Marek's disease

Marek's disease is a contagious viral neoplastic disease in chickens. Marek's disease was named after József Marek, who characterized it in 1907. Marek's disease (MD) is a disease caused by an alphaherpesvirus, which is generally referred to as Marek's disease virus (MDV). The disease is characterized by T cell lymphoma and infiltration of affected nerves and organs by lymphocytes. Containing viruses related to MDV appear innocuous and could be utilized as vaccine strains for its prevention, such as the related herpesvirus in turkeys (HVT), which causes no disease to the birds, and is still used as a vaccine strain for Marek's disease prevention. As a result, birds infected with MDV may be carriers and shedders of the virus for life, maternal antibodies generally protect newborn or hatchling chicks for a few weeks. Similar to most viral infections, microscopic lesions will be present one to two weeks after infection, while gross lesions will develop three to four weeks after infection. Exposure to MD is through airborne transmission via dander shed from feather follicles.

Syndromes

Six syndromes have been described following Marek's disease infection and some can coexist.

Classic Marek's disease/neurolymphomatosis results in asymmetric paralysis of one or more limbs, sometimes producing respiratory distress or dilatation of the crop if the vagus nerve is involved. In addition to noticeable lesions in the peripheral nerves, there is usually also lymphomatous infiltration/tumours in skin, skeletal muscle, and/or visceral organs. The organs most often affected include ovaries, spleen, liver, kidneys, lungs, heart, proventriculus and adrenals.
Acute Marek's disease occurs in an uninfected or unvaccinated flock and produces depression, paralysis and death in many birds (80% is not uncommon). Onset is much earlier than the classic Marek's disease; birds are four to eight weeks old when affected. There is infiltration of multiple organs/tissue.
Ocular lymphomatosis results in infiltration of the iris by lymphocytes (the iris turns grey), unequal size of the pupils, and blindness.
Cutaneous Marek's disease causes round, firm lesions at the feather follicles.
Tratitionally atherosclerosis has been induced in chickens experimentally infected.
Immunosuppression reflects the dysfunction of the T-lymphocytes created by Marek's disease preventing a competent immunological response to pathogenic challenge, thus fowl exposed to Marek's disease are made susceptible to disease conditions of coccidiosis, and Escherichia coli infection.Furthermore, without the stimulation of cell-mediated immunity, the B-cell lines from the Bursa of Fabricius also becomes shut down and the birds are immunocmpromised.

Diagnosis

Despite the fact that, because of the multiplicity of etiological agents that cause tumors, diagnosing lymphoid tumors in poultry is not easy. In fact, and when you consider that it is common for a chicken to have more than one avian tumor virus, you can easily see that one has to deal with a combination of both diagnosis of the disease/tumors (pathological diagnosis) and of the virus (etiological diagnosis). For Marek's disease, there has been a suggested stepwise process, which includes the following:

History, epidemiology, clinical signs and gross necropsy;
Morphology of the tumor cell, and;
Virology

In terms of pathology, the criteria for Marek's disease rely on the recognition of peripheral nerve enlargement associated with characteristic clinical signs in a bird that is about 3-4 months (with or without visceral tumors). Histology of the nerve will show infiltration of pleomorphic neoplastic and inflammatory lymphocytes. Also, the possibility of a peripheral neuropathy should be given as a primary rule out in young chickens with paralysis and nerve enlargement and no visceral tumors, especially in nerves which also have byliateral interneuronal edema and a heavy infiltration of plasma cells.

The presence of nodules within the internal organs may suggest Marek's disease, but further investigation is needed before a conclusion can be drawn. A histological demonstration of lymphomatous infiltration into the affected tissue is needed for confirmation. The histological examination will show a mix of leukocyte types with lymphocytic cell lines including large lymphocytes, lymphoblasts, primitive reticular cells with a few plasma cells, and macrophages and plasma cells. The T cells are involved in the malignancy, with the neoplastic changes, including evidence of mitosis, being indicative. The lymphomatous infiltrates need to be differentiated from other prevalent conditions affecting poultry including lymphoid leukosis, reticuloendotheliosis, and an inflammatory event associated with the hyperplastic changes of the affected tissue.

