Viral Disease in Ruminant

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Viral Disease in Ruminant

• Sukolrat Boonyayatra
• DVM, M.S.
• Clinic for Ruminant, FVM. CMU.

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Disease topic including

• Bovine Ephemeral Fever
• Bovine Respiratory Syncytial Virus
• Parainfluenza-3
• Bovine Viral Diarrhea
• Infectious Bovine Rhinotracheitis
• Foot and Mouth Disease
• Bovine Spongioform Encephalopathy
• Rinderpest
• Lumpy Skin Disease
• Papillomavirus
• Pseudocowpox

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BOVINE EPHEMERAL FEVER

• (Three-day sickness, Bovine Epizootic Fever,
  Three-day stiffsickness,
• Dragon boat disease)

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Definition

• a noncontagious epizootic arthropod-borne viral
  disease
• cattle and water buffaloes
• sudden onset of fever
• depression
• stiffness
• lameness
• rapid recovery

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Etiology

• Family Rhabdoviridae
• 1. Genus Vesiculovirus
• Type Species vesicular stomatitis Indiana virus
• 2. Genus Lyssavirus
• Type Species rabies virus
• 3. Genus Ephemerovirus
• Type Species Bovine ephemeral fever virus
• 4. Genus Cytorhabdovirus
• Type Species lettuce necrotic yellows virus
• 5. Genus Nucleorhabdovirus
• Type Species potato yellow dwarf virus

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Epidemiology

• first described in South Africa in 1906
• tropical, subtropical, and temperate countries in
  Africa, Asia, and Australia
• Thailand since 1984

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Transmission

• Insect bite
• not spread from cow to cow
• Culicoides
• Mosquitoes

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Clinical Signs (1)

• Depressed
• High fever (105-107 F) with biphasic or triphasic
  fever
• Serous ocular and nasal discharge
• Anorexia
• Decreased milk production
• Weight loss
• Stiffness and lameness
• More severe in high BW animals

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Clinical Signs (2)

• Severe case
• Muscle stiffness
• Drag feet when forced to walk
• Lying down, with hide limbs outstretched-
• to relieve muscle cramp
• Lie down for three days

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Clinical Signs (3)

• Morbidity may reach to 30
• Low mortality
• Causes of the death
• Pneumonia from secondary infection
• Muscle damaged and inflammation from long period
  lying down
• Pregnancy toxemia (fatty liver syndrome)

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Gross lesions

• the small amounts of fibrin-rich fluid in the
  pleural, peritoneal, pericardial cavities and
  joint capsules
• the synovial surfaces of the spine may have
  fibrin plaques.
• The lungs may have patchy edema.
• Lymphadenitis
• Focal necrosis can be found in major muscle
  groups in some cases.

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Hematology

• an absolute rise in leukocyte numbers
• a rapid fall in circulating lymphocytes
• a return to normal levels after 3-4 days
• The serum fibrinogen level rises to 3-4 times the
  normal level and returns to normal 1-2 weeks
  after recovery.
• The total serum calcium level falls to 1.8 mmol-1
  during the febrile phases and returns to normal
  on recovery.
• This is the biochemical event that causes the
  reversible early paralysis.

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Diagnosis

• Clinical signs
• Sero-conversion paired serum
• SN test
• ELISA
• Gross lesion

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Differential Diagnosis

• Bluetongue
• Babesiosis
• Blackleg

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Treatment

• Recovery with no treatment
• In severe cases
• Anti-inflammatory drug NSAIDs
• Fluid therapy and calcium
• Broad spectrum ABO
• Recovery period 3-4 wks.

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Prevention and Control

• Vector control
• Vaccine Attenuated lived virus vaccine
  (Australia)

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Bovine Respiratory Syncytial Virus (BRSV)

• Bovine respiratory disease complex (BRD)
• Synergistically infect with bacteria to cause
  pneumonia
• Pasteurella haemolytica
• P. multocida
• Haemophillus somnus
• 1960 The existence of BRSV
• 1970 Isolation of BRSV from an outbreak
  (Switzerland)
• 1974 Isolation of BRSV in USA
• 1978 An attenuated lived vaccine was available
  in Europe.
• 1984 An attenuated lived vaccine (USA)
• 1988 Inactivated vaccines were commercially
  available in USA

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Etiology

• Family Paramyxoviridae
• Genus Pneumovirus
• Human Respiratory Syncytial Virus (HRSV)
• Bovine Respiratory Syncytial Virus (BRSV)
• Ovine Respiratory Syncytial Virus (ORSV)
• Turkey Rhinotracheitis virus
• Single stranded RNA virus that replicate in the
  cytoplasm and mature by budding from apical cell
  membrane

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Epidemiology

• Worldwide distribution in the cattle population
• High seropositive ranging from 65-75 (USA)
  before vaccine was introduced
• BRSV was determined to be involved in
• 14 of respiratory infections in UK
• 32 of outbreaks of calf pneumonia in North
  Ireland
• 53 of respiratory outbreaks in Belgium
• 71 of the outbreaks of calf pneumonia in
  Minnesota

