Mucosal Diseases (with diarrhea) Flashcards
important mucosal diseases with diarrhea
Bovine Viral Diarrhea
Malignant Catarrhal Fever
Jejunal Hemorrhagic Syndrome
Rinderpest
BVDV family, genus, structure
Family: Flaviviridae
Genus: Pestivirus
Small single stranded positive sense RNA virus
BVDV is closely related to:
Border Disease virus: sheep
Classical Hog Cholera (Swine Fever) virus
does BVDV affect non-domesticated animals?
Serology and virus isolation evidence of BVDV replication in wild ruminants:
Antelope, giraffe, African buffalo, bison (European and American), big horn sheep, mountain goats, and various Cervidae (reindeer, kudu, roe deer, red deer, fallow deer, mule deer, white-tailed deer, and caribou)
BVDV; how common? what body systems does it affect?
Common
Multi-systemic viral disease
Can affect:
Enteric system
Respiratory system
Reproductive system
Immune system
Possible BVDV symptoms:
- neurological defects in calves
- nasal discharge
- oral ulcers
- immunotolerance vs immunosuppression
- GI ulcers
- Erosions
- Genital ulcers
- Infertility, abortions
> BRD (immunosuppression), reproductive disorders, BVDV, acute mucosal disease, chronic mucosal disease
biotypes of BVDV: what are they, what are they based on?
Based on their effects when grown in tissue culture
Non-cytopathic (NCP)
Cytopathic (CP)
Non-cytopathic BVDV; culture properties, virulence, prevalence in the wild, how it affects the fetus,, how it remains in a population
Do NOT harm cells when grown in tissue culture
The most VIRULENT strains of BVDV in vivo are non-
cytopathic (NCP) in vitro
85-99% of naturally acquired BVDV field isolates are non-
cytopathic
Crosses the placentome to establish BVDV in the fetus
NCP-BVDV maintained in population by production of persistently infected cattle
Cytopathic BVDV; properties in vitro, how it arises, how it establishes PIs, easy to isolate?
Produces cellular damage in vitro
Arise as mutations of NCP-BVDV
More easily isolated than NCP-BVDV
Do NOT establish persistent infections
BVDV strains; how many, how they vary
To date at least 25 BVDV- and BVDB-2 subtypes described
Many strains of BVDV
> BVDV-1: 21 subtypes (1a to 1u) ; BVDV-2: 4 subtypes (2a to 2d)
Vary in virulence
Genetic and antigenic variation
BVDV strains have distinguishable antigenic diversity
Two GENOTYPES of BVDV; what are they, uses, symptoms
Type 1:
> the older “classic” BVD viruses
> used in vaccines, diagnostic tests
Type 2:
> more virulent than Type 1
> Hemorrhagic syndrome, thrombocytopenia, death.
prevalence of BVDV, geographic spread, and PI prevalence
Many countries throughout the world
Herds: 20-90%
General prevalence of PI <2%.
Some individual herds may be higher
BVDV transmission overview; methods
Direct OR Indirect transmission
Highly infectious agent
Inhalation OR ingestion of BVD virus
PI animals:
> main source of virus: high amounts/long period
Acute infected:
> Low amounts/short period (4-10 days)
How is a BVDV PI calf created?
- Pregnant BVDV-PI female
> less common route (<10%)
>PI calf
-BVD shed from infected animals
- Pregnant female (non-PI) infected with BVD virus during first half of gestation
> most common route (>90%)
> PI calf
viral shedding rate of non-PI vs PI calf? Why do PI calves affect so many others?
- Normal Calf (non- PI) with a BVDV infection sheds 10,000 viral particles per day and recovers in 10–14 days.
- PI calf sheds 10 million viral particles EVERY DAY (1000 x non-PI).
- This is why one calf that is
persistently infected can affect so
many other cattle.
