RABIES taxonomy
Family: Rhabdoviridae
Order: Mononegaviraes
Genus: Lyssavirus
The genome of rabies virus
Linear (-) non segmented ssRNA, encodes 5 proteins (GLMNP)
Viral particle of rabies virus
Bullet-shaped
Helical nucleocapsid
Antigenic properties of rabies
Purified spikes (elicits antibodies) Antiserum against purified nucleocapisd (immunofluirescence)
How can you control rabies virus in the lab?
CO2 Trypsin Lipid solvents (0.1% sodium deoxycholate and ether) Heat (50C for 1 hr) UV rad or sunlight
T or F: all warm-blooded animals are susceptible to rabies
True
Natural reservoir of rabies
Bats and raccoons
T or F: the rabies virus can only be found in the blood
False, it is widely disseminated. Found in Nervous system, saliva, lymph, blood, urine, and milk
T or F: the bite of a rabid animal gives you a 20x greater chance of acquiring rabies than scratches
F 50x
Human-human transmission of rabies t or f
??? Not yet confirmed
How does rabies virus enter the body?
Adsorption
This step of the rabiesviral replication comes after uncoating wherein mRNAs are syntheisized and is important in order to replicate inside cell
Transcription
This step of the rabies viral replication process involves synth of 5 stuc proteins
Translation
G-protein glycosylation in rabies
Processing step (after translation)
How does rabies exit?
Budding
Preferred site of rabies virus in the CNS
Brain stem and medulla
Responsible for rabies viral replication in CNS
Endoneurium of schwann cells and associated spaces in sensory nerves
**reason why infected dog brains are examined
When is saliva infectious in rabies
Two weeks before appearance of signs
Other sites where rabies can replicate, produce cellular infiltrates and cause necrosis
Salivary glands and cornea
Effects of rabies on the body
Hyperemia
Nerve cell destruction in midbrain, basal ganglia, cortex, pons and especially the medulla
Degeneration of axons and myelin sheaths
Demyelinization in white matter
Posterior horns of spinal cord: neuronophagia and Cellular Infiltrates: mononuclear, perineural, perivascular
IP in dogs rabies
3-8 weeks, can be 10 days
Rabies IP in humans
30-90 days
*shorter in children than adults
Clinical stages of rabies virus in dogs
Prodromal
Excitative Paralytic
This stage in dogs is characterized by fever and sudden change in behavior
Prodromal
This stage in dogs is the most dangerous. Marked by irritability, restlessness, nervousness, exaggeration of response to light and sound, convulsive seizures, difficulty swallowing
Excitative
T or F: All rabid dogs undergo excitative phase
False, can be skipped
This stage in humans is marked by non-specific symptoms, pain or paresthesia in the inoculation site and involvement of symptoms in respiratory, GI, and CNS
Prodromal phase
**other symptoms
Agitation Photophobia Priapism (persistent & painful penile erection) Increased libido Depression Insomnia Nightmares Encephalitis Brain conditions Psychiatric disturbances
Begins with signs of CNS dysfunction in humans
Acute neurologic period
Form of acute neurologic period characterized by hyperactivity, hydrophobia and aerophobia
Furious (classic or encephalitis)
This form of acute neuro period in humans is marked by paralysis
Dumb rabies
T or F: microscopic examination of rabies is done through light microscopy
False, immunofluorescence of infected using anti-rabies hamster serum
Usual specimen if rabies virus
Cornea and brain
Definitve diagnosis of rabies in microscopy
Presence of negri bodies in brain or spinal cord
**not found in all cases
Considered as gold standard in diagnosing rabies virus
Isolation of virus
In virus isolation, what is usually observed for?
Rabies antigen and negri bodies
It is a serially passaged strain that cannot produce disease in animals so it is used for vaccination (LAV); found in chick embryos
Flury strain
T or F: rabies virus can still be extracted in dead humans for PCR
False
Why is immunogenic vaccine or antibody applied immediately
To prevent CNS invasion
To provide more time for stimulation of antibodies before CNS invasion
Immunization regimen for persons with high risk exposure to rabies
Pre-exposure (involves HDCV and DEV)
This immunization regimen involves thorough cleansing of the wound, administration of RIG and ARS and immunization with HDCV or DEV
Post-exposure
T or F: All rabies vaccines administered to humans contain inactivated rabies virus
True
Where is HDCV grown from?
WI-38 human normal fibroblast cell line (free of nervous system and foreign proteins (concentration of virus: ultracentrifugation then it is inactivated with tri-N-butyl phosphate, or Beta-Propiolactone)
Fetal rhesus monkey lung diploid cell line
It is sufficiently antigenic and elicits greatest efficacy in antibody response. 4-6 doses are needed.
HDCV
- pre-exposure: 3 times 1 ml
- post-exposure: 5x 1 ml
Developed to minimize post-vaccinal encephalitis, has low antigenicity and can be administered 3-25 times subcutaneously.
DEV
**needs multiple doses
Pre-exposure: 3-5x of 1 ml
Post-exposure: 16-25x of 1 ml
Rabies glycoprotein is inserted into vaccinia virus; orally given
Recombinant virus vaccine
It is prepared via cold ethanol fractionation of plasma of hyperimmunized individual. Dose: 20 IU/kg (intramuscular and around bite)
Rabies Ig
Concentrated horse serum that were hyperimmunized with the rabies virus
ARS, equine
Dose: 40 IU/kg
Factors to consider in administering post exposure prophylaxis
Nature of animal -HDCV and RIG Existence of Rabies in area Manner of attack and biting severity Advice
PEP measure if contact with suspected rabid animal: Touching/feeding animals Licks on intact skin
None
PEP if contact is nibbling and minor scratches and abrasions
Immediate vaccination
Local wound treatment
PEP if contact is: Single/multiple transdermal bites/scratches
Licks on broken skin
Contamination of mucous membrane with saliva from licks
Contact s with bats
Immediate vaccination
Administration of Ig
Local wound treatment
(3rd category)