Dr. Rodger Main - PEDV's Emergence in the US: Status Report, Diagnostics, & Observations

PEDV’s Emergence in US
“Status Report, Diagnostics, & Observations”
Iowa Pork Congress
1/22/2014

Department of Veterinary Diagnostic and Production Animal Medicine,
Veterinary Diagnostic Lab, Iowa State University, Ames, IA 50011

Veterinary Diagnostic Laboratory
Iowa State University

Faculty, Staff, & Students of ISU VDL

≈22 Faculty, 100 Technical Staff, & 20 Graduate Students/Residents Veterinary Diagnostic Laboratory

Serving Food Animal Agriculture
Comprehensive Diagnostic Service, Teaching, and Discovery
(Iowa’s only Full-Service & Fully Accredited Veterinary Diagnostic Laboratory)

Processing 55,000+ cases/year from livestock producers
Applying world-class technology to real-world problems


≈ 75% Swine, 10% Bovine, 10% Poultry, + 5% Everything Else

Where the Pigs Are Located in US

≈ 500,000 pigs/week imported to IA to be grown


What is PEDV ?
“Porcine Epidemic Diarrhea Virus”
• Corona-virus
• Villous atrophy

• Malabsorptive diarrhea
• Clinically Indistinguishable from TGE
– Fecal-Oral Pathogen
– ↑ Morality rates approaching 100% in naïve neonate populations
– ↓ Mortality and severity of clinical disease in growing-finishing pigs

• Not a Zoonotic Disease or Food Safety Concern

PEDV Historical Distribution
– TGE-like outbreaks  England  1971
• Multiple European Countries
» Most often in nursery/grow finish pigs
» Reportedly of minimal significance today

– More recently a disease of significance in SE Asia
» China
» South Korea
– Severe epizootic outbreaks
– Persists as endemic disease

– Not Confirmed in North America Prior to May 2013

Cumulative Positive PEDv Cases by Farm Type
2500

# PEDv Positive Cases

2000

1500

Unknown
Grow-Finish
Sow

1000

500

0

Date by Week
Rapidly spreading across US with more than 2,271 cases in 23 states Veterinary Diagnostic Laboratory

Positive PEDv Cases per Week by Farm Type
250

# PEDv Positive Cases

200

150

Unknown
Grow-Finish
Sow

100

50

0

Date by Week

PEDV Positive Swine Cases Ascertained from Multiple VDLs
Farm Type
Week
Total # of PEDv Positive
Received Diagnostic Case Submissions
Growing
@ VDL
(Premises) via PCR or IHC Sow
Pig
? CA CO IA IL IN KS KY MD MI MN MO NC NE NY OH OK PA SC SD TN TX WI WY ?
4/15/13
4/22/13
4/29/13
5/6/13
5/13/13
5/20/13
5/27/13
6/3/13
6/10/13
6/16/13
6/23/13
6/30/13
7/7/13
7/14/13
7/21/13
7/28/13
8/4/13
8/11/13
8/18/13
8/25/13
9/1/13
9/8/13
9/15/13
9/22/13
9/29/13
10/6/13
10/13/13
10/20/13
10/27/13
11/3/13
11/10/13
11/17/13
11/24/13
12/1/13
12/8/13
12/15/13
12/22/13
12/29/13
1/5/14
Total

2 (1)
1 (1)
9 (6)
17 (13)
10 (9)
44 (43)
32 (29)
55 (52)
48 (42)
47
37
10
34
33
24
31
27
36
30
26
31
28
32
40
42
43
56
68
85
90
92
116
96
141
132
187
118
134
188
2272

0
0
1
4
5
7
6
13
11
18
8
4
12
8
6
12
18
26
14
15
10
20
12
16
14
19
24
41
40
24
20
40
24
40
31
46
29
40
37
715

1
1
5
7
3
33
22
34
24
18
20
6
20
20
10
15
10
11
14
8
18
8
15
17
21
22
25
22
44
56
64
59
38
62
73
93
56
59
85
1119

0
0
0
3
1
3
1
5
7
14
9
0
3
6
9
7
1
1
2
3
3
3
5
8
8
2
7
5
4
12
12
21
34
42
29
52
36
44 1
70
472 1

