Discussion on PED virus

Bob Morrison, Dane Goede, Mike Murtaugh, Albert Rovira, Kurt

Rossow, Sagar Goyal

Projects

• Recent– Lateral spread

• Current– Swine Health Monitoring Project– National incidence– Production impact– Time to stability– Other current & proposed projects

PEDv Transmission Risks• U of MN Lateral Spread Study

– Oklahoma panhandle sites– Southeast US sites

• Known samples tested – Birds/pests– Feed– Feces/Lagoons– Transportation– Air

Lateral Spread Investigative team

• U of Minnesota:– Dane Goede, Peter Davies, Andres Perez, Bob Morrison

• USDA epidemiologists:– Andrea Beam, Charles Haley, Brian McCluskey, Bruce Wagner

• NPB & AASV– Paul Sundberg & Harry Snelson

• Participants:– OK cluster– Southeast

• Whole state• Case / control

Objective

• To determine if “my” farm is at increased risk of PED virus infection if my neighbor’s farm is infected.

OK cluster• Data collected from all sites

– Farm ID– Company– Location (geocoordinates)– Capacity– Cause of infection (lateral vs pig movement)

• Spatial Analysis on entire cohort performed– 90 positive sites out of 222 total

PEDv Risks - Airborne

• Infectious PEDv collected from in-barn air

• 11/64 air samples outside barns (60 ft-10 mi)– None were infectious– Since then, we have isolated infectious virus in air;

Alonso et al 2014.

• Oklahoma panhandle direction of spread similar to prevailing winds

NC - farm characteristics and spatial features as risk factors for PEDv infection

• 2,071 sites were followed from 7/1/2013 – 1/27/2014 for PEDv occurrence.

• Available data:– Company, production type, total capacity,

geographic coordinates and PEDv status

• 327 / 2,071 (15.8%) farms became infected with PEDv by unknown mechanisms (lateral)

• 286 / 2,071 (13.8%) became infected by vertical movement.

• Of the 327 laterally infected (cases) sites:– Median capacity 3,600 head– Median distance to nearest +’ve 1.4 miles

PEDv status Production type Negative Positive-

VerticalPositive- Lateral

Total

Sows only 139 2 78 219Sows and growing pigs 71 5 42 118Boar stud 18 0 1 19Growing pigs only 1,230 279 206 1,715Total 1,458 286 327 2,071

Conclusions• Density

– Risk of infection increases with density.– Distance to neighbor is diluted at high density.

• Rendering service– OR 1.19 / visit or 7.1x in last 2 weeks

• Birds, rodents & feral animals– OR 6-10 x in last 2 weeks

• Not significant– Recent manure application

SPECIFIC RISK FACTORS

Infectious Dose of PEDvVirus dilution Initial Ct value of the

virus dilutionExtent of diarrhea Ct value from

inoculated piglets

10-6 33.65 + 15.52

10-7 37.83 ++ 15.52

10-8 - + 16.03

10-9 - - 30.29

10-10 - - -

10-11 - - -

10-12 - - -

• Undiluted PEDv - 16.39 Ct.• PEDv is highly infectious.• Probably age dependent.• May be strain dependent.

PEDv risks - Birds

• Southeast US risk factor analysis (OR 6-10)• Samples (24 results volunteered)

– Buzzards & geese

PEDv risks - Feed

• Survival at room temp: 1-2 weeks (Goyal et al 2013)

• Field samples:– Bio-assay of PCR positive feed

• 4/4 were not infectious (Negative bio-assay)

• Herd infection from contaminated feed was reported and reproduced experimentally (Dee et al 2014; also plasma reported in Canada)

PEDv risks - Feces• Lagoon slurry PEDv survival

– Cold (-20C, 4C) – over 1 month– Room Temp – 14-28 days– 1/4 lagoons still infectious >5 weeks after

shedding stopped

• Fresh feces PEDv survival (Thomas, 2014)– Room temp – 1-7 days– Hot (71C or 165F) – <10 min

PEDv risks - Transportation• Southeast US risk factor analysis

– Renderer visits to sites (OR 7.1)

• Harvest plant transportation study (Lowe et al, 2013)– Each contaminated truck @ entry 0.96 new

trucks being contaminated

PEDv risks – Farms• Southeast US risk factor analysis

– High capacity herds (> 2,000 head) had 2.5x higher odds

– Sites w/ sows had 8.8x higher odds than sites w/ growing pigs only

– Sites w/ sows & growing pigs had 5.8x higher odds than sites with growing pigs only

PEDv risks – Region/Neighbors

• Southeast US risk factor analysis– Increased regional density (>5 sites/25 mi2)

– Distance to nearest neighbor• 10-19% increased odds of being positive each mile

closer• Not as important in high density area (>11 sites/25 mi2)

Swine Health Monitoring Report (SHMP@UMN.Edu)

Swine Health Monitoring Project (SHMP@UMN.Edu)

• Participants - 17 share logo

• 171 receive weekly report

• Proposed direction

PRRS PED

Participants 14 19

Farms 372 739

Sows 1.2 m 2.1 m

Present Day

National Incidence

National Incidence – NAHLN data

July 9, 2013

Dec 6, ‘13

National Incidence

Dec 13, ‘13

National Incidence - regions

January 24, ‘14

National Incidence – PED year

June 27, ‘14

EWMA – statistical analysis of incidence

372 herds with 1.2 m sows

EWMA math

• The smoothed trend line– Lambda = 0.28 for this week and (1-0.28) for last week.

