Flaviviridae, Caliciviridae, Astroviridaex Flashcards
Flavus =
yellow
Which viruses belong to the genus pestivirus?
- Genus Pestivirus
-Bovine viral diarrhea virus (BVDV)
-Border Diseases virus of sheep - Classical swine fever virus (CSFV)
Which viruses belong to the genus flavivirus?
These viruses are all?
-West Nile Virus (WNV)
-Japanese Encephalitis virus (JEV)
-Dengue hemorrhagic fever virus (DHFV)
-Yellow fever virus (YFV)
-Tick-Borne Encephalitis virus (TBEV)
Arboviruses
Hepatitis C is apart of Flaviviridae
Flaviviridae have ___ genera and ___ species?
4, 89
What viruses belong to Flavivirus?
-WNV
-JEV
-DENV
-TBEV
YFV
-Bat flavivirus
What viruses belong to Pestivirus?
-BVDV-1
-BVDV-2
- Border DV
- Hagr DV
General Properties of family Flaviviridae
Virion: ___ – __ nm in diameter,
_____ in shape contains a lipid ________.
_______ stranded (__ ve) sense ____ viruses with ____ ___-segmented genomes
The virion RNA: infectious and serves as both the ______ and the viral ______ RNA.
Replication takes place in the _________.
40, 60, Spherical, envelop, SS, +, RNA, linear, non, genome, messenger, cytoplasm
What virus is this?
What can you tell from this image?
Flaviviridae
SS (+ve) sense RNA viruses with linear
non-segmented genomes
What virus is this?
Flaviviridae
Describe the genome structure of Flaviviridae
Single stranded 5’ to 3’
At 5’ –> non coding region; plays an important role
Structural protein is closer to 5’ end. Non-structural region is closer to 3’ end.
Describe the replication cycle of Flaviviridae
What is the host range of Bovine viral diarrhea virus?
Infectious viral disease of a variety of domestic & wild
ruminants worldwide. Does not necessarily cause disease in all animals it infects.
How does BVDV contribute to reproductive loss?
BVDV and reproductive loss
* Low conception rates
* Abortion of early embryo
* Increase in return to service
What virus is pictured here? Label the image accordingly.
List the economic impacts of BVDV infection on dairy/beef industry
List the modes of transmission of BVDV
- Oro-nasal route
- Mechanical transmission of virus in blood
- Iatrogenic
- Endogenous: in utero* infections
- Semen
Explain the oro-nasal route of transmission of BVDV
I- Oro-nasal route: Saliva, nasal secretions and milk - lesser extent in feces
Explain the Mechanical transmission of virus in blood route of transmission of BVDV
II- Mechanical transmission: of virus in blood-
– via insect vectors
Explain the Iatrogenic route of transmission of BVDV
Iatrogenic methods relating to illness caused by medical examination or
treatment: [reused needles, nose tongs]
Explain the Endogenous:
in utero* infections route of transmission of BVDV
Explain the semen route of transmission of BVDV
from infected animal to susceptible animals
Immune tolerance is defined as?
state of unresponsiveness of the immune system to substances or tissues that have the potential to induce an immune response
Immunocompetent is defined as?
the host is capable of developing an immune response
following exposure to an antigen
Immunocompromised is defined as
the immune response attenuated by
administration of immunosuppressive drugs, by irradiation, by
malnutrition, or by certain disease processes such as the viral infection that
produces the acquired immunodeficiency syndrome (AIDS).
Persistent infection is defined as?
the virus is not cleared but remains in specific cells of infected individuals
Classification of BVDV is based on
Based on genomic characteristics and the severity of disease they produce in cattle,
BVD viruses are grouped into ____ genotypes?
- Each genotype is divided into two biotypes. List and explain.
*** Cytopathogenicity does not correlate with the ______ of disease ____ ______. - (Each biotype, cp and ncp contains ___ and ___ virulence strains. Cp and NCP are based on what?
two, : Type 1 and Type 2, severity, in vivo, high, low
cytopathic (cp) and non- cytopathic (ncp) based on how they replicate in cell culture.
Label accordingly.
PI animal means persistently infected animal
*** Important: Remember that BVDV biotype is only a _________ observation (in cell ______) and does not equate with virulence in ______ infections. Some cp strains are recovered from animals with _______ disease (MD), but most of the time ncp isolates are recovered from ________ animals.l
laboratory, culture, natural, mucosal, infected
BVDV Genotypes
Classification based on the ________ of genomic ______ sequences
–> Difference in 5’ UTR sequence between types 1 and 2: The difference is based on the _______ on the __’ UTR (_________ region) between type 1 and 2
** Type-1 BVDV
______ BVD isolates
Used in ________ tests
Used in commercial _______ preparation
** Type -2 BVDV
______ and ________ BVD (_______ outbreaks)
__________ and __________ syndrome
genotype, RNA, sequence, 5, untranslated, Classical, diagnostic, vaccines, Severe, hemorrhagic, recent, Thrombocytopenia, hemorrhagic
- **Non-cytopathic recovered _____ of the times (more common form in ______).
*** Cytopathic - recovered from animals with _______ disease.
N.B: BVDV biotype is only a laboratory observation (in cell culture) and does
not correlated with virulence in natural infections
Non-cytopathogenic (NCP) Cytopathogenic (CP)
Biotypes of BVDV
BVDV
most, nature, mucosal
What can be seen in the image below?
NCP BVDV
What virus can be seen below?