1
1
1
1
5

1
1
1
2
1
1
1
6
1
2

5
8
4
25
22
21
17
10
15
3
6
7
6
5
9
4
6
2
6

7
1
3
2
6
1
6
10
1 20
33
38
1 51
1 48
1 25
2 66
65
1 96
61
54
3 82
38 852

1
3

1

1

1
1

2
1
2
1
1
1
2
4
1
1
1
1
1
1
1
1

2
4
1

1
1
1

5

3
4
10
6
9
3
3
2
69

10
8
15
8
14
10
81

1
2

3
3
7
1
4
7
3
7
6
13
5
3
8
7
3
5
2
6
4
9
3
6
1
5
1
4
5
3
5
4
9
152

1

1
4
7
3
2
2
8
4
2
3
3
1

2
1

1
1
1
1

1

1
5

1

2
1
2
1
5
2
5
2
7
2
8
17
19
23
2 18
27
2 17
20
1 46
13 263

1
1

2

1

2
2
3
2
7
2
2
5
1
4
4
6
12
24
19
21
21
22
17
2
14
1
15
14
19
8
3
12
5
20
2
5
4
18
15
18 316

17 2
20 1
3 16
13
2
3
2 11
7
4
1 10
5
7
2 14
1 10 3
4
5
1 13
5
1
4
6
1
6
1
13 2
9
1
1 13 2
5 10 1
4
5
1
4 11 1
9 12
5
6
3
3
7
1
3
5
1
5
3
5
2
6
4
66 276 28

1

1

1

1
1
1
2
1
6

2

3
3

2
1

1
1
1

1
1
1

3

1
1
1
1

2
2

3
1
6

1
6

3
1
3
6
3
2
1
2
1
4
30

1
1

1

1
4

1

1
1
1
4
1
1
20

PEDV Diagnostics
Diagnostic Specimens
•
•
•
•
•

Intestine (Fresh & Fixed)
Feces
Fecal Swabs
Oral Fluids
Serum (PEDV Antibody)


• PEDV - PCR

Real-Time PCR

– Widely available
– Same day testing
– Highly sensitive… quickly transitioned to majority of testing being surveillance based testing

• Learning Curve on Extraction Techniques
• Sample types = Intestine, Feces, Fecal Swabs, & Oral Fluids


PEDV IFA test
(Serum = PEDV Antibody)
Development of IFA antibody over time
400

IFA antibody titer

350
300

250
200
150
100
50
0
0

5

7

14

21

28

35

Days post inoculation
(Source: Yoon, Sun)


PEDV IFA
(Serology / PEDV Antibody Based Assay)
Presently Offered As:
– PEDV IFA as a screening assay = ( + or - @ 1/40 dilution)
OR
– PEDV IFA as a 4-dilution ( - or + 40, 80, 160, 320)

Drs. Johnson, Yoon, Zhang et al

Other Antibody Test Development
• Multiple ELISA Development Efforts In-Process
– Iowa State University
– Kansas State University
– South Dakota Sate
– University of Minnesota
– … & likely others

• PEDV ELISA assays commercially available
proved to be of very poor quality

Use of PEDV IFA to Complement PEDV PCR Testing
? ‘s = Are these replacement females PEDV negative ?
?’s = What is the actual prevalence of PEDV in a region ?
•

Field reports suggest that the clinical presentation of PEDv infection in growing pigs can
be variable in its severity and not readily distinguishable from the myriad of other
causes of diarrhea in growing pigs.

•

Approach antemortem PEDv surveillance with the same rationale more commonly
used in PRRSv surveillance that incorporates the use of both antigen and antibody
based diagnostic tools.
PCR on Oral Fluids &/or Fecal Samples ( PEDV shedding and/or presence in the environment)

+++
PEDV IFA (Antibody-based assay to detect previous exposure / antibody development)
Drs. Johnson, Yoon, Main, et al


Virus Isolation (VI)

Research
Diagnostic Tool and Vaccine Development Purposes
Control cells

P2 (1 dpi)

P1 (4 dpi)

P3 (20 hpi)

(Source: Hoang, Chen, Yoon, Zhang)


Sequencing
To date ≈ Primarily Research Purposes

PEDV Sequencing (S-Gene) is Now
Available Epidemiological Purposes

USA (2013)

China (2011-2012)

Belgium (1977)
Korea (1998)
China (1989-2008)
Korea (2009)

NOTE: The analysis is based on full genome sequences via NGS technique.

