Porcine Respiratory and Reproductive Syndrome

1. Porcine Respiratory and Reproductive Syndrome Dr. Alex Ramirez Veterinary Diagnostic and Production Animal Medicine Iowa State University

2. General Overview

3. PRRS • THE most $$$ significant disease of swine • $560 million / year $5.60 / pig marketed1 • Comparison • PRV $36 million / year • Hog cholera $360 million / year • Outbreak estimated cost of $255 / sow2 • Continues to be a widespread cause of abortion and respiratory disease in Iowa and the United States 1Neumann et al 2005 2Holck and Polson 2003

4. Karriker et al

5. Relatively easy to do… Karriker et al

6. Relatively easy to do… Hard to maintain… Karriker et al

7. Characteristics of the Virus • RNA virus • High mutation rate • Enveloped • Does not survive well in the environment • Likes cold weather • Open Read Fragments (ORF) • Total of eight (1a, 1b, 2, 3, 4, 5, 6, 7) • Usually only sequence ORF 5 • Sequencing 600 bp (4%) out of ~15,000 bp

9. Characteristics of the Virus • Constantly changing • “Quasi-Species” • European versus American strains  only 60-70% similar • Variable expression of disease severity • PRRS “Lite” • “Acute PRRS”  new disease or just a “stretch” • Immunity induced by one “strain” does not protect against another “strain”

10. Characteristics of the Virus • Highly infectious • Takes only a few viral particles to infect a pig • Increasing dose  • Quicker onset of disease • Minimal influence on the ultimate severity of disease • Transmission Potential : Low?? • Research  not very easy to spread • Field  variable experiences • Body secretions including semen • Farm-to-farm: neighborhood spread seems to occur

11. PRRS transmission Hermann et al 2005

12. Characteristics of the Virus • Duration of shedding • Up to 5 months or longer • Experimental studies done in “clean” animals • Mycoplasma prolongs PRRS-induced pneumonia • Does mycoplasma prolong PRRS shedding? • Route • Semen • Oral secretions • Age • Younger  longer

13. PCR ResultsCohort 1 (9 pigs) Karriker et al submitted 2007

14. Available Tests • FATS: Fluorescent antibody examination of frozen tissue • PCR: Polymerase chain reaction   • RFLP: Restriction fragment length polymorphism • VI: Virus Isolation • Virus sequencing: Sequence analysis • IHC: Immunohistochemistry  • ELISA: enzyme-linked immunosorbent assay • IFA (NVSL): indirect fluorescent antibody test • FFN: fluorescent focus neutralization assay • VN: Virus neutralization

15. Available Tests • FATS: Fluorescent antibody examination of frozen tissue • PCR: Polymerase chain reaction   • RFLP: Restriction fragment length polymorphism • VI: Virus Isolation • Virus sequencing: Sequence analysis • IHC: Immunohistochemistry  • ELISA: enzyme-linked immunosorbent assay • IFA (NVSL): indirect fluorescent antibody test • FFN: fluorescent focus neutralization assay • VN: Virus neutralization XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX

17. Respiratory

18. PRRSv Diagnostics • Lesions • Interstitial pneumonia • Can visualize septa - fine pattern • Tan discoloration - mottled or coalescing • Rubbery texture • Fail to collapse • Enlarged lymph nodes • Sub-iliacs are best to view

19. PRRSv Diagnostics

20. Low virulent strain of PRRSv High virulent strain of PRRSv

21. PRRSv-infected alveolar macrophages PRRSv-infected intravascular macrophages PRRSv infects and destroys macrophages in the lungs. Macrophages are important for removing bacteria and inflammatory debris from the lungs.

