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Tanja Opriessnig The Roslin Institute, University of Edinburgh, UK Veterinary Diagnostic and Production Animal Medicine Iowa State University, USA PEDV Background PRDC • 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 (?) Background PEDV http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3397359 Spike PRDC Nucleocapsid • Structure: Envelope protein E – Nucleocapsid (N) protein • Highly conserved: Best for testing – Spike (S) protein – Integral membrane (M) protein – Small envelope (E) protein Membrane protein M Age group PEDV Diarrhea Mortality Suckling pigs ++++ 100% in naïve populations Nursery pigs +++ ++ Grow-finish pigs ++ - Adults + - PRDC PEDV Shedding PEDV PRDC Fecal shedding: • Up to at least 2835 + days post infection (neonatal and nursery pigs) • Large amounts • Possible contribution factors: – – – – Age dependency Differences in virulence between isolates? Cross-protection between strains? Interaction with other pathogens? Viremia: • Short (days) • Low amounts PEDV Global Importance PRDC USA: PEDV still spreading Europe: Epidemics until the late 80ies; Reports after 2000 are rare 1971 2013 1982 1993 China: Severe epidemics in recent years • Only infectious for pigs – No role in public health PEDV USA Discovery Timeline PRDC MON TUE WED THU FRI SAT SUN April 15 April 16 April 17 April 18 April 19 April 20 April 21 April 22 April 23 April 24 April 25 April 26 April 27 April 28 April 29 April 30 May 1 May 2 May 3 May 4 May 5 Diarrhea IA Diarrhea IA May 6 May 7 May 8 May 9 May 10 May 11 May 12 EM-CoV Diarrhea CO Pan-CoV PCR + May 18 May 18 Diarrhea IA Diarrhea IA May 13 Diarrhea IN May 14 NVSL Sequencing Source: ISU-VDL 2013 May 15 May 16 May 17 Sequencing PEDV China NVSL confirms USDA announces PEDV U.S. Pig Inventory 2007 PRDC Density Level http://www.factoryfarmmap.org/#animal:hogs;location:US;year:2007 PEDV April 2013 PRDC IA IN Introduction of PEDV into the USA OH TIMELINE PEDV May 2013 PRDC MN SD MI IA IL CO IN OH PA MO OK Introduction of PEDV into the USA TIMELINE PEDV June 2013 PRDC MN SD MI NY IA CO IL KS PA MO OK Introduction of PEDV into the USA IN OH NC TIMELINE PEDV July 2013 PRDC MN SD WI MI NY IA IL CO IN OH PA MO KS OK TN NC TX Introduction of PEDV into the USA TIMELINE PEDV October 2013 PRDC MN SD WI MI NY IA IL CO IN MO KS OH PA MD KY OK TN NC TX Introduction of PEDV into the USA TIMELINE PEDV December 2013 PRDC MN SD WI MI WY NY IA NE IL CO CA IN MO KS OH PA MD KY OK TN NC TX Introduction of PEDV into the USA TIMELINE PEDV January 2014 PRDC MN SD WI WY MI NY IA NE IL CO IN OH MD MO KS PA KY CA OK AZ TN NC SC TX Introduction of PEDV into the USA TIMELINE PEDV February 2014 PRDC ND MT MN SD ID WI WY MI NY IA NE IL CO IN OH MD MO KS PA KY CA OK TN SC AZ NC TX Introduction of PEDV into the USA TIMELINE PEDV March 2013 PRDC ND MT MN ID SD WY VT WI MI NE NY IA IL CO IN OH MD MO KS PA KY CA OK TN NC SC AZ MS TX Introduction of PEDV into the USA TIMELINE PEDV Distribution of PEDV in the U.S PRDC Source: AASV PEDV Total Number of Positive Pig Samples PRDC 15-Jun-13 to 8-May-14: Age group No. Suckling 1,366/2,343 (49.3%) Nursery 1,183/2,817 (36.8%) Grow/finisher 1,199/3,123 (28.3%) Sows/Boars 558/1,380 (28.6%) TOTAL 4,306/9,663 (44.6%) 29 (30) States are affected to date Image Source: ISU-VDL 2013 PEDV 2013 Genotyping PRDC Emerging PEDVs in Asia and the US Historical PEDVs in Europe and Asia Source: Huang Y et al. mBio 2013; doi 10.1128/mBio.00737-13 PEDV Origin of the U.S. PEDV strains PRDC Source: Huang Y et al. mBio 2013; doi 10.1128/mBio.00737-13 PEDV Evidence of 2nd PEDV Introduction 2014 PRDC Whole genome sequencing Spike protein sequencing Source: Wang et al. Emerging Infectious Disease 2014; No. 5, May 2014 Diagnostics PEDV PRDC • Diagnostic Specimens – Intestines (Fresh) – Feces – Oral fluids – Intestines (Fixed) – Serum Virus isolation Real-time RT-PCR Electron microscopy Immunohistochemistry Indirect Fluorescent Antibody, ELISA Sequencing PEDV Total Number of Positive Pig Samples Weekly Basis PRDC Source: AASV PEDV PRDC Cumulative Number of Positive Samples 7000 6000 5000 4000 3000 2000 1000 0 Source: AASV 6,421 PEDV Economic Impact PEDV PRDC • 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 PEDV Economic Impact of PEDV •PRDC Estimated shortfall in market hogs from PEDV to North American slaughters 0% • ((Source: Rabobank) Canada US -5% Mexico -10% -15% -20% -25% Dec 13 Mar 14 Jun 14 Sep 14 Dec 14 Mar 15 Jun 15 Sep 15 Dec 15 Porcine Deltacoronavirus (PDCV) PEDV PDCV PRDC • 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 PEDV PDCV Distribution of PDCV in the U.S. PRDC Source: AASV PEDV PRDC PEDV versus PDCV Cumulative US results Positive Accessions Total Accessions tested PEDV 6,421 17,468 PDCV 142 1,091 % Positive States 36.8% 29 (30) 13.0% 14 PEDV PEDV Transmission What is known so far PRDC • 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 PEDV Transmission PEDV Role of Feed PRDC • 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 PEDV 2014 ISU Experiment PRDC Group Designation No. of pigs Diet Inoculation NEG-CONTROL SDPP-CONTROL 8 8 No SDPP 5% SDPP Dpi 0 PBS PBS PEDV-CONTROL 8 No SDPP PEDV 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 Summary PEDV PRDC • 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