PRR

S Porcine Respiratory and Reproductive Syndrome

Dr. Alex RamirezVeterinary Diagnostic and

Production Animal MedicineIowa State University

PRR

S General Overview

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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

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Probability of Survival Through Time Period - All Farms (n=84)

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Karriker et al

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Probability of Survival Through Time Period - All Farms (n=84)

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Relatively easy to do…

Karriker et al

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Probability of Survival Through Time Period - All Farms (n=84)

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Relatively easy to do…

Hard to maintain…

Karriker et al

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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

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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”

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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

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PRRS transmission

Route ID50

SQ (parenteral) ~101

Intranasal 103.9

Artificial Insemination 104.5

Oral 105.2

Aerosol ??

Hermann et al 2005

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• 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

Characteristics of the Virus

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PCR ResultsCohort 1 (9 pigs)

ID 2 wk 4 wk 6 wk 8 wk 10wk 12 wk 14 wk 16 wk 18 wk 20 wk 22 wk 24 wk 26 wk 28 wk

1-152 NEG NEG POS POS POS POS NEG POS NEG POS        

1-156 NEG NEG POS POS POS POS NEG NEG NEG NEG NEG NEG NEG POS

1-177 POS POS POS POS POS POS POS POS POS POS        

1-186 POS POS POS POS POS POS POS POS POS POS        

1-189 POS POS POS POS POS NEG POS NEG NEG NEG POS      

1-191 POS POS POS POS POS POS NEG NEG NEG NEG POS      

1-194 NEG POS POS POS POS POS NEG NEG POS POS        

1-196 POS POS POS POS NEG POS POS POS POS NEG   POS NEG NEG

1-220 NEG POS POS POS POS POS NEG NEG NEG NEG NEG POS NEG NEG

Karriker et al submitted 2007

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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

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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

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PRR

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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

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PRRSv Diagnostics

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Low virulent strain of PRRSv

High virulent strain of PRRSv

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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.

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

PRR

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• 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

Clinical Outcomes

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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

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PRRSv-Infected Fetuses

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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

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Assumptions: Litter of 12

50% fetal infection rate

Confidence level for PRRSV detection in a

litter with PCR

Number of fetuses sampled per litter

99% 6

97.5% 5

95% 4

90% 4

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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

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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

PRR

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Zuckermann, 1999

Parameter PRRSV PRV .

Non-neutralizing 7-14 days NAantibodies

Neutralizing antibodies > 28 days 3-4 days

Peak gamma 8-10 months 1 monthinterferon levels

Duration of shedding > 3-4 months 3-4 weeks

PRRSV Immunity Development

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• 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

Vaccination

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• 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

Vaccination

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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

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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

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• 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

Serum Inoculation

PRR

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PRRS Management• Exposure

– Natural– Vaccine– Serum

• Herd closure– Target 200+ days

• Biosecurity– Location– Trucking Wash and Bake– Pig flow– Needles

Cycle

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Acknowledgements

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

PRR

S Questions?