Rabies

epidemiology

• endemic >150 countries
• 55,000 deaths/year
  • mostly children in Asia and Africa
  • mainly in rural areas
• most endemic in India followed by Bangladesh and China as well as Pakistan

• Latin "rabere" = to rage, to rave
• Sanskrit "rabhas" = to do violence

pathogen

• family Rhabdoviridiae, genus Lyssavirus
  • Rabies lyssavirus
  • Duvenhage lyssavirus
  • European bat lyssavirus
• negative polarity, monostrand RNA virus
• enveloped
• 5 component proteins
  • N, P, M, G, L
  • G (glycoprotein) is ligand to cellular invasion
    • target of vaccine
  • human receptor: nAChR, NCAM, p75NTR - all developed only in nerve cells

responsible animals

• domestic animal - dog, cat in Asia and Africa
• wildlife - bat, fox, raccoon, coyote in Europe and Americas
• Lyssavirus circulates within a same animal species
  • sometimes transmitted to other species - "spillover" phenomenon
• can infect all warm-blooded animals

pathophysiology

• retrograde fast axonal transport CNS 15-100mm/day
• spread from CNS to peripheral nerve
• incubation 4-13 weeks, occasionally up to 6 years
• despite catastrophic clinical outcome, histopathological changes in CNS are quite mild
  • macroscopically unremarkable
  • microscopically minimal changes characterized by perivascular cuffing of mild degeneration of neuron, microglial activation

transmission route to human

• 99.99% animal bites
• aerosol inhalation
  • in cave where infected bats live
• organ transplantation
• unrecognized exposure
  • ingestion of infected dog meat
  • butchering of infected dog

symptoms

1. prodromal symptoms 2-10 days
   1. itchy, tinglings, numbness around bitten site
2. acute neurological period 2-10 days
   1. furious rabies - 80%
      1. hydrophobia, aerophobia, hypersalivation, hallucination, high grade fever
   2. paralytic rabies - 20%
      1. urinary retention →incontinence, constipation
      2. hydrophobia uncommon - difficult to diagnose
   3. coma to death of 100%

• LANCET Rabies 1/3
• LANCET Rabies 2/3
• LANCET Rabies 3/3

diganosis

• most of cases are diagnosed postmortem
• history of animal bite
• histology of autopsy-obtained brain specimen
  • microscopic observation of Negri body
• immunofluorescnet
• RT-PCR of N gene

prevention

• PEP
• PreP