Myxomatosis is a disease caused by Myxoma virus, a rabbit poxvirus in the genus Leporipoxvirus. The natural hosts are tapeti (forest cottontail, Sylvilagus brasiliensis) in South and Central America, and brush rabbits (Sylvilagus bachmani) in North America. The myxoma virus causes only a mild disease in these species, but causes a severe and usually fatal disease in European rabbits (Oryctolagus cuniculus), the species of rabbit commonly raised for companionship and as a food source.
Myxomatosis is an example of what occurs when a virus jumps from a species adapted to the virus to a naive host, and has been extensively studied for this reason. The virus was intentionally introduced in Australia, France, and Chile in the 1950s to control wild European rabbit populations.
Cause
Myxoma virus is in the genus Leporipoxvirus of subfamily Chordopoxvirinae. Like other poxviruses, myxoma viruses are large DNA viruses with linear double-stranded DNA. Viral replication occurs in the cytoplasm of the cell. The natural hosts are tapeti (Sylvilagus brasiliensis) in South and Central America, and brush rabbits (Sylvilagus bachmani) in North America. The myxoma virus causes only a mild disease in these species, with signs limited to the formation of skin nodules.
Myxomatosis is the name of the severe and often fatal disease in European rabbits caused by the myxoma virus. Different strains exist which vary in their virulence. The Californian strain, which is endemic to the West Coast of the United States and Baja in Mexico, is the most virulent, with reported case fatality rates approaching 100%. The South American strain, present in South America and Central America, is slightly less virulent, with reported case fatality rates of 99.8%. Strains present in Europe and Australia were originally introduced from South America but have become attenuated, with reported case fatality rates of 50–95%. While wild rabbits in Europe and Australia have developed some immunity to the virus, this is not generally true of pet rabbits.
Transmission Myxomatosis is transmitted primarily by hematophagic arthropods. The myxoma virus does not replicate in these arthropod hosts, but is physically carried by biting arthropods from one rabbit to another. In North America mosquitoes are the primary mode of pathogen transmission, and multiple species of mosquito can carry the virus. In Europe and Australia the rabbit flea is the primary means of transmission, with the virus able to survive 3–4 months in the flea. Transmission via the bites of flies, lice, and mites have also been documented. Outbreaks have a seasonal nature and are most likely to occur between August and November, but cases can occur year round. Seasonality is driven by the availability of arthropod vectors and the proximity of infected wild rabbits.
The myxoma virus can also be transmitted by direct contact. Infected rabbits shed the virus in ocular and nasal secretions and from areas of eroded skin. The virus may also be present in semen and genital secretions. Poxviruses are fairly stable in the environment and can be spread by contaminated objects such as water bottles, feeders, caging, or people's hands. They are resistant to drying but are sensitive to some disinfectants.
Pathophysiology
A laboratory study in which European rabbits received intradermal injections of a South American strain of the myxoma virus demonstrated the following progression of disease. Initially the virus multiplied in the skin at the site of inoculation. Approximately two days following inoculation the virus was found in nearby lymph nodes, and at three days it was found in the bloodstream and abdominal organs. At approximately four days the virus was isolated from non-inoculated skin as well as from the testes. Slight thickening of the eyelids and the presence of virus in conjunctival fluid was detectable on day five. Testicular engorgement was noticed on day six.
Clinical presentation: South American strains
The clinical signs of myxomatosis depend on the strain of virus, the route of inoculation, and the immune status of the host. Signs of the classic nodular form of the disease include a subcutaneous mass at the site of inoculation, multiple cutaneous nodules, swelling and edema of the eyelids and genitals, a milky or purulent ocular discharge, fever, lethargy, depression, and anorexia. The Lausanne strain causes the formation of large purple nodules, a sign not seen in other strains. According to Meredith (2013), the typical time course of the disease is as follows:
Days after infection Clinical signs 2–4 Swelling at site of infection 4 Fever 6 Swelling of eyelids, face, base of ears, and anogenital area 6 Secondary skin lesions, including red pinpoint lesions on eyelids and raised masses on body 6–8 Clear ocular and nasal discharge that becomes mucopurulent and crusting 7–8 Respiratory distress 8–9 Hypothermia 10 Complete closure of eyelids due to swelling 10–12 Death
In peracute disease with a highly virulent strain, death may occur within 5 to 6 days of infection with minimal clinical signs other than conjunctivitis. Death usually occurs between days 10 and 12. In rabbits infected with attenuated, less virulent strains of the virus, the lesions seen are more variable and generally milder, and the time course is delayed and prolonged. Many rabbits will survive and the cutaneous lesions gradually scab and fall off, leaving scarring. A milder form of the disease is also seen in previously vaccinated domestic rabbits that have partial immunity. Vaccinated rabbits often present with localized scabbed lesions, frequently on the bridge of the nose and around the eyes, or multiple cutaneous masses over the body. The rabbits are often still bright and alert, and survive with nursing care.
