Marek’s Disease (Visceral Leukosis)

Definition/Introduction:

Marek's disease (MD) is one of the most common lymphoproliferative diseases of chickens which causes mononuclear infiltration of one or more of the following cells: peripheral nerves, gonad, iris, muscle, viscera, and skin. MD has been called by several names including "range paralysis", "neural lymphoma" and "skin leucosis".

Causative Organism: MD is caused by herpesvirus, which can be differentiated from other lymphoid neoplastic diseases. There are three serotypes of MDV which have many common antigens and are distinguished by serologic tests.

Serotype 1 Viruses	Serotype 2 Viruses	Serotype 3 Viruses( HVT)
Viruses grow best in duck embryo fibroblast or chicken kidney cell	Viruses grow best in chicken embryo fibroblast	Viruses grow best in chicken embryo fibroblast.
Virus grows slowly	Virus grows slowly	Virus grows rapidly.
Produce small plaques	Produce medium plaques	Produce large plaques

Jordan and Pattison, Poultry Diseases, 4^th ed.

Virulence and oncogenicity are associated only with serotype 1 MDV's.

Pathogenesis: There are four phases of infection: 1) degenerative changes caused by early productive-restrictive virus infection, 2) latent infection, 3) another phase of cytolytic infection associated with permanent immunosuppression, and 4) nonproductive infected lymphoid cells that may or may not progress to lymphoma formation, a "proliferative" phase. The route of infection is inhalation. The virus then replicates in the lungs (in non-lymphoid cells). An acute phase of the disease can be seen within 72-96 hours where the lymphoid system, primarily bursa and thymus, undergoes cytolytic changes. Infected birds normally recover from the acute phase of the infection after 6-7 days and become latent. Infected lymphocytes carry the virus throughout the body, causing cell-associated viremia. Eventually, virus will be shed in the environment via feather debris and dander after the secondary cytolytic infection occurs in the feather follicle epithelium (~2 weeks post infection).

Transmission: MDV can be transmitted by direct and indirect contact between birds. Transmission is primarily by airborne route as the virus is shed in epithelial cells of the feather follicle, dander, chicken house dust, feces and saliva. The virus has a long survival time in dander since viable virus has been isolated from houses that have been depopulated for many months. (Historically, prior to vaccine availability, control in broilers was based upon early brooding exposure to used broiler litter and dander, marketing survivors versus poorer results with the thoroughly cleaned and disinfected brooder houses). Transmission by egg has no significance (i.e., chicken hatched and reared in isolation will be free of MDV.

Clinical signs: MD commonly affects pullets between 12-24 weeks of age, but can infect broilers as early as 6 weeks of age. The incubation period ranges from 3-4 weeks to several months. Signs may vary according to the nerve or nerves affected. Asymmetric progressive paralysis of one or more of the extremities can be seen. Wing involvement is characterized by drooping of the limb. Torticollis of nerves controlling the neck are affected. Vagal involvement will lead to dilatation of the crop and/or gasping. If the iris is involved, eyes will lose their ability to accommodate light intensity and blindness may occur (once called "grey eye"). Many birds die suddenly without symptoms. There are nonspecific signs such as weight loss, paleness, anorexia, and diarrhea.

Pathology: Macroscopic lesions: Nerve lesions can be seen as grayish, edematous, two or three times the normal thickness, and loss of the normal striated white glistening appearance. Nerves commonly affected include the brachial and sciatic plexi, celiac plexus, abdominal vagus and intercostals nerves. Nerve enlargement may not always be seen in affected birds at necropsy, although characteristic lesions may be found histologically. Also, tumors such as lymphoma occur in the ovary along with the nerve lesions. Macroscopic appearance in affected viscera, with the exception of the bursa of Fabricius, are indistinguishable from leukotic lesions induced by other agents (e.g. lymphoid leucosis virus). Organs are enlarged with diffuse grayish discoloration.

Microscopic lesions: There are two main types of lesions in peripheral nerves. Type A is interpreted as neoplastic in character, consisting of masses of proliferating lymphoblastic cells. Sometimes, demyelination and proliferation of Schwann cells are seen with these lesions. Type B is inflammatory in nature and is characterized by diffuse infiltration of lymphocytes and plasma cells, edema, and sometimes demyelination and Schwann cell proliferation. Lymphomatous lesions in visceral organs are more uniformly proliferative in nature. Deposition and diffuse proliferation of small to medium lymphocytes, lymphoblasts, and primitive reticulum cells are seen. Plasma cells are rarely present.

