Rabies

Rabies Virus

General Information

  • Rabies (Hydrophobia)

    • Caused by an RNA virus.

    • Untreated mortality rate is almost 100%.

    • A rabies vaccine is available for both prevention and early treatment.

Forms of Rabies

  • Two lethal forms of rabies described:

    • Furious rabies (approximately 80% of cases):

    • Involves the brain.

    • Characterized by aggressiveness, excitability, and foaming at the mouth.

    • Paralytic or dumb rabies:

    • Primarily involves the spinal cord.

    • Animals exhibit weak limbs and are unable to raise their heads or make sounds due to paralysis of neck and throat muscles.

Rabies Virus Characteristics

  • Type: Viral infection.

  • Nature: Slow, progressive zoonotic disease.

  • Outcome: Fatal without treatment.

  • Distinct Pathogenesis and Symptoms.

  • Structure: Bullet-shaped virus.

Historical References

  • Bram Stoker:

    • Published Dracula in 1897.

    • Major rabies epidemic in the Balkans associated with rabies in dogs, wolves, and other animals.

Disease Correlations

  • Hypersensitivity to elements: Water, light, and odors.

    • Symptoms include spasms of facial and vocal muscles leading to hoarse sounds, bared teeth, and frothing saliva.

  • Garlic:

    • Used in ancient times for warding off evil and for medicinal purposes (as a repellent).

  • Site of the bite:

    • Disease outcome significantly affected by the location of the bite.

    • A man's tendency to bite in fighting and sexual activities noted.

  • Psychological symptoms:

    • Insomnia, hallucinations, and delirium due to brain infection affecting emotions and sleep patterns.

    • Hypersexual activity reported among rabid patients, characterized by extreme sexual behavior (up to 30 times a day).

  • Mirror reflection:

    • Traditionally, a man was not considered rabid if he could look at his own reflection, associating vampires with the idea that they do not have reflections.

  • Connection to Vampires:

    • Association of vampires with wolves and bats stems from their susceptibility to the disease.

    • Aggression linked to the biting behavior induced by rabies.

Rabies Epidemiology in the USA

Zoonotic Disease Overview

  • Reservoir hosts include:

    • Coyotes, Skunks, Foxes, Raccoons, and Bats.

  • Significant historical reference to Louis Pasteur in 1885 concerning rabies.

  • In the USA, most cases are associated with wildlife.

  • Annual incidents: approximately 2,500 cases per year.

Case Study: Bites and Symptoms

  • Incident Description:

    • A family reported an encounter with a bat occurring approximately 4-6 weeks before the onset of symptoms.

    • Patient caught the bat, which bit him on the left ear after crawling on his arm and neck.

    • Patient informed family about rabies but did not report the incident to health authorities or seek medical care, instead releasing the bat after 2 days.

Milwaukee Protocol Case Study

Jenna Giese's Case

  • Incident Description:

    • On September 12, 2004, Jenna Giese, a 15-year-old, picked up a bat, sustaining a small bite on her left index finger in Fond du Lac, Wisconsin.

    • 37 days after the bite, developed neurological symptoms: fever (102°F / 39°C), double vision, slurred speech, jerking in the left arm.

  • Medical Intervention:

    • Admitted to St. Agnes Hospital.

    • Developed by pediatrician Dr. Rodney Willoughby, coined the Milwaukee protocol:

    • Medically induced coma and treatment with an anesthetic (ketamine) that has some antiviral effect.

    • Followed treatment with antiviral medications: amantadine and midazolam, and added ribavirin after three days.

Outcomes and Controversies

  • After seven days, increased antibodies observed in blood serum and cerebrospinal fluid.

    • Reasons for Giese's survival are debated:

    • Infection with a weak virus strain?

    • Bite location far from the brain allowing immune response time?

    • Absence of live virus in body upon hospital admission?

    • Uncertainty regarding other patients’ outcomes and host genetics.

Rabies Virus Structure and Pathogenesis

Structure

  • Rabies virus as a (-) stranded RNA virus (antisense) classified in the Rhabdoviridae family.

  • Characteristics:

    • Enveloped virus.

    • RNA genome encodes five proteins:

    • Nucleoprotein (N)

    • Phosphoprotein (P)

    • Matrix protein (M)

    • Glycoprotein (G)

    • Polymerase (L)

Pathogenesis

  • Transmission predominantly through bites of infected mammals.

  • Virus can enter the peripheral nervous system directly or replicate in muscle tissue post-entry.

  • Upon reaching the spinal cord, the virus rapidly migrates to the brain, leading to irreversible and fatal symptoms.

  • Subsequently infects various tissues and organs, notably salivary glands, facilitating virus exit through saliva.

Human Transmission

  • Rare cases of human-to-human transmission have occurred, such as through corneal transplants.

  • Diagnosis Methods:

    • Immune fluorescence detection in brain tissue, or historically by identifying Negri bodies during histology.

Transmission Modes

Overview of Transmission

  1. Bite or Scratch:

    • Indicative of 70% transmission rates.

    • In the U.S., human cases primarily due to rabid bat bites. In Southeast Asia, rabid dog bites predominate.

  2. Aerosol Transmission:

    • Accounts for approximately 25% of cases from infected bats.

    • Must enter a wound or mucous membranes, such as eyes, nose, or mouth.

  3. Transplants:

    • About 5% of cases result from tissue or organ transplants from infected humans.

Incidence Rates by Bite Location

  • Likelihood of contracting rabies varies significantly by bite location:

    • Face: 60% chance of contracting rabies.

    • Upper Extremities: 15% to 40% chance.

    • Lower Extremities: 5% to 10% chance.

Ecological transmission and Epidemiology

Incubation Period

  • Typically ranges from 20 days to 2 months, but can be as short as a few days or extend beyond 6 years.

    • Influenced by various factors including:

    • Site of the bite (proximity to the central nervous system).

    • Severity of the bite.

    • Type of viral isolate.

    • Amount of virus introduced.

    • Age of the patient.

    • Immune status of the individual.

Symptoms

  • Initial symptoms may include:

    • General discomfort, nervousness, anxiety, insomnia, depression and apathy.

    • Localized pain at the bite site, fever, chills, cough, sore throat, headaches, nausea, and vomiting.

  • Neurological symptoms typically arise within 2 to 10 days after initial symptoms.

  • Rabies manifests in two forms:

    • Furious rabies.

    • Paralytic or dumb rabies (particularly from bat exposure).

Vaccination Schedule

Vaccination Procedure

  1. Pre-Exposure Vaccination:

    • For travel or occupational exposure, the schedule involves three doses:

      • Dose 1: Administered as appropriate.

      • Dose 2: 7 days after Dose 1.

      • Dose 3: 21 or 28 days after Dose 1.

  2. Post-Exposure Vaccination: a) For those unvaccinated against rabies:

    • 4 doses of rabies vaccine recommended: immediately (first dose), then additional doses on the 3rd, 7th, and 14th days.

    • Rabies Immune Globulin administered simultaneously with the first dose.
      b) For previously vaccinated individuals:

    • 2 doses of rabies vaccine recommended: first dose immediately, 3rd-day follow-up.

    • No Rabies Immune Globulin necessary.