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
30
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.
Antonio Jorge Nunes/shutterstock.com
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.
hkeita/shutterstock.com
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.
Communication services Web site Online visualisation of the sample chapter. Presentation brochure in PDF format. Author´s CV. Sample chapter compatible with iPad.
www.grupoasis.com/promo/marek_disease
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
8
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.
9
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.
12
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
13
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.
23
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.
40
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
41
7
Diagnosis a
Marek’s disease
b
48
Figure 29. (b) Nodular lymphomas in heart of an MDV infected chicken compared to (a) that in age matched uninfected chicken.
DIAGNOSIS
a
b
49
Figure 30. (a) Localised or (b) diffuse lymphomas in proventriculus of MDV infected chickens.
7
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.
8
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.
The publishing strength of Grupo AsĂs Editorial Servet, a division of Grupo AsĂs, has become one of the reference publishing companies in the veterinary sector worldwide. More than 15 years of experience in the publishing of contents about veterinary medicine guarantees the quality of its work. With a wide national and international distribution, the books in its catalogue are present in many different countries and have been translated into nine languages to date: English, French, Portuguese, German, Italian, Turkish, Japanese, Russian and Chinese. Its identifying characteristic is a large multidisciplinary team formed by doctors and graduates in Veterinary Medicine and Fine Arts, and specialised designers with a great knowledge of the sector in which they work. Every book is subject to thorough technical and linguistic reviews and analyses, which allow the creation of works with a unique design and excellent contents. Servet works with the most renowned national and international authors to include the topics most demanded by veterinary surgeons in its catalogue. In addition to its own works, Servet also prepares books for companies and the main multinational companies in the sector are among its clients.
Servet (División de Grupo Asís Biomedia S.L.) Centro Empresarial El Trovador, planta 8, oficina I Plaza Antonio Beltrán Martínez, 1 • 50002 Zaragoza (España) Tel.: +34 976 461 480 • Fax: +34 976 423 000 • www.grupoasis.com