGRA•HCWHCW
•TreatmentTreatment•RPT-INH 12 weeksRPT-INH 12 weeks
•SummarySummary
What’s New in LTBI?What’s New in LTBI?What’s New in LTBI?What’s New in LTBI?
Testing for Latent TB InfectionTesting for Latent TB InfectionTesting for Latent TB InfectionTesting for Latent TB Infection
Tuberculin Skin Test (TST)Tuberculin Skin Test (TST)
oror
Interferon-Interferon-γγ Release Assay (IGRA): Release Assay (IGRA):
QuantiFERONQuantiFERON®-TB®-TB Gold Gold
QuantiFERONQuantiFERON®-TB®-TB Gold-IT (In-Tube) Gold-IT (In-Tube)
T-SPOTT-SPOT®.®.TBTB
Tuberculin Skin Test (TST)Tuberculin Skin Test (TST)
oror
Interferon-Interferon-γγ Release Assay (IGRA): Release Assay (IGRA):
QuantiFERONQuantiFERON®-TB®-TB Gold Gold
QuantiFERONQuantiFERON®-TB®-TB Gold-IT (In-Tube) Gold-IT (In-Tube)
T-SPOTT-SPOT®.®.TBTB
New Insights in the Diagnosis of New Insights in the Diagnosis of Tuberculosis InfectionTuberculosis Infection
IFN-IFN-γγ Release Assays (IGRAs) Release Assays (IGRAs)
New Insights in the Diagnosis of New Insights in the Diagnosis of Tuberculosis InfectionTuberculosis Infection
IFN-IFN-γγ Release Assays (IGRAs) Release Assays (IGRAs)
• ESAT-6 and CFP-10 (and TB 7.7(p4))ESAT-6 and CFP-10 (and TB 7.7(p4)) • no cross reactivity withno cross reactivity with
• BCG (TST no impact)BCG (TST no impact)• most NTM, except M. kansasii, M. most NTM, except M. kansasii, M.
szulgai, marinum, and riyadhenseszulgai, marinum, and riyadhense• + reactivity with M. bovis, africanum, microti+ reactivity with M. bovis, africanum, microti
• Control antigensControl antigens• nil (negative) control antigennil (negative) control antigen• mitogen phytohemagglutinin (positive) mitogen phytohemagglutinin (positive)
control antigencontrol antigen
• ESAT-6 and CFP-10 (and TB 7.7(p4))ESAT-6 and CFP-10 (and TB 7.7(p4)) • no cross reactivity withno cross reactivity with
• BCG (TST no impact)BCG (TST no impact)• most NTM, except M. kansasii, M. most NTM, except M. kansasii, M.
szulgai, marinum, and riyadhenseszulgai, marinum, and riyadhense• + reactivity with M. bovis, africanum, microti+ reactivity with M. bovis, africanum, microti
• Control antigensControl antigens• nil (negative) control antigennil (negative) control antigen• mitogen phytohemagglutinin (positive) mitogen phytohemagglutinin (positive)
control antigencontrol antigen
New Insights in the Diagnosis of New Insights in the Diagnosis of Tuberculosis InfectionTuberculosis Infection
IFN-IFN-γγ Release Assays (IGRAs) Release Assays (IGRAs)
New Insights in the Diagnosis of New Insights in the Diagnosis of Tuberculosis InfectionTuberculosis Infection
IFN-IFN-γγ Release Assays (IGRAs) Release Assays (IGRAs)
Can IGRAs testing be used in place of TST?Can IGRAs testing be used in place of TST?• YesYes
CDC Guidelines QFT-Gold 2005:CDC Guidelines QFT-Gold 2005:
QFT-Gold can be used in QFT-Gold can be used in all circumstancesall circumstances in which in which the TST is used including:the TST is used including:
• contact investigationscontact investigations• evaluation of recent immigrants (BCG)evaluation of recent immigrants (BCG)• TB screening HCW, including serial screeningTB screening HCW, including serial screening
Can IGRAs testing be used in place of TST?Can IGRAs testing be used in place of TST?• YesYes
CDC Guidelines QFT-Gold 2005:CDC Guidelines QFT-Gold 2005:
QFT-Gold can be used in QFT-Gold can be used in all circumstancesall circumstances in which in which the TST is used including:the TST is used including:
• contact investigationscontact investigations• evaluation of recent immigrants (BCG)evaluation of recent immigrants (BCG)• TB screening HCW, including serial screeningTB screening HCW, including serial screening
MMWR 54: RR-15, 2005 MMWR 54: RR-17, 2005MMWR 54: RR-15, 2005 MMWR 54: RR-17, 2005MMWR 54: RR-15, 2005 MMWR 54: RR-17, 2005MMWR 54: RR-15, 2005 MMWR 54: RR-17, 2005
New Insights in the Diagnosis of New Insights in the Diagnosis of Tuberculosis InfectionTuberculosis Infection
New Insights in the Diagnosis of New Insights in the Diagnosis of Tuberculosis InfectionTuberculosis Infection
New Insights in the Diagnosis of New Insights in the Diagnosis of Tuberculosis InfectionTuberculosis Infection
New Insights in the Diagnosis of New Insights in the Diagnosis of Tuberculosis InfectionTuberculosis Infection
What’s New in LTBI?What’s New in LTBI?IGRAsIGRAs
What’s New in LTBI?What’s New in LTBI?IGRAsIGRAs
Clin Micro Rev 27: 3, 2014Clin Micro Rev 27: 3, 2014Clin Micro Rev 27: 3, 2014Clin Micro Rev 27: 3, 2014
What’s New in LTBI?What’s New in LTBI?IGRAs –Sources of variabilityIGRAs –Sources of variability
What’s New in LTBI?What’s New in LTBI?IGRAs –Sources of variabilityIGRAs –Sources of variability
Clin Micro Rev 27: 3, 2014Clin Micro Rev 27: 3, 2014Clin Micro Rev 27: 3, 2014Clin Micro Rev 27: 3, 2014
What’s New in LTBI?What’s New in LTBI?IGRAs –Sources of variabilityIGRAs –Sources of variability
What’s New in LTBI?What’s New in LTBI?IGRAs –Sources of variabilityIGRAs –Sources of variability
Clin Micro Rev 27: 3, 2014Clin Micro Rev 27: 3, 2014Clin Micro Rev 27: 3, 2014Clin Micro Rev 27: 3, 2014
What’s New in LTBI?What’s New in LTBI?IGRAs –Sources of variabilityIGRAs –Sources of variability
What’s New in LTBI?What’s New in LTBI?IGRAs –Sources of variabilityIGRAs –Sources of variability
Clin Micro Rev 27: 3, 2014Clin Micro Rev 27: 3, 2014Clin Micro Rev 27: 3, 2014Clin Micro Rev 27: 3, 2014
What’s New in LTBI?What’s New in LTBI?IGRAs –Sources of variabilityIGRAs –Sources of variability
What’s New in LTBI?What’s New in LTBI?IGRAs –Sources of variabilityIGRAs –Sources of variability
Clin Micro Rev 27: 3, 2014Clin Micro Rev 27: 3, 2014Clin Micro Rev 27: 3, 2014Clin Micro Rev 27: 3, 2014
What’s New in LTBI?What’s New in LTBI?IGRAs –Sources of variabilityIGRAs –Sources of variability
What’s New in LTBI?What’s New in LTBI?IGRAs –Sources of variabilityIGRAs –Sources of variability
Clin Micro Rev 27: 3, 2014Clin Micro Rev 27: 3, 2014Clin Micro Rev 27: 3, 2014Clin Micro Rev 27: 3, 2014
What’s New in LTBI?What’s New in LTBI?IGRAs –Serial testing phenotypesIGRAs –Serial testing phenotypes
What’s New in LTBI?What’s New in LTBI?IGRAs –Serial testing phenotypesIGRAs –Serial testing phenotypes
Clin Micro Rev 27: 3, 2014Clin Micro Rev 27: 3, 2014Clin Micro Rev 27: 3, 2014Clin Micro Rev 27: 3, 2014