CP - BVDV
BVDV Pathogenesis
** BVDV has a tropism for rapidly _______ cells e.g. ?
** BVDV replicates in ______ cells and has a predilection for the ______
– depletion of CD__+ and CD__+ T lymphocytes
immunosuppression
**—> Bone _______ and intestinal _____ are often infected, the lymphoid tissue of the ________ ______ is frequently depleted.
** –> Tissue distribution varies between strains and highly virulent strains are associated with ______ tissue distribution *** highest concentrations in the ?
dividing, Lymphocytes, mononuclear phagocytes and epithelial cells
epithelial, tonsil, 4, 8, marrow, mucosa, Peyer’s patches, wider
tonsil, thymus and ileum
BVDV infection causes?
Respiratory syndromes
Immuno-suppression
Reproductive syndromes
Enteric Syndrome
Bovine viral diarrhea Virus (BVDV) - Three forms (syndromes)
Type I
Bovine viral diarrhea Virus (BVDV) - Three forms (syndromes)
Type 2
Bovine viral diarrhea Virus (BVDV) - Three forms (syndromes)
Type 3
**Mucosal disease : is clinicopathologic syndrome occurs when PI animals become infected with a closely related ____ strain of _____
CP, BVDV
NPC and CP behave differently in pregnant animal.
NCP vs CP
NCP = from 0-120, _______ and _____ infection occurs, if happens after 120, will __ affect pregnant animal and calf = ______.
CP = more severe action. If infection happens around 90-100 days = ______ , _______, _______ can occur; 100-150 = __________, 150-200 = ______.
Calf born seroposiitve produces ? (see image)
tolerance, persistent, not, normal, abortion, resorption, mummification, malformation, normal
***BVDV immune evasion strategies have effects on both the _______ and __________ immune system. Describe the effects on innate immune response:
-Reduction in ___ and ___ receptor expression on phagocytes.
-Suppress ___-inflammatory cytokines
-Suppress ______ production
innate, adaptive, Fc, C3, pro, interferon
***BVDV immune evasion strategies have effects on both the innate and adaptive immune system. Describe the effects on adaptive immune response
-Depletion of CD__+ and CD__+ T cells
-Decrease in MHC__ and MHC __
production
BVDV immune evasion strategies
Effects on innate immune response
-Reduction in ___ and __ receptor expression
on phagocytes.
-Suppress pro-inflammatory cytokines
-Suppress interferon production
8, 4, I , II, Fc, C3
Fc: protein found on the surface of certain cells – including, among others, ___ lymphocytes, follicular ______ cells, natural killer
* C3: Complement receptors type-3
B, dendritic
Virus enters calf.
Inhibits t cell function, plasma cell, b cell. No antibodies or cytotoxic t cells? Hyjacks immune system to ensure replication.
Study table.
BVDV Persistent Infected carrier development:
*****PI animal: produced when _____ heifer/cow is infected between ____-____ days of pregnancy and the foetus survives
* PI calf is a ______ of BVDV for _____
* ___ animal is a virus factory
* PI animals are poor doer animals: grow at ______ rate than other calves
naïve, 30-125, carrier, life, PI, slower
***Persistent infected carriers will produce ________ ______% of the time.
PI’s, 100
Mechanism of BVDV persistence
****Acute MD
Onset of clinical symptoms within ___-____ days post- infection.
* ________ fever, ________, __________, _________,
* Nasal-ocular _________, corneal ________,
hypersalivation,
* Decreased ____ production
* ____ diarrhea. Diarrhea is often characterized by the
presence
* of mucosal shreds, fibrinous casts, blood and foul
odor.
* Erosions and ulcers - on the tongue, palate, and gingiva
* Epithelial erosions may be pronounced in the
interdigital regions,
* coronary bands, teats, vulva, and prepuce.
* Cattle with acute MD become progressively dehydrated
and usually die within 3-10 days. Although mortality
usually approaches 100%, a few animals may survive
the acute MD but are prone to develop the chronic MD.
10-14, Biphasic, anorexia, tachycardia, polypnea, discharge, opacity, milk, Watery
****Chronic MD
Affected cattle are “poor _____” and may
have ________ diarrhea, chronic ___,
decreased ______, and weight __.
* ________-________ __________ is commonly
seen.
* Cattle with chronic MD rarely survive
past ___ months and are usually _____
due to low performance or die of severe ___________.
doers, intermittent, bloat, appetite, loss, Nasal-ocular discharge, 18, culled, debilitation
Infection in
immunocompetent
non-pregnant cattle
(subclinical infections)
(acute infections)
Sub-clinical
Mild fever, leukopenia,
decreased milk production
Mild BVD - mild erosive
lesions, ulcerative stomatitis,
diarrhea, respiratory
Severe disease - lesions
mimic MD,
thrombocytopenia,
hemorrhagic syndrome,
hyphemia
Infection in
immunocompetent
pregnant cattle
(fetal infections)
All syndromes described above
Embryonic death
Abortions
Birth defects
Persistently infected calves
Infection
In persistently infected-
immunotolerant
cattle
(mucosal disease)
Continuously shed
millions of virus all its
life from all its secretions
- Feces - urine - saliva -
nasal
- milk - semen - uterine
secretions
- aborted membranes, fluids,
fetus - Across fences.
-Virus survives in
environment up to 7 days
***PI animals shed the virus throughout life and are a main source of infection for other animals in a herd
Spot the PI among this group of heifers
Two calves in the picture are persistently infected.
* One of them is indistinguishable from the other healthy calves.
