r.b. baker, dvm, ms senior clinician
TRANSCRIPT
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Food Supply Veterinary Services Veterinary Diagnostic and Production Animal Medicine
Iowa State University 1
Porcine Circovirus - What Do We Know and What Can We
Do?"
R.B. Baker, DVM, MS Senior Clinician
[email protected] 515-294-9358
Food Supply Veterinary Services Veterinary Diagnostic and Production Animal Medicine
Iowa State University 2
Acknowledgements
• Iowa State University Diagnostic Lab • Pat Halbur – ISU • Ken Schwartz -ISU • Tonya Opriessnig – ISU • Locke Karriker - ISU • Matthew Turner – Prestige NC • Darrin Madson – ISU
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PCVAD Web Resources • ISU VDPAM
– http://www.vetmed.iastate.edu/departments/vdpam/swine/diseases/pcv2/default.asp
• The Pig Site: PMWS and PCVD – http://www.thepigsite.com/pmws/
• Control of Porcine Circovirus Associated Diseases (PCVDs):
– http://www.pcvd.org/ • American Association of Swine Veterinarians
– http://www.aasp.org/ • National Pork Board
– http://www.pork.org/ Food Supply Veterinary Services
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PCVAD
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PCVAD
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PCV2 Associated Spiking Finisher Mortality
PCVAD
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PCV2 Associated Spiking Finisher Mortality PCVAD
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PCV2 Associated Spiking Finisher Mortality
PCVAD
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Circoviruses • Circoviridae
– Circovirus, Gyrovirus (plants), TT viruses • Beak and Feather Disease: 1920 • Pigeon, Duck…..circovirus • Porcine circovirus type 1: 1975
– Tissue culture contaminant – Avirulent for swine
• Porcine circovirus type 2: 1995 – PCV2a – PCV2b
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Characteristics • Circular single stranded DNA • Very hardy: think parvovirus/FMD
– Disinfectants: • Infection has affinity for lymphoid
system • Vaccines are efficacious in poultry &
now pigs - IF given prior to infection
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PCV2 Associated Disease (PCVAD): History
• First identified in Canada 1991
• Reported in 1996/97/98 – US and Canada
• France and Spain in 1997
• Until 2006 No clear case definition in the US
– Diagnosis was based on pathology reports
– Recently the AASV developed a specific case
description
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PCV2 à PCVAD Clinical presentation
• Wasting pigs • Fever
• Anemic pigs • Jaundice
• Respiratory symptoms • Ulcers
• Lymphadenopathy • Some PDNS
• HIGH (doubling) of MORTALITY
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PCV2 Associated Spiking Finisher Mortality
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Current Observations
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PCVAD • PCV-2 virus has been declared the Primary agent by almost all investigators – global
• Canada and the US have reported significant outbreaks beginning 2004/05 continuing today – Vaccine has shut this down in most
cases but not all
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Current Observations
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PCV2 Associated Spiking Finisher Mortality
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The European Experience with PCV2
• Sow vaccinations appear to be successful in France
• Spain, Netherlands, and Great Britain declining epidemics without vaccine
• Only PCV2 is clearly associated with the European experience
• The disease continues to expand its range
– Recently Poland, Croatia, Asia, & South America, China, Viet Nam
– All pig rearing areas around the world
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US & CANADIAN EXPERIENCE
• Why this sudden change? – The virus has been in most pigs for
many years (>100?)
– New more virulent strains? PCV2b
– A new more elusive agent?
– Changes in genetics?
– Changes in management?
– Changes in the PCV2 virulence factors?
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New PCV2 or New Pathogenicity?
– There is significant circumstantial evidence that another yet unknown factor is involved
– Two studies that indicate no difference in pathogenicity between PCV2a and PCV2b
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PCVAD Finisher Mortality • No clear indication of other agents
– PRRSv most frequent co-agent • No FAD’s • Pigs often do not respond to
antimicrobial treatment – Most bacterial agents are unlikely co-factors • Injecting pens or barns increases
mortality? Food Supply Veterinary Services
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PCV2 Associated Spiking Finisher Mortality
PCVAD
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Current Observations
PCVAD
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Diarrhea similar to Ileitis
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Mesocolonic edema was a significant finding in grow-finish pigs in early
outbreaks
Courtesy of Dr. Matthew Turner Food Supply Veterinary Services
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Interlobular edema was frequently reported in grow-finish pigs in early
outbreaks
Courtesy of Dr. Matt Turner
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Porcine Dermatitis and Nephropathy Syndrome (PDNS):
A Significant Finding in Early Outbreaks Food Supply Veterinary Services
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PDNS Field Case Courtesy of Dr. Mike Yaeger ISU VDL
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The US Experience • In the field mostly endemic/mild or misdiagnosed until 2005 – Occasional pigs with PMWS/PDNS – Usually nursery pigs associated
with Hps, PRRS, & Flu • Epidemics spread like “wildfire”
– To all pig producing states
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The Recent US Experience
• High Mortality – Often affected and unaffected in same
pens and barns – Affected die – Unaffected perform well – > 50% barn mortality was common before
vaccine – Outbreaks last 4-6 weeks – Usually start 2od to 3rd week post
placement – Deaths rates high by 3rd week – Taper off to destroyed by week 6/7
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Dendogram based on entire PCV2 sequencing and comparison of PCV2 sequences available from the GenBank.
