Myxomatosis

 

Young wild rabbits are infected with myxomatosis from fleas from the mother that live in the nest. This rabbit had just emerged so it was about 4 weeks old. It was caught by a dog. Although there were no injuries from the dog, the swollen eyelids indicate that it was in the initial stages of myxomatosis.Myxomatosis is a fatal disease of the European rabbit (Oryctolagus cuniculus). It is caused by a poxvirus and is characterised by subcutaneous swellings that exude a mucoid secretion when sectioned (myxomas). Lesions occur around body orifices and on the face especially on the eyelids.

Disease spread

Myxomatosis is mainly spread by biting insects, especially mosquitoes (Aedes and Anopheles spp.) and fleas. Midges (Culicoides spp.) can also transmit infection when the weather conditions are right.  Any insect that penetrates the skin can transmit the disease. In UK, the European rabbit flea Spilopsyllus cuniculi is the main vector. Its life cycle is synchronised with the reproductive status of rabbits.  The fleas can be carried on adult rabbits but need to be in the vicinity of a pregnant female in order to become sexually mature. They feed on the nestling rabbits before they mate and reproduce. This results in heavy flea burden in neonates. Fleas infected with myxomatosis virus can maintain infectivity throughout the winter and act as a reservoir of infection for the following year when the young rabbits are born (Mead-Briggs & Vaughan 1969).

In rabbits that live in close proximity with other rabbits, myxomatosis can also be spread directly between rabbits by contact or inhalation. The risk of infection in pet rabbits depends on their contact with wild rabbits and weather conditions. In those countries where myxomatosis is transmitted by mosquitoes (Aedes and Anopheles spp.) there is a high seasonal incidence and the disease spreads rapidly. It is frequently transmitted to pet rabbits housed in hutches. In UK, transmission of the virus from wild rabbits to pet rabbits usually requires close proximity for direct infection or to transfer infected fleas although mosquitoes or midges can transmit infection if the weather conditions are right. The virus persists in hutches that have been contaminated with fluid from lesions from infected rabbits and will infect unvaccinated rabbits that are put into them. Cheyletiella parasitovorax and cat and dog fleas (Ctenocephalides spp.) can act as vectors in the spread of disease. 

Virus strains

Different strains of the myxoma virus show a variation in virulence. Rabbits infected with highly virulent strains die so quickly that the disease is not transmitted as readily as the less virulent strains. Environmental temperature also has an effect on mortality rates with the disease being more lethal at low temperatures. There is a genetic resistance to myxomatosis in some individuals.

In wild rabbits, outbreaks of myxomatosis wax and wane according to the virulence of the strain and the immune status of the native rabbit population.  Myxomatosisis can occur in hares but infection is rare and usually mild.

Clinical signs of myxomatosis

The most common route of infection is through an insect bite. Replication of the virus takes place at the inoculation site and in the regional lymph node. It is followed by cell associated viraemia and generalised infection throughout the body. The disease starts with a skin lesion, which typically develops 4-5 days after inoculation of the virus and enlarges to become about 3cm in diameter 9-10 days after infection. The rabbit is viraemic, with virus replication taking place throughout the lymphoid system. The eyelids become thickened and eventually the eyes are completely closed by the ninth day with a semipurulent ocular discharge. Secondary swellings develop throughout the body, typically on the nares, lips, eyelids and base of the ears and on the external genitalia and anus. Histologically, the swellings contain large stellate mesenchymal cells within a seromucinous matrix, with few inflammatory cells. The epidermis overlying the swellings is hyperplastic and both epidermal and conjunctival cells may contain intracytoplasmic inclusions. Hypertrophy of endothelial cells can result in narrowing of capillaries causing a necrosis. Clinically, this is manifested by visual changes in the lesions. Initially, there is hyperaemia followed by soft swellings that enlarge, harden and become crusty. The epithelium becomes increasingly necrotic until, eventually (if the rabbit survives), the dead tissue falls away and the skin heals although there may be some deformity.

The severity and distribution of the lesions affects the outcome of the disease. It takes 6-8 weeks for the lesions to regress. If the rabbit can survive this period it may recover but many cases do not. At the outset, it is hard to know which rabbits will survive and which ones will die. Lesions around the nose can block the nares and cause severe respiratory distress. Secondary infection and pneumonia are common.  The cause of death is not always clear.

In male rabbits that recover, inflammation of the testicles makes them infertile for up to 12 months.

Recovery from myxomatosis

It is possible for rabbits to survive myxomatosis but it can take 6-8 weeks for the to recover. At the end of that period any crusty or nodular lesions fall away and the skin heals. Several factors determine whether rabbits survive or die from myxomatosis and how long they live after infection. Experimental studies have shown that infected rabbits mount an immune response about seven days after infection and reach peak levels by about 28 days. Antibodies persist for prolonged periods and give absolute immunity for many months. Maternal transfer of antibodies takes place and passive immunity lasts for 4-5 weeks in baby rabbits. Very young rabbits without passive immunity are particularly susceptible to infection and die more rapidly than adult animals. Some rabbits seem to have a genetic resistance to infection. 

Relationship of myxomatosis with Shope fibroma virus

The virus that causes myxomatosis is a member of the Leporipoxvirus genus that cause fibromas in their natural hosts. The natural host of the myxoma virus is not the European rabbit (Oryctolagus cuniculi) but the Forest rabbit (Sylvilagus brasiliensis) or Brush rabbit (Sylvilagus bachmani) that are native to North or South America. Another important member of the Leporipoxvirus genus is rabbit fibroma virus (Shope fibroma virus), which causes generalised fibromatosis in the Cottontail (Sylvilagus floridanus) that lives in US. In the European rabbit (Oryctolagus cuniculi) Shope fibroma virus causes a benign fibroma that regresses within 3 weeks of inoculation.  Cross immunity between Shope fibroma virus and myxomatosis occurs.  European rabbits that recover from infection with Shope Fibroma virus are immune to myxomatosis

Vaccination

Vaccination against myxomatosis has progressed through the years and there are differences between countries. In the UK a live, attenuated freeze-dried virus vaccine containing Shope fibroma virus grown in cell-line tissue culture (Nobivac Myxo, Intervet) was used until 2012.  This vaccine was not always effective has been replaced in UK and Europe by Nobivac Myxo RHD. This is based on a recombinant attenuated myxoma vector virus that contains the RHD VP60 capsid gene to produce a single vaccine virus that immunises against myxomatosis and Rabbit Haemorrhagic Disease (RHD). The vaccine is based on a novel approach that disables the myxoma virus in a way that renders it unable to cause disease but preserves its ability to provide protection against myxomatosis and  RHD. This vaccine appears to be more effective in controlling myxomatosis than its predecessor although it offers little or no protection against new variant RHD (RHDV2). A separate vaccine is required against this disease.