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Swine Influenza – Host Range and Zoonotic Considerations

Swine Influenza – Host Range and Zoonotic Considerations. R.B. Baker, DVM, MS Senior Clinician ISU Swine Section VDPAM 445. Swine Influenza A (H1N1) Infection in Two Children — Southern California, March–April 2009.

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Swine Influenza – Host Range and Zoonotic Considerations

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  1. Swine Influenza – Host Range and Zoonotic Considerations R.B. Baker, DVM, MS Senior Clinician ISU Swine Section VDPAM 445

  2. Swine Influenza A (H1N1) Infection in Two Children — Southern California, March–April 2009 • On April 17, 2009, CDC determined that two cases of febrile respiratory illness occurring in children who resided in adjacent counties in southern California were caused by infection with a swine influenza A (H1N1) virus. The viruses from

  3. http://healthmap.org/promed/en

  4. Swine Influenza (SI) • Acute and highly infectious single strand RNA viral disease of pigs and many other species • SI is a type A influenza in the family Orthomyxoviridae

  5. Influenza • Swine - (A) • Many Avian species – waterfowl (A) • Canines – (B) • Felids - Exotics and domestic (A) • Equine – (B) • Primates – Homo sapiens (A,B) • Marine Mammals (A)

  6. Influenza • Enveloped Virus • Single strand, Negative sense RNA genome • Eight ORF – Segmented • Code for 10 (11) viral proteins • HA – Hemagglutinin } • NA - Neuraminidase } • M - Matrix • NP - nucleoprotein • NS – nonstructural protein • PB1 - polymerase B1 • PB2 – Polymerase B2 • PA – Polymerase A

  7. Influenza • HA and NA are imbedded in the envelope • The major surface glycoprotein's • Virulence • Immunity • Diagnostics

  8. Influenza • HA • attaches to the host receptor • NA • Releases new virus from infected cells • M2 • Uncoating and release of viral genetic material • PA, PB1, PB2 • Virus replication

  9. H4 H8 H9 H13 H10 H16 H6 H11 H14 H3 H2 H1 H5 H15 H12 H7 N8 N2 N4 N3 N1 N5 N9 N7 N6 “SUBTYPE SOUP” Yoon (Hinshaw et al. 1980. Can. J. Microbiol. 26:622-629; Webster et al. 1978. Virology 84:268-278 ) (V.S. Hinshaw)

  10. Influenza Evolution • Antigenic Drift: • Point mutations due to polymerase errors • Minor antigenic changes over time • Antigenic Shift: • Reassortment occurring when one cell is infected by two viruses, allowing for shuffling of the segmented genome • Major antigenic changes • Both can lead to immune evasion

  11. SI Divergence • Three swine sub-types of H3N2 in US • Several swine H1N2 re-assortments • Numerous swine H1N1 drift and shift strains • 15 H and 9 N possibilities • High and low Path in Poultry

  12. Host Specificity • HA binds to sialic acid linked to galactose as its receptor • Human viruses prefer α-2,6 linkage on respiratory epithelium • Avian viruses prefer α-2,3 linkage on G.I. epithelium • Pig respiratory epithelium express both receptor linkages • “Mixing vessel” for avian-human reassortant viruses with pandemic potential • Human and quail also shown to express both receptor linkages

  13. Influenza A • Avian and Swine Influenza A viruses • Avian viruses infect humans but rarely human to human transmission to date • Why are we concerned about HP- H5N1? • Are we close to another Pandemic? • Probably not from the H5N1 viruses

  14. (Smithsonian, January 1989) Influenza Pandemics • 1918-1919 Spanish flu (H1N1) - world wide • 1957-1958 Asian flu (H2N2) - US 1957 • 1968-1969 Hong Kong flu (H3N2) – US 1968 • 1976 Swine flu scare (Fort Dix, US) • 1977 Russian flu scare • 1997 Avian flu scare (H5N1, H9N2) Slide complements of KJ Yoon

  15. Recycling of H1, H2, and H3 Subtypes Slide Complements of Amy Vincent Hilleman. 2002. Vaccine 20: 3068-87.

  16. Influenza A • However, The stage is set: • Significant global movement of people • Significant H5N1 activity in wild birds, domestic birds • Significant illegal and legal bird trade in Asia • Spread from East and Central Asian to Mediterranean/African and other domestic birds • > 250 human mortalities globally • Multi-species involvement – virus appears species promiscuous • Disruption of global eco-systems • It all looks bleak?

  17. Influenza - (H5N1 & others) Slide complements of KJ Yoon

  18. Zoonosis and SE Asia

  19. THE “BIRD FLU” - ASIA, 2003-2007 (AP, Kambayashi) (AP, Kuwana) (AFP) (Reuters, Stringer) (Reuters, Stringer) (Reuters, Sukplang) Yoon

  20. High Path in Chickens

  21. Crested Eagles intercepted in Belgium with Thai-Viet H5N1 High Path

  22. Global Water Fowl Flyways

  23. *Investigation of morbidity and mortality events *Surveillance of live wild birds *Surveillance of hunter-killed birds *Surveillance of sentinel species *Environmental sampling. 116,000 samples - 2007

  24. Avian Influenza • Serological surveillance • Commercial Poultry (NPIP) • poultry flocks (meat & layers) • Agent surveillance (targeted surveillance) – PCR based • Wildlife (USDA APHIS WS) • migratory water fowls (geese, ducks, gulls) • pharynx or cloacal swab • Backyard Poultry (IDALS) • to expand surveillance efforts (AI and END) in poultry • Upland Gamebirds (Iowa Poultry Assoc, USDA APHIS VS) • Dead bird surveillance – oropharyngeal and cloacal swab • Live bird surveillance – cloacal swabs U of GA Photo

