RABIES

It is a neurotropic virus contracted from bite of an infected animal. It is preventable by vaccine,

zoonotic and infectious. It is transmitted through the saliva of infected animals and it affects the
CNS.

Lyssavirus of family Rhabdoviridae. RNA virus, single stranded.The virus is a bullet-shaped

virion with single stranded RNA nucleocapsid core and lipoprotein envelope. The nucleocapsid
consists of Negri bodies which are normally found in the cytoplasm of infected neurons. It has a
marked affinity for nervous tissue and the salivary glands.

Substances that inactivate the virus

Detergents
Trypsin
X-rays
1% sodium hypochlorite
50-75% ethanol
Formaldehyde
Soap solution
Chloroform
Iodine preparations
Low pH
UV radiation
Povidone iodine
Drying(quick)
Ether

Transmission of the virus

The virus is transmitted through the saliva of an infected rabid animal via bites, scratches or
direct exposure of mucosal surfaces commonly from dogs. Others include fox, wolve, skunk,
bats, cats, ferret.
Through exposure to their CNS tissues
Through human to human organ transplants
There can be iatrogenic infection through improperly inactivated vaccine or while working in the
laboratory with the virus

NB: The virus cannot replicate in low temperatures. And this explains why the the lowest risk
species in terms of transmission is the opossum which thrives in winter regions where it's very
cold.

The bites of bats are most often inconspicuous

So someone in contact with a bat may not even know the person has been bitten so just the
presence of the bat is enough to warrant prophylaxis because bat bites are difficult to identify

Identifying a rabid animal

Examination of the brain tissue for negri bodies
Initially the animal may be restless, exhibit fear and it rapidly progresses to drooling(saliva
dripping form the mouth), foaming, snapping(gasping thing), and increased restleness-
described as furious syndrome. Some few animals may however be lethargic, described as
dumb syndrome
Others include;
Agitated behavior
Vicious behaviour
Weakness
Being docile (uncharacteristically)
Paralyzed
Fear of people
Inability to fly (mostly bats)

It is often said that rabid animals become aggressive when provoked

Aetiology
After a bite or an exposure, the virus is deposited in the muscle or subcutaneous tissue where it
remains for a long incubation period(20-90days), then it travels by retrograde axonal transport
along the spinal cord. It can bind to the post synaptic nicotinic acetylcholine receptors and move
along the axon to the CNS via retrogade flow. On getting to CNS, it replicates in the gray matter
and spreads along peripheral nerves centrifugally to virtually all organs and tissue systems, a
reason for its presence in the saliva of rabid animals
Points to note
- Virus attacks neurons
- it is initially hidden from immune responses
- when it moves into the CNS it amplifies greatly
- the action of the virus is in the synapse (neuromuscular junction)

Pathophysiology
Points to note
-If inoculum is high or after enough replication, or when exposure is direct to the neurons, the
viral particles bind to nicotinic receptors and are taken up along the neuron into the CNS
-Once the virus gets high up the neurons into the CNS proper, it is moved along quickly because
there are a lot of nicotinic receptors in the brain
-Then from the CNS, the sensory neurons and the ANS help to distribute the particles throughout
the body
-The virus is moved through the body by neurons, not the blood
-The viral particles bind to human RNA which make them evade immune response (seen as
normal body particles)
- The amino acid sequence of the viral particle resemble Acetylcholine usually (some have said it
may take after GABA as well)
-Also the closer the bite is to the brain, for instance the neck or head the quicker the fatal
symptoms manifest

So basically, movement of virus, site of injury to CNS to other body parts, all mediated by
peripheral nerves
It is important to note that once the virus climbs into the CNS and the symptoms start, our
vaccines and immunoglobulin cannot do anything
1. The vaccine will have to produce antibodies and the brain tissues don't have the capacity of
generating antibodies from vaccines
2. The immonuglobulin produces B lymphocytes and they cannot traverse an intact BBB. The
BBB is intact because there is little or no brain inflammation

Also, in the later stages of the disease, there is no more replication or actual virus, whatever
happens is from the neurons malfunctioning

Again, the virus doesn't destroy the integrity of the neuron, it just "poisons" it. CT scan or MRI
usually reveal normal brain tissue

Signs and Symptoms

Prodromal sypmtom: flu-like symptoms such as fever, malaise, local pain, headache, tingling at
site of bite, discomfort, paresthesia and pruritis

Encephalitis symptoms: hydrophobia, aerophobia, respiratory failure, CNS effects such as

aggressiveness, hallucinations, anisocoria

There are two clinical variants. The furious(classic) rabies and the dumb (paralytic) variety.
Dumb rabies presents with symmetrical ascending paralysis begining from the bitten extremity
and ending up in quadriparesis
Furious rabies presents with a prodomal phase followed by an acute neurologic phase which
presents with encephalitis, bizzaire behavior, confusion, seizures, autonomic dysfunction
(hypersalivation) and the classical symptoms of hyperexcitability, hydrophobia and aerophobia

