Myxomatosis 

Disease Summary

(B209.8.w8, B284.10.w10, B600.16.w16, B601.13.w13, B603.3.w3, B609.2.w2, B610.23.w23)

In rabbits:

• Oryctolagus - (Genus)
  • "Typical skin lesions that are associated with disease in the domestic rabbit include edema of the eyelids, ears, nose, anus, and genitals; blepharoconjunctivitis; hemorrhage; and nodules on the ears, head, body, and legs at the site of infection that may become congested or necrotic". (J213.8.w1)
  • Transmission of the disease occurs primarily via insect vectors but may also occur by direct contact with infected rabbits or inhalation. (B600.16.w16)

In hares: 

• Myxomatosis infection is mild and rare. Wild hares rarely exhibit clinical signs although they do have a limited serological response that indicates infection. (B284.10.w10, B600.16.w16)

Alternative Names (Synonyms)

• Bighead
• Mosquito disease 

(B64.22.w8)

Disease Type

Infectious/Non-Infectious Agent associated with the Disease

History of the disease

"Myxoma virus was one of the first viruses to be discovered". (B600.16.w16)

• 1896: 
  • Myxomatosis was first described in laboratory rabbits, Oryctolagus cuniculus domesticus - Domestic European rabbit, in Uruguay. (B209.8.w8, B601.13.w13, B611.10.w10, J213.8.w1)
    • These rabbits had been acquired for antiserum production but suddenly succumbed to a highly fatal disease that was characterised by numerous mucinous skin tumours. (B611.10.w10)
    • The virus that caused this first known outbreak of myxomatosis was thought to have originated from Sylvilagus brasiliensis - Tapeti in which the virus causes a relatively mild disease. Transmission from the wild to domestic rabbits was likely to have occurred via Aedes spp. mosquitoes. (B611.10.w10)
• The disease soon spread to other South American countries. (B611.10.w10)
• 1926: The myxoma virus was first introduced into Australia for use in experimental studies to determine the feasibility of its use in controlling the pest population of the Oryctolagus cuniculus - European rabbit. (B611.10.w10)
• 1927: Aragao identified myxoma virus particles in stained smears and remarked on its close resemblance with fowlpox and smallpox. The myxoma virus was later to be classified as a pox virus. (B600.16.w16)
• Brazilian workers discovered the transmission of the virus was by the mechanical vectors of mosquitoes and fleas. (B600.16.w16)
• 1928 (J213.8.w1) / 1930: Myxomatosis was first identified in North America. Natural outbreaks of a disease that was fatal and resembled myxomatosis, occurred in domestic rabbit colonies near San Diego in south California. This was thought to be due to spread of the myxoma virus from infected domestic rabbits that had been imported from Mexico. Myxomatosis became enzootic in western United States where Sylvilagus bachmani - Brush rabbit was thought to be acting as the natural reservoir for the myxoma virus. (B611.10.w10)
• 1950: 
  • The myxoma virus was released into Australia in an attempt to control wild Oryctolagus cuniculus - European rabbits that had spread in plague proportions across the continent, causing serious environmental and economic potential. (B209.8.w8, B601.13.w13, B611.10.w10)
  • This strategy was highly effective at first but its impact was reduced by subsequent emergence of attenuated strains and also genetically resistant rabbits. (B209.8.w8, B601.13.w13)
    • By the fourth year after the release of the virus, significantly attenuated strains of the myxoma virus had become the dominant virus strains instead of the original virulent virus. These naturally attenuated strains cause a milder disease that has a longer duration; this favours vector transmission and therefore the persistence of this virus in nature. (B611.10.w10)
    • Genetically resistant strains of rabbits emerged within a decade of the myxoma virus. (B611.10.w10)
• 1952:
  • Illegal introduction of the disease into France to control rabbits. Myxomatosis then spread to continental Europe. (B209.8.w8, B600.16.w16, B601.13.w13, B603.3.w3)
  • There was a deliberate release of infected rabbits onto the Heisker Islands (Outer Hebrides) as an experiment in pest control. Two years later the rabbit population was actually as large as ever despite significant mortality that resulted from the myxomatosis. (B600.16.w16)
• 1953: Spread of the disease to the UK with widespread decimation of the wild rabbit population despite efforts to eradicate myxomatosis. There was public outcry in the UK because rabbits were often kept as pets and people were disturbed by the site of sick, blind, wild rabbits in public places. Thus, in 1954, it became an offence to knowingly use or permit the use of infected rabbits to spread myxomatosis into an uninfected population. (B284.10.w10, B600.16.w16, B603.3.w3)
• Late 1950s: Myxomatosis was endemic in the UK. (B600.16.w16)
• 1966: Spilopsyllus cuniculi (rabbit flea) was introduced into Australia from Europe in 1966 in an attempt to improve the transmission of Myxomatosis. (B614.8.w8)

The myxoma virus has also been released on sub-Antarctic islands, and in Argentina, Chile and, unsuccessfully, in New Zealand. (B209.8.w8, B601.13.w13)

Different viral strains of myxomatosis

• There are many different strains of myxoma poxviruses; the ones that cause myxomatosis are at the more virulent end of the spectrum. (B604.5.w5) 
• One study of 92 strains of this virus reported a virulence spectrum that ranged from strains that cause over 99% mortality in Oryctolagus cuniculus - European rabbit to others that cause less than 30% mortality. 
  • Most virulent strains include:
    • California
    • Lausanne
    • Standard Laboratory 
  • Least virulent strains include:
    • Neuromyxoma
    • Nottingham
  • It is possible that ecological pressures such as those seen in Australia may have been responsible for the emergence of several of these strains of myxoma virus. 
  • "In many instances however, man himself has manipulated the viruses to the point of permanent modification". (B611.10.w10)

