key: cord-277703-sxt9lw0l
authors: Belz, Katie
title: Rabbit hemorrhagic disease
date: 2004-04-30
journal: Seminars in Avian and Exotic Pet Medicine
DOI: 10.1053/j.saep.2004.01.006
sha: 
doc_id: 277703
cord_uid: sxt9lw0l

Abstract Rabbit Hemorrhagic Disease (RHD) is a rapidly lethal infectious viral disease of the European Rabbit (Oryctolagus cuniculus) characterized by high mortality rates, acute hepatic necrosis, and disseminated intravascular coagulation. Although this disease is considered enzootic in Europe and parts of Asia, it is rarely seen in the Western Hemisphere since its eradication from Mexico in 1992. In recent years, three cases of RHD have been identified in the United States. Due to the quick action of veterinarians these cases were confined and controlled before the disease could spread.

R abbits are raised for food, for pets, and as show animals worldwide. Rabbits are particularly important in Asia and central Europe, where small-scale rabbitries are common and an integrated part of the culture. In this article an emerging disease, Rabbit Hemorrhagic Disease (RHD), is described. RHD already has had a major global impact and is a real threat to the rabbit industry and pet rabbits in the Americas.

Rabbit Hemorrhagic Disease was first recognized in China in 1984. The epicenter of the outbreak occurred in a group of commercially bred Angora rabbits recently imported from Germany to Jiangsu Province, China. These rabbits soon exhibited a contagious rapidly fatal disease that spread over 50,000 square kilometers in 9 months killing 470,000 rabbits. This disease was variously called "X-Disease of Rabbits," "rabbit viral sudden death," "picornavirus hemorrhagic fever in rabbits," "hemorrhagic septicemia syndrome in rabbits," and "infectious necrotic hepatitis of leporidae." Today, this disease is known as Rabbit Hemorrhagic Disease (RHD), Viral Hemorrhagic Disease of rabbits, or Rabbit Calicivirus Disease (RCD). Since 1984, RHD has disseminated widely and has been reported in over 40 countries from Asia, Africa, Europe, and the Americas. [1] [2] [3] [4] Disease RHD is caused by the Rabbit Hemorrhagic Disease Virus (RHDV). RHDV is a member of the family Caliciviridae, genus Lagovirus, and is closely related but distinct from the European Brown Hare syndrome virus, which causes similar symptoms and disease as RHDV in hares. 4 RHDV is readily disseminated. Virus is shed in the feces and nasal secretions of infected rabbits. Both ingested and inhaled virus can result in infection. The virus is stable in the environment. This allows RHDV to be spread by contact with contaminated caging, shavings, bowls, feedstuffs, and other fomites. The virus can also be passively transported by flies over short distances and can also travel by movement of people, equipment, wild or domestic animals, pelts, and rabbit carcasses. 3 The incubation period for RHDV is short, only16 to 48 hours. RHDV is highly infectious and highly virulent. As a result, morbidity and mortality rates may reach 90% to 100%. Death usually occurs between 2 and 3 days postinfection, although some rabbits may live for several days before they die. The disease is confined to rabbits over 2 months of age. It is believed maternal immunity protects the infant rabbits from this disease. As the maternal immunity declines at 2 months of age, the rabbits become susceptible to RHDV. [1] [2] [3] Three forms of the disease are recognized depending on past history of the disease in the affected rabbit population. A peracute form of the disease occurs in naïve rabbit populations. In this form of the disease, rabbits die suddenly, exhibiting no or very few signs. The acute form of the RHD is seen in rabbit populations where the disease is enzootic. These rabbits typically show some signs of disease before death. A subacute form of the disease is uncommon and occurs in the later stages of an epizootic. In this form of the disease, affected rabbits are clinically ill, but many survive. [1] [2] [3] Several clinical signs have been observed in rabbits both experimentally infected with RHDV and those that were naturally infected (Fig 1) . Not all clinical signs were present in every animal. Animals may have a temperature above 104°F (41°C), show rapid respiration, cyanosis, and become anorexic and recumbent. Severe diarrhea is common. In the late stages of the disease, various neurological signs are apparent, including lateral recumbency, paddling, ataxia, and terminally frenetic behavior sometimes accompanied by squealing. Opisthotonos has been observed in many animals, and 20% of infected rabbits have a bloody foamy discharge from their nose and, less frequently, from the vagina (Fig 2) .

Hematological findings in rabbits with the acute form of the disease include lymphopenia, thrombocytopenia, and alterations in the coagulation panel. Liver enzymes also are expected to be elevated. 2, 3 Typically, rabbits dying with RHD are in good body condition and have recently ingested food. RHD causes a severe diffuse necrotic hepatitis and disseminated intravascular coagulation. The liver may be pale, yellow, gray, friable, or congested and have a distinct lobular pattern. Multifocal petechial hemorrhages occur in the liver, lungs, kidneys and heart (Figs 3 and 4) . The spleen is often dark and engorged. Pneumotracheitis and tracheal hemorrhage are common, and jaundice has been occasionally noted. Lesions of the digestive tract are usually absent, although in some outbreaks, a catarrhal enteritis is a feature of RHD. In cases of acute RHD the characteristic hemorrhages might not be present. [1] [2] [3] Microscopic lesions of the liver are characterized by an acute diffuse hepatic necrosis and hemorrhage with minimal inflammation. Round eosinophilic inclusion bodies are seen in hepatocytes. Lymphoid necrosis in the spleen and lymph nodes is another characteristic lesion of RHD. Glomeronephritis, encephalomyelitis, and enteritis also may be seen histologically. 1-3 Figure 1 . Rabbit with Rabbit Hemorrhagic Disease. This animal is severely depressed and poorly responsive. In a sudden outbreak of rabbit hemorrhagic disease, the duration of signs in rabbits before death is usually less than a day (Photograph kindly provided by Elizabeth Morales Salinas). 

