Transmissible Spongiform Encephalopathies Flashcards
General on Transmissible Spongiform Encephalopathies
Infectious agents of uncertain structure
Spongiform degenerative lesions- no inflammation associated with lesions.
Slow, progresive onset of neurological disease (2-5 years before they show signs)- once they show signs they die relatively quickly
Uniformly fatal
Very atypical- most similar to viruses but are distinct
General on Transmissible Spongiform Encephalopathies
Infectious agents of uncertain structure
Spongiform degenerative lesions- no inflammation associated with lesions.
Slow, progresive onset of neurological disease (2-5 years before they show signs)- once they show signs they die relatively quickly
Uniformly fatal
Very atypical- most similar to viruses but are distinct
What diseases fall under Transmissible Spongiform Encephalopathies?
Scrapie, Bovine spongiform encephalopathy, Chronic Wasting disease, Transmissible mink encephalopathy, Kuru, Creutzfeldt-Jacob Disease, Familial Insomnia, and Gerstmann-Straussler Disease
What’s the problem with the lesions on the brain?
They happen normally with old age, so sometimes it is difficult to know if it occurred due to the disease or normal aging processes
Why is the agent unusual?
- Filterable (take infectious material- pass through a filter- removes infectivity of TSEs),
- about the same size as a virus, no virion-like structures * highly resistant to inactivation (tx with UV light, formalin, exposure to gamma radiation- much harder to kill off infectivity than any other virus)
- no nucleic acid identified, too small to encode protein * lipid associated
- Scrapie associated fibrils
- infectivity destroyed by protein disruption
Why is the agent unusual?
- Filterable (take infectious material- pass through a filter- removes infectivity of TSEs),
- about the same size as a virus, no virion-like structures * highly resistant to inactivation (tx with UV light, formalin, exposure to gamma radiation- much harder to kill off infectivity than any other virus)
- no nucleic acid identified, too small to encode protein
- lipid associated (concentrated in the fatty tissues of the brain, most viruses tend to be associated with aqueous parts)
- Scrapie associated fibrils (SAFs- associated but too big to be filtered)
- infectivity destroyed by protein disruption (might be infectious proteins)
Why is the agent unusual?
- Filterable (take infectious material- pass through a filter- removes infectivity of TSEs),
- about the same size as a virus, no virion-like structures * highly resistant to inactivation (tx with UV light, formalin, exposure to gamma radiation- much harder to kill off infectivity than any other virus)
- no nucleic acid identified, too small to encode protein
- lipid associated (concentrated in the fatty tissues of the brain, most viruses tend to be associated with aqueous parts)
- Scrapie associated fibrils (SAFs- associated but too big to be filtered)
- infectivity destroyed by protein disruption (might be infectious proteins)
Louping Ill Vaccine Contamination
One group of sheep they used to make vaccination were infected and they distributed Scrapie
Why are TSEs (the disease) unusual?
- Very long incubation period (2-5 years)
- No evidence of inflammation
- No apparent immune response
- Adaptation to the host species
- Effect of dose on incubation period
- Influenced by a single gene (PRP- prion protein gene)
- Strain characteristics
Why are TSEs (the disease) unusual?
- Very long incubation period (2-5 years)
- No evidence of inflammation
- No apparent immune response
- Adaptation to the host species
- Effect of dose on incubation period
- Influenced by a single gene (PRP- prion protein gene)
- Strain characteristics
How did they type different strains of Scrapie?
Imaging of the brain and mapping out the lesions and finding the pattern
How did they type different strains of Scrapie?
Imaging of the brain and mapping out the lesions and finding the pattern
What is the agent of TSE?
Prion hypothesis- infectious protein, post-translationally modified variant of host’s own PrP protein. Protein gets misfolded or refolded so it becomes much more resistant to destruction from proteases. So the cell has a hard time removing accumulation and eventually it messes up the function of the cell. PROPAGATES the CHANGE IN FOLDING- why it is INFECTIOUS. (there are some inheritable encephalopathies in humans which have a mutation in PrP gene)
What is the misfolded protein called in Scrapie?
PrPsc
What is the misfolded protein called in Scrapie?