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Clinical signs

• Initial signs
• A decreased appetite
• Milk depression
• Nasal and lacrimal discharge (serous to mucoid)
• Increased respiratory rate
• Progress signs
• Elevated BT (104-108 F)
• Dyspnea
• Opened mouth breathing
• Hyperpnea (abdominal breathing)
• Cough
• Increased bronchial and bronchovesicular sounds,
  and fine crackles
• Decreased milk production
• Duration of disease is variable, lasting from 1-2
  weeks
• Calf more severe

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Postmortem findings

• Atypical interstitial pneumonia (AIP)
• Gross findings
• Initially involves the cranioventral lobes
• Calves die from severe lung edema and
  interstitial pneumonia
• Lung fail to collapse
• Subpleural emphysema
• Bronchial and mediastinal lymphnodes are enlarged
  and edema.

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Histopathological findings

• Vary depending on stage of viral infection and
  the secondary bacterial infection
• Bronchointerstitial pneumonia with severe
  bronchiolitis in cranioventral part
• Alveolar edema and emphysema are diffusely
  present
• Multinucleated syncytial cells (bronchiolar
  epithelium)
• Bacterial pneumonia suppurative or fibrous
  bronchopneuminia

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Lung. Multinucleated syncytial cell is prominent
within the bronchiole and appears to be arising
from the epithelial layer. The lumen is packed
with neutrophils. A few neutrophils are also
transmigrating the bronchiolar wall and are in
the adjacent atelectactic parenchyma. 40X
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Immunohistochemistry staining
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Pathogenesis (1)

• Virus infects epithelial cells in the pulmonary
  airways
• Cytopathic changes and necrosis
• Necrotizing bronchiolotis
• Alveolar epithelium interstitial pheumonia
• Mixed inflammatory cell infiltration with a
  predominance of neutrophils

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Pathogenesis (2)

• May suppress the immune system
• Atypical interstitial pneumonia
• Necrotizing bronchiolitis
• Extensive viral replication at bronchiolar
  epithelium
• Dyspnea and forced expiration
• Emphysema

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Immune response to infection

• Both dies and recovery from clinically severe
  have antibody responses to proteins of virus (F
  and N) may not protective effect
• Colostrum IgG-1 do not prevent the infection but
  make disease less severe
• Cell-mediated immune responses may play a
  protective role

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Differential diagnosis

• Parainfluenza-3
• IBR
• Mycoplasma spp.
• Haemophilus somnus
• etc

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Diagnosis

• Clinical signs
• Necropsy
• Laboratory Diagnosis
• Viral isolation
• Antigen Detection Enzyme Immunoassay
• Immunofluorescent Antibody Staining
• Detection of Nucleic acids PCR
• Serological Diagnosis

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Treatment (1)

• ABO Bacterial pneumonia
• - Pasteurella haemolytica
• P. multocida
• Haemophilus somnus
• Anti-inflammatory agents
• Corticosteroid
• Antihistamine
• NSAIDs

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Treatment (2)

• Antiviral therapy Ribivarin HRSV
• Immunotherapy Hyperimmune serum HRSV
• Supportive treatment
• Dehydration and electrolyte imbalances
• Anorectic animals B-complex vitamins

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Prevention and Control

• Management
• Stress, ventilation, maternity pen, calf-rearing
  area
• Immunization
• Passive Immunization Modify severity of disease
• Vaccination Modified-lived BRSV vaccine
• Inactivated BRSV vaccine

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IBR, BRSV, PI-3, BVD killed vaccine Haemophilus
somnus bacterin
Killed vaccine protects against IBR, BVD, PI3 and
BRSV, and Pasteurella haemolytica and
Haemophilus.
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Infectious Agents Identified in the Bovine
Respiratory Disease Complex

• Viruses
• - Bovine herpesvirus type1 (IBR)
• - Bovine herpesvirus type3 (malignant catarrhal
  fever virus)
• - Bovine herpesvirus type4 (DN-599, Movar 33/63)
• - Bovine adenovirus types1 to 8
• - Bovine parainfluenza virus type3
• - Bovine respiratory syncytial virus
• - Bovine viral diarrhea virus
• - Reovirus types1 to 3
• - Bovine Rhinovirus types1 and 2
• - Bovine Enterovirus types1 to 7
• - Calcivirus
• - Influenza virus (reported from Russia)

• Bacteria
• Pasteurella haemolytica
• Pasteurella multocida
• Haemophilus somnus
• Mycoplasma mycoides subspecies mycoides
• Mycoplasma bovis
• Mycoplasma dispar
• Ureaplasma spp.
• Chlamydial agent
• - Chlamydia psittaci

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Parainfluenza-3 Virus (PI-3)

• Enzootic Pneumonia
• Etiology
• Family Paramyxoviridae
• Genus Paramyxovirus

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Pathogenesis

• Virus infects ciliated respiratory epithelium of
  the upper and lower respiratory tracts and also
  alveolar macrophage.
• Reduce alveolar macrophage
• Facilitate pulmonary bacterial colonization
• Infection of calves is rarely fatal, producing
  mild or subclinical cases.