(B611.10.w10)

• Highly virulent strains kill the rabbit quickly and so the disease will often not be transmitted as easily as the less virulent strains. (B600.16.w16)
• The California strain is a highly virulent variant of the myxoma virus that occurs in western California and Oregon. (B604.5.w5)
  • "The California strain continues to be highly virulent and is slightly different antigenically prompting some to consider the California strain to be distinct from other myxoma virus and give it the designation California rabbit fibroma". (J213.4.w4)
    • "However, the demonstrable antigenic differences are insufficient to justify this distinction". (B614.9.w9)
• The Californian and South American virus isolates are closely related but the two types can be distinguished by DNA restriction endonuclease profiles and also antigenically. (B209.8.w8, B604.5.w5)

• The myxoma virus has not undergone the rapid loss of virulence that was seen in the French and Australian viruses. Mild strains have emerged in Britain but moderately virulent strains are still predominant. This different pattern of evolution has been attributed to differences in the major vectors (fleas in Britain and mosquitoes in France and Australia). Fleas are less seasonal and far less mobile than the mosquitoes. Selection of virulent virus strains may be due to the fact that fleas move in large numbers from dead rabbits while only occasionally moving from live rabbits. (B611.10.w10)

Variable pathology of the myxoma virus:

• Pathogenicity and thus clinical signs, will vary with the strain of myxoma virus and the host immunity. Also, different portals of entry of the infection will cause variable pathology. (B602.19.w19, B603.3.w3, B608.21.w21, B609.2.w2) There may be:
  • different positions and sizes of myxomatous growths; (B603.3.w3)
  • different extent of systemic involvement; (B603.3.w3)
  • different degrees of pulmonary oedema. (B603.3.w3) 
• Standard Laboratory (Moses) strain causes relatively flat skin lesions. (B600.16.w16) 
• Lausanne strain is more virulent than the Moses strain and produces protuberant skin lesions. (B600.16.w16) 
• Some variants are associated with smaller and fewer skin lesion but may cause massive pulmonary oedema. (B600.16.w16) 
• In aerosol infection there is more likely to be pneumonic signs with mucopurulent nasal discharge and lacrimation. (B284.10.w10, B600.16.w16)

Pathogenesis of myxomatosis in lagomorphs

• The myxoma virus is usually transmitted passively by arthropods feeding on the rabbit (often the mosquito or rabbit flea). There is no replication of the virus within the vector. (B601.13.w13)
• Replication occurs at the inoculation site within the epidermis and dermis. (B209.8.w8, B600.16.w16, B601.13.w13, B603.3.w3).
  • In the natural Sylvilagus host, there is no systemic phase of infection. (B209.8.w8)
• However, in Oryctolagus cuniculus, the virus then spreads within leucocytes (rather than plasma) to the regional lymph node where it undergoes more replication and attains a high titre. (B209.8.w8, B600.16.w16, B601.13.w13, B603.3.w3)
• Often a skin lesion will develop four to five days post inoculation and then enlarge to 3 cm by ten days post inoculation. (B600.16.w16, B603.3.w3)
• Viral replication in the regional lymph node results in cell associated viraemia and generalised infection with dissemination to the skin away from the inoculation site, spleen, mucosal surfaces (e.g. conjunctiva), other lymph nodes, testes, liver and lungs. The replication occurs within the lymphoid system. (B600.16.w16, B601.13.w13, B603.3.w3)
• By day 9 there is eyelid swelling (the eyes may be completely closed) and secondary conjunctivitis with semipurulent ocular discharge. (B600.16.w16, B603.3.w3)
• Secondary lesions occur throughout the body especially on the lips, nares, eyelids, 
• Purulent swollen lesions develop on the mucocutaneous junctions and the base of the ears. (B603.3.w3)
• Although the virus may be shed in discharges, actual transmission by close contact is thought to be very unusual. (B601.13.w13)
• Virulent disease in farmed colonies often leads to spread by inhalation and thus a primary pulmonary site of infection. This results in pneumonia and a secondary pasteurellosis at seven to twenty days instead of the characteristic skin masses. (B603.3.w3)
• Myxomatosis in colonies may also present as rhinitis and ocular discharge. Transmission of the virus by aerosol is much more likely to give the affected animal respiratory signs than transmission by insect. (B600.13.w13)

Infective "Taxa"

• Myxoma virus (Poxviridae (Virus Family))
• Culicidae - Mosquitoes (Family)  (Primary vectors)
• Siphonaptera - Fleas (Order) (Primary vectors)

Non-infective agents

Physical agents

References

Disease Author

Referees

Major References / Reviews

Code and Title List

Other References

Code and Title List

Detailed Clinical and Pathological Characteristics

Clinical Characteristics

In Oryctolagus spp. 

• In Oryctolagus cuniculus - European rabbit and Oryctolagus cuniculus domesticus - Domestic European rabbit the clinical findings depend on how long the rabbit survives and on the strain of virus; many rabbits will die within two weeks. (B609.2.w2)
• In wild rabbits, outbreaks of the disease wax and wane according to the immune status of the local, native, rabbit population, and to the virulence of the virus strain. (B600.16.w16)

Clinical findings

• Oedema of the genitals and eyelids. 
  • In the early stages of the disease, scrotal skin oedema may be the only clinical sign. 
  • The oedema can also progress to the nares, lips, base of the ears, and the anus.
• Generalised swelling of the ears and face.
• Skin nodules / masses that usually range from 0.1 cm to 1 cm in diameter, on the body, face and legs. These nodules usually appear after 10-14 days and are commonly found at mucocutaneous borders; they generally disappear in three to four weeks concurrent with the body's antibody response. The skin lesions can sometimes become necrotic and haemorrhage.
• Mucopurulent blepharoconjunctivitis (due to secondary bacterial infections, e.g. with Staphylococcus or Pasteurella spp.), which often results in complete closure of both eyes.
• Lethargy  
• Pyrexia  
• Anorexia 
  • Although in some cases, surprisingly, the appetite of an affected rabbit may be maintained up until shortly before death. 
• Depression  
• Enlarged or shrunken testes

