Rabies virus
family Rhabdoviridae
Jack Lam
Atsuko Hilliard
Roger Salinas
What is Rabies?
• Rhabdovirus family,
• virus Neurotropic lyssavirus.
- single-stranded, neurotropic, negative-sense RNA
virus

The mature virus has a bullet shape, a protein coat, and a
lipid envelope. The outer surface of the virus is covered
with thumblike glycoprotein projections
Three possible vectors
• 1. The bite or scratch of an infected animal
• 2. Aerosol transmission from an infected animal
(usually a bat)
• 3. Tissue transplants – only six recorded cases
• The virus concentrates in the salivary glands,
which explains why bites cause approx 99% of
rabies cases worldwide
Mechanism
NEUROINVASIVE
• The rabies virus attacks nervous tissue
and appears to replicate almost
exclusively in neuronal cells
• After a typical human infection by bite, the
virus directly or indirectly enters the
peripheral nervous system
Mechanism
• The virus then travels along the nerves towards
the central nervous system
• During this phase, the virus cannot be easily
detected within the host
Mechanism
• The rabies virus replicates in CNS and then
travels down nerves to the salivary glands where
there is further replication
Incubation Period
• The period between infection and the first
flu-like symptoms is normally two to twelve
weeks, but can be as long as two years
• The rabies virus may lie dormant in the
body for several weeks or months, but
rarely much longer before symptoms
appear
Incubation Period
• The length of the
incubation period
depends on the location
of the wound – a bite on
the foot will have a very
much longer incubation
period than a bite on the
face
• Axonal transport of the
virus to the CNS is at a
rate of 3 mm per hour!
PEP – Post exposure prophylaxis
• The first step is immediately washing the
wound with soap and water, which is very
effective at reducing the number of viral
particles
• The virus travel along the nerves is usually
slow enough that vaccine and
immunoglobulin can be administrated to
protect the brain and glands from infection
Neurovirulent
• This virus can cause disease of nervous
tissue
• Prevention of disease after exposure is
only effective during the incubation period
• Once symptoms have developed, death
usually occurs in three to 20 days, and
recovery is very rare. There are only six
known cases of a person surviving
untreated rabies
Case Study
• An 11-year old boy was brought to the hospital in California
after falling: the symptoms were treated, and he was
released. The following day he refused to drink water with his
medicine and he became anxious. That night he began to act
up and hallucinate. He also was salivating and had difficulty
breathing. Two days later, he had a fever of 40.8oC and
experienced two episodes of cardiac arrest. Although rabies
was suspected, no remarkable data were obtained from a
computed tomographic image of the brain or cerebral spinal
fluid analysis. A skin biopsy from the nape of the neck was
negative for viral antigen on day 3, but positive on day 7. His
condition continued to deteriorate and he died 11 days later.
When the parents were questioned, it was learned that the
child had been bitten on the finger by a dog 6 months earlier
while on a trip to India.
Signs and Symptoms of Rabies
Initial symptoms include:
-a general feeling of discomfort or uneasiness
- nervousness
- anxiety
- insomnia
- depression
- apathy
- pain at the site of infection
- fever
-chills
-cough
-sore throat
- headache
- nausea
-vomiting
- Hydrophobia: affects 17% to 80% of rabies patients. Causes
forceful, painful muscle spasms of the throat, which expel any liquids
administered orally. The patient experiences apnea (interruption or halt
of breathing while swallowing). Cyanosis and death can occur in this
phase. Frothy saliva which drools from the patient's mouth is caused by
difficulty in swallowing because of growing muscular weakness.
Eventually, a variety of stimuli (the mention of water, a tactile sense or
scent of water, the thought of water, etc.) can cause uncontrollable
spasms and drool. Hydrophobic episodes last 1-5 minutes
Signs and Symptoms of Rabies
• Rabies manifests in two forms:
• Furious rabies: characterized by agitation, thrashing, biting,
viciousness, choking, gagging, hyperventilation, cardiac
arrhythmias, paralysis and death.
• Paralytic (dumb) rabies: characterized more by paralytic
symptoms, which may include apathy, apparent depression,
increased blood pressure, tachycardia, confusion,
hallucinations, and disorientation. These symptoms are
followed by increased periods of hyperactivity, stiffness in the
back of the neck, and an increase in the number of cells in the
cerebrospinal fluid. Dumb or paralytic rabies ends with coma
and death by respiratory failure. Most often experienced by
patients who have been exposed to the virus via bats.
.
Stages
Prodromal stage:
Prodromal or premontive symptoms are mild and nonspecific.
They include: a slight fever (100 F to 102 F), chills, malaise,
headache, anorexia, nausea, sore throat (the beginnings of
hydrophobia), photophobia, musculoskeletal pain, and a
persistent loose cough. This stage usually lasts 2-10 days. A
specific early symptom is local or radiating pain, burning, or
itching, a sensation of cold, and/or tingling at the inoculation
bite
.
