82. Rabies (aetiology, epidemiology, pathogenesis, clinical signs, post mortem lesions, zoon.).

Question 1

Occurrence?

Answer 1

Rabies (Lyssa, Tollwut) ʹ Notifiable!

Rhabdoviridae, Lyssavirus, Rabies virus (with serotypes!)

Occurrence: worldwide

• Epidemiological forms:
• Urban: Dog and cat
• Sylvatic: wild
• Bat: bat
• Rabies free countries͗͞ “ ab ovo” rabies free countries, rabies free country after vaccination

Question 2

Aetiology?

Answer 2

Aetiology

• Host change: arthopods to bats (reservoir)
• Genotypes (species)
• 1.: classical rabies virus: Worldwide
• 2.: Lagos-bat virus: Africa
• 3.: Mokola virus: Africa
• 4.: Duvenhage virus: S Africa
• 5.: European bat lyssavirus 1 (EBLV-1)
• 6.: European bat lyssavirus 2 (EBLV-2))
• 7.: Australian bat lyssavirus (ABLV)
• 8-15.: W-Caucasian bat virus, Aravan virus, Khujand v., Irkut v.
• Phylogroups
• I.: 1, 4, 5, 6, 7 genotypes
• II.: 2, 3 genotypes
• III.: others
• Difference in protection in same phylogroup
• Neurotropic virus Æ CNS signs
• Culture: lab. animal, egg, tissue culture
• Resistance: low BUT 3 weeks in brain of carcass
• Susceptibility: all warm blooded animals; fox, cat, jackal, bat, cattle, dog, sheep, goat, horse, human, birds ʹ
• difference in susceptibility
• High fox, jackal, bad (bird less)
• High: cat, dog, Ov, Cap, Bo, Eq, Ho (less)

Question 3

Epidemiology?

Answer 3

Epidemiology

• Shedding of the virus: saliva (hi titre!), (milk, urine ʹ if urine probably dead already)
• Infection: bite, contact with saliva/infected animal tissue (brain, s.c), per os, aerogenic: lessimportance
• Herbivores: dead end wont spread (wont bite others)
• Forms:
• Urban: Europe before World War II, Africa, Asia, South-America ʹ eradicated! Maintained by dog and
• cat
• Sylvatic:
• Europe: fox, magnut (racoon dog)
• America: skunk, raccoon, coyote
• Africa: jackal; Asia: wolf, hyena
• Bat: vampire bat (suck blood ʹ Africa), European bat (fruit)

Question 4

Pathogenesis?

Answer 4

Pathogenesis

1. Infection: bite
2. Remains at site of infection after infection, replication
3. Nerve cells
   - Peripheral nerves, retrograde axonal transport
   - Spinal ganglion
   - Spinal cord, brain inflammation
   - Centrifugal spread: salivary gland, cornea, organs, foetus, brown fat tissue
4. No viraemia
5. Virus shedding in saliva, milk, urine before clinical signs
6. Outcome of infection is dose dependent
7. Other genotypes ➝ slight differences in pathogenesis, less virulent
8. Good immunogenic
   - Avoids immune system
   - Immune modulation: inhibition of interferon production, dendritic cells, apoptosis of neuron, increase apoptosis of immune

cells

• Late immune response
  9. Humoral and cellular protection ➝ cytotoxic reactions, cytolysis

Question 5

Clinical signs?

Answer 5

Clinical signs

• Incubation: 2-8 weeks generally

• Amount of virus, place of entry, age, hibernation
• Exceptional cases: 2 years in human

• Clinical forms

• Furious rabies: alternation of behaviour, paralysis

‣ Introduction (stadium prodromorum)

‣ Excitation (stadium excitationis)

‣ Paralysis (stadium paralyseos)

• Silent rabies: paralysis

‣ Introduction (stadium prodromorum)

‣ Paralysis (stadium paralyseos)

• Alteration of behaviour, aggression
• Unexplained paralysis
• Phases of clinical signs