There may be secondary problems of:

• Rhinitis with mucopurulent nasal discharge due to secondary bacterial infection (see: Rhinitis in Rabbits). 
• Pneumonia (often pasteurellosis - see: Pasteurellosis in Lagomorphs)
• Gastrointestinal stasis
• Infertility: 
  • "Experimental infection of European rabbits with an attenuated form of mxyoma virus resulted in transient systemic illness with orchitis and epididymitis; animals recovered from infection and demonstrated normal fertlity by 60 to 90 days following infection". (J213.8.w1)
• Abandoned litters

• In highly virulent strains, death may occur within four to eight days due to the pantropic effects of the acute viraemia.
• In lower virulence strains, death usually occurs within two to five weeks and is often due to inanition, overwhelming secondary bacterial infection (usually due to secondary Pasteurella pneumonia), or predation.
• Terminal convulsions frequently precede death.

(B64.22.w8, B209.8.w8, B284.10.w10, B600.13.w13, B600.16.w16, B601.7.w7, B601.13.w13, B603.3.w3, B606.4.w4, B611.10.w10, J3.150.w5)

Angora rabbits

• Myxomatosis was reported in a group of depilated Angora rabbits. 
• Skin nodules were erythematous and plaque-like, a few mm to three cm in diameter. The lesions became necrotic and haemorrhagic.

(B608.21.w21)

Previously vaccinated rabbits - Atypical myxomatosis

• Multiple benign fibromas may sometimes be seen in vaccinated rabbits that are exposed to a natural myxoma virus infection. It is thought that this milder type of myxomatosis may be more likely to be seen in rabbits that have not been given the intradermal dose of the vaccination as it is this portion of the vaccination dose that is important in conferring full immunity. (B600.9.w9, B601.13.w13) See: administration of vaccine, in the Preventative Measures section below.
  • However, it has also been seen in rabbits known to have been vaccinated correctly. (V.w121) 
• The vaccinated rabbit should be protected from the myxoma virus's lethal effects but not from the dermatological effects of the viral infection. Clinical findings include: (B601.13.w13)
  • Myxomatous skin lesions with scabbing may be seen around the eyes and/or the bridge of the nose. 
  • In some cases there may be multiple cutaneous masses over the rabbit's body. These nodules will regress with time. (B601.13.w13)
• No treatment is necessary unless there is superficial ulceration with secondary bacterial infection which will warrant treatment with antibiotics. (B600.9.w9)

Amyxomatous myxoma virus strain

• Acute haemorrhagic pneumonia. (B601.7.w7)

Californian strain of myxoma virus in Oryctolagus cuniculus domesticus - Domestic European rabbit

Peracute form (death within seven days): 

• Lethargy, oedema of the eyelids, pyrexia, red eyes and a watery ocular discharge may be seen. 

• Oedema and erythema of the eyelids that can then extend to:
  • Ears 
  • Face: lips and nares
  • Genitalia 
  • Perineum 
• Lethargy
• Dyspnoea 
• Pyrexia 
• Anorexia and dehydration
• Cutaneous haemorrhage and CNS signs (seizures or excitement, opisthotonus) preceding death. 

Few rabbits will live long enough to develop the chronic form of disease which produces clinical findings that are more often associated with other strains of myxoma virus. Clinical findings that may be seen in addition to the ones described above for the acute disease are:

• Generalised nodular cutaneous tumours.
• Oedema around the ear base.
• Purulent blepharoconjunctivitis. 
• Secondary Pasteurella infections that can cause additional deaths.

In the surviving rabbits, the lesions will regress over the course of one to three months. 

(B602.19.w19, B604.5.w5, B608.21.w21, B609.2.w2, B611.10.w10, J213.4.w4)

In Brachylagus spp.

Brachylagus idahoensis - Pygmy Rabbit  

• Experimentally, this species can be infected with the California myxoma virus, but the virus levels in the subsequent lesions was found to be too low for mosquito transmission. The disease has not been seen in this species in the wild. 

(B209.8.w8)

In Lepus spp.

Lepus europaeus - Brown hare and Lepus timidus - Mountain hare

• Occasionally, individuals of these species can develop clinical myxomatosis via natural infection although few animals exhibit disease experimentally. (B209.8.w8, B611.10.w10)
  • Mild to severe generalised myxomatosis has been seen in the occasional individual animal. (B611.10.w10)
  • Lepus europaeus - Brown hare has been found to be highly resistant to infection with myxoma virus under experimental conditions. (B611.10.w10)
  • Multiple subcutaneous masses on the head, back and legs. (J514.1.w1)

Lepus californicus - Black-tailed jackrabbit

• Resistant to infection with the California and South America myxoma viruses. (B209.8.w8)

In Sylvilagus spp. that are the natural host of the myxoma virus

• "Sylvilagus sp. of rabbits infected with Myxoma viruses develop skin tumors, resembling the fibromas in the Oryctolagus sp. caused by the rabbit fibroma virus (see Rabbit Fibroma Virus), at the site of virus entry, most often at the base of one or both ears. Tumors are rarely more than 1 cm in diameter, typically appear 4 to 8 days after exposure, and persist for over a month. Very young rabbits can become ill but rarely die". (J213.4.w4)

