1. Tanja Opriessnig The Roslin Institute, University of Edinburgh, UK Veterinary Diagnostic and Production Animal Medicine Iowa State University, USA

2. PRDC PEDV Background Discovered in 1971 in the UK –Acute outbreaks of diarrhea in feeder pigs and fattening pigs –Suckling pigs did not become sick –Oldham et al., 1972 Family Coronaviridae –Enveloped, positive stranded RNA viruses –Subfamilies: Coronavirinae & Torovirinae –Important for pigs: Genus Alphacoronavirus –PEDV, TGEV: Diarrhea –PRCV: Respiratory disease Genus Betacoronavirus –Porcine haemaggluination encrophalomyelitis virus (HEV): Encephalomyelitis Genus Deltacoronavirus –Porcine deltacoronavirus (PDCV): Diarrhea (?)

3. PRDC PEDV Background Structure: –Nucleocapsid (N) protein Highly conserved: Best for testing –Spike (S) protein –Integral membrane (M) protein –Small envelope (E) protein http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3397359 Membrane protein M Envelope protein E Spike Nucleocapsid

4. PRDC PEDV Age groupDiarrheaMortality Suckling pigs++++ 100% in naïve populations Nursery pigs+++++ Grow-finish pigs++- Adults+-

5. PRDC PEDV PEDV Shedding Possible contribution factors: –Age dependency –Differences in virulence between isolates? –Cross-protection between strains? –Interaction with other pathogens? Fecal shedding: Up to at least 28- 35 + days post infection (neonatal and nursery pigs) Large amounts Viremia: Short (days) Low amounts

6. PRDC PEDV Global Importance 1971 2013 1993 1982 China: Severe epidemics in recent years Europe: Epidemics until the late 80ies; Reports after 2000 are rare Only infectious for pigs –No role in public health USA: PEDV still spreading

7. PRDC PEDV USA Discovery Timeline MONTUEWEDTHUFRISATSUN April 15 Diarrhea IA April 16April 17April 18April 19April 20April 21 April 22April 23April 24April 25April 26April 27April 28 April 29 Diarrhea IA April 30 Diarrhea IA May 1May 2May 3May 4May 5 May 6 Diarrhea IA May 7May 8 Diarrhea IN May 9May 10 EM-CoV May 11 Diarrhea CO May 12 Pan-CoV PCR + May 13 NVSL Sequencing May 14May 15 Sequencing PEDV China May 16 NVSL confirms May 17 USDA announces May 18 Source: ISU-VDL 2013

8. PRDC PEDV U.S. Pig Inventory 2007 http://www.factoryfarmmap.org/#animal:hogs;location:US;year:2007 Density Level

9. PRDC PEDV April 2013 IA IN OH Introduction of PEDV into the USA TIMELINE

10. PRDC PEDV May 2013 IA IN OH MI PA OK CO SD MN IL Introduction of PEDV into the USATIMELINE MO

11. PRDC PEDV June 2013 IA IN OH MI PA OK CO SD MN KS NY IL Introduction of PEDV into the USATIMELINE MO NC

12. PRDC PEDV July 2013 IA IN OH MI PA OK CO SD MN KS NY TX TN WI IL Introduction of PEDV into the USA TIMELINE MO NC

13. PRDC PEDV October 2013 IA IN OH MI PA OK CO SD MN KS NY TX TN WI IL Introduction of PEDV into the USA TIMELINE MO NC MD KY

14. PRDC PEDV December 2013 IA IN OH MI PA OK CO SD MN KS NY TX TN WI IL Introduction of PEDV into the USA TIMELINE MO NC MD KY NE WY CA

15. PRDC PEDV January 2014 IA IN OH MI PA OK CO SD MN KS NY TX TN WI IL Introduction of PEDV into the USA TIMELINE MO NC MD KY NE WY CA AZ SC

16. PRDC PEDV February 2014 IA IN OH MI PA OK CO ND MN KS NY TX TN WI IL Introduction of PEDV into the USA TIMELINE MO NC MD KY NE WY CA SD MT ID AZ SC

17. PRDC PEDV March 2013 IA IN OH MI PA OK CO SD MN KS NY TX TN WI IL Introduction of PEDV into the USA TIMELINE MO NC MD KY MT ID ND SC AZ CA NE WY MS VT