(Source: Yoon, Zhang et al)


Immunohistochemistry (IHC)
1

3

2

Late PEDv infection (~36 hrs PI):
Severe villus atrophy & loss of
absorptive epithelium

Normal neonatal pig:

4

Healthy, long intestinal villi

Early PEDv infection (~8 hrs PI):

Late PEDv infection (~36 hrs PI):

Infected cells (brown stain) line the villi

Few infected cells remain (brown
stain) & absorptive cells destroyed

(Source: Schwartz, Madson, Magstad et al.)


PEDV
• Rapidly Spread Across Broad Regions
– Role of Transport Vehicles, Lairage at Collection Points, & Animal Movement
– Lowe et al..... PEDV negative trucks returning from plant positive (amplifier)
– Turner, Battrell et al…..PEDV positive sow collection stations prior to PEDV in NC

• Ability “Break-Through” Conventional Biosecurity Measures

• Area Spread – Clear & Present Danger
– Most apparent in areas of high breeding herd concentration
• Concentrated areas of sow farms in panhandle OK/TX and SE NC...... & now IA, MN, et al

Porcine Epidemic Diarrhea Virus (PEDV)
PEDV - Immediate Costs of Disease on Naïve Breeding Herds

≈ 4 weeks of weaned pigs losses + 1 more week of losses 18

– 20 weeks later

≈ 10% of affected sow units annual output…. 2.2 to 2.5+ PSY...... ≈ $150+/Sow

Severity of Disease → Very age / stage of production dependent.
• Clinical disease can be readily missed in growing pig populations
Turner, Dufrense, Ackermann, et al


PEDV
• Shedding
• Amount of PEDV being shed is extraordinary
– Ability to persist in the presence of protective maternal antibody

• Controlled studies up to 35 days (Yoon, Madson, Bower, Magstad et al)
• Commercial sow units taking at least 90 days to produce PEDV negative pigs
• OF Samples staying PEDV positive for up to 6 – 8 weeks post-exposure

• Mixed Response to TGE-Like Mgt Strategies
– ?...≈70% Success rate…. ..≈30% recurring challenges

– “Dose” in farrowing rooms seems to recurring theme
• Endemic Phase of Disease ?
– Singular largest & looming concern

•

PEDV on Fast-track to Become Endemic US

Key Lessons Being Learned on Broader State of Preparedness
Suppliers
Of Health
Products

Producer
Genetics
Facilities / Environment

Production Practicing
Animal
Veterinarian
Medicine
Veterinary
Diagnostic
Labs

Nutrition
Health

Food
Animal
Agriculture

Consumer

Management
Business / Finance

Pathology
Virology
Bacteriology
Serology
Toxicology
Pharmacology
Epidemiology

Strategic Alliances in Service, Teaching, & Research

Regulatory
Agencies


Data courtesy of NPB & Dr. Steve Meyer

Food Animal Industries → Changed Dramatically
↑ Demand Globally for High Quality Protein Based Diets

↑ Advances in Logistics

Are we keeping pace to support them? Veterinary Diagnostic Laboratory

Globalization

↑ Opportunities & Challenges of Our Time
Opportunities:
• ↑ US Animal Agriculture’s Role in High Quality Food to the World
• ↑ Global Leaders in Advancing Systems of Food Production

Challenges:
• ↑ Risks associated with Transboundary Disease Introductions
• ↑ Animal Health Management Infrastructure Needs
– Sustain Market Access & a Competitive Production Environment
--------------------------------------------------------------------------------------------------Globalization of the Food Supply Chain Provides a Tremendous Opportunity to
Advance Practice of Veterinary Diagnostic and Production Animal Medicine.