Sylvilagus brasiliensis - Tapeti 

• Localised fibromas that may be up to several centimetres in diameter and are formed at the inoculation site. (B209.8.w8)
• The fibromas generally appear four to eight days after exposure and can persist for ten to forty days. (B209.8.w8, B611.10.w10)
• There are no clinical signs of systemic disease in the adult rabbit but there may be the potential for this to occur in rabbits with immature immune systems. (B209.8.w8)
  • Very young rabbits may succumb to generalised disease. (B611.10.w10)

• A firm localised fibroma may be found at the site of transmission (scratch, bite), often the ear base, lips, or feet. (B209.8.w8, B602.19.w19, B609.2.w2)
• The South American virus causes slightly more prominent lumps compared with the California strain. (B611.10.w10)
• The fibroma will eventually scab and regress over a period of weeks or months. (B209.8.w8)
• The fibromas may be the only clinical sign (B602.19.w19, B609.2.w2); systemic disease or the prolonged persistence of the tumour is not seen, even in the young rabbit. (B209.8.w8)

• In experimental infections, small local skin lesions developed after the California strain of virus was inoculated. (B611.10.w10)

In other Sylvilagus spp.

Incubation

• Eight to twenty one days (B601.13.w13, B610.23.w23)
• In Oryctolagus cuniculus - European rabbit, a skin lesion may occur four to five days after virus inoculation. (B284.10.w10, B600.16.w16, B603.3.w3)
• In Sylvilagus spp., the tumours usually occur four to eight days after exposure. (J213.4.w4)
• Infection via inhalation: if infection is via inhalation then the resultant clinical signs of pneumonia and secondary pasteurellosis occur within seven to twenty days. (B600.16.w16, B603.3.w3)
• California strain of myxoma virus: often the incubation period is as short as one to three days. (B609.2.w2)

Mortality / Morbidity

• Myxomatosis is reported to be endemic on four continents: South America, North America, Australia and Europe. (B614.9.w9)
• "an endemic disease of wild rabbits throughout Europe". (B600.16.w16)
• In the USA, the disease is seen primarily in California. The strain here is particularly virulent with mortality rates exceeding 99%. (B609.2.w2)
• In wild rabbits in the UK when myxomatosis first appeared, mortality rates were about 99.5%. (B617)

Prognosis

• If a rabbit is systemically affected then the prognosis is very poor. Quality of life, welfare and euthanasia need to be considered at the outset of the disease. (B603.3.w3)
  • Note: "given the severe and distressing nature of the condition and the very poor prognosis, euthanasia is generally recommended on humane grounds". (B601.13.w13)
  • Apparent respiratory failure with bleeding into the airway and sneezing blood has been seen about three weeks into the clinical course, when the rabbit otherwise appeared to be improving. (V.w121)
• Wild Oryctolagus cuniculus - European rabbit:   
  • Very poor prognosis although the occasional individual will survive. (B284.10.w10)
  • There have been reports of some survivors that were apparently releasable after 19 days. (B151)
• Oryctolagus cuniculus domesticus - Domestic European rabbit: some rabbits have survived this disease although their chances are poor. (B600.16.w16, B601.13.w13)
  • Previously vaccinated rabbits will often only have a mild form of the disease and will need supportive medication until their immune systems can overcome the virus. (B601.7.w7)
• Many of the clinical signs and the causes of fatality are a result of secondary bacterial infections, dehydration and inanition (due to lethargy and also an inability to see) and predation. (B603.3.w3)

In Oryctolagus cuniculus domesticus

• Domestic rabbits (Oryctolagus cuniculus domesticus) often have severe disease and a high mortality rate. (B602.19.w19, B608.21.w21)
• Previously vaccinated rabbits who have the milder form of disease, often survive with nursing care. (B601.13.w13)
• Myxomatosis is generally not seen as a clinical problem in the domestic rabbit population in the USA. However, it has been described in Oregon and California. (B601.13.w13)
• There are occasional disease outbreaks in Oryctolagus cuniculus domesticus - Domestic European rabbit in Mexico and the United States of America (usually California), which are thought to represent accidental transmission from Sylvilagus bachmani - Brush rabbit via an insect vector. (J213.8.w1)
• Myxomatosis was reported in a group of depilated Angora rabbits. In this particular case, morbidity was low and mortality in the group was infrequent. (B608.21.w21)

In Oryctolagus cuniculus

In wild European rabbits (Oryctolagus cuniculus):

• In Chile, myxomatosis is considered enzootic in the wild population of Oryctolagus cuniculus - European rabbit. (B611.10.w10)

Australia and Europe

• Myxoma virus initially killed nearly 100% of infected animals after it was first introduced to populations of Oryctolagus cuniculus - European rabbit in Australia and Europe; however the combination of attenuated myxoma viral strains and selection for resistant hosts, has greatly decreased the prevalence of mortality due to this disease. (J213.8.w1)
• "Estimates of the impact of myxomatosis on infected rabbits in endemic areas range from 30%-40% mortality in Australia to 47%-69% in Britain". (B209.8.w8)

Australia

• Genetically resistant strains of wild rabbits (Oryctolagus cuniculus - European rabbit) emerged through a process of natural selection in Australia and in these rabbits, there was only a 25% mortality caused by a virulent strain of myxoma compared to the 90% mortality that occurred in the non-resistant strains of rabbit. (B611.10.w10)

Spain

• A study in Spain found that there was endemic myxomatosis in wild populations of Oryctolagus cuniculus - European rabbit but there was no evidence of adult mortality associated with this prevalence. (J213.8.w1)

Pathology

Gross pathology in Oryctolagus spp.

