View the presentation slides - Veterinary Teaching Hospital

Demystifying EHV-1
Epidemic Neurological Disease Outbreak in 2011:
How Do We Prevent It in the Future?
Hosted by
College of Veterinary Medicine and Biomedical Sciences

Tonight’s Panelists
• Dr. Paul Lunn, BVSc, MS, PhD, MRCVS, Dip. ACVIM
Professor and Department Head, Clinical Sciences
Past President, American Association of Veterinary Clinicians
Chairman, Research Advisory Committee, Grayson-Jockey Club Research Foundation
• Dr. Lutz Goehring, DVM, PhD, Dip. ACVIM
Assistant Professor, Equine Internal Medicine, Clinical Sciences
Clinician, Veterinary Teaching Hospital
• Dr. Jerry Black, DVM, '67, '71
Director of Undergraduate Programs, Equine Sciences
Board Member, National Cutting Horse Association
Trustee, American Horse Council Board

NCHA Western National Championship
April 29 to May 8, 2011

April 29‐May 8: Ogden, Utah
National Cutting Horse Association
Western National Championships:
>700 Horses
Map outline from www.eflatfeerealty.com
Courtesy Dr. Paul Morley

Significant EHV-1 Outbreak Facts
• 708 entries in Western National Championships
– Significant number of ancillary horses
• Most horses left Ogden event on or before May 8,
2011
• Colorado horse that participated at Ogden event
displayed significant signs of EHM and was
euthanized on May 11, 2011

Following This Event:
Horses Dispersed to at Least 21
States and Provinces
Map outline from www.eflatfeerealty.com
Courtesy Dr. Paul Morley

Following This Event:
Horses Dispersed to at Least 21
States and Provinces
Map outline from www.eflatfeerealty.com
Courtesy Dr. Paul Morley

Significant EHV-1 Outbreak Facts
• Horse that had competed in Ogden was euthanized at a cutting
event in central California after showing neurological signs
EHV-1 on May 13, 2011
– Show was immediately cancelled
– Several hundred horses potentially exposed
• Pacific Coast Cutting Horse Assn. cancelled major show the
following week
– May 19-22

Significant EHV-1 Outbreak Facts
• Breeder Invitational Cutting Event cancelled May 14
– Mercuria World Series of Cutting cancelled after Open goaround
(rescheduled)
• Industry request for USDA-APHIS assistance May 16
• All NCHA approved shows cancelled May 14- June 6, 2011
– Bio-security measures strongly recommended as shows
reopened

5/26/2011 ‐ Status of Horses that
Attended the Ogden Competition
‐‐ and in‐contact horses
Sources: USDA/APHIS and
other official statements
States with Confirmed or Suspected EHV‐1
Infections Among Horses with 1 o ,2 o ,or3 o
Exposures from the Ogden Competition
States Where No Confirmed or Suspected EHV‐1
Infections have been Reported Among Horses with
1 o ,2 o ,or3 o Exposures from the Ogden Competition
Map outline from www.eflatfeerealty.com
Courtesy Dr. Paul Morley

• Epidemic with Unprecedented Spread in the U.S.
• Majority of neurological disease associated with primary
exposure at Ogden
– However, secondary and tertiary cases are reported
– No new premises affected in the last week
– A total of 242 premises exposed to date, 62 of them with EHV-1/EHM cases

Lutz S. Goehring
EHM
Equine Herpesmyelopathy
• The neurological form of EHV-1
– History
– How does disease develop?
– How to treat horses during an
outbreak…
– Circumstances that allow disease to
develop…

Time line:
• (1872: Paris, France)
• (1934: ? Germany)
• 1966: Oslo, Norway
• 197x: Lexington, KY
• 197x: Lexington, KY
• 1981: National Stud, Newmarket (UK)
• 1983: Lipizzaner Stud, Piber (AT)
• 1985: Ontario (Canada)
• 1993: Neumarkt (Germany)
• 1997: Doorn (Netherlands)
• 2001: Sydney (Australia)
• 2003: Hasselt (Belgium)
• 2003: Findlay (OH)
• 2007: West Palm Beach (FL)
EHM
Equine Herpesmyelopathy
• 2004: Stuttgart (Germany)
• 2008: San Francisco (CA)
• 2009: Milan (Italy)
• 2010: Madrid (Spain)
• 2011: Algarve (Portugal)
• 2011: Ogden (UT)
�Europe
�North America
�Australia
�(South) Africa
�Japan

