Exam 3 Flashcards
Basics & Clinical Features of Arboviruses
- Arthropod borne viruses
- usually RNA = mutation
Clinical Features
o Fever, encephalitis, hemorrhagic and reproductive diseases
o disease is typically seasonal
Defining Features
o Vector: usually a blood-feeding arthropod ->
o A well-adapted vertebrate reservoir host (enzootic host) ->
o Occasional spillover into epizootic hosts (diseased animals)
Arthropod Vectors of Arboviruses
o Mosquitos, ticks, etc
o Virus replicates & persists in
o Required for virus to exist in nature
Enzootic Hosts of Arboviruses
o Birds or small mammals
o Well adapted reservoir
o Non clinical or long survival w/ high viremia
o Must have many naïve & susceptible animals
Epizootic Hosts of Arboviruses
o Humans or domestic animals (horses) o “accidental” or “incidental” hosts o less well-adapted to virus = disease o Do not typically have persistent infections o Usually lower viremias o Frequently dead-end hosts
Enzootic Cycle for Arboviruses
o Virus is maintained in well- adapted vertebrate hosts (often birds or small mammals) ->
o Virus is transmitted between hosts by a blood-feeding arthropod vector ->
o Virus replicates in the vector, and is required = biologic vector
o Typically NO disease in enzootic host
Triggers for Epizootic Outbreaks
o Increased number of susceptible reservoirs o Increased number of vectors o Vector feeding habits o Change in vector distribution o Enzootic habitat invasion o Change in viral virulence o Human interventions o Increased vector/susceptible host interaction
Important Arboviruses in Vet Med
Eastern/Western/Venezuelan Equine Encephalitis
• encephalitis
West Nile Virus
• encephalitis
Bluetongue Virus
• Endothelial hemorrhage & infarction
Equine Encephalitis Viruses Basics
- arboviruses
- EEV, WEV, VEV, WNV
- 20-100% mortality
- Eastern is most virulent
- Venezuelan is the only transmitted btwn horse & human
Pathophysiology of Systemic Disease in Equine Encephalitus Viruses
- Initial replication in dendritic cells and regional lymph node (near bite) = primary viremia ->
- Amplification in central depot/amplifying organs = secondary viremia ->
- seeds target organs = disease
- Target organ (brain) is usually not source for shedding.
- Portal of exit = blood
Clinical Signs of Equine Encephalitis Virus
Most common febrile illness
o Fever & malaise w/ or w/o infection of target organs
o Due to cytokines
Encephalitis
o Virus enters the brain
o Virus replicates in the brain/spinal cord
o CNS signs = virus usually not in blood or other tissue
Why has West Nile Spread so Quickly?
- > 40 species of mosquito vectors
- presence of suitable naive reservoir hosts
- Many susceptible naïve epizootic hosts
- Suitable environment
Clinical Features of West Nile
Subclinical
o 90% of cases
Infection w/o CNS Dz
o 9% of infections
o fever, non - specific “flu -like” clinical signs
o Most not brought to attention of the veterinarian
CNS Dz
o 1% of infections
o most severe in brainstem and spinal cord
o Ataxia, Hyperesthesia, Muscle tremors, Depression, Rarely seizures, Behavioral changes, Fever, Death in 33%
Diagnosis of West Nile
- CSF: mononuclear pleocytosis, normal to increased protein
- Titer for anti WNV IgM antibody by ELISA
- Post mortem - detect virus in CNS by isolation, PCR, IHC
Control & Prevention of West Nile
Control
o Eliminate mosquito breeding sites (i.e. standing water)
o Control mosquito larvae
o Reduce exposure to biting mosquitos
Prevention o Killed virus vaccine, o DNA vaccines, o recombinant vaccine o all require annual boosters
Orbiviruses
- Bluetongue Virus (BTV)
- Epizootic Hemorrhagic Disease Virus (EHDV)
- African Horse Sickness (AHS)
- Non-enveloped
- RNA,
- segmented genome (prone to reassortment)
- transmitted by Biting Midge
Bluetongue Virus Tropisms
MACROPHAGES
