Dr. Amy Vincent - H3N2 influenza A virus in swine and the human-animal interface

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The growing diversity of H3N2 influenza A virus in swine and the impact on control in swine and at the human animal interface - Dr. Amy Vincent, Research Veterinary Medical Officer, National Animal Disease Center, USDA-ARS, from the 2013 Allen D. Leman Swine Conference, September 14-17, 2013, St. Paul, Minnesota, USA.

More presentations at http://www.swinecast.com/2013-leman-swine-conference-material

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  • 1. Similarly, this is a phylogeny of north american HA genes of the H3N2 (560 sequences)It has 4 characteristic cluster types, with Cluster IV representing much of the onward transmission, and I’ve highlighted in red those viral isolates detected in 2012.Now, though it’s not as well structured as the H1s, there appears to be an increase in the diversity we’re getting in North America.There are at least 6 strongly supported (bootstrap support greater than 60%) monophyletic clusters that have emerged in 2012. (the very bottom cluster is the H3N2v cluster IV, Clade A)
  • Matrix lineage. NAm is being slowly but surely wiped out by the pandemic matrix.
  • This figure depicts the proportion of persons with hemagglutination inhibition antibody titer > 40 to H3N2v by age cohort on the x axis from the 3 countries with the youngest children at the left x axis and the oldest cohort at the right x axis. The age cohorts have been smoothed a bit to make them line up with one another for comparison purposes. The overall trends are similar in the 3 countries within age groups.
  • Dr. Amy Vincent - H3N2 influenza A virus in swine and the human-animal interface