A time line following infection
temp in °C
42
41
40
39
38
37
36
35
34
viremia
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14
nasal shedding
Days following intranasal infection

Disease Development EHM
EHV-1 viremia:
Intracellular
viremia in
leukocytes
reaches the vasculature of the SPINAL CORD
endothelial cells
glial cells

Virus replication in
endothelial cells and cellto-cell
spread
EHM
Equine Herpesmyelopathy

EHM
Equine Herpesmyelopathy
Inflammation of (small vessels) – activation of
coagulation: Thrombi or ‘clots’

Thrombosis of vessels causes acute bleeding, lack of
oxygen and nutrients: neuron cell damage and loss of
function
blood vessel
Edington and Bridges 1986 – Equine Stroke
EHM
Equine Herpesmyelopathy
white matter
spinal cord
gray matter

macroscopic and microscopic
pathology of the spinal cord (courtesy Dr. EJ Ehrhart, CSU)

Clinical Signs:
commonly:
o incoordination and stiffness
(spasticity)
o weakness
often: hind limbs more
affected than fore
o complete recumbency
o dysuria – spastic bladder
rarely:
o cranial nerve involvement

A time line following infection
temp in °C
42
41
40
39
38
37
36
35
34
nasal shedding
viremia
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14
Days following intranasal infection

Treatment:
EHM
Equine Herpesmyelopathy
The neurologic horse
• supportive care
– isolation, stall-rest, support sling, bladder
catheterization, antibiotics, fluid support
• anti-inflammatory
– NSAIDs: Equioxx> Banamine> Bute
– corticosteroids: dexamethasone
– (DMSO: osmotic, anti-inflammatory?)
• anti-viral?
– ganciclovir may have advantage over val-aciclovir
• restorative: Vitamin E, Vitamin B

Treatment:
The febrile horse
EHM
Equine Herpesmyelopathy
• supportive care & observation:
– isolation! stall-rest, TLC
– pay attention to ‘regular urination and defecation’
• anti-inflammatory
– NSAIDs: Equioxx> Banamine! Aspirin?
– don’t do corticosteroids!
• anti-viral: yes!
– val-aciclovir
– ganciclovir
• restorative: Vitamin E, Vitamin B

Treatment:
The non-febrile, non-
neurologic horse
• supportive care & observation:
– isolation! stall-rest, TLC
– taking rectal temperatures twice daily. Cut-off: 100.8°F
– pay attention to ‘regular urination and defecation’
• anti-viral therapy: ?
• restorative: Vitamin E, Vitamin B
EHM
Equine Herpesmyelopathy

Farm Outbreak EHM
INDEX CASE:
Hasselt, Belgium 2003
Ogden, Utah 2011

The index case – and then what?
EHM
Equine Herpesmyelopathy
© Cowgirls at Round-up in Pendleton, Oregon 1911

Affected Horses
on a Farm
EHM
Equine Herpesmyelopathy

EHM Epidemiology
• Winter & Spring
• ‘Tall Breeds’
• Severe disease in
older or in female
animals
• July - September
•

Affected Horses on a Farm
EHM
50 – 25 – 18 50 – 25 – 4? 50 – 25 – 1?

Is This A “Mutant” Virus?
• Common question – Complicated issue
• Short Answer:
– No, this is not a new mutation in EHV-1
• Longer Answer:
– ~7 years ago researchers found a one molecule DNA difference between most EHV-1
viruses isolated from abortion cases and neurological cases
• The strains are labeled N752 and D752, or:
– Abortion vs. Neurologic strains
– Non-Neuropathogenic vs. Neuropathogenic

Allen, Kydd, Slater,
& Smith, 2005

EHV-1 D/N752: key questions
Is there a particular EHV‐1 strain that causes
neurological disease?
Are all outbreaks of neurological disease
caused by D752 viruses?
No
No
Are N752 viruses nonpathogenic? No
What proportion of horses carry D752
Viruses?
Not known,
probably 5‐20%
Is D/N752 testing useful? Limited…

