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Rabbit haemorrhagicdisease 1 and 2

Diagnosis and treatment of the highly contagious viral disease

14 October 2019, at 12:00pm

Rabbit haemorrhagic disease (RHD) has regained attention recently due to a new strain causing out-breaks across the United Kingdom, Europe and the rest of the world. The virus is difficult to eliminate, highly contagious and difficult to diagnose.

History and classification

RHD was first identified in China in 1984, where a highly lethal strain of calicivirus killed more than 140 million rabbits within the space of a year (Abrantes et al., 2012). The disease first spread to Korea, then to Italy in 1988 and from there to the rest of Europe via the fur and meat trades. The disease was even identified as far away as Mexico within four years of the first reports in China (Gregg et al., 1991).

The causative agent of RHD was identified in the early 1990s as rabbit haemorrhagic disease virus (RHDV) from the Caliciviridae family (Ohlinger et al., 1990). This has been further classified as a single-stranded RNA virus of the genus Lagovirus (Green et al., 2000). In 1991, the Czech strain of RHDV was released onto Wardang Island off the coast of South Australia as a biological control for wild rabbit populations. By 1995 the virus had spread to the mainland where it decimated rabbit populations, with a fatality rate estimated up to 95 percent (Mutze et al., 1998).

Several strains of RHDV now exist following mutations of the original calicivirus. The most recent strain is RHDV2, becoming widely talked about in the veterinary community. RHDV2 was first identified in France in 2010, affecting rabbits already vaccinated for RHDV. Affected rabbits showed similar clinical signs to those seen with RHDV; however, clinical signs developed more slowly, and emergency vaccination took longer to reduce mortalities when compared with previous RHDV outbreaks (Le Call-Reculé et al., 2013).

Transmission

RHDV is hardy in the environment and difficult to eradicate, with studies from New Zealand showing that it can survive outside for up to three months within a rabbit carcass (Henning et al., 2004), which poses a transmission threat via scavenging predators. The virus is not inactivated by freezing or by temperatures of up to 50°C for up to an hour (Harcourt-Brown, 2018).

Transmission can be via live animals or fomites. In live animals, routes of transmission include conjunctival secretions, oral and nasal secretions and parenterally (Abrantes et al., 2012). This means that any bedding, food or water bowls and any items coming in contact with affected rabbits are a possible vector for spread. Insect vectors have also been shown to spread RHDV, via their own secretions (Asgari et al., 1998), posing a serious threat for spread of the disease. At the time of writing, the carrier status of rabbits recovered from RHDV1 and RHDV2 is unknown.

Clinical signs

The incubation period for RHDV ranges from 24 to 72 hours, with affected rabbits usually succumbing within 36 hours with a pyrexia of greater than 40°C. There are four main presentations of RHD: peracute, acute, subacute and chronic. Peracute presentations often manifest as sudden or unexpected death (Abrantes et al., 2012).

FIGURE (1) Jaundice of the sclera of a young rabbit that was later diagnosed with RHDV2
FIGURE (1) Jaundice of the sclera of a young rabbit that was later diagnosed with RHDV2

Acute presentations are characterised by anorexia, lethargy and the sudden onset of neurological signs such as opisthotonos, ataxia, paresis and sometimes excitement. Respiratory signs can be seen including dyspnoea and a foamy, blood-tinged nasal discharge (Marcato et al., 1991). Haematuria and bloody vaginal discharge may also be seen (Harcourt-Brown, 2018). Subacute infections often have milder clinical signs with rabbits recovering without incident, leading to seroconversion and therefore protection from reinfection (Patton, 1989). Chronic presentations are seen less commonly and result in rabbits showing signs of lethargy, anorexia and jaundice (Figure 1), with most succumbing to the disease one to two weeks after the onset of clinical signs (Abrantes et al., 2012).

Clinical signs of RHDV2 are similar but often have a lower mortality rate as subacute infections are more common with RHDV2. Signs are more likely to manifest as chronic weight loss and jaundice (Le Call-Reculé et al., 2013).