What’s New in LTBI?What’s New in LTBI?IGRAs – HCW ScreeningIGRAs – HCW Screening
What’s New in LTBI?What’s New in LTBI?IGRAs – HCW ScreeningIGRAs – HCW Screening
Am J Respir Crit Care Med 189: 77, 2014Am J Respir Crit Care Med 189: 77, 2014Am J Respir Crit Care Med 189: 77, 2014Am J Respir Crit Care Med 189: 77, 2014
What’s New in LTBI?What’s New in LTBI?IGRAs – HCW ScreeningIGRAs – HCW Screening
What’s New in LTBI?What’s New in LTBI?IGRAs – HCW ScreeningIGRAs – HCW Screening
Am J Respir Crit Care Med 189: 77, 2014Am J Respir Crit Care Med 189: 77, 2014Am J Respir Crit Care Med 189: 77, 2014Am J Respir Crit Care Med 189: 77, 2014
What’s New in LTBI?What’s New in LTBI?IGRAs – HCW ScreeningIGRAs – HCW Screening
What’s New in LTBI?What’s New in LTBI?IGRAs – HCW ScreeningIGRAs – HCW Screening
• Prospective longitudinal study 2563 HCWs Prospective longitudinal study 2563 HCWs
• Four centers: Denver, Baltimore, Houston, NYCFour centers: Denver, Baltimore, Houston, NYC
• 12% foreign-born high TB burden countries, 9% BCG reported12% foreign-born high TB burden countries, 9% BCG reported
• TST, QFT-GIT, and T-SPOT.TB baseline and every 6 months for 18 monthsTST, QFT-GIT, and T-SPOT.TB baseline and every 6 months for 18 months
• Sub-studies for repeatability, reproducibility, and boostingSub-studies for repeatability, reproducibility, and boosting
• Baseline:Baseline:• Positive – overall (previously screened)Positive – overall (previously screened)
• TST: 5.2% (1.8%)TST: 5.2% (1.8%)• QFT-GIT: 4.9% (3.8%)QFT-GIT: 4.9% (3.8%)• T.SPOT-TB: 6.0% (5.0%)T.SPOT-TB: 6.0% (5.0%)
• Prospective longitudinal study 2563 HCWs Prospective longitudinal study 2563 HCWs
• Four centers: Denver, Baltimore, Houston, NYCFour centers: Denver, Baltimore, Houston, NYC
• 12% foreign-born high TB burden countries, 9% BCG reported12% foreign-born high TB burden countries, 9% BCG reported
• TST, QFT-GIT, and T-SPOT.TB baseline and every 6 months for 18 monthsTST, QFT-GIT, and T-SPOT.TB baseline and every 6 months for 18 months
• Sub-studies for repeatability, reproducibility, and boostingSub-studies for repeatability, reproducibility, and boosting
• Baseline:Baseline:• Positive – overall (previously screened)Positive – overall (previously screened)
• TST: 5.2% (1.8%)TST: 5.2% (1.8%)• QFT-GIT: 4.9% (3.8%)QFT-GIT: 4.9% (3.8%)• T.SPOT-TB: 6.0% (5.0%)T.SPOT-TB: 6.0% (5.0%)
Am J Respir Crit Care Med 189: 77, 2014Am J Respir Crit Care Med 189: 77, 2014Am J Respir Crit Care Med 189: 77, 2014Am J Respir Crit Care Med 189: 77, 2014
What’s New in LTBI?What’s New in LTBI?IGRAs – HCW ScreeningIGRAs – HCW Screening
What’s New in LTBI?What’s New in LTBI?IGRAs – HCW ScreeningIGRAs – HCW Screening
• Reversions (baseline positive tests):Reversions (baseline positive tests):• TST: 29 of 54 (54%) retested negative TST: 29 of 54 (54%) retested negative • QFT-GIT: 67 0f 118 (57%) QFT-GIT: 67 0f 118 (57%) • T.SPOT: 92 of 144 (64%)T.SPOT: 92 of 144 (64%)
• Conversions:Conversions:• TST: 21 of 2293 (0.9%)TST: 21 of 2293 (0.9%)• QFT-GIT: 138 of 2263 (6.1%)QFT-GIT: 138 of 2263 (6.1%)• T.SPOT: 177 of 2137 (8.3%)T.SPOT: 177 of 2137 (8.3%)
• No association with TB exposureNo association with TB exposure• No patient converted all three testsNo patient converted all three tests
• Reversions (baseline positive tests):Reversions (baseline positive tests):• TST: 29 of 54 (54%) retested negative TST: 29 of 54 (54%) retested negative • QFT-GIT: 67 0f 118 (57%) QFT-GIT: 67 0f 118 (57%) • T.SPOT: 92 of 144 (64%)T.SPOT: 92 of 144 (64%)
• Conversions:Conversions:• TST: 21 of 2293 (0.9%)TST: 21 of 2293 (0.9%)• QFT-GIT: 138 of 2263 (6.1%)QFT-GIT: 138 of 2263 (6.1%)• T.SPOT: 177 of 2137 (8.3%)T.SPOT: 177 of 2137 (8.3%)
• No association with TB exposureNo association with TB exposure• No patient converted all three testsNo patient converted all three tests
Am J Respir Crit Care Med 189: 77, 2014Am J Respir Crit Care Med 189: 77, 2014Am J Respir Crit Care Med 189: 77, 2014Am J Respir Crit Care Med 189: 77, 2014
What’s New in LTBI?What’s New in LTBI?IGRAs – HCW ScreeningIGRAs – HCW Screening
What’s New in LTBI?What’s New in LTBI?IGRAs – HCW ScreeningIGRAs – HCW Screening
• (“transient”) Conversions:(“transient”) Conversions:• TST: 11 of 12 retested (92%) negativeTST: 11 of 12 retested (92%) negative• QFT-GIT: 81 of 106 (76%)QFT-GIT: 81 of 106 (76%)• T.SPOT: 91 of 118 (77%)T.SPOT: 91 of 118 (77%)
• (“transient”) Conversions:(“transient”) Conversions:• TST: 11 of 12 retested (92%) negativeTST: 11 of 12 retested (92%) negative• QFT-GIT: 81 of 106 (76%)QFT-GIT: 81 of 106 (76%)• T.SPOT: 91 of 118 (77%)T.SPOT: 91 of 118 (77%)
Am J Respir Crit Care Med 189: 77, 2014Am J Respir Crit Care Med 189: 77, 2014Am J Respir Crit Care Med 189: 77, 2014Am J Respir Crit Care Med 189: 77, 2014
What’s New in LTBI?What’s New in LTBI?IGRAs – HCW ScreeningIGRAs – HCW Screening
What’s New in LTBI?What’s New in LTBI?IGRAs – HCW ScreeningIGRAs – HCW Screening
Am J Respir Crit Care Med 189: 77, 2014Am J Respir Crit Care Med 189: 77, 2014Am J Respir Crit Care Med 189: 77, 2014Am J Respir Crit Care Med 189: 77, 2014
What’s New in LTBI?What’s New in LTBI?IGRAs – HCW ScreeningIGRAs – HCW Screening
What’s New in LTBI?What’s New in LTBI?IGRAs – HCW ScreeningIGRAs – HCW Screening
Am J Respir Crit Care Med 189: 77, 2014Am J Respir Crit Care Med 189: 77, 2014Am J Respir Crit Care Med 189: 77, 2014Am J Respir Crit Care Med 189: 77, 2014
What’s New in LTBI?What’s New in LTBI?IGRAs – HCW ScreeningIGRAs – HCW Screening
What’s New in LTBI?What’s New in LTBI?IGRAs – HCW ScreeningIGRAs – HCW Screening
Am J Respir Crit Care Med 189: 77, 2014Am J Respir Crit Care Med 189: 77, 2014Am J Respir Crit Care Med 189: 77, 2014Am J Respir Crit Care Med 189: 77, 2014
What’s New in LTBI?What’s New in LTBI?IGRAs – HCW ScreeningIGRAs – HCW Screening
What’s New in LTBI?What’s New in LTBI?IGRAs – HCW ScreeningIGRAs – HCW Screening
Am J Respir Crit Care Med 189: 77, 2014Am J Respir Crit Care Med 189: 77, 2014Am J Respir Crit Care Med 189: 77, 2014Am J Respir Crit Care Med 189: 77, 2014
What’s New in LTBI?What’s New in LTBI?IGRAs – HCW ScreeningIGRAs – HCW Screening
What’s New in LTBI?What’s New in LTBI?IGRAs – HCW ScreeningIGRAs – HCW Screening
• Boosted:Boosted:• 9.1% QFT-GIT9.1% QFT-GIT• 11% T.SPOT11% T.SPOT• More boosting (qualitatively and quantitatively) in those baseline positive TSTMore boosting (qualitatively and quantitatively) in those baseline positive TST
