Rabies - Microbiology Notes

1. Classification

2. Morphology & Structure

3. Street Virus vs. Fixed Virus

• Street virus: Virus recovered from naturally occurring (wild) cases of rabies. It is pathogenic for all mammals, forms Negri bodies, and has a long, variable incubation period (20-60 days in dogs).
• Fixed virus (Pasteur strain): Produced by serial intracerebral passage of street virus in rabbits. The incubation period becomes fixed and constant at 4-6 days. It no longer forms Negri bodies, does not replicate in extra-neural tissues, and is used to prepare anti-rabies vaccines. Under certain conditions (e.g., inadequately inactivated vaccine), fixed virus can still be pathogenic. - Park's Textbook of Preventive and Social Medicine

4. Pathogenesis

Figure: Pathogenesis of rabies following peripheral inoculation (Harrison's 22E)

1. Inoculation - Virus enters through a bite wound, scratch, or mucosal contact with infected saliva.
2. Local replication - Virus replicates in muscle or connective tissue at the bite site.
3. Receptor binding - Virus binds to nicotinic acetylcholine receptors at neuromuscular junctions.
4. Centripetal spread - Virus travels via retrograde fast axonal transport (up to ~250 mm/day) along peripheral nerves toward the spinal cord and brainstem.
5. CNS infection - Rapidly disseminates through the CNS via axonal connections. Neurons are prominently infected; astrocyte infection is unusual.
6. Centrifugal spread - After CNS infection, virus spreads outward along sensory and autonomic nerves to salivary glands, skin, cornea, heart, adrenal glands, and other organs.
7. Salivary excretion - Virus replicates in acinar cells of the salivary glands and is shed in saliva (in dogs, virus appears in saliva 3-4 days before clinical signs). The submaxillary salivary gland has the highest viral titers.

5. Negri Bodies (Pathognomonic Finding)

Negri bodies in neuronal cytoplasm - H&E (A) and immunohistochemical stain (B) (CDC/Jawetz 28E)

• Negri bodies are eosinophilic, cytoplasmic inclusions in infected neurons composed of viral nucleocapsids (N protein + RNA).
• They are pathognomonic for rabies.
• Commonly found in Purkinje cells of the cerebellum and hippocampal neurons (pyramidal cells).
• Seen in only ~80% of cases - their absence does NOT rule out rabies.
• Absent in infections with fixed virus.
• Modern diagnosis relies on fluorescent antibody (FAT) and RT-PCR, which are more sensitive. - Jawetz Medical Microbiology 28E

6. Reservoir & Transmission

• Primary reservoir: Dogs (worldwide), bats (USA), raccoons, skunks, foxes.
• Transmission: Bite of a rabid animal (most common). Rarely through scratches, mucous membrane contact, or corneal transplants.
• Source of infection: Saliva of infected animals (virus present 3-4 days before symptoms in dogs/cats).
• All warm-blooded animals are susceptible. Rabies in humans is a dead-end infection (no survival value for the virus).

7. Incubation Period

• Usually 20-90 days (range: days to >1 year).
• Shorter in children than adults.
• Shorter when bite is on the face or head (shorter nerve distance to CNS) - highest attack rate.
• Lowest mortality when bitten on the legs. - Jawetz Medical Microbiology 28E

8. Laboratory Diagnosis

9. Vaccines

• Human vaccines contain only inactivated (killed) rabies virus (e.g., HDCV - Human Diploid Cell Vaccine, PCECV).
• Animal vaccines may contain live attenuated virus.
• Surface glycoprotein is the key immunogen - neutralizing antibody titers are the index of protection.
• Serum antibody titer is used to assess protection level. - Jawetz Medical Microbiology 28E; Park's Textbook

10. Key Microbiological Facts at a Glance