Rhabdoviruses

Rabies virus
• Rhabdoviruses are rod- or
bullet-shaped particles

• They are enveloped, single-

stranded, negative-sense RNA
viruses

• The RNA genome of the virus

encodes five proteins;
nucleoprotein (N),
phosphoprotein (P), matrix
protein (M), glycoprotein (G),
and the viral RNA polymerase
(L)
 Pathogenesis
• The infection usually results from the bite of a rabid animal

• Rabies virus is not very cytolytic and seems to remain cell-associated

• The virus directly multiplies in the muscle at the site of the bite, with
minimal or no symptoms (incubation phase, takes weeks to months)

• The virus infects the peripheral nerve endings by binding to

nicotinic acetylcholine or ganglioside receptors of neurons or muscle
(prodrome phase, lasts for 2 to 10 days)

• The virus remains at the site for days to months before progression
to the CNS

• The virus reaches the spinal cord and CNS in very short time causes
classic symptoms , coma, and death (neurologic phase, last from 2 to
14 days)
• The virus must be
amplified in muscle
near the site of
inoculation until
the concentration
of virus is sufficient
to accomplish
infection of the
CNS
• During the neurologic phase, the virus disseminates from the
CNS via afferent neurons to different sites such as the skin
of the head and neck, salivary glands, retina, cornea, nasal
mucosa, adrenal medulla, renal and pancreatic cells.

• After the virus invade the brain and spinal cord, an

encephalitis develops and neurons degenerates.

• With rare exception, rabies is fatal once clinical disease is

apparent

• Unfortunate, neutralizing antibodies are not apparent until

after the clinical disease is well-established
The length of the incubation period is determined
by:

1-) the concentration of the virus in the inoculum

2-) the proximity of the wound to the brain

3-) the severity of the wound

4-) the host’s age

5-) the host’s immune states

 Clinical syndromes
The disease goes through three stages.

The initial, or prodromal, stage involves itching and burning at the portal of
entry (bite wound), fever, malaise, headache, nausea, vomiting, and
possibly a downhearted mood

In the second or excitative stage, cramps and spasms of the pharynx and
larynx are the main symptoms, rendering swallowing very painful. The
spasms can be induced by the mere sight of water (“hydrophobia”). Other
mild acoustic and visual stimuli may elicit exaggerated reactions including
attacks of cramps and violent anger, hitting, biting, and screaming. Death
occurs within three to four days at the earliest

The third, paralytic, stage may develop instead of early death, with ascending
paralysis and asphyxia, leading to death. Focal and generalized seizures,
disorientation, and the hallucinations are common during the neurologic
phase
 Transmission
• The virus is widely distributed in infected animals, especially in the nerve
system, saliva, urine, lymph, milk, and blood

• Rabies is the classic zoonotic infection, spread from unvaccinated animals to

humans principally in saliva

• The principle reservoir for rabies in most of the world is the dog

• Rabies is maintained and spread in two ways:

1-) in urban rabies, dogs are the primary transmitter
2-) in sylvatic (forest) rabies, many species of wildlife such as raccoons,
bats, foxes, skunks, wolves, farm animals and cats can serve as the
transmitter

● Rabies containing aerosols, bites, and scratches from infected bats spread the
disease

The distribution of human rabies approximates the distribution of animal cases

in each country
 Immunity to rabies infection

• Unfortunate, neutralizing antibodies are not apparent until after the

clinical disease is well-established (when the virus has spread from the
CNS to other sites)

• This is because little antigen is released, and the virus remains hidden
from the immune responses

• The neutralizing antibodies can block the spread of virus to the CNS
and to the brain if administered or generated during the incubation
periods

• The incubation period is usually long enough to allow generation of a

therapeutic protective antibody response after active immunization
with the killed rabies vaccine

• Cell-mediated immunity appears to play no role in protection against

rabies virus infection
 Treatment, prophylaxis and prevention

• Post-exposure prophylaxis is the only hope for preventing overt

clinical illness in the affected person

• Prophylaxis should be initiated for anyone exposed by bite or by

contamination of an open wound or mucous membrane to the saliva
or brain tissue of an animal suspected to be infected with the virus

• The first protective measure is local treatment of the wound. The

wound should be washed immediately with soap and water ,
detergent, or any substance that inactivate the virus.

• The instillation of antirabies serum (antibodies) around the wound is

recommended by WHO committee
• Immunization with antirabies vaccine in combination with
administration of one dose of human rabies immunoglobulin
(HRIG) is highly recommended

• Passive immunization with HRIG is to neutralize some of the

inoculated virus and lower the concentration of virus in the
body, providing additional time for a vaccine to stimulate active
antibody production to prevent entry into CNS

• Passive immunization with human rabies immunoglobulin

(HRIG) is begun, whereby half of the dose is instilled around
the wound and the other half is injected i.m. Concurrently,
active immunization is started with six doses of HDCV injected
i.m. on days 0, 3, 7,14, 30, and 90
• The prevention of human rabies depends on the effective
control of rabies in domestic and wild animals

• Vaccination all dogs and cats against rabies in the surrounding

is the foremost way to prevent infection with the virus

• Oral bait vaccination programs have been successfully used to

vaccinate wild animals. This vaccine is injected into a bait and
parachuted into the forest where it can be taken orally by the
animals

• The avoidance of the contacts with the suspected animal is a

recommended strategy for any one to control the infection

• Good hygiene practice is always recommended in such cases