* Usually there is notable variation in weaning weight of
persistently infected calves
BVDV Disease – Acute (TI)
Incubation 5-7 days
Viremia (virus in blood circulation)
4-5 d after infection (up to 15 d)
Seroconversion 2-4 wk later
Virus shedding for 1-2 weeks
Low concentrations compared to PI
Diarrhea, slobbering, fever
Ulcers - lips, gums, esophagus, etc.
Immune suppression
Fetal infections
Most infections are not noticed -
estimate 70-90% are subclinical but
can be severe (death) if virulent
strain
Severe BVD type 1: Clinical Manifestations
Severe, diffuse _____ erosions
Effects on _____ stock
(3-12 months of age)
Unthrifty/Rough ______
Diarrhea
Coughing
Ulcers in mouth (sometimes!!)
Lameness
** ________
_______
** _____ /____ discharge
______
** Oral _________
Immunosuppression
Often confused with parasitism
High morbidity
Low mortality
gingival, young, coats, Leukopenia, Depression, Ocular, nasal, Pneumonia, ulcerations
BVD Type 1
The Hemorrhagic Syndrome associated with BVDV-type 2
* Fever
* Bloody diarrhea
* Epistaxis
* petechiae & ecchymoses
* Hyphema
bleeding from injection sites
* Marked thrombocytopenia
and leukopenia
* IHC staining of infected
megakaryocytes from bone
marrow aspirates of BVDV
type II calf expressing BVDV
antigens
BVDV-Type 2
***BVDV in-utero infections and reproductive outcomes
- ___________ defects
- ____________ in calf with BVDV
- _________/____________
- Cerebellar __________
___________-difficulty getting up and is with broad stance
Congenital, Arthrogryposis, Alopecia, hypotrichosis, hypoplasia, Hypermetric
***Some congenital defects associated with BVDV Infection
Nervous system
Immune system
Musculosketal system
Respiratory system
Eye
Embryonic death -Abortions
Congenital defects -Stillbirths
Normal calves born seropositive to BVDV
Calves born immunotolerant & persistently
infected (PI )
–> Outcomes of BVDV infection in immun-tolernat cattle
1. PI animals may appear normal but go through cycles of clinical diseases marked by ______ and ____
**2. Mortality of PI calves prior to weaning is high
- Congenital defects
- Secondary infections: enteritis, pneumonia, arthritis
** PI animals are the primary _______ for & _____ of BVD virus
** Shedding large amounts of virus in the _____
* Shedding BVDV for life
– Est. in general US cattle population
that prevalence of PI animals is 0.13-
2.0%
anorexia, edema, reservoir, source, environment
Virus Isolation in Cell Culture
**1. Sample types:
WBCS Whole blood Urine
Scrapings from affected gum lesions
Post-mortem tissues (Tonsil, thymus)
* Identification: FA, IHC, RT-PCR
Persistent infection (PI): elevated virus titer
** Rapid tests:
-IHC (ear notch initially)
-Antigen Capture ELISA, RT-PCR
-RT-PCR- Whole blood
Further Confirmatory tests (not rapid)
virus isolation from body fluids, whole
blood
What can be seen in this image?
Diagnosis of BVDV infection
Acute Infection (typically clear infection by 2-3 wks
post-infection)
* Rapid Tests:
* EDTA blood - Buffy coat (RT-PCR)
IFA/IHC on buffy coat cells
After necropsy – tonsil, thymus – RT-
PCR,FA,IHC,
Further Confirmatory - Isolate virus from buffy
coat or affected tissues and ID by _____-____ or ____/_____ (Takes long but considered most reliable test - gold standard)
_______ - (60-85% of cattle have BVDV titers)
**Must know ______ status
– Paired samples: sero-conversion (Four-fold or more)
Submit both samples to same lab at the same time
RT-PCR, IFA/IHC, Serology, vaccination
By blood or milk testing
By skin testing
Testing tissues of a dead
animal
Virus isolation
Small numbers
Herd screening -
microtitre
Antigen capture ELISA
Herd screening
Serology
VN
ELISA
PCR
Genotyping
Pooled samples
_______ _______ samples in the diagnosis of BVDV. This becomes the tissue of choice for screening for PI animals because
1) ____ to collect
2) Equipment requirements are _____
3) **They are not affected by presence of _______ __________
4) They can be used as the sample for a wide variety of tests
-immunohistochemistry,
-real-time polymerase chain reaction and
-antigen-capture ELISA.
Pooling of ear notch samples has been proposed for reducing the cost of surveillance programs
Easy, Ear notch, minimal, passive, antibodies
***BVDV-PI -Diagnostic Tests
PI Management: identification & elimination of PI carriers (Beef feedlots)
** Determine if BVD is active in a herd
– Serology on ________ sentinel animals
* Identify ___ animals
Pooled ear notch/serum samples, then RT-PCR detection
*****a single PI animal can be detected in pools of ___-__ negative samples
Individual skin IHC (ear notch)
Micro plate virus isolation
Any positive test for PI in valuable animals can be confirmed by segregating the animal
then retesting with serum ELISA or whole blood VI/PCR at least 3 weeks later to
eliminate TIs and false positives.
