Download Rabbit Viruses - CL Davis Foundation

C. Brayton September 2007
RABBITS
Order Lagomorpha
Family Leporidae
Genus Oryctolagus
Species Oryctolagus cuniculus
07RabbitPathSumTable
Rabbits in research
New Zealand White (4-6Kg)
Dutch (1.5-2.5Kg)
Watanabe – LDL receptor deficiency
Interesting RABBIT features (phenotypes)
General /Misc
Does, Bucks
Stamp / kick when startled  broken back
Behavior
Kindling  kits; induced ovulators
Gestation 25-35 D
Nutrition
need fiber
Integument: (Skin)
Patchy fur growth
Dewlap
Bigger in female
Gastrointestinal (Int)
Hypsodont incisors; Hypsodont molars
Teeth
Peg teeth = incisors behind maxillary incisors
Stomach
Simple glandular stomach, hairballs are common
Sacculus rotundus
At ileocecal junction near cecal tonsil – thick wall dt lymphoid tissue
Large Intestine
Hindgut fermenters
GALT
Gut Associated Lymphoid Tissue (> 50% of total rabbit lymphoid tissue)
Night Feces
Coprophagy cecotrophy important in nutrition
Respiratory (Resp)
Obligate nose breathers
Lungs
Relatively small lung volume– small thorax relative to abdominal viscera
Genitourinary
Alkaline, Turbid yellow with hi protein + calcium carbonate crystals
Urine
May be brown-red dt porphyrins
 Wt gain, nesting, lactation
Pseudopregnant
Musculoskeletal
Skeleton
Fragile only ~6-8% of body wt (muscle > 50%)
Hematopoietic
Neutrophils called ‘Heterophils’ have eosinophilic granules ~ Guinea pigs,
Hematology
hamsters;
Spontaneous RABBIT Pathology (phenotypes) NON Neoplastic
RABBIT Pathology (phenotypes) Non Neoplastic
Systemic (multi system)
Metabolic Nutritional
Aorta (clay pipe aorta) etc arteries; renal tubule- glomerular basement
Metastatic calcification
membrane ; gastric mucosa inetsine, lung
Nutritional myopathy
Degeneration necrosis mineralization +/- inflam
Pregnancy toxemia
Obese rabbit; Fatty liver, adrenal glands; ketosis, metabolic acidosis
Integument: (skin)
Alopecia
r/o hair pulling for nesting
Related genera
Sylvilagus sp. (American cottontails)
Lepus sp (hares)
Use fur for nests
need fiber!!
Esp B vitamins
Induced ovulators
Lymphocytes > neutrophils
Nutritional – hypervitaminosis D
Vit E Se, etc
Assoc with obesity & fasting
r/o ringworm
1
C. Brayton September 2007
Slobbers
Pododermatitis
Gastrointestinal (Int)
Malocclusion –
Stomach
Large intestine
Respiratory (Resp)
Pulmonary granulomas
Endocrine
Genitourinary
Endometrial venous
aneurysms
Cardiovascular
Atherosclerosis
Arterial mineralization
‘Cardiomyopathy”
Musculoskeletal
Nutritional myopathy
Splayleg
Spine Fracture
Special sense
Eyes
07RabbitPathSumTable
RABBIT Pathology (phenotypes) Non Neoplastic
Moist dermatitis esp @ dewlap; may isolate Staphylococcus, Streptococcus,
Pseudomonas; Fusobacterium
Bumblefoot similar opportunists isolated esp Staph.
Associated with malocclusion; also rhinitis,
conjunctivitis
Big rabbit on wire floor
Incisors earlier (grow faster) AND premolars, molars later (grow slower)
Hairballs, may be incidental or associated with obstruction, rupture
Mucoid enteropathy – diffuse goblet cell hyperplasia/metaplasia
hypsodont
Grooming - barbering
Multifactorial, enteritis complex
Adjuvant associated
Vs Infectious
Endometrial varices rupture & bleed periodically  bloody vaginal discharge
Blood & varices in uterus
See nutritional myopathies
Lipid deposition arterial media, intima; skin (Xanthomas), cornea etc
Usually metastatic calcification dt hypervitaminosis D, with mineralization in
other soft tissues, kidney basement membranes etc
Myocardial degeneration, replacement fibrosis
With mineralization (+/- inflammation r/o nutritional)
See nutritional myopathies
Degeneration necrosis mineralization +/- inflam
‘Swimmers’ – can’t adduct limbs
Frequently L6-7 – after kicking
Buphthalmos (~ glaucoma) soft sclera so usually normal IOP
Spontaneous Rabbit Pathology (Phenotypes) Neoplastic – NOT A LOT
Rabbit Neoplasms
Integument: (skin)
Mammary
Hyperplasia (cystic often) -- Adenocarcinoma
Endocrine
Pituitary
Adenomas (may secrete prolactin)
Genitourinary
Uterus
Adenocarcinoma – metastasis to serosa, nodes, lung, liver
Testes
Interstitial cell tumor > Sertoli cell tumor
Hematopoietic
Lymphoma
Kidney, Stomach mucosa > liver spleen lymph nodes GALT marrow etc
Sarcomas (neurofibrosarcoma? PNST like), osteosarcoma, hemangiosarcoma
Etc occasional
Squamous cell carcinomas, etc
Congenital ?