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Epidemiology

• World wide distribution
• Subclinical
• Stress produce more severe clinical case
• Disease is commonly seen in calves 2-8 mths.
• Thailand
• 1994- 1,788 of 2,070 bulk milk samples were
  antibody positive (86.3)

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Transmission

• Aerosal
• Direct contact

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Clinical signs

• Fever 104-105 F
• Rhinitis and pneumonia
• Cough (easily by pinching the trachea)
• Recovery in few days

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Diagnosis

• Virus isolation
• Immunofluorescent or immunoperoxidase test
• Serology Hemagglutination-Inhibition (HI)
  Viral Neutralization

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Bovine viral diarrhea virus (BVDV)

• BVD was first recognised in Canada and the United
  States in the 1940's.
• In 1987, outbreaks of BVD occurred affecting veal
  calves and older cattle in New York and
  Pennsylvania.
• Beginning in 1992, an outbreak of BVD affected
  veal calves and dairy herds in Quebec.
• Today BVDV infections are seen in all ages of
  cattle throughout the world and has significant
  economic impact due to productive and
  reproductive losses.

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Etiology

• RNA virus
• Family Flaviviridae
• Pestivirus
• 2 biotypes cytopathogenic (cp) or
  noncytopathogenic (ncp)
• Both biotypes of BVDV infect cattle and cause
  disease, but only ncp BVDV causes persistent
  infections.

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Effect of BVDV infection on cattle

• Reproductive failure Embryonic death,
  Mummification, Abortions, Stillbirths
• Repeated breeding syndrome
• Immunosuppression
• Congenital defects Cerebellar hypoplasia,
  Cataract
• Persistent infections Carrier animals
• Acute BVD
• Bovine respiratory tract disease
• Mucosal disease

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Transmission

• Persistent infected animals
• Acute infected cattle
• Semen
• Embryo transfer
• Rectal sleeves
• Contaminated water
• Biting insect (experimentally)

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Effect of Pregnant Cow Infection

• Days pregnancy Effect
• 0-40 Embryonic death
• 40-120 Abortion or
• Persistent Infected calf
• 90-160 Abortion or
• Congenital defect
• 160-Parturition Abortion or normal calf

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Critical concerns

• Prenatally infected cattle and that are
  persistently viremic after birth
• Postnatally infected cattle that are transiently
  viremic for about 2 to 10 days or possibly longer
• Both groups of animal are considered as source
  of infection in herd.

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Prevalence

• Prevalence survey in many areas of cattle raising
  countries 60-80 of animals antibody positive
• 1-2 PI animals
• Variation in cattle population structure and herd
  management can account for the difference.

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Interspecies transfer

• Sheep
• Wild ruminants
• Natural infections (caribou 40-100)
• Transfer (llamas dead end)

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Prevalence of BVDV infections

• Seroprevalence Antigen/virus isolation
• United Kingdom
• Germany NK
• Denmark
• Sweden
• Norway NK
• United state
• Thailand (Bulk milk) NK
• NK Not Known

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Thailand

• Muaglek area 4.4 (7/160) of dairy herds were
  positive for antibodies to BVDV in bulk tank milk
  samples (Aiumlamai et al, 1992)
• And colleague reported 22.8 of bulk tank milk
  samples (473/2,070) form all over the country
  Muaglek and area close by (Livestock area1) had
  15.8 (Veerakul et al, 1996)
• There are evidences of BVDV infections among pigs
  in Thailand (Ornveerakul et al, 1994)
• 158 of 522 bulk milk samples are antibody
  positive in survey study (Ajariyakhajorn, 1999)
• Evidences of natural exposure of BVDV in dairy
  cattle

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Clinical signs (1)

• Acute BVDV of young animals, 6-24 months old
• Fever, ulcers in mouth, throat (esophagus) and
  intestine, diarrhea (some bloody), high
  mortallity
• Mild infection off feed, depressed, mild
  diarrhea and recovery
• Subclinical infection with no visible signs are
  most common
• Colostral antibodies protect most calves until
  4-8 months

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Clinical signs (2)

• Acute BVDV in adult cattle (gt 2 years)
• Fever, off feed, decreased milk production,
  diarrhea
• Occasionally ulcers in mouth
• Outbreaks occur in unvaccinated cattle after
  introduction of new animals shedding BVD or in
  first calf heifers when they enter the milk
  string
• During outbreaks up to 25 of adult cattle may
  become ill