• Control limits– 2.2 * SD of cases / week for June - August– The choice of this number is rather empirical, trying to

minimize false alarms, but not delay signal of a new epidemic.

– CDC uses 1.645 for human influenza epidemic confidence interval

EWMA – smoothed presentation of trend

Jan 3, ‘14

EWMA – Re-defined denominator

June 6. ‘14

May 30, ‘14

EWMA – year end

National Incidence – 2014/15;EWMA has re-set control limit

National Incidence

• Incidence & status changes– 1 – Positive– 2v – Stable, on going exposure– 2 – Stable– 3 – Provisionally Negative– 4 - Negative

Prevalence in 739 herds

Production impact

Time to baseline production (TTBP):EWMA chart, back to “in control” level

TTBP(24 weeks)

Montgomery DC. Introduction to statistical quality control. 2012. 7th ed. John Wiley & Sons, Inc.

Quantifying the production losses:AUC to sum “pigs not weaned”

TTBP(24 weeks)

3,754.8 pigsBelow expected 15,229 pigs

Below expected

“Δ pigs A”“Δ pigs B”

TTBP

Production Impact: Aggregate

Rapid Response

Prototype vs. INDEL PEDv

Prototype PEDv (124 herds)

Avg TTBP (3 SD) = 72% @ 12.6 wks Net loss 2.6 pigs/sowAvg TTBP (100%) = 38% @ 15.4 wks Net loss 4.7 pigs/sow

INDEL Variant PEDv (3 herds)

Avg TTBP (3 SD) = 100% @ 4.3 wks Net loss 0.4 pigs/sowAvg TTBP (100%) = 100% @ 6 wks Net loss 0.9 pigs/sow

4 more Indel herds24 31 7 14 21 28 5 12 19 26 2 9 16 23 30 6 13 20 27 4 11 18 25 1 8 15 22 29 6 13 20 27 3 10 17 24 31 7 14 21 28 7 14 21 28 4 11 18 25 2 9 16 23 30 6 13 20 27 4 11 18 25 1 8 15 22 29 5 12 19 26 3 10 17 24 31 7 14 21 28 5 12 19 26

5 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10 11 122013 2014

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11/29/2013 1/31/2014 63

11/29/2013 1/31/2014 63

11/22/2013 1/17/2014 56

11/15/2013 1/17/2014 63

Reproductive, endemic infection, re-infection, virulence??

PWM?

Repro?

Time to Stability

• 26 sites so far enrolled

Time to StabilityWeeks Post-Exposure

Wee

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Site 1Site 2Site 3Site 4 Site 5Site 6Site 7Site 8Site 9Site 10Site 11Site 12Site 13Site 14Site 15Site 16Site 17Site 18Site 19Site 20Site 21Site 22

Tested: Positive Tested: Neg (too few litters) Tested: Negative Stable

12 / 26 sites (4 not shown) reached stability so far

Average TTS in those 12 sites is 16.7 weeks(13.8-19.5 )

Risk factors for prolonged TTS

Other current & proposed projects• Sow challenge

– Does previous infection with Indel strain confer protection to challenge with prototype strain?

– Collaborative effort with Goede, Dvorak, Murtaugh, Nerem, Yeske, Rossow, Morrison.

• Impact of PEDv in growing pigs• Duration of immunity in gilts?• Effectiveness of vaccination?• Evaluation of immunity within endemic herds?

Acknowledgements• Study participants• USDA APHIS CEAH – Lateral spread data analysis• SHMP

– Companies sharing logos & other participants– NPPC, AASV, USDA, NPB

• U of MN Veterinary Diagnostic Laboratory• Funding

– National Pork Board & UMN SDEC

Emerging Infectious Diseases

• Volume 20, Number 10—October 2014• Research• Distinct Characteristics and Complex Evolution of PEDV Strains,

North America, May 2013–February 2014• Anastasia N. Vlasova1, Douglas Marthaler1 , Qiuhong Wang,

Marie R. Culhane, Kurt D. Rossow, Albert Rovira, James Collins, and Linda J. Saif

• Author affiliations: The Ohio State University, Wooster, Ohio, USA (A.N. Vlasova, Q. Wang, L.J. Saif); University of Minnesota Veterinary Diagnostic Laboratory, St. Paul, Minnesota, USA (D. Marthaler, M.R. Culhane, K.D. Rossow, A. Rovira, J. Collins)

Figure 1. Phylogenetic tree based on complete genome sequences of 112 North American porcine epidemic diarrhea virus strains. Blue font represents US non–S INDEL strains; red font represents US S INDEL strains;

brown font represents Mexican strains; purple font represents worldwide non–S INDEL strains; and pink font represents global S INDEL strains. Bootstrap values are represented at key nodes. Scale bar indicates nucleotide substitutions per site. CH, China; IA, Iowa; S INDEL, insertions and deletions in the spike gene; IN, Indiana; ISU,

Iowa State University; MEX, Mexico; MN, Minnesota; USA, United States of America.