In Oryctolagus spp. there may be:

• General: reduced body fat. There may be haemorrhages of organs and the body cavity (including thymus, trachea and lungs).
• Skin:
  • Cutaneous fibrous nodules that have mucinous material centrally. 
  • Oedema of the eyelids and anogenital region.
  • Subcutaneous ecchymoses.
• Eyes: Conjunctiva swollen, mucopurulent discharge, crusting. 
• Respiratory:
  • Nasal mucosa is usually swollen and there is often a mucopurulent discharge and crusting.
  • Lungs: there may be patchy consolidation (lung lesions are usually associated with secondary bacterial infections) or haemorrhage.
• Lymph nodes: enlarged, oedematous, commonly haemorrhagic.
• Spleen: may be markedly swollen 
• Liver: there may be necrosis
• Gastrointestinal tract: serosal surfaces may have ecchymoses.

(B209.8.w8, B336.42.w42, B609.2.w2, J213.8.w1)

Peracute cases: there may be no gross lesions. (B609.2.w2)

Histopathology in Oryctolagus spp.

• Epidermis: this is proliferative and thickened when overlying the cutaneous tumours, and there may be eosinophilic inclusions present. Necrosis is evident and intraepithelial pustules may occur. 
• Dermis: this is oedematous and there is evidence of breakdown of fibrillar elements. Myxoma cells, which are large stellate or elongate basophilic stromal cells, are particularly associated with small vessel walls. It may be possible to see cytoplasmic inclusions within these cells. Acute inflammation and local haemorrhage are common in the dermis and also in superficial muscle, but these lesions do not spread through underlying fascial planes.  
• Lymph nodes: acute inflammation and the destruction of lymphocytes occur together with a proliferation of reticulum cells, but there may still be persisting foci of normal lymphoid tissue. The lymph node can be depleted of lymphocytes. There are similar vascular changes to that found in the dermis and haemorrhage is common. 
• Other lymphoid tissues: microscopic changes that resemble a less severe form of those found in the lymph nodes can occur in cecal tonsil, thymus, peribronchial lymphoid tissue, and the spleen. 
• Testes: acute orchitis may occur; myxoma cells may be seen in the interstitium. 
• Other organs: myxoma cells may be present (e.g. in the bone marrow). 

(B209.8.w8)  

In adult Sylvilagus spp.

• In adult Sylvilagus spp. there may be local skin tumours that resemble the fibromas found in Shope Fibroma Virus Infection in Oryctolagus spp.. (B614.9.w9)

In Lepus spp. or young Sylvilagus spp.

• In hares (Lepus - (Genus)), or young Sylvilagus spp., there is usually a mild localised infection although sometimes there may also be disseminated cutaneous fibromatous to myxomatous nodules that are similar to those found in acute myxomatosis. (B614.9.w9)

Human Health Considerations

Disease has been reported in either the wild or in captivity in:

• Various wild rabbits and hares including Sylvilagus bachmani - Brush rabbit, Sylvilagus brasiliensis - Tapeti, Sylvilagus floridanus - Eastern cottontail, Lepus europaeus - Brown hare, Lepus timidus - Mountain hare and Oryctolagus cuniculus - European rabbit. (J213.4.w4)
• Common disease of Oryctolagus cuniculus - European rabbit; occasional individual cases in Lepus europaeus - Brown hare. (J514.1.w1)
• Sylvilagus bachmani - Brush rabbit, Sylvilagus brasiliensis - Tapeti, Sylvilagus floridanus - Eastern cottontail, Lepus europaeus - Brown hare, Lepus timidus - Mountain hare and Oryctolagus cuniculus - European rabbit (including Oryctolagus cuniculus domesticus - Domestic European rabbit) are naturally susceptible to myxoma virus. However, several additional species of Sylvilagus can be infected under experimental conditions. (B611.10.w10)
• Experimentally infected species include Brachylagus idahoensis - Pygmy rabbit, Sylvilagus audubonii - Desert cottontail and Sylvilagus nuttallii - Mountain cottontail. (B209.8.w8).
• A study in Spain during 1993-1996 found myxomatosis to be an endemic disease in a population of Oryctolagus cuniculus - European rabbit. No deaths from myxomatosis were seen in adults and all had antibodies. In juveniles, rabbits with typical lesions were seen, with increasing percentages of juveniles developing antibodies through the year. (J3.150.w5)

Note:

• "Very intensive investigations have been done to determine the host range of the myxoma virus since this information was required by the Australian authorities before the decision could be made to release the virus. Numerous species of wild and domestic animals and birds were tested for susceptibility to the virus and ultimately it was shown that under natural conditions the myxoma virus would produce disease in leporids only". (B611.10.w10) 

Host Species List

• Oryctolagus cuniculus - European rabbit
• Oryctolagus cuniculus domesticus - Domestic European rabbit
• Lepus europaeus - Brown hare
• Lepus timidus - Mountain hare
• Sylvilagus brasiliensis - Tapeti
• Sylvilagus bachmani - Brush rabbit
• Sylvilagus floridanus - Eastern Cottontail

Experimentally infected species:

• Brachylagus idahoensis - Pygmy rabbit  
• Sylvilagus audubonii - Desert cottontail
• Sylvilagus nuttallii - Mountain cottontail

Disease has been specifically reported in Free-ranging populations of:

• Various wild rabbits and hares including Sylvilagus bachmani - Brush rabbit, Sylvilagus brasiliensis - Tapeti, Sylvilagus floridanus - Eastern cottontail, Lepus europaeus - Brown hare, Lepus timidus - Mountain hare and Oryctolagus cuniculus - European rabbit. (J213.4.w4)
• A study in Spain during 1993-1996 found myxomatosis to be an endemic disease in a population of Oryctolagus cuniculus - European rabbit. No deaths from myxomatosis were seen in adults and all had antibodies. In juveniles, rabbits with typical lesions were seen, with increasing percentages of juveniles developing antibodies through the year. (J3.150.w5)