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Lesion on Nose
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Lesion on nose, foamy saliva
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Mucosal lesions on tongue and GI tract
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Lesion on hard palate
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Ataxia resulting from congenital infection
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Cerebellar hypoplasia resulting from congenital
infection
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Fluorescent Antibody test for noncytopathic virus
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Figure 1 Choroid plexus, filly EHV-1 within
endothelium and circulating macrophages.
Peroxidase immunohistochemistry and hematoxylin.
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Figure 2 Lung, calf persistently infected with
bovine pestivirus (BVD virus) with bacterial
bronchopneumonia. BVDV is contained within the
cytoplasm of numerous cells (macrophages,
endothelia, alveolar epithelium). Peroxidase
immunohistochemistry and hematoxylin.
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Diagnosis (1)

• Virus Isolation
• Persistent Infection 
• Adults Serum 
• Calves Serum if pre colostrum or older than 4
  months of age. 
• Calves Whole blood if post colostrum and less
  than 4 of months age.
• Acute Infection
• Whole blood. 
• Post Mortem 
• Spleen, Peyer's patch, lymph nodes.
• Abortion 
• Spleen, thymus. 

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Diagnosis (2)

• Serology
• Virus neutralization
• FA
• Immunohistochemistry test
• ELISA
• PCR

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Herd screening

• Bulk milk tank (Antibodies or PCR)
• Pre immunization antibody titers at 6-12 months
  of age (serology) (5-10 of unvaccinated calves)
• Test all animals
• Skin Biopsy Immunoperoxidase (IPX)
• Blood from lt4 mths, serum gt4 mths for
• Virus isolation
• Test again in 3 months (isolation serology)

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Prevention and control

• Elimination of Carrier Animals
• Herd testing
• Test calves at birth
• Immunization
• Modified live or killed vaccines
• Maximize immunity pre-breeding and early
  gestation
• Biosecurity
• Closed herd
• Test all new arrivals
• Test newborns of new arrivals
• Quarantine all new arrivals and reintroduced
  cattle for 21 days

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Infectious Bovine Rhinotracheitis (IBR)

• Red nose

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Etiology

• Herpes virus (DNA virus)
• 3 genotypes
• BHV1 IBR
• BHV2 Infectious pustular vulvovaginitis (IPV)
• Infectious balanoposthitis (IBP)
• BHV3 Neurologic signs

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Transmission

• Nasal and ocular viral shedding is detected for
  10-14 days after infection.
• Aerosal
• Venereal transmission
• Carrier animals virus persist in trigeminal
  ganglia-reactivated-viremia-shedding

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Pathogenesis

• In the respiratory disease syndrome, the virus
  replicates in the nasal cavity and the mucosa of
  the upper respiratory tract resulting in
  inflammation of the nasal cavity, larynx and
  trachea.
• The virus may spread to the eyes causing ocular
  lesions.
• The virus can become systemic and localize in
  various tissues including the placenta that
  results in fetal infection and abortion.
• Localization in the brain leads to encephalitis.

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Clinical signs (1)

• The incubation period can be variable.
• In feedlot cattle the disease tends to occur
  10-20 days after the introduction of susceptible
  cattle.
• Nasal discharge
• Inflammation of nostrils (Red nose)
• Erosion of nasal mucosa

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Clinical signs (2)

• Lacrimation
• Conjunctivitis
• High fever
• Inappetance
• Drop in milk production
• late abortion (between the 5th and 8ht month of
  pregnancy) and placenta retention
• 10 mortality in severe outbreak

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Gross lesions

• Swelling and congestion of respiratory mucosal
  surfaces
• Secondary bacterial infections produce
  mucopurulent nasal discharge
• Cervical lymphnode become swallen
• Conjunctivitis (edema and inflammation) resulting
  in excessive lacrimation
• Clear ocular discharge progresses to mucopurulent

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Histopathological lesions

• Secondary bronchopneumonia or interstitial
  emphysema due to labored breathing
• Rhinitis
• Laryngotracheitis
• Bronchitis

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Epidemiology

• Infectious Bovine Rhinotracheitis (IBR) was
  originally recognized as a respiratory disease of
  feeder cattle in the western United States during
  the early 1950s.

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Epidemiology (Thailand)

• 1990- Survey in central part of Thailand (12
  provinces) 558/1,780 (31.3) serum samples were
  positive (SNgt12)
• 1990- BHV1 was isolated from nasal and vaginal
  swab of seropositive cow after administration of
  dexamethazone
• 1992- 26/40 bulk milk samples were antibody
  positive (37.3)

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Diagnosis

• Clinical signs
• Necropsy
• Laboratory diagnosis
• Virus isolation
• Direct fluorescent antibody test
• ELIZA (serum and milk)
• SN (serum)
• PCR

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Vaccination (1)

• Replicating IBR Vaccine
• Modified Live Virus - should not be used in
  pregnant cows or in calves nursing pregnant cows.
• one injection to provide protection.
• A booster is recommended when an IBR exposure is
  anticipated.
• Non-Replicating IBR Vaccine
• Killed Virus and Chemically Altered Virus are
  safe to use in all cattle.
• Requires two doses initially and an annual
  booster to provide adequate protection.

