7 Viral Encephalitic Diseases

Viral Encephalitic Diseases

• This includes Eastern, Western, and Venezuelan Equine Encephalomyelitis, West Nile Virus, and Rabies.
• It is important to understand the AAEP core vaccine recommendations for these diseases.
• Develop treatment plans.
• Identify risks to human health regarding handling CSF and performing necropsies.

Togaviridae Family

• This family includes the Genus Alphavirus which are unsegmented, single-stranded, positive-sense, RNA viruses.
• Alphavirus includes Eastern Equine Encephalomyelitis (EEE), Western Equine Encephalomyelitis (WEE), and Venezuelan Equine Encephalomyelitis (VEE).
• Genus Flaviviridae includes West Nile Virus (WNV).

Disease Distribution

• WEE hasn't had a reported case in the US since 2005.
• EEE occurs in coastal areas of the Atlantic, SE US (FL), MI, and TX
• VEE is found in South and Central America

EEE and WEE Transmission

• The diseases are maintained by cycling between birds and mosquitos.
• Snakes may also be overwintering hosts for EEE.
• Birds are amplifying hosts.
• Horses are "dead-end" hosts.

VEE Transmission

• VEE is maintained by cycling between mosquitos and small rodents.
• Horses are amplifying hosts.

Epizootic Occurrence (EEE and WEE)

• It lasts for 1-3 months.
• Most common in the summer and fall.
• Warmth and humidity favor mosquito populations.

Clinical Signs

• Disease forms:
  • Inapparent infection with low-grade viremia and fever.
  • Generalized febrile illness with anorexia, depression, tachycardia, and diarrhea.
  • Clinical encephalomyelitis (classic form).
• Young horses most susceptible
• EEE is the most severe and rapidly progressive

Neurologic Signs

• Neuroanatomic localization: initially cerebral.
• Can progress to brainstem and spinal cord, especially EEE.

Cerebrum Signs

• Obtunded mentation.
• Head pressing.
• Hyperesthesia.
• Compulsive walking.
• Blindness and lack of menace.
• Brainstem signs: abnormal PLR (pupillary light reflex), head tilt, nystagmus, facial and tongue paralysis, especially EEE.
• Spinal cord signs: ataxia and paresis.

Clinicopathologic Abnormalities

• May see leukocytosis or hyperfibrinogenemia.

CSF Analysis for EEE

• High protein and high cell count.
• Neutrophilic pleocytosis.

CSF Analysis for WEE

• High cell count.
• Lymphocytic pleocytosis

Diagnosis

• Serology via Hemagglutination-inhibition (HI) or plaque-reduction neutralizing titer (PRNT) tests.
  • A 4-fold rise between acute and convalescent samples is significant.
• IgM capture (MAC) ELISA can distinguish between vaccination and natural infection.

Necropsy

• The CNS is a human health hazard.
• Perform Virus isolation, IHC (immunohistochemistry), or PCR of brain tissue.
• Meningoencephalomyelitis, multifocal to diffuse, predominantly affecting gray matter.
  • Neutrophilic infiltration with EEE.
  • Lymphocytic infiltration with WEE.

Treatment

• Focus on treating cerebral inflammation and edema.
• Provide supportive care.

Supportive care

• Administer IV fluids and nutritional support.
• Use prophylactic antibiotics.
• Control hyperthermia.
• Provide slinging, limb bandages, and sedation as needed.
• Mortality may result from injuries during acute neurologic disease, such as lacerations, head trauma, fractures, and contaminated joints.

Prognosis

• EEE has the highest mortality rate at 75-95%.
  • 2/3 of survivors have residual CNS signs.
  • Treatment is usually ineffective.
• WEE has a mortality rate of 19-50%.
  • Many horses can recover completely.
• VEE has a mortality rate of 19-83%.
  • If horses survive, gradual improvement is expected over weeks to months.

Prevention

• EEE and WEE have AAEP core vaccines.
• These should be administered before the onset of mosquito season.
• Vaccination is annual to biannual depending on mosquito activity.
• Use formalin-inactivated adjuvanted whole virus vaccines.
• Control mosquitos and quarantine VEE suspect/infected horses.

Venezuelan Encephalitis

• Prestige V + VEE is available.
• There hasn't been a disease outbreak in over 20 years in the US.
• During an outbreak, an MLV vaccine may be conditionally released.

Public Health Significance

• These diseases are zoonotic
• Can infect humans and cause subclinical, febrile, or neurologic disease.
• Human mortality rates: EEE 74% vs. WEE 4% and VEE 1%.
• Remember that horses are amplifying hosts in VEE.
• Other species affected:
  • EEE: New World camelids, emus, pigs.
  • VEE: pigs, domestic rabbits, goats, dogs, sheep.

