Transcript Caprine Arthritis and Encephalitis

Caprine
Arthritis and
Encephalitis
KATIE SIMPSON, DVM, MS, DACVIM
CROSS TIMBERS LARGE ANIMAL CLINIC
APRIL 30, 2016
Outline
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Etiology
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Transmission
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Pathogenesis
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Clinical Signs
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Diagnosis
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Prevention
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Other Lentiviruses
Introduction
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1st recognized1974 in USA
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Switzerland 1969
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Worldwide
Economically important
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↑ Cull rates
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5-10% arthritis
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↑ Incidence
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↓ Productivity
Etiology
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Family Retroviridae
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Oncogenic
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Non-oncogenic
Genus Lentivirus
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“Slow Viruses”
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Chronic degenerative disease
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Long incubation
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Life-long persistence! Once they are infected, they
are infected for life
Etiology…
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Lentiviruses…
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Caprine Arthritis-Encephalitis Virus (CAEV): Goats
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Maedi-Visna Virus (MVV): Sheep
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Bovine Immunodeficiency Virus (BIV)
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Equine Infectious Anemia (EIA)
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Feline Immunodeficiency Virus (FIV)
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Human Immunodeficiency virus (HIV)
Etiology…
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Closely related to MVV
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Genetically distinct
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Morphologically/physically the same
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Comparable syndromes
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Cross-species transmission
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Experimental
Etiology…
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Serum antibodies = infection
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Different strains
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No tissue tropism
Transmission
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Lactogenic (milk, colostrum)
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Target organ
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Mammary gland
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Macrophages
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Epithelial cells
Transmission…
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Lactogenic…
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Nursing dam
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Even subclinical
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Pooled colostrum
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Adams et. al. 1983
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Cell free and cell-associated virus
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Survived concentration and freezing
Transmission…
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Transplacental
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Occurs, unknown rate
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5-10%
Lamara et. al. 2001
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In vitro infection of oviduct epithelial cells
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No reports of in vivo occurrence
Transmission…
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Horizontal transmission (one juvenile/adult to
another)
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Intense management
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High stocking density
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Also poor management, poor hygiene
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Possibly through saliva, nasal secretions, urine, feces,
blood
Older animals
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Possible delayed latent neonatal infection
Transmission…
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Other means
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Shared milking facilities
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Milking infected w/non-infected
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Iatrogenic
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Venereal
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Not proven
Transmission…
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Factors…
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Breed
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↓ Prevalence in Saanen, Golden Guernsey
Genetic factors
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Saanens tend to have lower risk of arthritis
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Stress
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Immunosupression
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2° infections
Pathogenesis
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Mechanisms unclear
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Subclinical infections common
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Prepatent period varies
Host cell
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Monocyte/macrophage (type of white blood cell)
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Restricted replication
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Transcription monocytes → macrophages
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Undetected in monocytes
Pathogenesis…
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Viral load ↓ in asymptomatic
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Cell mediated immunity
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Synovial fluid/tissues
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CD8+ cytotoxic T-cells
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↑ [IgG]
↓ level immune stimulation
Genetic predisposition
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Similar to Rheumatoid Arthritis (RA)
Pathogenesis…
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Infected macrophages in all tissues
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Alter cytokine production
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Stimulate immune response
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Released in RA
Nitric oxide synthase
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↑ In joints
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Role unknown
Pathogenesis…
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Antibody detection
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May take weeks → months
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Suggested that Abs
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Don’t protect…
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Enhance infection
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Immune complexes taken up by macrophages
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Seen w/ HIV and FIV
Pathogenesis…
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Arthritis: Similar to RA
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Infiltration of synovial membranes
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Disease related changes of articular (joint) surface
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↓ IL-2 expression
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Cytokine pattern altered
Clinical Signs
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Chronic inflammatory lesions
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Most subclinical (NOT apparent)
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Seroprevalence 0-81%
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25-30% develop disease
Clinical Signs…
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4 (5) clinical manifestations:
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Arthritis
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Encephalitis
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Interstitial pneumonia
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Indurative mastitis
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+/- Chronic weight loss
Clinical Signs…
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Arthritis
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“Big Knee”
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Adults >1 year
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Predominant form
Course varies
Clinical Signs…
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Carpal joints > tarsal, stifle, fetlock joints, atlantooccipital bursa > coxofemoral joint
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All synovial membranes
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Tendons, bursa, periarticular tissues
Clinical Signs…
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Arthritis…
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Early signs subtle
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Periarticular swelling of carpus (knee)
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Fluctuant, cool, not painful to palpation
Painful & debilitating
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Collapse of joint, ankylosis
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Severe flexion of carpus
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“Knee walkers”
Hindlimb swelling less obvious
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Gait may resemble incoordination
Clinical Signs…
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Arthritis…
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Synovial (joint or tendon) fluid
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Acute
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Serous
