Highlights of the IPFA/PEI 17 th Workshop on Surveillance and Screening of Blood Borne Pathogens Cees L. van der Poel, MD, PhD Transfusion Technology Assessment Group (TTA) Julius Centre Health Sciences & Primary Care
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Highlights of the
IPFA/PEI 17th Workshop on Surveillance and Screening of
Blood Borne Pathogens
Cees L. van der Poel, MD, PhD
Transfusion Technology Assessment Group (TTA) Julius Centre Health Sciences & Primary Care
Session 1 Welcome address
• Dr. Perry (IPFA) – “Not that blood is not safe, but how do we keep it safe”
• Dr. Sindik-Milolevic (Croatia) – Institute of Immunology, 117 years -> Inc – Vaccins and plasma products – Priority on self sufficiency (IVIG) – New facilities and new products
• Ms. Mihaljevic (Croatia) – Institute of Transfusion Medicine and Blood Safety – Screening tests used in BTC (n=5) from 2 -> 8 – Residual Risk for HBV and HCV down since 1995 – 0,2-0,5% pregnant women HBV pos, vaccination programme 1999 – HIV and Syph trends up, MSM
Session 2 Malaria and Babesiosis
• Prof. Chiodini (UK) – Immigration renders “London as the window to the Globe” – Malaria 50% underreported, trends down in reporting countries – Case mix more dangerous -> Falc. and Vivax – Pathogenicity Vivax underestimated – Knowlesi, tourism and ARDS, not Duffy dependent – two major types detected, but plea for broader sensitivity of Ab test – cross reactions <-> mixed infections common – Donors who transmitted had high Ab titers
• Dr. Kumar (FDA, USA) – 150.000 donors / yr deferred – Limited detection of PCR – Recombinant antigens for broader tests – Risk assessment model donor deferral: 60% travel to a Mexican region 1 case
per 61 years – 60% deferral reduced by Ab testing
Session 2 Malaria and Babesiosis
• Dr. Owusu-Ofori (Ghana) – Costs of newer treatments -> testing options – Better and cheaper tests needed – TTM study !!! -> PTM 3.1% attack rate,
• but where did it come from? 5/6 PTM donor no parasitaemia • 7 parasitaemic donations -> 1 parasitaemic recipient
– Consider patient characteristics, semi-immune protected against clinical M
• Dr. Leiby (ARC, USA) – Distribution of B. spp changing and more complex (EU) – Babesiosis significant transfusion risk (Microti, US), – 80-100 Txm cases, 12 fatal outcomes – Tick deferral no solution – TEST NEEDED
Session 3 Emerging infections
• Dr. Dodd (ARC, USA) – Of mice and men: “XMRV a virus searching for disease” and “CFS a
disease searching for a virus” – Association with PC and CFS not established – Donor prevalence up to 3,7 % (NAT) – Blood Txm a “theoretical risk” (where did we hear that before?) – “A causal role of XMRV in CFS is an intriguing possibility….”
– (Mikovitz and Ruscetti, Science, 14 May, 2010) • Ms Lam (Singapore)
– Malaysia, 2 mosquito’s and 2 infections, CHIKV and DHF – Testing or PR or “beware of the mozzies” – Few reported Txm cases: immunity, clinicians do not associate
• Dr. Velati (Italy) – WNV in NE Italy, regional 0,7% donors Ab pos – WNV NAT in outbreak, 2009: 1:25.000 donors NAT pos – Region is essential for blood supply – Rest of Italy: 28 day deferral – Mozzies largely extinguished, WNV (low) endemic but CHIKV imported
(2007)
Session 3 Emerging infections
• Prof. Zaaijer (Netherlands) – Q fever in NLD, largest outbreak ever
• Coutinho: “We don’t need terrorists, we can produce it ourselves” – One Txm case in Lit in 1977 – 3/1000 donors (second half outbreak 2009) PCR confirmed pos,
seroprev 13%, incidence 3% – 2 possible Txm cases
• IgG in 2 recipients: 1x PCR positive donor (study), 1x PCR negative donor (look-back) who reported Q fever after donation
– Screening since march 15th, 2010 • Round table
– Look for Coxiella partitioning in blood – Coming next in this theatre: Does EU have XMRV?
• MSM no risk group for XMRV (in Amsterdam) – XMRV disease after blood Txm? – Will companies make smaller scale tests or can we do it ourselves?
