Topic 73 - Rabies (RED) Flashcards
What is Rabies?
a contagious and fatal viral disease of dogs and other mammals that causes madness and convulsions, transmissible through the saliva to humans
Why is Rabies of such high importance?
- Zoonosis + notifiable !!!
- Present worldwide with high case numbers
- Extremeley fatal, close to 100%
- No treatment
- Very broad host range
- Unique pathogenesis - Goes to the CNS
- Different cycles of epidemiology
Name the different cycle of transmission for rabies:
- Urban cycle
- Sylvatic cycle
- Bat cycle
What is the Urban cycle of rabies?
The virus is maintained by DOGS
What is the Sylvatic cycle of rabies?
The virus is maintained by wild animals: Foxes, racoons, skunks
What is the Bat cycle of rabies?
The virus is maintained by bats
Occurrence of rabies, urban cycle:
Asia
Africa
Occurrence of rabies, sylvatic cycle:
Eastern Europe
Asia, but urban cycle is most problematic
Africa
North America
Occurrence of rabies, bat cycle:
Worldwide !
Europe
Africa
North America, big problem there
Latin America, the vampire bat
Areas free of Rabies:
Islands:
UK
Ireland
Iceland
Japan
Australia
New Zealand
Which parts of Europe is mostly affected by Rabies today?
Eastern Europe
Which countries of Europe does have the highest numbers of Rabies today?
Belarus
Georgia
Moldova
Romania
Turkey
Ukraine
Russia
Causative agent of rabies:
Rabies virus, genotype 1
RABV
Lyssavirus genus
Serotypes and genotypes of the lyssavirus:
16 other genotypes. Mainly present in bats. They are restricted to geographical areas, but they might also overlap. They rarely cause disease in humans
The genotypes are divided into 3 phylogroups
Which phylogroup is rabies genotype 1 placed?
Group 1, this is where most of the genotypes are placed
Resistance of rabies virus:
WEAK
How long can rabies survive in the environment?
They cannot !!
They can survive in an infected brain for weeks
Rabies have 5 different proteins, which all have different roles. Name the proteins:
G - Glycoprotein
N - Nukleoprotein
M - Matrix protein
L - Large protein
P - Phosphoprotein
What is the role of Glycoprotein in rabies virus?
- It is the receptor binding protein of the virus, which enables attachement/absorption of the virus to the infected cell.
- The G-protein is also responsible for the antigenicity, triggering the antibody response.
- They are also the cause of the virulence, there is a neurotropism, where the virus invades the CNS
What is the role of Nucleoprotein in rabies virus?
Stabilizes the nucelic acid
What is the role of Matrix protein in rabies virus?
Controls the exit of the virus, the budding
What is the role of Large protein in rabies virus?
Responsible for the virus replication
What is the role of all the proteins together, in rabies virus?
All, except L-protein, plays a role in the immune-evasion. The virus invades the immunsystem, the immune response, and all the proteins have their own role for that
Host range of Rabies:
All warm blooded animals
Original host of rabies:
The bat
The virus underwent a co-evolution, usually we observe a lower virulence. The virus can survive longer and the pathogenesis is not as quick
Hosts with highest susceptibility of rabies:
Foxes, wolfs, jackals !!
Less:
Cat, cattle, bats, skunks, rodents
Hosts with moderate susceptibility of rabies:
Dog
Horse
Humans
Small ruminants
Hosts with Low susceptibility of rabies:
- This does not mean the infected do not die, this depends on the efficiency of the spread and how many virus particles are present !!
Oppossums
Accidental hosts of rabies:
Humans
Horse
Ruminants
Swine
They are also dead-end-hosts
Which of the 3 cycle of rabies, is the most common one?
Urban !!