BVDV
Direct transmission:
PI animals continuously shed large amounts of NCP-BVD virus in:
ocular discharge
nasal discharge
saliva
semen
feces
urine
milk
BVDV
Indirect transmission:
Indirect contact with fomites
clothing, boots
cattle equipment
blood, hypodermic needles, surgical instruments, oral dosing guns
visitors
transport trucks
BVD Pathogenesis: how cows get infected, what cells?
Inhalation or ingestion of BVDV
Multiplication of BVD virus at mucosal surfaces
> within the epithelial cells of the oro-nasal mucosa (palatine tonsil)
Viremia
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BVDV has tropism for actively-dividing cells: Reproductive tissues
Fetal tissues
Gastrointestinal tract mucosa
Intestinal crypts
Peripheral lymphoid tissue Bone marrow
Pituitary gland
Pancreas
what does a subclinical BVDV infection look like? how common?
Mild fever
Leukopenia
Serum neutralizing antibodies
70-90% of BVDV infections occur without manifestations of clinical signs
what animals are generally acutely ill with BVDV? incubation time and signs?
Immuno-competent cattle of 6-24 month of age
Incubation: 5-7 days
Fever, leukopenia, depression, ocular discharge, oral erosions/ulcerations, drop milk production, diarrhea.
when do we see severe acute BVDV? what types produce this syndrome? clincal signs?
Post-natal infection of immuno-competent cattle with virulent NCP-BVDV
BOTH type 2 and type 1 BVDV can produce this syndrome
Clinical signs: fever, pneumonia, sudden deaths
what is hemorrhagic syndrome? what are the signs? associated with what type of BVDV? Ddx?
Bloody diarrhea, epitaxis, hemorrhage on mucosal surfaces, bleeding from injection sites, hyphema, pyrexia, death
Thrombocytopenia and leukopenia
Associated with non-cythopathic isolates, type II
Experimentally induced in calves
DDx: DIC, sweet clover and bracken fern poisoning
Hemorrhagic syndrome pathogenesis? in what cells has BVDV antigen been found?
Pathogenesis in not clear
Virus induces thrombocytopenia:
> Virus appeared to be associated with platelets
> Altered platelets function
BVDV antigen has been demonstrated in megakaryocytes
BVDV - Acute infections and respiratory disease - associations?
Associated with bovine respiratory disease syndrome (BRD)
Synergistic affects with: Manhemia haemolytica, bovine herpesvirus type I, and bovine syncytial virus
The contribution to BRD may be related to immunosuppressive effects
how can immunosuppression arise from BVDV? coinfections with what other pathogens are common?
Acute infection and modified live vaccines induced immunosuppression
Co-infections with: M. haemolytica, bovine herpesvirus type I, and bovine syncytial virus
Co-infections with: E. coli, bovine papular stomatitis, rotavirus, coronavirus
Acute infections and immunosuppression
- BVDV pathogenesis for this effect
BVDV targets lymphocytes and macrophages
Lymphopenia with lymphoid depletion
decreased CD 4+ and CD8+, and B lymphocytes and neutrophils
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Reasons for immunosuppression:
decreased Production of interferon, monocyte IL-1, IL-2, TNF-α and
decreased chemotactic response
Impaired: neutrophil-mediated; antibody dependent, cell mediated cytotoxicity
Prostaglandin production of infected cells
BVDV infection and reproductive outcomes based on month of gestation infected
0: infertility
0-2: EED
1.5-4.5: immunotolerance/PI
2-9: abortion
3-6: congenital defects
4-9: normal/abnormal and seropositive
venereal spread of BVDV? effects?
Semen of acutely infected or PI bulls may contain virus → source of
infection
Virus shedding in semen extend beyond period of viremia
Can affect fertility (decreased conception)
Oophoritis
In-utero transmission of BVDV to fetus can cause:
Early embryonic losses
Severe congenital abnormalities
Life-long persistent infections
Reproductive Consequences of BVDV - when do we see abortions and why?
