NS06-Rabies

Thomson

Characteristics of rabies

Family: belongs to family Rhabdoviridae

Structure: enveloped virus that is bullet shaped. Its genome is ssRNA

Proteins: encodes 5 proteins

Disease: Rabies, fatal neurologic disease if Postexposure Prophylaxis (PEP) not given timely

Ecology: virus is enzootic in variety of mammals

What is the cytopathic effect (CPE) found in the brain:

Negri bodies

Negri bodies are inclusion bodies made up of nucleocapsids

pathogenesis: bodies are found when neurons degenerate. They are typically detected via a brain biopsy post-mortem

How is rabies transmitted usually?

bite or scratch from an infected animal

where does rabies originate from in US? worldwide?

bats; dogs

Other ways rabies can be transmitted (non-bite exposures)

• scratches, abrasions, or wounds exposed to infectious saliva or material. The sources note that a bat scratch can transmit the virus

• mucosal membrane inoculation

• transplant of infected tissue

• aerosolization of infected virus, such as in caves inhabited by bats

How does rabies disease progress

rabies begin locally at site of infection and moves systematically towards CNS

1. initial local multiplication: after bite or scratch, virus multiplies quietly in cells at site of infection in human host

2. peripheral nerve entry: virus enters peripheral nerves, potentially involving both sensory and motor neurons

3. CNS travel and multiplication: virus travels retrograde (backward) up the spinal cord to the brain, where it multiplies, causing encephalitis (inflammation of the brain). During this stage in the brain, neurons degenerate, and Negri bodies are formed

4. outward spread (systemic dissemination): once in brain, virus spreads outward from the brain to other tissues. Notably, this includes salivary glands, eyes, fatty tissue under the skin, and vital organs like the heart.

Clinical stages of Rabies

1. Prodrome and early symptoms (2-10 days): paresthesias (tingling or burning), fever, malaise, anorexia, nausea and vomiting. Initial symptoms include pain and paresthesia near site of exposure

2. Neurologic phase (4-14 days): hallucinations, disorientation, seizures, agitation, and hydrophobia, followed by flaccid paralysis. Others can include insomnia, anxiety, confusion, slight or partial paralysis, excitation, difficulty swallowing, and hypersalivation.

3. Coma and Death (2-10 days): pt enters coma. Death is due to respiratory failure or cardiac arrest

what is the incubation period and what leads to the variability

incubation period for rabies infection is highly variable

duration: <30 days to >1 year

• approximately 50% of cases occur within 30-90 days

factors leading to variability: duration of incubation period depends on several factors

• site of infection: proximity of the wound to the brain

• severity of the wound

• inoculum: amount of virus introduced

• host age and immune status

what happens if rabies goes untreated and clinical signs present

once clinical signs or symptoms of rabies appear, its overrr. you dead.

fatality: once symptoms appear, disease is almost always fatal within days. Rabies is fatal once clinical disease is apparent.

lack of treatment efficacy: no treatment after symptoms appear

mechanism of death: death occurs rapidly in later stages of disease, resulting from respiratory failure or cardiac arrest

what blocks the spread of the virus from the infected muscle after a bite to the CNS

antibody response; Postexposure Prophylaxis (PEP) vaccine

what animals are most likely to be infected with rabies in US

in US, wild animals

• bats

• raccoons

• skunks

worldwide

• dogs

domestic

• rabies more prevalent in cats than dogs in US

why do bats account for most transmission in US

exposures to them frequently go unrecognized or untreated by the patient, preventing the administration of life-saving Postexposure Prophylaxis (PEP)

what is the reason for increased human fatality

nature of exposure and resulting failure to seek medical care

How do we prevent rabies?

1. immunization programs

• dogs and domestic animals

• wildlife: injected into bait and parachuted into forest

2. pre-exposure prophylaxis (vaccine) of those at high risk:

• veterinarians

• lab workers using rabies virus, spelunkers

• These people receives booster doses every 2-3 yrs

3. Avoidance and awareness

• individuals should avoid contact with wild animals and seek immediate medical attention

What is the Post-Exposure Prophylaxis (PEP) Process?

PEP is critical treatment administered after potential EXPOSURE to rabies and is nearly 100% successful. PEP involves 3 main steps: 

1. wound cleaning

• clean and rinse with soap and water (15 minutes)

• irrigate with virucidal agent (povidone-iodine)

2. Human rabies immune globulin (HRIG) → artificial passive

• injected into the area around and into wounds

• must be administered at a different anatomical location than the vaccine

3. vaccination (Active immunization):

• inactivated vaccine (killed virus), intramuscular injection

• involves 4 doses administered on Days 0,3,7, and 14 (4 doses in 2 weeks)

• immunocompromised may require fifth dose on day 28

why is post-exposure vaccination of rabies so successful as it relates to course of disease?

long incubation period of rabies virus

• delayed spread: after a bite, virus multiplies quietly in cells at the site of infection in human host. Takes time before virus enters peripheral nerves and begins its retrograde up spinal cord to brain. incubation period >30 days to >1 year

• time for antibody generation: allows vaccine time to generate antibody response

• blocking mechanism: generated antibody can block spread of the virus to CNS and brain. Once virus reaches the brain and clinical symptoms appear, disease is fatal, emphasizing necessity of timely PEP admin

what is course of action if you are bitten?

1. immediate wound care

2. seek medical attention: crucial to administer PEP before symptoms appear

3. provide animal info

4. check for other concerns, worry about tetanus booster since it comes from soil and animals have soil in their teeth