(EU)
With every breath you take …..
• “See your GP in case
of coughing, headache or
fever…..”
Session 4 Updates
• Dr. Alter (NIH, USA) – PR is good if we can do it, the question is whether we can
• For plasma doable • For cells more difficult…
– HOVON study more bleeding, is there DNA in platelets?
– “The precautionary principle asserts that measures need to be taken to face potential serious risks (in absence of conclusive evidence)”
• ……but the measures need to be proportional…… – “Soft PR” (low viral loads, OBI’s) plus multiplex testing
(100-10 c/ml) would yield 100% safety
J-L Kerkhoffs et al, British Journal of Haematology, April 6th, 2010
Session 4 Updates
• Prof. Busch (BSRI, USA) – (57 slides in 20 minutes….) – Global screening with NAT …..in 22 countries – Global NAT yield 2/M for HIV and HCV, but 7/M for HBV – 50% of HCV NAT yield tackled by HCV Ag testing
• NLD 1 HCV yield case in 9 million donations – 10-100 copies needed for HIV Txm
• but 1-10 for HBV / HCV – Nat yields better data on seroconversion time frames – IL28B polymorphism and HCV clearance – Future in multiplex testing
Virus titre modeling: HIV
* Viral doubling time: 0.85 days * NAT pool size: 48 donations * Test characteristics: X95 = 25 gEq/ml
X99.9 = 75 gEq/ml
Session 4 Updates
• Prof. Allain (Cambridge, UK) – In type D OBI more often (escape) mutations, may escape serological detection – HBsAg assays vary in ability to detect OBI variants – HBsAg assays may benefit to use OBI mutants to reach broader sensitivity – Before diagnose OBI use other HBsAg tests
• Dr. Coste (EFS, France) – New screening technologies incl. vCJD – Sample size and prep: tennis court preferred – Bio-receptors and transducers, quantum dots, bio barcodes – micro arrays: limited options for use – Micro / nano arrays (2nd gen): not before 2020 – One realistic candidate vCJD screening test, ELISA format
• good specificity • good anlytical sensitivity • dissappointing in-vovo sens (0/3 human vCJD cases) • PMCA possible as confirmation test (cell lines)
Session 5 Manufacturers
• mr. Schochetman (Abbott) – Mol tools for pathogen discovery:
• virochip DeRisi 2003 (SARS) 60 K oligonucleotides, all 2500 viruses, including plants and animals
• Solexa™ sequencing tool, 80 Million reads / run – XMRV
• Macaques can have it in their reproductve tract • Dr. Petti (Novartis)
– Concern for the patient…..future public heath threats……Wilson&Jungner?
– Clinical relevance? Global tolerable risk? • Dr. Linnen (Gen-Probe)
– B19/HAV ready, XMRV prototype, Dengue in Brazil studies planned……
– Panther ™ instrument – XMRV 0/1435 ARC donors, no XMRV in HIV+ samples – HIV viral load in WB similar to plasma
• so HIV is in the plasma and not in the RBC
Session 5 Manufacturers
• Dr. Saldanha (Roche) – Multi-dye technology RT PCR Cobas s201
• Rapid development of CHIKV etc “if the need is shown to us”
– HAV/B19, SD and pools, B19 types 1,2,3 • High titer of one may mask the other
– HBV, HCV, HIV-1+O and HIV-2 • Detection of combined infections at different titers
• Prof Roth (GFE Blut mbH) – “in-house testing” GFE Blut RT PCR’s licensed by Roche for
GFEB associates, CE marked, 2,5 M donations/yr – One tube process HCV, HIV-1+O, HIV-2, HBV, HAV, B19 – HCV, HIV, HBV sens 500-600 c/ml – HBV sens balanced by anti-HBc
Session 6 Plasma screening
• Mr. Matsubayashi (Hokkaido, Japan) – HEV world wide spread, Japan mostly type 3 &4, type 4 more
pathogenic – in Japan 2% of cases BTx related (3/5 from Hokkaido) – In-house HEV NAT in pools@20 pos in 1 : 8,000 donations
• 57% ALT up, RNA pos up to 2 months • 12% long term IgG neg (?) • Eating history of viscera
– Lookback 4/8 transmissions, – More heat stable than expected, 20nm nanofiltration is OK
• Dr. Baylis (PEI, Germany) – EDQM Proficiency testing B19 NAT: type 3a dissapointing – 0/109 ALT elevated samples SD NAT neg for HEV (HCV and HBV) – 10% plasma pools HEV NAT pos, Type 3 EU and US, type 4 Asia – Labs 2-3 log difference in sensitivity, international standard? – Include PARV4 DNA? Present in 4% of plasma pools, IVDU related, no
pathology yet
Session 6 Plasma screening
• Dr. Ayob (Malaysia) – Global market changes: mergers, dramatic rise in IVIG use – Concentrates safe, (life long) Rx cryo is not – Fractionated products costly for developing world – not affordable – Strengthen National Blood Programs, regulate imported products,
contract fractionation local plant/joint venture – Centralize hemophilia treatment – Change cultures and not tests !!