Diagnosis

Ante-mortem diagnosis is difficult due to the non-specific clinical signs. Biochemistry can show an elevation in liver enzymes, coupled with hypoglycaemia, azotaemia, hyperbilirubinemia and hyperlipidaemia (Kerr and Donnelly, 2013). Elevation in liver enzymes and jaundice seen in chronic cases can be explained by the virus’s predilection for hepatocytes where viral-induced apoptosis results in acute hepatic necrosis (Alonso et al., 1998). Liver biopsy can be performed for polymerase chain reaction (PCR) testing; however, the risk of fatal haemorrhage due to hepatopathy should be considered. Serology can be performed on animals that have recovered from subacute infections as they will develop high antibody titres (Kerr and Donnelly, 2013).

Most cases are diagnosed on post-mortem, where typical lesions include a pale, friable liver, splenomegaly, foamy tracheal exudate and unexplained haemorrhage within any organ (Harcourt-Brown, 2018). Histopathology usually shows an acute, necrotic hepatitis and haemorrhage, splenic lymphocyte depletion and congestion within a number of organs (Kerr and Donnelly, 2013). PCR of blood, urine and faeces can often yield false negative results; however, definitive diagnosis is via PCR testing of fresh or frozen liver samples, as the liver is a target organ for the virus (Abrantes et al., 2012).

FIGURE (2) Barrier nursing with full PPE of a patient with unknown disease status
FIGURE (2) Barrier nursing with full PPE of a patient with unknown disease status

Differences between RDHV1 and RDHV2

Rabbits under the age of four weeks tend to have natural immunity to RHDV1 which wanes as they approach 10 weeks. If they are exposed within this period, they develop a lifelong immunity. This natural immunity has not yet been shown to be present for RHDV2 (Harcourt-Brown, 2018). RHDV1 has been shown to only affect rabbits; however, RHDV2 has been identified in a number of hare species in Sardinia, Italy, Spain, France and Australia (Bell et al., 2019).

Treatment control and vaccination

Currently, no specific treatment exists for RHD, although experimental treatment with melatonin or cardiotrophin has been shown to improve patient outcomes (Tunon et al., 2011 and Laliena et al., 2012). Supportive care, including feeding, fluids and treatment for secondary complications such as gastrointestinal stasis, should be administered and strict quarantine should be implemented for affected animals. The prognosis for affected rabbits is guarded.

All rabbits suspected to have RHD should be isolated from all other susceptible rabbits with separate cleaning and feeding supplies. If the rabbit is hospitalised, any attending staff should be wearing full personal protective equipment, including gloves, gown and shoe covers as a minimum (Figure 2). Disinfection following a suspected or known case of RHD should be carried out using a viricidal disinfectant known to be effective against feline calicivirus.

FIGURE (3) Nobivac Myxo-RHD and Eravac are both licensed for pet rabbits and when used correctly together can provide full cover for RHDV1 and RHDV2, as well as myxomatosis
FIGURE (3) Nobivac Myxo-RHD and Eravac are both licensed for pet rabbits and when used correctly together can provide full cover for RHDV1 and RHDV2, as well as myxomatosis

Vaccination is available to protect against RHDV1 and RHDV2 (Figure 3). Nobivac Myxo-RHD, available in single-use vials, is licensed for use in rabbits from five weeks of age and provides immunity against myxomatosis and RHDV1 for one year’s duration. Filavac VHD K C+V is available as single-use, 50-dose and 200-dose vaccinations, licensed for use in meat rabbits from 10 weeks of age and provides immunity for RHDV1 and RHDV2 for a one year duration. Eravac emulsion for injection for rabbits is avail-able as single-use vials, is licensed for use in rabbits from 30 days of age and protects against RHDV2 for nine months’ duration. A combination of vaccinations can be administered to fully protect rabbits; however, based on manufacturer recommendations, a two-week gap should be observed between vaccinations (personal communication, 2019).

Suspicion of RHD should be based on vaccination status, clinical signs and known exposure. When the disease status is unknown it is best to quarantine and barrier nurse the patient until a diagnosis has been reached. It is important to ensure that rabbit owners are educated and aware of RHD and the measures that can be taken to prevent the spread of this disease.