• TNF and other vasoactive mediators -> increased vascular permeability -> EDEMA
ENDOTHELIAL CELLS
• direct injury -> thrombosis, infarction, and hemorrhage
Bluetongue Virus Clinical Syndromes
Vasculitic/Hemorrhagic Disease
• Sheep and wild ungulates/deer
• greatest clinical importance
Reproductive Disease • Cattle • Abortion and reproductive failure • Hydranencephaly in offspring • mostly economically importance
Bluetongue Virus Diagnosis
o Symptoms in sheep
For cows
• PCR & Virus isolation from blood during viremic stage or tissues at post -mortem
• Serology of VP7 (inner capsid) & VP2 (outer capsid)
Bluetongue Virus Management
o Indoor housing during peak vector activity
Vaccination
• Modified -live vaccine available in California
• CAUTION: Use during vector season not recommended, may reassort with field virus
• PROBLEM: No/little cross -protection with other serotypes
Basics of Reproductive Viruses, ideal samples for diagnosis
o Most viral infections of the dam DO NOT cause abortion from fetal infection
o Teratogenic viruses = Developmental abnormalities
o Ex: Flaviviridae & Arteriviridae
Ideal sample for diagnosis
o Fetus
o Placenta
o Dam serum
Basics of Bovine Viral Diarrhea Virus (BVD)
o Flaviviridae = pestivirus
o Enveloped
o (+) RNA
o non-segmented
o mostly cattle but also sheep, goats, pigs, ruminats
o affects repro, GI, respiratory, neuro
o immunosuppression & secondary infections
2 Biotypes & 2 Genotypes of Bovine Viral Diarrhea Virus
2 Biotypes • Non-cytopathic • 90% of BVD • establish persistent infection • Cytopathic • No persistent infection
2 Genotypes
• type 1 & 2
• Both contain cytopathic and non biotypes
• Based on genetic differences in the viral genome
• BVDV-2 associated w/ severe hemorrhagic disease
Pathogenesis of Transient (acute) Bovine Viral Diarrhea Virus infection in non-fetus
- Tonsil & lymph node replication ->
- Enters circulation & transported to lymph & subepithelial tissues of GI & skin ->
- Spreads to epithelial cells ->
- Lymphoid & epithelial necrosis ->
- Shed in bodily fluids ->
- Seroconversion & immunity
3 Outcomes of Transient (acute) Bovine Viral Diarrhea Virus infection in non-fetus
Mild
• Mild erosions of mucuous mebranes
Viral Induced Immunosuppression • Damage to lymphoid tissue • Lymphopenia and neutropenia • Opportunistic infections • Compenent of bovine respiratory dz complex
Peracute BVDV & hemorrhagic syndrome
• some BVDV-2 strains
• High morbidity and mortality in all age groups
• Sudden fever, death, diarrhea and pneumonia
• Thrombocytopenia, neutropenia, myeloid
• Highly fatal (death in 48 hrs)
Transient (acute) infections of BVD in reproduction
- Seronegative pre-breeding or early bred cows
- Compromised ovarian function
Transplacenta infection
• fetal infection leading to persistently infected (PI) calves
Non Cytopathic BVD & Transplacental BVDV Infection
Early gestation (0-45 days) • Abort/embryonic death
Early-mid gestation (45-125 days)
• immunotolerance
• persistent infection
Mid-late gestation (125-175 days)
• Congenital abnormalities
(microphthalmia, cataracts)
• Or normal
Late gestation (175 days to term) • Normal
Immunotolerence due to BVD & Outcomes
- Recognize virus as “self”
- high viral load (Ag positive) but no measurable specific Ab response
- PI cows give birth to PI calves (100% vertical transmission)
Outcomes
• weak and succumbs to disease by 1 year of life
• normal, grows and has babies
• death within hours/days
Character of PI Calves
- Clinically small/unthrifty or normal
- More susceptible to other diseases
- constant source of virus
- susceptible to fatal mucosal disease
Mucosal Dz associated w/ BVD
- Only affects PI animals
- Uncommon and typically 6-12 months of age
- Superinfection with CP-BVDV Or
- NCP-BVDV viral mutation (common)
- HIGH mortality rate (almost 100%) w/in 2 weeks
