Viruses are not important causes of clinical disease of rabbits in the USA but include the infectious fibromas, papillomatosis, rabbitpox, myxomatosis, and a herpesvirus infection (virus 3). Rotaviral enteritis also has been diagnosed in the USA and seems to contribute to the overall problem of intestinal disease in rabbits. Rabbit hemorrhagic disease (RHD) is found in almost every country that raises rabbits. In April 2000, the USDA diagnosed RHD in a backyard facility in Iowa. Rapid response and cooperation between federal and state agencies contained this outbreak and eliminated the source of infection. In 2020, an outbreak of RHD began in wild rabbits in New Mexico and was quickly identified in additional western states of the USA.
Myxomatosis is a fatal disease of all breeds of domesticated rabbits caused by myxoma virus, a member of the poxvirus group. Myxomatosis is called “big head” and is characterized by mucinous skin lesions or myxedema of the head. Wild rabbits such as the cottontail (Sylvilagus) and jackrabbits (Lepus) are quite resistant. Myxoma virus–infected Sylvilagus develop fibroma-like lesions similar to those caused by rabbit fibroma virus. All other mammals are refractory to the virus. Myxomatosis has a worldwide distribution. In the USA, myxomatosis is restricted largely to the coastal area of California and Oregon, where epidemics occur infrequently but sporadic cases are common. These areas correspond to the geographic distribution of the California brush rabbit (S bachmani), the reservoir of the infection. Losses in rabbitries may be 25%–90%. Transmission occurs via mosquitoes, fleas, biting flies, and direct contact.
The initial sign is conjunctivitis that rapidly becomes more marked and is accompanied by a milky ocular discharge. The rabbit is listless and anorectic, with a fever that frequently reaches 108°F (42°C). In acute outbreaks, some rabbits may die within 48 hours after signs appear. Those that survive become progressively depressed and develop a rough coat. The eyelids, nose, lips, and ears become edematous, which gives a swollen appearance to the head. In females, the vulva becomes inflamed and edematous; in males, the scrotum swells. A characteristic sign at this stage is drooping of the edematous ears. A purulent nasal discharge invariably appears, breathing becomes labored, and the rabbit goes into a coma just before death, which usually occurs within 1–2 weeks after clinical signs appear. Occasionally, a rabbit survives for several weeks; in these cases, fibrotic nodules appear on the nose, ears, and forefeet. Rabbits inoculated experimentally with laboratory strains of the virus invariably develop small nodules at the point of injection after several days; similar nodules develop later on other parts of the body, particularly the ears.
Few characteristic gross lesions are found at necropsy in the acute form of the disease. The spleen is occasionally enlarged and is almost always devoid of lymphocytes when examined histologically. In rabbits that survive longer, subcutaneous edema and nodular skin tumors are seen. The seasonal incidence of the disease, clinical signs (especially the swollen genitalia), and high mortality are all of diagnostic significance. Large, eosinophilic, cytoplasmic inclusion bodies in the conjunctival epithelial cells are also helpful in diagnosis. Outside the USA, vaccination is an option and highly recommended in endemic areas.
An attenuated vaccine prepared from a myxomatosis virus has protected rabbits infected under both field and laboratory conditions. Multiple case reports of adverse reactions (mild and local) to the live vaccine have been published. This vaccine is not available in the USA, and because there is no effective treatment, euthanasia and burying or burning of affected rabbits is indicated. Preventive measures include protecting rabbits from exposure to arthropod vectors.
Shope fibromas are found under natural conditions only in cottontails, although domestic rabbits can be infected by inoculation of virus-containing material. Fibromas may be found in domestic rabbits in areas where they are endemic in wild rabbits and where husbandry practices allow contact with arthropod vectors.
A fibroma virus, a member of the poxvirus group, causes this tumor, which is found on the legs, feet, and ears. The earliest lesion is a slight thickening of the subcutaneous tissues, followed by development of a clearly demarcated soft swelling. These tumors may persist for several months before regressing, leaving the rabbit essentially normal. Intracytoplasmic inclusion bodies are seen when sections of the tumor are examined histologically. Because Shope fibromas are of little significance in domestic rabbits, no control measures have been developed.
Rabbitpox is an acute, generalized disease of laboratory rabbits (Oryctolagus spp) that apparently has not been recognized in wild rabbits (Sylvilagus spp). A few outbreaks have been reported in the USA since 1930. The causative virus is closely related to vaccinia virus, and some outbreaks may have been caused by a virulent strain of vaccinia. Pox lesions may be present on the skin. Most rabbits develop a fever and nasal discharge. The mortality rate varies but is always high. The most characteristic lesions seen at necropsy are a skin rash, subcutaneous edema, and edema of the mouth and other body openings. Because of the edematous condition, “poxless” rabbitpox may be confused with myxomatosis. The virus may be isolated or the infection diagnosed serologically by methods appropriate to vaccinia. (See also Pox Diseases.) Spread through a rabbitry is rapid, but rabbits inoculated with smallpox vaccine (vaccinia virus) are immune. Rabbitpox virus does not infect people.
