Marek's diseases is a herpes viral disease of 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 8-17 wk of age, were reported recently 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, an avirulent strain related to Marek’s disease virus. 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, may be 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.
Three serotypes of the cell-associated herpesvirus are recognized. Serotypes 1 and 2 designate virulent and avirulent chicken isolates, respectively; serotype 3 designates the related avirulent turkey herpesvirus. Serotypes 2 and 3, as well as attenuated serotype 1 viruses, have been used as vaccines. Serotypes are identified by reaction with type-specific monoclonal antibodies or by biological characteristics such as host range, pathogenicity, growth rate, and plaque morphology. Currently, virulent serotype 1 strains are further divided into pathotypes, which are often referred to as mild (m), virulent (v), very virulent (vv), and very virulent plus (vv+) Marek’s disease virus strains.
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 serotypes 1 and 2, which are highly contagious, turkey herpesvirus is not readily transmissible among chickens (although it is easily transmitted among turkeys, its natural host). Attenuated serotype 1 strains vary greatly in their transmissibility among chickens; the most highly attenuated are not transmitted. Marek’s disease virus is not vertically transmitted. 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, other concurrent diseases, and several environmental factors including stress.
Currently, 4 arbitrary 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 serotype 1 strains and is characterized by antigen production, which leads to cell death. 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 lymphocytes by co-cultivation with susceptible cells in tissue cultures. Some T cells, latently infected with oncogenic serotype 1 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.
Typically, affected birds show only depression before death, although emaciation may be noted. A transient paralysis syndrome (unilateral leg paresis) has been associated with Marek’s disease, causing a characteristic posture of one leg held forward and the other held backward as lesions progress. Chickens become ataxic for periods of several days and then recover. This syndrome is rare in immunized birds.
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. Lymphoid infiltrates may expand the iris muscle and distort the shape of the pupil. 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 both tumor cells and reactive inflammatory cells. When the bursa is involved, the tumor cells typically appear in interfollicular areas.
Usually, diagnosis is based on enlarged nerves and lymphoid tumors in various viscera. The rareness of bursal tumors helps distinguish this disease from lymphoid leukosis (see Leukosis/sarcoma Group); also, Marek’s disease can develop in chickens as young as 3 wk of age, whereas lymphoid leukosis typically is seen in chickens >14 wk of age. 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 better, by demonstration of predominant T-cell populations and Marek’s viral DNA in lymphomas by histochemistry and PCR, respectively. Furthermore, Marek’s disease lymphomas will usually lack evidence of clonally integrated avian retroviruses or alteration of the cellular oncogene c-myc.
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. Bivalent vaccines consisting of turkey herpesvirus and either the SB-1 or 301B/1 strains of serotype 2 Marek’s disease virus have been used to provide additional protection against challenge with virulent serotype 1 isolates. Several attenuated serotype 1 Marek’s disease vaccines are also available; of these, the CV1988/Rispens strains appears particularly effective. A synergistic effect on protection, noted mainly between serotype 2 and 3 strains, has prompted the empirical use of other virus mixtures. 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. Using fowlpox virus and herpesvirus of turkeys as vectors, experimental recombinant vaccines have been shown to be effective against challenge with virulent Marek’s disease virus.