Transmission of BVD
- active for days- wks under ideal conditions
- Biologic AI material derived from PI animal
- Breeding
- Fomites or iatrogenic
- Introducing new PI animal
- Aerosol transfer from neighbor farm
Transient infection
• Shedding for 1-2 wks
Persistent infection
• Shedding for life
Control of BVD
- Biosecurity
- Elimination of PIs
Vaccination
• Prevention of acute disease
• Prevention of reproductive losses
• Prevention of creating PIs
Diagnostics for BVD
- Viral Ag found in serum, milk, ear notches
- Ab in serum
- Herd screening thru bulk milk testing
- PCR
- Ag ELISA
Immunohistochemistry on skin
• Highly sensitive & false (+) from transient infections
Rabies Basics
o Rhabdoviridae
o Enveloped
o (-)RNA
Envelope Causes:
o Transmission and epidemiology are usually based on direct contact (bite)
o Topical wound (bite) treatment can be of significant benefit
o Glycoprotein G – ligand & target of neutralizing antibodies
Rabies Hosts, Human Infection, & Control
Hosts
o Cats, cows, dogs, horses
o Raccoons, skunks, bats, foxes
Human Infections
o 59,000 annual deaths
o predominant source worldwide = dogs
o predominant source US = raccoons, skunks, bats
Control
o Wound treatment immediately
Vaccination
• All inactivated accept recombinant canarypox for cats
• Viral vectored Vx in bait for wildlife
Rabies Transmission
o Bite wounds ->
o Replicates in muscle cells at site ->
o Quiescent stage in muscle (5days – wks) (time to treat) ->
o Entry into peripheral nerves at motor end-plate ->
o Migrates centripetally, towards CNS (1 inch / day) ->
o Dorsal root ganglion ->
o Spinal cord ->
o In CNS - minor inflammation, neuronal replication & damage, widespread inclusions ->
o Centrifugal spread back to nerves
o NO VIREMIA
Rabies Diagnosis, Shedding Sites/Time
Diagnosis
o Negri bodies in purkinje cells (Inclusion bodies)
o Post mortem
o Direct fluorescent antibody (DFA) test
o PCR (not a public health approved test)
Shedding Sites & Time
o Urine
o SALIVA
o Saliva (+) for virus no more than 10-13 days before signs
Clinical Features of Rabies, incubation, classic presentation, morbidity/mortality
Variable incubation determined by • Location of bites • Severity of trauma • Dose • Viral variant
Classic Presentations
• Furious – excitability & aggressiveness
• Dumb – paralysis & depression
Morbidity / Mortality
• IF disease signs appear, usually fatal
• Post-exposure prophylaxis (PEP) is very effective if done properly (humans only)
Border Disease Virus Basics
o Closely related to BVDV
o Western US
o Subclinical & transient infections in adults
o Barren ewes, abortions, stillbirths, small weak lambs
o PI lambs: BDV infection day 30-70 of gestation
o Hair replaces wool due to thyroid dysfunction
Border Disease Virus Pathogenesis, Diagnosis, Transmission, Prevention
Pathogenesis
• BDV destroys schwann cells & infects thyroid ->
• Low T3 & T4
• Low cyclic nucleotide phosphodiesterase (CNP) ->
• Hypomyelination
Diagnosis
• Ag in tissue,
• PCR for virus,
• no Ab
Transmission
• Body fluids
• Close contact w/ PI animal
Prevention & Control
• Test & removal
Equine Arteritis Virus (EAV); basics, related dz, transmission
o Arterivirus
o Enveloped, (+) RNA
o Infection common but Dz uncommon
Related Dz
• Porcine reproductive and respiratory syndrome virus (PRRSV)
Transmission
• From acutely infected horses
Equine Arteritis Virus (EAV); Pathogenesis, Target Systems, Clinical Signs
Pathogenesis
• enters via respiratory or venereal route ->
• Infects macrophages and endothelial cells ->
• Spreads to regional and central lymphoid organs ->
• Infection of endothelium of blood and lymphatic vessels ->
• Generalized vasculitis and leakage of fluid
Target Systems
• Respiratory
• Vascular
• Reproductive
Clinical Signs
• Fever, depression, anorexia, lymphopenia
• Edema - limbs, prepuce, scrotum
