Efficacy of HBV screening assays in an international survey

Transcription

1 Efficacy of HBV screening assays in an international survey Nico Lelie and the international NAT study group 19 th IPFA-PEI workshop, Budapest May This work is sponsored by Blood Systems Research Institute (BSRI SF, USA) and the National South African National Blood Service (SANBS)

2 Ratio of virions to subviral particles in ramp up phase and highly viraemic HBeAg positive carriers ~1 : Ratio in HBeAg-negative low-viremic carriers2 is 1 : 108 ± 103 Ratio in case of primary occult infection3 was ~ 1 : Gerlich et al. Journal of Viral Hepatitis 2007:14 (Suppl 1): El Ekiaby M et al. Vox Sang 96, Suppl 1, ISBT abstract p23, Cairo, March Bremer et al. Transfusion 2009;49:

3 Course of HBV markers and residual transmission risk in ID-NAT 1 st WP ~10 days (Ultrio Plus) 2 nd WP < 1day (Ultrio Plus) OBI transmission risk unknown Vermeulen et al, Transfusion 2012;52:

4 HBV DNA load transfused in non-infected and infected recipients of anti-hbs negative OBI blood ID (probit no CI) copies ID ( ) copies not infected infected not infected infected Tested (n=17) Allain JP et al, manuscript submitted All (n=63) projected from tested

5 Poisson distribution Probability of infection or detection in WP infectious virion no virion 5 Presentation Title Presenter Name Date Subject Business Use Only

6 Poisson distribution Probability of infection or detection in WP infectious virion non infectious virion no virion 6 Presentation Title Presenter Name Date Subject Business Use Only

7 Poisson distribution Probability of infection or detection in OBI infectious and non infectious virions only non infectious virions 7 Presentation Title Presenter Name Date Subject Business Use Only

8 Transmission risk during WP or with OBI Weusten J et al, Transfusion 2011;51: Probability of non-detection Probability of infection Area under the curve gives the overall risk in days ( Window phase risk days equivalents ) Product of the two log viral load (cps/ml)

9 Viral load distribution in different stages of HBV infection 83% of HBV NAT yields were qpcr nonreactive copies/ml (n=22) (n=10) (n=15) (n=27) (n=29) (n=32) qpcr HBsAg+/DNA+ not done Probit analysis Vermeulen M et al. manuscript, in preparation Case number

10 Probability of HBV transmission by RBC transfusion from WP and OBI donations screened by ID and MP6-NAT Window Period no testing ID virions HBV transmission risk Occult HBV infection ID virions Ultrio Plus ID Taqscreen MP6 no testing Taqscreen MP6 Ultrio Plus ID Vermeulen M et al. manuscript, in prep copies/ml HBV-DNA

11 Projected OBI transmission cases with and without NAT expressed as percentage of 29 anti-hbs negative OBI cases interdicted Allain et al manuscript submitted

12 Analyses multi-center HBV study Epidemiological data Sensitivity of HBV assays Transmission risk Efficacy of screening scenarios

13 ID-NAT users (n=20) in 15 countries provided data for international HBV NAT study Central, North and East Europe Mediterranean Egypt HBV screening data donations 9458 infections South East Asia South Africa South Pacific

14 On-site co-investigators I Marion Vermeulen, Ravi Reddy, South African National Blood Service, Johannesburg, South Africa Arthur Bird, Russell Cable, Western Province Blood Transfusion Service, Cape Town, South Africa Heidi Goubran, Faten Moftah, National Blood Transfusion Service, Cairo, Egypt Magdy El Ekiaby, Shabrawishi Hospital, Dokki, Egypt Sylvia Sauleda, Banc de Sang I Teixits, Barcelona, Spain Roberto Roig, Manolo Alvarez, Valencia Regional Blood Tx Center, Valencia, Spain Paola Ghiazza, St Anna Hospital, Turin, Italy Paola Manzini, University of Turin, Turin, Italy Cecilia Peduzzi, S.O.D University of Careggi, Florence, Italy Flavia Favilli, S. Chiara Hospital, Italy Rocio Gonzalez, Emma Castro, Red Cross Blood Center, Madrid, Spain