**BVDV Serum Neutralization Test- ________ and ________ antibodies.
**Differentiation of titers due to ________ or ____ virus exposure is difficult
unvaccinated, PI, 10-25, detects, quantifies, vaccination, field
***Controlling BVDV infections
Biosecurity program for Dairy cattle herds
Management and control of BVD
* _____ and ______ PI animals
* Test all new born calves for ___ months
For 9-12 months segregate age groups
** ____________ replacements
Vaccination with _____-_______
BVD infections may persist for some time after removal
of PI animals
* Vaccinate calves after __ months of age
Modified Live: __ dose is protective; ___ doses best
Killed: ___ shots, __-____ weeks apart is required
Best if done at least two weeks before anticipated _____ (weaning/transport/commingling)
***___ months protection against clinical disease
Test, remove, 9 months, Vaccination, MLV-BVDV, 4, 1, 2, Two, 3 - 4 , stress, 12
Border Disease of Sheep
**_________ in sheep, and also is known as “_______ ______ disease” or “____ lamb syndrome.”
* _______ syndrome characterized by ____ birth weight and poor _____, poor _______, tremors because of
delayed _____ of the central nervous
system, and an excessively ____ birth coat
resulting from ___-_____ infection with a _________
*** Note ___ rather than wool
* This lamb trembles and ataxic
Worldwide, hairy shaker, fuzzy, Congenital, low, viability, conformation, myelination, hairy, in-utero, pestivirus, hair
What disease are these lambs suffering from?
Border disease - sheep
Transmission of Border disease of sheep
Transmission typically by direct contact between sheep, and persistently infected
carrier animals
Classical swine fever virus (CSFV)
**Highly contagious viral disease of pigs
(domestic and feral) replicates in ____ ticks (__________ spp)
** Varies in virulence
**** Environmentally ____
**- In tissues (_____)
** - ____ temperatures
* Hog Cholera,
* Peste du Porc,
* Colera Porcina
**** First confirmed in US, 1833
* Endemic in late 19th and 20th century
* Eradicated by late 20th
* Reported in the UK, 1864
**** Recognized in 36 countries
* Eradication
* Australia, Canada, New
Zealand, and the US
* **US last outbreak in 1976
* 1978 US declared Hog
Cholera free
soft, Ornithodoros, stable, meat, Cold
Classical swine fever virus (CSFV)- Hog Cholera
_____ fever (105oF)________, weakness
Anorexia, Conjunctivitis, Diarrhea
Staggering Cyanosis Skin hemorrhages Death
_________: Similar to acute form, but symptoms ___ severe
Pigs ____ survive
Subacute and chronic forms
Chronic: Anorexia, depression, fever, diarrheal; Poor reproductive performance including abortions, stillbirths, and deformities
Persistently infected piglets
Highly variable
Hemorrhage
Necrotic foci in tonsils
Petechiae/ecchymoses on serosal and mucosal surfaces
Kidney, larynx, trachea,
intestines, spleen, lungs
*****________ ____ (“_______ ulcers”)
High, Huddling, Subacute, less, may Necrotic foci, button
Classical swine fever - cold
CSV - Morbidity and Morality
Age and immune status important
Varies with viral strain
**Acute
** ______mortality (up to 100%)
****Subacute
**Lower morbidity and mortality rates
**Chronic
**** _____ animals affected – always fatal
**Some cases are asymptomatic
High, Few
Animal Transmission - Class Swine Fever
* ______ contagious
* Infection via contact with?
* Transmission: Ingestion of contaminated ____ or ___ products, ___ or _____ contact (______)
* Less common: ?
Congenital
Infected pigs are the only reservoir
CSFV only infects pigs
Highly, Blood, saliva, urine, feces, tissues,
garbage, meat, Direct, indirect, fomites
aerosol, semen,
vectors
Clinical Signs Varies: Acutely fatal to asymptomatic
***Acute Disease
Incubation period: __ to __ days
____ fever (___oF)
______, weakness
Anorexia -Conjunctivitis
Diarrhea - _______
____
Skin ______ -Death
**Subacute
Similar to acute form, but symptoms less
severe
Pigs may survive
**Chronic
Anorexia, depression, fever, diarrhea
Poor reproductive performance including
abortions, stillbirths, and deformities
2, 14, High, 105, Huddling, Staggering, Cyanosis, hemorrhages
Congenital Forms of CSF
**Weak “______” piglets
**_______, ________, ________,
***born dead, or congenital tremors.
Persistently infected (immunotolerance) –
become persistent _____ to maintain CSF in ______ herd;
Viremic - seronegative piglets
Highly variable
Hemorrhage
Necrotic foci in tonsils
Petechiae/ecchymoses on serosal and
mucosal surfaces
Kidney, larynx, trachea,
intestines, spleen, lungs
Shaker, Stillbirths, deformities, mummies, shedders, breeding
CSF-Post Mortem Lesions: Chronic Disease
**________ foci (“ ______ ulcers”)
Intestinal mucosa
Epiglottis
Larynx
* Congenital infection
− Cerebellar hypoplasia,
− Thymic atrophy, hemorrhages
− deformities
* ***CSFV can survive long periods in ____ or body ___, particularly if _____ or ______, therefore, feeding of ______ swill should be avoided.
Necrotic, button, meat, fluid, chilled, frozen, uncooked
Diagnostic Tests - Classic Swine Fever Virus
* Detect virus, antigens, nucleic acids
** Tissue samples (?)- Frozen/cryosections for
IHC/FA, Nucleic acids for RT-PCR
Whole blood/buffy coat
***____-PCR
**_____, ____) or direct immunofluorescence,
Serology: ELISA
Diagnostic testing can only be performed @ ?
