Difference between revisions of "Rabies"

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==Virulence and Pathogenesis==
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== Introduction  ==
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*Rabies is moderately resistant: it can survive well in dark places at low temperatures for several days
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[[Image:480px-Dog with rabies.jpg|thumb|right|175px|<p><b>Close-up of a dog's face during late-stage "dumb" paralytic rabies</b></p>Source: Wikimedia Commons; Author: Centres for Disease Control and Prevention's Public Health Image Library (1963)]]
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*Infection occurs through a '''penetrating bite''' in which virus is transmitted via '''saliva'''
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Rabies is very severe and almost always fatal notifiable, zoonotic disease seen to affect any mammal in the world. The UK, Australia and New Zealand are free of rabies. All animals are susceptible, but canines, especially jackals, foxes and wolves are particularly so. In many countries where the disease is endemic, there are certain mammals which can act as reservoir species for the virus. Below is a table of reservoir species in certain regions:<br>
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*'''Incubation''' period is variable but can be long (10 days to 12 months), and increases with distance of the bite to the CNS
 +
**80% show signs within 4 months
 +
*Primary replication of the virus occurs in the '''muscle'''
 +
*The virus gains access to nervous tissue and travels toward the '''brain''', where it continues to replicate
 +
*It then migrates down cranial nerves to infect salivary glands and the cornea
 +
*Virus is shed in '''saliva''' and '''tears''' and can be shed BEFORE the onset of classical signs
 +
*The onset of clinical signs in dogs and cats includes:
 +
**Behavioral changes
 +
**Pyrexia
 +
**Salivation
 +
**Dilation of pupils
 +
*Two forms of the virus exist:
 +
**'''Furious''' form:
 +
***Common to cats and dogs
 +
***Abnormal aggression, salivation, and attack without provocation
 +
***Disordered wandering, "copulatory" movements.
 +
***Incoordination, convulsions, coma and death within 3-10 days
 +
**'''Dumb''' form
 +
***May or may not follow Furious form
 +
***Common to ruminants and horses
 +
***Ruminal tympany, tenesmus, diarrhoea
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***Paralysis of lower jaw, drooling saliva, tremors and progressive paralysis
 +
***In dogs, a change in voice may be observed (bellowing)
 +
*Human infection is characterized by '''hydrophobia'''
  
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{| cellspacing="1" cellpadding="1" border="1" style="width: 424px; height: 171px;"
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==Epidemiology==
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*Rabies is a '''NOTIFIABLE''' zoonosis
 +
*Rabies is found worldwide, though currently considered exotic to the UK and Australia
 +
Host Range:
 +
*All mammals are susceptible
 +
**Very susceptible: foxes, jackals, wolves
 +
**Susceptible (10,000x virus necessary to infect): cats, rodents, bats, skunks, cattle, mongooses
 +
**Moderately susceptible (100,000x virus necessary to infect): dogs, sheep, goats, horses, primates
 +
*Isolates can show to some species specificity in their reservoir host
 +
Reservoir species by region:
 +
{| style="width:60%; height:200px" border="1" align=center
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!'''Region'''
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!'''Reservoir Species'''
 
|-
 
|-
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| '''Region<br>'''
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|Europe
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| '''Reservoir species'''<br>
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|Red fox
 
|-
 
|-
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| Europe<br>
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|Russia, Turkey, Middle East
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| Red Fox<br>
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|Dog, Raccoon
 
|-
 
|-
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| Russia, Turkey, Middle East<br>
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|USA
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| Raccoon<br>
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|Raccoon, Fox, Skunk
 
|-
 
|-
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| USA<br>
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|Africa
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| Raccoon, Fox, Skunk<br>
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|Dog, Jackal, Mongoose
 
|-
 
|-
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| Africa<br>
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|Asia
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| Dog, Jackal, Mongoose<br>
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|Dog, Mongoose
 
|-
 
|-
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| Asia<br>
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|South America
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| Dog, Mongoose<br>
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|Dog, Vampire bat
 
|-
 
|-
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| South America<br>
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|Worldwide
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| Dog, Vampire Bat<br>
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|Insectivorous Bats
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|-
 