So it starts with the incubation where the patient is usually asymptomatic, then to the prodromal
phase where you have the initial symptoms, then the acute phase (Encephalitis or furious rabies
or Paralysis or Dumb rabies) then the "Jesus take the wheel" phase

The incubation period can range from a few days to over a year but is usually between
20-90days but shorter if the bite was anywhere close to the CNS

Exposure
- A bite from any such animal that breaks the skin
- Contact between mucous membrane or broken skin and animal saliva

Risk factors
Lab workers handling live rabies virus
Traveling to an endemic area
Veterinary doctors
Veterinary students
Animal control officers
Park officers
Animal handlers
Spelunkers- cave evaluators

Diagnosis of rabies
-EEG
-CT
-MRI
-Direct fluorescent antibody test of a biopsy specimen obtained from the nape (back) of the
neck ( GOLD STANDARD)
-Indirect fluorescence assay
-Mouse inoculation technique-- reliably detects the antigen of the virus
-Tissue culture inoculation technique
-PCR- most specific and sensitive
Most apt sample-- brain tissue.
Others are: saliva, liver, spleen, urine, CSF

NB: The direct finds the rabies antigen and the indirect finds the antibody. The indirect may
even be positive after a vaccination, it doesn't necessarily tell that you have rabies so it can't be
classified as a diagnostic tool

Before a diagnosis is made though, it is paramount to consider the history of the animal bite,
and the animal itself, as well as any other form of exposure that there could have been

Management
Non pharmacological management
1. Flush wound for 15mins with water only or soap and water
2. Disinfect with detergent, ethanol, iodine or other viricidal substance
3. Dress wound appropriately but leave wound open because virus can't survive on dry surfaces
and in order to infiltrate properly with immunoglobulin

NB: There is no cure for rabies, all treatment is supportive once the symptoms start

Pharmacological management
Category II Rabies Vaccine
Category III Rabies Immunoglobulin and Rabies Vaccine

Pre exposure prophylaxis

1. The condition of the animal and the person exposed are important as to how the vaccine
and IG are to be given. If the animal is healthy, as in vaccinated, then it should be confined and
observed for 10 days. The victim likely doesn't need vaccine or immunoglobulin therapy
So we have the immunoglobulin (passive immunity) obtained from human sera of those
previously vaccinated or who have had the disease and produced antibodies and also the equine
(horse) sera which is rarely used because of increased side effects.
Then we have the vaccine itself (active immunity)
- The human diploid cell vaccine (HDCV) from humans
- The Chick Embryo Cell Vaccine (CECV)
The HDCV is mostly used and recommended
Administration
Immunoglobulin: from the first day till day 7, thus when rabies is suspected.
- 20IU/kg
- infiltrate around the wound and if there is excess give IM
- STG says 10IU/kg around the wound and 10IU/kg IM
(Whether the person has had preexposure prophylaxis or not)
- This should be given on the day of the bite or within 7 days of giving the vaccine
(The vaccine produces antibodies by the 7th day so if you've not given by then, there is no need
to)
Giving the remainder by IM is usually into the upper and outer side (anterolateral) of the thigh.
Injecting in the gluteus may result in lower antibody titers leasing to prophylactic failure
RIG should be injected into the wound site so that it attacks the rabies virus in the area and stop
or slow it's progression.

Other supportive management

Cardiac arrhthmias- antiarrhythmic drugs
Tranquillisers- agitation and hyperactivity
Seizures - BZD and Barbiturates
Hyperventilation- Oxygen supplementation and mechanical ventilation
Hypotension- fluid resuscitation and vasopressor therapy
CHF- fluid restriction, diuretics, digoxin

Vaccine: If the person has not been vaccinated before

- 1ml each time
- 5 doses per month
- day 0 (day of exposure)
- then days 3, 7, 14 and any day between 28 and 30

Post exposure prophylaxis

If the person has been vaccinated before (within the last 3 years)
- 1 ml each
- 2 doses
- Day 0 and any day between 3-7
The vaccine is given by IM into the deltoid or anterolatetal thigh (in children)
Never give both the IG and vaccine together or at the same site to prevent the RIG from
interfering with the immune uptake of the RV, in effect from neutralising it rendering it ineffective.

Pre exposure prophylaxis is given to individuals at high risk. Further booster doses are given
to people who remain at frequent risk every 2-3 years, that's if serum antibody is less than 1:5
dilution based on RFFIT results (Rapid fluorescent focus inhibition test). Checking for the serum
antibody titer is mostly for those travelling to enzootic areas to be sure they are adequately
protected
Individuals at low risk go for booster shots every 10 years

Antibiotic prophylaxis
-Stg suggests combination of amoxicillin and flucloxacillin
The injury is on the surface of the skin so it's likely to be infected by Staph and Strep. Staph
aureus is beta lactamase producing and is therefore resistant to amoxicillin but flucloxacillin has
anti beta lactamase activity which is why it's effective against staph aureus. -Amoxiclav alone
would also be an alternative to the combination
-Erythromycin is given to those who are allergic to penicillin

Anti tetanus is also given to all person with animal bite to prevent secondary infections