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Vaccination (2)

• Intra-Nasal IBR Vaccine
• Intra-nasal IBR Vaccine is safe to use in all age
  cattle regardless of pregnancy status.
• short-lived Immunity
• The vaccine of choice to stimulate rapid
  resistance when an outbreak of IBR is occurring
  or is anticipated.
• A booster vaccination with a replicating or a
  non-replicating form of IBR vaccine is required
  to provide longer protection.
• The basic principle of establishing an immune
  population before a disease appears is
  particularly important in the control of IBR,
  especially the abortion form of IBR.

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Prevention and Control

• Once introduced it is difficult and expensive to
  eradicate IBR/IPV especially because as the
  disease establishes animals tend to become
  unapparent carriers. Systematic testing and
  elimination of positives has been successful in
  some countries. 

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Bovine Leukosis

• Etiology
• Family Retroviridae (Oncogenic RNA virus)
• Genus Bovine leukaemia virus (BLV)
• 2 forms
• Enzootic form (Enzootic Bovine Leukosis)
• Sporadic form

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Epidemiology

• Worldwide distribution
• Prevalence increases with age
• Dairy cattle generally have higher prevalence
  rates than beef cattle
• Management factors
• Breed susceptibility differences?

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Clinical signs (1)

• Enzootic Bovine Leukosis
• Persistent lymphocytosis (40 of infected cow)
• Most infected animals (70) do not develop the
  disease.
• Cattle 4-8 years old
• Weight loss with/with out no appetite

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Clinical signs (2)

• Anemia
• Decreased milk yield
• Enlarged external and enlarged internal lymph
  nodes
• Partial paralysis of the hind legs
• Abnormal breathing
• Bulging eyes
• Diarrhea
• Constipation

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Clinical signs (3)

• Sporadic form
• Rarely cases
• Calve lt3 years old
• 3 forms of pathological lesions
• Calf form animals less than 6 mths old
• general lymphadenopathy
• widespread tumour metastasis
• Thymic form animals of 6-8 mths old
• thymic tumour
• sometimes extension into the thorax
• Skin leucosis a non fatal form
• Young adults develop superficial cutaneous
  tumour that disappear spontaneously after a few
  weeks.

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Gross lesions

• Firm white tumour masses in any organs and more
  commonly in lymph nodes.
• Organs most frequently involved
• abomasum,
• right auricle of the heart,
• spleen, intestine, liver, kidney,
• omasum, lung, and uterus

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Diagnosis

• Virus isolation
• PCR
• Sheep inoculation
• Serology can be first detected 3-8 wks after
  infection
• - calves lt 6 mths old can be false positive
• Agar Gel Immunodiffusion (AGID)
• Milk ELISA

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Transmission

• Mechanical transmission
• Blood suckling insects Tabanus spp.
• Natural transmission
• Transfer of infected cell Ex. Parturition.
• Artificial transmission
• Blood contaminated needles
• Surgical equipment
• Gloves used for rectal examination

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Important (1)

• Direct Losses
• Condemnation at slaughter
• Higher culling rates
• Decreased reproductive performance
• Decreased milk yields
• Most all economic analyses have failed to
  distinguish various clinical entities of BLV

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Important (2)

• Indirect Losses
• Loss of export market
• Loss of sales to AI industry
• Loss of sales to embryo transfer industry
• Loss of consumer confidence
• Expenses involved in status testing

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Important (3)

• Zoonotic Potential
• BLV will infect human cells
• No study has linked BLV to human disease
• Most not willing to deny potential exists
• Molecular technology should be able to provide
  definitive answer

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Prevention and Control

• Use individual sterile needles for transdermal
  injection or blood collection.
• Disinfect tattoo equipment between animals.
• Use electric dehorners, or disinfect dehorning
  equipment between animals.
• Replace examination gloves and sleeves between
  animals.
• Use milk replacer to feed preweaned calves.
• Heat-treat or pasteurize colostrum.
• Use BLV-seronegative recipients for embryo
  transfer.
• Wash and rinse instruments in warm water, then
  submerge in an appropriate disinfectant.

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Eradication

• Tested all calves gtsix months of age
• removal or segregation of infected cattle from
  non-infected cattle
• Three consecutive negative herd tests at 60- to
  90-day intervals are then required for the herd
  to be certified as BLV-free.
• recertified annually by a repeated negative test
  of the entire herd

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Foot and Mouth Disease(FMD)
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Etiology

• Family Picornaviridae
• Genus Aphthovirus
• Serotypes
• O, A, C, Asia1, SAT1, SAT2 and SAT3
• Asia1 in Asia and Middle East
• SAT1-3 in Africa
• O, A, C in European country and world wide
• Free from FMD Scandinavia, Great Britain, North
  and Central America, Australia and New Zealand

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Resistant and Sensitivity

• Sensitive
• Sunlight
• UV
• Temp gt50 C
• pH changes

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FMD survival times in animal samples
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Host

• All domestic and wild cloven-footed animals
• Susceptibility cattlegtpiggtsheepgtgoat
• Pigs are amplifying host which can cause airborne
  transmission.