• Periorbital swelling and conjunctivitis
• Abortion
• Neonates: pneumonia & enteritis
Pathogenesis of Equine Arteritis Virus (EAV) Abortion
- Leukocyte viremia ->
- Infection of uterine endothelium & myometrium ->
- Placental damage -> abortion
OR
- Leukocyte viremia ->
- High virus in fetus ->
- Stress ->
- Abortion
Maintenance of Equine Arteritis Virus (EAV) in population
- 30-70% of exposed stallions/colts become carriers
- Asymptomatic carriage, weeks to life-long
- Virus persists in genital tract and shed in semen
- Persistence is testosterone-dependent
- Source of venereal transmission of virus to mares
- Restrictions on international movement of horses and semen
Control & Diagnosis of Equine Arteritis Virus (EAV)
Control
• Non-stallion clears virus ~28 days
Vx
• Modified live and inactivated
• long-lasting immunity for stallions & non-pregnant mares
• Complicated by import/export regulations regarding seropositive horses
Breeding
• Breed (+) stallions to (+) mares
• Breed (-) stallions to (-) mares
Diagnosis
• Need both virology and serology
• Serum Ab detected by neutralization assay or ELISA
• Virus isolation and/or RT-PCR
Equine Herpesvirus & Reproductive Dz
EHV-3 - Coital exanthema (genital disease)
• Similar to genital disease from BHV-1
• Pustules & ulcers on vagina, penis, prepuce
• Localized infection
• No abortion or infertility
• Loss of libido
Exotic Vesicular Dz Viruses; basics, example Dz’s, DfDx
o Eradicated from US but endemic in other countries
o Must control import
o Vets responsible for detection/surveillance
Viruses o Foot and mouth disease (most important) o Vesicular exanthema of swine o Swine vesicular disease o Vesicular stomatitis (not exotic) o Seneca Valley Virus (not exotic)
DfDx
• Autoimmune diseases
• Chemical, thermal burn or frictional trauma
• Drug reactions (secondary autoimmune)
• Photosensitization
Foot & Mouth Dz features & basics
- World’s most economically important dz
- country is required to notify the World Organization for Animal Health (OIE) of an outbreak within 24
- endemic in Africa, south Asia, south America
Features
• Highly contagious picorna virus
• non-enveloped RNA virus
• survives well in environment
• dz of cloven hooved animals (some wildlife)
• virus shed in all bodily fluids before clinical signs
Foot & Mouth Dz; Clinical Signs & how it Affects calves, pigs, sheep, camelids
Clinical Signs
• 2-14 day incubation
• fever lameness, anorexia, salivation, decreased milk
• ulcers/vesicles in mouth, nares, muzzle, feet, teats
• best location = coronary band of hoof
• high morbidity
• prolonged recovery & shed of virus after recovery
Who does it affect
• Neonates & calves – myocardial infection
• Pigs – most severe lesions in feet
• Sheep/goats/camelids – asymptomatic to mild
Foot & Mouth Dz; Prevention/Control & Disadvantages of Vx
Prevention/Control • Vx (serotype must match) • Heat treatment of swill • Quarantine • Disinfection • Euthanasia • Wildlife control
Disadvantages to Vx
• Loss of OIE status
• Vx not cross-protective for 7 serotypes
• Immunity short
Horse, Cow, Pig Susceptibility to Vesicular Dz
Horses
• vesicular stomatitis
Cows
• Foot & mouth
• Vesicular stomatitis
Pigs • Foot & mouth • Vesicular stomatitis • Vesicular exanthema • Swine Vesicular Dz • Seneca Valley Virus
Vesicular Exanthema of Swine
o Calicivirus
o Exotic but affects feral US swine & sea lions
o Indistinguishable form foot and mouth
o Transmitted by feeding undercooked infected meat
Seneca Valley Virus
o Picornavirus o Looks like FMD o Present in the US o Symptoms = Ds, Lethargy, fever o 30-70% morbidity & mortality o resolves w/in 7-10 days
Swine Vesicular Dz
o Picornavirus o Looks like FMD o Exotic o Endemic in Italy o Transmitted by feeding undercooked infected meat
Vesicular Stomatitis Virus; Basics & Transmission
