Transcript BOVINE EPHEMERAL FEVER - Chiang Mai University

Viral Disease in Ruminant
Sukolrat Boonyayatra
DVM, M.S.
Clinic for Ruminant, FVM. CMU.
Disease topic including:
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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
BOVINE EPHEMERAL
FEVER
(Three-day sickness, Bovine Epizootic Fever,
Three-day stiffsickness,
Dragon boat disease)
Definition
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a noncontagious epizootic arthropod-borne
viral disease
cattle and water buffaloes
sudden onset of fever
depression
stiffness
lameness
rapid recovery
Etiology
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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
Epidemiology
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first described in South Africa in 1906
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tropical, subtropical, and temperate countries
in Africa, Asia, and Australia
Thailand since 1984
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Transmission
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Insect bite
not spread from cow to cow
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Culicoides
Mosquitoes
Clinical Signs (1)
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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
Clinical Signs (2)
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Severe case
Muscle stiffness
Drag feet when forced to walk
Lying down, with hide limbs outstretchedto relieve muscle cramp
Lie down for three days
Clinical Signs (3)
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Morbidity may reach to 30%
Low mortality
Causes of the death
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Pneumonia from secondary infection
Muscle damaged and inflammation from long
period lying down
Pregnancy toxemia (fatty liver syndrome)
Gross lesions
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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.
Hematology
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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.
Diagnosis
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Clinical signs
Sero-conversion: paired serum
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SN test
ELISA
Gross lesion
Differential Diagnosis
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Bluetongue
Babesiosis
Blackleg
Treatment
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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
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Vector control
Vaccine: Attenuated lived virus vaccine
(Australia)
Bovine Respiratory Syncytial Virus
(BRSV)
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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
Etiology
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Family Paramyxoviridae
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Genus Pneumovirus
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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”
Epidemiology
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Worldwide distribution in the cattle population
High seropositive ranging from 65-75%
(USA) before vaccine was introduced
BRSV was determined to be involved in
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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
Clinical signs
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Initial signs
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Progress signs
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A decreased appetite
Milk depression
Nasal and lacrimal discharge (serous to mucoid)
Increased respiratory rate
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
Postmortem findings
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Atypical interstitial pneumonia (AIP)
Gross findings:
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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.
Histopathological findings
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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
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
Immunohistochemistry staining
Pathogenesis (1)
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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
Pathogenesis (2)
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May suppress the immune system
Atypical interstitial pneumonia
Necrotizing bronchiolitis:
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Extensive viral replication at bronchiolar
epithelium
Dyspnea and forced expiration
Emphysema
Immune response to infection
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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
Differential diagnosis
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Parainfluenza-3
IBR
Mycoplasma spp.
Haemophilus somnus
etc…
Diagnosis
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Clinical signs
Necropsy
Laboratory Diagnosis
Viral isolation
Antigen Detection Enzyme Immunoassay
Immunofluorescent Antibody Staining
Detection of Nucleic acids: PCR
Serological Diagnosis
Treatment (1)
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ABO: Bacterial pneumonia
- Pasteurella haemolytica
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P. multocida
Haemophilus somnus
Anti-inflammatory agents
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Corticosteroid
Antihistamine
NSAIDs
Treatment (2)
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Antiviral therapy: Ribivarin: HRSV
Immunotherapy: Hyperimmune serum :
HRSV
Supportive treatment
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Dehydration and electrolyte imbalances
Anorectic animals: B-complex vitamins
Prevention and Control
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Management:
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Stress, ventilation, maternity pen, calf-rearing
area
Immunization
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Passive Immunization: Modify severity of disease
Vaccination: Modified-lived BRSV vaccine
Inactivated BRSV vaccine
IBR, BRSV, PI-3, BVD killed
vaccine + Haemophilus somnus
bacterin
Killed vaccine protects against IBR,
BVD, PI3 and BRSV, and
Pasteurella haemolytica and
Haemophilus.
Infectious Agents Identified in the Bovine
Respiratory Disease Complex
Viruses
Bacteria
- 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)
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Pasteurella haemolytica
Pasteurella multocida
Haemophilus somnus
Mycoplasma mycoides subspecies
mycoides
Mycoplasma bovis
Mycoplasma dispar
Ureaplasma spp.
Chlamydial agent
- Chlamydia psittaci