Host Species List

• Oryctolagus cuniculus - European rabbit
• Lepus europaeus - Brown hare
• Lepus timidus - Mountain hare
• Sylvilagus brasiliensis - Tapeti
• Sylvilagus bachmani - Brush rabbit
• Sylvilagus floridanus - Eastern cottontail

General Information on Environmental Factors/Events and Seasonality

• Myxomatosis is more lethal at low temperatures. (B600.16.w16)

• Myxomatosis is often a seasonal disease with outbreaks more likely in late summer and autumn when insect vectors are numerous. (B10.45.w47, B600.3.w3, B609.2.w2)
• Often there is an annual increase in myxomatosis in August through to November. (B604.5.w5)
• In warm, wet, years the disease may be seen throughout the year. (B10.45.w47)

Link with population immune status:

• A study in Spain during 1993-1996 found myxomatosis to be an endemic disease with increase in incidence linked to the recruitment of susceptible juvenile rabbits into the population. This was seen when a delayed onset of breeding one year was accompanied by a delayed onset in the annual outbreak of the disease. (J3.150.w5)

Regions / Countries where the Infectious Agent or Disease has been recorded

• Myxomatosis is reported to be endemic on four continents: South America, North America, Australia and Europe. (B614.9.w9)
• In the USA, the disease is seen primarily in California. (B609.2.w2)

Europe

• Belgium 
• The Netherlands 
• Germany 
• Luxembourg 
• Spain 
• England 

(B611.10.w10, B614.9.w9)

• Myxomatosis has been described in Oryctolagus cuniculus - European rabbit in the following countries:
  • Uruguay 
  • Brazil 
  • Argentina 
  • Columbia 

(B209.8.w8)

• Myxomatosis has been described in Oryctolagus cuniculus - European rabbit in:
  • Panama (B209.8.w8)

• In the USA, the disease is seen primarily in the coastal mountain ranges of California and also in California's Sacramento foothills. (B10.45.w47, B209.8.w8, B609.2.w2)
  • The strain here is particularly virulent with mortality rates exceeding 99%. (B209.8.w8, B609.2.w2)
• Coastal mountain ranges of Oregon (B209.8.w8)

New Zealand. (B614.9.w9)

Regions / Countries where the Infectious Agent or Disease has been recorded in Free-ranging populations

• Myxoma viral infection was reported to be enzootic in rabbits of the Sylvilagus- (Genus) in:
  • South America  
    • In the forested part of Argentina. 
    • In particular, Sylvilagus brasiliensis - Tapeti, in Uruguay and Brazil. This situation is similar in Panama and Columbia but the virus strains that are isolated from these two countries are more closely related, antigenically, to the California virus strains although their virulence is similar to the South American strains. 
  • North America  
    • The California strains of virus are enzootic in wild Sylvilagus, particularly Sylvilagus bachmani - Brush rabbit which serves as the main source of infection of domestic rabbits. 

• Myxomatosis is enzootic in wild Oryctolagus cuniculus - European rabbit in:
  • South America  
    • In the southern part of Argentina and in Chile. 
  • Europe  
  • Australia  

(B611.10.w10)

General Information on Investigation / Diagnosis

• Clinical signs 
  • If a domestic rabbit has clinical signs of myxomatosis and a Spilopsyllus cuniculi flea infestation, then this is suggestive of a positive diagnosis.
• Biopsy and histopathology of affected tissue
• PCR of tissue extracts 
• Electron microscopy
  • A sample of the lesion material may reveal the typical poxvirus particles. 
• Virus isolation from infected tissues or conjunctival swabs. Tissue culture (various cell lines) or inoculation into rabbits or into chorioallantoic membrane, embryonated hen eggs. 
• Serological testing
  • There are various tests available for research purposes including ELISA, complement fixation assays, or virus neutralisation assays. 
  • They may not be available commercially in North America.
  • See: Clinical Pathology of Lagomorphs

(B209.8.w8, B336.42.w42, B601.13.w13, B602.19.w19, B603.3.w3, B604.5.w5, B608.21.w21, B609.2.w2, J213.4.w4, J213.8.w1)

• Environmental Assessment
• History & Documentation
• Physical Examination of Mammals
• Necropsy of Mammals
• Imaging in Lagomorph Diagnosis and Treatment
• Clinical Pathology of Lagomorphs
• Chapter 2 - B36 Field Manual of Wildlife Diseases - Specimen Collection and Preservation
• Chapter 3 - B36 Field Manual of Wildlife Diseases - Specimen shipment
• Appendix A - B36 Field Manual of Wildlife Diseases - Sample specimen history form

Similar Diseases (Differential Diagnosis)

For skin tumours that are found in Sylvilagus spp: 

• Shope Fibroma Virus Infection in Rabbits (J213.8.w1)

For perioral, periocular and perineal rash:

• Treponematosis  
  • This disease is not usually associated with fever or oedema and the animal is often otherwise healthy. (B603.3.w3, B609.2.w2)

For neurological signs:

• Rabies 
• Otitis interna/media 
• Meningitis 

For respiratory or conjunctival signs:

• Pasteurellosis (B603.3.w3)
• Keratoconjunctivitis (B209.8.w8)

For high mortality rates in rabbit populations:

• Rabbit haemorrhagic disease. 
  • This disease is easy to distinguish from myxomatosis. 

