Marek's disease

Marek's disease
Virus classification
Group:	Group I (dsDNA)
Order:	Herpesvirales
Family:	Herpesviridae
Subfamily:	Alphaherpesvirinae
Genus:	Mardivirus
Species:	Gallid herpesvirus 2 (GaHV-2)

Marek's disease is a highly contagious viral neoplastic disease in chickens. It is named after József Marek, a Hungarian veterinarian. Occasionally misdiagnosed as an abtissue pathology it is caused by an alphaherpesvirus known as 'Marek's disease virus' (MDV) or Gallid herpesvirus 2 (GaHV-2). The disease is characterized by the presence of T cell lymphoma as well as infiltration of nerves and organs by lymphocytes.^[1] Viruses related to MDV appear to be benign and can be used as vaccine strains to prevent Marek's disease. For example, the related Herpesvirus of Turkeys (HVT), causes no apparent disease in turkeys and continues to be used as a vaccine strain for prevention of Marek's disease (see below). Birds infected with GaHV-2 can be carriers and shedders of the virus for life. Newborn chicks are protected by maternal antibodies for a few weeks. After infection, microscopic lesions are present after one to two weeks, and gross lesions are present after three to four weeks. The virus is spread in dander from feather follicles and transmitted by inhalation.^[2]

Syndromes

Left—normal chicken eye. Right—Eye of a chicken with Marek's disease

Six syndromes are known to occur after infection with Marek's disease. These syndromes may overlap.

• Classical Marek's disease or neurolymphomatosis causes asymmetric paralysis of one or more limbs. With vagus nerve involvement, difficulty breathing or dilation of the crop may occur. Besides lesions in the peripheral nerves, there are frequently lymphomatous infiltration/tumours in the skin, skeletal muscle, visceral organs. Organs that are commonly affected include the ovary, spleen, liver, kidneys, lungs, heart, proventriculus and adrenals.
• Acute Marek's disease is an epidemic in a previously uninfected or unvaccinated flock, causing depression, paralysis, and death in a large number of birds (up to 80%). The age of onset is much earlier than the classic form; birds are four to eight weeks old when affected. Infiltration into multiple organs/tissue is observed.
• Ocular lymphomatosis causes lymphocyte infiltration of the iris (making the iris turn grey), unequal size of the pupils, and blindness.
• Cutaneous Marek's disease causes round, firm lesions at the feather follicles.^[2]
• Atherosclerosis is induced in experimentally infected chickens.^[3]
• Immunosuppression – Impairment of the T-lymphocytes prevents competent immunological response against pathogenic challenge and the affected birds become more susceptible to disease conditions such as coccidiosis and Escherichia coli infection .^[4] Furthermore, without stimulation by cell-mediated immunity, the humoral immunity conferred by the B-cell lines from the Bursa of Fabricius also shuts down, thus resulting in birds that are totally immunocompromised.

Diagnosis

Diagnosis of lymphoid tumors in poultry is complicated due to multiple etiological agents capable of causing very similar tumors. It is not uncommon that more than one avian tumor virus can be present in a chicken, thus one must consider both the diagnosis of the disease/tumors (pathological diagnosis) and of the virus (etiological diagnosis). A step-wise process has been proposed for diagnosis of Marek’s disease which includes (1) history, epidemiology, clinical observations and gross necropsy, (2) characteristics of the tumor cell, and (3) virological characteristics^[5]

The demonstration of peripheral nerve enlargement along with suggestive clinical signs in a bird that is around three to four months old (with or without visceral tumors) is highly suggestive of Marek's disease. Histological examination of nerves reveals infiltration of pleomorphic neoplastic and inflammatory lymphocytes. Peripheral neuropathy should also be considered as a principal rule-out in young chickens with paralysis and nerve enlargement without visceral tumors, especially in nerves with interneuritic edema and infiltration of plasma cells.^[6]

The presence of nodules on the internal organs may also suggest Marek's disease, but further testing is required for confirmation. This is done through histological demonstration of lymphomatous infiltration into the affected tissue. A range of leukocytes can be involved, including lymphocytic cell lines such as large lymphocyte, lymphoblast, primitive reticular cells, and occasional plasma cells, as well as macrophage and plasma cells. The T cells are involved in the malignancy, showing neoplastic changes with evidence of mitosis. The lymphomatous infiltrates need to be differentiated from other conditions that affect poultry including lymphoid leukosis and reticuloendotheliosis, as well as an inflammatory event associated with hyperplastic changes of the affected tissue.

Key clinical signs as well as gross and microscopic features that are most useful for differentiating Marek’s disease from lymphoid leukosis and reticuloendotheliosis include (1) Age: MD can affect birds at any age, including <16 weeks of age; (2) Clinical signs: Frequent wing and leg paralysis; (3) Incidence: >5% in unvaccinated flocks; (4) Potential nerve enlargement; (5) Interfollicular tumors in the bursa of Fabricius; (6) CNS involvement; (7) Lymphoid proliferation in skin and feather follicles; (8) Pleomorphic lymphoid cells in nerves and tumors; and (9) T-cell lymphomas.^[7]

In addition to gross pathology and histology, other advanced procedures used for a definitive diagnosis of Marek’s disease include immunohistochemistry to identify cell type and virus-specific antigens, standard and quantitative PCR for identification of the virus, virus isolation to confirm infections, and serology to confirm/exclude infections.

