29. Marek’s disease.

Question 1

History?

Answer 1

• Mareks disease usually acute, lymphoproliferative/less frequently chronic, central nervous disease of chicken
• History:
• 1907: Marek - chronic form “mareks hen paralysis” = mild viral strain
• neurolyphomatosis, polyneuritis
• from 1950s acute form: visceral lymphomatosis = virulent strains, tumour formation
• “acute form of mareks disease”
• 1967 ʹ identification of the pathogen, the same agent causes the 2 diseases
• 1969-1970 ʹ description of the pathogenesis, the 1st vaccines

Question 2

Occurrence; worldwide?

Answer 2

Occurrence: worldwide,

• practically in ever larger chicken farm
• Visceral form
• enzootic, neurological form
• sporadic
• In all factories
• 1 day old chickens must be immunised before being let out of the hatchery!!!

Question 3

Causative agent?

Answer 3

Causative agent:

• Gallid herpesvirus 2 & 3 (GaHV-2 & 3) ʹ Alphaherpesvirinae, Mardivirus
• GaHV2: Mareks disease virus serotype 1cause marek disease
• Virulent strains: GHV-2 = MDV- 1
• A) Very virulent: visceral tumours (can break through vaccination)(vvMDV)
• B) Virulent: tumours, transient paralysis (vMDV)
• C) Less virulent: chronic, mainly neurological (mild - mMDV)
• D) Avirulent: subclinical infections
• GaVH-3 Mareks disease virus serotype 2 apathogenic strains
• (MeHV-1 ʹ turkey herpes: apathogen, vaccine strain)
• (For vaccination the 3rd serotype is used & the turkey herpes virus is also used)
• Propagation in embryonated eggs & in cell culture
• Susceptibility: chicken, rarely turkey or other bird sp.
• Resistance ʹ very high!!
• In feather follicular epithelial cells & in dust 1 year!
• In litter for about 4 months
• Disinfection: halogenids, formaldehyde, (+detergents)

Question 4

Epizootiology?

Answer 4

Epizootiology

• (not a germinative infection)
• Chickens are most susceptible in 1-2 weeks of age
• Infection after 8 weeks of age: carry & shedding without clinical signs
• Indirect & direct infections
• Fomites (racks, boxes, vehicles)
• Egg shell, hatching machine (Not real germinative!)
• Air-borne (i.e. btwn stables)
• Long-term carrier & shedder birds
• Any farm where chicken are kept recently are potentially infected
• Mainly airborne infections, rarely PO, in large-scale, crowded flocks it spreads easily

Question 5

Factors influencing the enzootics?

Answer 5

Factors influencing the enzootics

• The virulence of the strain
• Genetic resistance (MHC dependent & MHC independent)
• Gender (hens are more susceptible than roosters)
• Immunological stage, maternal immunity, vaccination
• Infectious dose (~keeping conditions, hygiene, crowded flock)
• Simultaneous infections (CAV, IBDV, ALV, REV)

Question 6

Course?

Answer 6

• Course: always a chronic disease (never appears before 6 weeks ʹ rarely seen in broilers)
• ” classical neurological form(hen paralysis) mainly in the legs
• Low virulent strains
• In growers & in (young) hens
• Usually sporadic, long lasting (for months)
• Recovery after the age of 1 year
• Transient paralysis
• More virulent strains
• Usually in 6-7 weeks (16-18 weeks) old, non-vaccinated chicken
• Sporadic, quick, transient recovery (within 24h)
• May lead to visceral form
• Acute, lymphoproliferative ʹ tumour formation all over body
• In non-vaccinated flocks: after 6 weeks of age, en masse
• In vaccinated flocks
• Growers or in the beginning of laying, sporadic
• Long-lasting disease in the flock; new case again
• CNS signs may develop
• Peracute, or anaemia ʹ in 5 week old chicken

Question 7

Pathogenesis?