o Rhabdovirus o Serotypes from New Jersey & Indiana o Endemic in SE US o Vesicles -> ulcers on & around mouth o Looks like FMD o Affects horses o Zoonotic (flu-like in humans) o Reportable
Transmission • Arthropods • Transmucosal & transcutaneous • Animal to animal thru direct contact w/ vesicle fluid, saliva, nasal secretions • Plants & soil • Spreads during summer
Vesicular Stomatitis Virus; Symptoms, Diagnosis, Treatment, Control
Symptoms • Mortality rare • Fever • Vesicles, ulcers, crusting of muzzle, lips • Excess salivation • Can involve coronary band, interdigital space, teats • Quick healing • Sheep/goats rarely have signs
Diagnosis • Contact state vet • VSV Ag test of vesicular fluid • Virus isolation • PCR of vesicular fluid & tissue
Ab serology
• Complement fixation = recent infection
Treatment
• Supportive care
Control/Prevention
• Quarantine
• Disinfection
• Control insects
Rinderpest; Basics & Symptoms
o Highly contagious morbilivirus
o Africa & Asia
o High morbidity & mortality
o Similar to distemper minus CNS signs
Symptoms • Nasal, lacrimal secretions • Salivation • Severe bloody Ds • Necrosis & ulceration in GI
Goat Plague; Basics, Transmission, Symptoms
o Rinderpest of sheep & goats
o Morbilivirus
o Africa & Middle East
o Abs to Goat Plague & Riderpest are corss-reactive
Transmission
• Close contact & inhalation
Symptoms • Fever • Inappetence • Depression • Nasal/ocular discharge • Oral hyperemia & erosion • Watery or bloody Ds • Abortion • Dyspnea • cough
Basics of African Swine Fever, type of virus, Hosts, & sources of virus
- Asfivirus
- Enveloped DNA virus
- Multiplies in soft ticks
- Incubation = 5-14 days
Hosts
• Reservoirs – African wild pigs
• Clinical – domestic & wild European pigs
Sources of virus
• Persistently infected animals
• Arthropods
• Environment/fomites
Peracute, Acute, Subacute, & Chronic Clinical Signs of African Swine Fever
Peracute
o sudden death
Acute
o fever, red skin, anorexia, V & Ds, incoordination, abortion,
o 100% death
Subacute
o Less intense
o Fever, anorexia
o 30-70% death
Chronic
o Weight loss, intermittent fever, red skin, respiratory signs, arthritis
o Low death
African Swine Fever Pathogenesis & Gross Lesions
Pathogenesis
• Inhalation, ingestion, or tick bite ->
• Replication in macrophages of of tonsils & LNs ->
• Downregulation of cytokines & immunosuppression ->
• Apoptosis of T & B cells & endothelial cells ->
• Lymphoid necrosis & hemorrhage
Gross Pathology • ENLARGED SPLEEN (important marker) • Cutaneous Ecchymosis (reddening) • Petechial mucus membranes & viscera • Hemorrhagic lymph nodes • Petechial kidneys (turkey egg)
African Swine Fever Diagnosis & Control
Diagnosis
• Ab ELISA of serum
• PCR on blood/tissue
• others
Control
• Import control
• Slaughter
• disinfection
Basics of Classical Swine Fever
- Pestivirus
- Enveloped RNA virus
- transmission through placenta is possible
Basic, Acute, Chronic, In Utero, & transient Clinical Signs of Classical Swine Fever
- Infarcts on margin of SPLEEN
- Hemorrhage of skin, tonsils, kidneys, spleen, LNs
- Fluid in body cavities
Acute
o fever, huddling, lethargy, hyperemia and hemorrhagic skin, lymphadenomegaly, V & Ds, conjunctivitis, incoordination, cyanosis, convulsions
o death of young in 1-3 weeks
Chronic
o Persistent Fever, Ds, poor growth,
o Button ulcers in cecum & large intestine
o apparent recover with eventual relapse
o death w/in 3 months, any age animal
In Utero Transmission
o CNS deformities
o abortion
Transient
o Older animals
o Transient like BVD
Control & Diagnosis of Classical Swine Fever
Control
• Surveilence (test tonsils)
• Slaughter
Diagnosis
• Ab ELISA on serum
• PCR on blood/tissue
• Others
Basics of African Horse Sickness
- 70-95% death
- orbivirus (retrovirus)
- transmitted by biting midges (not contagious)
