Viruses of the Nervous System 2024 PDF

Viruses of the Nervous System 1 1 3/22/2024 Objectives Construct a differential diagnosis list of the major neurotropic viruses for companion and food producing animals Describe the pathogenesis of the major neurotropic viruses Identify the clinical signs and pathologic lesions associated with each...

Viruses of the Nervous System 1 1 3/22/2024 Objectives Construct a differential diagnosis list of the major neurotropic viruses for companion and food producing animals Describe the pathogenesis of the major neurotropic viruses Identify the clinical signs and pathologic lesions associated with each of the major viruses Identify the appropriate samples to take and diagnostic tests available to test for individual pathogens Infection vs. Disease *The best diagnostic test varies based on the question asked Organism ID without lesions = infection Organism ID + lesion = disease (clinical or subclinical) Organism ID + lesion + clinical signs = clinical disease Serology = gives a history of exposure but says nothing about disease status Evidence of infection only may be important for diseases with regulatory importance Neurotropic Viruses in Companion Animals Rabies virus in ALL species Dogs Canine distemper virus Canine herpes virus (encephalitis in puppies less than 6 weeks of age) Cats Feline infectious peritonitis virus Feline immunodeficiency virus Feline leukemia virus (myelitis) Feline panleukopenia virus (cerebellar hypoplasia) Horses Equine herpes virus 1 West Nile virus Equine Togaviruses (EEE, WEE, VEE) Equine infectious anemia viruses (rarely neutrotropic) Clinical scenario A 6-month-old puppy presents with behavioral changes, ataxia, and occasional seizures that have been progressing over the last few days. The vaccination history is unknown Non-specific neurologic signs are localized to: Differential list Rabies virus Canine distemper virus Canine Distemper Virus Paramyxovirus Highly contagious Infects dogs and a number of wildlife species including lions, foxes, pandas, wolves, ferrets, raccoons, etc. Infects many cell types, including epithelial, lymphoid, and oligodendroglial cells, and causes generalized infection Affects the skin, the respiratory, gastrointestinal, and urinary tract, and the brain Produces both intracytoplasmic and intranuclear inclusion bodies Infection occurs between 3 – 6 months when maternal antibody declines Canine Distemper Virus Pathogenesis Following infection, the virus is carried to the CNS by infected lymphocytes, monocytes, and platelets Once in the brain, the virus spreads in the CSF Lesions in the brain are inflammatory and demyelinating Lymphoplasmacytic perivascular cuffing Demyelination may progress to necrosis and infiltration by gitter cells Canine Distemper Virus Acute disease is followed by recovery and lifelong immunity or neurologic disease and death Clinical signs Leukopenia Diarrhea, vomiting Conjunctivitis, nasal discharge Coughing Hardening of the nose and footpads Diagnosis is by PCR or virus isolation Canine Distemper Virus Cwm = cerebellar white matter M = meninges CC = cerebellar gray matter Perivascular cuffing Intranuclear inclusions White matter vacuolation (from demyelination Rabies virus Rhabdovirus Infects the nervous system of all mammals, including humans Infection is invariably fatal Endemic on all continents except Australia and Antarctica Usually maintained in and transmitted by a particular host, depending on the geographic region Urban rabies in dogs accounts for 95% of all human cases Sylvatic rabies is maintained in raccoons, skunks, bats and foxes Rabies virus Transmission is by contact with saliva from an infected animal The incubation period varies by location of the bite, size of inoculum, immune status of the host, and strain of the virus The incubation period can be up to 6 months The clinical course is short, lasting for a few days to a few weeks Clinical signs range from excitation to depression Diagnosis is only post-mortem Control is by vaccination of pets to break the urban cycle Rabies virus pathogenesis Following inoculation, initial replication is in myocytes Virus passes to axon terminals of motor neurons and sensory axon terminals Virus moves by retrograde axoplasmic flow to neurons in the CNS Eosinophilic intracytoplasmic inclusions (Negri bodies) in the neurons Diagnosis is postmortem only by demonstration of viral antigens in the brain Negri bodies http://vet.uga.edu/ivcvm/courses/VPAT5316/02_neuropath/ 09_viral/viral04.htm Differentiating between CDV and Rabies Age of onset Course of neurologic signs Presence of other clinical signs Progression of the disease Laboratory diagnosis Clinical scenario A 2-month-old cat presents with depression and lethargy The cat is one of 4 indooroutdoor cats and was recently adopted from a shelter Vaccines are up-to-date but the first rabies vaccine has not yet been given Neurologic signs are localized to: Differential list Rabies virus Feline infectious peritonitis virus Feline immunodeficiency virus (uncommon) Would feline parvovirus (panleukopenia) be on the differential list? Feline infectious peritonitis (FIP) Feline coronavirus (FCoV) replicates in intestinal epithelium Enteritis in young kittens is possible but not common Mutation in select strains of the enteric coronavirus results in feline