Parainfluenza-3 Virus (PI-3)
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Enzootic Pneumonia
Etiology
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Family Paramyxoviridae
Genus Paramyxovirus
Pathogenesis
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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.
Epidemiology
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World wide distribution
Subclinical
Stress produce more severe clinical case
Disease is commonly seen in calves 2-8
mths.
Thailand:
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1994- 1,788 of 2,070 bulk milk samples were
antibody positive (86.3%)
Transmission
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Aerosal
Direct contact
Clinical signs
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Fever 104-105 F
Rhinitis and pneumonia
Cough (easily by pinching the trachea)
Recovery in few days
Diagnosis
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Virus isolation
Immunofluorescent or immunoperoxidase
test
Serology: Hemagglutination-Inhibition (HI)
Viral Neutralization
Bovine viral diarrhea virus
(BVDV)
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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.
Etiology
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RNA virus
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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
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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
Transmission
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Persistent infected animals
Acute infected cattle
Semen
Embryo transfer
Rectal sleeves
Contaminated water
Biting insect (experimentally)
Effect of Pregnant Cow Infection
Days pregnancy
0-40
40-120
90-160
160-Parturition
Effect
Embryonic death
Abortion or
Persistent Infected calf
Abortion or
Congenital defect
Abortion or normal calf
Critical concerns
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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.
Prevalence
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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.
Interspecies transfer
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Sheep
Wild ruminants
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Natural infections (caribou: 40-100%)
Transfer (llamas: dead end)
Prevalence of BVDV infections
Seroprevalence
United Kingdom
Germany
Denmark
Sweden
Norway
United state
Thailand
NK: Not Known
Antigen/virus isolation
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NK
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+(Bulk milk)
NK
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NK
Thailand
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Muaglek area: 4.4% (7/160) of dairy herds were positive for antibodies
to BVDV in bulk tank milk samples (Aiumlamai et al, 1992)
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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)
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There are evidences of BVDV infections among pigs in Thailand
(Ornveerakul et al, 1994)
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158 of 522 bulk milk samples are antibody positive in survey study
(Ajariyakhajorn, 1999)
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Evidences of natural exposure of BVDV in dairy cattle
Clinical signs (1)
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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
Clinical signs (2)
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Acute BVDV in adult cattle (> 2 years)
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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
Lesion on Nose
Lesion on nose,
foamy saliva
Mucosal lesions on tongue and GI tract
Lesion on hard
palate
Ataxia resulting from congenital infection
Cerebellar hypoplasia resulting from congenital infection
Fluorescent Antibody test for noncytopathic virus
Figure 1: Choroid plexus, filly: EHV-1 within endothelium and
circulating macrophages. Peroxidase immunohistochemistry and
hematoxylin.
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.
Diagnosis (1)
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Virus Isolation
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Persistent Infection
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Acute Infection
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Whole blood.
Post Mortem
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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.
Spleen, Peyer's patch, lymph nodes.
Abortion
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Spleen, thymus.
Diagnosis (2)
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Serology
Virus neutralization
FA
Immunohistochemistry test
ELISA
PCR
Herd screening
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Bulk milk tank (Antibodies or PCR)
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Pre immunization antibody titers at 6-12 months of
age (serology) (5-10% of unvaccinated calves)
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Test all animals
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Skin Biopsy : Immunoperoxidase (IPX)
Blood from <4 mths, serum >4 mths for
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Virus isolation
Test again in 3 months (isolation + serology)
Prevention and control
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Elimination of Carrier Animals
 Herd testing
 Test calves at birth
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Immunization
 Modified live or killed vaccines
 Maximize immunity pre-breeding and early gestation
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Biosecurity
 Closed herd
 Test all new arrivals
 Test newborns of new arrivals
 Quarantine all new arrivals and reintroduced cattle for 21 days
Infectious Bovine
Rhinotracheitis (IBR)
Red nose
Etiology
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Herpes virus (DNA virus)
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3 genotypes
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BHV1: IBR
BHV2: Infectious pustular vulvovaginitis (IPV)
Infectious balanoposthitis (IBP)
BHV3: Neurologic signs
Transmission
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Nasal and ocular viral shedding is detected
for 10-14 days after infection.
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Aerosal
Venereal transmission
Carrier animals : virus persist in trigeminal
ganglia-reactivated-viremia-shedding
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Pathogenesis
