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Marek's Disease in Poultry
Chickens are the most important natural host for
Marek's disease virus, a highly cell-associated but readily transmitted
alphaherpesvirus with lymphotropic properties of gammaherpesviruses.
Quail can be naturally infected, and turkeys can be infected
experimentally. However, severe clinical outbreaks of Marek's disease in
commercial turkey flocks, with mortality from tumors reaching 40%–80%
between 8 and 17 wk of age, were reported in France, Israel, and
Germany. In some of these cases, the affected turkey flocks were raised
in proximity to broilers. Turkeys are also commonly infected with turkey
herpesvirus (HVT), an avirulent strain related to Marek's disease virus
that is commonly used as a Marek's disease vaccine in chickens. Other
birds and mammals appear to be refractory to the disease or infection.
Marek's disease is one of the most ubiquitous avian
infections; it is identified in chicken flocks worldwide. Every flock,
except for those maintained under strict pathogen-free conditions, is
presumed to be infected. Although clinical disease is not always
apparent in infected flocks, a subclinical decrease in growth rate and
egg production may be economically important.
Etiology
Marek's disease virus is a member of the genus Mardivirus within the subfamily Alphaherpesvirinae. Within the genus Mardivirus
are three closely related species previously designated as three
serotypes of Marek's disease virus. Gallid herpesvirus 2 (MDV-1)
represents all virulent Marek's disease virus strains and is further
divided into pathotypes, designated as mild (m), virulent (v), very
virulent (vv), and very virulent plus (vv+). Gallid herpesvirus 3
(MDV-2) and Meleagrid herpesvirus 1 (turkey herpesvirus, MDV-3)
represent avirulent virus strains isolated from chickens and turkeys,
respectively, and are commonly used as vaccines against Marek's disease.
Transmission and Epidemiology
The disease is highly contagious and readily
transmitted among chickens. The virus matures into a fully infective,
enveloped form in the epithelium of the feather follicle, from which it
is released into the environment. It may survive for months in poultry
house litter or dust. Dust or dander from infected chickens is
particularly effective in transmission. Once the virus is introduced
into a chicken flock, regardless of vaccination status, infection
spreads quickly from bird to bird. Infected chickens continue to be
carriers for long periods and act as sources of infectious virus.
Shedding of infectious virus can be reduced, but not prevented, by prior
vaccination. Unlike virulent strains of Marek's disease virus, which
are highly contagious, turkey herpesvirus is not readily transmissible
among chickens (although it is easily transmitted among turkeys, its
natural host). Attenuated Marek's disease virus strains vary greatly in
their transmissibility among chickens; the most highly attenuated are
not transmitted. Marek's disease virus is not vertically transmitted.
Pathogenesis
Currently, four phases of infection in vivo are
recognized: 1) early productive-restrictive virus infection causing
primarily degenerative changes, 2) latent infection, 3) a second phase
of cytolytic, productive-restrictive infection coincident with permanent
immunosuppression, and 4) a proliferative phase involving
nonproductively infected lymphoid cells that may or may not progress to
the point of lymphoma formation. Productive infection may occur
transiently in B lymphocytes within a few days after infection with
virulent Marek's disease virus strains and is characterized by antigen
production, which leads to cell death. Because few if any virions are
produced, this has also been termed a restrictive-productive infection.
Productive infection also occurs in the feather follicle epithelium, in
which enveloped virions are produced. Latent infection of activated T
cells is responsible for the longterm carrier state. No antigens are
expressed, but virus can be recovered from such lymphocytes by
co-cultivation with susceptible cells in tissue cultures. Some T cells,
latently infected with oncogenicMarek's disease virus strains, undergo
neoplastic transformation. These transformed cells, provided they escape
the immune system of the host, may multiply to form characteristic
lymphoid neoplasms. Cell-mediated and humoral immune responses are both
directed against viral antigens, with cell-mediated immunity probably
being the most important.
Clinical Findings
The incidence of Marek's disease is quite variable in
commercial flocks and depends on strain and dose of virus, age at
exposure, maternal antibody, host gender and genetics, strain and dose
of vaccine virus, and several environmental factors, including stress.
In addition to lymphoid neoplasms, Marek's disease virus can also induce
other clinically distinct disease syndromes, including transient
paralysis, early mortality syndrome, cytolytic infection,
atherosclerosis, and persistent neurologic disease. Typically, affected
birds show only depression before death, but a transient paralysis
syndrome has been associated with Marek's disease; chickens become
ataxic for periods of several days and then recover. This syndrome is
rare in immunized birds. Death is usually the result of paralysis,
rendering the birds unable to reach food and water.