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Transmission

• 2 main routes of infection
• Aerosal
• Ingestion
• Modes of Transmission
• Direct contact
• Indirect contact (mechanical transfer)
• Air borne spread up to 10 kms

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Factors favoring the spread of FMD

• 1. Massive production and excretion of FMDV by
  infected animals (incubatory carrier)
• 2. Prolonged survival of FMDV outside animal body
• 3. Airborne spread of virus over long distances
• 4. Persistent carrier stage in domestic and wild
  animals recovered from apparent and inapparent
  infection.
• 5. The ready spread of infection either by direct
  contact or through animal products, formites or
  aerosals.
• 6. The multiplicity of virus antigenic forms
  which do not confer cross-protection against each
  other.

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Clinical signs (1)

• Incubation period 2-14 days
• Fever (usually fall in about 48 hrs)
• Anorexia
• Depression
• Drop in milk production
• Development of vesicles on mouth and feet
• Ruptured vesicles leading to salivation and
  lameness

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Clinical signs (2)

• Vesicular lesions occuring on udder and teats may
  become permanently infected.
• Loss of condition and cessation of growth which
  may prolonged.
• Lameness is prominent sign in pig.
• Mortality is limited to young animals.
• Inapparent infection goatgtsheepgtpiggtcattle

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Period of excretion of FMDV related to onset of
clinical signs
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Pillars of rumens
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Biological Basis for Vaccination (1)

• Lack of cross-protection
• RNA virus, like FMDV, mutate at a rate higher
  than DNA virus.
• The wide range of antigenic variants within the
  serotypes.
• Vaccinated ruminants may become subclinical
  carrier of FMDV following contact with virus.
• Parenteral immunization with inactivated FMDV
  vaccine is poor stimulator of mucosal humoral
  immunization.

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Biological Basis for Vaccination (2)

• The rapidity of FMDV replication allows little
  opportunity for immunological memory to play a
  role in immunity to infection.
• Repeated prophylactic vaccination is necessary
  for the maintenance of protective serum antibody
  titers in susceptible livestock.
• Recovery from and protection against reinfection
  with FMD are related to the development of
  serum-neutralizing antibody in the cattle.

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The Role of Vaccination in FMD Control Strategy
(1)

• Antigenically appropriate vaccine
• Regularly ascertained the relationship between
  field isolates and the vaccine strains
• In calf, the primary vaccination should be 4
  months.
• Revaccination may be given 4-12 mths intervals
  depending upon local epidemiological advice and
  the quality of vaccine.

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The Role of Vaccination in FMD Control Strategy
(2)

• Prophylactic
• Annually, bi-annually, tri-annually
• Common practice gt1 strain of a particular
  serotype in FMD vaccine
• Mass prophylactic vaccination
• Emergency in FMD free country
• Slaughter of all infected and susceptible
  in-contacted animals
• Define zone around the outbreak
• Control virus spread by movement control and
  disinfection
• Emergency vaccination ring vaccination

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The Role of Vaccination in FMD Control Strategy
(3)

• Emergency in FMD infected country
• Treat animal, mild disinfection, protective
  dressing to inflammed area, administration of
  flunixin meglumine.
• Declare infected zone, ring zone within a radius
  of 16-24 km.
• Control human and animal movement
• Disinfection 1-2 of NaOH or Formaline,
• 4 of Sodium carbonate
• Mass Vaccination

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Cautions and Remarks

• The maintenance of a serum antibody-negative
  national herd is essential for international
  trade.
• Find the source of outbreak
• Confirm subtype of virus
• Complement fixation test
• ELISA
• RT-PCR and sequencing for molecular epidemiology
• Careful imitative virus
• The carrier stage in vaccinated and unvaccinated
  cattle may persist for as long as 6 mths and be
  capable of causing new out break in all species.

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Bovine Spongiform Encephalopathy

• BSE, Mad cow disease

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Etiology

• Prion protein
• (PrP)

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History

• Great Britain in 1985
• Dead cattle with clinical signs of nervous system
  abnormality atxia, salivation, etc.
• Mad cow disease
• 167,000 cases and death animals
• Infectious agent prion protein (PrP)
• Contaminated in meat and bone meal

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Jekyll and Hydes Prions

• The wild type prion (PrPc) is found in the
  secretory pathway of
• cells expressing the protein(1) and moves to the
  plasma
• membrane where it is anchored by its GPI tail
  (2). There it may
• bind to an extracellular ligand (possibly copper)
  (3) before being
• cycled from the membrane into endocytic vesicles
  (4). At some
• point its cargo is released and the protein
  either passes to the
• lysozome for degradation or back to surface for
  another round of
• ligand binding. In this respect it resembles many
  other
• membrane-resident proteins. The pathogenic
  form(PrPSc) also
• finds its way to endocytic vesicles where it
  co-opts some of the
• wild type form to become pathogenic (5). PrPSc is
  resistant to
• degradation, a hallmark of the infectious form,
  so accumulates.
• Neurotoxicity is probably linked to the
  conversion event itself,
• perhaps through its interference with normal PrPc
  turnover,
• because there is considerable evidence to show
  that the accrued
• PrPSc is not inherently toxic.