(B209.8.w8)

Specific Medical Treatment

• There is no specific treatment for myxomatosis but supportive care is important although often unsuccessful. (B602.19.w19, B608.21.w21, B609.2.w2)
• Acyclovir: this has been tried in the treatment of myxomatosis but the results were inconclusive. (B604.5.w5)

• Treatment and Care

General Nursing and Surgical Techniques

• Previously vaccinated rabbits who have the milder form of disease often survive with nursing care. (B601.13.w13)
• High environmental temperatures (85°F/29.4°C) increase the recovery rate. (B284.10.w10, B600.16.w16, B603.3.w3)
• Good nursing is important in the success of recovery of these patients. (B600.16.w16)
• Euthanasia is recommended on humane grounds unless the disease is very mild. (V.w127)

General treatment and care

• Aggressive fluid therapy, antibiosis, NSAIDs, supportive feeding and good nursing may be enough to control the disease until the immune response is strong enough to result in viral clearance in some rabbits. However, this all depends on the host's immune status and the virulence of the particular strain of myxoma virus involved. Some cases may survive for many weeks before finally developing kidney failure. (B603.3.w3)
• Antibiotics. (B600.16.w16)
• NSAIDs. (B284.10.w10, B600.16.w16)
• Opioid analgesics:
  • Not thought to be particularly effective in improving signs of pain in this condition. (B284.10.w10, B600.16.w16)
    • A study was conducted into whether buprenorphine had any effect on the course of this disease in laboratory rabbits. The results showed that there was no difference in the survival time. Rabbits treated with buprenorphine refused water and food one day earlier than the untreated rabbits and they had lower rectal temperatures immediately before their death. It was concluded that buprenorphine was not effective at relieving clinical signs of myxomatosis which may be due to pain. (J83.33.w2)
• Contraindications: 
  • Corticosteroids should not be administered due to their immunosuppressive effects. They will delay the potential development of natural immunity and the resolution of lesions in atypical myxomatosis. (B600.9.w9, B600.16.w16)

Previously vaccinated rabbits - Atypical myxomatosis

• No treatment is necessary unless there is superficial ulceration with secondary bacterial infection which will warrant treatment with antibiotics. (B600.9.w9)
  • Note: these lesions may look horrific, but generally do well, even for lesions on the eyelids. Nose lesions can be more of a problem and may leave a non-healing wound with exposed bone. (V.w121)

• Treatment and Care

Preventative Measures

Vaccine containing live attenuated Shope fibroma virus (available in Europe)

• The myxoma virus is a pox virus and a member of the Leporipoxvirus genus. Viruses in this genus cause fibromas in their natural hosts. Another member of this genus is the Shope Fibroma Virus. The natural host for this virus is Sylvilagus floridanus - Eastern Cottontail. This virus causes a benign fibroma in the European rabbit (Oryctolagus sp.) and those that have recovered from infection are immune to myxomatosis. (B600.16.w16)
  • Infection with the Shope Fibroma Virus stimulates a cross immunity to myxomatosis because the two viruses are antigenically related. This led to the development of a live attenuated freeze-dried Shope Fibroma Virus vaccine for myxomatosis. (B603.3.w3)
  • The Shope Fibroma Virus used in these vaccines is grown in cell-line tissue culture. (B600.16.w16)
  • The cross-immunity is short-lived and may be poor in some animals. (B601.13.w13, B610.23.w23)
• Time taken for immunity to develop post-vaccination: fourteen days. (B601.13.w13, B610.23.w23)
• Duration of immunity: six to ten months. (B603.3.w3)
• House rabbits: even if rabbits don't have access to the outdoors, they should still be vaccinated as insect vectors may expose them to this disease. (B601.1.w1)
• USA: routine vaccination is not carried out because of the very low incidence of myxomatosis. (B601.1.w1)
• Europe: combined VHD and myxomatosis vaccines are now available in continental Europe. (B601.1.w1)
  • In France, the rabbit is an important game animal therefore large-scale myxomatosis vaccination has been carried out in both domestic and wild rabbits. (B209.8.w8)
• In Australia, where this disease is still regarded as a useful adjunct to controlling the wild rabbits, there are no control measures undertaken and it is illegal to vaccinate domestic rabbits against myxomatosis. (B209.8.w8)

Dosing regime and administration

• The first dose is given from 6 weeks of age. (B600.3.w3, B601.13.w13)
• Boosters: every 6-12 months depending on perceived risk. (B601.13.w13)
  • If there is a high risk of myxomatosis in the local area or the pet rabbit is potentially exposed to wild rabbits that are infected with myxomatosis or insects, then vaccinate every six months; if there is no obvious local risk then perhaps only vaccinate annually in spring to cover the main risk period. (B600.3.w3, B603.3.w3)
  • Note: in some areas myxomatosis may be actively transmitted year round. (V.w121)
  • Absence of obvious wild rabbits with myxomatosis in an area does not necessarily mean absence of myxomatosis in the area. (V.w121)mean 

• Optimum time for vaccination: 
  • Late spring to provide effective immunity during the summer months. (B600.3.w3)
  • Give one to two months before the mosquito season starts. (B10.45.w47)
• Administration of vaccination:
  • It is vital that the vaccination is given correctly for a good immune response to be achieved. (B601.13.w13)
  • One tenth (0.1 mL) of the vaccination dose must be given intradermally and the rest (0.9 mL) can be given subcutaneously. (B600.3.w3, B601.13.w13)
    • The base of the ear is a useful site for the intradermal injection and the subcutaneous portion can either be given at this site also or in the scruff. (B600.3.w3)
    • Alternatively, both the intradermal and the subcutaneous dose may be given via a single injection into the scruff of the neck:
      • 0.9 mL of the 1 mL dose is given subcutaneously using a 23-25 gauge needle then with the needle orientated bevel up, it is slowly advanced up into the overlying dermis and 0.1 mL is injected into the dermis from underneath. A bleb of vaccine should be felt forming in the dermis by pinching the skin that is over the end of the needle between the forefinger and thumb. (B600.3.w3) 
  • Intradermal immunisation will produce maximum antibody response due to the following effects:
    • Langerhans cells are present within the dermis and they act as antigen-presenting cells and also increase the activation of the T-helper cells. (B600.3.w3)
    • Provision of a depot effect for the vaccination by minimising diffusion into surrounding tissues. (B600.3.w3)
    • Maximisation of the exposure of the immune cells to to the antigen and therefore the subsequent antibody response because of the excellent lymphatic drainage of the dermis. (B600.3.w3)
  • The skin must not be swabbed with alcohol or disinfectants prior to injection. (B601.13.w13)
  • See: Intradermal Injection of Rabbits

Contraindications

• The vaccination should only be administered to healthy rabbits and is not safe to use in pregnant does. (B600.3.w3, B601.13.w13, B610.23.w23). 