• Repeatability (w/i 2 weeks):Repeatability (w/i 2 weeks):• QFT-GIT: neg to pos: 10 of 134 (7.5%)QFT-GIT: neg to pos: 10 of 134 (7.5%)• T.SPOT: neg to pos: 9 of 111 (8.1%)T.SPOT: neg to pos: 9 of 111 (8.1%)
• Reproducibility (same time 2 tubes):Reproducibility (same time 2 tubes):• QFT-GIT: discordant: 10 of 172 (5.8%)QFT-GIT: discordant: 10 of 172 (5.8%)• T.SPOT: discordant: 10 of 153 (6.5%)T.SPOT: discordant: 10 of 153 (6.5%)
• Boosted:Boosted:• 9.1% QFT-GIT9.1% QFT-GIT• 11% T.SPOT11% T.SPOT• More boosting (qualitatively and quantitatively) in those baseline positive TSTMore boosting (qualitatively and quantitatively) in those baseline positive TST
• Repeatability (w/i 2 weeks):Repeatability (w/i 2 weeks):• QFT-GIT: neg to pos: 10 of 134 (7.5%)QFT-GIT: neg to pos: 10 of 134 (7.5%)• T.SPOT: neg to pos: 9 of 111 (8.1%)T.SPOT: neg to pos: 9 of 111 (8.1%)
• Reproducibility (same time 2 tubes):Reproducibility (same time 2 tubes):• QFT-GIT: discordant: 10 of 172 (5.8%)QFT-GIT: discordant: 10 of 172 (5.8%)• T.SPOT: discordant: 10 of 153 (6.5%)T.SPOT: discordant: 10 of 153 (6.5%)
Am J Respir Crit Care Med 189: 77, 2014Am J Respir Crit Care Med 189: 77, 2014Am J Respir Crit Care Med 189: 77, 2014Am J Respir Crit Care Med 189: 77, 2014
What’s New in LTBI?What’s New in LTBI?IGRAs – HCW ScreeningIGRAs – HCW Screening
What’s New in LTBI?What’s New in LTBI?IGRAs – HCW ScreeningIGRAs – HCW Screening
Am J Respir Crit Care Med 188: 1005, 2013Am J Respir Crit Care Med 188: 1005, 2013Am J Respir Crit Care Med 188: 1005, 2013Am J Respir Crit Care Med 188: 1005, 2013
What’s New in LTBI?What’s New in LTBI?IGRAs – HCW ScreeningIGRAs – HCW Screening
What’s New in LTBI?What’s New in LTBI?IGRAs – HCW ScreeningIGRAs – HCW Screening
• Retrospective Retrospective
• 9153 HCWs with 2 or more QFT June 2008 and July 20109153 HCWs with 2 or more QFT June 2008 and July 2010
• Stanford Medical Center, Palo Alto, CAStanford Medical Center, Palo Alto, CA
• Conversion: 4.4% (361)Conversion: 4.4% (361)
• Reversions: 169 of 261 repeated tests <60 days (65%)Reversions: 169 of 261 repeated tests <60 days (65%)
• Reversions: 38 of 60 repeated tests >60 days (63%)Reversions: 38 of 60 repeated tests >60 days (63%)
• Reversions and conversions most 0.35 – 1.0 IU/mlReversions and conversions most 0.35 – 1.0 IU/ml• 74% reversions, 62% conversions, 28% persistent +ve74% reversions, 62% conversions, 28% persistent +ve
• 12 of 16 (75%) ‘persistently’ positive REVERTED12 of 16 (75%) ‘persistently’ positive REVERTED
• Retrospective Retrospective
• 9153 HCWs with 2 or more QFT June 2008 and July 20109153 HCWs with 2 or more QFT June 2008 and July 2010
• Stanford Medical Center, Palo Alto, CAStanford Medical Center, Palo Alto, CA
• Conversion: 4.4% (361)Conversion: 4.4% (361)
• Reversions: 169 of 261 repeated tests <60 days (65%)Reversions: 169 of 261 repeated tests <60 days (65%)
• Reversions: 38 of 60 repeated tests >60 days (63%)Reversions: 38 of 60 repeated tests >60 days (63%)
• Reversions and conversions most 0.35 – 1.0 IU/mlReversions and conversions most 0.35 – 1.0 IU/ml• 74% reversions, 62% conversions, 28% persistent +ve74% reversions, 62% conversions, 28% persistent +ve
• 12 of 16 (75%) ‘persistently’ positive REVERTED12 of 16 (75%) ‘persistently’ positive REVERTED
Am J Respir Crit Care Med 188: 1005, 2013Am J Respir Crit Care Med 188: 1005, 2013Am J Respir Crit Care Med 188: 1005, 2013Am J Respir Crit Care Med 188: 1005, 2013
What’s New in LTBI?What’s New in LTBI?IGRAs – HCW ScreeningIGRAs – HCW Screening
What’s New in LTBI?What’s New in LTBI?IGRAs – HCW ScreeningIGRAs – HCW Screening
Am J Respir Crit Care Med 188: 1005, 2013Am J Respir Crit Care Med 188: 1005, 2013Am J Respir Crit Care Med 188: 1005, 2013Am J Respir Crit Care Med 188: 1005, 2013
What’s New in LTBI?What’s New in LTBI?IGRAs – HCW ScreeningIGRAs – HCW Screening
What’s New in LTBI?What’s New in LTBI?IGRAs – HCW ScreeningIGRAs – HCW Screening
Am J Respir Crit Care Med 188: 1005, 2013Am J Respir Crit Care Med 188: 1005, 2013Am J Respir Crit Care Med 188: 1005, 2013Am J Respir Crit Care Med 188: 1005, 2013
What’s New in LTBI?What’s New in LTBI?IGRAs – HCW ScreeningIGRAs – HCW Screening
What’s New in LTBI?What’s New in LTBI?IGRAs – HCW ScreeningIGRAs – HCW Screening
Am J Respir Crit Care Med 188: 1005, 2013Am J Respir Crit Care Med 188: 1005, 2013Am J Respir Crit Care Med 188: 1005, 2013Am J Respir Crit Care Med 188: 1005, 2013
What’s New in LTBI?What’s New in LTBI?IGRAs – HCW ScreeningIGRAs – HCW Screening
What’s New in LTBI?What’s New in LTBI?IGRAs – HCW ScreeningIGRAs – HCW Screening
• Retrospective Retrospective
• 2303 HCWs – QFT-GIT Nov 2008 and Jan 2011, 2303 HCWs – QFT-GIT Nov 2008 and Jan 2011, >>2 IGRAs >1yr apart2 IGRAs >1yr apart
• Central Arkansas Veterans Healthcare SystemCentral Arkansas Veterans Healthcare System
• Baseline positive tests: 69 (3.1%)Baseline positive tests: 69 (3.1%)
• Reversions (baseline): 31 of 69 (45%) Reversions (baseline): 31 of 69 (45%)
• Conversion: 71 of 2232 (3.2%) only two of 71 TST positiveConversion: 71 of 2232 (3.2%) only two of 71 TST positive
• Reversions: 37 of 41Reversions: 37 of 41of 71 of 71 (90%)(90%)
• Retrospective Retrospective
• 2303 HCWs – QFT-GIT Nov 2008 and Jan 2011, 2303 HCWs – QFT-GIT Nov 2008 and Jan 2011, >>2 IGRAs >1yr apart2 IGRAs >1yr apart
• Central Arkansas Veterans Healthcare SystemCentral Arkansas Veterans Healthcare System
• Baseline positive tests: 69 (3.1%)Baseline positive tests: 69 (3.1%)
• Reversions (baseline): 31 of 69 (45%) Reversions (baseline): 31 of 69 (45%)
• Conversion: 71 of 2232 (3.2%) only two of 71 TST positiveConversion: 71 of 2232 (3.2%) only two of 71 TST positive
• Reversions: 37 of 41Reversions: 37 of 41of 71 of 71 (90%)(90%)
10.1513/AnnalsATS.201310-378OC 21Jan1410.1513/AnnalsATS.201310-378OC 21Jan1410.1513/AnnalsATS.201310-378OC 21Jan1410.1513/AnnalsATS.201310-378OC 21Jan14
What’s New in LTBI?What’s New in LTBI?IGRAs – HCW ScreeningIGRAs – HCW Screening
What’s New in LTBI?What’s New in LTBI?IGRAs – HCW ScreeningIGRAs – HCW Screening
• Prospective Prospective
• 258 HCWs – TST and QFT-GIT at baseline(2-step TST) and 1 year later258 HCWs – TST and QFT-GIT at baseline(2-step TST) and 1 year later