  25. Testing Summary (2006) • Wild birds – 418 • 19 pool positive (M and/or H5) • Positive species: Teal (AGWT), MALL, Wigeon (AMWI), Pintail (NOPI) • County: Tama, Johnson, Emmet, Sac, Worth, Winnebago, Jackson, Louisa, Polk, Marion, Greene, Lucas • Subtype of AIV found: H5N2 (LPAI), H6N1 and H6N5 (LPAI), H3N2, H4N6 • Backyard poultry – 77 • 5 positive (no H5 or H7) • Gamebirds – 1 • All negative

  26. History of SI - US • SI is now believed to be an outcome of the 1918 global pandemic • Prior to 1918 had not been reported in pigs • Remained very stable for 75 years • The US appears to be ~unique • Resurrection of the 1918 virus (2005) • This is a classic Zoonosis – bird to human – (to the pig?)

  27. Swine Influenza in North America 1930 Slide Complements of Amy Vincent

  28. Circulating SIV In North America • H3N2 • cH1N1 • rH1N1 • H1N2 • huH1N1 • huH1N2 • Triple reassortant internal gene (TRIG) cassette Slide Complements of Amy Vincent

  29. SI – Pathogenesis/lesions • Tropism for bronchial epithelium • Incubation very short < 24hrs. • Cranioventral to patchy diffuse pneumonia • Interlobular edema • Fibrinous exudate in bronchi • Sequelae is bacterial pneumonia and gastric ulcers

  30. Influenza Virus

  31. Swine Influenza

  32. Swine Influenza (SI) • Nomenclature • Type (A) • Host (swine - Sw) • Place first isolated • Strain # if there is one • Year of first isolation • Antigenic subtype • A/Sw/MN/02-Novel H1N1 w/avian internals

  33. SI - Epidemiology • People to Pigs / waterfowl to pigs • Waterfowl to domestic birds to humans • In parts of Asia people, ducks, chickens, pigs, & wild animals/birds live together • In the US is water supply is important? • Cross protection between strains? • HI tests are misleading • Virus isolation and sequencing

  34. 25 D03-52335-H1 Rockshish, Oct 30 D04-9303-H1 Warren Kennedy, Feb 6 D03-29178-H1-R Jarman-Autog VAX, Jun 22 D03-48465-H1 Carrol, Oct 20 D03-41680 H1 Outback, Aug 28 D04-366-6-H1 Vandiford9, Jan 7 D03-29179-H1 G Kennedy, Jun 32 D04-14307-3-H1 J Humphrey, Mar 33 D04-15869-1-OM-H1 Tearshirt, Mar 10 D02-054399 H1 Webby Honeycutt, Dec 4 A/Sw/IN/00-H1N2 11 D01-34839 H1 PSF MO 8 D03-29180-H1 RM Hayes-Autog VAX, Jun 27 D03-62598-4 H1 J&J2, Dec 23 D03-55141-H1 L&W, Nov 26 D03-58605-H1 M Hope, Dec 13 D03-31608-4 H1 R Porter, July 3 A/Sw/MN/02-Novel H1N1 w/avian internals 12 D03-14870 H1 PSF MO 9 D02-043029 H1 Webby Sandhill, Sept 29 D04-425-H1 BR Daughtry, Jan 2 A/Sw/WI/97-Newer classic H1N1 1 A/Sw/IN/88-Classic H1N1 5 A/Sw/IA/30-Classic H1N1 14 A/Sw/NC/98-Dbl reassortant H3N2 15 A/Sw/TX/98-Trpl reassortant H3N2 16 A/Sw/CO/99-H3N2 17 A/Sw/IL/99 H3N2 21 D03-48822 H3 S1, Oct 31 D04-9304-H3 Combs, Feb 24 D03-54707-H3 Brice Usher, Nov 19 D02-039926 H3 Webby Judson Henning,Aug 18 D03-31608-4 H3 R Porter, July 49.3 45 40 35 30 25 20 15 10 5 0 Nucleotide Substitutions (x100) H1 and H3 NC Swine SI Isolates H1N2-like and H1N2-VAX group Novel H1N1-like group and H1N1-like VAX group H3N2 group

  35. Iowa Swine Isolates

  36. H2N3 H5N1? H4N6 What’s Next? Photo courtesy of Alex Ramirez

  37. 2 “Untypable” SIV isolates • Dr. Marie Gramer at MN-VDL • April 2006 and Sept 2006 • 2 farms with respiratory disease outbreaks in growing pigs (~5-12 weeks of age) • Isolates were not typable using SIV specific assays • Virus isolation positive on MDCK cells and by NP RT-PCR • Non-reactive with reference sera • HA and/or NA RT-PCR negative

  38. Case Histories • 2 Missouri farms with different owners • Multiple sow farms fed pigs into both sites • 4 miles apart • Did not share: • Pigs • Feed • Personnel • Trucks • Both used surface pond water for drinking and cleaning • Slide Complements of Amy Vincent

  39. ? 2007 County Fair • Pigs and people sick • Identical virus in pigs and people • Pig virus highly virulent and transmissible in the NADC experimental model • Nearly identical virus (whole genome) identified in Kansas finishing pigs 4 mos later Slide Complements of Amy Vincent

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