Two types of infectious papillomas occur infrequently in domestic rabbits. The oral papilloma, caused by the rabbit oral papillomavirus, is the most important clinically. The lesions consist of small, grayish white, pedunculated nodules or warts on the undersurface of the tongue or floor of the mouth. The second type, caused by the cottontail (Shope) papillomavirus, is characterized by horny warts on the neck, shoulders, ears, or abdomen and is primarily a natural disease of cottontail rabbits. Arthropod vectors transmit the Shope papillomavirus; therefore, arthropod control could be used as means of disease prevention. The oral papillomavirus is distinct from the Shope papillomavirus (which is also distinct from the Shope fibroma virus). Skin tumors caused by the Shope papillomavirus never occur in the mouth. Neither type of papillomatosis is treated, and the condition usually resolves spontaneously over time.
Rotavirus has been isolated from rabbits with diarrhea in many different countries. In serologic studies of rabbit colonies around the world, almost 100% of the adult rabbits in some rabbitries were positive for rotavirus, demonstrating its widespread nature. Rotavirus is shed in the feces of infected rabbits and, therefore, is probably transmitted by the fecal-oral route. Young rabbits of weaning age are most susceptible. It is probable that rotavirus is only mildly pathogenic, but most rotavirus infections are complicated with pathogenic bacteria such as Clostridium spp or Escherichia coli. The mixed infection results in a much more deadly syndrome. There is no treatment, but the infection appears to be self-limiting if susceptible rabbits are not continually introduced into the population. Experimentally, the virus is shed for only 1 week after inoculation. Therefore, cessation of breeding for 4–6 weeks seems to allow the disease to run its course, because seropositive does do not infect their offspring.
(Viral Hemorrhagic Disease, Rabbit Calicivirus Disease)
Rabbit hemorrhagic disease (RHD) was first reported in 1984 in the People’s Republic of China, from whence it spread through the domestic and wild rabbit populations in continental Europe. It is caused by a calicivirus, rabbit hemorrhagic disease virus (RHDV). The first report of the virus in the Western hemisphere was in Mexico City in 1988. Mexico successfully eradicated the virus by 1992. Outbreaks of rabbit calicivirus disease have since occurred in Australia (1995), New Zealand (1997), and Cuba (1997). In 1995, as a result of a laboratory accident in southern Australia, the virus escaped from quarantine and killed 10 million rabbits in 8 weeks. A second form of the virus, RHDV2, was isolated from an outbreak in France in 2010 and was also found in wild rabbits in Australia in 2015.
RHD is a reportable disease in the USA. RHD was confirmed in a group of 27 rabbits in Iowa in April 2000 in the USA. The source of infection was not determined. Rapid response and cooperation between federal and state agencies contained this outbreak and eliminated the source of infection. The USA was considered free of RHD, but in September 2018 the first case of RHDV2 in the USA was confirmed in a pet rabbit in Ohio. A new outbreak of RHDV2 in the USA in 2020 was confirmed in wild rabbits in New Mexico, Arizona, Nevada, California, Colorado, Texas and more.
RHD is highly infectious in European rabbits (Oryctolagus), but cottontail rabbits and jackrabbits are not susceptible to RHDV1. It is not a zoonotic disease but can be transmitted by humans indirectly via contaminated shoes and clothing. The calicivirus is highly contagious and can be transmitted by direct contact with infected rabbits or indirectly by fomites. Infection results in a peracute febrile disease causing hepatic necrosis, enteritis, and lymphoid necrosis, followed by massive coagulopathy and hemorrhages in multiple organs. It is important to note that RHDV2 causes even fewer signs than RHDV1, often just occurring as sudden death. It has an incubation period of approximately 3–9 days, during which time the virus is already highly contagious. Rabbits show few clinical signs and die within 6–24 hours of fever onset. The morbidity rate is often 100%, and mortality 60%–90%. A killed vaccine effectively reduced the incidence of rabbit calicivirus in Europe in the late 1980s. Vaccines protective against RHDV1 and RHDV2 are available in several countries, but are not approved in the USA. Due to the outbreak in the USA in 2020, the FDA granted permits to some veterinarians to import vaccine for pet rabbits from France. Rabbits are vaccinated at 10 weeks, and annual boosters are recommended. In the USA, there are no FDA approved vaccines for RHDV2. Use of the European vaccines is possible via special permit under USDA rules. More information can be found from the USDA.