    1. 1. Growing diversity of H3N2 influenza A virus in swine: Impact on control in swine and at the human animal interface. Amy L. Vincent, DVM PhD Research Veterinary Medical Officer National Animal Disease Center USDA-ARS USDA-NADC Team USDA-NVSL USDA-NAHLN Laboratories USDA-NSU US Swine Producers and Veterinarians
    2. 2. USDA IAV Surveillance in Swine • Implemented in 2009 – Samples began being submitted in November • 39 participating NAHLN labs – Approved diagnostic assays • • • • Matrix FluA screening PCR HA and NA subtyping PCR Virus Isolation – Isolates sent to NVSL repository Sequencing – priority on HA, NA and M genes – Sequences deposited to GenBank public database • Passive Surveillance – Primary source of samples are from diagnostic samples from clinically affected pigs, voluntary and anonymous – Small number of samples sent directly to NVSL associated with zoonotic events as identified by Public Health: H3N2v 2
    3. 3. Systematic approaches to monitor IAV in swine Genetic Analysis Sequencing Antigenic Analysis Swine Studies • Regional/national efforts – USDA, CEIRS, ESNIP, etc. • International networks – CEIRS, ESNIP, OFFLU
    4. 4. U.S. swine IAV surveillance results • What does the USDA data tell us ? – Trends in HA and NA dynamics • Subtypes: H1N1, H1N2, and H3N2 • Phyloclusters: defined using genetic distance of the HA – H1s with alpha, beta, gamma, pdm09, and delta (human seasonal origin) – H3s with historical Clusters I, II and III, along with a rapidly expanding contemporary Cluster IV – Evidence of reassortment • Matrix Lineage: Classical swine origin or pandemic matrix gene as an indicator of reassortment and virus evolution. • Viruses for further research (NADC and others) • Viruses for vaccine development
    5. 5. H3 & H1 Phyloclusters in 2009-2013 200 180 Number of Swine Isolates 160 140 H3N2 120 no data H1N1 pdm 100 H1N2 delta2 H1N2 delta1 80 H1N1 gamma H1N1 beta 60 H1N1 alpha 40 20 0 09Q410Q110Q210Q310Q411Q1 11Q2 11Q3 11Q412Q112Q212Q312Q413Q113Q213Q3 Year by quarter
    6. 6. Phylogenetic relationships of H3 swine IAV Phylogenetic clade Cluster I Cluster II Cluster III Cluster IV 6 clusters evolving forward into 2013 HA associated with H3N2v 0.02 Between clade amino acid identity ~94%: within clade amino acid identity ~98% Tavis Anderson, IRV accepted
    7. 7. 200 180 160 140 120 100 80 60 40 20 0 09Q4 10Q1 10Q2 10Q3 10Q4 11Q1 11Q2 11Q3 11Q4 12Q1 12Q2 12Q3 12Q4 13Q1 13Q2 13Q3 Number of Swine isolates Matrix lineage 2009-2012 No data Year by quarter North American Pandemic • pdm09 Matrix gene currently ~75% 0.02 Tavis Anderson, IRV accepted
    8. 8. Reassortment generates new viruses
    9. 9. Reassortment patterns of H3N2 virus in U.S. swine Genotypes associated with H3N2v (Kitikoon et al., 2013, J Gen Virol)
    10. 10. Are the H3 genetic clusters impacting cross-reactivity? H3 antibodies had inconsistent cross-reactivity among sub-clusters and with vaccines D F TX/2011 IA/2011 IA/2011 IL/2011 IN/2011 IN/2012 NY/2011 IN/2011 PA/2010 IV I&IV I Vaccine 3 C Vaccine 2 A IL/2009 MN/2009 (IV) IA/2007 (I) IV MN/2006 TX/1998 Virus (cluster) TX/1998 MN/2006 IA/2007 MN/2009 IL/2009 PA/2010 IN/2011 NY/2011 IN/2012 IL/2012 MI/2012 MN/2012 MN/2012 MN/2012 IA/2012 IN/2011 IL/2011 IA/2011 IA/2011 IA/2012 IA/2011 TX/2011 IL/2012 IA/2012 NE/2012 I Vaccine 1 Sera Homologous < 4-fold reduction = 4-8-fold reduction > 8-fold reduction (A) (B) (C) (D) (F) Pravina Kitikoon, IRV accepted
    11. 11. Cause or Consequence? • What is driving the observed increase in diversity? – Reassortment? – Pig movement? – Ineffective vaccines? – Unknown factors? • With all this antigenic diversity, how well are control measures working on a national level? • Can we develop a system for more efficient updates of commercial vaccines? • What are the implications for human health?
    12. 12. Human Infections with variant IAV - USA Case Count: Detected U.S. Infections with Variant Influenza Viruses by State since December 2005 Reporting State Hawaii Illinois Indiana Iowa Kansas Maine Maryland Michigan Minnesota Missouri Ohio Pennsylvania South Dakota Texas Utah West Virginia Wisconsin Total H3N2v 1 5 154 5 1 2 12 8 8 108 16 Total H1N1v H1N2v 2011 1 2 3 3 H3N2v 2012 1 4 138 1 2013* 1 14 2 2 2 2 12 6 5 1 4 3 107 11 2 1 1 1 1 5 21 2 2 347 14 5 366 1 3 20 12 309 18 339 *2013 human cases recently report associated with county fair swine exposure http://www.cdc.gov/flu/swineflu/variant-cases-us.htm
    13. 13. H3N2v, 2011-13 • >339 cases in humans primarily associated with children at swine barns at agricultural fairs in summers of 2011, 2012 and again in 2013 – All genotype 1 H3N2 – Nearly all HA cluster type A – Nearly all NA 2002 lineage – Low serologic cross-reactivity in children and teenage population • Many questions regarding recommendations to fair officials, exhibitors, and exhibited stock – How to screen stock before entering exhibit – Recommendations on vaccines for kids and pigs – Animal movement practices at fairs/venues – Multi-disciplinary team drafted guidance documents early 2013
    14. 14. Epi-Curve for Confirmed H3N2v Cases State of Isolation July - Sept 28, 2012 (N=306) MN (n=4) 40 MD (n=12) 35 PA (n=11) 30 WI (n=20) 25 MI (n=5) WV (n=3) 20 IL (n=4) 15 OH (n=106) 10 IN (n=138) HI (n=1) 5 0 7/9 7/16 7/23 7/30 8/6 8/13 8/20 8/27 9/3 Illness Onset Date (Includes illness onset dates imputed from specimen collection dates and report dates) http://www.cdc.gov/vaccines/acip/meetings/downloads/slides-oct-2012/02-influenza-Finelli.pdf 9/10
    15. 15. Proportion of Persons with Hemagglutination Inhibition Antibody Titer >40 to Influenza A (H3N2)v Virus by Year of Birth NORWAY CANADA USA 90 80 Proportion 70 60 50 40 30 20 10 0 2011 2001 1991 1981 1971 1961 1951 1941 1931 1921 1911 Slide courtesy of Dr. Nancy Cox, CDC Skowronski DM. et al. JID. 2012 August 12; CDC, Unpublished data, 2012; Waalen et al., Euro Surveill 17:pii=20170, 2012
    16. 16. Future Challenges and Gaps for Swine Exhibits • Swine IAVs in a period of frequent reassortment and HA evolution. – Continued monitoring and timely dissemination of information required. • Currently available vaccines for swine do not prevent nasal shedding, some performed better than others. • There is no uniform system to select swine IAV for vaccine updates. – Mass vaccinating has been shown to dramatically decrease viral shedding. – Mixed immune populations comingled together will continue to be difficult to manage. • A sensitive and specific pen-side test is not available and clinical signs are not sufficient for identifying shedding pigs at points of concentration. • Pig movement and mixing is difficult to track with fair and show pigs. • There is variability among exhibition venues and markets for animal movement and show requirements. • Guidelines & recommendations for swine IAV implemented in a number of states for the 2013 Fair season. Partnerships between animal health, human health, and the swine industry are critical to minimize the impact of these events.
    17. 17. Acknowledgments • • • • • • NADC Michelle Harland Gwen Nordholm Daniela Rajao Alessandra Dias Matt Sandbulte Brian Campbell • • • • • • • Kelly Lager Crystal Loving Mark Kehrli Jason Huegel Jason Crabtree Tyler Standley Darrell Bayles • • • • • • • • • • • • • • • • • • • Pravina Kitikoon Tavis Anderson Phil Gauger Jamie Henningson Alessio Lorusso Doug Braucher Janice Zanella Eraldo Zanella Sabrina Swenson John Korslund Marie Gramer Nicola Lewis Daniel Perez Martha Nelson Richard Webby James Roth Ruben Donis Hana Golding Surender Khurana • U.S. Producers and Swine Vets • Funding: USDA-ARS USDA-APHIS National Pork Board CDC Many thanks to USDA NCAH Visual Services

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