Flaviviridae Flashcards
Name the clinically important flaviviridae in horses in Europe
WNV, Tick borne encephalitis viris, louping ill virus, hepacivirus
which of the 5 clinically important flaviviridae is not in the flavivrus family?
EqHV
What are the 4 most common clinical signs with WNND?
fever, ataxia, weakness, muscle fasiculation
Is disease presentation different between WNV lineage 1/2 infections?
No
What % of WNV infections in horses are subclinical/ result in mild clinical signs
> 80%
Is there an age/breed/sex predilection for WNND?
No
What is the main RF for developing WNND?
WNV vaccination status
What clinical signs are associated with equine TBEV infection?
Generally asymptomatic.
Peracute->subacute non-specific neurological signs
Clinical signs of Usutu virus
clinical disease not described in equids
In which countries has seropositivity to USUV been reported in equids?
Poland, Croatia, Austria
Clinical signs of Louping ill virus in horses
pyrexicup to 40.5C, muscle tremors, paralysis, obtunded mentation
Clinical signs of EqHV
generally subclinical- mild clinpath abnormalities indicating hepatopathy.
Against which protein of EqHV do horses tend to seroconvert?
NS3
When is seroconversion observed with EqHV?
Is delayed- 3-8 weeks post infection. May predate viral clearance
How long does hepatitis last post EqHV infection>
1-4 months
What histopathological changes are observed in the liver following acute EqHV infection?
scattered individual hepatocyte necrosis, mononuclear cell infiltrated
T/F adult horses are more likely to develop persistent EqHV infection than ~<8mo
Falso
What histopathological changes are observed in the liver following chronic EqHV infection?
fibrosis, hepatocyte necrosis, mononuclear inflammation, and biliary reaction.
(only 2 case reports)
Complete
Complete
What species of mosquito is responsible for WNV transmission?
Culex spp
Are mosquitoes capable of vertical WNV transmission?
yes
How does WNV overwinter?
In mosquitoes- diapause, hibernation or in infected females (transovarial transmission)
During which seasons is WNV most prevalent?
starting in summer and continuing through autumn
How is TBEV transmitted?
tick-borne, Ixodes spp. Ticks active when temps >5-7C
How long after the first onset of tick activity would you expect the first clinical cases of TBEV?
2-4 weeks
Other than by ticks, how else may LIV be transmitted?
goat and sheep milk
How is EqHV transmitted
blood, plasma, serum, vertical transmission to foal
Which WNV lineage was responsible for the European 2018 outbreak?
Lineage 2
Complete
Complete
In which year was USUV first identified in the UK, and in which species?
2020- wild birds (blackbirds and house sparrow)
Which countries seem to have the greatest equine infection rate wit TBEV?
high infection rate between 20% and 30% of TBEV in Austria, Germany and Lithuania
Where is LIV most commonly identified as a cause of neuro disease in horses?
Britain
What is the prevalence on PCR of EqHV?
2-40%
What is the prevalence on serology of EqHV?
22% and 84% i
EqHV is on every continent except….
Antartica
Complete
Complete
Complete
What CSF changes are typically found wtih WNND?
mononuclear or neutrophilic pleocytosis, increased protein and mild xanthochromia
List the differentials for WNND
- USUV, TBEV, LIV- similar seasonal presentations and cross react in most diagnostic tests
- EHV-1
- Borna virus
- Verminous meningoencephalitis
- Bacterial meningitis
- Botulism
- Toxicosis
- Trauma
- CVM
EMP
Whi is PCR of blood/CSF rarely diagnostic in WNND?
short lived and low level viraemia
What protein do WNV serological tests target?
E protein
How should WNV rapid assay results be confirmed?
All positive serological results using rapid assays should be confirmed by the more specific virus neutralization test (VNT) with the viruses known to circulate in the area.
Which part of the brian has the highest viral load on WNV?
Medulla
How may WNV diagnosis be confirmed post mortem?
RT-PCR: brain, intracerebral inoculation of mice, IHV, ISH of freshor formalin fixed neural tissue.
What seological tests are employed for LIV?
HI, PRNT
How us EqHV infection confirmed?
- RNA isolation from serum or liver specimens, quantitative RT-PCR. Highly conserved UTR (untranslated region)
- Serologic detection of anti-EqHV specific IgG antibodies (LIPS)
= luciferase immunoprecipitation system= semiquantitative - Are sero+ in acute hepatitis and persistent infection
- NS3 protease is target as highly conserved
T/F Horses are not sero+ in acute hepatitis and persistent infection with EqHV
F
What protein does EqHV serology target?
NS3 protease
What region is targeted by EqHV PCR?
UTR: utranslated region- highly conserved
T/F EqHV viraemia is short lived
F: Horses may be viraemic for months to years without hepatitis
How is an acute EqHV infection confirmed?
a single positive serum or liver PCR does not confirm that EqHV is the cause of hepatitis.
* In acute EqHV infections, viremia should decline or clear within a few weeks after the onset of hepatitis, and hepatitis (especially elevated GGT) might continue past viral clearance.
How is a chronic EqHV infection confirmed?
- In chronic hepatitis, persistent infection should be confirmed by repeated serum RT-PCR, and other causes should be ruled out by anamnesis, hematology, liver biopsy with culture, and investigation of the diet.
Should corticosteroids be used in the treatment of flavivirus infections?
controversial because of their immunosuppressive effect that might increase viremia.
immunomodulatory effects of corticosteroids might hold benefits by reducing the amount of immune-mediated inflammation of the CNS.
no scientific evidence supporting the use of corticosteroids, but also there are no contraindications
What agent has been proposed as an antiviral for the treatment of EqHV infection?
sofosbuvir, has been predicted to also bind EqHV by computer modeling.
Why is the investigation of sofosbuvir in the treatment of EqHV infection controversial?
sourcing such medications for equine use when they are not easily obtained for human patients
What WNV vaccines are available in the EU?
inactivated chimeric Yellow Fever Flavivirus vaccine expressing the structural prM/E proteins of WNV
whole inactivated vaccine containing a lineage 1 strain
modified-live attenuated recombinant canarypox-based vaccine expressing the WNV prM/E protein
Which WNV vaccine type is recommended?
Current evidence does not suggest a clear benefit of 1 vaccine over another
All 3 vaccines induced protective antibody levels for a minimum of 6 to 12 months, and protected animals against the severe neurologic form of the disease in field and clinical trials.
What is the recommended WNV vaccination protocol?
- First vac: 5 to 6 months of age
- annual boost immunization (usually recommended in spring before the mosquito season)
- frequency could be adjusted based on the epidemiological situation (eg, semiannual or more frequently in case of active circulation, at the start of the mosquito season).
- Vaccination of pregnant mares is recommended before the breeding season, with a boost-immunization a few weeks before foaling to provide passive immunity to foals through colostrum.
Individual recommendation varies from country to country- is generally recommended in endemic areas,
Does the WNV vaccine provide cross protection against other flaviviruses?
There is no evidence to support this.
What % WNV clinically affected horses display neuro signs?
10% present with neurological disorders as compared to 1% of humans
Why is the passive surveillance of WNV in horses problematic as a monitoring tool for human WNV?
Large numbers of horses have been exposed to WNV in many parts of Europe and have not developed clinical signs, while developing protective immunity. This, in combination with widespread vaccination, should eventually decrease the pool of susceptible horses and decrease their role in syndromic surveillance systems.
(On the other hand, clinical findings in horses might be of help for syndromic surveillance for WNV activity in countries so far considered to be free of WNV)
For which virus may EqHV be used as a model in order to study immune responses/ pathogenesis?
Human hepatitis C (HCV)
