17/05/2011. Preventing Donor Derived Infections Through Virology Screening Reducing Risk and Increasing Organ Availability OUTLINE OUTLINE

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1 Preventing Dnr Derived Infectins Thrugh Virlgy Screening Reducing Risk and Increasing Organ Availability Cristina Balerila BBV Labratry Manager SEALS, Prince f Wales Hspital May Backgrund Infectins Risks OUTLINE 2. Testing Prtcls Australia Current guidelines 3. NAT and Serlgy testing Windw perid (WP) Testing Algrithm at SEALS Parallel testing Results ver a 20 mnth perid 1. Backgrund Infectins Risks OUTLINE 2. Testing Prtcls Australia Current guidelines 3. NAT and Serlgy testing Windw perid (WP) Testing Algrithm at SEALS Parallel testing Results ver a 20 mnth perid Estimated Number f Persns with Chrnic Bld-brne Virus Infectins 2000 Regin Ppulatin Chrnic infectins (millins) (millins) HIV HCV HBV Africa Asia 3, Latin America Eurpe Oceania Nrth America Ttal 5,

2 Glbal burden f BBV Cumulative number f infectins by HBV, HIV, HCV: 1/10 th f wrld ppulatin Mrtality related t HIV 2.1 millin HBV millin HCV ~> 1 millin Chrnic infectins Cst f HCV therapy ~ 8,500 / year Cst f HAART $ 12,000 24,000 / year ( less in develping cuntries) Cst f HBV therapy $3,500 (lamivudine) $7,400 9,000 (adefvir, entecavir, telbivudine) $24,000 peginterfern Liver transplant Testing $ 100, ,000 in develped cuntries $ 18,500 in develping cuntries > $ 1.3 Billin Risk f acquisitin f a BBV thrugh rgan transplantatin The prevalence f the virus in the dnr ppulatin The viral lad in the dnr The specific rgan transplanted The efficiency f virus transmissin after cntact with bld and tissues Organ dnatin in Australia Ppulatin ~22 millin DOD ~247 dnrs (2009) DODR 11.3 dnrs/millin ppn Tx frm DOD 1,187~ (2009) Waiting List 1650 patients (2009) Dialysis Px 2,337 patients (2009) Prevalence f BBV in Australia Virus Infected Ppulatin in Australia Prevalence rate (%) Prevalence rate in High Risk (%) HIV 17, HBV 88, HCV 210, Ttal 315,

3 Prevalence amng rgan dnrs at SEALS NAT Labratry Virus HIV HCV HBV BBV Marker Anti-HIV HIV RNA Anti-HCV HCV RNA HBsAg Anti-HBc HBV DNA Prevalence at SEALS (%) Increased Risk Dnrs Aiming t increase dnatin rate Testing prtcls nt natinally agreed yet, but in prgress Draft BBV plicies in place in a number f States, managed by State Organ Dnatin Agencies Dnr assessment NSW 1. Clinical assessment then BBV assays 2. Prspective NAT OUTLINE 1. Backgrund Infectins Risks 2. Testing Prtcls Australia Current guidelines 3. NAT and Serlgy testing Windw perid (WP) Testing Algrithm at SEALS Parallel testing Results ver a 20 mnth perid 3