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| Worldwide<br>
 
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| Insectivorous Bats<br>
 
 
|}
 
|}
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*The current position of DEFRA holds bat lyssaviruses to be present in the UK
 +
*Human infection and death an occur after infection with bat rabies
 +
**Nocturnal bat bites account for 50% of human cases in the USA
 +
*Humans develop disease but excrete little virus
 +
*Immune recovered animals are rare, but are not shown to be infections
  
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The current position of [http://www.defra.gov.uk/ DEFRA] holds bat lyssaviruses to be present in the UK. Human infection and death can occur after infection with bat rabies; nocturnal bat bites account for 50% of human cases in the USA. Humans develop the disease but excrete little virus.
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==Diagnosis==
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*'''Isolate''' and monitor for clinical signs
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The virus is moderately resistant and can survive well in dark places at low temperatures for several days. Infection occurs through a '''penetrating bite''' in which virus is transmitted via '''saliva'''. '''Incubation''' period is variable but can be long (10 days to 12 months), and increases with distance of the bite to the CNS (80% of cases show signs within 4 months). Primary replication of the virus occurs in the '''muscle''', then the virus gains access to nervous tissue and travels toward the '''brain''', where it continues to replicate. It then migrates down cranial nerves to infect salivary glands and the cornea. Virus is shed in '''saliva''' and '''tears''' and can be shed BEFORE the onset of classical signs.
+
*In the field:
−
 
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**Remove brain core sample via straw through occipital foramen in the direction of an eye
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== Clinical Signs ==
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**Place contents in a 50% glyerol/PBS for FAT or virus isolation, or in 10% formaldehyde for histology
−
 
+
**Whole head can also be removed and sent to lab
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The onset of clinical signs in dogs and cats includes behavioral changes, pyrexia, salivation and dilation of pupils.
+
*In the lab:
−
 
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**'''Fluorescent Antibody Test (FAT)''' on smears or frozen sections of hippocampus or cerebellum should show presence of Negri bodies
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Then, the virus will either take the furious form or the dumb form. The '''furious form''' is mostly seen in dogs and cats, however, contrary to popular belief, the dumb form is actually the most common form in dogs. Signs of the furious form include abnormal aggression, salivation, and attack without provocation. There may also be disordered wandering, "copulatory" movements, incoordination, convulsions, coma and death within 3-10 days. The '''dumb form''' may or may not follow the furious form, or it may appear alone. This form is most common in ruminants or horses affected with the disease. Signs include [[Bloat|ruminal tympany]], tenesmus, diarrhoea, paralysis of lower jaw, drooling saliva, tremors and progressive paralysis. In dogs, a change in voice may be observed (bellowing).
+
***Being replaced by testing for monoclonal antibodies to nucleoprotein
−
 
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**Histological detection of Negri bodies using Mann's or silver stains
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== Diagnosis  ==
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**Intracerebral inoculation of mice followed by FAT testing of brain smears of affected mice
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**RT-PCR on brain or saliva can be performed to determine genotype
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Immediately isolate any animal suspected of having rabies. If the animal has died or been put to sleep, then remove brain core sample via straw through occipital foramen in the direction of an eye and place contents in a 50% glycerol/PBS for [[Immunofluorescence|FAT]] or virus isolation, or in 10% formaldehyde for histology. Or, the whole head can also be removed and sent to the laboratory.
 
−
 
 
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In the lab, specialist teams will perform a '''Fluorescent Antibody Test (FAT)''' on smears or frozen sections of hippocampus or cerebellum. They should show presence of Negri bodies. Histological detection of Negri bodies using Mann's or silver stains can also be performed, as can the intracerebral inoculation of mice followed by FAT testing of brain smears of affected mice. RT-PCR on brain or saliva can be performed to determine genotype.
 
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== Rabies Control  ==
 
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For countries where rabies is considered exotic, 6 month quarantine of carnivores and ruminants  is required (Norway, Sweden, Portugal, Australia, New Zealand). In the UK, this has been replaced by the '''Pet Travel Scheme''' ([http://www.defra.gov.uk/wildlife-pets/pets/travel/pets/ PETS]).
 
