Marek’s disease - By Hybro B.V., Boxmeer, The Netherlands - MD was first described by Marek in Hungary (1970). Since then it has been described by numerous authors in many countries. In the nineteen fifties and sixties MD was responsible for enormous losses in the poultry industry: mortality up to 80 % could be seen in some flocks.

At the end of the sixties vaccines for MD were developed - THV and CVI 988 – which solved the problem almost instantly, although some incidental breaks were known to occur. Since then however, the incidence of Marek’s increases occasionally, causing sometimes high mortality in properly vaccinated flocks. Very virulent pathotypes and multiple age production systems are blamed for this.

Etiology

The disease is caused by a Herpes virus, of which several types are known and can be divided in three different groups:

1. Group 1: This group consists of Herpes viruses, isolated from chickens that are pathogenic, which means that viruses in this group can cause clinical symptoms of MD.

2. Group 2: Viruses in this group are isolated from chickens, but they are not pathogenic.

3. Group 3: Herpes virus isolated from turkeys. Not pathogenic for chicken.

The group 1 Herpes viruses are isolated worldwide. Almost all flocks worldwide carry this type of virus and will shed the virus even if the flock is properly vaccinated and shows no clinical signs of Marek’s disease.

Clinical symptoms and pathology

1. Classical type of MD:
   This form of MD is nowadays almost only found in white egg layers. It occurs at an age of 2 – 4 months and is characterised by asymmetrical paralysis of the birds. They are not able to walk, and they die from starvation. At post mortem thickened peripheral nerves can be observed, that lost their normal transversal stripes. Mainly the condition of the nervus ischiadicus is used for diagnosis, although also other nerves are involved.

2. Transient paralysis:
   Here we see a sudden paralysis, especially of legs and neck. Normally only a low number of birds in a flock are affected. A quick recovery, within a few days, is the normal pattern. Very low mortality.

3. Ocular form of MD:
   Very rare, occurs mainly in adult birds. The iris – normally having a bright orange colour - is greyish, and the pupils form an irregular shape. The birds become blind but will not die, provided they are able to find feed and water.

4. Skin lesions:
   Can be seen in broilers and breeders. The feather follicles are swollen and haemorrhages in skin and follicles can be observed. This condition is mainly a severe problem for the processing plant.

5. Visceral form of MD
   Although this form can be noticed already at an early age, nowadays it starts usually at the end of rearing and continues until 40 – 45 weeks of age. It is the most common form of MD at the moment in several countries, causing high mortality – up to 30 % - even in vaccinated flocks. Lymphoid tumours can be found in liver, spleen, ovaries, kidneys, heart, proventriculus, mesenterium, muscles and skin. The birds are pale and look distressed and they loose body weight and die after several weeks.
   Production in affected flock is usual about 5 % below standard, as many affected birds continue to produce eggs for some time. Differential diagnosis with other tumour-like diseases, especially Avian Leukosis, can be difficult and the final diagnosis can only be made by further laboratory investigation.

Pathogenesis

Birds most of the times get infected by inhalation of the virus when it is transmitted to the lymphoid organs, mostly B cells are affected. After the initial infection further spread to several lymphoid organs takes place. from here feather follicle cells are infected which take care of further spread into the environment. The development of lymphomas is the last step. The entire incubation period takes several weeks.

Therapy

There is no therapy that has been proven to be effective.

Prevention

As there is no therapy for MD the only way to fight the disease is by preventive measures. For this purpose we have several possibilities at our disposal:

1. Vaccination
   At the moment there are several MD vaccines commercially available:
   
   

   • Monovalent vaccines:
     HVT: Herpes Virus of Turkeys (MDV Group 3). Widely used in many countries. It has been given very good results in the past, but protection is now insufficient in many countries. HVT is marketed in cell-free (Lyophilized) and cell-associated (under liquid nitrogen) form.
     
     CVI 988: This is the so-called “Rispens” strain. It is an attenuated Group I MD virus, which means that originally it was a pathogenic chicken Herpes virus, weakened by attenuation. In the past there was a fear that this vaccine could turn into a pathogenic form again and therefore it was not allowed in some countries. Experience in the field during many years proved there was no risk whatsoever in using this vaccine. In some countries where Rispens is not allowed, a cloned strain called CR6 is used on a small scale. Rispens vaccine is a cell-associated strain, so it has to be stored under liquid nitrogen.
     
