Viral Disease in Ruminant

Sukolrat Boonyayatra

DVM, M.S.

Clinic for Ruminant, FVM. CMU.

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

BOVINE EPHEMERAL FEVER

(Three-day sickness, Bovine Epizootic Fever, Three-day stiffsickness,

Dragon boat disease)

Definition

a noncontagious epizootic arthropod-borne viral disease

cattle and water buffaloes sudden onset of fever depression stiffness lameness rapid recovery

Etiology

Family Rhabdoviridae1. Genus Vesiculovirus

Type Species vesicular stomatitis Indiana virus

2. Genus LyssavirusType Species rabies virus

3. Genus EphemerovirusType Species Bovine ephemeral fever virus

4. Genus CytorhabdovirusType Species lettuce necrotic yellows virus

5. Genus NucleorhabdovirusType Species potato yellow dwarf virus

Epidemiology

first described in South Africa in 1906 tropical, subtropical, and temperate countries

in Africa, Asia, and Australia Thailand since 1984

Transmission

Insect bite not spread from cow to cow

Culicoides Mosquitoes

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

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

Clinical Signs (2)

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)

Clinical Signs (3)

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.

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 nor

mal 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

Clinical signs Sero-conversion: paired serum

SN test ELISA

Gross lesion

Differential Diagnosis

Bluetongue Babesiosis Blackleg

Treatment

Recovery with no treatment In severe cases

Anti-inflammatory drug: NSAIDs Fluid therapy and calcium Broad spectrum ABO

Recovery period 3-4 wks.

Prevention and Control

Vector control Vaccine: Attenuated lived virus vaccine

(Australia)

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

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”

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

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

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.

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

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)

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

May suppress the immune system Atypical interstitial pneumonia Necrotizing bronchiolitis:

Extensive viral replication at bronchiolar epithelium

Dyspnea and forced expiration Emphysema

Pathogenesis (2)

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

Differential diagnosis

Parainfluenza-3 IBR Mycoplasma spp. Haemophilus somnus etc…

Diagnosis

Clinical signs Necropsy Laboratory Diagnosis

Viral isolation Antigen Detection Enzyme ImmunoassayImmunofluorescent Antibody StainingDetection of Nucleic acids: PCRSerological Diagnosis

Treatment (1)

ABO: Bacterial pneumonia

- Pasteurella haemolytica P. multocida Haemophilus somnus

Anti-inflammatory agents Corticosteroid Antihistamine NSAIDs

Antiviral therapy: Ribivarin: HRSV Immunotherapy: Hyperimmune serum :

HRSV Supportive treatment

Dehydration and electrolyte imbalances Anorectic animals: B-complex vitamins

Treatment (2)

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

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

Infectious Agents Identified in the Bovine Respiratory Disease ComplexViruses

- 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)

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

Bacteria

- 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)

Enzootic Pneumonia Etiology

Family Paramyxoviridae Genus Paramyxovirus

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.

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%)

Transmission

Aerosal Direct contact

Clinical signs

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

Diagnosis

Virus isolation Immunofluorescent or immunoperoxidase

test Serology: Hemagglutination-Inhibition (HI)

Viral Neutralization

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.

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.

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

Transmission

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

Effect of Pregnant Cow InfectionDays pregnancy Effect

0-40 Embryonic death40-120 Abortion or

Persistent Infected calf90-160 Abortion or

Congenital defect160-Parturition Abortion or normal calf

Critical concerns

1. Prenatally infected cattle and that are persistently viremic after birth

2. 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

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

Sheep Wild ruminants

Natural infections (caribou: 40-100%) Transfer (llamas: dead end)

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

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

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

Acute BVDV in adult cattle (> 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

Clinical signs (2)

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)

Virus Isolation Persistent Infection 

Adults — Serum  Calves — Serum if pre colostrum or older than 4 months of ag

e.  Calves — Whole blood if post colostrum and less than 4 of mo

nths age. Acute Infection

Whole blood.  Post Mortem 

Spleen, Peyer's patch, lymph nodes. Abortion 

Spleen, thymus. 

