Rabbit hemorrhagic disease (RHD) identified in Ontario

Emily Martin, Andrew Brooks, Siobhan O’Sullivan, Heindrich Snyman, Emily Rätsep, Jamie McGill Worsley, Linda Johnson, Taylor Cockburn

Animal Health Laboratory, University of Guelph, Guelph, ON (Martin, Brooks, O’Sullivan, Snyman, Rätsep); Forest Veterinary Clinic, Forest, ON (McGill Worsley), Guelph ON (Johnson), Windsor ON (Cockburn).

AHL Newsletter 2022;26(3):18.

AHL recently diagnosed rabbit hemorrhagic disease (RHD) in rabbits from 2 households.  At the beginning of June, the initial household had 4 of 5 rabbits die within 6 days.  The rabbits presented with lethargy and inappetence, proceeding to sudden death.  The clinician performed postmortem examination on 3 of these rabbits.  One rabbit had hydroureter and hydronephrosis of the right kidney, 1 rabbit (dwarf) had jaundice (Fig. 1A), and 1 rabbit had hemorrhagic fluid in the abdomen.  Fixed tissues were submitted to AHL from the jaundiced rabbit.  The same week, the 5th rabbit (Mini Rex) from this household was submitted to AHL from another clinic for postmortem examination.  The history indicated the loss of the other rabbits and the problem list included anorexia (GI stasis), jaundice and kidney stones.  On postmortem examination of the 5th rabbit, there was pulmonary congestion and mild abdominal hemorrhage consisting of multiple small blood clots and approximately 1mL of free hemorrhagic fluid.

On histopathology, the jaundiced dwarf and the Mini Rex both had acute hepatic necrosis ranging from single cell to multifocal coalescing areas of necrotic hepatocytes with primarily periportal distribution (Fig. 1B).  The dwarf rabbit also had microvascular thrombi within renal glomeruli (Fig. 1C).  Due to the number of acute deaths in 1 household and lesions of acute hepatic necrosis, tissues were directed to the National Centre for Foreign Animal Diseases in Winnipeg for rabbit hemorrhagic disease virus (RHDV) confirmatory testing.  The tissues were positive for RHDV2 by PCR.

Due to widespread social media coverage, several subsequent rabbit postmortem submissions to the AHL requested testing for RHD; however, the next positive case of RHD was not detected until the end of June.  This rabbit (dwarf) presented with seizures, became laterally recumbent, developed agonal breathing, and died within 2 hours of onset.  Bloody fluid was noted at the nose and mouth.  On postmortem examination at AHL, there was significant pulmonary hemorrhage.  Histopathology identified alveolar hemorrhage and acute hepatic necrosis, similar to the rabbits from the initial household.  Tissues were also directed to NCFAD for RHDV confirmatory testing, where they tested positive for RHDV2 by PCR.

In both households, the rabbits were noted as living indoors and there were multiple rabbits in each household.

Rabbit hemorrhagic disease virus (RHDV) is a calicivirus causing rabbit hemorrhagic disease (RHD).  It was first reported in China in 1984 from imported rabbits.  Since then, another strain has evolved and the nomenclature is being updated (Table 1).  In general, the virus primarily affects European rabbits (Oryctolagus cuniculus), and is now endemic in multiple geographic areas where European rabbits also exist in the wild, including Europe, Asia, Africa, Australia, and New Zealand.  The virus is highly contagious, has a short incubation period, and is rapidly lethal.  The classical RHDV results in death of adult domestic and wild rabbits within 12 – 35 hours after onset of fever (>40°C).  The virus targets the lung, liver and spleen, causing B and T lymphocyte depletion in the latter two organs that subsequently impairs the immune response.  Lesions primarily include acute necrotizing hepatitis, but hemorrhages can also be identified in lungs, heart and kidney due to DIC which is the usual cause of death.

Routes of transmission are through oral, nasal, conjunctival and parenteral routes (blood-feeding insects) as well as mechanical vectors.  Transmission can be by direct contact (urine, feces, respiratory secretions from infected animals), fomites (contaminated food, bedding, water, clothing, cages), or vector-borne (mammals, birds, insects such as flies).

There are multiple forms of RHD described (*most common):

Peracute*: No clinical signs. Sudden death.

Acute*: Anorexia, depression, conjunctival congestion, neurologic symptoms (opisthotonos, ataxia, paddling, paralysis), respiratory signs (dyspnea, cyanosis, foamy and bloody nasal discharge), lacrimation, ocular hemorrhages, and epistaxis.

Subacute: Similar presentation to acute, but milder symptoms and most rabbits survive and develop protective antibodies.

Chronic: Can be seen in an outbreak.  A few rabbits may have severe generalized jaundice, anorexia and lethargy.  They tend to die in 1-2 weeks, but may survive and seroconvert.  Surviving rabbits can continue to shed virus for up to a month after recovery.

NOTE: Rabbits less than 2 months of age usually have subclinical infection but rarely die.  If infected, young rabbits develop immunity to related strains.

Since caliciviruses are non-enveloped, they are hardy and stable in the environment.  Virus can be viable on carcasses for prolonged periods (months).  Control relies on biosecurity measures such as surveillance, sanitation, disinfection, and quarantine, as well as vaccination.  There is no specific treatment for RHD other than supportive care.

RHD has been previously identified in Canada: (RHDV (single rabbit): Winnipeg in 2012 (RHDV, single rabbit); Quebec in 2016 (RHDV2 outbreaks), Vancouver Island in 2018, and southern mainland of BC in 2019.  This is the first identification of RHD in Ontario.   AHL

Table 1. Rabbit hemorrhagic disease virus classification.

Figure 1. Postmortem changes and histologic lesions of RHD. (Photo A courtesy of Dr. Jamie McGill Worsley; Photos B and C by Dr. Emily Martin)

Figure 1. Postmortem changes and histologic lesions of RHD. (Photo A courtesy of Dr. Jamie McGill Worsley; Photos B and C by Dr. Emily Martin)

A. Jaundiced dwarf rabbit from first household.

B. Acute hepatic necrosis. H&E stain.

C. Microvascular thrombi in renal glomeruli. H&E stain.

References:

1. Abrantes J, et al. Rabbit haemorrhagic disease (RHD) and rabbit haemorrhagic disease virus (RHDV): A review. Vet Res 2012; 43(12).  https://doi.org/10.1186/1297-9716-43-12

2. Ambagala A, et al. Incursions of rabbit haemorrhagic disease virus 2 in Canada - Clinical, molecular and epidemiological investigation. Transbound Emerg Dis. 2021;68(4):1711-1720.

3. https://www.cfsph.iastate.edu/Factsheets/pdfs/rabbit_hemorrhagic_disease.pdf