PrPsc
What are the clinical signs and symptoms of Scrapie
Pruritis, tremors, ataxia, paralysis, wasting, subacute- most die in 4-6 weeks, generally 2-5 yo
Pathogenesis of Scrapie
Vacuolation and degeneration of neurones of CNS, hypertrophy of astrocytes; tonsils, spleen, lymph nodes, probably in dendritic cells, spinal cord, ascends the spinal cord to the brain
Pathogenesis of Scrapie
Vacuolation and degeneration of neurones of CNS, hypertrophy of astrocytes; tonsils, spleen, lymph nodes, probably in dendritic cells, spinal cord, ascends the spinal cord to the brain
Epi of Scrapie
Spread horizontally, vertically?, injection of infected material, new strain IDed in resistant sheep- unrecognized infected population or spontaneous disease
Epi of Scrapie
Spread horizontally, vertically?, injection of infected material, new strain IDed in resistant sheep- unrecognized infected population or spontaneous disease (called atypical Scrapie)
Diagnosis of Scrapie
Animal inoculation, histopathology, ELISAs, or Western Blots specific for protease resistant PrP
Control of Scrapie
Eradication by aggressive slaughter campaigns (i.e. NZ), quarantine regulations, failure in North America and Europe (long incubation period), breeding resistant sheep (select for resistant genetics), atypical scrapie
Bovine Spongiform Encephalopathy general (Mad Cow Disease)
Britain- 1986- 1994 peak of epidemic 30K cases in the UK
Hyperaesthetic (non-noxious stimulus causes pain), apprehensive, nervous, frenzied
Eventually ataxic, then debility, recumbency, and death
Death in weeks to months
Incubation period of several years
Typical spongiform lesions
Feline spongiform encephalopathy
Epi of BSE
In British dairy cattle, shift from batch to continuous processing of meat meal (takes less time, but the temperatures are lower)
- Temps were high enough to kill most agents, but not BSE
- Also reduced use of lipid solvents which allowed BSE to get through
- ban on feeding meat meal to cattle- so very little vertical or horizontal transmission since
Epi of BSE
In British dairy cattle, shift from batch to continuous processing of meat meal (takes less time, but the temperatures are lower)
- Temps were high enough to kill most agents, but not BSE
- Also reduced use of lipid solvents which allowed BSE to get through
- ban on feeding meat meal to cattle- so very little vertical or horizontal transmission since
Diagnosis of BSE
Histopathology- specific detection of PrPsc
Control of BSE
Ban on feeding meat meal, average age of infected cattle increased, numbers of cases declined dramatically, slaughter of all suspected cases
Transmissible Mink Encephalopathy
Rare outbreaks in farmed mink, feeding scrapie infected sheep meat to mink, experimental feeding of scrapie to mink, downer cows- BSE?
Transmissible Mink Encephalopathy
Rare outbreaks in farmed mink, feeding scrapie infected sheep meat to mink, experimental feeding of scrapie to mink, downer cows- BSE?
Chronic Wasting Disease general
Mule deer and elk (wild and farmed), captive deer and in free ranging animals, not food borne exposure, progressive weight loss, behavioural changes, salivation, polydipsia, polyuria, increasing evidence- infectivity in venison
Kuru general
Progressive paralysis, fore people of New Guinea highlands, women and children, familial, ritual cannibalsim practised on dead relatives, changing religious practices
Creutzfeldt- Jacob Disease general
Presenile dementia of humans, rarely throughout the world, including AUS, familial, iatogenic or sporadic,, contaminated instruments, corneal grafts, growth hormone
Can BSE infect humans?
Yes from eating beef 177 deaths (every case becomes a death) since 1996. Risk is 1 in 7 million per year.
Family Arteriviridae- Family Arterivirus- general & 2 main viruses?
Host specific (horses, pigs, mic, monkeys), Antigenically unrelated, macrophages are the target cell Equine Arteritis Virus (EAV) and Porcine Respiratory and Reproductive Syndrome Virus (PRRSV)
Equine Arteritis Virus (EAV)
ss negative sense RNA viruses, nested replication, enveloped, replicate in perinuclear cytoplasm- macrophages, relatively labile- sensitive to heat, low pH, detergents, etc
Where does Equine arteritis virus occur?
Worldwide, most infections are asymptomatic, outbreaks of clinical disease are rare
Clinical signs of Equine arteritis virus (EAV)?
Incubation: 3-14 days, present with fevere, excessive lacrimation, conjunctivitis, rhinitis, nasal discharge, stiff gait, ventral oedema
Urticaria of head and neck
More severe in very young and old animals
Abortions (storms)
Clinical signs of Equine arteritis virus (EAV)?
