Lecture 24 & 25: Infectious Diseases & Disorders of Equine Nervous System

What is the most frequent protozoal disease affecting the equine nervous system?

sarcocystis neurona

What are the 3 hosts of sarcocystis neurona?

definitive host = source of transmission (possums)

intermediate hosts = cats, raccoons, armadillos, skunks

aberrant hosts = horses

What is the speculated neospora hughesi life cycle?

What is the pathogenesis of EPM?

• Inflammation, neuronal necrosis

• Lack of clearance from CNS

MACROSCOPIC

• Multifocal areas of hemorrhage

• Foci of malacia & areas of discoloration

• Spinal cord and brain stem

• Gray & white matter

MICROSCOPIC

• Confirm parasite and/or typical lesions

• Diffuse nonsuppurative inflammation &

necrosis

• Perivascular infiltration - mononuclear cells

What are the clinical signs of EPM?

• any neurologic sign - acute or chronic, focal or multifocal

• brain, brainstem, spinal cord - white/grey matter

• AAA = ataxia, asymmetry, atrophy

• behavioral changes

• cranial nerves

• weakness, ataxia, atrophy → recumbency

What are the two etiologic agents of equine protozoal myelocephalitis?

Sarcocystis neurona

Neospora hughesi

How is EPM diagnosed?

ANTEMORTEM – not definitive

1. Consistent Clinical signs

2. Positive serum/CSF ratio (intrathecal Ab)

3. Rule out other diseases

POSTMORTEM – definitive

But…harder in chronic cases

What are the 3 FDA approved EPM treatments?

1. Sulfadiazine/Pyrimethamine (ReBalance)

2. Ponazuril

3. Diclazuril

What are the potential adverse reactions to sulfadizaine (ReBalance)?

anorexia, intestinal issue, bone marrow suppression

What are the unofficial, off-label, and illegal drugs used to treat EPM?

• Sulfadiazine/pyrimethamine - compounded: illegal

• Diclazuril sodium salt or IV formulation: illegal

• Toltrazuril: (Baycox ®, Bayer): not approved in US, Compounded Toltrazuril ± pyrimethamine: illegal

• Decoquinate with Levamisole: (Orogin ®, Pathogenes) – NOT FDA approved, Not allowed in performance horses

What supportive treatments are used in an EPM treatment plan?

• anti-inflammatories: NSAIDs, steroids if danger of recumbency

• anti-oxidants: DMSO, vitamin E

• supportive care: nutrition, preventative care

What is the prognosis of EPM?

• 60% improve (1 grade or negative test)

• 10% relapse in 1-3 years

How is EPM prevented?

• No vaccine available

• Avoid stress

• Reduce exposure to opossum feces: Feed off ground, Separate fresh water source

• No wildlife access to pastures or stalls

• Intermittent anti-protozoals?

What are the different equine herpes viruses?

What is the emerging, worldwide neurologic disease affecting 80-100% of horses?

EHV-1 (dsDNA): 3 genotypes

• D752: “neuropathogenic”

• N752: “non-neuropathogenic”

• H752: “new”

• All can cause neuro disease

What are the risk factors of EHV?

• Shedding horse(s) close to susceptible horses

• Stress

• Season

• Crowding, mingling – shared air space

• Adult horses of tall breeds

How is EHV transmitted?

• Incubation 4-7 days

• Direct contact: Respiratory (often before clinical signs), Aborted materials

• Indirect: Tack, equipment, People

What is the pathogenesis of EHV?

Phase 1: respiratory epithelium, local lymph nodes, PBMC

Phase 2: PBMC associated viremia

Phase 3: endothelial cells, vasculitis, hemorrhage, thrombosis, ischemia

Neurologic disease, abortion

What are the clinical signs of EHV?

• biphasic fever: most consistent initial sign

• acute (ascending) ataxia & paresis: posterior ataxia, anterior ataxia, recumbency

• cauda equina signs: urinary & fecal incontinence, loss of anal tone, loss of sensation perineum

• stabilizes in 24-48 hours

How is EHV diagnosed?