• 38% BCG-vaccinated 71% Canadian born38% BCG-vaccinated 71% Canadian born
• McGill University Health Centre Montreal, CanadaMcGill University Health Centre Montreal, Canada
• Baseline positive TST tests: 17 of 258 (6.5%)Baseline positive TST tests: 17 of 258 (6.5%)
• Baseline positive QFT-GIT tests: 13 of 258 (5.0%)Baseline positive QFT-GIT tests: 13 of 258 (5.0%)
• Reversions QFT: 8 of 13 (62%) Reversions QFT: 8 of 13 (62%) • (baseline median QFT : reversion: 1.0 persist positive 2.59)(baseline median QFT : reversion: 1.0 persist positive 2.59)
• Conversion TST: 1 of 241 (0.4%) Conversion TST: 1 of 241 (0.4%)
• Conversion QFT: 13 of 245 (5.3%) Conversion QFT: 13 of 245 (5.3%)
• Prospective Prospective
• 258 HCWs – TST and QFT-GIT at baseline(2-step TST) and 1 year later258 HCWs – TST and QFT-GIT at baseline(2-step TST) and 1 year later
• 38% BCG-vaccinated 71% Canadian born38% BCG-vaccinated 71% Canadian born
• McGill University Health Centre Montreal, CanadaMcGill University Health Centre Montreal, Canada
• Baseline positive TST tests: 17 of 258 (6.5%)Baseline positive TST tests: 17 of 258 (6.5%)
• Baseline positive QFT-GIT tests: 13 of 258 (5.0%)Baseline positive QFT-GIT tests: 13 of 258 (5.0%)
• Reversions QFT: 8 of 13 (62%) Reversions QFT: 8 of 13 (62%) • (baseline median QFT : reversion: 1.0 persist positive 2.59)(baseline median QFT : reversion: 1.0 persist positive 2.59)
• Conversion TST: 1 of 241 (0.4%) Conversion TST: 1 of 241 (0.4%)
• Conversion QFT: 13 of 245 (5.3%) Conversion QFT: 13 of 245 (5.3%)
PLOS ONE 8: e54748, 2013PLOS ONE 8: e54748, 2013PLOS ONE 8: e54748, 2013PLOS ONE 8: e54748, 2013
Interferon-Gamma Release Assays Interferon-Gamma Release Assays and the 12-week INH/RPT Regimen and the 12-week INH/RPT Regimen
for Latent TB Infection:for Latent TB Infection:
Public Health ImplicationsPublic Health Implications
Deborah Sodt, RN, PHN, MPHDeborah Sodt, RN, PHN, MPH
TB Program ManagerTB Program Manager
Minnesota Department of HealthMinnesota Department of Health
March 6, 2014March 6, 2014
ObjectiveObjective
• Describe public health perspectives on the Describe public health perspectives on the advantages and limitations of IGRA testing advantages and limitations of IGRA testing and shorter LTBI treatment regimens.and shorter LTBI treatment regimens.
DisclosureDisclosure
Relevant Financial RelationshipsRelevant Financial RelationshipsNoneNone
Off-Label/Investigational UsesOff-Label/Investigational Uses NoneNone
TB Burden, Worldwide, 2010TB Burden, Worldwide, 2010
•Source: WHO: Global Tuberculosis Source: WHO: Global Tuberculosis Control Report, 2010 Control Report, 2010
Latent TB Infection (LTBI)Latent TB Infection (LTBI)
• Estimated 5-10 million Estimated 5-10 million people with LTBI in the U.S. people with LTBI in the U.S. (4-5% of population)(4-5% of population)
• Most U.S. cases result from Most U.S. cases result from reactivation of LTBI. This is reactivation of LTBI. This is the most infectious form of the most infectious form of TB TB
• Persons with LTBI are the Persons with LTBI are the reservoir of future TB reservoir of future TB
Adapted from Ann Settgast, Adapted from Ann Settgast, M.D. March 2010M.D. March 2010
•Active Active TBTB
•LTBILTBI
Module 3 – Targeted Testing and the Diagnosis of Module 3 – Targeted Testing and the Diagnosis of Latent Tuberculosis Infection and Tuberculosis DiseaseLatent Tuberculosis Infection and Tuberculosis Disease
Targeted TB Testing (1)Targeted TB Testing (1)
• Targeted testing is a TB control strategy used to identify and Targeted testing is a TB control strategy used to identify and treat persons:treat persons:
• At high risk for infection with At high risk for infection with M. M. tuberculosistuberculosis
• At high risk for developing TB disease At high risk for developing TB disease once infected with once infected with M. tuberculosisM. tuberculosis
Module 3 – Targeted Testing and the Diagnosis of Module 3 – Targeted Testing and the Diagnosis of Latent Tuberculosis Infection and Tuberculosis DiseaseLatent Tuberculosis Infection and Tuberculosis Disease
• Identifying persons with LTBI is an important goal of TB Identifying persons with LTBI is an important goal of TB elimination because LTBI treatment can:elimination because LTBI treatment can:
• Prevent the development of TB diseasePrevent the development of TB disease
• Stop the spread of TBStop the spread of TB
Targeted TB Testing (2)Targeted TB Testing (2)
••* Risk categories are not mutually exclusive.* Risk categories are not mutually exclusive.
• † †Alcohol abuse and/or illicit drug use.Alcohol abuse and/or illicit drug use.
•** Conditions or therapies that increase risk for progression from latent TB infection to active TB disease.** Conditions or therapies that increase risk for progression from latent TB infection to active TB disease.
Medical Medical conditions*conditions*
CasesCases(N=806)(N=806)No. ( %)No. ( %)
DiabetesDiabetesOther Immunosuppressive TherapyOther Immunosuppressive TherapyEnd Stage Renal DiseaseEnd Stage Renal DiseaseProlonged Corticosteroid TherapyProlonged Corticosteroid Therapy•Weight loss/UndernutritionWeight loss/UndernutritionHematologic/Reticuloendothelial Disease Hematologic/Reticuloendothelial Disease
65 ( 8)65 ( 8)41 ( 5)41 ( 5)13 ( 2)13 ( 2)2 (<1)2 (<1)6 ( 1)6 ( 1)1 (<1)1 (<1)
*Patients could have > 1 medical condition.*Patients could have > 1 medical condition.
Disadvantages of IGRAsDisadvantages of IGRAs
• Potential for false positive or negative Potential for false positive or negative resultsresults
• Requires trained phlebotomists and careful Requires trained phlebotomists and careful specimen handlingspecimen handling
• Not universally availableNot universally available
• Cost/perceived costCost/perceived cost
Advantages of IGRAs (1)Advantages of IGRAs (1)
• One visit; results available within 24 hoursOne visit; results available within 24 hours
• High level of specificity makes it a good High level of specificity makes it a good test for persons who have received BCG test for persons who have received BCG
• Convenience makes it a good test for Convenience makes it a good test for groups that historically have low rates of groups that historically have low rates of return for TST reading (homeless persons, return for TST reading (homeless persons, drug-users, [HCWs?]) drug-users, [HCWs?])
