Seril Testing Using QuntiFERON TB Gold In tue Assy in High Risk Popultion Richrd S. Grfein, PhD, MPH Professor Division of Glol Pulic Helth, School of Medicine University of Cliforni Sn Diego rgrfein@ucsd.edu Tel: 858 822 3018 (Jnury 14, 2012) IGRA s for Injection Drug Users (IDUs) Avoids need for timely return visits Avoids prolems with plcement nd reding TST
Bckground Tijun, B.C., Mexico nd Sn Diego, CA shre the world s usiest torder crossing Tijun hs the 2 nd highest TB rte in Mexico HIV prevlence is low in Tijun, ut incresing due to injection drug use nd sex work IDUs with LTBI re t high risk for HIV coinfection nd susequent LTBI rectivtion Little dt on TB infection incidence mong IDUs Ojectives To estimte the prevlence nd incidence of M. tuerculosis infection nd identify risk ik fctors mong IDUs in Tijun, Mexico To evlute seril QFT testing in high prevlence popultion
Methods Proyecto El Cuete Phse III (PI: S. Strthdee) Design: Prticipnts were recruited etween April 2006 nd April 2007 for longitudinl cohort study. Eligiility criteri: Age 18 yers-old injected drugs in the pst month Spnish or English speking Intended to reside in Tijun for the next 18 months Recruitment: vi respondent driven smpling (RDS) Study visits t seline (BL), 6, 12, nd 18 months Behviorl risk ssessments nd HIV testing t ll visits TB testing t BL nd 18-month visits Methods Detecting M. Tuerculosis Infection QuntiFERON TB Gold In Tue (QFT) ssys performed per mnufcturer s instructions Whole lood collected directly into three heprinized tues contining TB specific ntigens, mitogen (positive control), or heprin only ( nil negtive control) Filled tues incuted t 37 C for 16 24 hours nd centrifuged Tues refrigerted until trnsported to UCSD for ELISA I t t ti (IFN l l i ti i il t ) Interprettion (IFN γ levels in ntigen minus nil tues): 0.35 IU/ml Positive <0.35 IU/ml Negtive <0.5 or >8.0 IU/ml in the nil tue indeterminte
Dt Anlysis Included only IDUs who were QFT negtive t BL nd retested t 18 months Clculted incidence of QFT seroconversion t 18 months using mnufcturer s recommended cutoff (>0.35 IU/mL) nd multiple lternte cutoffs Used univrite nd multivrite logistic regression nlysis, djusted for RDS popultion weights, to identify fctors ssocited with QFT seroconversion All models repeted using lternte cutoffs Results 1,020 IDUs hd complete test results t BL 67% QFT positive 4.0% HIV positive 354 IDUs tested QFT negtive t BL 153 (43.2%) were retested t 18 months 24 (15.7%) indetermintes were excluded 129 (36.4%) IDUs included in this nlysis
Univrite Chrcteristics of IDUs y 18 month QFT Sttus sed on Mnufcturer s Recommended Cutoff (>0.35 IU/mL) QFT-positive QFT-negtive n (%) n (%) Totl n (%) P-vlue Totl Incidence 67 (51.9) 62 (48.1) 129 (100) --- Age in yers: Men (SD) 38.2 (9.4) 37.5 (6.7) 37.9 (8.2) 0.83 Age 50 yers 10 (14.9) 1 ( 1.6) 11 ( 8.5) 0.01 Mle gender 57 (85.1) 50 (80.6) 107 (82.9) 0.64 Speks some English 37 (55.2) 40 (64.5) 77 (59.7) 0.37 Homeless 10 (14.9) 3 ( 4.8) 13 (10.1) 0.08 Lived in household of 3 persons 41 (61.2) 24 (38.7) 65 (50.4) 0.01 Monthly income <3000 pesos 60 (89.6) 44 (71.0) 104 (80.6) 0.01 Tested HIV-positive 3 ( 4.5) 5 ( 8.1) 8 ( 6.2) 0.48 Assessed t 18 month visit. Other vriles ssessed t seline. All p vlues re djusted for RDS popultion weights. Chnge in IFN γ Levels etween Bseline nd 18 month Visits mong IDUs in Tijun, MX (n=129) IFN γ (IU/mL) 0.35
