r.b. baker, dvm, ms senior clinician

1

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



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



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

Veterinary Diagnostic and Production Animal Medicine Iowa State University

4

PCVAD



PCVAD



PCV2 Associated Spiking Finisher Mortality

PCVAD

2



PCV2 Associated Spiking Finisher Mortality PCVAD




PCVAD



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



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



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



PCV2 à PCVAD Clinical presentation

• Wasting pigs • Fever

• Anemic pigs • Jaundice

• Respiratory symptoms • Ulcers

• Lymphadenopathy • Some PDNS

• HIGH (doubling) of MORTALITY

3








Current Observations



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






4






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



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?



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



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


24


PCVAD

5




PCVAD



Diarrhea similar to Ileitis


Iowa State University



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



Porcine Dermatitis and Nephropathy Syndrome (PDNS):

A Significant Finding in Early Outbreaks Food Supply Veterinary Services




PDNS Field Case Courtesy of Dr. Mike Yaeger ISU VDL

6





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



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



Dendogram based on entire PCV2 sequencing and comparison of PCV2 sequences available from the GenBank.

PCV2b

RFLP 321 “new”

PCV2a

RFLP 422, 321 “old”



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



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



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



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



PCVAD Finisher Mortality Case



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



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


Iowa State University



Submission for a PCVAD Investigation

Liver

Lung

Kidney

Spleen

Ileum

Colon

Heart

ADD lymph nodes and tonsil

8



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


44

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



Transport is a likely source of PCV2



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



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?



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



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



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



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



PRRS ELISA

• All 10 pigs were negative at day 0

• All 10 pigs were negative at day 30



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



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?

r.b. baker, dvm, ms senior clinician

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