Advantages of IGRAs (2)Advantages of IGRAs (2)
• Less likely to have incorrect reading of Less likely to have incorrect reading of results as compared to TSTresults as compared to TST
• Does not boost responses measured by Does not boost responses measured by subsequent tests subsequent tests
• Potential for cost savings by decreasing Potential for cost savings by decreasing the number of persons receiving follow-the number of persons receiving follow-up medical evaluation and LTBI up medical evaluation and LTBI treatmenttreatment
• As with TST, IGRAs generally should not As with TST, IGRAs generally should not be used for testing persons at low risk of be used for testing persons at low risk of infection and low risk of disease due to infection and low risk of disease due to M. M. tuberculosistuberculosis. .
• Birth in an area of the world where TB is Birth in an area of the world where TB is common is by far the primary risk factor common is by far the primary risk factor for TB in Minnesotafor TB in Minnesota
• IGRA is recommended for individuals who IGRA is recommended for individuals who have had BCG vaccine have had BCG vaccine
Key Points: IGRA Testing (1) Key Points: IGRA Testing (1)
• Caution should be used when interpreting Caution should be used when interpreting results in certain populations because of results in certain populations because of limited data on IGRAslimited data on IGRAs
• Each facility should evaluate the feasibility Each facility should evaluate the feasibility of IGRAs in deciding whether to use them of IGRAs in deciding whether to use them
• IGRAs are preferred in certain groups and IGRAs are preferred in certain groups and TSTs are preferred in others, but use of TSTs are preferred in others, but use of either test is acceptable medical and either test is acceptable medical and public health practicepublic health practice
Key Points: IGRA Testing (2) Key Points: IGRA Testing (2)
•BackgroundBackground
•Diagnostics – IGRADiagnostics – IGRA•HCWHCW
•TreatmentTreatment•RPT-INH 12 weeksRPT-INH 12 weeks
•SummarySummary
•BackgroundBackground
•Diagnostics – IGRADiagnostics – IGRA•HCWHCW
•TreatmentTreatment•RPT-INH 12 weeksRPT-INH 12 weeks
•SummarySummary
What’s New in LTBI?What’s New in LTBI?What’s New in LTBI?What’s New in LTBI?
Initiating TreatmentInitiating Treatment Initiating TreatmentInitiating Treatment
Before initiating treatment for LTBIBefore initiating treatment for LTBI
• Rule out TB disease (i.e., wait for culture result if Rule out TB disease (i.e., wait for culture result if specimen obtained) – PULMONARY or specimen obtained) – PULMONARY or EXTRAPULMONARYEXTRAPULMONARY
• Determine prior history of treatment for LTBI or TB Determine prior history of treatment for LTBI or TB diseasedisease
• Assess risks and benefits of treatmentAssess risks and benefits of treatment
• Determine current and previous drug therapyDetermine current and previous drug therapy
Before initiating treatment for LTBIBefore initiating treatment for LTBI
• Rule out TB disease (i.e., wait for culture result if Rule out TB disease (i.e., wait for culture result if specimen obtained) – PULMONARY or specimen obtained) – PULMONARY or EXTRAPULMONARYEXTRAPULMONARY
• Determine prior history of treatment for LTBI or TB Determine prior history of treatment for LTBI or TB diseasedisease
• Assess risks and benefits of treatmentAssess risks and benefits of treatment
• Determine current and previous drug therapyDetermine current and previous drug therapy
LTBI RegimensLTBI RegimensLTBI RegimensLTBI Regimens
• ISONIAZID (INH)ISONIAZID (INH) * *• 9 months 9 months
• Combination: Combination: RIFAPENTINE (RPT) plus ISONIAZIDRIFAPENTINE (RPT) plus ISONIAZID * *• 3 months, weekly dosing3 months, weekly dosing
• RIFAMPIN (RIF)RIFAMPIN (RIF)• 4 months4 months
• Others: 6INH, intermittent INH, 3IROthers: 6INH, intermittent INH, 3IR
*preferred*preferred
• ISONIAZID (INH)ISONIAZID (INH) * *• 9 months 9 months
• Combination: Combination: RIFAPENTINE (RPT) plus ISONIAZIDRIFAPENTINE (RPT) plus ISONIAZID * *• 3 months, weekly dosing3 months, weekly dosing
• RIFAMPIN (RIF)RIFAMPIN (RIF)• 4 months4 months
• Others: 6INH, intermittent INH, 3IROthers: 6INH, intermittent INH, 3IR
*preferred*preferred
Isoniazid RegimensIsoniazid RegimensIsoniazid RegimensIsoniazid Regimens
• 9-month regimen of DAILY isoniazid (INH)9-month regimen of DAILY isoniazid (INH) self- self-administered is the historical preferred regimenadministered is the historical preferred regimen
• Alternative: Alternative: 3-month, WEEKLY RPT and INH3-month, WEEKLY RPT and INH, DOT, DOT
• Age >12, LTBI and risk for developing TB Age >12, LTBI and risk for developing TB disease: disease:
• Recent exposure, new conversion, or x-ray Recent exposure, new conversion, or x-ray healed TBhealed TB
• 9-month regimen of DAILY isoniazid (INH)9-month regimen of DAILY isoniazid (INH) self- self-administered is the historical preferred regimenadministered is the historical preferred regimen
• Alternative: Alternative: 3-month, WEEKLY RPT and INH3-month, WEEKLY RPT and INH, DOT, DOT
• Age >12, LTBI and risk for developing TB Age >12, LTBI and risk for developing TB disease: disease:
• Recent exposure, new conversion, or x-ray Recent exposure, new conversion, or x-ray healed TBhealed TB
Latent TB Infection (LTBI)Latent TB Infection (LTBI)Treatment – 3RPT/INHTreatment – 3RPT/INH
Latent TB Infection (LTBI)Latent TB Infection (LTBI)Treatment – 3RPT/INHTreatment – 3RPT/INH
NEJM 365: 2155, 2011 NEJM 365: 2155, 2011 NEJM 365: 2155, 2011 NEJM 365: 2155, 2011
Latent TB Infection (LTBI)Latent TB Infection (LTBI)Treatment – 3RPT/INHTreatment – 3RPT/INH
Latent TB Infection (LTBI)Latent TB Infection (LTBI)Treatment – 3RPT/INHTreatment – 3RPT/INH
• PREVENT TB Study – TBTC Study 26PREVENT TB Study – TBTC Study 26
• N= 8,053, 10 years; US, Brazil, and Spain 33wk f/uN= 8,053, 10 years; US, Brazil, and Spain 33wk f/u
• Randomized 9INH versus 3Rifapentine plus INH(weekly)Randomized 9INH versus 3Rifapentine plus INH(weekly)
• PREVENT TB Study – TBTC Study 26PREVENT TB Study – TBTC Study 26
• N= 8,053, 10 years; US, Brazil, and Spain 33wk f/uN= 8,053, 10 years; US, Brazil, and Spain 33wk f/u
• Randomized 9INH versus 3Rifapentine plus INH(weekly)Randomized 9INH versus 3Rifapentine plus INH(weekly)
NEJM 365: 2155, 2011 NEJM 365: 2155, 2011 NEJM 365: 2155, 2011 NEJM 365: 2155, 2011
Latent TB Infection (LTBI)Latent TB Infection (LTBI)Treatment – 3RPT/INHTreatment – 3RPT/INH
Latent TB Infection (LTBI)Latent TB Infection (LTBI)Treatment – 3RPT/INHTreatment – 3RPT/INH
• PREVENT TB Study – TBTC Study 26PREVENT TB Study – TBTC Study 26
• N= 8,053, 10 years; US, Brazil, and Spain 33wk f/uN= 8,053, 10 years; US, Brazil, and Spain 33wk f/u
• Randomized 9INH versus 3Rifapentine plus INH(weekly)Randomized 9INH versus 3Rifapentine plus INH(weekly)
• PREVENT TB Study – TBTC Study 26PREVENT TB Study – TBTC Study 26
• N= 8,053, 10 years; US, Brazil, and Spain 33wk f/uN= 8,053, 10 years; US, Brazil, and Spain 33wk f/u
