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Proposal for a Hepatitis A genotype panel Rob Anderson.

Proposal for a Hepatitis A genotype panel Rob Anderson. Hepatitis A. Hepatitis A (HAV) is a non-enveloped, positive stranded RNA virus HAV is a member of the genus hepatovirus of the picornavirus family The genome is approximately 7.5kBp in length The genome has two UTRs

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Proposal for a Hepatitis A genotype panel Rob Anderson.

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  1. Proposal for a Hepatitis A genotype panelRob Anderson.

  2. Hepatitis A • Hepatitis A (HAV) is a non-enveloped, positive stranded RNA virus • HAV is a member of the genus hepatovirus of the picornavirus family • The genome is approximately 7.5kBp in length • The genome has two UTRs • The 5’ UTR is longer, being around 600-1200 BP in length, compared to that of the 3’ UTR, which is around 40-80bp. • Like most positive sense RNA genomes, the genetic material alone is infectious

  3. Hepatitis A • Nucleotide sequence analysis of HAV has allowed classification of the virus into six different genotypes • Genotypes I, II, and III are associated with human infections whereas genotypes IV, V and VI cause infections in simians • Subtype IA appears to be responsible for the majority of HAV cases worldwide, whereas subtype IB viruses tend to be found only in the Mediterranean region • There is no published clinical correlation to genotype

  4. Hepatitis A Disease • Hepatitis A infection-is an acute, self-limiting infection of the liver without a chronic stage usually transmitted by the faecal-oral route • The infection may be asymptomatic or may cause an acute hepatitis syndrome of varying degrees of severity up to and including fulminant hepatitis. • Peak viraemia is seen 10-12 days after infection • This means that it is possible for donations from asymptomatic individuals to occur as there is a short period (several days) between viraemia and symptoms • Hepatitis A can be transmitted by the parenteral route but very rarely by blood and blood products

  5. Screening for Hepatitis A • HAV is rarely transmitted by transfusion and is much rarer in whole blood donors than B19 (estimated to be between 1 : 500 000 - 1 000 000 donors) • Transmission by pooled derivatives has occurred in the case of FVIII • Chudy et al. J Med Virol (1999) 57: 91-9 • Principle reason is that HAV is not inactivated during the manufacturing process and is resistant to detergent, acid (pH 1), solvents, drying, and temperatures up to 60oC • Therefore NAT is performed for plasma intended for manufacture of blood products/derivatives

  6. HAV assay kits • Two principle manufacturers of diagnostic HAV assay kits • LightCycler Hepatitis A virus quantification kit (Roche Diagnostics) • RealArt HAV LC RT PCR kit (Qiagen artus GmbH) • Study was performed and published • G Sánchez et al. J Virol Methods (2006) 132: 160-5. • They used HM-175 (Genotype IB) and HAS15 (genotype IA) • Conclusion was that both assays are very suitable for detection and quantification of the mostprevalent HAV subtypes • However not all genotypes may be picked up as sensitively as each other

  7. 27 HAV isolates with complete sequence information. Endo et al. Virus Research 126 (2007) 116–127

  8. Percentage comparison of the complete ORF nucleotide and amino acid sequence identities of 26 known HAV isolates Endo et al. Virus Research 126 (2007) 116–127

  9. Proposal • As many samples of Hepatitis A positive serum/plasma as possible covering all of the identified genotypes • Amplification (if possible) in animals - macaques at the HPA • NIBSC co-ordinated collaborative study to assess and validate the panel • Genotype panel as a catalogue item analogous to the Hepatitis C panel • The panel will be available to kit manufacturers and others intending to validate “in-house” assays for HAV

  10. Contact address Rob.Anderson@nibsc.hpa.org.uk Thank you for your help.

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