But also sylvatic cycle, where they infect dog/cat and they infect humans
Reservoir host in urban cycle of rabies:
Dog, sometimes cats if the dog infects the cat
Reservoir host in sylvatic cycle of rabies:
In Europe: Fox - most common, raccon, wolf
In America: Raccon, skunk, coyote
In Africa: Jackal, hyena
Reservoir host in bat cycle of rabies:
Insect eating bats
Vampire vats - America
Infection route of rabies:
- Infectious saliva gets under skin or to the mucous membrane if it is injured
- Infected with bite, or a wound, even a scratch
Rarely: milk, organ transplantation
Pathogenesis of rabies:
- The virus gets into the muscle, skin or mucous membrane
- 1st phase is slow and there is along incubation time, this is where the virus replicates in the periphery and the virus accumulates near the neuromuscular junctions
- If the dose of virus is high, it gets into the peripheral nerves within the axons and there will be a slow spread towards the CNS, the spinal cord and brain
- The virus travels within the axons via retrograde axonal transport which used the motorprotein called dynenin, this is the “vehicle” protein for the virus transmission
- There are two affects, two ways the virus gets to the brain, one slow and one faster.
- Fast: The virus affects the motor nerves which transmits the virus to spinal cord and then the brain
- Slow: Affects the sensory nerves, there are several synapses to pass through in the spinal ganglia and further to the spinal cord and then the brain
- Once the virus enters the brain there will be a mass virus replication in many areas of the brain, which causes encephalitis
- Once in the encephalitis phase, there is a centrifugal sprad, towards the periphery and the virus is spread to salivary glands, cornea, skin, organs, fetus
Simpler explanation of the pathogenesis of rabies, picture:
Important about the pathogensis of rabies:
- There is no viramiea !!
2.There is an immune invasion, so the immune response will be altered and blocked. - The non-specific immune system is turned off
- There will be apoptosis of the T-cells
- Antibodies will appear in the blood, but not until later in the terminal phase
Incubation time for rabies:
long, 2-8 weeks, but depends on several factors
Factors influencing incubation time of rabies:
- Host specie
- Age
- Site of infection: close or far from nerves, brain etc
- Virus strain
- Virus dose
Shedding of virus:
shedding with saliva shortly after onset of clinical signs
General clinical signs of rabies:
CNS signs
Alterations of behaviour
Paralysis
BUT, clinical signs vary between species
General forms identified in case of rabies:
Furious rabies
Dumb/paralytic
Phases during the furious form of rabies:
- Introduction/Prodromal phase
- Excitation phase
- Paralytic phase
Clinical signs during introduction phase of furious form of rabies:
Shyness
Anorexia
Salivation
Hoarse voice due to the paralysis or the throat
Clinical signs during excitation phase of furious form of rabies:
Aggressiveness
Biting on to everything, even objects, and not letting go
Abnormal appetite, eating undigested objects
Paralysis of cranial nerves, causing swallowing disorders, salivation, strabismus
Clinical signs during paralytic phase of furious form of rabies:
Progressive paralysis.
It starts with paralysis of the jaw, then the limbs then an ascending paralysis of the trunk and respiratory muscles resulting in suffocation of the animal
Phases of dumb/paralytic of rabies
The excitation phase is missing, the animal wont show aggressive behaviour
Confusion
Species where these 2 forms of rabies are mostly differentiated:
Humans
Dogs
Clinical signs of dogs infected with rabies:
Furious rabies, most common
Dumb rabies, sometimes
Clinical signs of cats infected with rabies:
Furious rabies almost everytime
The cats attacks bigger animals/humans, they will go for injuries to the face and neck and this is a big problem because of the short incubation time - closer to the brain
Clinical signs of cattle infected with rabies:
Introductory signs: incertain GI signs, rimunal tympany, diarrhoea ⭢ misleading symptoms !!
More evident: agressiveness, rage, causing broken horns, salivation
Later: paralysis, death
Clinical signs of swine infected with rabies:
Rarely infected due to the pigs being held inside.
If they are infected, it is an agressive form.
Clinical signs of horses infected with rabies:
Often seen.
Itching at site of exposure
Colic ⭢ misleading !!
