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Porcine Respiratory and Reproductive Syndrome. Dr. Alex Ramirez Veterinary Diagnostic and Production Animal Medicine Iowa State University. General Overview. PRRS. THE most $$$ significant disease of swine $560 million / year $5.60 / pig marketed 1 Comparison PRV $36 million / year - PowerPoint PPT Presentation
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PRR
S Porcine Respiratory and Reproductive Syndrome
Dr. Alex RamirezVeterinary Diagnostic and
Production Animal MedicineIowa State University
PRR
S General Overview
PRR
S
3
PRRS
• THE most $$$ 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
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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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S
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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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S
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Probability of Survival Through Time Period - All Farms (n=84)
0
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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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PRR
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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
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
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PRR
S Respiratory
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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
S Reproductive
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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
S Vaccination
PRR
S
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
S PRRS Management
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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?