(FADDL), Plum Island
Differential diagnosis
tonsils, spleen, kidneys, distal ileum
RT, ELISA, IHC, foreign animal disease diagnostic lab
Prevention and control
Do not feed uncooked garbage or meat
products to swine
Minimize visitors on the farm
Especially those who have traveled
internationally in the last 5 days
Implement biosecurity measures
***Clean/disinfect boots
**Clean coveralls
Vaccines for CSF
Available in endemic countries
Protects from disease
Does not eliminate infection
Helpful in outbreak control
**Differential Diagnosis
African swine fever
Acute PRRS
Porcine dermatitis and
nephropathy syndrome
Recommended actions
IMMEDIATELY notify
authorities
Federal Area Veterinarian in
Charge (AVIC)
West Nile Virus (WNV)
* First identified in 1937 in ____ in
the eastern region of Africa;
*****Outbreaks spread to ?
* Virus is spread when a _____
bites an infected ____ and then bites a ___
* Mosquitoes carry highest amount of
the virus during ____ fall (late August to early September).
Uganda, Europe, Asia, and the Middle East
mosquito, bird, person, early
Human infection with WNV
Most asymptomatic
Fever, “flu” like symptoms
(fatigue, anorexia, nausea,
vomiting, arthralgia, rash,
lymphadenopathy)
Encephalitis, meningoencephalitis
- ataxia, painful eyes, seizures,
change in mental status
(confusion)
Case fatality rate in hospitalized
patients - 10-12% risk factor for
severe disease (age 50-60 yr are
10 times and >80 yr are more than
40 times likely)
Most people infected with WNV have
no signs or symptoms.
Common signs and symptoms of West
Nile fever include:
Fever
Headache
Muscle aches
Backache
Lack of appetite
Nausea, vomiting and diarrhea
Skin rash
Swollen lymph glands
At risk group of people
Adults over 50 years old.
People with immune systems weakened
by long-term steroid use, chemotherapy
drugs or anti-rejection drugs following
transplant surgery.
Pregnant women.
People with certain genetic mutations.
skipped this
know this
Biological transmission of WNV-in the mosquito
know this
Phases of WNV infection
know this
Replication cycle of WNV-In mammals
know this
WNV Neurological disease in horses
Ataxia 86% Depression 51%
Hind limb weakness 49%
Difficulty or inability to rise 46%
Muscle tremors 41% Fever only 24%
Differentials: Rabies, EHV 1, EEE, WEE, botulism
10% to 50% of horses with neurological signs die
What disease is this horse suffering from?
West Nile Virus
Transmission cycle of WNV
Reservoir: ____ (Jays and
Crows)
Transmission vector: Mosquitoes from
the genus ____
Incubation period: ___-___ days
Birds, Culex, 3-14
WNV and JEV transmission cycles
* Enzootic cycles are maintained by ___________ vectors host
* WNV-predominantly ____
* JEV- ___ and ____
* Both _______, _______ and other _____ are considered dead-end hosts: incapable of participating in enzootic cycle
mosquitoes, birds, birds, swine, Humans, horses, mammals
Some common causes of Stumbling in horses
None infectious causes
* Long toes are commonly known to cause
stumbling
* Foot pain can lead to stumbling
* Osteoarthritis, such as ringbone (high or low)
or arthritis in the carpus (knee)
* None infectious Neurological problems
(trauma trauma to the spine in the back or
neck)
* A “Wobbler“ diseases in horses (horse with a
damaged spinal cord)
* Some liver diseases
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Infectious Neurological problems
* Equine Protozoal Myloencephalitis (EPM)
* Verminous encephalitis
* West Nile virus (WNV)
* Equine Herpesviruses (EHV-1)
* Eastern Equine Encephalitis (EEE)
* Western Equine Encephalitis (WEE)
* Venezuelan Equine Encephalitis (VEE)
* Rabies virus
* Tetanus
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Mortality rates:
EEE, 90%
WEE, 50%
Tetanus, 75%
West Nile, 33%
Rabies, 100%
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WNV-Vaccines
* No TBEV licensed vaccines available
in __
* Two _________ cell culture derived
TBEV vaccine are available in Europe
US, inactivated
Japanese Encephalitis virus (JEV)
1870s: Japan “_______ encephalitis” epidemics
1924: Great epidemic in Japan
6,125 human cases; 3,797 deaths
1935: Virus first isolated
Fatal human encephalitis case
1938: Virus isolated from mosquito ____ tritaeniorhynchus
Ecconomic impact
Porcine: high mortality in piglets
Equine: up to 5% mortality rate
Humans: -Cost for immunization and medical treatment
-Vector control measures
Summer, Culex
JEV - Horses
* IP: 8 to 10 days
* Usually subclinical
Fever, impaired ________, _____, teeth _____ Blindness, coma, death (rare)
* PM lesions
Horses
Non-specific
Nonsuppurative
meningoencephalitis
locomotion, stupor, grinding
JEV - Pigs
IP unclear
Exposure _____ in pregnancy more harmful
Birth of _____ or ________ fetuses
Piglets: _______ signs, death
Boars: _______, _____ testicles
Swine (fetuses)
Mummified
Hydrocephalus, cerebellar hypoplasia
Spinal hypomyelinogenesis
early, stillborn, mummified, Neurological, Infertility, swollen
JEV - Human
Acute _________
Headache, high ____, ____ neck, stupor
May progress to ?