Vaccines containing live attenuated strains of myxoma virus

• Problems occurred with virulence of this vaccine and possible immunosuppression. (B600.16.w16, B603.3.w3)
• "Vaccination with an attenuated myxoma virus vaccine may provide temporary protection; not available in the United States; vaccination may cause atypical myxomatosis". (B609.2.w2)
• "Rabbits with latent pasteurellosis may develop acute pneumonia when modified live virus vaccines for myxomatosis are used". (B10.45.w47)
• "attenuated strains have been used as vaccines in Europe with some success, and experiments with a live virus vaccine (SG33) using a flea, Xenopsylla cunicularis, as the vector appears promising (Delobette, 1991)". (B614.9.w9)
• A recombinant combined myxomatosis-rabbit haemorrhagic disease vaccine has been produced, using a naturally attenuated field strain myxoma virus modified to give expression of the RHDV major capsid protein (VP60) (together with a "tag" of expression of nucleoprotein from transmissible gastroenteritis virus (TGEV). The vaccine was shown to be protective against VHD and myxomatosis in Oryctolagus cuniculus - European rabbit following either subcutaneous or oral vaccination, with limited horizontal transmission by direct contact or by fleas, producing immunisation of in-contact animals which had not themselves been vaccinated, and increased survival of such rabbits (about 50% protected, compared with no survivors on challenge of unvaccinated rabbits). Re-transmission from those rabbits to further individuals did not provide protection (no or minimal antibodies and no protection against challenge). (J80.74.w2)
  • The vaccine was shown to be safe even at 100 times vaccination dose, safe in pregnant and immunosuppressed rabbits (no undesirable effects) and to maintain its attenuated phenotype even after 10 passages in vivo. (J70.19.w1)
• In a field trial on a 34 hectare island populated by about 300 rabbits, subcutaneous vaccination of 76 rabbits with recombinant attenuated myxoma virus expressing RHDV capsid protein VP60 elicited development of specific antibodies against both RHDV and myxomatosis in all the vaccinated rabbits and in about 50% of unvaccinated rabbits, indicating limited horizontal transmission. No adverse effects of the vaccine were detected. (J70.19.w2)

--

• Flea control. (B601.13.w13, B609.2.w2)
  • Fleas may be brought into the house by cats and then these may infect house rabbits so make sure all other household animals (dogs and cats) are kept up to date with their flea treatments. (B601.13.w13) See: Flea Infection in Mammals
• Fur mite control (J213.4.w4). See: Cheyletiellosis
• Consider use of insect repellent chemicals as recommended for prevention of Myiasis:
  • Xenex (Genitrix): a plant-based insect repellent that contains octanoic and decanoic acid. (J15.28.w2)
  • Household flea spray: Vet-Kem Acclaim Plus (Sanfoni Animal Health Ltd.) can be used to spray the hutch. This product contains 0.09 % w/w S-methoprene and 0.58 % permethrin. (B606.4.w4)
• Mosquito netting can be used to keep insects out of hutches. (B600.9.w9, B603.4.w4, J15.28.w2)

• Intradermal Injection of Rabbits
• Subcutaneous Injection of Mammals
• Preventative Medicine for Mammals

Environmental and Population Control Measures

Lagomorphs

• Use screening on enclosures to keep out insects in endemic areas. 
• Avoid contact with wild rabbits. 
• Keep rabbits indoors in endemic areas. 
• Ultraviolet fly killers in colony housing. 

(B209.8.w8, B601.13.w13, B603.3.w3, B608.21.w21, B609.2.w2, B610.23.w23, J213.4.w4)

Disinfection

"10% bleach, 10% NaOH, 1-1.4% formalin". (B609.2.w2) See: Hypochlorites and Formalin

• Do not house domestic pet rabbits with wild rabbits. (B609.2.w2)
• In Australia, where this disease is still regarded as a useful adjunct to controlling the wild rabbits, there are no control measures undertaken and it is illegal to vaccinate domestic rabbits against myxomatosis. (B209.8.w8)
• In France, the rabbit is an important game animal therefore large-scale vaccination has been carried out in both domestic and wild rabbits. (B209.8.w8)

Management implications of myxomatosis

• Epidemic myxomatosis can interfere with hunting of Oryctolagus cuniculus - European rabbit due to collapse of the rabbit population. (B209.8.w8)
• There may also be effects on the predators that are dependent on rabbits, and on the vegetation that is grazed by rabbits. (B209.8.w8)
• In North America, Sylvilagus nuttallii - Mountain cottontail and Sylvilagus audubonii - Desert cottontail, have the potential to support the Brazilian strains of the myxoma virus, and this could lead to an adverse effect on the populations of Sylvilagus nuttallii. (B209.8.w8)
• USA: myxomatosis is seen primarily in rabbits in California and there is currently concern over the ease of transportation of pet rabbits being able to cause the spread of the disease to other parts of the USA. (B609.2.w2)

• New rabbits should be quarantined in an insect proof environment for two weeks. (B209.8.w8, B609.2.w2, B611.10.w10, B614.9.w9)
• All sick rabbits should be isolated to prevent spread within a colony. (B614.9.w9)

• Environmental and Population Management - General