Watanabe LDLr deficient
‘clay pipe aorta’
Dietary vitamin D
Not too common r/o Ketamine/xylazine
Vit E Se, etc
Heritable genetic ?
Broken back
Autosomal recessive, 1 or both eyes
Assoc pituitary lesions?
Most common tumor
In young rabbits; Retrovirus? Herpesvirus?
2
C. Brayton September 2007
07RabbitPathSumTable
FELASA RECOMMENDATIONS FOR RABBIT TESTING (2001) 1
Viruses
Bacteria, mycoplasma and fungi
Rabbit hemorrhagic disease virus 3 months
Bordetella bronchiseptica 3 months
Rabbit rotavirus
3 months
Clostridium piliforme
3 months
Dermatophytes
3 months
Pasteurella multocida
3 months
Other Pasteurellaceae
3 months
Salmonella spp.
3 months
Parasites
Ectoparasites:
Endoparasites:
Encephalitozoon cuniculi
3 months
3 months
3 months:
Rabbit enteritis complex – multifactorial – consider:
Rotavirus, Coronavirus, Clostridia, E coli, Lawsonia, Salmonella, Campylobacter, Coccidia, diet etc ..
VIRUSES in RABBITS
Virus order
Virus
/family
Adenoviridae
Rabbit enteric
Mastadenovirus?
adenovirus
Herpesviridae
Leporid Herpesvirus 1
Rhadinovirus?
(H Sylvilagus)
Herpesvirus
Leporid Herpesvirus 2
Rhadinovirus?
(H cuniculi)
Herpesvirus
Herpes simplex-like
Alphaherpesvirus?
virus
Polyomaviridae
Rabbit kidney
Polyomavirus
vacuolating virus
Papillomaviridae
Cottontail Rabbit
Kappapapilloma(Shope) papilloma
virus
virus
Papovavirus
Rabbit oral papilloma
Kappapapillomavirus
virus
Parvoviridae
Lapine parvovirus
Parvovirus
Myxoma virus
Poxviridae
Rabbit (Shope) fibroma
Leporipoxvirus
virus
Hare fibroma virus
1
2
3
4
Spp specif
O / S / L2
Prevalence
Dx/Detection
Rare ?
VI serol 3
?
Path, VI
?
VI
?
Path VI EM
Common in S?
Sero VI
Rabbit Disease ~
Pathology ~ Phenotypes
S, O
Common in S?
Path
Papillomas esp ear 
Carcinoma in Oryctolagus
1st virus identified with Tag
Origin of VX2 carcinoma cell line
O, S
Sporadic
Path
Oral papillomas benign
young rabbits in rabbitries, may regress
Exp  Fibromas in hamsters
O
Common
Serology
+/- Enteritis ?
S, O, L
Variable prev
Path VI serol PCR
Fibroma  myxoma 
dissemminated  death
Stellate mesenchymal cells
ICIB
O
S only
O
O
S, O
Diarrhea, enteritis INIB?
