Rabies Flashcards
What is rabies?
Rabies is a zoonotic viral disease (a virus that is transmitted to humans from animals).
The disease affects domestic and wild animals and is spread to people through close contact, usually saliva, via bites or scratches
Dogs are the main host and transmitter of rabies.
Bats are important in the Americas and W.Europe. Other wild carnivore species e.g fox, raccoon, skunk, jackal are also reported
Rabies virus
Family: Rhabdoviridae
Genus: Lyssavirus
Species: Rabies virus
Bullet-shaped
- 180nm long and
- 75nm wide
- Single strand, negative sense RNA
Rabies is virtually 100% fatal.
Pathway of virus to brain
- Virus inoculated
- virus replication in muscle
- virus binds to nioctinic acetylcholine receptors at neuromuscular junction
- virus travels within axons in peripheral nerves via retrograde fast axonal transport
- replication in motor neurons of spinal cord and local dorsal root ganglia and rapid ascent to brain
- infection of brain neurons with neuronal dysfunction
- centrifugal spread along nerves to salivary glands, skin, cornea and other organs
Clinical rabies
The virus spreads along nerves towards the spinal cord and brain.
First symptoms usually appear after 1-3 months. Death is inevitable.
Furious rabies – hyperactivity and excited behaviour, fear of water and sometimes air movement. After a few days death occurs by cardio-respiratory arrest
Paralytic rabies – gradual muscle paralysis starting at the site of the bite: a coma slowly develops and eventually death occurs
Rabies is a neglected disease of the poor
Rabies is a neglected disease of the poor and vulnerable populations whose deaths are rarely reported. Occurs mainly in remote rural communities
The average cost of emergency treatment in US$40 in regions where the average daily income is US$ 1-2 per person
40% of people who are bitten by suspect rabid animals are children under 15
Defeating rabies
WHO targeted elimination of human and dog rabies in latin american by 2015 and of human rabies transmitted by dogs in SE asia by 2020
- Information and education campaigns
- Eliminate rabies in dogs through vaccination
- Human population immunisation campaign
- Post-exposure prophylaxis
Rabies vaccine development
First gen: produced using nerve tissues from animals infected with the virus
Second gen: used virus cultures in duck embryos
Third gen: virus propagation in cell culture
Fourth gen: recombinant rabies virus strains or the rabies antigen glycoprotein (G protein)
Rabies prevention in humans
Human rabies vaccine is made from killed rabies virus
Pre-exposure vaccination in 3 doses given:
- Dose 1: as appropriate
- Dose 2: 7 days after dose 1
- Dose 3: 21 days
Population vaccination programmes are costly and difficult to administer
Post exposure prophylaxis (PEP)
- wound cleansing
- vaccination
- rabies immunoglobulins (RIG) - human RIG and horse RIG
Rabies immunoglobulins
Human RIG (HRIG) from vaccinated donors
- Costs about us$250 per patient
- HRIG is available only in specific global markets
Equine RIG (ERIG) from immunised horses
- Is cheaper, but available in limited quantities
- Many manufacturers are discontinuing production
- Side effects – anaphylatic reactions, serum sickness
alternatives to RIG - virus binding antibodies, virus-neutralising antibodies
What is molecular pharming?
Production of recombinant pharmaceutical proteins by plant biotechnology
An unprecedented opportunity to manufacture medicines to improve global health
Plants used to provide inexpensive, scalable supply of anti-rabies antibodies to improve access to anti-rabies treatment in LMICs.
Antibody development pathway
Isolate antibody genes
Agrobacterium
Transfer genes to plants
Confirm plant-made antibodies
cultivation
harvesting
extraction
filtration
purification
final product