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For virus-endemic countries, control in pets is achieved by annual vaccination. Antigenicity allows a single antigenic type to vaccinate. The vaccine is either '''inactivated virus''' or '''canarypox''' recombinant viruses. Control is also achieved by control of the stray population, enforcing all dogs to be muzzled in public and attempts to control wildlife hosts by feeding vaccinated bait.
 
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In humans that may be working with animals and be at risk of contracting the disease, prevention is by vaccination with a single booster if bitten. The current vaccine is grown in human diploid cells (HDCV) and is BPL-inactivated, and is therefore costly. Developing countries utilize older vaccines passaged from a 1939 case ("Flury" vaccines). If bitten and unvaccinated, one should clean and disinfect the wound and human '''anti-rabies immunoglobulin''' should be administered around the bite. Then, an intramuscular vaccination program: 2 dose - 1 dose - 1 dose at 0, 7, and 14 days post-bite should be started.
 
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For more on Rabies control in Europe, see [http://www.who-rabies-bulletin.org/About_Rabies/Control.aspx here]
 
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== References  ==
 
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Blood, D.C. and Studdert, V. P. (1999) '''Saunders Comprehensive Veterinary Dictionary '''(2nd Edition) ''Elsevier Science''
 
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Bridger, J (2007) '''Virology Study Guide, '''''Royal Veterinary College''
 
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{{review}}
 
  
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{{OpenPages}}
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==Rabies Control==
 +
For countries where rabies is considered exotic:
 +
*6 month quarantine of carnivores and ruminants (Norway, Sweden, Portugal, Australia, New Zealand)
 +
*In the UK, this has been replaced by the '''Pet Travel Scheme''' ([http://www.defra.gov.uk/animalh/quarantine/index.htm PETS])
 +
For virus-endemic countries:
 +
#Control in pets:
 +
#*Annual Vaccination:
 +
#**Antigenicity allows a single antigenic type to vaccinate
 +
#**'''Inactivated virus''' or '''canarypox''' recombinant viruses
 +
#*Control of stray population
 +
#*Muzzling in public
 +
#Control of wildlife reservoir hosts:
 +
#*Feeding vaccinated bait
 +
#*Secondary consequence of increasing reservoir host population (eg European foxes)
 +
#Control in humans
 +
##Prevention by vaccination with a single booster if bitten
 +
##*The current vaccine is grown in human diploid cells (HDCV) and is BPL-inactivated, and therefore costly
 +
##*Developing countries utilize older vaccines passaged from a 1939 case ("Flury" vaccines)
 +
##If bitten and unvaccinated:
 +
##*Clean and disinfect wound
 +
##*Human '''anti-rabies immunoglobulin''' administered around bite
 +
##*Intramuscular vaccination program: 2 dose-1 dose-1 dose at 0, 7, and 14 days post-bite
  
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[[Category:Rhabdoviridae]] [[Category:Zoonoses]] [[Category:Neurological_Diseases_-_Cat]] [[Category:Cat_Viruses]] [[Category:Neurological_Diseases_-_Dog]] [[Category:Dog_Viruses]] [[Category:Cattle_Viruses]] [[Category:Neurological_Diseases_-_Cattle]] [[Category:Sheep_Viruses]] [[Category:Neurological_Diseases_-_Sheep]] [[Category:Pig_Viruses]] [[Category:Neurological_Diseases_-_Pig]] [[Category:Goat_Viruses]] [[Category:Neurological_Diseases_-_Goat]] [[Category:Expert_Review]] [[Category:Neurological_Diseases_-_Horse]] [[Category:Horse_Viruses|Horse_Viruses]]
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For more on Rabies control in Europe, see [http://www.who-rabies-bulletin.org/About_Rabies/Control.aspx here][[Category:Rhabdoviridae]][[Category:Cat]][[Category:Dog]][[Category:Horse]][[Category:Cattle]][[Category:Sheep]][[Category:Pig]][[Category:Goat]][[Category:Zoonoses]]