Sub clin  lymphoid
hyperplasia  lymphoma
Rash INIB
Corneal lesions
Multiorgan Hemorrhage
necrosis INIB syncytia
Subclinical - INIB4 in renal
tubule epithelium
Comments
Young rabbit diarrhea
Role in enteritis complex ?
leukocytosis Splenomegaly
lymphadenopathy Exp lymphoma
Isolated from Oryctolagus cell cultures 
exp infections
Rabbitry epizootics
Isolated from Sylvilagus cell cultures
Non oncogenic
Detected /isolated from clinically normal
rabbits some with enteritis
SWB ‘Big happy of family of viruses ‘ with
varying virulence
Wild (resistant) reservoirs  Oryctolagus
Arthropod vectors
Nicklas W & al. 2002. Recommendations for the health monitoring of rodent and rabbit colonies in breeding and experimental units. Lab Anim. 36(1):20-42.
http://www.felasa.eu/recommendations.htm
O = Oryctolagus; S = Sylvilagus; L = Lepus
Path = Pathology, histopathology; Serol = serology; VI = virus isolation
INIB = intranuclear inclusion bodies; ICIB = intracytoplasmic inclusion bodies
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C. Brayton September 2007
Virus order
/family
Poxviridae
Orthopoxvirus
Caliciviridae
Lagovirus
F$
07RabbitPathSumTable
Virus
Spp specif
O / S / L2
Rabbitpox virus
O
Hemorrhagic disease
virus
European brown
hare virus
O
L
Coronaviridae
Coronavirus?
Coronaviridae
Coronavirus?
Rhabdoviridae
Lyssavirus
Rabbit Enteric
Coronavirus
Pleural effusion disease
virus
Rabies virus
Mammals
Paramyxovirus ?
Rabbit syncytium virus
S
Sendai virus
O (rodents)
Paramyxoviridae
Respirovirus
Reoviridae
Rotavirus
Bunya, Toga, Flavi
typical (type 1)
rotavirus
Encephalitis viruses
O
O
O
SLO
NON Viral infectious/infesting agents in RABBITS
Site
Gram, AF,
AGENT in RABBITS
Primary
Silver
II. BACTERIA
Actinobacillus spp.
Var
G-
Bordetella bronchiseptica
F
Resp
G-
Brucella spp.
Var
Cilia-associated respiratory
(CAR) bacillus
Chlamydophila psittaci
Resp
Prevalence
Dx/Detection
Sporadic
Path VI Sero
?  spreading ?
Path Serol
Widespread?
Path EM
?
Vi
Rare
PCR VI Etc
?
Vi
+
Sero
Common
Serol EM VI
?
Prev
Dx/Detection
Rare in O
Path Cult
Common
Cult Path
Rabbit Disease ~
Pathology ~ Phenotypes
Skin Mucosa papules
Multifocal necrosis
Epistaxis hemorrhage
Liver necrosis hemorrhage;
Hepatocyte vacuolation
dissociation; thrombi;
Erythrophagocytosis
Diarrhea enteritis
Villus atrophy
Comments
Rabbitry epizootics
Prob an introduced Vaccinia strain
Coagulopathy
Species specific viruses
Economic importance
Young rabbit diarrhea
Role in enteritis complex ?
No natural disease
Exp Effusion, necrosis, etc
Died
Several pet rabbit reports
None
Syncytia in cell cultutes
Sub clin
Exp rhinitis
Young rabbit diarrhea
Villus blunting fusion edema
No Dz reported
Important factor in enteritis complex ?
Wild rabbit reservoirs ??
Rabbit Disease ~ Pathology ~
Phenotypes
Comments
Granulomas
Common in wild hares, rabbits
Interstitial pneumonitis, rhinitis
tracheitis otitis
Bronchopneumonia copathogen
with Pasteurella etc
B suis B abortus, B mellitensis
isolated from hares
Rare in O
Granulomas repro Liver Spleen
Sil
Common
Silver stain
No Dz – just argyrophilic bacilli among
cilia trachea bronchi
Clostridium difficile
Clostridium perfringens
Clostridium spiroforme
Int
G+
?
Path Serol toxins
Clostridium piliforme
F$
Int Liv 
Sil
Common?
Path Serol
clostridial enteropathy
Enterotoxemia  acute death
Cecum colon Necrosis hemorrhage
edema
Ileitis Typhlocolitis hepatitis carditis
hemorrhage, necrosis
Intracell argyrophilic bacilli
Post weaning, Hi Carb,
antibiotics, dysbiosis
Spiroforme common  G+ spiral
$$ important in EU rabbitries
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C. Brayton September 2007
AGENT in RABBITS
Escherichia coli
(Z EHEC)
Francisella tularensis
Z
Site
Primary
07RabbitPathSumTable
Gram, AF,
Silver
Int
Prev
Dx/Detection
Common
Cult
Rare in O
Rabbit Disease ~ Pathology ~
Phenotypes
AE in LI – role in enteritis complex
EHEC hemorrhagic colitis
0-death; sepsis pneumonia ulcer
Necrosis Liver spleen marrow
Comments
Not normal flora
EHEC zoonotic
Common in some wild
populations
Var
G Sil
Fusobacterium necrophorum
Skin Var
G
Klebsiella pneumoniae
Resp
G
Lawsonia intracellularis
Int
Sil
COMMON
Path PCR
Listeria monocytogenes
Z
Repro fetus
G+ SIL
Sporadic
Path Cult
Mycobacterium spp.
