Viral haemorrhagic disease is a highly contagious, acute and deadly disease of the rabbit. The causal agent is a virus belonging to the Caliciviridae family, genus Lagovirus, called RHDV, a single-stranded, non-enveloped RNA virus. The virus is very stable and has a long survival time in the environment. It is highly specific for the rabbit and does not affect other species, humans included.
The virus was first identified in China in 1984 and then rapidly spread throughout the world. It was identified in Italy in 1986. The virus is now endemic in most of Europe and Asia, in parts of Africa, Australia and New Zealand. The origin of the virus is unknown; it is assumed to be either an endemic, nonpathogenic virus of a different species which completed a species jump or the mutation of a rabbit calicivirus which has become virulent.
VHD is transmitted orally and aerogenically. The virus is shed in secretions and excretions. The disease is spread either by direct contact between sick and healthy rabbits, or indirectly, for example through ingestion of contaminated food or water or via passive vectors such as insects, rodents, birds and humans. A single fecal pellet of a fly which came into contact with infected rabbits contains enough virions to infect a rabbit. In previously disease-free populations the morbidity of the disease is high (90-100%) and the mortality rate is of 40-90%. Rabbits under 4 weeks of age are not affected and develop lifelong immunity if exposed to the virus. In young rabbits susceptibility to the disease starts from 5-6 weeks of life and gradually increases up to 8-9 weeks, age at which the animals are fully vulnerable.
The virus may infect via the oral, nasal or conjunctival route. Following replication in the cells of the mucous membranes, viraemia occurs, with subsequent infection of the hepatic cells and massive replication of the virus. Death is caused by acute necrotizing liver splenitis. As a consequence of hepatic necrosis, coagulation factors are released into the circulation, resulting in disseminated intravascular coagulation and thrombus formation. Pulmonary, brain, kidney and heart vessels are obstructed, and death occurs. In subacute cases thrombus formation does not occur, but there is liver failure with jaundice and ascites, and death in two weeks; in rare cases, liver regeneration is present and the subject survives, with the development of lifelong immunity.
The incubation time is very short, only 16-72 hours; death occurs 12-36 hours after the onset of fever. VHD manifests itself suddenly with high fever (above 40°C), bleeding from the nose, mouth and anus, sneezing, excitatory-type seizures, dyspnoea, spasms and death. Sometimes there is directly sudden death, with eventual nasal and vaginal bleeding.
Necropsy confirms the presence of internal haemorrhages, in particular of the tracheal mucosa and lung parenchyma, hepatomegaly and splenomegaly. The certainty of diagnosis is obtained with an Elisa test of the liver or spleen. The histological examination of liver tissue is also diagnostic and shows the presence of acute hepatic necrosis. The virus cannot be replicated in cell cultures.
No effective therapy is available. In Italy, Veterinary Regulatory Authorities mandate the euthanasia and destruction of infected and suspected infected subjects and the communication of any immunizing treatment to the local Health Authorities.
vaccination is with attenuated vaccines. Due to the impossibility of cultivating the virus in vitro, vaccines are prepared from organ suspensions from experimentally infected rabbits, which are then chemically inactivated. These vaccines are also available in combination with the vaccine against myxomatosis. Recently, a bivalent vaccine has been marketed in which the myxomatosis virus, rendered harmless by the elimination of two pathogenic factors, induces immunity also against VHD by encoding the capsid of the VHD virus itself. Depending on the type of vaccine used, the booster doses are administered every 6-12 months and are to be repeated for life.
RHDV2 variant (RHD France 2010)
In 2010 a viral form with epidemiological characteristics and methods of transmission similar to VHD appeared in France, caused by a new serotype of RHDV, called RHDV France 2010, and subsequently called RHDV2; the following year the disease made its appearance in Italy, in the Regions of Veneto and Sardinia. The disease subsequently spread to several Italian Regions. In France, the RHDV2 strain has almost completely replaced the classic form, among both domestic and wild rabbits.
The antigenic structure of the new RHDV2 virus strain is sufficiently different from that of the original strain to make vaccines against the classical VHD poorly protective. Given the antigenic difference with the original strain it is assumed that RHDV2 resulted from the mutation of a preexisting non-pathogenic lagovirus which completed a species jump (the same hypothesis devised to explain the sudden appearance of VHD in 1984 in China).
The new variant affects rabbits of all ages, especially after 15 days of life. Unvaccinated subjects have a mortality rate of 40-90%. The microscopic and macroscopic lesions are comparable to those of classical VHD. Contrary to the classic strain, the new variant also affects the Sardinian hare (Lepus capensis mediterraneus); this is the first lagovirus known which can cause fatal hepatitis in both the rabbit and in a species of hare.
In Italy, the Zooprophilactic Institutes of Brescia and Perugia may prepare upon request a herd vaccine prepared from the livers of animals which died on the farm, after typing of the virus.