4 Serlgy: Anti-HIV-1/2 Anti-HCV Anti-HTLV-I/II HBsAg Anti- HBc Anti-HBs anti-ebv anti-cmv Syphilis antibdy (TPHA ) NAT: HIV-1 RNA HCV RNA (HBV DNA) Prspective in increased risk Retrspective Universal Viral Screening Markers [NSW DOH Organ Dnatin and Transplantatin Managing Risks f transmissin f HIV, HCV and HBV] Dnrs with identified risk factrs MSM IV Drug Users Incarceratin in previus 12 mnths Sexual partners f abve Unexplained fever /weight lss/ LAD/cugh etc Partner with HIV/HBV/HCV Prstitutin STD in past 12 mnths Csmetic bdy piercing/tatting (ccaine snrting) Physician cncern TSANZ CONSENSUS STATEMENT ON ELIGIBILITY CRITERIA AND ALLOCATION PROTOCOLS Submitted t AOTDTA in July 2010 Hepatitis B testing and use f hepatitis B psitive dnr Hepatitis C testing and use f hepatitis C psitive dnr rgans Use f prspective NAT fr increased risk dnrs Internatinal Guidelines GUIDANCE ON THE MICROBIOLOGICAL SAFETY OF HUMAN ORGANS, TISSUES AND CELLS USED IN TRANSPLANTATION UK, Feb 2011 Clear guidelines fr labratries testing dnatins, including parallel testing Well defined testing algrithms fr interpretatin f results and management f repeat reactive results Dnr bld/plasma samples must be archived fr at least 10 years in a retrievable manner and testing recrds fr a perid f 30 years, Current Testing Prtcls in Australia Bld dnr screening Serlgy testing fr HIV1/2, HBV, HCV, HTLV I/II, Syphilis, Malaria, CMV NAT testing fr HIV1, HCV Organ dnr screening Serlgy testing fr HIV1/2, HBV, HCV, HTLV I/II, Syphilis Serlgy fr CMV, EBV, T. gndii Frm Octber 2009, BBV SEALS NAT HIV-1, HCV, HBV fr rgan dnrs in NSW and Victria Optimal use f NAT in SOT Being assessed thrugh evaluatin f n-ging requests and results f testing increased risk dnrs 4

5 1. Backgrund Infectins Risks OUTLINE 2. Testing Prtcls Australia Current guidelines 3. NAT and Serlgy testing Windw perid (WP) Testing Algrithm at SEALS Parallel testing Results ver a 20 mnth perid Antigen Nucleic acid TARGET AMPLIFICATION HCV RNA HIV1 RNA [HBV DNA] Pathgen detectin (Glyc)prtein HBsAg [HBV cre] ELISA, EIA [Cmb] Antibdies Anti-HIV 1,2 Anti-HCV Anti-HTLV [Anti-HBc] Screening fr Infectius Diseases Eclipse Serlgic cnversin Viraemia Serlgic testing Nucleic acid testing WINDOW Expsure [AST IDCOP Guidelines AJT 2009] Stages f Infectivity Surrgate fr infectivity is viraemia detectable by NAT (PCR) Can define fur stages f viraemia Pre-ramp up Ramp-up (expnential increase) Plateau phase Pst-ser-cnversin phase 5

6 What is NAT Infectius Windw Perid? HIV markers during early infectin DT = 21.5 hrs HCV RNA (plasma) HIV Antibdy HIV p24 Ag Theretical Infectivity Day 0 HIV RNA Day 11 HIV p24 Ag Day 16 HIV Antibdy Day 22 5 Days 6 Days HBV markers during early infectin HBV DNA (PCR) Anti-HBc HCV markers during early infectin Plateau phase = 57 days HBsAg ALT HCV RNA Anti-HCV Infectin Infectin Day 0 HBV DNA Variable, up t 31 days prir t HBsAg by ID NAT( 9-11 days by MP NAT) HBsAg Day 59; disappears Day Infectin Day 0 HCV RNA Day 12 HCV Antibdy Day 70 6

7 NAT and Serlgy Windw Perids Limitatins f Serlgical Tests Lnger windw perid than NAT D nt distinguish between HCV present r past infectin HBV scape mutants are nt detected Occult HCV and HBV infectins are nt detected 1. Backgrund Infectins Risks OUTLINE 2. Testing Prtcls Australia Current guidelines 3. NAT and Serlgy testing Windw perid (WP) Testing Algrithm at SEALS Parallel testing Results ver a 20 mnth perid Current prcesses fr screening Nat Tests dne at SEALS HCV HIV-1 HBV 3 Mlecular tests run in parallel LOD 10 IU/ml, TAT 8 hrs Additinal tests being develped: CMV Serlgy EBV Serlgy BK/JC Txplasma 7