Abortions
> Transplacental infections is common
> Fetal infection (50-100 days of gestation) → fetal death → fetal expulsion→days or months later
Late term infections usually do not result in abortions but have been reported
> Incidence is low (immune herds) but may be high in non-immune herds
> Incidence is high in acute infections with type II BVDV
BVDV During Late Gestation - what do we see?
Calves infected transplacentally can be born normal
Born seropositive
Serum should be tested before
colostrum ingestion in order to detect these animals
Weak calves
Outcomes of Fetal Infection with BVDV
Between 45 and 110-120 days gestation
From the end of embryonic stage -to- the development of immune competence of the fetus to BVDV antigens
> immunotolerance / PI
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Transplacental infection of the fetus between 100-150 days gestation
Numerous **congenital defects **
BVDV is an important teratogen
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Over 175 days gestation to term:
Fetus is immunologically competent to BVDV
Calf eliminates BVDV
Calf is born BVD virus-free and with BVD antibodies
Teratogenic effects of BVDV?
Nervous system - many
Ocular effects - many
Thymic aplasia
Growth retardation
Hypotrichosis
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when do the cerebellum and retina develop in the bovine fetus?
Organs being developed between 80-150 days gestation
possible nervous system effects of fetal BVDV? signs?
Cerebellar hypoplasia
Hydranencephaly
> (absent cerebral hemispheres)
Hydrocephalus
> (water on the brain)
Hypomyelinogenesis
> (inadequate synthesis of myelin)
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Ataxic, uncoordinated
Reluctant or unable to stand
“Wide-based” stance
Unable to walk, suckle
Intention tremors
BVDV fetal infection possible ocular system effects?
Retinal atrophy and dysplasia
Cataracts
Microphthalmia
Hypoplasia of optic tract
fetal BVDV infection possible immune system effect
Immune system: thymic hypoplasia
fetal BVDV infection possible skin effect
Skin: hypotrichosis, alopecia
fetal BVDV infection possible musculoskeletal system effect
Growth retardation
Brachygnathism
when do we get a persistent infection with BVDV? what is the nature of this infection? what type of virus?
Fetal infection with NCP-BVDV before development of immune competency
Immuno-tolerance and PI with BVDV
Immuno-tolerance is rare after 100 day but can occur up to 125
days of gestation
Viremic, continuously shed virus and appear healthy
Immuno-tolerance is specific to NCP-B VDV → immune response to heterologous isolates can occur→seropositive for BVDV
BVDV PI prevalence? how do PI family lines arise? significance?
Prevalence is low (1 in every 100 to 1000 births)
PI females produced PI offspring → may result in PI family lines
May be the way BVDV is maintained in the cattle population
PI survival rate
50% survival rate in the 1st year
PI animals are at risk of:
mucosal disease, other diseases and
survivorship
what % of PI heifers reach lactating herd?
Low % of PI heifers (10%) reach
lactating herd
characteristics of PI calves?
Undersized, slow growth, predisposed to infections (enteritis, pneumonia), unresponsive to treatments
Alteration of immune response
> neutrophil and lymphocyte function
Diseases of PI cattle - mucosal disease pathogenesis?
Immuno-tolerant and PI animal (NCP- biotype)→infected with a CP biotype of close homology with the persistently infecting NCP
Not every NCP-CP combination result in MD
Source of CP virus:
External (modified live virus)
Internal (molecular rearrangement of NCP infecting biotype)
mucosal disease clinical presentation options? why is there clinical variation?
