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3. Food Animal 2 > Mucosal Diseases (with diarrhea) > Flashcards

Mucosal Diseases (with diarrhea) Flashcards

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1
Q

important mucosal diseases with diarrhea

A

 Bovine Viral Diarrhea
 Malignant Catarrhal Fever
 Jejunal Hemorrhagic Syndrome
 Rinderpest

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2
Q

BVDV family, genus, structure

A

Family: Flaviviridae
 Genus: Pestivirus
 Small single stranded positive sense RNA virus

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3
Q

BVDV is closely related to:

A

 Border Disease virus: sheep
 Classical Hog Cholera (Swine Fever) virus

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4
Q

does BVDV affect non-domesticated animals?

A

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)

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5
Q

BVDV; how common? what body systems does it affect?

A

 Common
 Multi-systemic viral disease

Can affect:
 Enteric system
 Respiratory system
 Reproductive system
 Immune system

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6
Q

Possible BVDV symptoms:

A
  • 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

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7
Q

biotypes of BVDV: what are they, what are they based on?

A

Based on their effects when grown in tissue culture
 Non-cytopathic (NCP)
 Cytopathic (CP)

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8
Q

Non-cytopathic BVDV; culture properties, virulence, prevalence in the wild, how it affects the fetus,, how it remains in a population

A

 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

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9
Q

Cytopathic BVDV; properties in vitro, how it arises, how it establishes PIs, easy to isolate?

A

 Produces cellular damage in vitro
 Arise as mutations of NCP-BVDV
 More easily isolated than NCP-BVDV
 Do NOT establish persistent infections

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10
Q

BVDV strains; how many, how they vary

A

 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

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11
Q

Two GENOTYPES of BVDV; what are they, uses, symptoms

A

 Type 1:
> the older “classic” BVD viruses
> used in vaccines, diagnostic tests

 Type 2:
> more virulent than Type 1
> Hemorrhagic syndrome, thrombocytopenia, death.

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12
Q

prevalence of BVDV, geographic spread, and PI prevalence

A

 Many countries throughout the world
 Herds: 20-90%
 General prevalence of PI <2%.
 Some individual herds may be higher

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13
Q

BVDV transmission overview; methods

A

 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)

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14
Q

How is a BVDV PI calf created?

A
  1. Pregnant BVDV-PI female
    > less common route (<10%)
    >PI calf

-BVD shed from infected animals

  1. Pregnant female (non-PI) infected with BVD virus during first half of gestation
    > most common route (>90%)
    > PI calf
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15
Q

viral shedding rate of non-PI vs PI calf? Why do PI calves affect so many others?

A
  • 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.
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16
Q

BVDV
Direct transmission:
PI animals continuously shed large amounts of NCP-BVD virus in:

A

 ocular discharge
 nasal discharge
 saliva
 semen
 feces
 urine
 milk

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17
Q

BVDV
Indirect transmission:

A

Indirect contact with fomites
 clothing, boots
 cattle equipment
 blood, hypodermic needles, surgical instruments, oral dosing guns
 visitors
 transport trucks

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18
Q

BVD Pathogenesis: how cows get infected, what cells?

A

 Inhalation or ingestion of BVDV
 Multiplication of BVD virus at mucosal surfaces
> within the epithelial cells of the oro-nasal mucosa (palatine tonsil)
 Viremia
<><><><>
 BVDV has tropism for actively-dividing cells:  Reproductive tissues
 Fetal tissues
 Gastrointestinal tract mucosa
 Intestinal crypts
 Peripheral lymphoid tissue  Bone marrow
 Pituitary gland
 Pancreas

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19
Q

what does a subclinical BVDV infection look like? how common?

A

 Mild fever
 Leukopenia
 Serum neutralizing antibodies
 70-90% of BVDV infections occur without manifestations of clinical signs

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20
Q

what animals are generally acutely ill with BVDV? incubation time and signs?

A

 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.

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21
Q

when do we see severe acute BVDV? what types produce this syndrome? clincal signs?

A

 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

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22
Q

what is hemorrhagic syndrome? what are the signs? associated with what type of BVDV? Ddx?