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RESISTANCE TO PHYSICAL AND CHEMICAL ACTION

• TemperaturePreserved by refrigeration and
  freezing. Recommended physical inactivation is
  porous load autoclaving at 134138C for 18
  minutes (this temperature range may not
  completely inactivate).
• pHStable over a wide range of pH.
• DisinfectantsSodium hypochlorite containing 2
  available chlorine, or 2 N sodium hydroxide,
  applied for gt1 hour at 20C, for surfaces, or
  overnight for equipment.
• SurvivalRecommended decontamination measures
  will reduce titres but may be incompletely
  effective if dealing with high titre material,
  when agent is protected within dried organic
  matter, or in tissue preserved in aldehyde
  fixatives. Survives in tissues post-mortem after
  a wide range of rendering processes. Related
  hamster scrapie infectivity can survive interment
  in soil for 3 years and dry heat of 1 hour at
  temperatures as high as 360C.

150
Transmission

• BSE occurs as a result of dietary exposure to
  feedstuffs containing infected meat and bone meal
  (MBM).
• No cases of BSE have been recorded as a result of
  iatrogenic transmission, but this is a potential
  means.
• There is some evidence of a maternally associated
  risk for calves born to affected cows. The
  biological mechanisms involved are unknown, but
  this effect is insignificant in the
  epidemiology.
• There is no evidence of horizontal transmission
  of BSE between cattle.
• Occurrence of new variant Creutzfeldt-Jakob
  disease (CJD) suggests zoonotic potential via
  oral exposure.

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SOURCES OF AGENT

• Central nervous system (including eye) of
  naturally occurring clinically affected cases.
  Infectivity detected in the distal ileum of
  experimentally infected cattle is presumed
  associated with lymphoreticular tissues.

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Clinical signs (1)

• Mean incubation period is 4-5 years.
• Subacute or chronic, progressive disorderThe
  main clinical signs are neurological
• Apprehension, fear, increased startle, or
  depression
• Hyper-aesthesia or hyper-reflexia
• Adventitial movements muscle fasciculations,
  tremor and myoclonus
• Ataxia of gait, including hypermetria
• Autonomic dysfunction reduced rumination,
  bradycardia and altered heart rhythm.

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Clinical signs (2)

• Pruritis, seen in scrapie, occurs also but is not
  usually a prominent sign.
• Loss of body weight and condition.

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Lesions

• There are no gross post-mortem changes.
• A characteristic spongiform encephalopathy is
  present in most cases.

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Diagnosis (1)

• Identification and Isolation of the agent
• There is no available diagnostic test for the BSE
  agent.
• Bioassay of brain tissue of terminally affected
  cattle or other species by parenteral inoculation
  of mice is the only method currently available
  for detection of infectivity. This is impractical
  because of minimum incubation periods approaching
  300 days.

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Diagnosis (2)

• Serological test
• The absence of detectable immune responses in BSE
  or other transmissible spongiform
  encephalopathies precludes serological tests.
• Other test
• Histopathological examination of the brain from
  clinically affected cases for characteristic
  bilaterally symmetrical spongiform changes of
  grey matter and subsequent immunohistochemical
  demonstration of accumulations of disease
  specific PrP.
• Examination for fibrils, homologous with
  scrapie-associated fibrils (SAF) by electron
  microscopy or electrophoretic separation and
  immunoblotting for detection of the disease
  specific isoform of PrP in extracts of unfixed,
  fresh or frozen brain.

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Prevention and control

• Free countries
• Targeted pathological surveillance to occurrences
  of clinical neurological disease.
• Safeguards on importation of live ruminant
  species and their products.
• Policy and procedures for importation of embryos.
  
• Countries with cases in cattle
• Slaughter and compensation for ascertainment of
  cases.
• Controls on recycling of mammalian protein.
• Effective identification and tracing of cattle.

http//www.oie.int/eng/maladies/fiches/a_B115.htm
166
Thailand Actions to Prevent BSE

• ?????????????????????
• ????????????????????????????????????????????????
  ?????? ???????? ??????????????? (13 ??.?. 2540)
• ???????????
• ????????????????? ????????????????????????????????
  ????????????????????????????????????????
  (England, Denmark, etc.)
• ??????????? ?????????????? ???????????????????????
  ?????
• Review article Prof. Peerasak Chantaraprateep et
  al., 1998. Thai J Vet Med. Vol. 28, No. 117-55

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Rinderpest

• Cattle Plague

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Etiology

• Family Paramyxoviridae
• Genus Morbilivirus
• Only one serotype
• Susceptible species
• Cattle and buffaloes
• Sheep and goats
• Asiatic pigs
• Wildlife

