RABIES

What is rabies?

Rabies, also known as

hydrophobia is an

acute, highly fatal viral disease of the CNS (brain and spinal cord), cause by Lyssavirus type 1.

Rabies

The leading viral zoonosis as regards global public health significance.

It is primarily a disease of warm blooded animals particularly carnivorous such as dogs, cats, jackals and wolves.

The virus is secreted in saliva, and is usually transmitted when an infected animal bites another animal or person.

Geographic Distribution

Rabies is distributed on all continents (with the exception of Antarctica)

Canine rabies continue to exist in 87 countries or territories of the world and this accounts for 99% of all human rabies cases.

Geographic Distribution

Globalization may threaten the disease-free status of many localities, due to the introduction of rabid animals It is estimated that more than 55,000 people die from rabies every year, mainly in Asia and Africa. Children are especially at risk from rabies.

Etiology

Rabies results from infection by the rabies virus, a neurotropic virus in the genus Lyssavirus, family Rhabdoviridae. It is classified as genotype 1, serotype 1 in this group. There are many strains of the rabies virus, with each strain maintained in particular reservoir host(s)

Rabies virus
Rabies is a Lyssavirus in the family Rhabdoviridae Lyssaviruses: Australian Bat Lyssavirus European Bat Lyssavirus -1 European Bat Lyssavirus -2 Duvenhage virus Mokola virus Lagos Bat virus Rabies virus

Lyssavirus

distinctive rod- or bullet-shaped morphology. -ve sense, non-segmented, ssRNA helical virus measuring approximately 60 nm x 180 nm It is composed of an internal protein core or nucleocapsid, containing the nucleic acid, and an outer envelope, a lipidcontaining bilayer covered with transmembrane glycoprotein spikes

Fig. Virion structure of rabies virus.

Transmission of Rabies

Is zoonotic disease, and most commonly contracted from the bite of an animal that is infected with the virus. The virus is found in the saliva of the infected animal.

Transmission of Rabies

Can also enter via any mucous membrane, such as the eye, nose or mouth. Handling and skinning of infected animal carcasses. Few cases of human to human transmission. Can be transmitted via aerosol, but thats also uncommon.

Transmission of Rabies

Transmission of Rabies
The rabies infection and the symptoms that accompany it is classified by five stages: 1. Incubation (1-3 months) 2. Prodromal, where first symptoms occur 3. Acute neurological phase 4. Coma 5. Death or recovery

Transmission of Rabies
1.

Incubation
The animal or human is bitten by rabid animal.
Rabies enters the body via the saliva of the infected animal.

The virus binds to nerve or muscle cells at the site of the inoculation via nicotinic acetylcholine receptors. Here the virus can remain for a prolonged period of time (up to several months). The virus can replicate in muscle cells at the site of the bite with no obvious symptoms.

Transmission of Rabies
2. Prodromal Stage

The virus then moves along the nerve axons to the central nervous system using retrograde transport. The virus arrives at the dorsal root ganglion of the spinal cord. This is where the immune system detects the virus and starts creating antibodies. First symptoms are felt: fever, muscle ache, agitation, anxiety, nausea, vomiting, ache in the bitten extremity. From this point the virus replicates and travels up to the brain, and the immune system cant keep up with fighting the virus.

Transmission of Rabies
3. Acute Neurological Stage

Infection of the brain leads to encephalitis . Involvement of the brain leads to coma and death. This is the neurological phase and during this period, the virus can spread from the central nervous system, via neurons, to the skin, eye and various other sites (adrenals, kidneys, pancreatic acinar cells) and the salivary glands Symptoms include: Fluctuation between consciousness and confusion, Aggressive behavior, violent episodes, Convulsions and seizures, Hallucinations, Hydrophobia, Aerophobia, Sensitivity to lights, sounds and smells ,Respiratory spasms.

Transmission of Rabies
4.
-

Coma
Spasms decrease because paralysis occurs Heart arrhythmias and irregular heartbeat persist Cerebral encephalitis causes major organs to collapse Fixed pupils that are unresponsive to light

5. Death or Recovery
- Death results from encephalitis of the brain. - Heart failure along with major organ failure are the main causes of death. - Only four known cases of human recovery, and they were permanently brain damaged.

RABIES DIAGNOSIS

Based upon history of animal exposure and typical neurological clinical signs The reference method for diagnosing rabies is by performing PCR or viral culture on brain samples taken after death.

Diagnostic Techniques
Histological examination for Negri bodies
-negri bodies are cytoplasmic masses of viral nucleocapsids found in the brain tissue -problem is that negri bodies are only present in 20% of rabies
Negri body

Diagnostic Techniques

Antemortem diagnosis may include virus isolation, antigen detection or serology. More than one test is usually necessary for a diagnosis. RT-PCR may be able to detect the rabies virus in serum or CSF. Viral antigens may also be detected, using RT-PCR or immunofluorescence, in skin biopsies taken from the nape of the neck; the antigens are found in the cutaneous nerves at the base of the hair follicles.

Pre- and Post-exposure Prophylaxis

Pre-exposure Prevention
1.

2.
3.

4.

Avoid contact with wild animals Do not handle dead animals People that work with wild or domestic animals should be vaccinated Vaccination of domestic and reservoir wild animals

POSTEXPOSURE PROPHYLAXIS (PEP)

Provided to subjects after rabies exposure Consists of wound care, rabies immune globulin, and vaccine

RABIES BIOLOGICALS

Rabies Vaccines (for pre- and PEP) Rabies immunoglobulin (only in PEP)

Main Types of Vaccines

1.

Brain-tissue vaccine
-synthesized from infected brain tissue originally by Pasteur -use both adult and suckling mammal brain tissue (SMB) -causes neural complications
associated with immune response to neural antigens and foreign proteins contained in the vaccine these complications are lower in SMB vaccine relatively cost-effective 90% of human vaccination still uses this

2.

Cell-culture vaccine
-prepared from supernatant of virus-infected cells -two main types
a. chicken-embryo
major neurological complications due to embryo antigens not generally used in U.S. for this reason

b. human-diploid cell vaccine

virion preparations grown in human diploid cells requires fewer doses and causes fewer complications used as standard for preparation of other vaccines very costly

3.

Genetically engineered vaccines

-the goal is to conserve the antigenic structure of the G-protein, while reducing its pathogenic ability -the recombinant G-protein is modified in such a way that:
it is almost identically similar to challenge virus it decreases viral uptake, and/or prevents budding, and/or stimulates high expression of the G-protein

-induces high levels of neutralizing antibodies, allowing protection against several rabies strands -safe, potent, cost-effective -but through recombinant processes in body, wild-type virus could be regenerated

RABIES IMMUNE GLOBULIN

In passive vaccination, rabies immune globulin (RIG) from adults who have been immunized with rabies vaccine is administered to previously unimmunized people so as to passively impart antibodies.