Marek's disease

Medicina pediĂĄtrica en pequeĂąos animales

Presentation brochure

Marek’s disease

Author: Mohamed Faizal Abdul-Careem.

Format: 17 x 11 cm.

Number of pages: 80.

Binding: Paperback, wire-o.

RETAIL PRICE

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Atlas entirely dedicated to Marek’s disease (MD) based on a handy and visual approach of the topic. This handbook has been developed by a prestigious and renowned author highly experienced in this disease, being expert in the area of avian viral immunology (especially MD). An up-to-date and complete review has been carried out including the most significant contents, such as aetiology, epidemiology, pathogenesis, clinical manifestations, etc.

Furthermore, it is worthy to mention the information related to diagnosis, emphasising the high quality images from gross postmortem lesions and histological changes included in this chapter.

Moreover, vaccination has been properly developed in order to provide the main guidelines to avoid vaccination failures and control its prevalence and incidence. The atlas format helps to make the contents understandable and affordable for the readers.

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Marek’s disease

Presentation of the book MD is a lymphomatous and neuropathic disease of domestic birds caused by an alphaherpesvirus. Fowls get infected by inhalation of infected dust from the poultry houses and the virus is shed from the feather follicle of infected birds.

Chickens are the most important natural hosts for MD, which usually takes place at 12-30 weeks of age. Besides, MD is one of the most ubiquitous avian infections. It has been reported in chicken flocks worldwide. Every flock, except those maintained under strict pathogen-free conditions, is presumed to be infected. MD may cause important economic losses through a subclinical decrease in growth rate and egg production.

Clinical signs observed include paralysis of the legs and wings and enlargement of peripheral nerves. Moreover, chickens may become persistently infected without developing clinical disease.

According to the current situation, it is necessary to review and update this severe and widespread problem. To make it easier, the author, a prestigious specialist in this field, has developed a thorough assessment of this topic in a didactic and visual way. Many resources (images, tables, graphs, etc.) have been included to facilitate the comprehension of this disease by the reader. This precise and straightforward information will help the veterinarians to know everything about this condition and tackle it properly.

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Marek’s disease

The author Mohamed Faizal Abdul-Careem BVSc, MVM, PhD, Diplomate ACPV, Diplomate ACVM (Virology).

Dr. Mohamed Faizal Abdul-Careem is Assistant Professor (virology) at the University of Calgary (Canada) since 2010. He has obtained his basic veterinary degree (BVSc) from the University of Peradeniya (Sri Lanka) and a Master of Veterinary Medicine degree (MVM) from the University of Glasgow Veterinary School (UK) in 1995. He completed his PhD degree from the University of Guelph (Canada) in 2008. His doctoral thesis entitled ‘Characterization of Host Responses Following Marek’s Disease Virus Infection or Vaccination Against Marek’s Disease’. Following his PhD degree, he was awarded a prestigious Canadian Institutes of Health Research Fellowship to conduct post-doctoral research on innate immune responses generated against mucosal viral infections at the Center for Gene Therapeutics of the McMaster University (Canada). He is diplomate of American College of Poultry Veterinarians (ACPV) and American College of Veterinary Microbiologists (ACVM).

He has expertise and strong interests in the area of avian viral immunology. He has around 31 manuscripts published in peer-reviewed journals and 90 % of these manuscripts are on avian viral immunology. His research programme at the University of Calgary is supported by grants from Canadian federal, provincial and poultry industry sources such as Natural Sciences and Engineering Research Council of Canada, Alberta Livestock and Meat Agency (ALMA), and Canadian Poultry Research Council. He has established stateof-the-art research facility for his experimental animal and laboratory work at the University of Calgary.