Incubation: 3-14 days, present with fevere, excessive lacrimation, conjunctivitis, rhinitis, nasal discharge, stiff gait, ventral oedema
Urticaria of head and neck
More severe in very young and old animals
Abortions (storms)
Epi of EAV- transmission, who? clinical signs and symptoms?
All equids (donkeys mules horses)
SB more seropositivity than TBs
Outbreaks of disease are sporadic
** Abortions are most obvious sign of disease
** Resp. spread is the most common way of transmission
** Shed virus in semen as well (via genital tract)- mare gets infected from venereal spread
- Transplacental transmission as well
Epi of EAV- transmission, who? clinical signs and symptoms?
All equids (donkeys mules horses)
SB more seropositivity than TBs
Outbreaks of disease are sporadic
** Abortions are most obvious sign of disease (this is through respiratory spread from mares who mated with an infected stallion)
** Resp. spread is the most common way of transmission
** Shed virus in semen as well (via genital tract)- mare gets infected from venereal spread (CHRONICALLY INFECTED STALLION IS THE KEY- they are chronically shedding this virus in their SEMEN– mate with the mare and you get respiratory spread from mare)
- Transplacental transmission as well
Clinical signs of Equine arteritis virus (EAV)?
Incubation: 3-14 days, present with fevere, excessive lacrimation, conjunctivitis, rhinitis, nasal discharge, stiff gait, ventral oedema
Urticaria of head and neck
More severe in very young and old animals
Abortions (storms)- lots of pregnant females- lots of abortions
Epi of EAV- transmission, who? clinical signs and symptoms?
All equids (donkeys mules horses)
SB more seropositivity than TBs
Outbreaks of disease are sporadic
** Abortions are most obvious sign of disease (this is through respiratory spread from mares who mated with an infected stallion)
** Resp. spread is the most common way of transmission
** Shed virus in semen as well (via genital tract)- mare gets infected from venereal spread (CHRONICALLY INFECTED STALLION IS THE KEY- they are chronically shedding this virus in their SEMEN– mate with the mare and you get respiratory spread from mare)
- Transplacental transmission as well
* again don’t run non-pregnant animals with pregnant animals*
Pathogenesis of EAV
Aerosol transmission- replication in alveolar macrophages- spread to bronchial lymph nodes
Viraemia (extracellular and in macrophages)
FOUND in all tissues and body fluids
Primary targets- macrophages and endothelium
Secondary- most organs (kidney, liver, seminiferous tubules)
Abortions follow viraemia and transplacental spread
Pathology EAV
Oedema, congestion and haemorrhage; aborted foetus expelled with placenta, no premonitory signs (not likely to spread from foetus)
Diagnosis EAV
RT-PCR or virus isolation from semen, respiratory samples
Serology- neutralisation, CF, ELISA
Diagnosis EAV
RT-PCR or virus isolation from semen (MAINLY WHAT IS DONE NOW WITH VIRUSES), respiratory samples
Serology- neutralisation, CF, ELISA
Why do you need to differentiate? Containment and quarantine. Need to differentiate EHV from EAV- source of the Herpes will be reactivation. Whereas source of EAV would be carrier stallion and/or a mare (respiratory spread)
Diagnosis EAV
RT-PCR or virus isolation from semen (MAINLY WHAT IS DONE NOW WITH VIRUSES), respiratory samples
Serology- neutralisation, CF, ELISA
Why do you need to differentiate? Containment and quarantine. Need to differentiate EHV from EAV- source of the Herpes will be reactivation. Whereas source of EAV would be carrier stallion and/or a mare (respiratory spread)
Control of EAV
Vaccinations available, carrier stallion- future?? Mated to mares infected previously and are immune- “endemic situation”- no problem (would see mild clinical signs in younger horses and nothing in older horses). But in a naive population it would be a problem.
Control of EAV (2 main points)
Vaccinations available, carrier stallion- future?? Mated to mares infected previously and are immune- “endemic situation”- no problem (would see mild clinical signs in younger horses and nothing in older horses). But in a naive population it would be a problem.
