Rabies

Question 1

What’s rabies infection?

Answer 1

• Rabies is an acute, fatal CNS infection caused by the rabies virus, the only medically important member of the Rhabdoviridae family.
• It has a broad host range (infects all mammals), but only specific animals (e.g., dogs, bats, foxes) are common sources of human transmission.

Question 2

What’s the structure of rabies virus
And which among the are the key for immune recognition and vaccine targets

Answer 2

• The virus structure:
• Single-stranded, negative-sense RNA genome
• Enclosed in a bullet-shaped capsid
• Surrounded by a lipoprotein envelope
• Glycoprotein spikes on the envelope are the sole antigenic determinants — key for immune recognition and vaccine targets
  
  • Carries RNA-dependent RNA polymerase to initiate transcription upon entry

Question 3

Explain the Replication Cycle of Rabies virus

Answer 3

Replication Cycle (Key Clinical Insights)

1. Attachment:
   • Virus binds to acetylcholine receptors on neuronal or muscle cell membranes.
     ➡️ Explains tropism for neuromuscular junctions and CNS.
2. Entry:
   • Enters via endocytosis and fusion with host cell membrane.
3. Transcription:
   • Viral polymerase transcribes genome into five mRNAs coding for structural and functional proteins.
     ➡️Host machinery is hijacked without integrating into host DNA.
4. Genome replication:
   • Full-length copies of the viral genome are synthesized.
5. Assembly:
   • New nucleocapsids are formed in the cytoplasm.
6. Budding:
   • Virus acquires envelope and spikes by budding through the plasma membrane.
     ➡️ This step is non-lytic, so infected neurons remain intact for a while—contributing to the long incubation period.

Question 4

What are the possible method of Transmission

Answer 4

• Main route: Bite from a rabid animal, especially dogs in developing countries.
  ⏩ The virus is present in saliva and gains entry through broken skin.
• Other sources:
  • Bats, cats, raccoons (wild reservoirs)
  • Aerosolized virus from bat caves (rare but documented)
• Aggressive biting behavior in infected animals is due to viral encephalitis.

Question 5

Explain the Pathogenesis (with “why” explained)

Answer 5

1. Local replication at the bite site.
   ⏩ Why? It buys time to infect nearby nerves before immune response kicks in.
2. Entry into sensory neurons, travels retrograde via axons to CNS.
   ⏩ This is why incubation depends on distance of bite from brain.
3. CNS involvement:
   • Virus multiplies in the brain causing encephalitis
   • Neuron death and demyelination explain confusion, seizures, paralysis
4. Anterograde spread via peripheral nerves to salivary glands, eyes, skin.
   ⏩ Explains presence of virus in saliva—facilitates transmission.
5. Negri bodies:
   • Eosinophilic inclusions in neurons (diagnostic)

Question 6

Clinical features
Incubation period

Answer 6

Clinical Features

• Incubation period: 2 to 16 weeks or longer
  ⏩Shorter if bite is close to head or richly innervated area.
• Prodrome (early signs):
  • Fever, malaise, anorexia
  • Paresthesia or pain at bite site (unique and helpful sign)
• Neurologic phase:
  • Confusion, agitation, excess salivation
  • Hydrophobia: painful spasms during swallowing due to brainstem involvement
  • Aerophobia, photophobia (seen in furious rabies)
• Terminal stage:
  • Seizures, paralysis, coma
  • Death occurs without intensive care—few survive

Question 7

Diagnosis of Rabies

Clinical diagnosis is critical—most cases are suspected based on symptoms and exposure history. Laboratory confirmation helps but often comes late.

Question 8

What are the lab diagnostic methods for rabies

Answer 8

Diagnostic Methods

• Fluorescent antibody test:
  ⏩ Detects viral antigen in a skin biopsy from the nape of the neck (hair follicles).
• Virus isolation:
  ⏩ From saliva, CSF, or brain tissue—used in reference labs.
• Serology:
  ⏩ Rising antibody titers (paired sera) indicate infection, especially post-vaccination.
• Negri bodies:
  ⏩ Eosinophilic inclusions found in brain autopsy, sometimes in corneal scrapings.

Question 9

What are the possible treatment for rabies

Then it’s preventive regiments

Answer 9

Treatment

• No effective antiviral exists once symptoms appear.
  ⏩Mortality is nearly 100%.
• Supportive care only:
  ⏩ ICU support, ventilatory care, fluid and electrolyte management.

Prevention
Preexposure Prophylaxis

• Indicated for:
  • Veterinarians
  • Zookeepers
  • Travelers to endemic areas
  • Lab staff working with rabies virus
• Schedule:
  • Three doses on days 0, 7, and 21 or 28
  • Booster doses based on antibody titers (keep ≥1:5)

Postexposure Prophylaxis (PEP)

• Key principle: Begin immediately after exposure—before symptoms start.
• Components:
  • Rabies vaccine (HDCV):
    ⏩ Five intramuscular doses on days 0, 3, 7, 14, and 28
  • Rabies immune globulin (RIG):
    ⏩ Given once on day 0, injected around the wound and distant from vaccine site
  • Tetanus booster:
    ⏩ Given if immunization status is incomplete
• If patient was previously vaccinated:
  ⏩Give 2 booster doses of HDCV (days 0 and 3); no RIG needed