Marek's disease

Marek's disease
Virus classification
Group:	Group I (dsDNA)
Family:	Herpesviridae
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

There are five syndromes 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 percent). 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), anisocoria, 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 prevent 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

The demonstration of nerve enlargement, especially with the ischiatic nerve along with suggestive clinical signs in a bird that is around three to four months old is highly suggestive of Marek's Disease. 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 with another condition that affects poultry known as Lymphoid Leukosis as well as an inflammatory event associated with hyperplastic changes of the affected tissue.

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 non-sterilizing.^[1] However, it does reduce the amount of virus shed in the dander and hence reduce 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. Benjamin Roy Burmester.^[5] 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 sub-cutaneous 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.^[6] However, because vaccination does not prevent infection with the virus,^[7] 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).^[8]

Eponym

The disease is named after Dr. József Marek.

References

1. ^ ^{a b} 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. ^ ^{a b c} 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 (1999). "Atherosclerosis induced by infection with Marek's disease herpesvirus in chickens". Am Heart J 1999 Nov;138(5 Pt 2):S465-8 (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 volume= 31:449-461. 
5. ^ 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 
6. ^ Carter, G.R.; Flores, E.F.; Wise, D.J. (2006). "Herpesviridae". A Concise Review of Veterinary Virology. http://www.ivis.org/advances/Carter/Part2Chap11/chapter.asp?LA=1. Retrieved 2006-06-10. 
7. ^ 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 
8. ^ 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