Epi of EAV
After acute infection- virus is elimated from mares and geldings, persistent infection of 35% stallions, asymptomatic carriage and shedding by stallions, persistent infection does not affect stallion fertility, 80% of mares become infected (only a temperary reduction in fertility due to hyperthermia)
Procine resp and repro syndrome virus general
Reproductive failure in sows (reduced conception and farrowing rates, abortions, mummifications and stillbirths, weak neonates, longer return to service interval
* Pneumonia in young pigs (resp distress and cyanosis of skin particularly around ears, vulva, and abdomen)
Exacerbated by concurrent infection (Mycoplasma spp., Streptococcus suis)
PRRSV
Exotic to AUS, infect pigs only, vaccines
Birnaviridae
Non-enveloped, ds RNS
** Infectious bursal disease of chickens- occurs worldwide
Economic and scientific importance as IBDV replicates in Bursa of Fabricius in dividing B lymphocytes- immunodeficiency (UNUSUAL because it is a B CELL)
Morbitidy- 100%, mortality- 100%
Caliciviridae- 2 important genera?
vesivirus (vesicular exanthema of swine and feline calicivirus infection) and lagovirus (rabbit haemorrhagic disease virus)
Caliciviridae general
IMPORTANT IN PRAC TOO: ** Non-enveloped, ss RNA viruses, replicate in the cytoplasm of infected cells, released by cell lysis, relatively resistant to heat and detergent based disinfection, no resistant to acid pH (99% inactivated pH
Caliciviridae general
IMPORTANT IN PRAC TOO: ** Non-enveloped, ss RNA viruses, replicate in the cytoplasm of infected cells, released by cell lysis, relatively resistant to heat and detergent based disinfection, no resistant to acid pH (99% inactivated pH
Vesicular exanthema of swine- why is it important?
LOOKS like FMD which is why it is important!
Laboratory diagnosis is essential: isolation from vesicles
Stop feeding them ground of animal products
Feline Calicivirus Infection General
Significant upper respiratory tract pathogen of cats, isolated from domestic cats and also Large cats in zoos, Feline herpesvirus, calicivirus and chlamidophyla commonly cause URT disease (worldwide)
Epi of Feline Calicivirus Infections
Cats of all ages susceptible, acute disease most common in kittens, 2-6 months as maternal Ab wanes, Excrete large amounts of virus in oronasal secretions
Persistent infection (small percentage) these cats maintain the virus in the population (vs. herpes where every indiv will have latent infection)
** shed virus for months to years from oropharynx
Pathogenesis of Feline Calicivirus Infections
Transmission by inhalation of aerosol or direct contact via oral nasal or ocular route, virus replication in oropharynx, rapid spread through URT/ conjunctiva, transient viraemia, Disease severity related to strain differences
Clinical Signs of Feline Calicivirus Infections
Short incubation period- 5 days (normal for resp spread)
Conjuncitivitis, rhinitis, tracheitis and pneumonia
Vesiculation and ulceration of tongue and oral mucosa
( Cat is drooling- doesn’t want to swallow because it hurts, crusty eyes)
* blister breaks with vesicular fluid- vesicles
Shifting lameness associated with kittens
Virus detection of Feline Calicivirus
Virus detection in swab material, paired sera
Control of Feline Calicivirus
Inactivated and attenuated vaccines available
** feline herpes virus, feline calicivirus, feline panleukopaenia virus
Rabbit haemorrhagic disease
Highly contagious and often fatal disease of EU rabbits
Rabbits less than 2 months old are not susceptible
First reported in China in 1984, RHDV is considered a mutant of non-pathogenic rabbit calicivirus
Endemic in EU, Central america, and Africa
Biological control agent in AUS and NZ
Control of Feline Calicivirus
Inactivated and attenuated vaccines available
** feline herpes virus, feline calicivirus, feline panleukopaenia virus
Rabbit haemorrhagic disease general
Highly contagious and often fatal disease of EU rabbits
Rabbits less than 2 months old are not susceptible
First reported in China in 1984, RHDV is considered a mutant of non-pathogenic rabbit calicivirus
Endemic in EU, Central america, and Africa
Biological control agent in AUS and NZ
Epi of Rabbit haemorrhagic disease
Virus is shed in all secretions and excretions, virus survives in environment
Transmission of Rabbit haemorrhagic disease
Faecal-oral route (rabbits in close contact), inhalation, through conjunctiva, mechanical transmission (by mosquitos and fleas), fomites
Pathogenesis of Rabbit haemorrhagic disease
replicates in mononuclear phagocytic cells, causes acute hepatic necrosis, DIC
Clinical signs of Rabbit Haemorrhagic Disease
SUDDEN DEATH (
Clinical signs of Rabbit Haemorrhagic Disease
SUDDEN DEATH (