• Dr. Smeds (Sweden) – New EMA guideline on EPI – BE and PMF holder responsibilities on
• Monitoring, reporting, setting alert limits and acceptability risk • Trends and residual risk analysis • Common alert limits so far not feasible
– Harmonization with CoE !!!
Session 6 Plasma screening
• Dr. Over (Netherlands) – Probabilistic risk models of plasma products major advantages
• comprehensive, fewer assumptions • scientifically sound, avoids unrealistic outcomes • insight in levels of uncertainty • reveals most influential factors (sens analysis) • predicts effect of additional measures (cost-effectiveness)
– Donor incidence and process reduction factor highest impact – Not all criteria defined yet (e.g. acceptable safety margin) – Harmonization highly desirable – A (generic) simplification of the probabilistic model is feasible – Consensus on remaining assumptions needed – Communications on simple stats to be developed
Session 7 Cost-effectiveness
• Dr. Kleinman (Univ. British Columbia, Canada) – Selective testing: example MP-> SD NAT, based on risk – Frequent-infrequent donor
• (harmonize with EU? repeat donor, regular donor) – Will it reduce cost? (CEA?), it may increase safety? – Large multi-centre study on SD NAT: standardization !! – Many options to be analyzed, including CEA – HBV difficult to model – How to handle false negatives in the model
• Dr. Custer (BSRI, USA) – CEA means value for money ( € or $ ) – HCV and HIV Ab screening = cost saving – For children may interventions are cost-effective – CEA or total cost / benefits? – Multiplex NAT reduces cost and combines benefits – ICER may not be appropriate model for blood safety – But: what else?
Session 7 Cost-effectiveness
• Mr. Hardiman (Ortho-Clinical Diagnostics, USA) – Where and why do we invest? – Heart break hotel or Babes’s bug? – Emotions maybe more important than science – The Chagas event – Additional 20-30 $ per donation for selective testing?
• (Sanquin estimate: deferred donor + 75 € ) – There is emotion in the companies vision to Btx – But ROI is leading
Of mice and men (and cheese) 1
• Ideally pathogens are reduced (get the Golden Star if we can), • In real life we see pathogen discovery….
– potential interest No 1 = blood Txm agents – Patient concern in the banner – but priority order seems: B19/HAV > XMRV > Dengue in Brazil…..
• Soft pathogen reduction + simple tests? Around 100 c/ml • XMRV in 3,7% of donors, but not at ARC…. • Macaques have it in their genito-urinary tract but MSM not…..
– (screening diseases with a new test @ alpha = 0,05, will yield one in 20 chance of “associated” disease)
• We need a (better) Malaria Ab test, – so London can remain the Window to the Globe – in high endemic countries consider recipient characteristics
• We need a Babesiosis test • We need tests also on small scale, if Germany can have in-house NAT why
can’t we? • Mozzies need to be extinguished • NLD Q fever transmissions @ every breath you take…..
Of mice and men (and cheese) 2
• Now we use 3 screening tests for HBV but JPA says HBsAg is a good test • Can we skip some serology? Beware of elite controllers…. • Non-env viruses and plasma products: use a test or PR or both?
– If important they will use both…. • Nano tech not before 2020, No test for vCJD • Regional self sufficiency – contract fractionation • Beware of the EPI thing….(free after Dodd in 1996) • Risk assessments to valuate testing strategies • Over’s sight model, to Schreiber or to Weusten? • For blood safety we do not look at the West but the North-East
– Companies look at the South-West • If they make it will we use it?
• Emerging threat of retirement in
the USA
• Emerging threat of retirement in
Bilthoven
• (Q-area)
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