- zebras & donkeys are subclinical reservoirs
- causes vasculitis -> severe edema & hemorrhage
- can rarely be zoonotic
Clinical Signs & Key Lesions of African Horse Sickness
Clinical signs • Fever • Edema of face and neck • sweating • Respiratory signs • Cardiac failure • Death
Key Lesions • Peracute dz w/ high death rate • Respiratory distress (froth coming form nares) • Edema of supraorbital fossa • Pulmonary edema
Diagnosis & Control of African Horse Sickness
Diagnosis
• ELISA on serum
• PCR on blood, spleen, lung, LN
• gelatinous edema around nucal ligament on necropsy
Control
• Vx in endemic areas
• Quarantine & testing of imported animals
Basics of Papillomaviruses & lesions
o Papoviridae o Small dsDNA o Non enveloped o Environmentally resistant o Often seen in young
Cutaneous & mucosal neoplastic lesions (warts)
• Usually benign
• Can become malignant
• Can involve fibroblasts -> fibropapilloma
• Highly species specific
Papillomaviruses; clinical features & Pathophysiology
Clinical Features
• Localized infections
• Slow process (6-8 wks)
• Proliferating/thickened stratum basale and spinosum (acanthosis) -> hyperkeratosis
Pathophysiology
• Basal epithelium through abrasion ->
• Clonal expansion & continued S phase ->
• Differentiation and viral shedding at/near surface ->
• In healthy animals, immune response controls & wart regresses
Bovine Papilloma Virus; features of different serotypes
• Many serotypes
Serotypes 2 & 4
• bladder & GI warts
• can become malignant w/ co-factors such as brackenfern
• “enzootic hematuria”
Serotype 1 & 2
• Associated w/ equine sarcoid
• Locally aggressive fibroblastic tumor
• Not malignant
Equine Paipilloma Virus; 3 lesions
Cutaneous & benign
• Head & nose
Invasive warts
• Usually sarcoids
• Associated w/bovine papillomavirus
Aural Papillomas
• Rarely regress
• Black flies are mechanical vector
Canine Papillomavirus
- Cutaneous/mucosal warts on/around oral cavity, pharynx
- Sometimes on other parts of the body (digits)
- Pigmented plaques on ventrum and limbs in pugs and min schnauzers
Basics of Poxviruses
o Mild localized or severe systemic o Brick-shaped virion o Enveloped but highly resistant o dsDNA genoma o show cytoplasmic inclusions
Lesions of Poxviruses
o can be both
Proliferative Lesions
• Induces hyperplasia of epithelial cells
• raised edges and depressed center, the classic “pock” nodule
Vesicular Lesions
• Replication, necrosis in deeper epidermal cells, with overlying cells intact ->
• fluid, exudate accumulate in the space, leading to vesicle initially, pustule later ->
• After rupture, exudate forms a crust ->
• Macule -> papule -> vesicle -> pustule -> ulcer -> crust -> scar
Orthopoxvirus; 3 types
Variola (smallpox)
• Systemic dz of humans
Cowpox
• Cutaneous poxviral disease of cattle with lesions on teats, udder
• Rodents -> cow or cat -> human
Monkeypox (exotic)
• Systemic dz of rodents & monkeys in Africa
• Zoonotic
Parapoxviruses; 2 types
Orf & Bovine Papular Stomatitis Virus
• zoonotic
• Very Contagious ecthyma
• Localized infections on lips, mouth (lambs, calves usually) and udders (ewes, cows)
• Interferes with nursing/eating
• Weight loss, trauma (can predispose to secondary infections)
Pseudocowpox (Milker’s Nodules)
• Teat lesions
• Zoonotic
• Causes painless itchy red nodules on humans
Control & Treatment of Orf
Control of Orf
• Live virus Vx
• Disinfection
Treatment
• Ab for secondary infections
Capripoxviruses
- Sheep pox, goat pox, bovine lumpy skin dz
- severe, systemic diseases
- High morbidity and up to 50% mortality.
- All are currently exotic
Avipoxviruses
- Many
- Highly host-specific
- Systemic or localized infections
- lesions on non-feathered areas of legs/face
- Some cause mucosal lesions (pigeon pox)
- Interfere with eating, predator avoidance, secondary infections