Neuropsychiatric sequelae ___ to ___% of survivors. In ___ infection possible, Abortion of fetus
PM lesions
Pan- _________
Infected ______ throughout CNS
Occasional microscopic ________ __
___________ generally severely affected
encephalitis, fever, stiff
paralysis, seizures, convulsions, coma, and death
45, 70, utero, encephalitis, neurons, necrotic foci, Thalamus
Diagnosis of JEV
Laboratory diagnosis required
Tentative diagnosis
Antibody titer: HI, IFA, CF, ELISA
JE-specific IgM in serum or CSF
Definitive diagnosis
Virus isolation: CSF, brain
No specific treatment
Supportive care
nothing specific or special; taking right samples, looking at antigens, Ab
Dengue Hemorrhagic fever virus (DHFV)Virus-General criteria
Grade 1
- ______ and _________ constitutional symptoms
-Positive _________ test is only __________ manifestation
Grade 2
-Grade 1 manifestations + ___________ bleeding
Grade 3
-Signs of circulatory ______ (rapid/weak pulse, narrow pulse pressure, hypotension,
cold/clammy skin)
Grade 4
-Profound _____ (________ pulse and BP)
fever, nonspecific, tourniquet, hemorrhagic
spontaneous, failure
shock, undetectable
Transmission and pathogenesis of Dengue virus
The most common epidemic vector of dengue in
the world is the _______ ________ ________. It can be identified by the white _____ or ____ patterns on its legs and thorax
Aedes aegypti mosquito, bands, scale
Pathogenesis of DHFV
Aedes aegypti - see bottom right
DHFV clinical profile
Diagnosis and control of DHFV
* Virus isolation
** Increased IgM as a marker
* Detection of the viral Ag
* IHC
* IFA
* ELISA
* PCR
* ***CBC: __________ and ________
*Reduce vector density to a level below
which epidemic vector transmission will not
occur
Leucopenia, thrompocytopenia
Tick borne encephalitis virus (TBEV)
Louping-ill virus (LIV)
Ticks bite human, incubation period, first phase = uncharacteristic phase, 28 days, curve up again and is in neurological phase.
Pathogenesis and control of TBEV
went through this
Transmission and pathogenesis of TBEV
went through this
TBEV diagnosis
went through this
Yellow fever virus (YFV)
** Caused by __________ that is spread by the _____ ____ or ________ mosquito
*** Cause _______ in patients due to liver damage
Jungle cycle - Between monkeys and forest mosquitoes.
Humans can only get infection occasionally during their ____ visits.
Urban cycle - Occurs between humans and ____ mosquitoes (Aedes aegypti
Flavivirus, Aedes egypti, Haemagogus, jaundice, forest, urban
yellowish coloration of mucous membrane = liver dysfunction
albumin produced by liver
Clinical signs - (YFV)
Muscle aches, hepatomegaly, etc.
*Wesselsbron disease
Acute, ________-borne _______ infection of
mainly which species?
* ________ lambs and goat ___ are most
susceptible, and mortality may occur
* Occasional abortion in ewes, together with congenital malformation of the CNS with arthrogryposis of the ovine (and also the bovine) fetus and hydrops amnii in ewes
* (Incidental spillover occurs to ____, causing a ______, _____-like disease
* Moderate to severe icterus and hepatomegaly, the liver is yellowish to orange brown
arthropod, flavivirus, sheep, cattle, and goats
Newborn, kids, people, nonfatal, influenza
General properties of the family Caliciviridae
* **Calici: latin word ___ or __ (small _____ structures viruses)
* **Virions: non-________, 27-40 nm in diameter, ________
* Some virions have characteristic shape with 32 cup-shaped depressions on their surface
***** Genome: ____ molecule of ____ (__ Ve) sense ___ RNA, 7.4- 8.3 kb in size
* Genomic RNA is polyadenylated
* ________ replication
chalice, Cup, round, enveloped, icosahedral, single, linear, +, SS, Cytoplasmic
insert photo of calici virus here
Caliciviridae- Phylogenetic tree
Four genera:
1- Vesivirus,** = feline callicivirus, swine?, others
2- Lagovirus (rabbit) and
Two genera contain
human caliciviruses
3- Norovirus
4- Sapovirus
Genome structure and organization of Caliciviridae
* Genome organization of human noroviruses into three overlapping open reading frames (ORF1–ORF3).
*** ORF1, -2, and -3 encode for ?
Classification
-VP-1
-RdRp
ORF-1: polyprotein,
ORF-2: major capsid protein VP1
ORF-3: minor capsid protein viral protein 2
Diseases caused by Caliciviruses affecting various species of animals
Good table!
Lagovirus- Rabbit Hemorrhagic Diseases virus
RHDV: belongs to genus Lagovirus
* **RHDV: a deadly disease that can infect rabbits affecting the _____ & blood _________-
* **RHDV: remain in the environment for up to ____ months, making it resilient
* RHDV: capable of surviving both ______ and very ____ temperatures
* RHDV: original strain emerged in China in 1984
* RHDV: second strain called RDHV2 found in France in 2010
* ***RHDV: Rabbits under ____ months of age are not susceptible
*
** RHDV: It is a mutant form of a non-pathogenic virus, termed rabbit ________
* RDHV2: continued to spread throughout Europe and now the US & Western Canada
liver, vessels, 3.5, freezing, hot, two, calicivirus
*******RHDV-Clinical Signs
* Fever
* Shortness of breath
* Loss of appetite
* Listlessness
* Neurological signs such
paddling, seizures, and
paralysis
* Jaundice
* Blood spots in eyes
* Sudden death
* Bleeding from nose at time of
death
Diagnosis of RHDV
-History, clinical signs, PM
-Detection of viral NA by RT-
PCR
-Detection of viral Abs
Feline Calicivirus (FCV)- clinical syndromes
** ______ contagious pathogen with a
widespread distribution in the feline
population
** Belongs to the _______ family,
genus _______; caliciviruses
** Cats can be infected with FCV via the
(3) routes
*** The _________ is the primary site of
replication
* Transient viraemia occurs 3 to 4 days after
infection
* FCV: induces necrosis of epithelial cells:
vesicles, typically on the tongue, develop
into ulcers; in the affected regions, the
mucosa is infiltrated with neutrophils
Highly, Caliciviridae, Vesivirus, nasal, oral or conjunctival
oropharynx
addd photo of ansal and ocular conjunctiva
Feline Calicivirus (FCV)- clinical syndromes
_____ and ____ disease
Erosive lesions on the _______
* FCV infection is ubiquitous and can induce severe disease.