Revision as of 10:16, 24 May 2010

Virulence and Pathogenesis

  • Rabies is moderately resistant: it can survive well in dark places at low temperatures for several days
  • Infection occurs through a penetrating bite in which virus is transmitted via saliva
  • Incubation period is variable but can be long (10 days to 12 months), and increases with distance of the bite to the CNS
    • 80% show signs within 4 months
  • Primary replication of the virus occurs in the muscle
  • The virus gains access to nervous tissue and travels toward the brain, where it continues to replicate
  • It then migrates down cranial nerves to infect salivary glands and the cornea
  • Virus is shed in saliva and tears and can be shed BEFORE the onset of classical signs
  • The onset of clinical signs in dogs and cats includes:
    • Behavioral changes
    • Pyrexia
    • Salivation
    • Dilation of pupils
  • Two forms of the virus exist:
    • Furious form:
      • Common to cats and dogs
      • Abnormal aggression, salivation, and attack without provocation
      • Disordered wandering, "copulatory" movements.
      • Incoordination, convulsions, coma and death within 3-10 days
    • Dumb form
      • May or may not follow Furious form
      • Common to ruminants and horses
      • Ruminal tympany, tenesmus, diarrhoea
      • Paralysis of lower jaw, drooling saliva, tremors and progressive paralysis
      • In dogs, a change in voice may be observed (bellowing)
  • Human infection is characterized by hydrophobia

Epidemiology

  • Rabies is a NOTIFIABLE zoonosis
  • Rabies is found worldwide, though currently considered exotic to the UK and Australia

Host Range:

  • All mammals are susceptible
    • Very susceptible: foxes, jackals, wolves
    • Susceptible (10,000x virus necessary to infect): cats, rodents, bats, skunks, cattle, mongooses
    • Moderately susceptible (100,000x virus necessary to infect): dogs, sheep, goats, horses, primates
  • Isolates can show to some species specificity in their reservoir host

Reservoir species by region:

Region Reservoir Species
Europe Red fox
Russia, Turkey, Middle East Dog, Raccoon
USA Raccoon, Fox, Skunk
Africa Dog, Jackal, Mongoose
Asia Dog, Mongoose
South America Dog, Vampire bat
Worldwide Insectivorous Bats
  • The current position of DEFRA holds bat lyssaviruses to be present in the UK
  • Human infection and death an occur after infection with bat rabies
    • Nocturnal bat bites account for 50% of human cases in the USA
  • Humans develop disease but excrete little virus
  • Immune recovered animals are rare, but are not shown to be infections

Diagnosis

  • Isolate and monitor for clinical signs
  • In the field:
    • Remove brain core sample via straw through occipital foramen in the direction of an eye
    • Place contents in a 50% glyerol/PBS for FAT or virus isolation, or in 10% formaldehyde for histology
    • Whole head can also be removed and sent to lab
  • In the lab:
    • Fluorescent Antibody Test (FAT) on smears or frozen sections of hippocampus or cerebellum should show presence of Negri bodies
      • Being replaced by testing for monoclonal antibodies to nucleoprotein
    • Histological detection of Negri bodies using Mann's or silver stains
    • Intracerebral inoculation of mice followed by FAT testing of brain smears of affected mice
    • RT-PCR on brain or saliva can be performed to determine genotype

Rabies Control

For countries where rabies is considered exotic:

  • 6 month quarantine of carnivores and ruminants (Norway, Sweden, Portugal, Australia, New Zealand)
  • In the UK, this has been replaced by the Pet Travel Scheme (PETS)

For virus-endemic countries:

  1. Control in pets:
    • Annual Vaccination:
      • Antigenicity allows a single antigenic type to vaccinate
      • Inactivated virus or canarypox recombinant viruses
    • Control of stray population
    • Muzzling in public
  2. Control of wildlife reservoir hosts:
    • Feeding vaccinated bait
    • Secondary consequence of increasing reservoir host population (eg European foxes)
  3. Control in humans
    1. Prevention by vaccination with a single booster if bitten
      • The current vaccine is grown in human diploid cells (HDCV) and is BPL-inactivated, and therefore costly
      • Developing countries utilize older vaccines passaged from a 1939 case ("Flury" vaccines)
    2. If bitten and unvaccinated:
      • Clean and disinfect wound
      • Human anti-rabies immunoglobulin administered around bite
      • Intramuscular vaccination program: 2 dose-1 dose-1 dose at 0, 7, and 14 days post-bite

For more on Rabies control in Europe, see here

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