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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.
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The virus may spread to the eyes causing ocular lesions.
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The virus can become systemic and localize in various tissues
including the placenta that results in fetal infection and abortion.
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Localization in the brain leads to encephalitis.
Clinical signs (1)
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The incubation period can be variable.
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In feedlot cattle the disease tends to occur
10-20 days after the introduction of
susceptible cattle.
Nasal discharge
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Inflammation of nostrils (Red nose)
Erosion of nasal mucosa
Clinical signs (2)
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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
Gross lesions
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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
Histopathological lesions
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Secondary bronchopneumonia or interstitial
emphysema due to labored breathing
Rhinitis
Laryngotracheitis
Bronchitis
Epidemiology
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Infectious Bovine Rhinotracheitis (IBR) was
originally recognized as a respiratory disease
of feeder cattle in the western United States
during the early 1950s.
Epidemiology (Thailand)
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1990- Survey in central part of Thailand (12
provinces) 558/1,780 (31.3%) serum samples were
positive (SN>1:2)
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1990- BHV1 was isolated from nasal and vaginal
swab of seropositive cow after administration of
dexamethazone
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1992- 26/40 bulk milk samples were antibody
positive (37.3%)
Diagnosis
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Clinical signs
Necropsy
Laboratory diagnosis
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Virus isolation
Direct fluorescent antibody test
ELIZA (serum and milk)
SN (serum)
PCR
Vaccination (1)
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Replicating IBR Vaccine
 Modified Live Virus - should not be used in pregnant cows
or in calves nursing pregnant cows.
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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.
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Requires two doses initially and an annual booster
to provide adequate protection.
Vaccination (2)
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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.
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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.
Prevention and Control
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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.
Bovine Leukosis
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Etiology
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Family Retroviridae (Oncogenic RNA virus)
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Genus Bovine leukaemia virus (BLV)
2 forms
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Enzootic form (Enzootic Bovine Leukosis)
Sporadic form
Epidemiology
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Worldwide distribution
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Prevalence increases with age
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Dairy cattle generally have higher prevalence
rates than beef cattle
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Management factors
Breed susceptibility differences?
Clinical signs (1)
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Enzootic Bovine Leukosis
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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
Clinical signs (2)
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Anemia
Decreased milk yield
Enlarged external and enlarged internal
lymph nodes
Partial paralysis of the hind legs
Abnormal breathing
Bulging eyes
Diarrhea
Constipation
Clinical signs (3)
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Sporadic form
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Rarely cases
Calve <3 years old
3 forms of pathological lesions
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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.
Gross lesions
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Firm white tumour masses in any organs and
more commonly in lymph nodes.
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Organs most frequently involved:
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abomasum,
right auricle of the heart,
spleen, intestine, liver, kidney,
omasum, lung, and uterus
Diagnosis
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Virus isolation
PCR
Sheep inoculation
Serology – can be first detected 3-8 wks after
infection
- calves < 6 mths old can be false
positive
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Agar Gel Immunodiffusion (AGID)
Milk ELISA
Transmission
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Mechanical transmission
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Natural transmission
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Blood suckling insects: Tabanus spp.
Transfer of infected cell Ex. Parturition.
Artificial transmission
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Blood contaminated needles
Surgical equipment
Gloves used for rectal examination
Important (1)
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Direct Losses
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Condemnation at slaughter
Higher culling rates
Decreased reproductive performance
Decreased milk yields
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Most all economic analyses have failed to distinguish
various clinical entities of BLV
Important (2)
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Indirect Losses
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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
Important (3)
Zoonotic Potential
 BLV will infect human cells
 No study has linked BLV to human disease
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Most not willing to deny potential exists
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Molecular technology should be able to provide
definitive answer
Prevention and Control
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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.
Eradication