• Reportable & actionable (e.g. TN, VA, KY)

• Samples to collect: Nasal swab (viral transport medium), EDTA blood

• PCR: gB-based test = recommended, D752 vs N752 marker (may miss new strain)

• CSF: xanthochromia (high protein & normal cells)

• Seroconversion

• Virus isolation

How is EHV treated?

Isolation & quarantine - No specific treatment

NSAIDs, steroids, antioxidants, antimicrobials (secondary infection), virustatic drugs (expensive), CRI detomidine in severe cases

Nursing care:

• Keep standing, sternal with props, repositioning

• Comfortable support

• Easy access to food and water

• Protection from trauma

• Hydration

• Evacuation of bladder and rectum if necessary

• !!! Attention neurologic horse = DANGER !!!

What is the prognosis of EHV?

• If stays standing: good

• If recumbent > 24 h: reserved

What are the outbreak management steps of EHV?

1. Quarantine of premise

2. Biosecurity (individual PPE &equipment, barriers)

3. Confirm diagnosis: 1. PCR - febrile and EHM horses 2. Complete postmortem 3. Freeze serum

4. Monitor rectal temperature 2x/day on all horses

5. Release premise (28 d or 21 d)

How is EHV prevented?

• Biosecurity & good monitoring

• Management

• EHV-1 vaccines do not protect against EHM

What 4 viruses are covered by the 5 AAEP core vaccines?

1. Rabies

2. West Nile

3. Eastern Equine Encephalomyelitis

4. Western Equine Encephalomyelitis

What are the equine mosquito-borne infections and where are they found?

What are the risk factors of the equine mosquito born diseases?

Horse:

• Any breed or sex

• Age (usually not in foals)

• Vaccination history (unvaccinated)

Environment:

• Region

• Season, weather, landscape

• NE: vector season, SE: year round

Young horse recently moved to endemic area and with incomplete vaccination

What are the amplifying hosts of equine mosquito borne diseases?

birds

What are the clinical signs of EEE?

How are equine mosquito born diseases (EEE) diagnosed?

• History & clinical signs

• Rule out: CBC, serum biochemistry, blood ammonia, Radiographs (rule out CVM), CSF tap, Nasal swab & EDTA blood (rule out EHM)

• Serology: IgM-capture ELISA

• CSF: cytology, PCR and virus isolation

• PCR

• Post-mortem exam

How are equine mosquito born diseases (EEE) prevented?

What is the EEE vaccination plan for adult unvaccinated and vaccinated horses?

vaccinated: annual before season, adapt to region

unvaccinated: 1. first dose 2. 4-6 weeks later 3. annual

What is the EEE vaccination plan for adult unvaccinated and vaccinated broodmares?

vaccinated: 1. annual 2. 4-6 weeks pre-partum

unvaccinated: 1. first dose 2. 4-6 weeks later 3. 4-6 weeks pre-partum 4. annual

What is the EEE vaccination plan for foals of unvaccinated and vaccinated mares?

foals of vaccinated mares: 1. first dose 4-6 months 2. 4-6 weeks later 3. annual

foals of unvaccinated mares: 1. first dose 4-6 months 2. 4-6 weeks later 3. annual

What are the 3 contagious neurological diseases of horses?

1. Rabies

2. Borna

3. Hendra and Nipah

What are the reservoir hosts of rabies (lyssa virus)?

• Racoon

• Skunk

• Fox, Coyote

• Bat

What are the risk factors of rabies?

• No sex or breed predilection

• Younger horses more curious

• Vaccination history

• 100% pasture

• Endemic area

How does rabies spread through the body?

bite infection (contact: mucous membranes, skin lesions) → retrograde/centripetal axonal transport → replication in spinal cord → brain → anterograde/centrifugal axonal transport → salivary gland

What are the clinical signs of rabies?

• Can look like any neuro disease or colic

• Long incubation time

• Rapidly progressive or diffuse neurologic signs

• 3 Forms

• Bite wound often NOT seen

• Non-specific: colic, lameness, fever, depression

What are the clinical signs of rabies based on CNS location?

How is equine rabies diagnosed?

NO ANTEMORTEM CONFIRMATION

• History and clinical signs

• CBC, biochemistry: normal

• CSF

POSTMORTEM

• ½ brain in 10% formaldehyde for histology

• ½ brain frozen for direct IFAT, etc

• Mild non suppurative encephalomyelitis

• Negri bodies

How is rabies prevented?