The World Organisation for Animal Health (OIE) reference laboratories for Marek’s disease include the Institute for Animal Health, Compton Laboratory, UK and the USDA Avian Disease and Oncology Laboratory, USA.^[8]

Prevention

Vaccination is the only known method to prevent the development of tumors when chickens are infected with the virus. However, administration of vaccines does not prevent transmission of the virus, i.e., the vaccine is not sterilizing.^[1] However, it does reduce the amount of virus shed in the dander, hence reduces horizontal spread of the disease. Marek's disease does not spread vertically. The vaccine was introduced in 1970 and the scientist credited with its development is Dr. Ben Roy Burmester.^[9] Before that, Marek's disease caused substantial revenue loss in the poultry industries of the United States and the United Kingdom. The vaccine can be administered to one-day-old chicks through subcutaneous inoculation or by in ovo vaccination when the eggs are transferred from the incubator to the hatcher. In ovo vaccination is the preferred method, as it does not require handling of the chicks and can be done rapidly by automated methods. Immunity develops within two weeks.^[2]

The vaccine originally contained the antigenically similar turkey herpesvirus, which is serotype 3 of MDV.^[10] However, because vaccination does not prevent infection with the virus,^[11] the Marek's disease virus has evolved increased virulence and resistance to this vaccine. As a result, current vaccines use a combination of vaccines consisting of HVT and gallid herpesvirus type 3 or an attenuated MDV strain, CVI988-Rispens (ATCvet code: QI01AD03).^[12]

References

1. Hirai, K (Ed.), ed. (2001). Current Topics in Microbiology and Immunology: Marek's Disease (Current Topics in Microbiology and Immunology). Springer: Berlin. ISBN 3-540-67798-4.
2. Fenner, Frank J.; Gibbs, E. Paul J.; Murphy, Frederick A.; Rott, Rudolph; Studdert, Michael J.; White, David O. (1993). Veterinary Virology (2nd ed.). Academic Press, Inc. ISBN 0-12-253056-X.
3. Fabricant CG, Fabricant J (November 1999). "Atherosclerosis induced by infection with Marek's disease herpesvirus in chickens". Am. Heart J. 138 (5 Pt 2): S465–8. doi:10.1016/S0002-8703(99)70276-0. PMID 10539849.
4. Islam AFMF, Wong CW, Walden-Brown SW, Colditz IG, Arzey KE, Groves PJ. "Immunosuppressive effects of Marek's disease virus (MDV) and herpesvirus of turkeys (HVT) in broiler chickens and the protective effect of HVT vaccination against MDV challenge". Avian Pathology 31: 449–461.
5. Witter, R. L., Gimeno, I. M., Pandiri, A. R., & Fadly, A. M. (2010). Tumor diagnosis manual: the differential diagnosis of lymphoid and myeloid tumors in the chicken (Vol. 1, pp. 1–84): American Association of Avian Pathologists.
6. Bacon, L. D.; Witter, R. L.; Silva, R. F. (2001). "Characterization and experimental reproduction of peripheral neuropathy in White Leghorn chickens". Avian Pathology 30 (5): 487–499. doi:10.1080/03079450120078680. PMID 19184938.
7. "Chapter 2.3.13. Marek’s Disease", OIE Terrestrial Manual 2010, Retrieved 2012-08-03
8. "Reference Experts and Laboratories", World Organisation for Animal Health, Retrieved 2012-08-03
9. Burmester, B. R.; Purchase, H. G.; Burmester, B. R. (1970). "Protection Against Marek's Disease by Vaccination with a Herpesvirus of Turkeys'". Avian Diseases (American Association of Avian Pathologists, Inc.) 14 (2): 413–429. doi:10.2307/1588488. JSTOR 1588488. PMID 4913403.
10. Carter, G.R.; Flores, E.F.; Wise, D.J. (2006). "Herpesviridae". A Concise Review of Veterinary Virology. Retrieved 2006-06-10.
11. Witter, R. L. (1997). "Increased Virulence of Marek's Disease Virus Field Isolates". Avian Diseases (American Association of Avian Pathologists, Inc.) 41 (1): 149–163. doi:10.2307/1592455. JSTOR 1592455. PMID 9087332.
12. Osterrieder, Nikolaus; Kamil, Jeremy P.; Schumacher, Daniel; Karsten Tischer, B.; Trapp, Sascha (2006). "Marek's disease virus: from miasma to model". Nature Reviews Microbiology 4 (4): 283–94. doi:10.1038/nrmicro1382. PMID 16541136.

External links

• Marek's Disease Information at poultrykeeper.com