7 - Rabies Flashcards
In latin, rabies means…
Madness, rage, fury
How many rabies cases worldwide? How many due to dog bites? Where do most deaths occur?
~60,000 deaths worldwide (most children in developing countries)
95% cases due to dog bites
99% deaths occur in Africa and Asia
Incubation period of rabies? signs of furious rabies
Typically 2-3 months, range from 1 week to 1 year
Furious rabies = signs of hyperactivity, excitable beh, hydrophobia, aerophobia. Cardio-respiratory arrest =death
Rabies dates back to…
Mesopotamians
Owner of a rabid dog was responsible for containment of the animal; pays for deaths
Aristotle on Rabies.
“Dogs suffer from the madness, this causes them to become irritable and all animals they bite become diseased”
Occurrence of rabies in europe and the americas
- few human deaths
- few transmissions from dogs (vaccinated)
- primarily via wildlife (bats, foxes, skunks, raccoons)
Name countries that are recognized by the CFIA as being free of rabies
- Australia
- Finland
- Ireland
- UK
Canada rules on dog importation
It is restricted due to prevalence of rabies in some countries
Rabies vaccination required
Basics of the WHO’s response to rabies
- involve all countries, emphasize one health approach
- access to prophylactic treatment
- can validate countries achieving 0 human deaths due to dog rabies
OIE is now the… What are their objectives
World Organization for Animal Health (WOAH): international org funded by UN
Objectives: transparency, scientific info, promote vet services, food safety, animal welfare
What % of dogs need to be vaccinated so no more human cases occur?
70%
What kind of virus is rabies? Shape?
RNA virus
Rhabdovirus family, Lyssavirus genus
Bullet shaped
Three Lyssavirus subgroups, what diseases they cause
Phylogroup 1: rabies virus, european bat lyssaviruses, australian bat lyssavirus
Phylogroup 2: lagos bat lyssavirus, mokola lyssavirus
Phylogroup 3: west caucasian bat lyssavirus
Describe the rabies RNA genome
12 kb negative sense genome
When it enters cell must be converted to positive sense through RNA polymerase
Outer coat of rabies virus? What does it do
Glycoprotein membrane
Interacts with cellular membrane to gain entrance into a cell; also is the target for neutralizing antibodies (antibodies to virus = antibodies to G protein)
Rabies virus is inactivated by:
Heat (50C for 15 min)
Sunlight, desiccation
Five structural proteins of the RNA virus
- N nucleoprotein
- P phosphoprotein
- M matrix protein
- G glycoprotein
- L RNA dependent RNA polymerase
Majority of human rabies from dog reservoirs are in what countries?
South America, Asia, India
Stages of rabies virus spread in the body
- peripheral nervous system to brain: 3-12 weeks
- virus replicates rapidly in the brain
- subsequent centrifugal spread to salivary glands and saliva
- clinical symptoms after virus enters brain = death within 1 week
Slide 29
When does rabies treatment need to occur? Why?
PRIOR to clinical signs (post-infection)
Takes so long to progress to the brain, so it works
Why is there little/no rabies transmission during the preclinical phase
Because transmission occurs from saliva, which does not get infectivity until after brain infection
How does rabies spread in the body
Neurotrophic: spreads along neural pathways and invades CNS
Travels to spinal cord at a rate of 50 to 100 mm/day
Why are clinical symptoms not useful for detecting rabies in dogs
Most of the infection is incubation or preclinical
Clinical symptoms can be difficult to identify
Three methods of rabies detection
Direct Fluorescent Antibody Technique:
- brain tissue
- look for antibodies against viral nucleoprotein
Polymerase Chain Reaction
- primers to rabies genome
Direct Rapid Immunohistochemical Test:
- light microscopy
- used for wildlife surveillance
How did Pasteur invent the live attenuated vaccine
Chicken Cholera
- bacterial disease of chickens
- Pasteur observed that old bacterial cultures lost virulence (did not produce disease but produced immune respone)
Describe the creation of the first rabies vaccine
By Louis Pasteur
Live attenuated vaccine using rabies in rabbits
Spinal cord of rabies-infected rabbit ground, left out to dry
Longer it dried = less virulent
Led to canine vaccine
First rabies vaccination of a human?