Answer 7

Pathogenesis

• Free virons are produced only in the epithelial cells of the feather follicles & surface of skin
• In the tissues direct transmission from cell to cell ʹ Ig cannot reach the virus
• Virulent, very virulent strains ʹ oncogene in the lymphatic cells
• Mononuclear cell tumours, mainly T cells
• Specific antigens are expressed on the surface of certain cells: mareks disease associated
• tumour surface antigen ʹ MATSA (not important anymore b/c diagnosed with PCR)
• o In peripheral nerves
• Lymphoid cell infiltration ʹ inflammation
• Lymphoproliferative & autoimmune processes
• Neurone damage ʹ paralysis
• Immune response:
• birds have to be vaccinated
• Virus & tumour specific factors
• Yolk immunity until about 3-4 weeks ʹ reduces but does not prevent infection
• VN antibodies on 6-12 days after infection ʹ long persistence together with cell associated
• viremia
• Cellular immunity plays the central role in the protection

Question 8

Clinical signs?

Answer 8

Clinical signs͗:

• always chronic , dont see until 6 weeks
• Incubation period: greatly varies
• Acute, visceral form: 4-6 weeks 7-16 weeks or longer
• Classical, neurological form: in 6-12 months of age
• Earlier infection ʹ more serious disease
• Peracute/anaemia: 3- 6 week old chicks
• Acute, visceral form (significant economic losses)
• Non-typical signs (loss of appetite, depression, anaemia, weight loss, death)
• Very virulent: immunosuppression, more serious signs, higher mortality
• In growers (after 7 weeks of age): skin tumours, nodules
• Classical, neurological form (1-2% mortality, chronic) > 6 months
• Weakness, ataxia, one-sided paralysis of the legs
• Wing paralysis, craw paralysis, depression, convulsions
• Eye lesions (mainly in older, rare): cloudy, reddish-greyish iris, irregular-shaped pupils, iris
• adhesion, angular pupils , photophobia, keratitis, conjunctivitis, blindness
• Recovery is exception or transien

Question 9

Pathology, histopathology?

Answer 9

Pathology, histopathology

• Acute, visceral form:
• Mainly ovaries, testicles, spleen, liver, kidneys: enlarged infiltrated with tumours (nut ʹ
• walnut sized, merging tumours)
• Any other organs can be involved (heart, muscles, lungs, intestines)
• Bursal atrophy
• Feather follicles are enlarged, knobbly surface
• In later stage peripheral nerve lesions may also emerge
• Classical, neurological form: plexus brachialis, plexus ischiadicus enlarged, knobbly, oedematic,
• asymmetric, merging; Sometimes knobbly ovaries
• In layers or household birds because requires time to form

Histopathology

• Visceral: focal or diffuse, non-differentiated lymphoblast proliferation, small lymphocytes &
• lymphoblasts incr in the feather follicles
• Neurological: peripheral nerves infiltrate with lymphocytes, histiocytes, plasma cells, neuron
• dystrophy, endoneural tissue proliferation

Question 10

Diagnosis?

Answer 10

Diagnosis

• Clinical signs, pathology, histopathology ʹ suspicion
• Virus isolation vaccine strain -> PCR + sequencing
• Serology
• AGID, VN ʹ vaccinations, frequent infections ʹ all flocks become positive
• MATSA

Question 11

Differential diagnosis?

Answer 11

Question 12

Prevention, control?

Answer 12

Prevention, control

• Preventing early infection
• Frequent egg collection, shell disinfection, hatching hygiene
• Cleaning, disinfection of stables (ventilators!)
• Overpressure ventilation, filtered air, separate stuff
• Cleaning & disinfection or destroying fomites
• Breeding of genetically resistant chicken lines

Question 13

Immunisation?

Answer 13

Immunisation:

• vaccination does not protect from infection!
• Attenuated serotype 1, (serotype 2): cell associated vaccine
• Special storing conditions (-196oC), immediate use, good immunity, lower inhibition
• of yolk immunity
• Turkey herpes: easier storage & application, weaker protection
• Bi & trivalent vaccines are also available
• Alternating use of different vaccines in generations (Chickens ʹ layers)
• Vaccination on the day of hatching! ʹ protection from day 7-8 on, booster does not increase
• In ovo vaccination: 18 day old embryo, bivalent vaccine (GaHV-3 & MeHV)
• Very virulent strains (vv+MDV) may break through the protection
• New vaccines: fowl pox-vectored Marek or turkey