Preparedness at the VDL’s
• High-Throughput Assays
– PCR (Antigen) and Elisa (Assays) in place

• High-Throughput / Ante-mortem Sample Types
– Needs to be in a “Tube”
• Serum / Whole-Blood / Oral Fluid / Swab / Scraping

• Index Case Diagnostic Tools / Protocols
–

Vitally Important... but limited utility in response-phase in an outbreak situation

High-Throughput Validated Assays & Sample Types


Integrated Information Management Systems
Veterinarians Across U.S. Submitting Cases to their VDL Service Providers in the NAHLN
Submission

All Dx Results Submission

VDL

VDL

All Dx Results

Submission

All Dx Results

VDL

All Dx Results

Submission

VDL

Standardized Messaging / Mechanisms for Information Transfer
Seamless,
Streamlined,

Centralized Database
Tools for Interpretation
Area Regional Disease
Management Tools

Permissioned Users

Management Tools

Animal Health Officials

&

Active in

Private & Public Sectors

Management Tools

Permissioned Users

Systems of Response Required for Effective Containment
(but not eliminate the food supply and industries we are trying to protect)

• Swift, Calculated, Coordinated, and Firm
– Built Around Continuity of Business Plans & Compartmentalization
– To safely & securely enable movement and continuity within the supply chain)

(e.g., Secure Egg, Milk, Turkey, & Pork Supply Plans)

1. Simple 2. Well Defined 3. Broadly Applicable 4. Active

• Surveillance = Passive Today & Active Tomorrow

(Although Somewhat Daunting)

Needs → Very Practical
– Integrated & active information management systems
• Submissions → Labs LIMS → Centralized Databases → Area Regional Mgt Tools
– Public and Private Sector Applications

• Swine Movement (Interstate, Intrastate, & Slaughter)

–
–
–
–

Existing / Validated / High Throughput / Antemortem Diagnostics
Robust / Real-Time Surveillance (Passive Today / Active Tomorrow)
Broadly Applicable Business Continuity &/or Compartmentalization Plans
Self-Serving Reason for Active Participation Throughout the Chain


Premises ID Barcode Labels
on VDL Submissions
Working together to enhance preparedness and capabilities

Using Premises ID #’s Is the Foundation


Premises ID Barcode Labels


How to Order Premises ID Barcode Labels
1. Go to the ISU VDL website
2. Click “Premises ID Barcode Label Information”
3. Download “Premises ID Label Spreadsheet”

4. Populate fields
5. Email spreadsheet to isuvdlv@iastate.edu

Veterinarian:
Clinic Name:
Clinic Address:

Veterinarian:
Clinic Name:
Clinic Address:

Premise ID

Official Site Name/Code

Owner

Premise ID
00ABC12
00ABC13
00ABC14
00ABC15
00ABC16
00ABC17
00ABC18
00ABC19

Dr. Smith
Smith's Vet Clinic
111 Main Street, Paradise, IA 55555

Official Site Name/Code
Bob's Finisher
Bob's Nursery
Bob's Sow
Bob's Farrowing
Bill's Finisher
Bill's Nursery
Bill's Sow
Bill's Farrowing

Outcome:
ISU VDL has bar-code labels pages printed
at remote location and mails back to client


Owner
Bob
Bob
Bob
Bob
Bob
Bob
Bob
Bob

How to Use Premises ID Barcode Labels
One sheet of Premises ID barcode labels per
site will be designed, printed, and mailed to
the address indicated in the email
Place premises ID barcode label in the
designated area on the submission form
• One premises ID per submission form
• Use premises ID barcodes on VDL submissions


Take Home Message on Prem ID#’s
• Premise ID #’s = Foundation for Preparedness
– FAD / Program Disease Response
– Continuity of Business Programs
– Area Regional Disease Control
• Producer Driven = Region, Practice, Production System

• Premise ID # ≠ Data Sharing
• “Affiliates” = Define Diagnostic Data Sharing
• (Beyond Submitting Vet, Clinic, & Bill Party for Non-Reportable Diseases)

Premises ID & Affiliate Code


*Revising paper based submission forms to enhance premise / lot / flow level
information as well as currently developing an improved VDL web-submission tool
that will incorporate use of Premises ID #’s and improved test selection format, etc..

PEDV’s Emergence in US
“Status Report, Diagnostics, & Observations”
Iowa Pork Congress
1/22/2014

Thank You
Questions ?

Many acknowledgments to ISU VDL faculty, staff, &clientele Veterinary Diagnostic Laboratory

Dr. Rodger Main - PEDV's Emergence in the US: Status Report, Diagnostics, & Observations

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