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Table of contents 1. Introduction

4. Pathogenesis

General definition

MDV pathogenesis cycle

Synonyms

Events at respiratory mucosa

Economic significance

Events at bursa of Fabricius

History

Events at FFE

2. Aetiology The virus, MDV Taxonomy Morphology MDV evolution

3. Epidemiology

Latency, transformation and lymphoma formation Immunosuppression

5. Clinical manifestations Clinical manifestations Nonspecific signs Transient paralysis

Hosts

Lymphomas

Age distribution

Other neurological manifestations

Geographic distribution

Immunosuppression

Environmental persistence Transmission Incubation period Incidence Mortality

6. Immunity

8. Prevention and control

Immunity

Control by vaccination

Innate host responses

Available vaccines

Adaptive host responses

Hatchery vaccination

7. Diagnosis Diagnosis History and clinical signs Gross postmortem lesions Histological changes Immunological techniques Antibody detection methods (serology) Antigen detection methods Virus isolation in cell cultures Molecular techniques

Mechanism of protection Vaccination failure Management control Biosecurity Cleaning and disinfection Genetic control

9. References

1

Introduction

Marek’s disease

Status of vaccination against MD

Vaccinated chickens

Unvaccinated chickens

Commercial layers Broiler breeders

Commercial broilers

Backyard flocks

Sporadic outbreaks

Minimum carcass condemnation rates

Sporadic outbreaks

Outbreaks with up to 60 % mortality rates

Carcass condemnation rates up to 10 %

Regular outbreaks

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Figure 2. MD associated losses could be reduced by vaccination.

INTRODUCTION

History In 1907, Dr. Joseph Marek described a disease in cockerels known as polyneuritis, which is currently known as MD. First description of fowl paralysis in USA and the Netherlands

Poultry production expanded

1907

1930-1950

1914-1924

First description of the polyneuritis

by Dr. Joseph Marek in Hungary

Fowl paralysis was named as MD

1950

1960

vMDV* pathotype emerged. Fowl paralysis incidence and severity increased

Figure 3. Important discoveries related to MD since first description of the disease in early 1900.

Infectious nature of MD and herpesvirus etiology was established

1963-1967

First MD vaccine introduced

1970

vvMDV* pathotype emerged. MD incidence and severity increased

Second MD vaccine introduced

1980

Third MD vaccine introduced

1990

vv+MDV* pathotype emerged. MD incidence and severity increased

* vMDV = virulent MDV; vvMDV = very virulent MDV; vv+MDV = very virulent plus MDV.

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2

Aetiology

Marek’s disease Lipid envelop

Morphology

Nucleopcapsid

Morphologically, MDV is similar to other herpesviruses. The main components of the virus particle include DNA core, nucleocapsid and lipid envelop with various glycoproteins (gB, gC, gD, gE, gH, gI, gK, gL, gM). Non-enveloped particles are hexagonal in shape and possess 162 hollow capsomeres. The non-enveloped MDV particles are 85-100Â nm in diameter and the enveloped virus particles are 150-160 nm in diameter.

Figure 4. Enveloped MDV particle.

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DNA core

Glycoproteins

AETIOLOGY

MDV evolution Currently, four pathotypes of MDV have been described. The evolution of vMDV from mMDV has occurred in the 1950s, presumably, due to the expansion of intensive poultry production worldwide. This trend of increasing virulence of the virus has continued resulting in the emergence of vvMDV in the late 1970s and vv+MDV in the early 1990s due to the selective pressure imposed on MDV predominantly by vaccination. Further increase in the virulence of MDV has been predicted with the containment of the disease using more efficacious vaccines.

Table 2. Emergence of various pathotypes of MDV has resulted in the changes in the clinical consequences of MD over the time.

mMDV Polyneuritis Visceral lymphoma Immunosuppression Transient paralysis Acute brain oedema

Susceptible

Resistant

Acute skin lesions

vMDV

vvMDV

vv+MDV

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4

Pathogenesis

Marek’s disease

MDV pathogenesis cycle Days post-infection

0 1 2 3 4 5 6 7

14

21

28

35

Lung infection Early cytolytic productive restrictive infection 22

Productive infection in FFE Latency establishment Late cytolytic productive restrictive infection Transformation of mainly CD4+ T cells Lymphoma formation

Figure 8. Pathogenesis of MDV infection consists of various stages that culminate in the formation of lymphomas.