* Feline chronic gingivostomatitis (FCGS)
* Limping syndrome
*
Virulent systemic feline calicivirus (VS-FCV) infection
Paw, mouth, tongue
Diagnosis of FCV
* History, clinical signs, PM lesions
* Viruses in modified live virus vaccines are occasionally shed post-vaccination
* PCR (RT-PCR)-positive result because of the poor correlation between the presence
of virus and clinical signs
* cat that has typical clinical signs and a positive RT-PCR result, a causal relationship
is likely
* Conventional, nested and real-time RT-PCR assays to detect FCV RNA in
conjunctival and oral swabs, blood, cutaneous scrapings or lung tissue
* Virus isolation : FCV replicates in cell lines of feline origin; Virus can be isolated
from nasal, conjunctival or oro-pharyngeal swabs
* Detection of FCV antibodies : ELISA
Therapeutic trials for the FCV
curve of virus goes down post treatment
Feline Calicivirus Prevention
* Both modified live and inactivated parenteral vaccines are available
** __________ ___ intranasal vaccines are still current in the USA
** There is currently no vaccine available that protects equally well against ____ FCV field strains
Modified live (I/M, nasal, conjunctival routes)
Potential hazards
Not in kittens <12 wks. (clinical signs and
persistence)
***Potential for post-vaccination infections
Killed (parental)
Pregnant queens
(Induce only relative not absolute protection)
IN administration of an experimental inactivated, non-
adjuvanted FCV vaccine has been shown to be better than a
S/C vaccine in terms of reducing clinical scores and virus
shedding following exposure
Modified, live, all
3- Noroviruses
* Nonenveloped viruses belonging to the Caliciviridae family
* According ICTV the genus Norovirus has one species, which is called “ _________ virus” named after ______, _____, USA
* Outbreak of acute gastroenteritis occurred among children at Bronson
Elementary School in Nov-1968
* ***Responsible for approximately 90% of epidemic non-________ outbreaks of _________ around the world
* Cause of 50% of all foodborne outbreaks of gastroenteritis
* Able to survive freezing and high temperatures
** Transmitted by ____ contaminated food or water, by person- to-person
contact, and via ______ of the virus and subsequent contamination of
surfaces
* Norovirus are Diverse Group Norovirus (NoV): genetically diverse group of
single stranded RNA
Norwalk, Norwalk, Ohio, bacterial, gastroenteritis, faecal, aerosolization
Noroviruses
* **Noroviruses are a diverse group of viruses in the family _________
* Named after the original Norwalk virus that caused an
outbreak of gastroenteritis in a school in Norwalk, Ohio,
in 1968.
* >25 different types of norovirus strains have been
identified within these groups and new strains continue
to emerge.
** It is possible to develop immunity to ________ types, but we don’t know how ____ that immunity lasts
Caliciviridae, specific, long
ECM picture of Norovirus
Classification of Norovirus
Because..
Food Handlers and Norovirus
* **Persons working with food who are sick with Norovirus gastroenteritis are a particular risk to others because they handle the food and drink many other people will consume
* Transmission:
* -Oral-fecal‖ route: Food (39%)
* -Hands, person-to- person (12%)
* -Water (3%)
** Indirect contact with the virus on contaminated surfaces
* Via contaminated food and water
** Shellfish from sewage contaminated water
Norovirus Signs and symptoms
Acute gastroenteritis (inflammation of the stomach and intestines)
diarrhea, vomiting, nausea, stomach pain
Fever, body aches, fatigue
* Dehydration (because of having diarrhea and vomiting many times per
day)
-Less urination -Dry mouth or throat -Dizziness
** When someone gets infected with norovirus, they may say they
have ‘food _________’ or ‘stomach ____’.
Food poisoning can be caused by _________, but other germs and
chemicals can also cause food poisoning.
* ***People can get infected by:
-Eating ___ or drinking ____ contaminated with norovirus
-Touching ______/______ have norovirus on them then putting fingers in ____
-Having direct contact with someone infected with norovirus caring for, or sharing food, drinks, or eating utensils with an infected person
poisoning, flu, noroviruses, food, liquids, surfaces, objects, mouth
Why are norovirus are difficult to deal with?
Noroviruses are a public health problem.
They are _______ contagious.
***People with norovirus illness shed _______ of virus particles in their ____ and ______, but it only takes a very ___ amount of them (<100 particles) to make someone sick.
They spread easily and ______, especially in closed places like daycare settings, nursing homes, schools, and cruise ships.