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History

• Host cattle, sheep, goats, camels, wild
  ruminants and pigs
• First established in 1754
• A major disease of livestock through most of the
  19th century in Great Britain
• An OIE Class A disease reflecting its serious
  economic impact

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Transmission

• By direct or close indirect contacts
• Shedding of virus begins 1-2 days before pyrexia
  in tears, nasal secretions, saliva, urine and
  faeces
• Blood and all tissues are infectious before the
  appearance of clinical signs
• Infection is via the epithelium of the upper or
  lower respiratory tract
• No carrier state

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Clinical signs (1)

• Incubation period 3 to 15 days (usually 4 to 5
  days)
• Peracute form
• This form is seen in highly susceptible and young
  animals.
• The only signs of illness are a fever of 104-107o
  F (40-41.7o C), congested mucous membranes, and
  death within 2 to 3 days after the onset of
  fever.

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Clinical signs (2)

• Classical form four stages
• Incubation period
• Febrile period (40-42C) with depression,
  anorexia, reduction of rumination, increase of
  respiratory and cardiac rate
• Mucous membrane congestion (oral, nasal, ocular
  and genital tract mucosae)
• intense mucopurulent lachrymation and abundant
  salivation
• anorexia - necrosis and erosion of the oral
  mucosae
• this phase lasts 2-3 days
• Gastrointestinal signs appear when the fever
  drops profuse haemorrhagic diarrhoea containing
  mucus and necrotic debris. Severe tenesmus.
  Dehydration, abdominal pain, abdominal
  respiration, weakness, recumbency and death
  within 8-12 days. In rare cases, clinical signs
  regress by day 10 and recovery occurs by day
  20-25

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Conjunctivitis and mucopurulent exudate in the
early stage of RP infection.
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Purulent discharge and conjuctivitis
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Excessive salivation in the early stage of RP
infection.
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Oral erosions
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Erosions of buccal mucosa and gingiva
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Clinical signs (3)

• Subacute form
• Clinical signs limited to one or more of the
  classic signs.
• Low mortality rate
• Atypical form
• Irregular pyrexia and mild or no diarrheoa.
• The lymphotropic nature of rinderpest virus
  favours recrudescence of latent infections and/or
  increased susceptibility to other infectious
  agents.

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Gross lesions

• Either areas of necrosis and erosions, or
  congestion and haemorrhage in the mouth,
  intestines and upper respiratory tracts
• Enlarged and oedematous lymph nodes
• White necrotic foci in Peyer's patches
• 'Zebra striping' in the large intestine
• Carcass emaciation and dehydration

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Sloughing of the epithelium over a necrotic
Peyer's patch
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Ulcerations in the mucosa of the upper colon
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Hyperemia of the cecum and colon with
accentuation of lesions (hemorrhage) at the
ceco-colic junction
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Hyperemia and hemorrhages in the longitudinal
folds of the colon - Zebra striping
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Hemorrhage in the mucosa of the gall bladder
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Epidemiology
The Global Rinderpest Eradication Program (FAO)
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Eradication

• Only one serotype
• Recovered or properly vaccinated animals are
  immune for life
• No vertical transmission, arthropod vector, or
  carrier state
• RPV is an ideal virus to be targeted for
  eradication.
• Thailand is a rinderpest free country.

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Lumpy Skin Disease

• Pseudo-urticaria, Neethling virus disease,
  exanthema nodularis bovis, knopvelsiekte

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Etiology and Host

• Family Poxviridae
• Genus Capripoxvirus
• Host Cattle, Buffaloes, Giraff
• First described in Northern Rhodesia in 1929
• An OIE list A disease

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Transmission

• Insect vector
• Mosquitoes (e.g. Culex mirificens and Aedes
  natrionus)
• Flies (e.g. Stomoxys calcitrans and Biomyia
  fasciata)

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Clinical signs

• Inapparent to severe disease
• Fever (40-41.5C) either transitory or lasting up
  to 2 weeks
• Swellings or nodules in the skin and
  generalization.
• Depression, anorexia, excessive salivation,
  oculonasal discharge, agalactia and emaciation
• The nodules may become necrotic and sometimes
  deep scabs form (which are called 'sittast')
• Lameness resulting from inflammation and necrosis
  of tendons, and from severe oedema of brisket and
  legs
• Superficial lymph nodes enlarged to four-to-ten
  times their normal size
• Complications severe mastitis and loss of the
  quarter
• permanent lameness
• abortion, intrauterine infection, and
  temporary sterility in bulls and cows may
  occur.

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A calf affected with LSD note the large skin
nodules
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Nodules (N) and sittasts (S) in a Balidy cow in
Egypt affected with LSD
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An LSD (pox) lesion in the trachael mucosa
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LSD lesions in the lung are areas of atelectasis
and interlobular edema
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Eradication

• Slaughter of all infected and in-contact cattle
• Vaccination

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Papillomavirus or Warts
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Pseudocowpox
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Pseudocowpox
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Questions?

• About the test