West Nile Virus

• It is in the Flaviviridae family as a positive-sense, single-stranded RNA virus.
• The Viral Lineage is Neurally invasive lineage type 1 which shows Clinical signs
• The African lineage type II is considered subclinical.

WNV Factors

• Vector-borne transmission through mosquitos from amplification hosts to dead end hosts.
• The incidence of the virus is Seasonal in temperate regions and Year-round in subtropical and tropical regions

Clinical Findings

• Fever, anorexia, and depression.
• The onset of neurologic signs will be sudden and progressive.
• Muscle fasciculations and changes in personality.
• Gait abnormalities can occur such as lameness/dragging limb, ataxia, and weakness.
• Cranial nerve abnormalities for short periods of Weakness of tongue, muzzle deviation, head tilt, and dysphagia.

Clinicopathologic Abnormalities

• CBC: +/- mild lymphopenia
• Serum biochemistry: +/- mildly elevated muscle enzymes (trauma).
• CSF has an increased mononuclear cell population.
• Elevated protein in the CSF (>70mg/dL)
• Xanthochromic CSF.

Diagnosis

• Serology via Plaque-reduction neutralization test.
  • Look for a four-fold increase between acute and convalescent titers.
• IgM-capture ELISA (MAC-ELISA) differentiates between vaccination and acute infection.

Post-Mortem Confirmation

• The CNS sample is a human health hazard and PPE is needed.
• PCR and Immunohistochemistry on CNS tissues should be performed.
• Polioencephalomyelitis occurs.

Treatment

• Cerebral inflammation and cerebral edema treatment.
• Supportive care such as for alphaviral encephalitides including Anti-viral support.
  • Interferon alpha.
  • High immunoglobulin/hyperimmune equine WNV plasma.

Prognosis

• There's a 22-30% mortality in horses.
  • 71% of recumbent horses are euthanized.
• There are residual weakness and ataxia in recovers.
• Full recovery can happen over weeks to months for 90% of patients if improving earyly in the disease.
• About 30% experience recrudescence of clinical signs within the first 7-10 days of apparent recovery.
• Another 30% can progress to complete paralysis of one or more limbs.

Prevention

• Vaccines are part of the AAEP core
  • Administer before mosquito season
  • Vaccine annually or biannually with mosquito activity depending.
• Vaccination options:
  • Inactivated whole-virus vaccine (2)
• Modified-live canarypox vector vaccine expressing prM and E proteins - Live Flavivirus chimeric YF17D vector vaccine expressing prM and E proteins
• Maintain Mosquito prevention and control

Public Health Considerations

• WNV is a zoonotic disease
• Humans are infected through mosquitoes.
• There is a risk during post-mortem examination for humans
• There is no Human vaccine
• Prevent with Mosquito control/protection
• Other species affected: squirrels, New World camelids

Rabies

• Belongs to the Family Rhabdoviridae, Genus Lyssavirus.
• Enveloped single-stranded RNA virus
• Wildlife are natural reservoirs.
  • Each rabies strain is maintained by a particular reservoir host.
  • Wildlife-adapted strains usually die out when passed into species to which they are not adapted.
  • Transmitted by saliva contaminated wounds.

Pathophysiology

• Subcutaneous or intradermal inoculation
  • Replicates locally
  • Binds to acetylcholine receptors of peripheral nerves and migrates retrogradely to CNS
  • Virus replication in cell bodies of CNS
  • Spreads centrifugally along rootlets of cranial nerves to salivary glands and nasal epithelium

Epidemiology

• A reportable zoonosis detected worldwide
  • Not found in Sweden, Norway, UK, Ireland, Australia, New Zealand, and Iceland.
  • Endemic to US, Canada, and Europe.
  • Epizootic in Central and South America, Africa, and parts of Asia.

Clinical SIgns

• Horses signs are highly variable
• Fever, hind limb lameness, hyperesthesia.
• Progression to paresis (paralytic form) and recumbency
• Mentation often normal until end-stage disease
• Mean survival is 4 days with a Fatal course of 1-8 days.
  • Can extend up to 14 days.
  • Usually due to cardiorespiratory failure.
• Different forms:
  • Cerebral or furious form
  • Brainstem or dumb form
  • Paralytic or spinal form

Cerebral or "Furious" Rabies

• Horses show aggressive behavior and photophobia.
• Other signs include hydrophobia, hyperesthesia, straining, muscular tremors, and convulsions/seizures.