18. PRDC PEDV Distribution of PEDV in the U.S Source: AASV

19. PRDC PEDV Image Source: ISU-VDL 2013 Total Number of Positive Pig Samples 15-Jun-13 to 8-May-14: Age groupNo. Suckling1,366/2,343 (49.3%) Nursery1,183/2,817 (36.8%) Grow/finisher1,199/3,123 (28.3%) Sows/Boars558/1,380 (28.6%) TOTAL4,306/9,663 (44.6%) 29 (30) States are affected to date

20. PRDC PEDV Source: Huang Y et al. mBio 2013; doi 10.1128/mBio.00737-13 2013 Genotyping Historical PEDVs in Europe and Asia Emerging PEDVs in Asia and the US

21. PRDC PEDV Origin of the U.S. PEDV strains Source: Huang Y et al. mBio 2013; doi 10.1128/mBio.00737-13

22. PRDC PEDV Evidence of 2nd PEDV Introduction 2014 Source: Wang et al. Emerging Infectious Disease 2014; No. 5, May 2014 Whole genome sequencing Spike protein sequencing

23. PRDC PEDV Diagnostics Diagnostic Specimens –Intestines (Fresh) –Feces –Oral fluids –Intestines (Fixed) –Serum Virus isolation Real-time RT-PCR Electron microscopy Indirect Fluorescent Antibody, ELISA Immunohistochemistry Sequencing

24. PRDC PEDV Total Number of Positive Pig Samples Weekly Basis Source: AASV

25. PRDC PEDV Cumulative Number of Positive Samples 6,421 Source: AASV

26. PRDC PEDV PEDV Economic Impact Approximately 5 million pigs have died in the U.S. –About 4.5% of the animals sent to processing plants last year in the U.S –Source: AgriTrends It is estimated 12.5 million fewer pigs will be slaughtered in 2014, which will result in an overall U.S. pork production decline of 6-7% –Largest estimated decrease in 30 years –Source: Rabobank

27. PRDC PEDV Economic Impact of PEDV Estimated shortfall in market hogs from PEDV to North American slaughters ((Source: Rabobank) 0% -5% -10% -15% -20% -25% Dec 13 Mar 14 Jun 14 Sep 14 Dec 14 Mar 15 Jun 15 Sep 15 Dec 15 US Canada Mexico

28. PRDC PEDV Porcine Deltacoronavirus (PDCV) Initially discovered in Hong Kong in 2009 (Woo et al., 2012) Described in the U.S. in 2014 –Associated with diarrhea in sows and their litters –No experimental data to date –Precise pathogenesis and role of PDCV is currently unknown PDCV

29. PRDC PEDV Distribution of PDCV in the U.S. Source: AASV PDCV

30. PRDC PEDV PEDV versus PDCV Cumulative US results PEDVPDCV Positive Accessions6,421142 Total Accessions tested17,4681,091 %36.8%13.0% Positive States29 (30)14

31. PRDC PEDV PEDV Transmission What is known so far Rapidly spread across U.S. –Transport vehicles PEDV negative trucks returning from abattoirs positive (Lowe et al., 2014) –Animal movement –Aerosol transmission? Source: Dr. Darin Madson

32. PRDC PEDV PEDV Transmission Role of Feed Detection of PEDV RNA in feed –Confirmation of PEDV RNA in porcine plasma derived products –Relationship with PEDV outbreaks in Canada? Recall of pelleted nursery feeds containing plasma ingredients in Ontario –CFIA (18-Feb-14); Feedstuffs (20-Feb-14) –4-Mar-14: CFIA could not confirm live virus in feed pellets containing blood plasma Ban of spray-dried porcine plasma products in the UK (Vet Rec, May 2014) Centre de développement due pork du Québec Inc (CDPQ) risk analysis –Feed is medium risk for PEDV transmission –Study by Scott Dee, Pipestone Applied Research

33. PRDC PEDV 2014 ISU Experiment Group Designation No. of pigs DietInoculation Dpi 0 NEG-CONTROL8No SDPPPBS SDPP-CONTROL85% SDPPPBS PEDV-CONTROL8No SDPPPEDV Viremia only in PEDV-CONTROL group Seroconversion only in PEDV-CONTROL group Conclusion: No evidence of infectivity of the PEDV present in the investigated plasma lot

34. PRDC PEDV Summary PEDV is now prevalent in the majority of swine producing states in the USA Epidemic situation Endemic situation? Lesion learned: Constant awareness –Globalization increases the risk of pathogen introductions –Need to invest in rapid epidemiological studies to document how PEDV was introduced to the US and learn from this situation –Need much more work on advancing understanding of transmission routes Pigs, people, trucks, fomites, feed, air, water etc… STOP PEDV