A

 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

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23
Q

Hemorrhagic syndrome pathogenesis? in what cells has BVDV antigen been found?

A

 Pathogenesis in not clear
 Virus induces thrombocytopenia:
> Virus appeared to be associated with platelets
> Altered platelets function
 BVDV antigen has been demonstrated in megakaryocytes

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24
Q

BVDV - Acute infections and respiratory disease - associations?

A

 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

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25
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
26
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 <><>  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
27
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
28
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
29
In-utero transmission of BVDV to fetus can cause:
 Early embryonic losses  Severe congenital abnormalities  Life-long persistent infections
30
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
31
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
32
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 <><>  Transplacental infection of the fetus between 100-150 days gestation  Numerous **congenital defects **  BVDV is an important teratogen <><>  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
33
Teratogenic effects of BVDV?
 Nervous system - many  Ocular effects - many  Thymic aplasia  Growth retardation  Hypotrichosis <><>
34
when do the cerebellum and retina develop in the bovine fetus?
 Organs being developed between 80-150 days gestation
35
possible nervous system effects of fetal BVDV? signs?
 Cerebellar hypoplasia  Hydranencephaly > (absent cerebral hemispheres)  Hydrocephalus > (water on the brain)  Hypomyelinogenesis > (inadequate synthesis of myelin) <><>  Ataxic, uncoordinated  Reluctant or unable to stand  “Wide-based” stance  Unable to walk, suckle  Intention tremors
36
BVDV fetal infection possible ocular system effects?
 Retinal atrophy and dysplasia  Cataracts  Microphthalmia  Hypoplasia of optic tract
37
fetal BVDV infection possible immune system effect
 Immune system: thymic hypoplasia
38
fetal BVDV infection possible skin effect
 Skin: hypotrichosis, alopecia
39
fetal BVDV infection possible musculoskeletal system effect
 Growth retardation  Brachygnathism
40
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
41
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
42
PI survival rate
 50% survival rate in the 1st year
43
PI animals are at risk of:
mucosal disease, other diseases and survivorship
44
what % of PI heifers reach lactating herd?
 Low % of PI heifers (10%) reach lactating herd
45
characteristics of PI calves?
 Undersized, slow growth, predisposed to infections (enteritis, pneumonia), unresponsive to treatments  Alteration of immune response > neutrophil and lymphocyte function
46
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)
47
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
48
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.
49
diagnostic testing for BVDV for subclinical dz
Samples: 1.Paired serology 2.Buffy coat 3.Serum <><> Tests: 1. SN test 2. Virus isolation 3. PCR <><> Serology for both types (1&2) Viremia may be transient
50
diagnostic testing for BVDV for acute dz
Samples: 1.Paired serology 2.Buffy coat 3.Serum 4. PM tissues <><> Tests: 1. SN test 2. Virus isolation 3. PCR 4. FA, IHC, PCR <><> Serology for 1&2. Type 2 more associated with mortality
51
diagnostic testing for BVDV for abortion / mummification
Samples: 1. Paired serology 2. Fetal fluid 3. Fetal organs <><> Tests: 1. SN test 2. SN, Virus isolation 3. PCR 4. FA, IHC, PCR <><> Antibody detection suggest B VD V induced-abortion but not definitive
52
diagnostic testing for BVDV for PI
Samples: 1. Serum or Buffy coat 2. Serum 3. Skin biopsy (ear notch) <><> Tests: 1. Virus isolation 2. PCR 3. IHC <><> SN repeat 3-4 weeks for PI. Buffy coat in young calves (<4w)
53
diagnostic testing for BVDV for MD
Samples: 1. Serum or Buffy coat 2. Serum 3. PM tissues <><> Tests: 1. Virus isolation 2. PCR 3. FA, IHC, PCR, virus isolation <><> Isolation of types 1&2
54
diagnostic testing for BVDV for repeat breeding
Paired serum, SN test
55
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)
56
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
57
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
58
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?
59
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
60
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
61
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
62
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
63
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
64
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)

3. Food Animal 2 (20 decks)

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