Rhabdoviruses, which include rabies and vesicular stomatitis virus
(VSV), are large, enveloped, bullet-shaped ss (-)RNA viruses. There are
over 200 known rhabdoviruses that can infect mammals, fish, insects,
arthropods and plants. However, rabies is the only rhabdovirus which
can "naturally" infect humans.
Cartoon
drawing of ultrustructure of Rabies virus. Virus particles are about
180 x 70nm with unique bullet-shaped appearance. The viral enveloped
has some prominent glycoprotein ("G-protein") spikes on its
surface which
hemagglutinate red blood cells. The envelope is lined by the matrix
protein and contains the
nucleocapsid wound helically inside the core. http://www.vet.ksu.edu/depts/rabies/index.htm
Rabies is an ancient disease shown to be of viral etiology by
Pasteur in the 1880's. For over a decade, Pasteur carried out the
serial passage of rabies virus in
rabbits, eventually succeeding in isolation of an attenuated
preparation which was used to treat people bitten by rabid dogs.
Deaths due to rabies is rare in the United States (1 or 2 each year).
This is primarily due to animal control and vaccination programs begun
in the
1940's that have nearly eliminated domestic dogs as reservoirs of
rabies in the U.S., and to the availability of effective rabies
vaccines
and immunoglobulins that can be used before or after exposure to the
virus.
Unfortunately, on a global scale, there are at least 50,000 reported
deaths per year due to rabies, which is a grossly underreported
disease. Rabies is the tenth leading cause of death due to infectious
disease on a world-wide basis. This is due to the reservoir of infected
dogs in underdeveloped countries (and the lack of resources to
accomplish control or mass vaccination of dogs), and the unavailability
of post exposure prohylaxis in poor or remote regions.
Transmission
Transmission of rabies virus usually occurs when infected saliva of a
host is passed to an uninfected animal. Most commonly this is
through a bite and virus-containing saliva of an infected animal.
Other routes of transmission that have been documented include direct
inoculation of mucous membranes (eye, nose, mouth) and aerosol
transmission.
Most of
the recent human rabies cases in the United States have been caused by
rabies virus from bats. Awareness of the facts about bats and rabies
can help people protect themselves, their families, and their pets.
This information may be found at the CDC website Bats_and_Rabies.
Pathogenesis
Following primary infection, the virus enters into an eclipse phase in
which it cannot be easily detected, which may last several days or
months. The virus replicates in muscle cells and connective tissue, and
it can directly or
indirectly enter into peripheral nerves in the vicinity. The virus is
transported to the CNS by retrograde axoplasmic flow. Dissemination of
the virus within the CNS is rapid and leads to active cerebral
infection (severe encephalitis). During replication in the CNS, the
virus
invades highly innervated tissues, including the salivary glands, from
where it is transmitted. The incubation period depends on
size and site of inoculation
(e.g. head/face/neck vs. hands or feet) and varies from a few days to
several years, but
is typically 1-3 months. Symptoms
Early symptoms include flu-like signs (malaise, fever or headache)
which last a few days. There may be abnormal sensation at
the site of the
infection progressing to hypersensitivity (to drafts, loud noises,
bright
lights, etc.), irritability, nervousness, hallucinations,
insomnia and anxiety. Muscle spasms,
salivation and perspiration are common. There is difficulty in
swallowing and
violent expulsion of fluids. The sight or sound of water can induce
contraction of the throat muscles (hydrophobia). The acute
period of disease lasts 2-10 days. When the virus invades the CNS, it
produces severe encephalitis.
Once clinical signs of rabies appear, the disease is almost always
fatal. To date there are only six documented cases of human survival
from clinical rabies.
Epidemiology
In the United States, the principal source or reservoir of Rabies virus
is wild mammals,
especially skunks, bats, foxes, raccoons, coyotes and squirrels.
Domestic animals such as cattle, dogs cats, horses, sheep or goats and
swine may acquire the disease accidentally. Humans also acquire the
disease accidentally and are a dead-end infection for the virus.
Globally,
in terms of human disease, dogs represent the most important
reservoir.