PATHOGENESIS

Inhalation of MDV

Lung infection Thymus

Visceral and neural lymphomas

Lung

Adrenal gland

Proventriculus

Spleen

Kidney Pancreas

Late cytolytic infection

Bursa of Fabricius

Infectious MDV formation in FFE Circulating latent MDV in CD4+ T cells

Latency mainly in CD4+ T cells Early cytolytic infection

Figure 9. MDV infection that begins as a lung infection leading to lymphoma formation and environmental contamination with infectious MDV involves various tissues and organs in the chickens.

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6

Immunity

Marek’s disease

Adaptive host responses Adaptive host responses also play significant roles against MDV infection and lymphoma formation. Such responses are generated following presentation of MDV specific antigens via major histocompatibility complex (MHC) class I and II molecules to CD8+ and CD4+ T cells respectively and comprise of antibody- and cell-mediated immune responses.

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IMMUNITY

MDV

Dendritic cells (DC) Presentation of MDV antigen

Plasma cells Th2* cytokines B cells

Antibody-dependent cellmediated cytotoxicity by NK cells

Complement mediated lysis

Activated CD4+ T cells

Th1* cytokines Activated CD8+ T cells

Cytotoxic T lymphocyte mediated killing MDV infected cell

Decrease MDV infected cells. Protect from lymphomas

Figure 23. Mechanisms of generation of adaptive immune responses against MDV infection in chickens.

* T helper

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Diagnosis a

Marek’s disease

b

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Figure 29. (b) Nodular lymphomas in heart of an MDV infected chicken compared to (a) that in age matched uninfected chicken.

DIAGNOSIS

a

b

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Figure 30. (a) Localised or (b) diffuse lymphomas in proventriculus of MDV infected chickens.

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Diagnosis

a

Marek’s disease

b

58

100.00 µm

100.00 µm

Figure 40. Focal areas of lymphoid infiltration leading to nodular lymphomas in heart due to vvMDV infection. (a) Section of a heart muscle from an uninfected chicken; (b) section of a heart muscle from an MDV infected chicken showing infiltration of lymphoid cells (arrow).

DIAGNOSIS

a

b

59

100.00 µm

100.00 µm

Figure 41. Lymphoid infiltration of a sciatic nerve leading to a neural lymphoma due to vvMDV infection. (a) Section of a sciatic nerve from an uninfected chicken; (b) section of a sciatic nerve from an MDV infected chicken showing infiltration of pleomorphic lymphoid cells.

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Prevention and control

Marek’s disease

Hatchery vaccination In ovo vaccination Solid immunity Potential MDV infection Age (days post-vaccination)

-2 (ED19)

-1 (ED20)

0 (Hatch)

1

2

3

4

Day of hatch vaccination

70 Solid immunity Potential MDV infection

Age (days post-vaccination)

1

2

3

4

5

6

7

Days post-vaccination

1

2

3

4

5

6

7

Figure 50. MD vaccines induce solid antigen specific immunity around 7 days post immunization. The window of susceptibility to MDV infection is smaller following in ovo immunization when compared to day of hatch vaccination.

PREVENTION AND CONTROL

Mechanism of protection Although the exact underlying mechanisms of MDV vaccine-induced protection are not known, it is believed that the chickens are protected due to elicitation of both innate and adaptive immune responses.

NO Macrophages

Reduce MDV infected cells

Antibodydependent cell-mediated cytotoxicity Reduce MDV infected cells

IFNÎł Cytotoxic T lymphocyte mediated killing

NK cells Days post-vaccination

71

1

2

3

4

5

6

7

Figure 51. Proposed mechanism of MDV vaccine induced immunity, which involves both innate and adaptive arms of the immune system.

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