Rabies

Rabies Virus
Rabies is caused by RNA viruses in
the family Rhabdoviridae, genus
Lyssavirus

At least 7 Lyssavirus species or

genotypes cause rabies (disease)

Recently, 4 new Lyssaviruses

collected from Eurasian bats have
been described

Bullet-shaped, RNA virus

Rabies Disease
Acute, progressive viral encephalitis
Highest case fatality of any infectious

disease
One of the most ancient diseases

described
Model zoonosis
 Rabies

Global Disease

Estimated >55,000 deaths

annually
 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
Rabies
Animal reservoirs maintain and transmit different rabies
virus variants
Dog, cat, bat, human;
wild carnivore, e.g.: fox, skunk, raccoon, jackal; mongoose
ce: http://www.rbe.fli.bund.de/About_Rabies/Epidemiology.aspx
 The infection cycle
4. Massive
replication Infection
in brain 3. Spread to Incubation very
central variable
nervous Neuronal
system2. Uptake transport
into
5. Spread to peripheral CNS replication
salivary nerves Salivary gland
glands and 1. replication
excretion in Inoculation Virus excretion
saliva by bite
Clinical signs
Death
Rabies infection
The average incubation period is one
to three months, but can range from
several days to one year after
exposure

The incubation period is shorter in

patients with an exposure that occurs
in richly innervated areas, such as the
face, compared with the extremities.
Signs of rabies in animals

Abnormal Behavior :
Nocturnal animals acting sick or
active during daylight hours.
Staggering, trembling, weakness,
paralysis, agitation, confusion,
hypersalivation, unprovoked
aggression, abnormal
vocalization, glazed eyes,
choking.

**Grounded bats.
Variable symptoms
Rabies in humans
prodromal phase, which starts with non-specific
symptoms, such as low-grade fever, chills,
malaise, myalgias, weakness, fatigue, anorexia,
sore throat, nausea, vomiting, headache, and
occasionally photophobia.
This stage lasts from a few days to

approximately one week

If a bite wound is present, reported paresthesias

radiating proximally from the site of the wound

would be suggestive of rabies infection
 Localised pain or paresthesia
Change in behaviour,
anxiety, fear,
Aerophobia, Pharyngeal
spasms
Hydrophobia
Hyperactivity,
hypersalivation, lacrimation,
sweating
Paralysis, coma, death

Full recovery extremely rare

Treatment must rely on
palliative care
Anxiolytics, pain relief
Counselling of family
Recovery from Rabies

Recovery from
human rabies
extremely rare and
has resulted in
profound disability

Recent case of more

complete recovery
in unvaccinated
teenage girl in USA
Lab Tes (Pre mortem)
Saliva include reverse transcriptase polymerase chain reaction
(RT-PCR) for the detection of virus RNA and viral culture for the
isolation of infectious virus.
Skin biopsy : RT-PCR and immunofluorescence staining for viral

antigen.
Serum and cerebrospinal fluid

If no vaccine or rabies immune globulin has been given, the

presence of antibody to rabies virus in serum is diagnostic of
infection.
A patient who has been immunized will have rabies antibodies in
serum. a second specimen should be obtained a few days later
to see if antibody titers are rising, which would be indicative of
infection
` However, antibody to virus in a CSF specimen, regardless of the
immunization history, suggests virus infection.
Lab Test (post mortem)
Both for animals and people.

Negri body in a Immunofluorescence

brain section of brain stem cells
Children are more likely to be bitten in high-
risk sites, such as the head and neck
Treatment
no proven antiviral therapy and no
licensed anti-viral drugs for rabies
suggested therapeutic interventions

designed to protect the brain from

injury, while waiting for the host
immune response to clear the virus
Milwaukee protocol
Induction of therapeutic coma to reduce
putative excitotoxicity : ketamine, a
dissociative anesthetic agent; at high
concentrations, ketamine may also inhibit
rabies virus replication in vitro or in animal
models. Benzodiazepines and barbiturates
have also been used in this protocol
Intensive supportive care
Use of drugs with potential antiviral activity
(eg, ribavirin, amantadine)
Therapeutic blockade of cerebral artery spasm
Rabies Post-Exposure
Prophylaxis (PEP)
Vaccine supply has been limited:
reserve for truly exposed
Cleanse wound immediately.
When needed, administer PEP as

soon after exposure as possible.

Rabies immunoglobulin: one dose
5 doses of rabies cell culture

vaccine
Animal Bites: Wash wounds and seek
medical consultation - especially those
from bats, wild animals and foreign dogs

Control rabies in pets:

Vaccinate pets
Keep pets away from wildlife (bats, raccoons..)
Follow leash laws
Control strays

Wildlife:
Avoid contact with sick
and injured wild animals.
Dont feed, handle or translocate wildlife
 Rabies immunoglobulin :"passive immunization";
rabies vaccine: "active immunization".

Vaccine alone is given for preexposure prophylaxis

Postexposure rabies prophylaxis, in previously

unimmunized persons, should always include both

passive and active immunization.
Vaccine alone is indicated in persons who have had

preexposure prophylaxis with rabies vaccinewith a

documented neutralizing antibody response.
Wound care
Thorough washing of bite wounds,
scratches, and non-bite exposures with
soap and water is recommended, if
feasible.
When available, a virucidal agent such

as povidone-iodine should also be used.

In animal studies of rabies, wound

cleansing alone reduced the likelihood of

rabies up to 90 percent
Vaccine
Human diploid cell vaccine (HDCV) & Purified chick embryo
cell vaccine (PCECV)
WHO guidelines still recommend a five-dose schedule for

intramuscular rabies immunization for category 2 or 3

exposures (days 0, 3, 7,14, 28) but now cite the four-dose
intramuscular schedule (days 0, 3, 7 and 14) as an
alternative for exposed people who receive wound care
plus high-quality RIG plus rabies vaccine.
Another alternative four-dose regimen (two doses on day 0,

and one dose on days 7 and 21) is sometimes used for

category 2 exposures, when postexposure treatment does
not include administration of RIG.
five-dose schedule in immunocompromised hosts
TERIMA KASIH