8 Technical labratry aspects NAT Service Increased-risk dnrs Residual risks Cnclusins NAT/BBV Labratry Prvide bld dnr screening fr HBV, HCV and HIV-1 in rgan and tissue dnatins Prspective/Urgent NAT fr increased-risk dnrs (NSW & VIC) Retrspective NAT screening in average-risk dnrs (NSW) Use f 3 different mlecular tests TGA licensed COBAS AmpliScreen assay COBAS AmpliPrep TNAI/AmpliScreen assay COBAS AmpliPrep/TaqMan assay Prspective NAT Algrithm fr discrdant result cnfirmatin Time (hr) Serlgy knwn/questinnaire 0 1 st Octber 2009 t 30 th August 2010 N = 35 prspective NAT perfrmed at SEALS, POWH Average-risk dnr 24 hr TAT Retrspective testing BBV sample Increased-risk dnr 8 hr TAT Prspective testing 5.02 Average delivery time frm cllectin f bld t hspital = 5.02 h (range 1 15 h) Average TAT frm specimen receipt t reprting f results = 7.75 h (range 7 10 h) Manual extractin in duplicate Assay 1: COBAS AmpliScreen test (TGA-licensed bld dnr screening assay) Autmated extractin Assay 2: COBAS AmpliPrep TNAI/COBAS AmpliScreen test Autmated extractin Assay 3: COBAS AmpliPrep/COBAS TaqMan test 7.02 LOD: HIV-1=48.37 IU/ml HCV= IU/ml HBV=12.84 IU/ml LOD: HIV-1=9.79 IU/ml HCV=21.02 IU/ml HBV=4.31 IU/ml LOD: HIV-1=68 IU/ml HCV=15 IU/ml HBV=12 IU/ml +/- +/- +/

9 Estimated prbability that a dnr is truly infectin psitive n given discrepant NAT assay results PCR Result Prbability f True Psitive CAS TNAI TaqMan HBV HCV HIV Reprted as < Neg Csts Ttal csts fr rgan dnr screening fr HIV-1, HCV and HBV Prspective NAT = $2,200 (salary $550, cnsumables $1650) * Neg Neg * Ps * Ps Ps Summary f BBV testing at SEALS since 1 st Octber 2009 t 30 th April 2011 Sample type Rutine (Average risk dnr) Prspective (Increasedrisk dnr) N. f dnrs tested by NAT N. f rgans retrieved (NSW & VIC) 98 Ttal Serlgy results NAT results Dnr n. Organ(s) retrieved HBs Ag HBc Ab HCV Ab HIV-1/2 Ab HBV DNA HCV RNA HIV-1 RNA Nt medically suitable Psitive serlgy n/a n/a n/a n/a n/a* a TOTAL 98 9

10 Recmmendatins fr Labratries perfrming NAT Issue Recmmendatin Status at SEALS Standards labs Cmpetency Prficiency Staff training Sampling and transprt Nt haemdiluted Stated in request frm Dedicated samples Standardised transprt Labratry Prcedures Single unit testing Rapid TAT Discriminatin f initial psitive results Humar et al. Am J Transplant 2010;10: Emerging issues Imprted infectins/znses/msquites WNV Bat lyssavirus, Hendra/Menangle/Nipah Dengue, Murray Valley encephalitis Lng-term immunsuppressin + cancer EBV Endgenus retrvirus HHV-8 Anti-HBc (+) dnrs Occult Hepatitis B Infectin (OBI) Residual risk NAT screening Cnclusins Diagnsis in 7-8 hr Enabled the use f rgans frm dnrs with psitive serlgy but nt active viral infectin New testing algrithms and additinal pathgens need t be cnsidered (i.e. CMV, EBV) fr dnr screening Imprvements Develpment f Natinal plicy fr tests dne, prtcls and infrmed cnsent Active surveillance (Bivigilance) Imprved knwledge by health prfessinals invlved in OD&Tx Pst diagnstic cunselling Acknwledgments NAT/BBV labratry team Prf William Rawlinsn Dr Cristina Balerila Sanghamitra Ray (Tuli) Kate Ryan Zin Naing Stuart Hamiltn NSW OTDS Dr Jnathan Gillis Ellie McCann State Dnr Nurse Cnsultants SEALS NSW Department f Health 10