22. All strains of PRRSv induce lymphadenopathy characterized by hyperplasia of lymphoid follicles

23. Reproductive

24. Clinical Outcomes • Gestation age  Animal response • Weak born pigs • Stillborn pigs • Mummies • Early embryonic death  reduced litter size • Return to estrus • Abortion • Boars • Shed in semen • Variable impact on semen quality

26. PRRSv - Abortion due to Fetal Infection • Gross Lesions: • Sow: typically none • Fetus: • Diagnostically useful gross lesions are uncommon • Meconium staining of fetal skin • Umbilical cord edema with segmental hemorrhage • Mesocolonic edema • Perirenal edema

27. PRRSv-Infected Fetuses

28. Distribution of PRRSv-Infected Fetuses in a Litter • ALL FETUSES IN A LITTER ARE TYPICALLY NOT INFECTED • An average of 48.6% of the fetuses/litter infected • Sow 10 • PRRSV-POSITIVE Fetuses 1, 2, 3, 4, 6 (#5 autolyzed) • PRRSV-negative fetuses 7, 8, 9, 10, 11, 12, 13 • Sow 12 • PRRSV-POSITIVE Fetuses 5, 6, 7, 8, 9, 10 • PRRSV-negative fetuses 1, 2, 3, 4, 11, 12

29. Assumptions: Litter of 1250% fetal infection rate

30. PRRSV Abortion Diagnostics PCR is the test of choice on fetal material • Extremely sensitive • Tissues and fetal thoracic fluid are equivalent • Samples from 1 positive fetus can be pooled with 7 negative fetuses (1:8) without loss of sensitivity • Limited impact of autolysis (can be detected following incubation at 37oC [99oF] for 4 days) Preferred diagnostic procedure: pool fetal thoracic fluid from 6 fetuses/litter for PRRSV PCR

31. Clinical Outcomes • Suckling and nursery pigs • Severe respiratory disease: interstitial pneumonia • Rapid breathing, especially after stress • Variable death loss • Often takes 30-45 days longer to reach market compared to groups ahead or behind • Severity of infection diminishes greatly after 8 weeks of age unless affected by another agent • M. hyo • PCV2 • SIV

32. Vaccination

33. PRRSV Immunity Development Parameter PRRSV PRV . Non-neutralizing 7-14 days NA antibodies Neutralizing antibodies > 28 days 3-4 days Peak gamma 8-10 months 1 month interferon levels Duration of shedding > 3-4 months 3-4 weeks Zuckermann, 1999

34. Vaccination • CONTROVERSIAL (to say the least!!) • Everyone has a different opinion • MLV vaccines • Several have been marketed • Patent infringement has resulted in only two available today: Boehringer Ingelheim • PRRS MLV • PRRS ATP • Variable benefit • “Strain” differences • Delay between vaccination and protective immunity  need at least 4 – 6 weeks

35. Vaccination • MLV vaccines (cont.) • Attenuated? • Not safe in NAÏVE pregnant females • Abortions • Danish experience: farms receiving vaccine virus contaminated semen experienced reproductive disease • Recombination? • Quarterly herd vaccination • Booster heterologous protection? • Interfere with future diagnostics

36. Vaccination • Sequence information • Does not predict virulence • Does not predict respiratory vs. reproductive • Does not predict cross-protection • Do not use to select best vaccine • Does help as a epidemiological tool • New vs. old • Possible source? • Does serve as a reference for the future

37. PRRSV Vaccination • Killed vaccines • None commercially available today • Appear to booster existing immunity • Unclear efficacy in naïve animals • Most likely of no value • Autogenous? • Quasispecies • Stability

38. Serum Inoculation • Based on the concept that the virus is shed 4-6 months after infection • Infect/vaccinated incoming animals >3-4 months before entry • Stop animal introductions for 4-6 months, then start introduction of negative animals • Gilts most likely to transmit virus to their offspring • Many programs developed off this strategy • Produce PRRSV free offspring from sow herd • Eliminate PRRSV reproductive failure • Eradicate PRRSV without depop-repop

39. PRRS Management

40. Cycle PRRS Management • Exposure • Natural • Vaccine • Serum • Herd closure • Target 200+ days • Biosecurity • Location • Trucking  Wash and Bake • Pig flow • Needles

41. Acknowledgements • I would like to recognize the contribution of others to this presentation: • Dr. Brad Thacker • Dr. Locke Karriker • Dr. Pat Halbur

42. Questions?