Stages
Acute neurological or excitation phase:
This stage usually lasts 2 to 7 days. Patients experience
nervousness, anxiety, agitation, marked restlessness,
apprehension, irritability, hyperesthesia, sensitivity to
loud noises, hydrophobia, excessive salivation (1 to 1.5
liters in 24 hours), lacrimation (secretion of tears), and
perspiration. As the virus begins replicating in the brain,
impairment of the cranial nerve occurs. This causes eye
conditions: palsies, lack of parallelism of the visual axes
of the eyes, asymmetrical dilation of constriction of the
pupils, and an absence of corneal reflexes. At the same
time, there is weakness of facial muscles and
hoarseness. Systemic symptoms are severe, and they
include: tachycardia or bradycardia, cyclic respirations,
urinary retention, and a temperature of 103 F. The patient
is often lucid between excitation and hydrophobic
Stages
Coma, or terminal phase:
This phase is characterized by generalized flaccid
paralysis. Eventually, the patient experiences
peripheral vascular collapse, coma, and death.
Diagnosis of rabies
• Rabies diagnosis can be very tricky due to the
similar symptoms of other viral infections that
cause encephalitis such as herpes simplex virus,
mumps virus and even bacterial meningitis
(syphillis).
• Detection can also be difficult due to long
incubation periods and is troublesome because
once the onset of symptoms occur treatment is
ineffective with a mortality rate of about 100% (3
rare cases of survival have been documented).
Differential Diagnosis
• Rabies virus is highly neuroinvasive and neurovirulent and is almost
exclusively transmitted through animal vectors through saliva
exchange – here epidemiology, the vector (animal) and injury type
can be a great diagnostic tool.
• Rabies shows invasion into the CNS and displays rapid and severe
symptoms shortly.
• Herpes simplex virus are highly virulent causing severe and rapid
symptoms as well but rarely enters the CNS, it usually enters the
PNS. Also causes inflammation of the temporal lobe and there is no
epidemiology associated with the infection.
• Mumps virus high neuroinvasiveness entering the CNS but low
neurovirulence displaying mild symptoms.
• To distinguish viral versus bacterial infection, a spinal tap displays
increases in WBC count for viruses with no detection of bacteria.
Methods of diagnosis
• No single test is sufficient, a battery of test
is required.
• Saliva can be tested using RT-PCR
• Serum and spinal fluid can be tested for
antibodies for rabies virus.
• Skin biopsies of hair follicles at the nape of
the neck (cutaneous nerves at the base of
hair follicles) can be examined for rabies
antigen.
Negri Bodies (viral nucleocapsid) found in
histological staining found in the cytoplasm of
neurons
Methods of diagnosis – post
mortem diagnosis
• Direct fluorescent
antibody test (dFA) –
uses fluorescentlylabeled anti-rabies
antibody which
detects rabies antigen
in neural tissue
viewable on a
fluorescence
microscope.
Treatment of Rabies Infection
• Upon injury with a bite, the wound should
immediately be cleansed and disinfected
using normal procedures to reduce the
number of viral particles entering the
wound site.
• A tetanus booster shot may be given to
prevent secondary infection.
• Antibiotics may also be given to prevent
secondary infection.
Treatment Options
• Following an injury due to a bite of a rabid animal,
human immune globulin (HRIG) is given at the site of
injury (exact weight data is used to calculate the
appropriate amount) to stimulate immune cells to confer
resistance and protection from the virus.
• Usually vaccines are administered prior to infection but
with rabies virus the vaccine is administered post
infection.
• This is effective due to long incubation period before the
virus is able to migrate into the CNS where it replicates
almost exclusively.
Treatment Options
• Five 1cc (ml) follow-up injections are administered on days 3, 7, 14
and 28 following the initial day 0 injection.
• These injections are selected from three possible vaccine boosters:
human dipliod cell, rabies vaccine absorbed, or purified chick
embryo cell culture vaccine and administered usually in the deltoid
or shoulder muscle in adults (must be away from target site and
readily absorbed).
• If a person has already been inoculated with rabies vaccine then
only 2 boosters shots are needed, one at day 0 and one at day 3.
• There are no other treatment options, and the timing of treatment is
crucial for protection and recovery.
References
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T.H.K. Virology Notes: Rabies. http://tarakharper.com/v_rabies.htm.
Accessed 11/03/07.
EmedicineHealth Online.
http://www.emedicinehealth.com/rabies/article_em.htm. Accessed 11/01/07.
Department of Health Services. Rabies Fact Sheet.
http://www.dhs.ca.gov/ohb/HESIS/rabies.htm. Accessed 10/31/07.
Virology Online. http://virology-online.com/viruses/Rhabdoviruses.htm.
Accessed 11/01/07.
Survive Outdoors Online.
http://www.surviveoutdoors.com/reference/rabies.asp. Accessed 11/01/07.
Health Scout. Health Encyclopedia – Diseases and Conditions: Rabies.
http://www.healthscout.com/ency/68/738/main.html. Accessed 11/01/07.
Flint, S. J., Enquist, L. W., Krug, R. M., Racaniello, V. R., & Skalka, A. M.
(2000). Principles of Virology: Molecular Biology, Pathogenesis, and
Control. Washington, D.C.: ASM Press.