Scraping with hood
Biting objects
Later: Droppin of head, laying down, penis prolapse, strange movement of the tail,
Death of horse infected with rabies
4-6 days after onset
Clinical signs of wild animals, fox, infected with rabies:
- Altered behaviour
- Often seek villages, populated areas at daytime
- Comes to humans and attacks
Clinical signs of wild animals, raccoon, infected with rabies:
Aggressiveness
Attacks
Clinical signs of wild animals, deer, infected with rabies:
comes close to humans
Painful voice
Aggressiveness
Dashing against trees
infected with bite from fox
Post mortem lesions in case of rabies:
No clear pathological findings
Can see: abnormal objects in the stomach, injuries (broken horns etc)
Histopathological lesions in case of rabies:
Much more specific !
We can see negri bodies which are eosinophilic inclusion bodies in the neurons outside the nucleus
How to diagnose rabies:
We look at:
Clinical signs
Epidemiology
Laboratory diagnostics
How to detect antigens in case of infection with rabies:
IF !! Immuno fluroessence test, the microcope will green stained infected cells
PCR
How to detect antibodies in case of infection with rabies:
Virus Neutralistation
ELISA
Why do we perform serology test for rabies?
To check for protection from the vaccine.
It the antibody titre is sufficient, the protective titre is higher than 0.5 IU/ml
IU = international unit
Differential diagnosis of rabies:
Every other disease with CNS signs
In horse: colic conditions
Prevention, control of urban cycle of rabies, in endemic countries:
Mass vaccination of dogs
Education of people
Prevention, control of urban cycle of rabies, in disease free countries:
Quarantine of dogs
Vaccination and serology test
Prevention, control of sylvatic cycle of rabies:
Formerly they eradicated the foxes, but it was not successful
Now: oral vaccine, it is thrown to the foxes, once in spring and once in autumn
there is control tetracycline marker in the vaccine, which causes coloration of the teeth
Is Hungary free of rabies?
no.
There is anew outbreak on the border to Ukraine, due to the war they stopped the vaccination
Vaccines against rabies, most common ones:
all vaccines contain the genotype 1.
We use:
1. Cell-cultured vaccine, it is reliable, safe.
⭢ inactivate or live attenuated
- Vector-vaccines, used for oral vaccination, mainly in the USA
Rabies vaccination of dogs:
Compulsory !!
Use an inactivated vaccine.
First at 3 month old, then a booster 3-6 weeks later and depending on area either yearly or every 3 years
Rabies vaccination of cats:
Recommended, especially in free roaming cats.
Similar to the dog
Rabies vaccination of horses:
Recommended, especially in areas close to endemic areas.
First vaccine at 3-6 months old + booster. then yearly or every 3 years
Post exposure vaccine for rabies:
Used in herbivores.
this is not done in all countries
Usually done with inactivated vaccine with sheep brain vaccine
Public health ascpects of rabies:
- Zoonotic !!
- Deadly, untreatable disease
- High case numbers, 20k-100k every year
- 99% of the cases are due to the urban cycle
- 40% of affected cases are children
How are humans infected with rabies?
- Through a bite, injury and saliva.
- Can also be infected from herbivores or bats
- Organ transplantation
Clinical signs in humans infected with rabies:
Furious form is more common !!
- Itching and muscle pain at entry site, and feeling unwell
- Excitation phase, with aggression, salivation, spasms
- Later: paralysis and death ⭢ due to respiratory arrest or multiple organ failure
Survival rate of rabies:
RARE
If they survive, they will have severe CNS symptoms
Prevention of humans being infected with rabies:
Eduaction
Vaccination
Treat wounds
Human vaccination type against rabies:
Use inactivated, cell cultured-based vaccines
Most common type of vaccine used for exposed people for rabies:
PrEP = Program for Preventative care
1st: 0 days
2nd: 28 days (4weeks)
3rd: 56 day (8 weeks)
Booster at 1 year and 5 years
