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Human Parvovirus PARV4 in Blood and Plasma Products

Human Parvovirus PARV4 in Blood and Plasma Products. Jacqueline Fryer National Institute for Biological Standards and Control SoGAT XX. Identification of PARV4 and detection in pooled plasma.

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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

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