They are hard to get rid of because they:
1. stay on objects and surfaces and still infect people after days or weeks
survive both freezing and heating (although not thorough cooking)
and even some disinfectants
2. They are constantly evolving. difficult to develop a vaccine
highly, billions, stool, vomit, small, quickly
Foods commonly involved in norovirus outbreaks
** _____ or _______ foods: such as ___ greens, fresh ____, or _____.
-Any food served raw or handled after being cooked can get contaminated with
noroviruses.
-Fresh produce: may be handled at several different points, including harvesting, processing, and preparing, before it is eaten.
-Water: used to ________ crops can cause norovirus contamination, which will persist
on raw food.
-Raw or undercooked shellfish: like _______, can be problematic when they are
harvested from contaminated water.
-** ___-to-eat foods: like sandwiches and salads.
Raw, undercooked, leafy, fruits, shellfish, irrigate, oysters, Ready
***Clinical signs of Norovirus infection
* Signs and symptoms include:
* Acute gastroenteritis (inflammation of the
stomach and intestines)
* diarrhea, vomiting, nausea, stomach pain
* Fever, body aches, fatigue
* Dehydration (because of having diarrhea and
vomiting many times per day)
* Less urination
* Dry mouth or throat
* Dizziness
* When someone gets infected with norovirus,
they may say they have ‘food poisoning’ or
‘stomach flu’.
How are Noroviruses spread?
* People with norovirus illness shed billions of virus
particles in their stool and vomit.
* People can get infected by:
* eating food or drinking liquids contaminated
with norovirus
* touching surfaces or objects that have norovirus
on them then putting fingers in mouth
* having direct contact with someone infected
with norovirus
* caring for, or sharing food, drinks, or
eating utensils with an infected person
Diagnosis of Norovirus
Specific diagnosis (PCR) assays or real-
time PCR assays, which give results
within a few hrs
* These assays are very sensitive and can
detect concentrations as low as 10 virus
particles
* Molecular detection of Norovirus
Specimen Processing (Faeces)
* RT-PCR Amplify by real-time PCR
Norovirus Genogroup I or II identified
Sequencing Genotyping
*******How to protect ourselves from Norovirus infection?
First: always wash your hands carefully with soap and water after using
toilet and changing diapers and before eating, preparing, or handling food.
Second: wash your fruits and vegetables thoroughly, and cook oysters and
other shellfish thoroughly before eating them.
Third: do not handle or prepare food for others when you are sick.
Fourth: clean and disinfect contaminated surfaces after throwing up or
having diarrhea.
Finally: wash any soiled laundry thoroughly after throwing up or having
diarrhea.
Control of Norovirus outbreak
* Secondary spread via aerosols and vomit is a major problem
* Isolation of patients, staff, and infected areas
* Staff may execrate NOV for up to 14 days (should be checked for clearance)
* Surface cleaning (benches, taps, fomites, fur natures, floors, etc)
* Good hand washing practices: some disinfectants are not effective
* Refer specimens for viral analysis and genotyping to help track movement
of epidemic strains
- Vesicular exanthema of swine (VE)
San Miguel Sea Lion Viral Disease (SMSL) - An acute, contagious disease characterized by
vesicles on the feet, snout, mucous membranes of
the mouth and tongue, and non-haired skin - The disease in sea lions causes vesicles on the
flippers - VE is quite contagious among swine and spreads by
direct contact and fomites - VE is transmitted by eating uncooked garbage
containing infectious meat scraps from swine or
certain fish
Vesicles on the flipper of an
affected animal
Histological appearance of
the vesicle, with
fluid accumulation within the
epidermis.
Family:
Astroviridae
104
Astroviridae: 2 genera, 22 species
:
Genus: Avastrovirus:
Genus: Mamastrovirus
Virion: non-enveloped, icosahedral
28-33 nm in diameter
Genome:
-ss linwar (+Ve) sense RNA
-Poly adenylated at 3’ end and it is infectious
-6-7 Kb in size
-A subgenomic RNA is developed during replication
-6 principle ORFs encoding at least 6 proteins (P, X,
M, G, & RdRp)
* Persistent infection reported in cell culture and
animals
* Virions are resistant to
-Heating at 50 °C for 1 h or 60 °C for 5 min
Classification of Astroviridae
Genome structure and organization of Astroviruses
106
* The astrovirus genome is arranged in three ORFs: ORF1__ and ORF1__ at the 5’ end encoding the ____-structural proteins, and ORF__ at the 3′ end encoding the ________ proteins
a, b, non, 2, structural
Replication cycle of Astroviruses
Transmission of Astroviruses
Pathogenesis of TAstV in turkey poults
Intestinal villi of turkey poults
* A: Control poults showing normal crypts
(3dpi)
* B: Infected poults showing significant _________ in the crypt ____
* C: : Control poults showing normal crypts
(7dpi)
* D: Infected poults showing epithelial _______ and multiple prominent _____
increase, depth, hyperplasia, nucleoli
Pathogenesis of TAstV in turkey poults
Ileum of turkey poults inoculated with TAstV
A:Ileum: cells containing aggregates of _________ inclusion bodies
B: aggregates of intracytoplasmic inclusion bodies
with few free in the cytoplasm
C: Aggregation of astrovirus in the lumen of the distal
ileum adjacent to the enterocytes
intracytoplasmic
Diagnosis & control
History, clinical signs
Sampling: fecal samples , intestine, blood
Detection of virus by EM
Detection of viral nucleic acids by PCR
Detection of viral antibodies by ELISA, SNT etc
Control: adoption of hygienic measures