Chnge in IFN γ Levels etween Bseline nd 18 month Visits, mong IDUs in Tijun, MX (suset ner cutoff) IFN γ (IU/mL) M. Tuerculosis Incidence y IFN γ Cutoff Levels IFN-γ cut-off vlues N Pos 18m Inc.(95% CI) 12m Risk (95% CI) Expected 5-yer Prev. c (95% CI) IFN >0.35 67 51.9% (43.1-60.7) 38.6% (31.5-46.2) 91% (84-96) IFN >0.50 60 46.5% (37.7-55.2) 34.1% (27.1-41.5) 88% (79-93) IFN >0.35 (>0.7 incr.) 50 38.7% (30.2-47.3) 27.8% (21.3-34.6) 80% (69-88) IFN >1.28 42 32.6% (24.4-40.7) 23.1% (17.0-29.4) 73% (60-82) IFN >1.67 37 28.7% (20.7-35.6) 20.1% (14.3-26.1) 67% (53-76) IFN-γ levels > 0.35 nd incresed > 0.70 IU/mL etween seline nd 18-month visits considered positive. Risk clculted using stndrd risk-to-risk formuls for different time periods c Estimted 5-Yer prevlence ssuming clculted incidence rtes in closed popultion. All estimtes re djusted using RDS weights sed on QFT35 cutoff. Alternte cutpoints sed on pulished studies: Diel R, et l., Am J Respir Crit Cre Med. 2008;177(10):1164 1170. Higuchi K, et l, Tuerculosis. 2008;88(3):244 248. Pi M. Nture reviews. Microiology. 2010;8(3):242; uthor reply 242. Ringshusen FC, et l., BMC Infect Dis. 2010;10:220. Torres Cost J, et l., J Occup Med Toxicol. 2011;6:19. Zwerling A, et l., Thorx. 2012;67(1):62 70.
M. Tuerculosis Incidence y IFN γ Cutoff Levels IFN-γ cut-off vlues N Pos 18m Inc.(95% CI) 12m Risk (95% CI) Expected 5-yer Prev. c (95% CI) IFN >0.35 67 51.9% (43.1-60.7) 38.6% (31.5-46.2) 91% (84-96) IFN >0.50 60 46.5% (37.7-55.2) 34.1% (27.1-41.5) 88% (79-93) IFN >0.35 (>0.7 incr.) 50 38.7% (30.2-47.3) 27.8% (21.3-34.6) 80% (69-88) IFN >1.28 42 32.6% (24.4-40.7) 23.1% (17.0-29.4) 73% (60-82) IFN >1.67 37 28.7% (20.7-35.6) 20.1% (14.3-26.1) 67% (53-76) IFN-γ levels > 0.35 nd incresed > 0.70 IU/mL etween seline nd 18-month visits considered positive. Risk clculted using stndrd risk-to-risk formuls for different time periods c Estimted 5-Yer prevlence ssuming clculted incidence rtes in closed popultion. All estimtes re djusted using RDS weights sed on QFT35 cutoff. Alternte cutpoints sed on pulished studies: Diel R, et l., Am J Respir Crit Cre Med. 2008;177(10):1164 1170. Higuchi K, et l, Tuerculosis. 2008;88(3):244 248. Pi M. Nture reviews. Microiology. 2010;8(3):242; uthor reply 242. Ringshusen FC, et l., BMC Infect Dis. 2010;10:220. Torres Cost J, et l., J Occup Med Toxicol. 2011;6:19. Zwerling A, et l., Thorx. 2012;67(1):62 70. M. Tuerculosis Incidence y IFN γ Cutoff Levels IFN-γ cut-off vlues N Pos 18m Inc.(95% CI) 12m Risk (95% CI) Expected 5-yer Prev. c (95% CI) IFN >0.35 67 51.9% (43.1-60.7) 38.6% (31.5-46.2) 91% (84-96) IFN >0.50 60 46.5% (37.7-55.2) 34.1% (27.1-41.5) 88% (79-93) IFN >0.35 (>0.7 incr.) 50 38.7% (30.2-47.3) 27.8% (21.3-34.6) 80% (69-88) IFN >1.28 42 32.6% (24.4-40.7) 23.1% (17.0-29.4) 73% (60-82) IFN >1.67 37 28.7% (20.7-35.6) 20.1% (14.3-26.1) 67% (53-76) IFN-γ levels > 0.35 nd incresed > 0.70 IU/mL etween seline nd 18-month visits considered positive. Risk clculted using stndrd risk-to-risk formuls for different time periods c Estimted 5-Yer prevlence ssuming clculted incidence rtes in closed popultion. All estimtes re djusted using RDS weights sed on QFT35 cutoff. Alternte cutpoints sed on pulished studies: Diel R, et l., Am J Respir Crit Cre Med. 2008;177(10):1164 1170. Higuchi K, et l, Tuerculosis. 2008;88(3):244 248. Pi M. Nture reviews. Microiology. 2010;8(3):242; uthor reply 242. Ringshusen FC, et l., BMC Infect Dis. 2010;10:220. Torres Cost J, et l., J Occup Med Toxicol. 2011;6:19. Zwerling A, et l., Thorx. 2012;67(1):62 70.
