Rabies Virus: Virology, Pathogenesis, Clinical Presentation, and Prophylaxis

Comprehensive review flashcards covering the historical perspective, taxonomy, viral structure, reservoirs, pathogenesis, clinical progression, diagnostic hallmarks, and post-exposure prophylaxis (PEP) protocols for rabies.

To which viral genus and family does the rabies virus belong?

The rabies virus belongs to the genus Lyssavirus within the family Rhabdoviridae.

What is the historical origin and linguistic meaning of the word "rabies"?

It originates from the ancient Indian Sanskrit word "rabhas", dating to 3000 B.C., which means "to do violence".

Who developed the first rabies vaccine, and who was the first patient successfully saved by it in 1885?

Louis Pasteur developed the first rabies vaccine using desiccated rabbit spinal cord and saved 9-year-old Joseph Meister in 1885 after 13 injections.

What structural and genomic characteristics define the rabies virion shown in this diagram?

It is an enveloped, bullet-shaped virus measuring $180 \times 75\,\text{nm}$ containing an unsegmented, linear negative-sense single-stranded RNA genome, matrix protein, nucleoprotein N, and knob-like glycoprotein spikes (G protein).

What are the primary animal reservoirs for rabies in Europe, Asia, and North America?

Europe: foxes and bats (sylvatic rabies); Asia: dogs (urban rabies); North America: foxes, skunks, raccoons, and insectivorous bats.

Which mammalian species are classified as susceptible "dead ends" for rabies transmission?

Beavers, woodchucks, pigs, humans, horses, cows, goats, and sheep.

What is the key virological difference between a "street virus" and a "fixed virus"?

A street virus is a naturally occurring virulent strain recovered from infected animals with a variable incubation period. A fixed virus is prepared by serial passage in rabbit brains, stabilizing its virulence and fixing a short, reproducible incubation period.

To which chemical agents and physical conditions is the rabies virus sensitive?

It is sensitive to ethanol, iodine, soap/detergents, ether, chloroform, and acetone. It is destroyed at $50^\circ\text{C}$ in 1 hour and at $60^\circ\text{C}$ in 5 minutes.

What cell receptor does the rabies virus glycoprotein bind to at the neuromuscular junction?

Nicotinic acetylcholine receptors (nAchR).

According to the pathogenesis pathway shown, by what mechanism and speed does the inoculated virus travel from peripheral nerves to the central nervous system?

The virus travels via retrograde fast axonal transport within peripheral nerves at a rate of $12\text{--}24\,\text{mm/day}$ to the spinal cord, followed by rapid ascent to the brain at $200\text{--}400\,\text{mm/day}$.

What is the earliest clinical neurological symptom and hallmark finding of rabies infection?

Pain, paresthesia, or fasciculations at or around the site of inoculation.

Why does rabies lead to fatal encephalitis without causing direct cytotoxicity or histological destruction of neurons?

Neuronal morphology and lifespan remain normal; death results from neurotoxic disruption of synaptic neurotransmission (affecting acetylcholine, GABA, and glycine receptor pathways), causing global neurological and autonomic dysfunction.

What are the four clinical stages of human rabies and their typical durations?

1. Incubation period (usually 20-90 days)
2. Prodrome phase (2-10 days)
3. Acute neurologic phase (2-7 days)
4. Coma (0-14 days), terminating in death.

What causes hydrophobia in 50% to 70% of patients during the acute neurologic phase of rabies?

Severe and violent pharyngeal spasms triggered upon attempting to swallow liquids, which produce choking and lead to an involuntary terror of water even when suffering intense thirst.

What pathognomonic diagnostic feature is indicated by the red arrow in this neural histological section?

A Negri body (a sharply outlined, eosinophilic cytoplasmic inclusion body measuring $2\text{--}10\,\mu\text{m}$ in diameter, diagnostic of rabies).

Where in the central nervous system are Negri bodies most abundantly found post-mortem?

In the pyramidal neurons of Ammon's horn (hippocampus), Purkinje cells of the cerebellum, cerebral cortex, brainstem, hypothalamus, and dorsal root spinal ganglia.

What was the experimental treatment protocol used to save unvaccinated patient Jeanna Giese in 2004?

The Milwaukee protocol, which utilized an induced coma combined with ketamine, midazolam, ribavirin, and amantadine to protect the brain while the patient generated an active immune response.

What initial local wound management is recommended immediately following a suspected rabid animal bite?

Flushing and scrubbing the wound thoroughly with soap and water for approximately 5 minutes, applying povidone-iodine or alcohol, and avoiding immediate suturing.

What serious adverse effect caused neural-tissue vaccines, such as the Semple vaccine (1911), to be replaced by modern cell-culture vaccines?

Severe neuroparalytic complications, including Landry-type ascending paralysis, caused by immune reactions to adult animal brain tissue.

Why is the gluteal region contraindicated as an injection site for rabies vaccine administration?

Injection into deep gluteal fat leads to lower antibody titers and significantly higher rates of vaccine failure; injections must be given intramuscularly in the deltoid region.

What is the correct dosing and administration guideline for Human Rabies Immunoglobulin (HRIG)?

A single dose of $20\,\text{IU/kg}$ body weight given within 7 days of exposure; infiltrate all or as much as possible around the wound site and inject the remainder intramuscularly (deltoid or thigh) distant from the vaccine site, never intravenously.

What defines a WHO Category II rabies exposure and what post-exposure prophylaxis measures are required?

Category II involves nibbling of uncovered skin or minor scratches/abrasions without bleeding; it requires immediate local wound treatment and immediate vaccination (no immunoglobulin).

What defines a WHO Category III rabies exposure and what post-exposure prophylaxis measures are required?

Category III involves single or multiple transdermal bites/scratches, licks on broken skin, mucous membrane contamination with saliva, or any contact with bats; it requires immediate local wound treatment, immediate vaccination, and rabies immunoglobulin administration.

On what date is World Rabies Day observed, and what is the World Health Organization's global elimination target?

Observed on September 28 (commemorating Louis Pasteur), with the global target of achieving "Zero human deaths from dog-transmitted rabies by 2030" ("Zero by 30").