     

   • Polyvalent vaccines:
     SBI: SBI is a group 2 MDV. By itself it does not give sufficient protection but in combination with HVT it gives better protection than HVT alone. This combination is used in some areas where HVT by itself does not give sufficient protection.
     
     HVT+CVI 988: This combination is used in some countries where MD is a very serious clinical problem. There are field experiences that this combination gives a good protection for MD, however there is little experimental or laboratory work to support these experiences.

   Besides the choice of the best vaccine for a certain area also the following aspects can influence the result of MD vaccination considerably:
   
   Dosage of vaccine
   Generally, this only plays a role when the vaccine contains insufficient vaccine virus. The minimum required virus content of vaccines is 2000 PFU for HVT and 1000 FFU for the Rispens vaccine. Beyond a certain limit further increasing the PFU and FFU does not make an essential difference anymore.
   
   Storage and reconstitution of the vaccine
   The utmost accuracy is required: the manufacturer’s instructions should be closely followed. A proper reconstitution is especially very important with the cell-associated vaccines. After reconstitution the vaccine has to be used quickly, preferably within a few hours time.
   
   Administration of the vaccine
   Also this should be done as accurately as possible. Quality, cleaning and disinfection of the material should be perfectly all right. Automatic vaccinators have to be checked on a regular basis.
   
   Maternal immunity
   Maternal immunity in one-day-old chickens can delay immunity build-up after vaccination. This effect can especially be observed with cell-free HVT. To avoid this, we recommend using HVT only for the last generation, which is vaccinated (e.g. for great grand parents: Rispens; for parent stock: Rispens+ HVT). In some countries birds are revaccinated after some time (at an age of 1 – 6 weeks) to avoid influence of maternal immunity. There is no scientific base for this system, but some organisation claims good response. To achieve a very early immunity for MD the vaccine can be given in ovo (in the egg). It is widely used for broiler now, but for layers and breeders, there is still insufficient data available to judge the effect.
   
   

2. Hygiene
   Early strong MD infections: As mentioned before MD virus can be isolated in almost all poultry areas worldwide. It is present in all the dust inside and around poultry houses. Furthermore it requires some time (10 – 14 days) for vaccinated day old chickens to develop a reasonable level of immunity. On top of this young birds are very susceptible for infection with Marek virus. The immune system is not fully matured at hatch. These afore mentioned facts show the high risk of young chickens getting the infection before immunity by the day old vaccination has developed.
   
   To prevent this early strong MD infection – against which really no vaccination can protect – it is important to keep the young chickens under good hygienic conditions. The houses must be totally clean (to assist prevention of MD a proper cleaning procedure is even more important than good disinfection). This includes cleaning and washing of the houses, ventilation systems, and if possible the area around the house. No adult birds, which almost all spread MD virus, should be close to the rearing houses.
   
   Other infections/ conditions influencing MD immunity. Some diseases, like Chicken Anaemia (C.A.V.), IBD (Gumboro Disease) and REO viruses are known to have a negative influence on the immunity for MD. Also any immunosuppressive agent will delay the build up of immunity. Examples here are stress factors and mycotoxins.
   
   

3. Genetics
   For a long time it is known already that there are differences in resistance to MD that are genetically determined. What these differences are exactly based on is not known. The genetic resistance will probably become more and more important as protection by vaccination becomes more and more difficult. At the moment breeding for MD resistance is an important goal in the breeding programs. Different systems can be used for this:

   • Selection of resistant birds based upon blood-typing (B-alleles)
   • Selection of resistant birds based upon challenge: non-vaccinated birds are placed under strong infectious conditions
   • Selection based upon marker genes

Summary

MD is a very serious threat to the poultry industry worldwide. Unfortunately there are no easy answers to this problem. Any solution has to be based upon co-operation of all the following areas in the poultry industry:

Laboratory:
Proper diagnosis
Virus isolation (to make the best choice of vaccine)

Vaccine industry:
Development of new vaccines (mono- or polyvalent)

Hatchery:
Proper storage of vaccine
Proper vaccination procedure

Farmers:
Prevention of strong early MD exposure
Prevention of other diseases influencing MD

Breeding organisation:
Development of more resistant strains Only with co-operation of all these levels, we will be able to keep Marek’s Disease under control. Veterinary Department Hybro B.V. Boxmeer, The Netherlands, January 2006

Source: Hybro B.V. - February 2006