Virology - Rabies Flashcards
What is rabies?
Rabies is an encephalitis, or brain disease, which is caused by the rabies Rhabdovirus. It is a fatal condition that is caused after being bitten by an infected animal, usually a rabid dog (99%) or cat, most occur in developing countries and the majority are children under 15.
It is a zoonosis: infection that has a lifecycle in an animal that can be spread to humans.
There is a vaccination against the disease that can be administered before or shortly after exposure, but once symptoms have developed the condition is almost always fatal.
Which animals can carry rabies?
- Europe: fox, bat
- Middle East: wolf, dog
- Asia: dog
- Africa: dog, mongoose, antelope
- Nort America: foxes, skunks, raccoons, bats
- South America: dog, vampire bats
Where does rabies sit in the Rhabdoviridae family?
What are the characteristics of the rabies virus?
- Lyassavirus of the Rhabdoviridae family
- ss, non-segmented, -ve sense RNA
- Enveloped, ‘bullet’ shaped, ~180x80nm
- RNA codes for 5 proteins: L (large polymerase), M (matrix), N (nucleoprotein), G (glycoprotein), P (phosphoprotein)
APTTRA
Describe the lifecycle of rabies. [6]
Infection is initiated as soon as the virus glycoprotein (G) attaches to the host cell.
- Adsorption: interaction of the glycoprotein spikes with cell-surface receptors. Neuron-specific receptors of the virus: p75 neurotrophin receptor (p75NTR) and neuron adhesion molecule (NCAM) may promote efficient entry.
- Penetration: internalisation proceeds by fusion of the viral envelop with the cellular membrane. Viral envelope then fuses with endosome and releases ribonucleoprotein (RNP). The endosome then fuses with a lysosome which enables the nucleocapsid to discharge into the cytoplasm.
- Transcription: RNP contains all the components needed to initiate viral transcription. The five viral proteins are encoded on one mRNA, produced by the transcriptase complex.
- Translation: mRNAs are processed using the cells ribosomes, translating L, M, N, and P. G is constructed in the RER, and transportation to the Golgi and cell membrane. In neuronal cells, large accumulation of viral protein can be seen as ‘Negri bodies’ (pictured).
- Replication: viral polymerase switches to replication due to an accumulation of N protein which makes a +ve sense RNA strand, which then acts as a template for the -ve strand.
- Assembly: RNA is encapsulated by M which forms a matrix surrounding the RNP core. The complete virion buds off from the cell.
What structure can be seen?
Negri body
Outline the epidemiology of rabies.
- Generally acquired from the bite of a dog.
- 99% of human rabies deaths are in Africa and Asia.
- Preventable either through pre-immunisation, or in the event of exposure, post exposure prophylaxis (PEP) which involves administration of rabies immunoglobulin.
- UK classified as ‘rabies free’, with only 25 cases since 1946.
- Control of spread in dogs is done through surveillance programs.
Outline the progression of symptoms of rabies infection.
- Exposure (contaminated animal saliva)
- Incubation 20-90 days
- Prodromal symptoms: fever, chills, malaise, fatigue, insomnia, anorexia, headache, irritability
- Local neurologic symptoms: pain, paresthesias (pins and needles), puritis (itching skin), weakness
- Classic (encephalitis) rabies symptoms ~80% cases
- Paralytic rabies ~20% cases
No pathogenetic basis for disease
What are the classic rabies symptoms?
- Hyper-excitability: lucid periods, confusion, aggression, hallucinations
- Autonomic dysfunction: hypersalivation, lacrimation (tears), sweating, piloerection (stiff), dilated pupils
- Cranial nerve dysfunction: difficulty swallowing, facial or tongue weakness
- Hydrophobic spasms, aerophobic spasms (fear of water and breathing)
- Cardiopulmonary complications and instability - cardiac arrst and death
What are paralytic rabies symptoms?
- Flaccid muscle weakness
- Laryngeal weakness (mute rabies)
- Facial muscle weakness
- Sphincter movement (urinary incontinence)
- Hydrophobia, less common
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Cardiopulmonary complications- heart attack and death
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How is rabies diagnosed?
- Can be difficult to diagnose if there is no record of animal bite or travel to rabies endemic area.
- Clinical presentation and patient history.
- Diagnostic tests look for virus neutralising antibodies, virus genome, or live virus.
- Tests on CSF, saliva, skin from nape of neck are the only reliable assays used ante-mortem.
- Fluorescent antibody test (FAT), which detects antigens in brain samples using fluorescently labelles anto-rabies antibodies.
- Virus isolation using rabies tissue culture isolation test (RTCIT).
- Histopathological examination, usually post-mortem, view Negri bodies.
- Serological assays using fluorescent antibody virus neutralisation assay (FAVN).
Outline the pathogenesis of rabies.
- Exposure from bite of animal
- Virus replicates in the striated muscle or connective tissue at the site of innoclation and enters the peripheral nerves through the neuromuscular junction
- Spreads to the CNS through Schwann cells
- Terminally, there is widespread CNS involvement
How is contact with a rabid animal treated?
Outline the treatment for rabies.
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Pre-exposure prophylaxis
- Vaccines are liscenced in the UK, given to labortory staff working with rabies, people travelling to endemic regions, animal workers. Involves three doses at day 0, 7, and 28. Lasts 2 years.
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Post-exposure prophylaxis
- Would cleansing (water and soap, alcohol or iodine if available) and immunisations as soon as possible. Post-exposure anti-rabies vaccine should always include passive antibody (HRIG) and vaccine.
Vaccines for humans a inactivated whole virus vaccines. Human Diploid Cell Vaccine (HDCV) best available, however it is expensive.
How can rabies be controlled?
- Killing rabid animals
- Strict quarantine when bringing animals into the country
- Vaccination programs (humans and domestic animals)
- Oral-bait vaccinations for wild animals