Acute MD
Chronic MD
MD with recovery
NCP-CP biotypes relatedness may be responsible for the difference in clinical variations
acute MD characteristics - mortality, incubation, clinical signs, lesions
Sporadic (5%)
High mortality (close to 100%)
Incubation period: 10-14 days
Clinical signs: biphasic fever, anorexia, tachycardia, polypnea, decreased milk production, diarrhea (frank blood, fibrinous casts, foul smell)
Blunted papilla, ulcers of tongue palate, buccal surfaces and pharynx.
diagnostic testing for BVDV for subclinical dz
Samples:
1.Paired serology
2.Buffy coat
3.Serum
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Tests:
1. SN test
2. Virus isolation
3. PCR
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Serology for both types (1&2)
Viremia may be transient
diagnostic testing for BVDV for acute dz
Samples:
1.Paired serology
2.Buffy coat
3.Serum
4. PM tissues
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Tests:
1. SN test
2. Virus isolation
3. PCR
4. FA, IHC, PCR
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Serology for 1&2. Type 2 more associated with
mortality
diagnostic testing for BVDV for abortion / mummification
Samples:
1. Paired serology
2. Fetal fluid
3. Fetal organs
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Tests:
1. SN test
2. SN, Virus isolation
3. PCR
4. FA, IHC, PCR
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Antibody detection suggest
B VD V induced-abortion but not definitive
diagnostic testing for BVDV for PI
Samples:
1. Serum or Buffy coat
2. Serum
3. Skin biopsy (ear notch)
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Tests:
1. Virus isolation
2. PCR
3. IHC
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SN repeat 3-4 weeks for PI. Buffy coat in young calves (<4w)
diagnostic testing for BVDV for MD
Samples:
1. Serum or Buffy coat
2. Serum
3. PM tissues
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Tests:
1. Virus isolation
2. PCR
3. FA, IHC, PCR, virus isolation
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Isolation of types 1&2
diagnostic testing for BVDV for repeat breeding
Paired serum, SN test
BVDV Treatment/Prognosis
No specific therapy
Supportive care
Prevention of secondary bacterial infections Broad spectrum antibiotics
Fluid therapy and electrolytes
Severely ill animal may have MD (usually fatal)
BVDV Prevention/Control
Vaccinate after 6 months-of-age due to maternal antibodies
Vaccinate ALL young females (6-14 months old) just prior to breeding
Aim is to ensure maximum protection of fetus before 120 days gestation
BVDV vaccination schedule, reasoning
Vaccination of all breeding females to protect cattle that are NOT persistently infected
To ensure that cattle are immune to B VDV BEFORE service or insemination
To prevent infection of fetus with B VDV
Reason for variation in efficacy in BVDV vaccine:
Antigenic composition of BVD viruses in vaccine
Type 1 or Type 2 strains of BVDV?
Number of doses of vaccine required?
Adjuvants used?
Methods used for viral inactivation?
Cell types used to grow virus?
Fetal calf serum used?
What constitutes a protective dose?
Inactivated (killed) vaccines limitations and schedule: (BVDV)
Limited immune response
Response to 1st vaccination is weak
Need 2 doses at 14-28 days intervals
Preferably 3 doses prior to breeding
BVDV killed vaccines availability in Canada? immunity duration?
Type 1 and Type 2 killed vaccines available in Canada
Duration of immunity is short
Yearly boosters required
BVDV killed vaccines safety profile? use in pregnancy?
SAFE vaccines
Can be used in pregnant animals
Do NO T cause immunosuppression
Do NOT replicate in host tissue
NO reports of post-vaccinial disease
Cost: low
BVDV modified live vaccines for what strain?
Contain Type-1 cytopathic strains of B VDV
Attenuation through repeated passage Either NADL, Singer, Oregon C24V strains
MLV vaccines available since 1959
BVDV modified live vaccines admin schedule and immune response?
Only need to administer ONCE by intramuscular or subcutaneous injection
Rapid immune response
Rapidly induces B VD VN antibodies in 90-95% of animals within 3 weeks
BVDV modified live vaccine limitations
Sporadic reports of post-vaccinial outbreaks of Mucosal Disease
Reports of reproductive failure following MLV vaccination
MLV vaccine contaminated with NCP-BVDV
> (contaminated cell lines, fetal calf serum)