References
Author Year Title
Abrantes, J., van der Loo, W., Le Pendu, J. and Esteves, P. J. 2012 Rabbit haemorrhagic disease (RHD) and rabbit haemorrhagic disease virus (RHDV): a review. Veterinary Research, 43.
Alonso, C., Oviedo, J. M., Martin-Alonso, J. M., Diaz, E., Boga, J. A. and Parra, F. 1998 Programmed cell death in the pathogenesis of rabbit hemorrhagic disease, Archives of Virology, 143, 321-332.
Asgari, S., Hardy, J. R., Sinclair, R. G. and Cooke, B. D. 1998 Field evidence for mechanical transmission of rabbit haemorrhagic disease virus (RHDV) by flies (Diptera: Calliphoridae) among wild rabbits in Australia, Virus Research, 54, 123-132.
Bell, D. J., Davis, J. P., Gardner, M. Barlow, A. M., Rocchi, M, Gentil, M. and Wilson, R. J. 2019 Rabbit haemorrhagic disease virus type 2 in hares in England, Veterinary Record, 184, 127.
Green, K. Y., Ando, T., Balayan, M. S., Clarke, I. N., Estes, M. K., Matson, D. O., Nakata, S., Neill, J. D., Studdert, M. J. and Thiel, H. J. 2002 Caliciviridae, Virus Taxonomy 7th report of the International Committee on Taxonomy of Viruses. Academic Press, Orlando.
Gregg D. A., House C., Meyer R. and Berninger M. 1991 Viral haemorrhagic disease of rabbits in Mexico: epidemiology and viral characterization. Revue Scientifique et Technique, 10, 435-451.
Harcourt-Brown, F. 2018 Rabbit haemorrhagic disease and its variants (Lagoviruses). (Accessed 29 August 2019).
Henning, J., Meers, J., Davies, P. R., and Morris, R. S. 2004 Survival of rabbit haemorrhagic disease virus (RHDV) in the environment, in Epidemiology and Infection, 133, 719-730.
Kerr, P. J. and Donnelly, T. M. 2013 "Viral infections of rabbits", Veterinary Clinics of North America: Exotic Animal Practice, 16, 437-468.
Laliena, A., SanMiguel, B., Crespo, I., Alvarez, M., González‐Gallego, J. and Tuñón, M. J. 2012 Melatonin attenuates inflammation and promotes regeneration in rabbits with fulminant hepatitis of viral origin, Journal of Pineal Research 53, 270–8.
Le Call-Reculé, G., Lavazza, A., Marchandeau, S., Bertagnoli, S., Zwingelstein, F., Cavadini, P., Martinelli, N., Lombardi, G., Guérin, J.L., Lemaitre, E., Decors, A., Boucher, S., Le Normand, B. and Capucci, L. 2013 Emergence of a new lagovirus related to Rabbit Haemorrhagic Disease Virus,Veterinary Research, 44, 81.
Marcato, P. S., Benazzi, C., Vecchi, G., Galeotti, M., Della Salda, L., Sarli, G. and Lucidi, P. 1991 Clinical and pathological features of viral haemorrhagic disease of rabbits and the European brown hare syndrome, Revue Scientifique et Technique 10, 371-392.
Mutze, G., Cooke, B. and Alexander, P. 1998 The initial impact of rabbit haemorrhagic disease on European rabbit populations in South Australia. Journal of Wildlife Diseases, 34, 221-227.
Ohlinger, V. F., Haas, B., Meyers, G., Weiland, F. and Thiel, H. J 1990 Identification and characterization of the virus causing rabbit haemorrhagic disease.The Journal of Virology, 64, 3331-3336.
Patton, N. M. 1989 Viral haemorrhagic disease. A major new disease problem of rabbits. The Journal of Applied Rabbit Research,12, 64-67.
Tuñon, M. J., San Miguel, B., Crespo, I., Riezu-Boj, J. I., Larrea, E., Álvarez, M., González, I., Bustos, M., González-Gallego, J. and Prieto, J. 2011 Cardiotrophin-1 promotes a high survival rate in rabbits with lethal fulminant hepatitis of viral origin, Journal of Virology, 85,13124–32

Ashton Hollwarth, BSc, BVMS, MRCVS, studied in Western Australia. Since graduation she has worked in exotic practices in England and is currently enrolled in her CertAVP Zoo Med certificate. Ashton recently started an ECZM residency in Avian Medicine and Surgery at Great Western Exotics.

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