Neuropathogenic EHV-1
• In outbreaks you isolate only one strain – True
• The N752 strain is the original wild-type EHV-1 virus
– Wrong - D752 strains are old, & is present in EHV-4
• EHV-1 can spontaneously mutate from N752 to D752 – Wrong - Never happened, never will
• The prevalence of these strains is changing
– More to learn, but this seems true
– Plus, there are more mutations to discover…

EHV-1 Vaccination

Allen, Kydd, Slater,
& Smith, 2005

Multifactorial
Immunity to EHV-1
• Nasal mucosal antibody
• Serum antibody
• Cytotoxic T lymphocytes (CTLs)

EHV – AAEP guidelines
• Pregnant mares: killed vaccine at 5, 7, and 9 mths
• General: 2 (3) dose primary
– one month, and then 3-6 month intervals
• Boost at 6-12 month intervals
– shorter intervals under 2 years of age, benefits uncertain
– timed EHV-1/4 at 4-6 weeks prior to foaling
• Start 3 dose series at 6 months

EHV-1 Vaccines
• Respiratory licensed killed products
– Pfizer Innovator
– Intervet-SP Prestige
– Boehringer Calvenza
• Boehringer modified live Rhinomune
• Intervet-SP abortion vaccine
– Prodigy
• Pfizer abortion vaccine
– Pneumabort-K

Research comparisons
• Serology: “abortion” out-perform “respiratory” products
– Should we use “abortion” vaccines more widely?
• Challenge trials
– Studies show that high antigen load (“abortion”), modified live
(Rhinomune), and enhanced adjuvant (Calvenza) vaccines:
• Reduce amount and duration of nasal shedding
• Can sometimes reduce viremia
• Do not prevent infection, even when recently boostered

EHV-1 vaccination take home message
• Best killed and live vaccines somewhat effective
against nasal shedding and possibly viremia
• NO VACCINE has a claim for EHM protection
• Best performance seen when recently boostered
• Do you vaccinate in the face of EHM exposure?
– It may decrease spread and shed of EHV-1
– This may limit movement or entry of disease in a barn
– Needs to be done early
– Beware of mixing horses during handling to vaccinate

Biosecurity

• Subdivide the population
– biosecurity
Key strategies
• Prevent introduction & reactivation (EHV-1)
– quarantine
– minimize stress
• Maximize immunity
– vaccination

Biosecurity Key Principles
• Prevent Exposure to Unexposed horses
– Horse-to-Horse contact
– People (hands, clothing, etc)
– Contaminated materials (tack, equipment, facilities)
• Control Contamination from Shedding Horses
– Early identification
– Isolation
– Decontamination (cleaning and disinfection)
• Communication and Education
Courtesy Dr. Paul Morley

High risk horses & situations
• Horses moving on and off premises
• Horses returning from shows/sales/events
• Isolate and check temperature
• Febrile horses
• CASES OF EHM!!

How long to quarantine?
• We recover virus for 10-16 days post-infections
– 14, 21 or 28 day quarantine?
• Can you “test out” with real-time PCR
– UC-Davis, Lucy Whittier lab – $57
– U. Kentucky diagnostic lab – $55 - $85
– IDEXX - $55 (2-11: $36; >12: $27)
• What is your level of “risk aversion”?

Concluding points
• current vaccinations are important to prevent
spread of EHV-1 among horses – future
vaccines will focus on diminishing viremia
• biosecurity measures are equally important to
vaccination in preventing the creation of an
Index Case

Future Vision for CSU
to Support the Equine Industry
• CSU is a leader in EHV-1 and EHM research
– Vaccine studies
– Development of IN VITRO models to study:
• how disease is caused
• how (existing & new) drugs can be used in EHM
prevention

Future Vision for CSU
to Support the Equine Industry
• Develop CSU into the top institute in the region for
equine neurological disease research to address:
• Diagnosis
• Treatment
• Prognosis
• Prevention

Thanks to the generosity of our
equine community
We have recently established the
Equine Neurologic Diseases Fund

The E.N.D. Fund will support:
• Clinically applied research to address EHV-1 and other
neurologic diseases.
• Purchase of the most advanced diagnostic/ treatment
modalities and fund associated staff training.
• Facility renovation/expansion associated with caring for
neurologic cases, especially those of an infectious nature.

Questions……

Additional Questions?
• Please contact us at (970) 297-5000
• Lutz.Goehring@Colostate.edu