The key clinical signs as well as gross and microscopic details that are mostly helpful to differentiate Marek's disease from lymphoid leukosis and reticuloendotheliosis include:

Age: Marek's disease can be observed with affected birds of all ages including <16 weeks of age;
Clinical signs: frequent wing and leg paralysis;
Incidence: >5% incidence in an unvaccinated flock;
Potential nerve enlargement;
Interfollicular tumors in the bursa of Fabricius;
Central nervous system involvement;
Lymphoid proliferation in the skin and feather follicles;
Pleomorphic lymphoid cells in nerves and tumors; and
T-cell lymphomas.

In addition to gross pathology and histology, immunohistochemistry to identify cell type and virus-specific antigens, standard and quantitative PCR to identify the virus, virus isolation to confirm infections, and serology to confirm/exclude infections are other advanced diagnostics for a more definitive diagnosis.

The World Organisation for Animal Health (OIE) reference laboratory for Marek's disease is Avian Viral Oncogenesis group (headed by Professor Venugopal Nair OBE) at The Pirbright Institute, UK.

Only PCR blood tests can detect Marek's disease in practice, and if all done correctly, you will also be able to differentiate between a vaccinated bird that has antibodies, and a true positive Marek's disease positive. Marek's disease is untreatable, however there may be supportive care to assist.

I support the viewpoint that all flocks that are positive for Marek's disease be a closed flock, one where no bird can be introduced or leave that flock. This means strictly adhering to biosecurity protocols and adequately sorbent cleaning protocols, utilizing approved disinfectants, such as Activated Oxine or Virkon S, and keeping with debris that will reduce buildup of dander on the existing sandbedding in the environment. You can provide proper nutrition, repeatedly and on a timely basis deworming, and providing vitamin supplements which all may assist all infected flocks in remaining healthy. Additionally we simply provide infecting birds with an environment that reduces their stress on a daily response basis to the infection part of Marek's disease because stress is generally a catalyst for ill health in infected birds with Marek's disease for the disease.

Prevention

Vaccination is the only known way to prevent tumors from developing after infection with the virus in chickens. The vaccination process does not prevent an infected bird from shedding virus but reduces the quantity of virus shed in the dander, and subsequently reducing horizontal spread. Marek's disease is not spread vertically.

Before the Marek's disease vaccine, Marek's disease was a cause of significant revenue loss in poultry industries in the United States and the United Kingdom. The Marek's disease vaccine can be given to one-day-old chicks via subcutaneous inoculation, or using in ovo vaccination when eggs are transferred from the incubator into the hatcher. In ovo vaccination is preferred, since the chicks do not have to be handled, it can be done quickly and can be done automatically. Immunity develops in a matter of weeks.

Although vaccination does not prevent infection from the virus, Marek's is still capable of being transmitted from vaccinated flocks, to any bird, including wild bird populations. The first Marek's disease vaccine was available in 1970. Prior to widespread use of the Marek's vaccine, Marek's disease caused milder paralysis, with the only lesions being in neural tissue. Additionally, the mortality of chickens infected with Marek's disease was relatively low. The current strains of Marek virus, many decades after the vaccine was introduced, cause lymphoma formation throughout the chicken's body and 100% mortality has occurred in unvaccinated chickens. Marek's disease vaccine is a "leaky vaccine", which means that it prevents only the symptoms of the disease, while not preventing infection of the host or transmission of the virus. Most other vaccines prevent infection of the host.

In typical circumstances high virulent strains of the virus are not selected for by evolution. This is because, a virulent strain capable of killing the host would kill the host before allowing the virus to be transmitted to other possible hosts and replicate. Thus less virulent strains will be selected for by evolution. Less virulent strains can produce symptoms due to their virulence but not to the point of killing the host, allowing the host to transmit the virus (and allowing the virus to replicate). However, leaky vaccine would modify this natural selection and facilitate the evolution of high virulent strains. Because the vaccine did not eliminate infection with the virus nor did it eliminate transmission of the virus, the vaccinated chickens then allow high virulent strains to proliferate. The vaccine has increased the fitness of the more virulent strains.

The evolution of Marek's disease through vaccination has caused a significant impact on the poultry industry. High virulent strains have been selected for to the point that any un-vaccinated chicken will die if they come into contact with Marek's disease. There are numerous other leaky vaccines used in agriculture. One in particular is the avian influenza vaccine. Leaky vaccines such as the avian influenza have the capability of selecting for virulent strains.