Serology

Virus neutralization

FA

Immunohistochemistry test

ELISA

PCR

Diagnosis (2)

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 <4 mths, serum >4 mths for

Virus isolation Test again in 3 months (isolation + serology)

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

Infectious Bovine Rhinotracheitis (IBR)

Red nose

Etiology

Herpes virus (DNA virus) 3 genotypes

BHV1: IBR BHV2: Infectious pustular vulvovaginitis (IPV)

Infectious balanoposthitis (IBP) BHV3: Neurologic signs

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

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 in

cluding the placenta that results in fetal infection and abortion.

Localization in the brain leads to encephalitis.

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

Clinical signs (1)

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

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

Histopathological lesions

Secondary bronchopneumonia or interstitial emphysema due to labored breathing

Rhinitis Laryngotracheitis Bronchitis

Epidemiology

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

1990- Survey in central part of Thailand (12 provinces) 558/1,780 (31.3%) serum samples were positive (SN>1:2)

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%)

Epidemiology (Thailand)

Diagnosis

Clinical signs Necropsy Laboratory diagnosis

Virus isolation Direct fluorescent antibody test ELIZA (serum and milk) SN (serum) PCR

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 t

o provide adequate protection.

Intra-Nasal IBR Vaccine Intra-nasal IBR Vaccine is safe to use in all age cattle regar

dless of pregnancy status. short-lived Immunity The vaccine of choice to stimulate rapid resistance when a

n 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.

Vaccination (2)

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. 

Bovine Leukosis

Etiology Family Retroviridae (Oncogenic RNA virus)

Genus Bovine leukaemia virus (BLV)

2 forms Enzootic form (Enzootic Bovine Leukosis) Sporadic form

Epidemiology

Worldwide distribution Prevalence increases with age Dairy cattle generally have higher prevalence rate

s than beef cattle Management factors Breed susceptibility differences?

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

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

Sporadic form Rarely cases Calve <3 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.

Clinical signs (3)

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

Diagnosis

Virus isolation PCR Sheep inoculation Serology – can be first detected 3-8 wks after

infection - calves < 6 mths old can be false

positive Agar Gel Immunodiffusion (AGID) Milk ELISA

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

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

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

Important (2)

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 d

efinitive answer

Important (3)

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 betwee

n 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 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

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 120 days

Bone marrow at 4 C 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.

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.

Biological Basis for Vaccination (2)

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.

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 (2)

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

The Role of Vaccination in FMD Control Strategy (3)

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 PrionsThe wild type prion (PrPc) is found in the secretory pathway of

cells expressing the protein(1) and moves to the plasmamembrane where it is anchored by its GPI tail (2). There it maybind to an extracellular ligand (possibly copper) (3) before beingcycled 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 ofligand binding. In this respect it resembles many other

membrane-resident proteins. The pathogenic form(PrPSc) alsofinds its way to endocytic vesicles where it co-opts some of thewild type form to become pathogenic (5). PrPSc is resistant todegradation, 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 accruedPrPSc is not inherently toxic.

RESISTANCE TO PHYSICAL AN D 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 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 360°C.

Transmission BSE occurs as a result of dietary exposure to feedstuffs containing infec

ted 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 an

d altered heart rhythm.

Pruritis, seen in scrapie, occurs also but is not usually a prominent sign.

Loss of body weight and condition.

Clinical signs (2)

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 a

gent. Bioassay of brain tissue of terminally affected cattl

e 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.

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.

Diagnosis (2)

Prevention and control

Free countries Targeted pathological surveillance to occurrences of clinica

l neurological disease. Safeguards on importation of live ruminant species and thei

r 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�

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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.

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

Clinical signs (2)

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

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.

Clinical signs (3)

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

EpidemiologyThe 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?

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