• Randomized 9INH versus 3Rifapentine plus INH(weekly)Randomized 9INH versus 3Rifapentine plus INH(weekly)
NEJM 365: 2155, 2011 NEJM 365: 2155, 2011 NEJM 365: 2155, 2011 NEJM 365: 2155, 2011
Latent TB Infection (LTBI)Latent TB Infection (LTBI)Treatment – 3RPT/INHTreatment – 3RPT/INH
Latent TB Infection (LTBI)Latent TB Infection (LTBI)Treatment – 3RPT/INHTreatment – 3RPT/INH
• PREVENT TB Study – TBTC Study 26PREVENT TB Study – TBTC Study 26
• N= 8,053, 10 years; US, Brazil, and Spain 33wk f/uN= 8,053, 10 years; US, Brazil, and Spain 33wk f/u
• Randomized 9INH versus 3Rifapentine plus INH (weekly)Randomized 9INH versus 3Rifapentine plus INH (weekly)
• 3Rifapentine plus INH 3Rifapentine plus INH safe and effectivesafe and effective
• TB dis: 7 cases 3RPT/INH (0.19%) vs 15 cases 9INH (0.43%)TB dis: 7 cases 3RPT/INH (0.19%) vs 15 cases 9INH (0.43%)
• Completion: 82% 3RPT/INH versus 69% 9INH (p<0.001)Completion: 82% 3RPT/INH versus 69% 9INH (p<0.001)
• AE: 4.9% vs 3.7% (p=0.009), hepatotoxicity: 0.4% vs 2.7% (p<0.001)AE: 4.9% vs 3.7% (p=0.009), hepatotoxicity: 0.4% vs 2.7% (p<0.001)
• Applicable to:Applicable to:• Countries with low-to-medium TB incidenceCountries with low-to-medium TB incidence• Treatment given via DOT (directly observed therapy)Treatment given via DOT (directly observed therapy)
• PREVENT TB Study – TBTC Study 26PREVENT TB Study – TBTC Study 26
• N= 8,053, 10 years; US, Brazil, and Spain 33wk f/uN= 8,053, 10 years; US, Brazil, and Spain 33wk f/u
• Randomized 9INH versus 3Rifapentine plus INH (weekly)Randomized 9INH versus 3Rifapentine plus INH (weekly)
• 3Rifapentine plus INH 3Rifapentine plus INH safe and effectivesafe and effective
• TB dis: 7 cases 3RPT/INH (0.19%) vs 15 cases 9INH (0.43%)TB dis: 7 cases 3RPT/INH (0.19%) vs 15 cases 9INH (0.43%)
• Completion: 82% 3RPT/INH versus 69% 9INH (p<0.001)Completion: 82% 3RPT/INH versus 69% 9INH (p<0.001)
• AE: 4.9% vs 3.7% (p=0.009), hepatotoxicity: 0.4% vs 2.7% (p<0.001)AE: 4.9% vs 3.7% (p=0.009), hepatotoxicity: 0.4% vs 2.7% (p<0.001)
• Applicable to:Applicable to:• Countries with low-to-medium TB incidenceCountries with low-to-medium TB incidence• Treatment given via DOT (directly observed therapy)Treatment given via DOT (directly observed therapy)
NEJM 365: 2155, 2011 NEJM 365: 2155, 2011 NEJM 365: 2155, 2011 NEJM 365: 2155, 2011
Latent TB Infection (LTBI) TreatmentLatent TB Infection (LTBI) Treatment3RPT-INH - CDC 20113RPT-INH - CDC 2011
Latent TB Infection (LTBI) TreatmentLatent TB Infection (LTBI) Treatment3RPT-INH - CDC 20113RPT-INH - CDC 2011
MMWR 60: 1650, 2011 MMWR 60: 1650, 2011 MMWR 60: 1650, 2011 MMWR 60: 1650, 2011
Latent TB Infection (LTBI) TreatmentLatent TB Infection (LTBI) Treatment3RPT-INH - CDC 20113RPT-INH - CDC 2011
Latent TB Infection (LTBI) TreatmentLatent TB Infection (LTBI) Treatment3RPT-INH - CDC 20113RPT-INH - CDC 2011
• 23 expert consultants, reviewed TBTC 26 as well as other INH-RPT trials23 expert consultants, reviewed TBTC 26 as well as other INH-RPT trials
• RECOMMENDEDRECOMMENDED via DOT! via DOT!• Age >12, LTBI and risk for developing TB diseaseAge >12, LTBI and risk for developing TB disease
• Recent exposure, new conversion, or x-ray healed TBRecent exposure, new conversion, or x-ray healed TB• DOT resources availableDOT resources available
• NOT RECOMMENDEDNOT RECOMMENDED::• Age < 2 yearsAge < 2 years• HIV / AIDS taking antiretroviralHIV / AIDS taking antiretroviral treatment treatment• Presumed infected with INH or RIF-Presumed infected with INH or RIF-resistant resistant M. tuberculosisM. tuberculosis andand• Pregnant Pregnant women or women expecting to become pregnant within the 12 week regimenwomen or women expecting to become pregnant within the 12 week regimen
• 23 expert consultants, reviewed TBTC 26 as well as other INH-RPT trials23 expert consultants, reviewed TBTC 26 as well as other INH-RPT trials
• RECOMMENDEDRECOMMENDED via DOT! via DOT!• Age >12, LTBI and risk for developing TB diseaseAge >12, LTBI and risk for developing TB disease
• Recent exposure, new conversion, or x-ray healed TBRecent exposure, new conversion, or x-ray healed TB• DOT resources availableDOT resources available
• NOT RECOMMENDEDNOT RECOMMENDED::• Age < 2 yearsAge < 2 years• HIV / AIDS taking antiretroviralHIV / AIDS taking antiretroviral treatment treatment• Presumed infected with INH or RIF-Presumed infected with INH or RIF-resistant resistant M. tuberculosisM. tuberculosis andand• Pregnant Pregnant women or women expecting to become pregnant within the 12 week regimenwomen or women expecting to become pregnant within the 12 week regimen
MMWR 60: 1650, 2011 MMWR 60: 1650, 2011 MMWR 60: 1650, 2011 MMWR 60: 1650, 2011
Latent TB Infection (LTBI) TreatmentLatent TB Infection (LTBI) Treatment3RPT-INH - CDC 20113RPT-INH - CDC 2011
Latent TB Infection (LTBI) TreatmentLatent TB Infection (LTBI) Treatment3RPT-INH - CDC 20113RPT-INH - CDC 2011
• FAVORED ALTERNATIVE FAVORED ALTERNATIVE (to 9INH):(to 9INH):• Practical advantage – correctional settings, recent Practical advantage – correctional settings, recent
immigrants, homeless sheltersimmigrants, homeless shelters• Social circumstances that makes adherence questionableSocial circumstances that makes adherence questionable
• Dosing Dosing 3RPT/INH - DOT• Completion 11 or 12 doses within 16 weeksCompletion 11 or 12 doses within 16 weeks• Doses separated by > 72 hours to be countedDoses separated by > 72 hours to be counted
• FAVORED ALTERNATIVE FAVORED ALTERNATIVE (to 9INH):(to 9INH):• Practical advantage – correctional settings, recent Practical advantage – correctional settings, recent
immigrants, homeless sheltersimmigrants, homeless shelters• Social circumstances that makes adherence questionableSocial circumstances that makes adherence questionable
• Dosing Dosing 3RPT/INH - DOT• Completion 11 or 12 doses within 16 weeksCompletion 11 or 12 doses within 16 weeks• Doses separated by > 72 hours to be countedDoses separated by > 72 hours to be counted
MMWR 60: 1650, 2011 MMWR 60: 1650, 2011 MMWR 60: 1650, 2011 MMWR 60: 1650, 2011
Latent TB Infection (LTBI) TreatmentLatent TB Infection (LTBI) Treatment3RPT-INH - CDC 20113RPT-INH - CDC 2011
Latent TB Infection (LTBI) TreatmentLatent TB Infection (LTBI) Treatment3RPT-INH - CDC 20113RPT-INH - CDC 2011
• 3RPT/INH for age 2 – 11 years old3RPT/INH for age 2 – 11 years old::• If completion of 9INH unlikelyIf completion of 9INH unlikely• (and) likelihood of TB high(and) likelihood of TB high
• 9INH monotherapy PREFERRED age 2-11 9INH monotherapy PREFERRED age 2-11
• 3RPT/INH for age 2 – 11 years old3RPT/INH for age 2 – 11 years old::• If completion of 9INH unlikelyIf completion of 9INH unlikely• (and) likelihood of TB high(and) likelihood of TB high
• 9INH monotherapy PREFERRED age 2-11 9INH monotherapy PREFERRED age 2-11
MMWR 60: 1650, 2011 MMWR 60: 1650, 2011 MMWR 60: 1650, 2011 MMWR 60: 1650, 2011
Latent TB Infection (LTBI) TreatmentLatent TB Infection (LTBI) Treatment3RPT-INH - CDC 20113RPT-INH - CDC 2011
Latent TB Infection (LTBI) TreatmentLatent TB Infection (LTBI) Treatment3RPT-INH - CDC 20113RPT-INH - CDC 2011