Skin lesions are mostly inflammatory and can also be lymphomatous. Inflammatory cells are localized around the infected feather follicle. With small lesions, the integrity of the skin is maintained, but disruption of the epidermis leading to ulcer formation may occur with massive proliferation.

Herpesviruses replicate in the bursa of Fabricius and the thymus which results in degenerative changes in these organs. Atrophy of the thymus can be severe and involve the cortex and medulla. In some cases, lymphoid proliferation in the thymus was seen. Arterial lesions may occur in the aorta, coronary, celiac, gastric and mesenteric arteries which may show fatty proliferative changes.

Diagnosis: Since there is no truly pathognomonic gross lesions of MD and because MD lesions can closely resemble those of lymphoid leucosis (LL), the clinical diagnosis of MD has been considered difficult in practice. Infection of MDV, not necessarily accompanied by the clinical disease, can be detected by virus isolation or agar gel precipitation tests of viral antigen in feather tips or antibody in serum. These are useful features to differentiate Marek's disease from lymphoid leucosis.

Feature	Marek's disease	Lymphoid leucosis
Age	6 weeks or older	16 weeks or older
Symptoms	Frequently paralysis	Non-specific
Incidence	Frequently 5%+ in unvaccinated flocks	Rarely above 5%
Macroscopic Lesions
-Neural enlargement	-Frequent	-Absent
-Bursa of Fabricius	-Diffuse enlargement or atrophy	-Nodular tumors
-Tumors in skin, muscle, proventriculus	-May be present	-Usually absent
Microscopic lesions
-Neural involvement	-Yes -Often perivascular	-No -Focal or diffuse
-Liver tumors	-Diffuse	-Often focal
-Spleen	-Either atrophy of follicles or interfollicular tumor	-Intrafollicular tumors
-Bursa of Fabricius CNS	-Yes	-No
-Lymphoid prolifer-ation of skin and feather follicles	-Yes	-No
Cytology of tumors	Pleomorphic lymphoid cells including lymphoblasts, small, medium and large lymphocytes and reticulum cells. Rarely may only be lymphoblasts	Lymphoblasts
Category of neoplastic lymphoid cell	T cell	B cell

(Jordan and Pattison, Poultry Diseases, 4^th ed)

Treatment: There is no effective practical treatment for MD.

Prevention: Vaccination: Vaccines are extremely effective (90%+) in the prevention of Marek's disease. There are three serotypes: Serotype 1 which is available commercially as attenuated virulent or attenuated mildly virulent, Serotype 2 vaccines which are naturally non-pathogenic strains of MDV, or Serotype 3 "Herpes Virus Turkey (HVT) which are effective against virulent MDV but less effective against very virulent MDV. HVT was standard for the poultry industry throughout the 1970s, starting at over $.05/dose to as low as $3.00/1000 doses in the late 70s. It was developed at the Regional Poultry Research Lab in East Lansing , MI, now known as the Poultry Disease and Oncology Lab. Progress in the USA is due largely to USDA scientists.

Bivalent and Trivalent Vaccines: Synergistic effect and good protection can be achieved by combining the serotype vaccines 1,2, or 3 as bivalent or trivalent vaccines. These have become standard for the layer chick hatcheries, administered subcutaneously at hatching. Broiler chicks are given vaccine in ovo at the time of egg transfer.

Genetic selection: MD resistant chicks are obtained.

FAPP (filtered air positive pressure) ventilation: Biological filters to keep out airborne viruses are used.

For the commercial chick (layer and broiler) today, Marek's disease is not common due to vaccine use. For backyard operations, ease of vaccine handling and effective administration remains a challenge.

- by George Khalil, ECFVG Student

- edited by Dr. Tom Bryan, ADDL Poultry Diagnostician

References

Diseases of Poultry, Calnek, B.W. ed., 9^th and 10^th editions
Harrison and Harrison: Clinical Avian Medicine and Surgery.
Jordan, FTW. Poultry Diseases, 4^th ed.
Poultry Health Handbook, Pennsylvania State University, 3^rd ed.
Boden E. Poultry practice.