• Vaccination = core vaccine

• Contact tracing, zoonosis!!!

• Exposed horse

  • Vaccinated (by licensed DVM with USDA approved vaccine) → Immediate revaccination, Observation as directed by state public health official

  • Unvaccinated → Contact public health state official

How often should horses be vaccinate for rabies?

Describe the etiologic agent of botulism.

• Gram +, anaerobic

• Spore-forming

• Ubiquitous

• 8 neurotoxins: A, B, Ca, Cb, D, E, F, G

• Rapidly progressive neurologic disease

• High mortality

What are the 3 forms of equine botulism?

Forage poisoning

• Toxin pre-formed

• Origin: food or water with decaying vegetable matter, carcass

Wound contamination

• Origin: contaminated wound

• Spores germinate

• Toxin produced

Toxiinfectious (Shaker foal)

• Origin: food with spores or bacteria

• Spores germinate in necrotic hypoxic condition (eg ulcers)

• Toxin produced

What is the MOA of botulism?

1. Binding and internalization

2. Translocation

3. Inhibition neurotransmitter release

Pre-synaptical action at peripheral cholinergic neuromuscular junction

Inhibition of neurotransmitter (Ach)

Neuroparalysis

What are the clinical signs of botulism?

• Generalized (symmetric) weakness with normal mentation

• Decreased tail, anal, eyelid, tongue tone

• Trembling worsened with exertion

• Recumbency

• Dysphagia (eating slow, unable to swallow, drooling)

• Mydriasis, sluggish pupillary light reflex

• Hypoventilation, respiratory arrest

• Colic, decreased GI motility

• Sudden death

How is botulism diagnosed?

• tongue stress test and grain test

• History and clinical signs

• CBC, biochemistry, monitor blood gas

• Identify toxin: Feces, Stomach or intestinal content, Dead animal, feed or water, soil, Mouse toxin assay

How is botulism treated?

• Neutralize circulating toxin - antitoxin

• supportive care

  • no stress, stall confinement

  • nutrition: remove food, tube feeding, fluids

  • positioning (sling), respiratory support

  • pain medication, sedation

  • antimicrobials: avoid aminoglycosides, PPG, tetracyclines; use ceftiofur or TMS

What is the prognosis of equine botulism?

Foals: depends

• Antitoxin & standing: good

• Respiratory distress: poor

Adults

• 3-5 days of weakness but standing: fair-good

• Recumbent or peracute signs: poor

How is botulism prevented?

• Feed and water management

• Vaccination in endemic areas (risk-based) – type B

What are the equine tetanus risk factors?

• Unvaccinated horse

• Wound: deep contaminated puncture wound (lower leg)

• Soft tissue: surgical, post-partum, injection site…

What is the MOA of tetanus?

1. Germination of spores

2. Exotoxin formation, spread

3. Retrograde transport by alpha-motoneuron

4. CNS: binds irreversibly to presynaptic inhibitory interneurons

What are the clinical signs of tetanus?

• Colic, vague stiffness

• Trembling, spasm, paralysis

• Protruding 3rd eyelid (upon stimulation), grimace

• Eyelid retraction, flared nostrils…locked jaw

• Sawhorse stance, stiff spastic gait, erect tail

• Rigid recumbency

• Stimuli may cause panic

How is tetanus diagnosed?

• History & clinical signs

• No diagnostic tests

• Anaerobic culture MAY be attempted

• DD: Severe neck pain, Hypocalcemia, Myopathy, EMND, Stiff horse syndrome, Shiver, Encephalitis

How is tetanus treated?

1. Environment

• Quiet, good footing, deep bedding

• Dark stall, cotton in ears

2. Muscle relaxation/tranquilization

• Acepromazine or Phenobarbital

• Diazepam and Methocarbamol

3. Remove source of infection

• Debride

• Local PPG, systemic K-Pen

4. Neutralize unbound toxin

• Antitoxin IV or IM

• Intrathecal

5. Maintain hydration & nutrition

6. Vaccinate

What is the prognosis of tetanus?

• Fair to poor (grave if recumbent)

• Depends on severity of clinical signs and horse