Latent TB Infection (LTBI) TreatmentLatent TB Infection (LTBI) Treatment3RPT-INH - CDC 20113RPT-INH - CDC 2011
Latent TB Infection (LTBI) TreatmentLatent TB Infection (LTBI) Treatment3RPT-INH - CDC 20113RPT-INH - CDC 2011
Latent TB Infection (LTBI) TreatmentLatent TB Infection (LTBI) Treatment3RPT-INH - CDC 20113RPT-INH - CDC 2011
Latent TB Infection (LTBI) TreatmentLatent TB Infection (LTBI) Treatment3RPT-INH - CDC 20113RPT-INH - CDC 2011
• Dosing Dosing 3 RPT/INH arm
• Rifapentine:
• Persons weighing > 50.0 kg received rifapentine 900 mg once-weekly
• Persons weighing < 50.0 kg were dosed once-weekly according to the following scale:
• 10.0-14.0 kg 300 mg
• 14.1-25.0 kg 450 mg
• 25.1-32.0 kg 600 mg
• 32.1-50.0 kg 750 mg
• Isoniazid:
• Persons 2-11 years old received isoniazid 25 mg/kg (rounded up to the nearest 50 or 100 mg; 900mg max) once-weekly
• Persons > 12 years old received isoniazid 15 mg/kg (rounded up to nearest 50 or 100 mg; 900mg max) once-weekly
• Dosing Dosing 3 RPT/INH arm
• Rifapentine:
• Persons weighing > 50.0 kg received rifapentine 900 mg once-weekly
• Persons weighing < 50.0 kg were dosed once-weekly according to the following scale:
• 10.0-14.0 kg 300 mg
• 14.1-25.0 kg 450 mg
• 25.1-32.0 kg 600 mg
• 32.1-50.0 kg 750 mg
• Isoniazid:
• Persons 2-11 years old received isoniazid 25 mg/kg (rounded up to the nearest 50 or 100 mg; 900mg max) once-weekly
• Persons > 12 years old received isoniazid 15 mg/kg (rounded up to nearest 50 or 100 mg; 900mg max) once-weekly
MMWR 60: 1650, 2011 MMWR 60: 1650, 2011 MMWR 60: 1650, 2011 MMWR 60: 1650, 2011
Short Course Therapy with RIF plus Short Course Therapy with RIF plus INH 3 Months versus Standard INHINH 3 Months versus Standard INH
Short Course Therapy with RIF plus Short Course Therapy with RIF plus INH 3 Months versus Standard INHINH 3 Months versus Standard INH
• Not CDC approved for LTBI (as of 2000 with updates)Not CDC approved for LTBI (as of 2000 with updates)
• Meta-analysis LTBI treatmentMeta-analysis LTBI treatment
• Pooled 1926 patients (5 studies) Hong Kong, Spain, and UgandaPooled 1926 patients (5 studies) Hong Kong, Spain, and Uganda
• Equivalent to standard therapy with INH (IR3 vs I6-12) :Equivalent to standard therapy with INH (IR3 vs I6-12) :• Efficacy (4.2% vs. 4.1%)Efficacy (4.2% vs. 4.1%)• Severe side effects (4.9% vs. 4.8%)Severe side effects (4.9% vs. 4.8%)• Mortality (9.5% vs. 10.4%)Mortality (9.5% vs. 10.4%)
• Also equally effective in pediatric population, better completion (Greece)Also equally effective in pediatric population, better completion (Greece)
• Not CDC approved for LTBI (as of 2000 with updates)Not CDC approved for LTBI (as of 2000 with updates)
• Meta-analysis LTBI treatmentMeta-analysis LTBI treatment
• Pooled 1926 patients (5 studies) Hong Kong, Spain, and UgandaPooled 1926 patients (5 studies) Hong Kong, Spain, and Uganda
• Equivalent to standard therapy with INH (IR3 vs I6-12) :Equivalent to standard therapy with INH (IR3 vs I6-12) :• Efficacy (4.2% vs. 4.1%)Efficacy (4.2% vs. 4.1%)• Severe side effects (4.9% vs. 4.8%)Severe side effects (4.9% vs. 4.8%)• Mortality (9.5% vs. 10.4%)Mortality (9.5% vs. 10.4%)
• Also equally effective in pediatric population, better completion (Greece)Also equally effective in pediatric population, better completion (Greece)
CID 40: 670-676, 2005CID 40: 670-676, 2005CID 45: 715-722, 2007CID 45: 715-722, 2007
CID 40: 670-676, 2005CID 40: 670-676, 2005CID 45: 715-722, 2007CID 45: 715-722, 2007
Latent TB Infection (LTBI) TreatmentLatent TB Infection (LTBI) TreatmentMonitoring RPT-INH - CDC 2011Monitoring RPT-INH - CDC 2011
Latent TB Infection (LTBI) TreatmentLatent TB Infection (LTBI) TreatmentMonitoring RPT-INH - CDC 2011Monitoring RPT-INH - CDC 2011
• Monitoring Monitoring 3RPT/INH arm• DOT:
• Symptom checklist: fever, yellow eyes, dizziness, paresthesias, rash, aches or > 1 day of nausea, vomiting, weakness, abdominal pain, dark urine, easy bruisability, bleeding, or loss of appetite
• REFER if positive
• Monthly:• Clinical assessment
• Assess adverse effects• Physical exam (icterus, liver tenderness, or rash)• Blood work
• (liver disease, post-partum, EtOH use, HIV)
• Monitoring Monitoring 3RPT/INH arm• DOT:
• Symptom checklist: fever, yellow eyes, dizziness, paresthesias, rash, aches or > 1 day of nausea, vomiting, weakness, abdominal pain, dark urine, easy bruisability, bleeding, or loss of appetite
• REFER if positive
• Monthly:• Clinical assessment
• Assess adverse effects• Physical exam (icterus, liver tenderness, or rash)• Blood work
• (liver disease, post-partum, EtOH use, HIV)
MMWR 60: 1650, 2011 MMWR 60: 1650, 2011 MMWR 60: 1650, 2011 MMWR 60: 1650, 2011
Latent TB Infection (LTBI) TreatmentLatent TB Infection (LTBI) TreatmentMonitoring RPT-INH - CDC 2013Monitoring RPT-INH - CDC 2013
Latent TB Infection (LTBI) TreatmentLatent TB Infection (LTBI) TreatmentMonitoring RPT-INH - CDC 2013Monitoring RPT-INH - CDC 2013
Latent TB Infection (LTBI) TreatmentLatent TB Infection (LTBI) TreatmentMonitoring RPT-INH - CDC 2013Monitoring RPT-INH - CDC 2013
Latent TB Infection (LTBI) TreatmentLatent TB Infection (LTBI) TreatmentMonitoring RPT-INH - CDC 2013Monitoring RPT-INH - CDC 2013
Latent TB Infection (LTBI) TreatmentLatent TB Infection (LTBI) TreatmentMonitoring RPT-INH - CDC 2013Monitoring RPT-INH - CDC 2013
Latent TB Infection (LTBI) TreatmentLatent TB Infection (LTBI) TreatmentMonitoring RPT-INH - CDC 2013Monitoring RPT-INH - CDC 2013
Latent TB Infection (LTBI) TreatmentLatent TB Infection (LTBI) TreatmentMonitoring RPT-INH - CDC 2013Monitoring RPT-INH - CDC 2013
Latent TB Infection (LTBI) TreatmentLatent TB Infection (LTBI) TreatmentMonitoring RPT-INH - CDC 2013Monitoring RPT-INH - CDC 2013
• “possible hypersensitivity”: INH-RPT 3.8% vs. SAT 9H 0.5%• Fever, chills, HA, fatigue, red eyes, urticaria , pruritus, petechiae
• Implementation and safety of the DOT INH-RPT regimen
• TBTC Study 33: “iAdhere study” – SAT INH-RPT
• Ongoing LTBI surveillance for severe AE (hosp or death)
• Post-marketing sentinel site evaluation DOT INH-RPT
• In-depth evaluation of “possible hypersensitivity” TBTC 26
• State health department evaluation of DOT INH-RPT
• Collaboration with Sanofi
• “possible hypersensitivity”: INH-RPT 3.8% vs. SAT 9H 0.5%• Fever, chills, HA, fatigue, red eyes, urticaria , pruritus, petechiae
• Implementation and safety of the DOT INH-RPT regimen
• TBTC Study 33: “iAdhere study” – SAT INH-RPT
• Ongoing LTBI surveillance for severe AE (hosp or death)
• Post-marketing sentinel site evaluation DOT INH-RPT
• In-depth evaluation of “possible hypersensitivity” TBTC 26
• State health department evaluation of DOT INH-RPT
• Collaboration with Sanofi
•BackgroundBackground
•Diagnostics – IGRADiagnostics – IGRA•HCWHCW
•TreatmentTreatment•RPT-INH 12 weeksRPT-INH 12 weeks
•SummarySummary
•BackgroundBackground
•Diagnostics – IGRADiagnostics – IGRA•HCWHCW
•TreatmentTreatment•RPT-INH 12 weeksRPT-INH 12 weeks
•SummarySummary
What’s New in LTBI?What’s New in LTBI?What’s New in LTBI?What’s New in LTBI?
