A multi-disciplinary research project on PMWS (2008-2012):

1. A multi-disciplinary research project on PMWS (2008-2012): Aetiology, pathogenesis and immunology of porcine post-weaning multi-systemic wasting syndrome: genetic-environmental interactions Presented by Dr. med. vet. Barbara Wieland, PhD Royal Veterinary College

2. Background • Epidemiology of PMWS has changed over the years (epidemic vs endemic) • Change in affected age groups reported • It is still unclear what triggers the onset of typical clinical signs • Porcine circovirus 2 (PCV2): necessary agent • Multi-factorial disease (environment, genetics, co-infections)

3. Project aims • Epidemiology • Establish risk factors affecting severity of PMWS on farms • 2. Immunology • Determine the cellular immune response to the putative microbial pathogens in vitro • 3. Disease model • Establish an in vivo model of PMWS to investigate role of environment • Our hypothesis is that PMWS occurs when the immune function is depressed in pigs with a specific genetic background following infection with PCV2 and • conjoint infection with a second microbial pathogen, and/or • exposure to one or more environmental stressors, which may be either physical or social in nature

4. Timeline of the project and interactions between the different parts 1a. Cross-sectional study D. Pfeiffer, B. Wieland, K.Staerk + BPEX year 1 2008 Retrospective Analysis- Knowledge Transfer & Data sharing Pig industry: BPEX Pfizer 1b. Longitudinal Study: Economic losses over time Recovery factors Risk factors Herd management Environmental & social stressors Presence of other pathogens Reproduction (Genetics) 2. Immunology D. Werling + Pfizer, Ark Genomics, IAH (Compton & Pirbright) a. Signalling pathways Effect of PCV-2 infection b. Secondary Infection c. Importance of host genetics year 2 2009 year 3 2010 3. Disease model M. Nevel, C. Wathes, T. Demmers +VLA Establish disease model Environmental stressors PCV-2 x Environment interaction PCV-2 + Co-infection with other pathogens x Environment interaction 1c. Epi model: Economic importance for pig industry Cost/benefit of control & preventive measures year 4 2011 year 5 2012

5. Objectives of Part 1, Epidemiology • Understand the impact of potential risk factors, and combinations of these, on the severity level of PMWS observed in English farms • Provide base-line data on the current endemic situation to assess the efficacy of PCV-2 vaccines • Develop epidemiological and economic models to identify appropriate and cost-efficient control strategies

6. Investigation of risk factors affecting severity of PMWS observed on farms: outline of studies carried out Cross-sectional study (1.4.2008-30.4.2009) 149 farms across England Follow-up visits on 50 farms (June 2009-January 2010) Economic models Definition of PMWS severity Severity category 1 approx 12. farms Severity category 2 approx. 12 farms Severity category 3 approx. 12 farms Non-vaccinating approx. 12 farms

7. Cross-sectional study: • 149 farm visits carried out • 3182 pigs sampled before PCV2 vaccination • Representing 65’000 sows (17% of pig herd) Locations of all farms included in the study, overlaid on a map of total pig numbers throughout England, aggregated into 10km squares (pig density data taken from the 2004 UK agricultural census).

8. Farm visit General information Health status Environment Productivity over time Management PMWS over time Reproduction Questionnaire Farm assessment Blood samples 20 samples Animal Welfare PCV-2 Elisa PCV-2 PCR PPV PRRS EP APP Age groups: Sows Weaners Growers Finishers Environment PMWS present (incl. post mortem)

9. Severity of PMWS observed by producers in different age groups from 2001 to 2008

10. Data collected PMWS severity Risk factors Pathogens PRRS, PPV, EP, APP, Salmonella Mortality: Records 2001-08 In age groups Health Other diseases, medication, vaccination Morbidity: % in age groups Qualitative and quantitative over time Reproduction AI, replacements parity of sows Productivity: FCR age at slaughter data 2001-08 Genetics % of different breeds Supplier, parent generation Environment housing, ventilation, light farm type PCV-2 prevalence: PCR Social stressors Stocking density, batch system, cross-fostering Correlated data  explore using factor analysis:basisto define PMWS severity at herd level Test for associated with PMWS severity

11. Laboratory results: Herd level Includes results of 147 farms PCV-2 Ab negative farms were PCR positive

12. Objectives of Part 2, Immunology • The objectives are : • Assess differences in cell type-specific signalling pathways perturbed by PCV2 infection • Analyse secondary responses of PCV2-infected cells isolated from different tissues; and • Investigate whether differences in PCV2/PMWS susceptibility are based on a genetic link attributable to a specific signalling pathway.

13. Objectives of Part 3, Disease model • The aim is to develop an in vivo disease model of PMWS to investigate the aetiology and pathogenesis of PMWS under controlled environmental conditions. • The objectives are: • to measure environmental effects on the aetiology and pathogenesis of PMWS; • to determine whether infection, immune and production responses to combined physical and social stressors in PMWS are additive or multiplicative; and • to quantify performance effects of PMWS, thereby informing the economic model developed in Part 1

14. Pablo Alarcon Martina Velasova Barbara Wieland Mandy Nevel Dirk Pfeiffer Katharina Staerk Christopher Wathes Bettina Schmidt Dirk Werling