1. Introductory phase

‣ Shyness, anorexia

‣ Salivation, hoarse voice

2. Excitation phase

‣ Aggression

‣ Increased sex drive

‣ Abnormal appetite

‣ Swallowing disorders, strabismus

3. Paralysis phase

‣ Jaw paralysis

‣ Salivation

• Dog

• Furious rabies ➝ disorientation, aggression, abnormal appetite, increased sex drive, hoarse voice, salivation, strabismus,

hydrophobia, paralysis

• Silent rabies

• Cat

• Furious rabies ➝ aggression

• Ruminants

• Not characteristic clinical signs (tympany)
• Excitation, outbreak, hoarse voice, painful swallowing
• Swine ➝ excitation, bites, paralysis
• Horse
• Furious rabies ➝ excitation, aggression, colic, itching at place of entry
• Silent rabies
• Poultry ➝ excitation, aggression, can be healed
• Wild living animals: altered behaviour (fox, deer, wild cat, marten, badger)
• Come close to humans, lose natural fear, become ‘brave’
• Aggression

Question 6

Post mortem lesions?

Answer 6

Post mortem lesions

• Abnormal bodies in stomach
• Histopathology
• Encephalomyelitis
• Lymphohistiocytic infiltration ➝ midbrain, medulla, Ammon-horn grey material
• Degeneration of nerve cells, glia cell foci, Babes-nodules
• Negri bodies (cytoplasmic inclusion body)

Question 7

Bat rabies europe australia?

Answer 7

Bat Rabies: Europe, Australia

Etiology

• North Europe, Hungary
• Infection rate: 5-20%
• Europe: EBLV-1 (Genotype 5), EBLV-2 (Genotype 6), W. Caucasic
• Australia: ABLV (Genotype 7)

Epidemiology

• Insect and fruit eating bats
• Limited spread to other species
• Spread with aerosols was not observed

Clinical signs

• Clinical signs are are
• Altered behaviour: navigation problems, attack
• Paralysis

Public health

• Humans can be infected: bite, contact
• Prevention with vaccination

Question 8

Bat Rabies: Vampire bat rabies?

Answer 8

Bat Rabies: Vampire Bat Rabies

Etiology

• Latin America: Mexico, North Argentina
• Genotype 1
• Can be differentiated from classical strains

Epidemiology

• Desmodus rotundus ➝ bird, amphibians, reptiles, rodents, farm animals, human
• Diphylla ecaudata: bird
• Diaemus youngii: bird
• Prefers feeding on farm animals
• Infection when blood sucking

Clinical signs

• Alteration of behaviour
• Paralysis

Public health

• Humans can be infected: bite, contact
• Prevention: avoid contact with bats, wounds, vaccination (post exposure)

Question 9

Public health impact?

Answer 9

Public health impact

• Infection

• Bite, saliva, wound ➝ carnivores, bat, farm animals
• Transplantation ➝ Germany 3/6 cases (2005), US 3/3 (2004), China 2/4 (2015)
• Aerosol (cave)

• Clinical signs

• Generally unwell, salivation, difficult swallowing
• Aggression, spasm, paralysis
• Death
• Prevention ➝ information, wound toilette, vaccination
• Survival ➝ Milwaukee protocol

Question 10

Public health importance?

Answer 10

Public health importance

• About 60,000 deaths/year worldwide
• More than 150 countries
• 40% children, 99% of human infections are caused by dogs
• Aim is to prevent human rabies by 2030
• Hungary: 1951-2006 8 death cases

Question 11

Vaccination of humans?

Answer 11

Vaccination of humans

• Inactivated vaccines
• Prevention: vaccine 0, 28, 56 days + 1 and 5 years later
• Post exposure
• 0 (x2), 7, 21 days
• 1 (x2), 3, 7, 14, 28 days ➝ increased risk
• Vaccination within 5 years ➝ shorter course
• Human hyperimmune serum + vaccine: 1, 3, 7, 14 days (USA)
• Immune deficient: hyperimmune serum, serological contol

• Vaccines ➝ Verorab (Vero cells), Rabivac (human diploid cell), Rabipur (chicken embryo fibroblast)