What’s New in LTBI?What’s New in LTBI?SummarySummary
What’s New in LTBI?What’s New in LTBI?SummarySummary
• IGRA testing for TB infection represents a new tool for the IGRA testing for TB infection represents a new tool for the evaluation of TB infection with increased specificity relative to evaluation of TB infection with increased specificity relative to TST, especially in BCG-vaccinated individualsTST, especially in BCG-vaccinated individuals
• IGRA testing used for annual screening (in HCW) has intrinsic IGRA testing used for annual screening (in HCW) has intrinsic variability and limits its general applicabilityvariability and limits its general applicability
• Shorter course therapy (RPT-INH) is an effective LTBI regimen Shorter course therapy (RPT-INH) is an effective LTBI regimen and has advantages over standard 9INH daily but may also and has advantages over standard 9INH daily but may also have unique side effects and needs to be administered by DOT have unique side effects and needs to be administered by DOT with close monitoringwith close monitoring
• IGRA testing for TB infection represents a new tool for the IGRA testing for TB infection represents a new tool for the evaluation of TB infection with increased specificity relative to evaluation of TB infection with increased specificity relative to TST, especially in BCG-vaccinated individualsTST, especially in BCG-vaccinated individuals
• IGRA testing used for annual screening (in HCW) has intrinsic IGRA testing used for annual screening (in HCW) has intrinsic variability and limits its general applicabilityvariability and limits its general applicability
• Shorter course therapy (RPT-INH) is an effective LTBI regimen Shorter course therapy (RPT-INH) is an effective LTBI regimen and has advantages over standard 9INH daily but may also and has advantages over standard 9INH daily but may also have unique side effects and needs to be administered by DOT have unique side effects and needs to be administered by DOT with close monitoringwith close monitoring
1/4 of high-priority LTBI patients in 1/4 of high-priority LTBI patients in Minnesota do not complete therapyMinnesota do not complete therapy
• In 2010, 90% of newly infected contacts in In 2010, 90% of newly infected contacts in Minnesota started LTBI treatmentMinnesota started LTBI treatment
- 73% completed treatment- 73% completed treatment
• In 2010, 87% of TB Class B immigrants and In 2010, 87% of TB Class B immigrants and refugees diagnosed with LTBI in Minnesota refugees diagnosed with LTBI in Minnesota started LTBI treatment started LTBI treatment
- 75% completed treatment- 75% completed treatment
Barriers to LTBI TreatmentBarriers to LTBI Treatment
• Inconvenient clinic hours/locationInconvenient clinic hours/location
• Cultural awareness of staffCultural awareness of staff
• Misinformation (e.g., BCG)Misinformation (e.g., BCG)
• Mistrust of public health or medical systemMistrust of public health or medical system
• Stigma of TBStigma of TB
• Length of treatmentLength of treatment
• Concern about potential side effectsConcern about potential side effects
• etc.etc.
INH-RPT: AdvantagesINH-RPT: Advantages
• Fewer doses/Shorter treatment timeFewer doses/Shorter treatment time
• May increase patient willingness to be May increase patient willingness to be treated for LTBItreated for LTBI
• Higher completion of therapy ratesHigher completion of therapy rates
INH-RPT: DisadvantagesINH-RPT: Disadvantages
• Not appropriate for all patients Not appropriate for all patients
• Higher cost (Rifapentine)Higher cost (Rifapentine)
• Large # of pills (up to 10)Large # of pills (up to 10)
• DOT requiredDOT required- Local public health agencies may vary in - Local public health agencies may vary in their ability to provide DOTtheir ability to provide DOT
Pre-treatment educationPre-treatment education
• Commit to 12 weeks of weekly DOTCommit to 12 weeks of weekly DOT- No moves; no travel- No moves; no travel
• Agree to take up to 9-10 tablets each timeAgree to take up to 9-10 tablets each time
• Avoid pregnancy Avoid pregnancy
• Schedule monthly physical examinations Schedule monthly physical examinations with providerwith provider
• If these cannot reasonably be assured, one If these cannot reasonably be assured, one of the other LTBI treatment regimens of the other LTBI treatment regimens should be usedshould be used
Reporting severe adverse eventsReporting severe adverse events
• With previous LTBI regimens (e.g., INH, With previous LTBI regimens (e.g., INH, rifampin-pyrazinamide), fatal liver injuries rifampin-pyrazinamide), fatal liver injuries came to attention only after the regimens came to attention only after the regimens were widely adopted. were widely adopted.
• Adverse events leading to hospitalization or Adverse events leading to hospitalization or death associated with the use of any LTBI death associated with the use of any LTBI regimen should be reported to regimen should be reported to
- MDH (651-201-5414) for inclusion in - MDH (651-201-5414) for inclusion in CDC’s adverse events surveillance system, CDC’s adverse events surveillance system, -AND--AND-- FDA MedWatch at - FDA MedWatch at http://www.fda.gov/medwatch
• As the incidence of TB disease in the United As the incidence of TB disease in the United States and Minnesota, focus on detecting and States and Minnesota, focus on detecting and treating LTBI will play an increased roletreating LTBI will play an increased role
• TB is decreasing but increasingly occurs in TB is decreasing but increasingly occurs in population subgroups where it can be hard to population subgroups where it can be hard to detect and treat.detect and treat.
• Low completion of LTBI therapy ratesLow completion of LTBI therapy rates
• The second most common risk factor is the The second most common risk factor is the presence of other medical conditions that increase presence of other medical conditions that increase the risk of active TBthe risk of active TB
Key Points: 12-week regimen Key Points: 12-week regimen
ReferencesReferences
• CDC, Division of TB Elimination CDC, Division of TB Elimination http://www.cdc.gov/tb/
• MDH TB Prevention and Control MDH TB Prevention and Control ProgramProgramwww.health.state.mn.us/tb651-201-5414651-201-5414