Respiratory signs are a common finding in rabbits that survive the first stages of myxomatosis. Mucopurulent nasal discharge occurs, leading to gasping and stertorous respiration with extension of the head and neck. Secondary bacterial pneumonia occurs in many cases. Chronic respiratory disease, such as nasal discharge, is common in surviving rabbits. Even in apparently recovered rabbits, it is not unusual to find lung lobes filled with fluid rather than air at necropsy.
Since the 1970s an "amyxomatous" form of the disease has been reported in Europe which lacks the cutaneous nodules typical of myxomatosis. This form is clinically milder and generally nonlethal. Respiratory signs, including clear or purulent nasal discharge, predominate. Perineal edema, swollen eyelids, and purulent blepharoconjunctivitis are generally still present. This form has been observed in wild rabbits, but is significant mainly in farmed rabbits.
Clinical presentation: North American strains of myxomatosis
The distribution of myxomatosis in North America is restricted to the native habitat of the brush rabbit, which extends from western Oregon and California to Baja California in Mexico. This is because the brush rabbit is the only carrier of myxoma virus in North America. Other native cottontail rabbits and hares are incapable of transmitting the disease.
California
A 1931 paper reported twelve cases of myxomatosis from Santa Barbara, Ventura, and San Diego counties of California. Affected rabbits developed mucopurulent conjunctivitis and swelling of the nose, lips, ears, and external genitalia. Rabbits that survived for over a week developed cutaneous nodules on the face.
A 2024 study found that myxomatosis caused by the MSW strain (California/San Francisco 1950) of the myxoma virus occurs regularly in the greater San Jose and Santa Cruz regions of California. Common physical examination findings included swollen eyelids, swollen genitals, fever, and lethargy. Swollen lips and ears and subcutaneous edema also occurred in some rabbits. Domesticated rabbits that spent time outdoors were at greater risk of acquiring the disease, and most of the cases occurred between August and October. It was postulated that the number of cases brought to veterinarians underestimated the total number of cases, as sudden death can be the first sign noted.
Oregon
A 1977 report from western Oregon described several cases of myxomatosis. The most common clinical signs observed were inflammation and swelling of the eyelids, conjunctiva, and anogenital region. Lethargy, fever, and anorexia were also observed. A single rabbit with confirmed myxomatosis eventually recovered.
A 2003 report of a myxomatosis outbreak in western Oregon reported sudden death as a common finding. Also noted were lethargy, swollen eyelids, and swollen genital regions.
Baja California
A 2000 report from the Baja Peninsula in Mexico described two outbreaks of myxomatosis in 1993. Affected domestic rabbits developed skin nodules and respiratory symptoms.
Diagnosis Because the clinical signs of myxomatosis are distinctive and nearly pathognomonic, initial diagnosis is largely based on physical exam findings. If a rabbit dies without exhibiting the classic signs of myxomatosis, or if further confirmation is desired, a number of laboratory tests are available.
Histopathology
Tissues from rabbits suffering from myxomatosis show a number of changes on histopathology. Affected skin and mucous membranes typically show undifferentiated mesenchymal cells within a matrix of mucin, inflammatory cells, and edema. Scattered intracytoplasmic viral inclusion bodies are present in epithelial cells. Spleen and lymph nodes are often affected by lymphoid depletion. Necrotizing appendicitis and secondary infections with gram-negative bacteria have also been described.
Polymerase chain reaction
The development of molecular methods such as polymerase chain reaction (PCR) and real-time polymerase chain reaction assays has created faster and more accurate methods of myxoma virus identification. PCR can be used on swabs, fresh tissue samples, and on paraffin-embedded tissue samples to confirm the presence of the myxoma virus and as well as to identify the viral strain.
Other testing
Other means of diagnosing myxomatosis include immunohistochemistry, electron microscopy, and virus isolation. Immunohistochemistry can demonstrate the presence of myxoma virus particles in different cells and tissues of the body. Negative-stain electron microscopic examination can be used to identify the presence of a poxvirus, although it does not allow specific verification of virus species or variants. Virus isolation remains the "gold standard" against which other methods of virus detection are compared. Theoretically at least, a single viable virus present in a specimen can be grown in cultured cells, thus expanding it to produce enough material to permit further detailed characterization.
Treatment At present, no specific treatment exists for myxomatosis. Given that the mortality rate of North American strains of myxomatosis nears 100%, euthanasia is often recommended in the United States. In other countries where less virulent strains are present and vaccines against the disease are available, supportive care may help rabbits to survive the infection. Careful monitoring is necessary to avoid prolonging suffering if treatment is attempted. Cessation of food and water intake, ongoing severe weight loss, or rectal temperatures below are reasons to consider euthanasia.
Prevention
Vaccination