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human parvovirus parv4 in blood and plasma products n.
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Human Parvovirus PARV4 in Blood and Plasma Products PowerPoint Presentation
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Human Parvovirus PARV4 in Blood and Plasma Products

Human Parvovirus PARV4 in Blood and Plasma Products

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Human Parvovirus PARV4 in Blood and Plasma Products

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  1. Human Parvovirus PARV4 in Blood and Plasma Products Jacqueline Fryer National Institute for Biological Standards and Control SoGAT XX

  2. Identification of PARV4 and detection in pooled plasma • Originally identified in a homeless drug abuser with acute viral infection syndrome; co-infected with HBV (Jones et al, J Virol. 2005) • PARV4 and related genotype (PARV5) detected in 4-5% of recent manufacturing plasma pools; higher prevalence in older pools • Both viruses found in approximately equal proportions • The highest viral loads in pools are ~ 106 copies/ml plasma • No correlation between B19V and PARV4/5 viral loads • PARV4 and PARV5 are highly conserved (92% nucleotide identity), but share limited homology with B19V and HBoV (Fryer et al. EID 2006; Fryer et al. Transfusion 2007)

  3. Genus Erythrovirus Primate, chipmunk, bovine parvoviruses Adeno-associated and avian parvoviruses Genus Dependovirus Porcine parvovirus 2 Human bocavirus, canine and bovine parvoviruses Genus Bocavirus Genus Amdovirus Parvoviruses from carnivores, rodents and pig Genus Parvovirus Phylogenetic analysis of parvovirus genomes

  4. Are PARV4 & PARV5 present in products derived from these plasma pools? • Clotting factor VIII concentrates • 175 lots, 12 products, 10 manufacturers • Expiry dates 1974-2005 (plasma sourced ~5 yrs prior to expiry date) • Reconstituted in sterile H20, 1ml extracted on MagNA Pure LC Extractor • PARV4/5 detection by conventional PCR (ORF2 primers) • Viral loads determined by consensus real-time PCR

  5. PARV4 and PARV5 in factor VIII concentrates

  6. Prevalence of PARV4, PARV5 and B19V in factor VIIIs manufactured over the past 30-35 years PARV4 and PARV5 B19V PARV4/PARV5 and B19V Negative for these viruses

  7. Analysis of PARV4/5-positive factor VIII concentrates • Prevalence of PARV4/5 vs. age of product • Pre-1990 expiry: 23% PARV4/5 (45% B19V) • Post-1990 expiry: 2% PARV4/5 (30% B19V) • Viral loads • PARV4/5; up to 3 x105 copies/ml product • B19V; up to 2.5 x108 copies/ml product • Sequence analysis • 7/28 PARV4 • 19/28 PARV5 • 2/28 both PARV4 and PARV5

  8. Summary • PARV4 and PARV5 present in coagulation factor VIII products manufactured over past 30-35 years • Prevalence of PARV4 and PARV5 higher in ‘older’ products (expiring pre-1990) compared to recent products (expiring post-1990) (23% vs. 2%) • Increased blood safety in early 1980s (HIV epidemic); Screening / exclusion of ‘high risk’ donors • PARV4 sequences from 30-35 year period highly conserved (>99% nucleotide identity), same for PARV5 • Prevalence of PARV5 higher in ‘older’ factor VIII products, analogous to parvovirus B19 genotypes 1 & 2 • Implications for recipients of plasma and plasma products in terms of PARV4/5 contamination are unknown • Nothing yet known of role of PARV4/5 in human disease

  9. Acknowledgements • NIBSC • Sally Baylis • Tony Hubbard • Nita Shah • Morag Ferguson • Janice Blinder • Philip Minor Blood Systems Research Institute, California/ University of California • Eric Delwart