Brainstem or "Dumb" Rabies

• Depression and anorexia.
• Possible head tilt, circling, ataxia, and dementia.
• Excess salivation, facial and pharyngeal paralysis, and blindness.
• Animals can also display a flaccid tail and anus, urinary incontinence, and self-mutilation.

Paralytic or Spinal Form

• Key signs include progressing ascending paralysis and ataxia.
• Shifting lameness with hyperesthesia and self-mutilation of extremity.
• Recumbency can occur in 3-5 days.

Diagnosis

• PPE is needed when handling suspect animal or diagnostic samples
• The diagnoses is a zoonotic.

CSF Analysis

• CSF may be normal or abnormal.
  • May show Moderate mononuclear pleocytosis. -Increased protein.

Necropsy

• Nonsuppurative meningoencephalomyelitis occurs.
• Definitive testing is needed.

Definitive Diagnoses

• Using the Hippocampus and cerebellum, also brainstem, pons, and medulla
  • Negri bodies on histopathology (aggregates of viral proteins and nucleic acids). -Direct or indirect fluorescent antibody, DFA is standard -Intracerebral inoculation of mice with CNS tissue in inconclusive testing and human exposure.

Treatment

• No specific treatment available, only supportive care.
• PPE if attempting any treatment.

Prevention

• There is an AAEP core vaccine.
• Vaccination should happen with an annual vaccine and Inactivated virus with adjuvant

Case Study 1

• An 18-month-old QH filly purchased from sale 1 month before presentation.
• The Fillie had an incomplete vaccination history indicating Only one set of vaccines as a yearling
• History of recumbency at home for 1 day in October.
• Physical exam finds:
  • Circling to the left
  • Spinal curve to the left -BAR and vital parameters within normal limits -Mild bilateral ptosis and weak eyelid tone -Grade 4/5 ataxia/paresis (L>R) -Turning to the right
• Differentials: -Grade 4/5 asymmetric ataxia/weakness, bilateral ptosis, turning to right -Lesion localization: spinal cord and brainstem
  • Considerations: -West Nile virus -Equine protozoal encephalomyelitis -Rabies -Botulism -Equine degenerative myeloencephalitis -Eastern equine encephalitis
• Diagnostics of case study find the following: -Serum Biochemistry -AST 561U/L; CK 3086 U/L -WNV IgM Capture ELISA: POSITIVE
• Treatments include -Flunixin -High Gamm Plasma -Vitamin E -DMSO -Omeprazole
• After care -Initially needed help rising from recumbency -There was progression and LH was severely paretic 1 week after presentation -Discharged 15 days after presentation with minimal paresis and Vitamin E therapy -Prognosis: Good for full recovery

Case 2

• A 2-month old Arabian Filly presented for evaluation of acute onset ataxia and inability to eat
• Physical Exam:
  • The Filly was Depressed, Ataxic and weak in all limbs with Tongue swollen and protruding from mouth. -Mucoid nasal discharge bilaterally and Temperature 38.7C (101.6F) -Heart rate measured at 68 bpm with a Respiratory rate of 24 brpm.
• Problems and Differentials: -Depressed, Ataxic and weak in all limbs, with the Tongue swollen and protruding from mouth and a Mucoid nasal discharge bilaterally -Mild hyperthermia and Tachycardia Cerebrum that consisted of: - Trauma -Infection within CNS Abscess and Meningitis and even Rabies

Diagnosis

• Blood samples finds: -WBC at 23,000/ul -Neutrophils at 21,000/ul with Fibrinogen measured at 800 mg/dl -Note Mild electrolyte derangements and evidence of dehydration
• Also, a CSF tap -Atlanto-occipital can indicate: -TNCC at 16 /ul -Protein at 43 mg/dl -Cytology measured at 60% lymphocytes showing Lymphocytic pleocytosis that indicate being viral. -And Endoscopy and Skull radiographs.
• Treatments consist of IV fluids and Anti-inflammatories with the administration of Antibiotics.

Progression Diagnosis And Follow Ups

• Despite therapy, the case study with the Arabian Filly progressed and showed recumbency and Struggling
  • Also showing a Demented and unresponsive
• The case was put down with Euthanasia and ran a necropsy.
• Immunofluorescence testing for rabies. -The Cerebellum and brainstem was shown to have the rabies and were declared Positive -The Mare Case study was a rescue that had not been vaccinated for rabies during gestation Recommendations Were sent out to: -Quarantine mare and other horses on property with the Follow up to vaccinate all horses on property -The Human exposure with Veterinary personnel that Were Vaccinated for rabies and wore PPE as Post-exposure prophylaxis depending on possible exposure level Owners! with Unvaccinated Owners! needing Post-exposure prophylaxis IMMEDIATELY