A presumptive diagnosis can be made on client history, clinical signs, and postmortem findings ( Table 1 ). In North America and Mexico, if this disease is suspected, a regulatory veterinarian should be immediately contacted. At specialized facilities, a diagnosis can be confirmed by electron microscopy of fixed tissues or homogenates of fresh tissue, immunofluorescense, a hemaglutination assay, or a viral antigen detection ELISA.

A complete set of tissues should be formalin-fixed for histopathology. Small intestine, lung, liver, spleen, and kidney samples should be saved fresh for virus detection. 5

Eradication is currently considered the best response to this disease when it is introduced to a country that does not have RHD. When infected rabbits are identified, all in contact rabbits are destroyed. The carcasses, all wooden caging and housing, and all organic material is buried. Metal cages and food bowels and glass water bottles are cleaned and then disinfected with 2% sodium hypochlorite solution. Buildings that housed rabbits are power washed and then disinfected with sodium hypochlorite solution. Soil that may have been in contact with rabbits, rabbit feces or urine is treated with the sodium hypochlorite solution and then calcium hypochlorite (lime). In the United States, sentinel rabbits were housed on the facilities and monitored for disease for 1 month before the facility was allowed to be repopulated. 1

Treatment is only an option in countries were this disease is enzootic. Because of the vigor and speed with which this disease kills rabbits, most rabbits are dead before any care can be administered. If rabbits are exhibiting clinical signs, isolation, supportive care, and symptomatic treatment is all that can be done.

In areas were RHD is enzootic, cleanliness is vital. The virus is inactivated with a 1% sodium hypochlorite solution. Rabbits should be housed indoors if possible. Stray animals should be kept away from rabbit housing and flying insects kept to a minimum. Access to the rabbitry should be limited, and caretakers should not have contact with other rabbits from other facilities. Maximizing sanitation within the rabbitry, especially cleaning and disinfecting cages between rabbits, may reduce the chance of disease transmission. New stock should be quarantined in a separate facility for 4 months, as rabbits that have survived RHD shed virus in their feces for up to 4 months. 2, 3 Immunization Vaccines against RHD are available in countries with enzootic RHD. There is a 6-month and a 1-year vaccine available. The vaccines are relatively safe, although illness, infections at injection sites, and death have been documented. RHD vaccines are not available in the United States and Canada at this time. The vaccine currently being used in Australia is Cylap HVD (Cyanamid, Spain) and is a killed vaccine. It is safe to consume a rabbit vaccinated against RHD. Rabbits can be immunized at 6 weeks of age or older. If the rabbit is less then 10 weeks old at first vaccine, a second immunization should be given in 4 weeks. Animals demonstrating any signs of ill health should not be immunized. 6 

The Americas were free of RHD until December of 1988 when it is thought that a shipment of -This is the most common disease seen in clinical practice. -Signs can range from soft stool and brown watery diarrhea with or without mucous or blood, to enterotoxemia, sepsis. Severely affected rabbits will become anorectic and depressed, and die. -Rabbits become hypothermic and moribund and die after 24-48 hours. Occasionally a chronic form of the disease is seen with rabbits ittermitedly having diarrhea, anorexia, and weight loss.

-Post mortem findings include petechial and ecchymotic hemorrhages on the serosal surface of the cecum, sometimes including the appendix and colon. -Gas may also be present in the small intestines, cecum, and colon. 

There have been three outbreaks of RHD in the United States. The first was an isolated rabbitry in Iowa in 2000. This premise was depopulated and additional cases were not found. The source of this outbreak was never determined. The second outbreak originated in Utah in 2001, but was first recognized in an Illinois facility that had received rabbits from the Utah source. Both facilities were depopulated and the disease eradicated. The source of this disease was not confirmed; however, individuals on the Utah facility had a history of traveling to countries where this disease was enzootic and may have brought the virus back on their clothing. The third outbreak occurred in a zoo in New York State. The veterinarian for the zoo suspected RHD and immediate action kept the disease from spreading from the zoo. The source of this outbreak is thought to be imported rabbit meat. 1

RHD is a disease with a potentially devastating impact on the rabbit industry in countries where this disease has previously been excluded. As the economy becomes increasingly global and rabbit products from RHD-infected countries are imported into RHD-free countries, the chance for outbreaks increases. Veterinarians are the first line of defense against RHD and are vital to its control. If RHD is suspected at your clinic, you should immediately contact local or national regulatory authorities. 9 

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