Tested all calves >six months of age

removal or segregation of infected cattle from
non-infected cattle

Three consecutive negative herd tests at 60to 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
Foot and Mouth Disease
(FMD)
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
Resistant and Sensitivity

Sensitive




Sunlight
UV
Temp >50 C
pH changes
FMD survival times in animal samples
Organ and condition
Time
Lymphnode at 4 C
Bone marrow at 4 C
120 days
210 days
Skeletal muscle at 4 C
2 days
Frozen carcass (no rigor)
6 months
Host



All domestic and wild cloven-footed animals
Susceptibility: cattle>pig>sheep>goat
Pigs are amplifying host which can cause airborne
transmission.
Transmission

2 main routes of infection:



Aerosal
Ingestion
Modes of Transmission:


Direct contact
Indirect contact (mechanical transfer)

Air borne spread up to 10 kms
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.
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
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: goat>sheep>pig>cattle
Period of excretion of FMDV related to
onset of clinical signs
Source
Time (days)
Saliva
-10 to +9
Airborne
-1 to +4
Milk
-4 to +4
Semen
-4 to +7
Feces/urine
-1 to +6
Lesions
0 to +11
Pillars of rumens
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.
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.
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.
The Role of Vaccination in FMD Control
Strategy (2)

Prophylactic




Annually, bi-annually, tri-annually
Common practice: >1 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
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
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.
Bovine Spongiform
Encephalopathy
BSE, Mad cow disease
Etiology

Prion protein
(PrP)
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
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.
RESISTANCE TO PHYSICAL AND
CHEMICAL ACTION

Temperature:Preserved by refrigeration and freezing.
Recommended physical inactivation is porous load autoclaving at
134–138°C for 18 minutes (this temperature range may not
completely inactivate).

pH:Stable over a wide range of pH.

Disinfectants:Sodium hypochlorite containing 2% available chlorine,
or 2 N sodium hydroxide, applied for >1 hour at 20°C, for surfaces,
or overnight for equipment.

Survival:Recommended 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 postmortem 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 360°C.
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.
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.
Clinical signs (1)


Mean incubation period is 4-5 years.
Subacute or chronic, progressive disorder
The 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.
Clinical signs (2)

Pruritis, seen in scrapie, occurs also but is
not usually a prominent sign.

Loss of body weight and condition.
Lesions

There are no gross post-mortem changes.

A characteristic spongiform encephalopathy
is present in most cases.
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.
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.
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
Thailand Actions to Prevent BSE



กระทรวงเกษตรและสหกรณ์
 ไม่ อนุ ญาตให้ นาเข้ าอาหารสัตว์ ท่ ม
ี ีส่วนผสมของเนือ้ กระดูก และเลือด จาก
ประเทศอังกฤษ (13 มิ.ย. 2540)
กรมปศุสัตว์
 ให้ ชลอการนาเข้ าโค และอาหารสัตว์ ท่ ม
ี ีส่วนผสมของเนือ้ ของสัตว์ เคีย้ วเอือ้ ง
จากกลุ่มประเทศยุโรป (England, Denmark, etc.)
สถาบันวิจยั และมหาวิทยาลัย จัดเผยแพร่ ความรู้ ส่ สู าธารณชน
 Review article: Prof. Peerasak Chantaraprateep et al., 1998. Thai J Vet
Med. Vol. 28, No. 1:17-55
Rinderpest
Cattle Plague
Etiology




Family Paramyxoviridae
Genus Morbilivirus
Only one serotype
Susceptible species




Cattle and buffaloes
Sheep and goats
Asiatic pigs
Wildlife
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
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
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.
Clinical signs (2)

Classical form: four stages
 Incubation period
 Febrile period (40-42°C) 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
Conjunctivitis and mucopurulent exudate
in the early stage of RP infection.
Purulent discharge and conjuctivitis
Excessive salivation
in the early stage
of RP infection.
Oral erosions
Erosions of buccal mucosa and gingiva
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.
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
Sloughing of the epithelium over a necrotic Peyer's patch
Ulcerations in the mucosa of the upper colon
Hyperemia of the cecum and colon with accentuation
of lesions (hemorrhage) at the ceco-colic junction
Hyperemia and hemorrhages in the longitudinal folds
of the colon - Zebra striping
Hemorrhage in the mucosa of the gall bladder
Epidemiology
The Global Rinderpest Eradication
Program (FAO)
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.

Lumpy Skin Disease
Pseudo-urticaria, Neethling virus
disease, exanthema nodularis bovis,
knopvelsiekte
Etiology and Host





Family Poxviridae
Genus Capripoxvirus
Host: Cattle, Buffaloes, Giraff
First described in Northern Rhodesia in 1929
An OIE list A disease
Transmission

Insect vector

Mosquitoes (e.g. Culex mirificens and Aedes
natrionus)

Flies (e.g. Stomoxys calcitrans and Biomyia
fasciata)
Clinical signs








Inapparent to severe disease
Fever (40-41.5°C) 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.
A calf affected with LSD; note the large skin nodules
Nodules (N) and sittasts (S) in a Balidy cow
in Egypt affected with LSD
An LSD (pox) lesion in the trachael mucosa
LSD lesions in the lung are areas of atelectasis
and interlobular edema
Eradication


Slaughter of all infected and in-contact cattle
Vaccination
Papillomavirus or Warts
Pseudocowpox
Pseudocowpox
Questions?
“About the test”