Var
AF
Pasteurella multocida
F
Resp
G+
Pseudomonas aeruginosa
Int Var
Sepsis
G-
Int Liv etc
G-
Staphylococcus aureus
Skin Mam
etc
G+
Streptococcus pneumoniae
Resp
G+
Streptococcus spp.
Sepsis
Mastitis
G+
Treponema paraluis-cuniculi
Repro
Sil
Yersinia pseudotuberculosis
Systemic
G
Resp
Sil
Sporadic
Path
Granulomas resp
Moldy bedding
Skin
ringworm
Sil
Rare
Scrape cult
RINGWORM crusty lesions, head ears
paws
Trichophyton mentagrophytes
more likely than M canis
Zoonotic  kids
Resp
Sil
Common?
Dz unusual interstitial pneumonia
Foamy material in alveoli
Opportunist in Young debilitated
Salmonella enteritidis
F (Z)
Sporadic
Path cult
Rare
Cult
Rare
Cult
Common
Cult path
Cult
Rare
Cult
Sporadic
Cult Pat
Rare
Cult Path
Sporadic
Cult
Var?
Path Sil
Rare
Path Cult
Schmorl’s Dz; Slobbers
opportunist
Hemorrhagic bronchopneumonia
Young rabbits
Proliferative (histiocytic) enteritis
PAS + macrophages; small bacilli in
apical cytoplasm
Placentitis + Big G+ bacilli
Fetal hepatitis splenitis adrenalitis
meningoencephalitis etc
Chronic diarrhea, often in young
rabbits
Rabbitry problem, abortions,
death of preg does
Granulomas
M bovis, avium tuberculosis
Snuffles Pneumonia, rhitis otits
pyometera mastitis etc
Dz uncommon – Smelly (+/- green
pus)
Suppurative lesions + Abscesses
anywhere
Opportunist – common in
water/environment
Sepsis diarrhea abortions death
DDX Listeria
Abscesses pododermatitis mastitis
(bluebag) rhinitis pneumonia
Sepsis death in kits
Rare respiratory dz
Mastitis  sepsis in kits
Venereal oral nasal Vesicles ulcers
Spirochetes Silver stain
Caseous necrosis in liver spleen nodes
MALT
Rabbit venereal Dz
III. FUNGI
Aspergillus fumigatus
Aspergillus flavus
Microsporum canis
T mentagrophytes
F
Pneumocystis carinii
IV. PROTOZOA
5
C. Brayton September 2007
07RabbitPathSumTable
AGENT in RABBITS
Site
Primary
Gram, AF,
Silver
Cryptosporidium cuniculus
Int
G Sil
Eimeria flavescens
intestinalis irresidua
magna media neoleporis
perforans piriformis
Int
Eimeria steidae
Liv
Encephalitozoon cuniculi
F
Kid Brain
etc
Hepatozoon cuniculi
Spleen
Sarcocystis cuniculi
Muscle
Toxoplasma gondii
Var
V. HELMINTHS
NEMATODES
Baylisascaris procyonis
(B mephisto; T canis)
Brain etc
Passalurus ambiguus
Cecum
Obeliscoides cuniculi
Stomach
Trichostrongylus calcaratus
Small int
Dirofilaria spp.
Subcutis etc
G+ Polar
Prev
Dx/Detection
??
Path fecal
Rabbit Disease ~ Pathology ~
Phenotypes
intracellular extracytoplasmic in SI
+/- enteritis
Common
Fecal
Path
Diarrhea enteritis ileum-cecum
Various stages in enterocytes 
oocysts in feces
Com wild
Path fecal
Com wild
Path Serol
Rare
path
Com wild
Path
Proliferative cholangitis - Various
stages in bile epithelium
Granulomas with G= birefringent
spores kidney brain (liver, lung etc)
Gametocytes in leukocytes, schizonts
in spleen
Pale streaks = cysts
No inflam unless rupt
Bradyzoite cysts or tachyzoites.