infectious peritonitis virus (FIPV) emergence FIPV has a tropism for macrophages Infection is invariably fatal Because the virus is a mutated form of FCoV, diagnosis is difficult and often post-mortem PCR is available but does not differentiate between FCoV and FIP Feline infectious peritonitis (FIP) The disease is sporadic and most common in catteries or multi-cat households Cats less than 1 year of age are most susceptible The virus is shed in the feces Transmission is by ingestion or inhalation Age, immune status, genetics of the host, virulence of the strain play a role in disease development An immune-complex disease, and occurs when cell mediated immunity is defective Feline infectious peritonitis Dry form Associated with moderate cell-mediated immunity Considered a chronic form Pyogranulomatous vasculitis in all organs including the eye and brain Clinical signs depend on the organs most severely affected Wet form Associated with weak cell-mediated immunity Accumulation of fluid in the abdomen, thorax, and lateral ventricles Fibrinous pleuritis, peritonitis, and/or pericarditis Cats present with breathing difficulty or a distended abdomen Feline infectious peritonitis Protein-rich fluid in the dilated ventricles Loss of cerebral white matter Feline infectious peritonitis Pyogranulomatous inflammation extending into the ventricle (arrows) Mo = medulla oblongata Cc = cerebral cortex Fibrinous vasculitis Lymphocytic inflammation Feline immunodeficiency virus Lentivirus (Retrovirus) 1.5 to 3% of healthy cats in the US are infected Transmitted by bites, therefore aggressive, free-ranging male cats have higher rates of infection Rarely transmitted from the dam to her kittens through the milk or during parturition FIV pathogenesis From the bite wound, the virus is picked up by dendritic cells and carried to the local lymph nodes In the lymph node, the virus infects T lymphocytes where it replicates The virus then spreads to other lymph nodes and can be associated with fever and non-specific neurologic disease Cats can be clinically normal or can progress to becoming immunodeficient FIV clinical disease Recurrent infection of the skin, eyes, respiratory tract, urinary bladder Persistent fever Gingivitis and stomatitis Meningoencephalitis or encephalitis with seizures or behavioral changes Diagnosis is by ELISA (for antibody) or PCR (for viral RNA) using blood Feline immunodeficiency virus Perivascular lymphocytic cuffing Gliosis Differentiating between Rabies, FIP, and FIV Age of onset Course of neurologic signs Presence of other clinical signs Progression of the disease Laboratory diagnosis Clinical scenario A 20-year-old pony was purchased through an ad on the internet and bought as a companion to an 8-year-old mare The pony was mostly wild and could not be handled Four weeks after purchase, the other horse became ataxic and had difficulty walking Differential list Rabies virus Equine herpesvirus 1 West Nile virus Eastern equine encephalitis virus (EEE) Western equine encephalitis virus (WEE) Venezuelan equine encephalitis virus (VEE) Equine Herpes virus 1 Alphaherpesvirinae Three strains EHV1 D752, N752, H752 D752 – respiratory (rhinopneumonitis)/reproductive (abortion)/ neurologic N752 – respiratory and reproductive only Equine Herpes Myeloencephalopathy Typically associated with the D752 strain Follows an outbreak of respiratory disease or abortion on the farm The neurologic form is reportable in Virginia to the State Veterinarian Vasculitis, necrosis, and hemorrhage in the spinal cord and brain Diagnosis is typically by PCR on nasal swabs Postmortem diagnosis is done on brain or spinal cord by immunohistochemistry or PCR PCR can differentiate between D and N strains but not H EHM in Virginia Arthropod borne viruses (Arbovirus) Flaviviruses West Nile Virus Togaviridae Eastern Equine Encephalitis Western Equine Encephalitis Venezuelan Equine Encephalitis West Nile Virus Flavivirus Mosquito-borne Infects horses, humans, and birds First detected in New York in 1999 Transmission cycle occurs between birds and mosquitos Horses and humans are an incidental host Clinical signs in horses are primarily neurologic and need to be differentiated from other encephalitides EEE Togavirus (alphavirus) Eastern equine encephalitis is occasionally seen in the eastern US First recognized in 1831 in Massachusetts when 75 horses died Mosquito-borne, maintained in a bird-mosquito cycle Infects humans Incubation period is 4-10 days After infection, the virus travels to the lymph node and replicates in macrophages and neutrophils Death occurs 3-4 days after onset of neurologic signs The mortality rate is 70-90% WEE Alphavirus (Togavirus) Typically seen west of the Mississippi river Disease is milder than EEE, and has a 15-20% mortality rate Mosquito-borne, maintained in a bird-mosquito cycle Infects humans but is often subclinical Diagnosis of arboviral encephalitides is by IgM ELISA on serum and PCR or IHC on brain and spinal cord post-mortem Killed vaccines are available and are considered standard of care Equine neurotropic viruses Hemorrhage in the gray matter Equine neurotropic viruses Perivascular cuffing Gliosis Differentiating among the viruses Course of neurologic signs Presence of other clinical signs Time of year Presence of similar disease in other animals Laboratory diagnosis