15 On-site co-investigators II Christoph Niederhauser, Blood Transfusion Service SRC Berne, Berne, Switzerland Snezna Levicnik, Polona Nograsek. Blood Transfusion Center of Slovenia, Ljubljana, Slovenia Joan O Riorden, Irish Blood Transfusion Service Sussanne Wessberg, Sussane Elkblom, Mervi Lankinen, Finnish Red Cross Blood Service, Helsinki, Finland, Christian Erikstrup, Aarhus University Hospital Ewa Brojer, Piotr Crabarzyk, Institute of Haematology and Transfusion Medicine, Warsaw, Poland Jolanta Gdowska, Dariusz Piotrowski, Warsaw Blood Center, Warsaw, Poland Tsoi Wai Chiu, Kit Che Lin,, Hong Kong Red Cross Blood Center, Hong Kong Diane Teo, Sally Lam, Sze Sze Chua, Health Systems Agency, Singapore Abdul Hamid Bon, Sally Lam Tsuey Peng, National Blood Centre, Malaysia Peter Flanagan, New Zealand Blood Service, Auckland, New Zealand

16 HBV prevalence and NAT yield rates in first time donors per region South Africa Mediterr anean ECN Europe South Pacific SE Asia Egypt first time donations HBV prevalence 1.07% 1.06% 0.80% 0.20% 0.15% 0.08% acute NAT yield rate 1: : :7677 1: : : chronic NAT yield rate 1:7550 1: :3880 1: : :30 592

17 Proportion HBV-DNA(Ultrio) positive first time HBsAg carrier donors in regions 2632/ / / / / / 123

18 Higher proportion HBV-DNA positive HBsAg carrier donors with Ultrio Plus 1491/ / / / / / / 44 43/ 44 Different donations Same donations Vermeulen et al, manuscript in prep Tsoi et al. manuscript in preparation. El Ekiaby et al. ISBT 2009, Cairo. Grabarzcyk et al, manuscript in prep

19 Proportion HBsAg and HBV-DNA positive in repeat donors per region 23,8% 11,5% 7,0% 8,7% 0,0% 16,4% 19,5% 55,1% 42,6% 73,5% 72,1% 90,2% 56,7% 30,4% 39,3% 0,0% 13,3% 18,6% 1,8% 2,3% 5,8% 7,3% 2,4% Classified as chronic carriers with HBsAg fluctuating around cut off

20 Proportion HBsAg positive acute infections in repeat donors per region 207/ 207/ / 15/ / 8/ / 54 3/ 3/ 3 275/

21 Increase in proportion of WP NAT yield in acute infections among South African repeat donors after conversion to Ultrio Plus WP NAT yield rate 1:25,546 2-fold HBsAg seroconversion rate 1:10,644 WP NAT yield rate 1:12,650 HBsAg seroconversion rate 1:11,000 Vermeulen, ISBT abstract, Cancun 2012 Acute NAT yield rose 1.58 fold from 1:18,248 to

22 Proportion ID-NAT reactive in 12 replicate assays on HBsAg+/Ultrio- yield samples Vermeulen et al, manuscript in preparation 50% LOD (CI) probit in cps/ml Ultrio Plus Ultrio 3.9 ( ) 65 (42-111) 16.6 (7.0-57) fold difference* *2.5 ( ) fold difference Ultrio NAT yield samples copies/ml

23 Two-fold increase in WP NAT yield in South Africa explained by doubling of WP reduction after conversion to Ultrio Plus cps/ml Start WP Ultrio Plus Ultrio HBsA g HBsAg S/CO= cps/ml Ultrio 50% LOD 65 cps/ml Ultrio Plus 50% LOD 3.9 cps/ml ID cps/ 20 ml eclipse 13.0 days WP *Two-fold window period reduction with Ultrio Plus can be explained by 17(7-57) fold lower analytical sensitivity of Ultrio as found in HBsAg+/Ultrio- samples in South Africa (Vermeulen et al, manuscript in preparation) 20.6 days Ultrio Plus 10.2 days Ultrio days HBsAg * in SA repeat donors, in all donors 2.5 fold

24 Efficacy of HBV screening assays MP-NAT efficacy HBsAg efficacy Anti-HBc efficacy MP-NAT NAT yield Concordant HBsAg and HBV-DNA reactive Anti-HBc ID-NAT WP NAT yield Concordant HBsAg and NAT yield Post WP NAT yield More sensitive ID-NAT WP NAT yield Concordant HBsAg and NAT yield Post WP NAT yield Pre- NAT risk pre-hbsag WP risk ID-NAT efficacy Transient (or undetectable) HBsAg post WP risk occurrence of infectious donations over time *

25 Efficacy of screening scenarios modeled on South African data Lapsed + repeat First time

26 ID-NAT, MP-NAT and serology yield in first time and repeat donors Repeat donors ID-NAT MP-NAT Serology WP NAT yield highly infectious First time donors Serology yield: low probability to be infectious Acute phase infectivity Late chronic or recovery phase