Infection of humans usually follows bites by rabid animals and is
almost invariably fatal, once signs of disease occur. More than 2.5
billion people live in regions where rabies is endemic. It is
estimated that each year at least 50,000 people die from rabies,
and more than 10 million receive post-exposure vaccination against this
disease. Children aged 5–15 years are at particular risk. More than 99%
of all human deaths from rabies occur in Africa, Asia, South
America and India. India alone reports 30,000 deaths annually.
In the United States and many
other countries, veterinary rabies vaccines are widely applied for
immunization of domestic animals (mostly dogs and
cats), and oral vaccines have been used for the
immunization of wildlife hosts. However,
most attempts to control animal rabies have largely failed in poor
undeveloped
regions of the world.
Treatment
There is no
treatment for rabies after symptoms of the disease appear.
However, an extremely effective rabies
vaccine regimen can provide immunity to rabies when administered
after an exposure (post exposure prophylaxis) or for protection before
exposure occurs (preexposure prophylaxis). Although rabies among
humans is rare in the United States, every year an
estimated 18,000 people receive rabies preexposure prophylaxis and
an additional 40,000 receive post exposure prophylaxis.
Prevention
Because
rabies is a fatal disease, the goal of public health is twofold: 1. to
prevent human exposure to rabies by education, and 2. to prevent
the disease by anti-rabies treatment if exposure occurs. Tens of
thousands of people are successfully treated each year after being
bitten by an animal that may have rabies. A few people die of rabies
each year in the United States, usually because they do not recognize
the risk of rabies from the bite of a wild animal and do not seek
medical advice.
Rabies Vaccines and Immunoglobulin
Several classes and types of immunizing agents exist for rabies.
They may be used for preexposure prophylaxis or post exposure
prophylaxis as described below.
Inactivated Vaccines of Crude Tissue Origin - as originally
pioneered by Pasteur in the 1880's,
and used
until the 1950's, these vaccines contain up to 5%
nervous tissue from infected animals and tend to provoke severe immune
reactions in recipients, although they
save lives. Unfortunately, the majority of post exposure
immunizations against rabies are still performed with vaccines of crude
nerve tissue origin.
Inactivated Cell-Derived Vaccines - A purified duck embryo vaccine,
composed of virus grown in embryonated duck eggs, partially replaced
crude nerve tissue vaccines, but these vaccines caused severe
encephalitis in some recipients, and are no longer manufactured.
The human diploid cell rabies vaccine
was introduced un 1967 and is regarded as the gold standard of rabies
vaccines. The vaccine is produced by
growing the virus in human diploid fibroblasts. The vaccine is
effective and without the side effects of other inactivated vaccines,
but
expensive.
The more recently developed purified
chick embryo vaccine and purified
Vero cell rabies vaccine are less expensive and have comparable
immunizing characteristics to human diploid cell vaccine.
Live attenuated Virus - has
been used to vaccinate domestic
animals and livestock. It is effective but not considered sufficiently
safe
for human use.
Recombinant Vaccine - recently developed recombinant vaccinia
virus/G protein vaccine is being used to eradicate rabies in foxes in
Europe. It has not been licensed for use in humans.
Human Rabies Immune Globulin (HRIG)
- Immune serum for passive immunization.
Preexposure Prophylaxis
Preexposure
vaccination is recommended for persons in high-risk groups, such as
veterinarians, animal handlers, and certain laboratory workers. Other
persons whose activities bring them into frequent contact with rabies
virus or potentially rabid bats, raccoons, skunks, cats, dogs, or other
species at risk of having rabies should also be considered for
preexposure prophylaxis.
In the U.S. preexposure prophylaxis consists of three doses of rabies
vaccine given
on days 0. 7, and 21 or 28.
Post Exposure Prophylaxis (PEP)
Post exposure
prophylaxis (PEP) is indicated for persons possibly exposed to a rabid
animal. Possible exposures include animal bites or mucous
membrane contamination with infectious tissue such as saliva.
PEP using crude nerve tissue vaccines involves a prolonged and painful
immunization course of up to 23 injections.
Vesiculovirus
or vesicular stomatitis virus (VSV). The virus normally causes an
epidemic, self-limited disease of cattle which is of
some economic importance in countries where it is endemic, including
North America. The disease is similar in appearance to foot and mouth
disease. VSV can infect humans, causing a relatively mild febrile
illness. http://www.virology.net/Big_Virology/Written and Edited by Kenneth Todar. All rights
reserved.