PCV2b
RFLP 321 “new”
PCV2a
RFLP 422, 321 “old”
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Genomic Analysis of PCV2 at the ISU VDL
– Currently doing sequencing of ORF2 • Only a few sequenced in 2005
– 6 of 7 were genotype “2a”, the other was “2b” • 2006
– 131 cases were “2b” (aka, European genotype) – 78 cases were “2a” (aka, North American genotype) – 79 cases could not be sequenced mainly due to low
amount of virus
– Sequencing for RFLP prediction of the virus is under validation
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Trends in total cases of PCVAD at ISU
Sporadic 97-05 / Epidemic 05-06
11 14 15 18 37130
449
665749
1116
852719
964
2045
896
0
500
1000
1500
2000
2500
1993 1995 1997 1999 2001 2003 2005 2007
7
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Grand Total 14611Respiratory 9332Enteric 2082Systemic 2019Abortion 272Heart 269Liver 165CNS 160Urinary 77Skin 39Arthritis 32Anemia 8
Porcine Diagnosis by System Affected ISU VDL in 2007
Diagnosis Number
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Total
108
6983
107 105126
73
119
76103
148
111
0
20
40
60
80
100
120
140
160
june
200
6
July
200
6
Aug
200
6
Sep
t 200
6
Oct
200
6
Nov
200
6
Dec
200
6
Jan.
200
7
Feb
2007
Mar
ch 2
007
Apr
il 20
07
May
200
7
Total
Drop Page Fields Here
Count of Diagnosis
Receive Date2
Drop Series Fields Here
PCV2 Systemic Cases
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PCVAD Finisher Mortality Case
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Six months diagnostics
6247
6 1 621
820 19
7 3 1
63
010203040506070
PCV2
PRRSV SIV
Rotavirus
HPS
S.suis
Salmonella
Pasteurella m
ult...
M.hyo
Other bacteria
l
Lawsonia intra
ce...
Cryptosporid
iu...
Total submissio
ns
viral and bacterial isolations
subm
issi
ons
Potential Co-agents in a High Mortality Field Case
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Diagnosis of PCVAD • Clinical Signs and Gross lesions • Microscopic lesions
– Hallmark lymphoid lesions • Immunohistochemistry
– Main confirmatory test • Serology
– ELISA, IFA – PCR: Quantitative, nested, multiplex
• Virus isolation • Sequencing • Antigen capture ELISA
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Submission for a PCVAD Investigation
Liver
Lung
Kidney
Spleen
Ileum
Colon
Heart
ADD lymph nodes and tonsil
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Bottom-line Knowledge • PCV2 isolates that are genetically close may differ
in virulence – study and field supported?
• Immune stimulation is associated with PCVAD
• There appears to be Individual/line genetic susceptibility
• Most high mortality cases have European like isolates
• Commercial Vaccine is very effective Food Supply Veterinary Services
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Bottom-line Knowledge
• Virus is very stable and resistant to heat and disinfection (248˚F) – steam is better than dry heat
• Easily tracked across continents?
• PCV2 is in semen of recently infected boars – does not appear to be infectious
• Fecal-Oral most likely route of transmission
• Other opportunities of transmission? i.e. airborne
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Transport is a likely source of PCV2
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CONTROL Vaccination and immune stimulation:
– Role of other vaccines as cofactors? • Literature – Immune stimulation
appears necessary for PCVAD • Field experience – Yes – No - Unknown
– Oil adjuvant vaccines – ‘milky’ – Timing of all vaccinations are
important • At least 3 weeks prior to PCV2
infection/field exposure • After maternal antibodies disappear
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Control Diseases • Maximize colostrum intake/neonatal
husbandry • Vaccinate Pigs with commercial vaccine early but based on maternal antibody levels
• Use of anti-inflammatory drugs is reported to be marginally beneficial
– Salicil MixTM (Acetylsalicylic Acid) • Pulsing the group with spray dried plasma
protein is reported to be beneficial • Additional Vit. E?
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Commercial Vaccine 5 week old Trial
00.10.20.30.40.50.60.70.80.91
0 14 28 42
Time post vaccination
S/P ra
tio Vacc
Non-Vacc
Six week trial
00.10.20.30.40.50.60.70.80.91
0 14 28 42
Time post vaccination
S/P
Vacc
Non-Vacc
9
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CONTROL
• “Homemade” tissue homogenate vaccines were popular before commercial vaccine
– Due to commercial shortage – Marginally effective? – Inexpensive to make <$.25 – May not be killed – Pig hemolytic anemia – Highly controversial – adulterant – May be illegal? – Has become an Ethics? Food safety? Issue
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IgM Antibody Response PCV2 IgM
00.10.20.30.40.50.6
0 7 14 21 30
Day post Initial Vaccination
SP
Ra
tio
Vaccine A
Vaccine F
Vaccine CPostive Control
Vaccine FVaccine X
Vaccine C
Vaccine AVaccine X
Negative Control
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ISU IgG ELISA
I S U I g G E L I S A
-‐0. 2
-‐0. 1
0
0. 1
0. 2
0. 3
0. 4
0. 5
0 7 14 21 30
D a y s P o s t V a c c i n a t i o n
V ac c i ne A
V ac c i ne F
V ac c i ne C
P os i ti v e C ontr ol
V ac c i ne F
V ac c i ne X
V ac c i ne C
V ac c i ne A
V ac c i ne X
Negati v e C ontr ol
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PRRS ELISA
• All 10 pigs were negative at day 0
• All 10 pigs were negative at day 30
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Serum PCR Results
1. Positive Control – positive at day 7
2. Vaccine F • Two pigs positive by day 7
3. Vaccine C • One of two positive at day 7
Two of four vaccines were infectious
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Conclusions • Multi-factorial & PCV2b • Still many mysteries
– Risk factors and agents?
• Science is still incomplete? • Commercial Vaccine is Effective
– Availability is no longer an issue – Vaccine failures are becoming more
common? – Vaccine effectiveness is falling?