CVM 6472-Small Animal Infectious Diseases
Jody Lulich DVM, PhD (CVM 346, 625-7277, lulic001@umn.edu)
WAS DRACULA RABID?
Understanding the clinical course of rabies and factors associated with transmission will
unravel the similarities between the vampire legend and modern medicine (Neurology.
1998;51:3;856).
Rabies is an acute, infectious, often fatal viral disease capable of infecting most warmblooded animals. The agent is a single-stranded, neurotropic, negative-sense RNA virus
which encodes 5 proteins: a glycoprotein, a nucleoprotein, and three others. The virus
has a strong affinity for cells of the nervous system. At the site of entry, the virus enters
nerve cells, travels to the brain, and then out of the brain along other nerve pathways to
organs that become uniquely affected (e.g.; salivary glands).
Worldwide, approximately 50,000 people die annually from rabies. Although most are
associated with dog bites, rabies is comparatively rare in domestic animals in the United
States. In 2006, 2615 cases were diagnosed in the USA; 92% were in wild life species
(e.g. raccoons, bats, skunks and foxes). Rabies control is possible; not by cure, but
through prevention measures such as vaccination, avoidance, surveillance, eradication,
and testing.
LECTURE GOALS
1. Recognize the clinical presentation of a Rabies suspect; it may save your life.
2. Know the laws and procedures regulating veterinary care delivered to rabies-suspect,
companion animals that bite humans, and companion animals bitten by rabies
suspects; it may save your license.
KEY DEFINITIONS
1. Hydrophobia, literally "fear of water” is an older synonym for rabies. Because of this
name, many people think that rabies makes one afraid of water. In fact, this is not the
case (although rabies does cause mental confusion of many other kinds). The name
hydrophobia comes from the fact that animals and people with rabies get spasms in their
throat muscles that are so painful that they cannot eat or drink, and so will refuse water in
spite of being very thirsty.
2. Limbic System is a complex set of structures that lies underneath the thalamus, just
under the cerebrum. It includes the hypothalamus, the hippocampus, the amygdala, and
several other nearby structures. It appears to be primarily responsible for our emotional
life, and the formation of memories. Limbic system neurons are preferentially infected
with rabies virus. This explains why rabid animals exhibit signs of anxiety, confusion
agitation, delirium, insomnia. This also explains why the hippocampus is the common
section of the brain evaluated to confirm a diagnosis in rabid animals.
3. Negri Bodies are eosinophilic intracytoplasmic inclusions formed by aggregates of
rabies virus nucleocapsids in neurons of about 50 to 80% of rabid brains. They are typical
of rabies, but there can be false positives results. Therefore, the detection of negri bodies
needs to be confirmed by more contemporary diagnostics, the direct fluorescent antibody
test.
KEY CONCEPTS
1. How is rabies transmitted?
There are three vectors for rabies:
a. BITE: Usually the bite or scratch of an infected animal introduces virus
through broken skin or mucous membranes.
Bites (vs. nonbite exposure) cause approximately 99% of rabies cases
worldwide; the highest risk of human infection is a rabid dog that has
rabies virus in its saliva. Wild animals account for 70% of rabies cases
in the U.S. Rodents as rabies vectors are rare.
b. TRANSPLANT: Six cases of human rabies were documented following
cornea transplants from infected humans.
c. AEROSOL: Rare and questionable associations between spelunkers and
caves infested with rabid bats, or laboratory personal and aerosolized
virus have been reported in popular press.
2. What is the Course of Infection?
BITE
Disease Course
Virus inoculation
Clinical Signs Supporting a Rabies Suspect
Bite Wound from wild life (raccoons, skunks, etc.)
Virus replication at inoculation
site
Virus enters Neuromuscular
junctions
Retrograde intra-axonal
(centripetal) spread of virus
from peripheral nerves to
spinal cord.
Virus replication in spinal cord
damages cell bodies of
peripheral nerves
Retrograde intra-axonal
spread of virus to brainstem.
Virus replicates and spreads
throughout the central nervous
system
Inflammation at wound
Virus spreads centrifugally in
peripheral and cranial nerves
to enter the salivary glands
and other tissues.
CNS Inflammation
accelerated.
Accelerated and global nerve
cell apoptosis
Virus glycoprotein is homologous to neurotoxins
and attach to terminal axons
Subtle, but progressive ascending flaccid
paralysis
Prodromal Phase is characterized by
apprehension, nervousness, and variable fever.
Friendly ones become shy, and fractious ones
become affectionate. Prutitis develops at the
inoculation site. Virus has been recognized in
experimentally induces rabies in cats several days
prior to the onset of clinical signs.
Furious phase: Forebrain involvement heralds the
onset of restlessness, irritability, viciousness, and
hyperesthesia (photophobia, hyperacusis, etc.)
Reports of dogs barking and snapping at
imaginary objects that may progress to seizures.
Paralytic Phase (also called the dumb phase):
Paralysis of muscles leading to dropped jaw,
laryngeal paralysis, inability to swallow (and thus
appear to hyper-salivate creating excessive froth
from the mouth).
Death
The paralytic phase often ends with animals
becoming comatose and dying of respiratory
failure.
Although clinical signs are classically divided into distinct phases, the progression of
infection and development of clinical signs are variable.
Mandatory Reading
Feline Rabies: ABCD guidelines on prevention and management. J Fel
Med and Surg. 2009;11:585-593.
Valuable Resources
1. Compendium of Animal Rabies Prevention and Control, 2008
http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5702a1.htm
2. Animal Bites and Rabies Risk: A Guide for Health Professionals
http://www.health.state.mn.us/divs/idepc/diseases/rabies/risk/index.html
Are You Prepared for the Test?
1. Complete the following chart by filling in the appropriate actions and procedures of an
informed veterinarian. You answers should be based on the Compendium of
Animal Rabies Prevention and Control, 2008
Clinical Scenario
Appropriate Veterinary Action(s)
A client’s dog that is currently vaccinated
against the rabies virus, is bitten by a skunk
A stray dog of unknown vaccination status
recently acquired by a shelter is bitten by a
raccoon.
A dog appropriately vaccinated against
rabies bites a child on the face.
A stray dog with unknown vaccine status is
recently acquired by a shelter, and bites a
worker on the hand.
2. A 6 month old Yorkshire terrier is examined for central nervous system
depression. Because the dog is unusually small, the veterinarian makes a
presumptive diagnosis of a hepatic porto-systemic shunt. Blood is sampled to
assess the concentrations of bile acids. The dog’s condition rapidly deteriorates,
and the dog is euthanized. Thankfully, the head was submitted for rabies virus
isolation to the state diagnostic lab; the test is positive. Assimilate a variety of
people and scenarios that would have contact with this patient, its bodily fluids,
and/or tissues. For each scenario, discuss the likelihood of rabies transmission
and why. Here are some examples to get you started; the little girl who let the
dog lick her mouth at bed time after she brushed her teeth, the pathologist who
cut her finger using a band saw to cut the skull and its contents in half to remove
the brain, etc.