Marek's disease, leg paresis, chicken
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Lesions
Enlarged nerves are one of the most consistent gross
lesions in affected birds. Various peripheral nerves, but particularly
the vagus, brachial, and sciatic, become enlarged and lose their
striations. Diffuse or nodular lymphoid tumors may be seen in various
organs, particularly the liver, spleen, gonads, heart, lung, kidney,
muscle, and proventriculus. Enlarged feather follicles (commonly termed
skin leukosis) may be noted in broilers after defeathering during
processing and are a cause for condemnation. The bursa is only rarely
tumorous and more frequently is atrophic. Histologically, the lesions
consist of a mixed population of small, medium, and large lymphoid cells
plus plasma cells and large anaplastic lymphoblasts. These cell
populations undoubtedly include tumor cells and reactive inflammatory
cells. When the bursa is involved, the tumor cells typically appear in
interfollicular areas.
Diagnosis
For the diagnosis of Marek's disease, it is critical
to diagnose the tumors and not the infection because Marek's disease is
considered ubiquitous within commercial poultry flocks. Usually,
diagnosis is based on enlarged nerves and lymphoid tumors in various
viscera. The absence of bursal tumors helps distinguish this disease
from lymphoid leukosis (see Lymphoid Leukosis in Poultry),
although the presence of bursal tumors does not exclude Marek's
disease. Marek's disease can develop in chickens as young as 3 wk old,
whereas lymphoid leukosis typically is seen in chickens >14 wk old.
Reticuloendotheliosis, although rare, can easily be confused with
Marek's disease, because both diseases feature enlarged nerves and
T-cell lymphomas in visceral organs. A diagnosis based on typical gross
lesions may be confirmed histologically, or preferably by demonstration
of predominant T-cell populations and Marek's viral DNA in lymphomas by
histochemistry and PCR, respectively. There is a quantitative
association between viral load and Marek's disease tumors; most
tumor-bearing chickens have high viremia titers and are usually PCR
positive. Thus, the demonstration of high quantities of virus, viral
DNA, or viral antigens in tumor cells and the exclusion of other
relevant tumor viruses should be sufficient for a specific diagnosis of
Marek's disease. Furthermore, Marek's disease lymphomas usually lack
evidence of clonally integrated avian retroviruses or alteration of the
cellular oncogene c-myc.
Control
Vaccination is the central strategy for the prevention
and control of Marek's disease. The efficacy of vaccines can be
improved, however, by strict sanitation to reduce or delay exposure and
by breeding for genetic resistance. Probably the most widely used
vaccine consists of turkey herpesvirus (HVT), which has seen rapidly
increased use in recent years as a backbone in recombinant vaccines
featuring the insertion of genes from other poultry viruses, such as
Newcastle disease virus (see Newcastle Disease and Other Paramyxovirus Infections), infectious bursal disease virus (see Infectious Bursal Disease), or infectious laryngotracheitis virus (see Infectious Laryngotracheitis).
These recombinant vaccines offer protection against both Marek's
disease virus and the inserted virus. Bivalent vaccines consisting of
HVT and either the SB-1 or 301B/1 strains of Gallid herpesvirus 3 have
been used to provide additional protection against challenge with
virulentMarek's disease virus isolates. The most protective commercial
vaccine currently available appears to be CVI988/Rispens, an attenuated
Marek's disease virus strain that is also commonly mixed with HVT at
vaccination. Because vaccines are administered at hatching and require
1–2 wk to produce an effective immunity, exposure of chickens to virus
should be minimized during the first few days after hatching.
Vaccines are also effective when administered to
embryos at the 18th day of incubation. In ovo vaccination is now
performed by automated technology and is widely used for vaccination of
commercial broiler chickens, mainly because of reduced labor costs and
greater precision of vaccine administration.
Proper handling of vaccine during thawing and
reconstitution is crucial to ensure that adequate doses are
administered. Cell-associated vaccines are generally more effective than
cell-free vaccines, because they are neutralized less by maternal
antibodies. Under typical conditions, vaccine efficacy is usually
>90%. Since the advent of vaccination, losses from Marek's disease
have been reduced dramatically in broiler and layer flocks. However,
disease may become a serious problem in individual flocks or in selected
geographic areas (eg, the Delmarva broiler industry). Of the many
causes proposed for these excessive losses, early exposure to very
virulent virus strains appears to be among the most important.
Last full review/revision July 2013 by John Dunn
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