M. Tuerculosis Incidence y IFN γ Cutoff Levels IFN-γ cut-off vlues N Pos 18m Inc.(95% CI) 12m Risk (95% CI) Expected 5-yer Prev. c (95% CI) IFN >0.35 67 51.9% (43.1-60.7) 38.6% (31.5-46.2) 91% (84-96) IFN >0.50 60 46.5% (37.7-55.2) 34.1% (27.1-41.5) 88% (79-93) IFN >0.35 (>0.7 incr.) 50 38.7% (30.2-47.3) 27.8% (21.3-34.6) 80% (69-88) IFN >1.28 42 32.6% (24.4-40.7) 23.1% (17.0-29.4) 73% (60-82) IFN >1.67 37 28.7% (20.7-35.6) 20.1% (14.3-26.1) 67% (53-76) IFN-γ levels > 0.35 nd incresed > 0.70 IU/mL etween seline nd 18-month visits considered positive. Risk clculted using stndrd risk-to-risk formuls for different time periods c Estimted 5-Yer prevlence ssuming clculted incidence rtes in closed popultion. All estimtes re djusted using RDS weights sed on QFT35 cutoff. Alternte cutpoints sed on pulished studies: Diel R, et l., Am J Respir Crit Cre Med. 2008;177(10):1164 1170. Higuchi K, et l, Tuerculosis. 2008;88(3):244 248. Pi M. Nture reviews. Microiology. 2010;8(3):242; uthor reply 242. Ringshusen FC, et l., BMC Infect Dis. 2010;10:220. Torres Cost J, et l., J Occup Med Toxicol. 2011;6:19. Zwerling A, et l., Thorx. 2012;67(1):62 70. Multivrite Odds Rtios for QFT Seroconversion y IFN γ Cutoff Levels Model 1 IFN 0.35 Model 2 IFN 0.35 & incr. >0.7 Model 3 IFN 0.50 Model 4 IFN 1.28 Model 5 IFN 1.67 Vrile OR OR OR OR OR Homeless c 6.9** 4.2* 6.0** 3.4 4.0* Lived entire life in Tijun 3.5* 2.3 3.1* 2.2 2.3 Age 50 yers 9.7* 16.5* 12.4* 11.4** 8.8** Self-perceived HIV risk 0.3** 0.4 0.3** 0.5 0.6 Use mrijun dily c 6.2* 2.4 8.1* 3.1 3.7 * p<0.05; *** p<0.01 Arevition: IFN = chnge in IFN gmm levels from seline to 18 month follow up visit Odds rtios (OR) re djusted for ll other vriles in ech model. All models re weighted for respondent driven smpling using popultion weights. Assessed t seline visit. c Assessed t 18 month visit.
Limittions Given the 18 month intervl etween QFT tests, the exct time of infection is unknown; thus, fctors ssocited with seroconversion my e correlted with, rther thn predictive of, infection. Respondent driven smpling might hve overestimted incidence due to network clustering; however, incidence estimtes were djusted for RDS weights. Conclusions Regrdless of IFN γ cutpoints used, IDUs in Tijun re t very high risk for Mt infection. Modifile risk fctors for incident Mt infection were identified nd interventions re needed to prevent Mt trnsmission nd LTBI rectivtion mong IDUs. Mnufcturer s recommended cutoff ppers pproprite, ut dditionl guidnce is needed regrding the interprettion of repet testing results in popultions t high risk for Mt infection.
Ptronto Pro Comusid Dr. Remedios Lozd Dr. Jorge Alvelis Dr. Mnuel Gllrdo Proyecto El Cuete Stff PreveTB Stff Acknowledgements ISESALUD Dr. Rfel Lnido Lorin Dr. Pris Cerecer Mri Luis Volker Soerenes Luis Sntn Oregon UCSD Dr. Steffnie Strthdee Dr. Antonino Ctnzro Dr. Roert Deiss Dr. Timothy Rodwell Dr. Jose Luis Burgos Jzmine Cuevs Alici Ver Pricilind Orozovich Andre Mntsios Sn Diego County DHS Dr. Kthleen Moser Alerto Colordo Dr. Chris Peter NIDA (Proyecto El Cuete: DA019829) NIDA T32 (DA023356): Drs. Deiss, Burgos, Rodwell UCSD Acdemic Sente grnt: Chest x rys Dr. Blnc Lomeli (PCI) for dvice nd TB trining Dr. Antonino Ctnzro (UCSD) for clinicl guidnce Specil thnks to the prticipnts who gve their time for this study