Rabbit Hemorrhagic disease

What is RHDV?

1. Viral form of Hepatitis that is HIGHLY infectious

2. Genus logovirus, family caliciviridae

3. Positive-sense

4. Single stranded

5. NOn-enveloped

6. Main viral strains

   1. RHDV (classical) aka RHDV1

   2. RHDV22

      1. Broader host range and more virulent

Who is affected?

1. Lagomorphs (rabbits, hares, pikas)

2. Reservoir hosts - european rabbits

3. Cottontail and jackrabbits have resistance to RHDV1

4. Susceptibility depends on:

   1. Viral genotype

   2. Age

   3. RCV exposure

   4. Species

History

1. Virus likely originated from EUrope

2. In US

   1. Classic RHDV is sporadic but was contains

   2. Currently Endemic

RHDV in the Environment

1. Stability

   1. Has a icosahedral capsid

      1. Very hard and resistance to dry climate/absence of moisture as well as low pH

      2. Can survive freeze-thaw cycles

   2. Can survive for weeks to months in environment within blood, tissues, respiratory discharge, feces, urine, and even on surfaces

2. Transmission

   1. Fomites - Food, water, cages, bedding, soil

   2. Mechanical factors - flies, fleas, birds, and other predators

   3. Carcasses are infectious and RHDV last months in tissues

Pathogenesis and Disease Progression

1. Viral entry and spread

   1. Inhalation or ingestion → respiratory or intestinal mucosa → bloodstream → organs (primary liver, lung, and spleen)

2. Hepatic pathogenesis

   1. Target cells include hepatocytes and Kupffer cells

   2. RAPID replication which causes necrosis at a massive level as well as apoptosis in lymphocytes

   3. Acute necrotizing hepatitis in the liver → rapid death within 48-72 hours post infection

3. Hemorrhaging

   1. Within lungs, kidneys, trachea, muscles (including the hears), CNS, and digestive track

   2. Caused by disseminated intravascular coagulation (DIC)

Immune evasion mechanisms

1. rapid replication

   1. Occurring in hepatocytes, antigen is seen within hours

   2. In 36-48 hours post infection infected cells reaches the maximum

2. Immune cell apoptosis

   1. Host induces cell death to contain virus spread. RHDV exploits innate defense pathway

   2. Leads to lethal amount of hepatocyte loss

3. Interferon suppression

   1. RHDV suppresses interferon and quickly replicates

Epidemiology: Population transmission and host susceptibility

1. Population transmission: rabbit-rabbit

   1. Direct contact between infected animals

      1. Secretions and excretions of infected enter via oral, nasal, or conjunctival

   2. Recovery period does not mean safe rabbits: RHDV can shed up to a month post-infection

2. Hosts susceptibility

   1. Age

   2. Species: european rabbits are FATALLY susceptible

   3. Immunity - rabbits may produce antibodies post infection

Seasonal - RHDV outbreaks occur in spring (linked to rabbit breeding season)

Morbidity and morality

90-100% morbidity

RHDV1 mortality - 70-90%

RHDV2 mortality - varies

Clinical signs and observations

1. Paracute form - sudden death with no clinical sign

2. Acute form - anorexia, paralysis, ataxia, congested palpebral conjunctive, apathy, and foamy or bloody nasal discharge along with ocular hemorrhages are possible “is the most common”

3. Subacute form - milder than acute signs: most rabbits with this form survive and produced antibodies

4. Chronic form - SEVERE jaundice anorexia and lethargy, commonly the small percentage who have this form die within weeks. However, those who survive develop strong immunity.

Pathology

1. Post-mortem findings

   1. Liver - enlarged, yellow-greyish, and brittle with marked lobular patterns; massive hepatic necrosis

   2. Spleen - enlarged, black to dar red in color, engorged rouded edges, multifocal hemorrhages

   3. Lung - congestion, edema, multifocal hemorrhages, frothy bloody fluid in trachea and airways, disseminated intravascular coagulation

      1. Widespread microthrombi that leads to multisystem hemorrhages

      2. Main cause of death

Diagnostic techniques

1. RT-PCR: gold standard

2. ELISA

3. Histopathology (lesions and characteristics especially in spleen and liver, looking for necrosis and DIC)

4. Best practice for diagnosis

   1. RT-PCR in combination with gross and histologic liver lesions

Treatment, prevention, and control

1. No treatment

2. Management care in domestic rabbit

   1. Biosecurity (quarantine, limit contact with wild rabbits

3. Wild rabbit prevention and control methods

   1. Importation restriction

   2. Population-level management is important as spill over can happen

   3. Carcasses removal at die-off sites

Wildlife management implications

1. Ecological impacts

   1. RhDv causes massive decrease of rabbit populations, most notably when the virus was first introduced

   2.  Europe and european rabbis as a keystone species that effects endangered predators

2. Eradication status

   1. Once the virus is established in population eradication is near impossible

   2. Eradiation efforts are complication with endemics in various regions and with RHDV2 expanding wildlife host range to hares that can potentially infect other lagomorph species

   3. Non-susceptible wild rabbits have a more feasible eradication while those regions where european rabbits are least likely to accomplish eradication

3. Management challenges

   1. Limited tools for wild populations

   2. Spill over- wild rabies can re-establish the virus in domestic populations and vice versa

   3. Virus evolution and host responses - reduces the effectiveness of vaccines that already exist along with host immune responses

Summary

1. RHDV is a highly infectious non-enveloped, positive- sense ssRNA virus in the family Caticiviridae in genus Lagovirus

2. The virus reservoir host is european rabbits. Hosts are susceptible due to viral genotype. Host immunity response/pre-existing exposure and seasonal change. Age susceptibility is also a factor in which adult European rabbits are more at risk of fatality in classical RHDV and younger rabbits are more at risk with RHDV1

3. The primary mechanism that is responsible for death and causes hemorrhages is disseminated intravascular coagulation (DIC)

4. Pathologically, we will see necropsies with enlarged friable liver with a lobular pattern along with a massive level of necrosis, a spleen that is dark in color, congested lungs and foamy.bloody airways, and multifocal hemorrhages throughout target organs

5. The best and most appropriate conformation of RHDV infections is RT-PCR in combination with observations of gross and histological lesions

6. Managing the virus is difficult especially with RHDV2 and its expansion on host range. Spillover and evolving strains are also factors in implications of wildlife management. Most importantly, the emergence of RHDV effects ecosystems of endangered species