Rabies

• Rabies is an acute infection of the central nervous system that is almost always fatal
• The virus is usually transmitted to humans from the bite of a rabid animal

  
• Although the number of human cases is small, rabies is a major public health problem because it is widespread among animal reservoirs

  
• The virus presents in the nervous system, saliva, urine, lymph, milk, and blood of infected animals

  
• Rhabdoviridae


  Family of viruses the rabies virus is classified in

  
• Lyssavirus


  Genus of rhabdoviruses that includes the rabies virus

  
• The rhabdovirus family involves a wide array of viruses with a broad host range infecting vertebrate, invertebrate, and plants

  
• Rabies is the only medically important rhabdovirus

  
• There is a single serotype of rabies virus

  
• Rabies virus


  • Rod- or bullet-shaped particles
  • Surrounded by a membranous envelope with protruding spikes composed of the viral glycoprotein
  • Inside the envelope is a ribonucleocapsid (helical nucleocapsid)
  • The matrix protein lines the envelope

  
• Genome


  Single-stranded, linear nonsegmented, negative-sense RNA
• Virion (nucleocapsid) contains an RNA-dependent RNA polymerase
• Replication

  Cytoplasm; virions bud from plasma membrane

  
• Rabies virus pathogenesis


  1. Multiplies in muscle or connective tissue at the site of inoculation

  2. Enters peripheral nerves at neuromuscular junctions and spreads up the nerves to the central nervous system

  3. Can also enter the nervous system directly without local replication

  
• Rabies virus multiplies in the central nervous system and progressive encephalitis develops

  
• The virus then spreads through peripheral nerves to the salivary glands and tissues

  
• The organ with highest titers is the submaxillary salivary glands

  
• Rabies virus has not been isolated from the blood of infected persons

  
• There is a higher attack rate and shorter incubation period in persons bitten on the face or head; the lowest mortality occurs in those bitten on the legs
• Rabies virus


  • Produces a specific eosinophilic cytoplasmic inclusion, the Negri body, in infected nerve cells
  • Negri bodies are filled with viral nucleocapsids
  • The presence of such inclusions is a diagnostic feature of rabies but is not observed in at least 20% of cases

  
• The absence of Negri bodies does not rule out rabies as a diagnosis

  
• Rabies


  Primarily a disease of lower animals spread to humans by bites of rabid animals or by contact with saliva from rabid animals

  
• Incubation period


  Typically 1–2 months in humans, usually shorter in children than in adults
• Clinical spectrum of rabies

  • Prodromal phase
  • Acute neurologic phase
  • Coma

  
• Prodromal phase


  May show any of the following nonspecific symptoms: malaise, anorexia, headache, photophobia, nausea and vomiting, sore throat, and fever
• Acute neurologic phase


  Lasts 2–7 days, patients show signs of nervous system dysfunction such as nervousness, and hallucinations, a large fraction will exhibit hydrophobia (fear of water)
• This phase is followed by convulsive seizures or coma and death, the major cause of death is respiratory paralysis
• Diagnosis


  Based on detecting virus or viral RNA in saliva, neck skin biopsy or epithelial cells of the cornea

  
• Fluorescent antibody test (FAT)


  The most widely used method for diagnosing rabies infection in animals and humans, considered the gold standard

  
• First aid for animal bite

  1. Wash and flush wound immediately with soap and water for 10–15 minutes

  2. Clean thoroughly with 70% alcohol/ethanol or povidone-iodine, if available

  3. Take the person to a healthcare facility for further treatment as soon as possible
• Avoid applying irritants to the wound, covering the wound with dressings or bandages, and suturing of the wound
• There is no successful treatment for clinical rabies

  
• Post-exposure treatment (PEP)


  Includes inactivated rabies virus (Killed vaccine) + Human Rabies immune globulin (HRIG)

  
• Rabies PEP vaccinations


  1. Dose of human rabies immune globulin and four doses of rabies vaccine given on the day of the exposure, and then again on days 3, 7, and 14

  2. Vaccine is given in a muscle, usually in the upper arm

  
• Pre-exposure vaccination

  Desirable for all persons who are at high risk of contact with rabid animals, such as veterinarians, animal care personnel, certain laboratory workers

  
• Pre-exposure vaccination schedule

  One dose of vaccine administered intramuscularly on each of days 0, 7 and 21 OR 28
• Rabies is included in WHO's new 2021-2030 road map, as a zoonotic disease it requires close cross-sectoral coordination at the national, regional and global levels

  
• WHO is working on the achievement of zero human deaths from dog-mediated rabies by 2030

  
• Neurotropic virus


  Can infect neuronal cells, infection may occur by neural or hematogenous spread initiating from a peripheral site

  
• Types of viral infection of the nervous system

  • Viral encephalitis
  • Viral meningitis
  • Viral myelitis