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Dark-yellow or blood tinged
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Fibrin, lymphocytes/macrophages
Chronic
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Normal
Clinical Signs…
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Viral Leukoencephalomyelitis (brain/spine
involvement)
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2-6 months old
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Develop slowly
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Afebrile progressive paralysis
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Lameness, ataxia, hindlimb CP deficits
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Asymmetric
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Hypertonia, hyperreflexia
Clinical Signs…
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Viral Leukoencephalomyelitis…
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Initially BAR
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Continue to eat and drink
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Progresses to paralysis, usually
Can also see CNS signs
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Depression, blindness, abnormal PLRs, nystagmus,
opisthotonos (stargazing), head tremor, head tilt,
circling, facial nerve deficits, dysphagia, paddling
Rarely recover
Clinical Signs…
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Interstitial pneumonia
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Not reproducible
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Secondary to other processes
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Viral, bacterial agents
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Parasitic
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Chronic, non-suppurative
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Progressive dyspnea (difficulty breathing)
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Usually after stress
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Weeks to months
Clinical Signs…
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Interstitial pneumonia…
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Exercise intolerance, wasting, cough
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Arthritis
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Similar to pulmonary CL
Clinical Signs…
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Indurative mastitis
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“Hard udder” or “Hard bag”
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Non-suppurative
Agalactia/hypogalactia
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Milk appears normal
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Come into milk over weeks
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Symmetrical enlargement of udder
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Enlarged supramammary lymph nodes
Clinical Signs…
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Indurative mastitis…
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Smith and Cutlip 1988
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Associated w/ poor production
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Milk production, butter fat content, solids nonfat content,
somatic cell count
Predisposed to nonhemolytic staph. mastitis
Clinical Signs…
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Indurative mastitis…
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Greenwood 1995
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↑ reproductive failure, ↓ kid birth weights
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↓ Growth rate, ↓ milk yields, ↓ days in milk
Diagnosis
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Presumptive
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History
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Clinical signs
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R/O other causes
No “Gold Standard”
Diagnosis
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Virus isolation
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Most definitive diagnosis
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Viral load low
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Usually negative
Indicator cell lines
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Goat synovial membrane
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Milk epithelial cells
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Fetal membrane cells
Diagnosis…
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Serology (detecting antibodies)
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Most convenient
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Ab fluctuations
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Agar Gel Immuodiffusion (AGID)
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Enzyme-linked Immunosorbent Assay (ELISA)
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Radioimmunoprecipitation (RIPA)
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Radioimmunoassay (RIA)
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Western Blot (WB)
Diagnosis…
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AGID
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Most common
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Detects Abs
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p28 core antigen
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gp135 envelope antigen
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Sensitivity 91%
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Specificity 100%
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No false positives
Diagnosis…
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ELISA
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Many different types
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Whole virus
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Recombinant
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Competitive
Sensitivity and specificity vary
Diagnosis…
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Competitive ELISA
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Most common ELISA used
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Sensitivity 93-100%
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Specificity 96.4-100%
Diagnosis…
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ELISA vs. AGID
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ELISA > proportion of Abs detected
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ELISA detects seroconversion earlier
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AGID ↓ Sensitivity
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AGID less $$$
Diagnosis…
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PCR (finding viral DNA)
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Less sensitive than ELISA
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Detect infection before seroconversion
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Not fully developed
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Combination w/ELISA
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Optimal detection
Prevention
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Based on
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Minimize doe → kid transmission
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ID infected animals
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Minimize contact between (-) and (+)
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Eliminate infected animals
Prevention…
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Adams et. al. 1983
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5 steps to prevent transmission to kids
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Immediate removal from dam
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+/- wash kids
Isolate kids
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2 meters btw kids & infected animals
Prevention
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Steps to prevent transmission
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Use CAEV-free or heat treated colostrum
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56˚ C for 1 hour
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Use CAEV-free milk, pasteurized milk
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Test at 6 month intervals
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Separate (+) and (-)
Prevention…
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Test and Cull
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Not an option if
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No virus free replacements
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High seroprevalence
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Not economically feasible
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Lose genetic potential
Prevention…
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Test and Segregate
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Keep 2 herds
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Regular testing
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To be effective must
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Eliminate shared feeders/waters
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Walls, double fences
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Record escapees/exposures
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Avoid commingling
Prevention…
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Current recommendations
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Multifaceted
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Realize seronegative ≠ negative infection
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Prevent perinatal/lactogenic transmission
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Serologic surveillance
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Segregate/cull (+)
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Milk seronegative 1st
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Avoid
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Iatrogenic transmission
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Potential venereal
Prevention…
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Vaccination
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Not effective
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McGuire et. al. 1986
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Vaccinated w/inactivated CAEV
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Increased severity, onset of arthritis
Immune response plays a role in CAE arthritis
QUESTIONS?