Joseph Meister
Young boy repeatedly bitten by rabid dog
Received 13 inoculations over 3 weeks from Pasteur (progressively more virulent samples)
Did not develop rabies
Vaccination protocol for the 1911 rabies vaccine
25 injections total
- 3 on day 1
- 2 on day 2
- 2 no day 3
- 1 injection each day for 18 days
- each dose slightly more virulent
Differences in rabies vaccination of dogs vs humans
Dogs: prevent infection
Humans: post bite
Two steps of Rabies Postexposure Prophylaxis (PEP)
(rinse wound with soap and water thoroughly)
- dose of human rabies immune globulin (provides antibodies)
- rabies vaccine (on day of exposure, followed by days 3, 7 and 14)
How many does of PEP administered worldwide? Deaths without it?
29 million /year
~ 3 million more deaths without it
Average cost of PEP vs dog vaccination
Rabies treatment in humans per patient: US $108.07
Mass dog vaccination per dog: US $4.03
Herd immunity level for rabies in dogs
70%
What is R0?
Reproductive number of an infection (how fast its expected to spread; ability to spread between individuals)
- not necessarily a measure of severity
A couple factors considered in calculating a pathogens R0?
Infectious period (length of time it is contagious)
Contact rate (# contacts while contagious - variable)
Mode of transmission (air = rapid transmission, direct contact = less transm)
Example of pathogen with slow vs fast spread
Slow = ebola
Fast = measles
Second definitely of R0
Expected number of secondary cases produced by a single infection in a completely susceptible population
R0 values assume..
everyone in a population is completely vulnerable to the disease
i.e. nobody vaccinated, nobody has had the disease before, no ways of controlling the spread
What is Re (or Rt)?
Numerical estimate that captures transmission once a virus becomes more common
Public health measures initiated
Typically lower than R0
R0 <1 vs R0 = 1 vs R0 > 1
R0 <1 : disease will die out on its own, for every sick individual less than 1 new infection arises
R0 = 1 : existing infection causes one new infection. Stable rate (no epidemic)
R0 >1 : existing infection causes more than one new infection. Spread in pop can cause epidemic
R0 of rabies in humans vs dogs
Humans = zero, dead-end host. Cannot decrease rabies by only treating humans
Dogs = >1 (social, interact with teeth)
What is herd immunity? Provides…
When enough people are immune due to vaccination, previously having the disease and recovering this stops disease spread
Provides indirect protection to susceptible individuals when most of the pop is not susceptible
How does R0 affect herd immunity? Herd immunity level (hC formula)
% needed to be vaccinated in pop affected by R0 (higher R0 = higher herd immunity needed)
hC = 1 - (1/R0)
Why is dog vaccination not used in India? How could it help decrease cases?
Viewed as prohibitively expensive: say 70% number is not attainable due to cost, which is inhibiting vaccination bc they will not reach it
But if they vaccinate 200,000 stray dogs annually (13% of canine pop) could reduce human rabies by 90%
Rabies in Sri Lanka
Has virtually been eliminated thanks to dog vaccination combined with PEP
First rabies case in Canada
Charles Lennox, 4th Duke of Richmond
Fox bit his pet dog, he died of rabies
Reservoirs in Canada
Artic foxes, red foxes, skunks, raccoons, bats
Most rabies cases in Canada are in what animal?
Bats (70%)
In Canada, rabies is common in what kind of bat?
The Big Brown Bat (5 to 10% of those tested were infected)
Rabies in Mexico
No cases of dog-mediated rabies since 2006
Hs been improving its vaccination program
Validated by WHO in 2019 (free of human rabies transmitted by dogs)
How do we go about vaccinating wild animals for rabies?
Oral vaccine bait (can significantly decrease cases)
- does not work on bats
Most recent human rabies case in Canada
2019
21 yr old male in BC
Bat ran into him, died of rabies
Describe the five rabies deaths that occurred in the US in 2021
- 80 year old illinois man: not vaccinated due to longstanding fear
- idaho man and texas boy not vaccinated: did noy believe bat broke the skin
- minnesota man bitten by bat: vaccinated but undiagnosed immune deficiency
- man bitten by rabid dog in Philippines refused vaccination
Statistical blip