Necrosis in lymphoid tissue liver heart
lungs Granulomatous encephalitis
Unlikely
Path Serol
Larvae
Adult
eggs
Adult
Eggs
Adult
Eggs
Unlikely
Path
Common
Float Path
Rare
Float Path
Rare
Float Path
Comments
Usually Incidental
Intestinal coccidiosis
Vary in pathogenicity
Sanitation
Hepatic coccidiosis
Urine transmission of shed spores
Fleas?
Cat poop
0-fatal Dz.
Cat poop
Granulomas with larvae with lateral
alae; malacia gliosis in brain
Adult worms in cecum
Flattened crescentic eggs in feces
larval migrans from raccoon
skunk cat dog in wild
Adult worms in stomach
Common in wild
Adults in lumen; duodenitis
Common in wild
Rare
Path Blood
Adults in subcutis trunk (D. uniformis)
or around tendons(hock stifle) (D.
scapiceps). Microfilaria in blood
Aberrant host for D. immitis, 
thrombi in pulmonary arteries
Rare
Path
Adult tapeworms in SI
enteritis, perforation, obstruction in
heavy infestations
Common in wild;
Mite intermediate host
Rare
Path
Rare
Path
Cysticerci in liver, lungs, mesentery
mesenteric nodes etc
Coenurus cysts (multiple scolices) in
intermuscular fascia, esp flank.
Adults in small intestine of
carnivores, esp canids
Adults in small intestine of dogs
and foxes
Rabbit pinworms
Misc. in wild lagomorphs.
CESTODES
Cittotaenia variabilis
Small int
Misc. tapeworms in wild
lagomorphs
Taenia pisiformis
Taenia serialis
VI. ARTHROPODS
Liver, lungs
etc
Fascia
muscle
FLEAS
6
C. Brayton September 2007
AGENT in RABBITS
25 species!
Cediopsylla simplex
Odontopsyllus multispinosus
Ctenocephalides felis
Ctenocephalides canis
Spilopsyllus cuniculi
Site
Primary
07RabbitPathSumTable
Gram, AF,
Silver
Prev
Dx/Detection
SO
SO
Dog  O
Cat  O
Rabbit Disease ~ Pathology ~
Phenotypes
Common Eastern rabbit flea
Giant eastern rabbit flea
Dog flea
Cat flea
Common European rabbit flea
Comments
Important vectors of plague etc
Sylvilagus flea  Oryctolagus
Sylvilagus flea  Oryctolagus
Dog flea  Oryctolagus
Cat flea  Oryctolagus
MITES
Psoroptes cuniculi
Ear
O > wild
Common
Direct exam
Notedres cati
Sarcoptes scabei
Skin
Various
(human)
Rare
Direct exam
Cheyletiella parasitovorax
Fur
Listrophorus gibbus
Fur
Common
Fur
Uncommon?
Fur
Serous  crusty exudate; moist
dermatitis, secondary bacteria
Intense pruritus  alopecia
Serous exudate  scabs
Nares labia  eyes, face, genitalia
Pruritus hyperkeratosis dandruff esp
dorsum; may be only few mites
Subclinical – fur mites under tail – on
hair shaft
D. OTHER
Ticks in wild
Simuliids, Mosquitoes
Ear Mange  head shake
pruritus self mutilation
Notoedric mange
Sarcoptic mange (Scabies)
Can  emaciation, death.
Agitated behavior
Handlers may itch
Wild rabbits
Vector for myxomatosis etc?
Cuterebra spp.
Skinsubcutis
Var
Cochliomyia hominivorax
Wohfahrtia vigil
Skin
Var
unlikely
Subcutaneous large larvae
Wild rabbits
Maggots – flystrike
Outdoor rabbitries; injured,
debilitated wild rabbits
References / Resources
Baker, D.G. Ed. 2007. Flynn's Parasites of Laboratory Animals, 2nd Edition, Blackwell
Fox, JG & al eds. 2002. Academic Press. Laboratory Animal Medicine. 2nd ed. ISBN: 0122639510.
Manning, & al. Ed.’s 1994. The Biology of the Laboratory Rabbit, 2nd ed Academic Press. ISBN: 0124692354.
Percy, Barthold, B. Pathology of Laboratory Rodents & Rabbits, 3rd Edition, Blackwell
University of Missouri, Columbia RADIL DORA http://www.radil.missouri.edu/info/dora/Dora.htm
Acknowledgments
Steve Barthold; Charlie Clifford CRL; Dean Percy; Nadine Forbes
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