Rabies virus

Virology & Morphology - Bullet-Shaped Menace

• Family: Rhabdoviridae; Genus: Lyssavirus.
• Genome: Enveloped, single-stranded, negative-sense RNA virus.
• Key Feature: A helical nucleocapsid is coiled into a pathognomonic bullet shape, a crucial identifier.
  • Virulence Factor: Glycoprotein (G) spikes on the envelope mediate neurotropism by binding to host cell receptors like the nicotinic acetylcholine receptor (nAChR).

⭐ The distinct bullet-shaped morphology is a classic, high-yield visual identifier for Rabies on board exams.

Pathogenesis - A Slow, Deadly Climb

• Entry: Virus inoculated via bite replicates locally in muscle tissue.
• CNS Invasion: Binds to nicotinic acetylcholine receptors (nAChR) at the neuromuscular junction.
• Travel: Utilizes retrograde axonal transport to reach the central nervous system (CNS).

⭐ Histologic Hallmark: Eosinophilic intracytoplasmic inclusions, known as Negri bodies, are pathognomonic for rabies. Found primarily in pyramidal neurons of the hippocampus and Purkinje cells of the cerebellum.

Clinical Presentation - Fear of Water

• Hydrophobia: A pathognomonic sign of furious rabies, triggered by the sight or attempt of drinking liquids.
• Mechanism: Involves agonizing, involuntary spasms of the pharynx, larynx, and diaphragm.
  • This leads to a terrifying inability to swallow, causing intense fear.
• Associated Signs:
  • Hypersalivation and difficulty swallowing saliva results in classic “foaming at the mouth.”
  • Aerophobia (fear of air drafts) can also trigger spasms.

⭐ The severe pharyngeal spasms mean even the thought of swallowing can provoke terror and laryngospasm, leading to respiratory distress.

Diagnosis & Histology - Finding Negri

• Antemortem (before death):
  • Direct fluorescent antibody (dFA) test on a nuchal (neck) skin biopsy is the gold standard.
  • Other samples: Saliva (RT-PCR), CSF & serum (for antibodies).
• Postmortem:
  • dFA test on brain tissue is the most definitive test.
• Histology:
  • Negri bodies: Pathognomonic eosinophilic intracytoplasmic inclusions.
  • Found in pyramidal cells of the hippocampus & Purkinje cells of the cerebellum.

⭐ Absence of Negri bodies does not rule out rabies!

Post-Exposure Prophylaxis - A Shot of Hope

• Immediate Action: Vigorous wound cleansing with soap and water.
• Unvaccinated Individuals:
  • Human Rabies Immune Globulin (HRIG): 20 IU/kg dose infiltrated around the wound.
  • Rabies Vaccine: 4 doses in deltoid muscle on days 0, 3, 7, and 14.
• Previously Vaccinated Individuals:
  • Rabies Vaccine only: 2 doses on days 0 and 3.

⭐ Never give HRIG to previously vaccinated individuals; it can blunt the anamnestic (memory) immune response.

High‑Yield Points - ⚡ Biggest Takeaways

• A bullet-shaped rhabdovirus transmitted by animal bites (bats, raccoons, skunks).
• Undergoes retrograde axonal transport to the CNS, causing fatal encephalitis.
• Classic symptoms include hydrophobia, aerophobia, and pharyngeal spasms.
• Pathognomonic finding: Negri bodies, which are eosinophilic inclusions in the cytoplasm of neurons.
• Post-exposure prophylaxis with rabies immune globulin and vaccination is critical and life-saving.