Diseases of Laboratory Rabbits PAT 707, Pathology of Laboratory Animals Prepared by Trenton R. Schoeb Department of Comparative Medicine University of Alabama at Birmingham Winter Quarter 1989-90 Myxomatosis 1. Agent: A poxvirus of the genus Leporipoxvirus (includes rabbit fibroma virus and squirrel and hare fibroma viruses). Nearly 100 strains are known; some, e.g., "standard laboratory" and California, are highly virulent for Oryctolagus cuniculus (mortality up to 99%). Recently described is a rabbit poxvirus called "malignant rabbit fibroma virus" (MRFV). Analysis of its genome indicates that it is a recombinant of Shope fibroma virus and myxoma virus. Despite the name given the virus, the disease it causes is similar to myxomatosis caused by other virulent poxvirus strains. 2. Epizootiology: Enzootic among Sylvilagus spp. in areas of North and South America, and in wild O. cuniculus in Europe and Australia. In Europe some hares (Lepus spp.) also are naturally susceptible. Transmission can occur by contact but is usually by arthropod vectors, especially fleas (in U.S., Cediopsylla simplex and Odontopsyllus multispinosus; in Europe Spilopsyllus cuniculi) and mosquitoes (Aedes, Anopheles, Culex, et al.). Fleas also are a good reservoir, having a long life (up to 1 yr). 3. Clinical: Great range in severity depending on species and strain of host and strain of virus. Sylvilagus rabbits usually have only a localized fibroma at site of inoculation. Hares (Lepus spp.) are resistant although a few individuals can develop generalized myxomatosis. In O. cuniculus, the California strain can cause a "peracute" form in which rabbits die within a week and have only depression and palpebral edema. In the "acute" form, palpebral edema becomes more pronounced, and inflammation and edema develop around any or all body orifices. Thus, myxomatous masses are not characteristic of these forms. The "standard laboratory" strain (a South American isolate) more typically causes generalized tumors which appear about 1 week after inoculation, and are accompanied by palpebral edema, mucopurulent ocular discharge, and edema of the base of the ears, genitalia, and lips. Poorly defined hard convex lumps appear by about 10 days, and these can become soft (necrotic) if the rabbit lives long enough (about 2 weeks). Virulent European strains (e.g., Lausanne) cause disease similar to that caused by the laboratory strain except that the masses proliferate rapidly, become purple or black within a week, and can break open and ooze serous discharge a few days later. MRFV causes severe disease accompanied by immunosuppression (decreased responses of lymphocytes to T- and B-cell mitogens). Inoculated rabbits die in 12-14 days with myxomatous masses on the head and extremities. 4. Pathology: Lesions range from typical fibromas in adult Sylvilagus spp., through more myxomatous but still localized masses in young Sylvilagus spp., to extensive masses characterized by proliferation of mesenchymal cells (origin uncertain), large stellate "myxoma cells", and large amounts of mucinous intercellular matrix which contains scattered mixed inflammatory cells. "Myxoma cells" may contain cytoplasmic inclusions. The overlying epidermis is unaffected, hyperplastic, or degenerated, and may contain inclusions, but the epithelial changes are minor compared to the connective tissue lesions. Other changes include vascular endothelial proliferation, and multifocal hemorrhagic necrosis in many organs, especially lung, liver, spleen, and lymph nodes. "Myxoma cells" can occur in lymphoid and other organs. Rabbits inoculated with MRFV tend to have exacerbations of pasteurellosis or bordetellosis. 5. Diagnosis: Signs and lesions usually are sufficient for presumptive diagnosis although California strain disease can lack distinctive characteristics. Other methods include virus isolation (chick embryo and various cell lines) and identification and animal inoculation. (Myxoma virus causes disease similar to fibromatosis in young Sylvilagus spp. but severe in young O. cuniculus.) 6. Control: Good barrier technique and vector control. A vaccine has been developed, but is not needed if vector control adequate. 7. References: Block W et al. 1985. Tumorigenic poxviruses: genomic organization of malignant rabbit virus, a recombinant between Shope fibroma virus and myxoma virus. Virology 140:113-124. Boag B. 1988. Observations on the seasonal incidence of myxomatosis and its interactions with helminth parasites in the European rabbit (Oryctolagus cuniculus). J Wildl Dis 24:450-455. Chapple PJ, Lewis ND. 1965. Myxomatosis and the rabbit flea. Nature 207:388-389. Corbeil LB et al. 1983. Immunity to pasteurellosis in compromised rabbits. Am J Vet Res 44:845-850. Edwards KM et al. 1988. Poxvirus deletion mutants: virulence and immunogenicity. Microb Pathog 4:325-333. Grodhaus G et al. 1963. Studies on the epidemiology of myxomatosis in California. II. The experimental transmission of myxomatosis in brush rabbits (Sylvilagus bachmani) by several species of mosquitoes. Am J Hyg 77:205-212. Marcato PS, Simoni P. 1977. Ultrastructural researches on rabbit myxomatosis. Lymphnodal lesions. Vet Pathol 14:361-367. Patton NM, Holmes HT. 1977. Myxomatosis in domestic rabbits in Oregon. J Am Vet Med Assoc 171:561-562. Rivers TM, Ward SM. 1937. Infectious myxomatosis of rabbits. J Exp Med 66:1-14. Rivers TM. 1930. Infectious myxomatosis of rabbits. Observations on the pathological changes introduced by virus myxomatosum (Sanarelli). J Exp Med 51:965-976. Ross J et al. 1989. Myxomatosis in farmland rabbit populations in England and Wales. Epidemiol Infect 103:333-357. Sell S et al. 1986. Leporine acquired immune deficiency disease. Symp Fundam Cancer Res 38:97-111. Skaletsky E et al. 1984. Immunologic dysfunction during viral oncogenesis. II. Inhibition of cellular immunity to viral antigens by malignant rabbit fibroma virus. Cell Immunol 86:64-74. Strayer DS et al. 1983. Immunologic dysfunction during viral oncogenesis. I. Nonspecific immunosuppression caused by malignant rabbit fibroma virus. J Immunol 131:2595-2600. Strayer DS et al. 1983. Malignant rabbit fibroma virus causes secondary immunosuppression in rabbits. J Immunol 130:399-404. Strayer DS et al. 1983. Malignant rabbit fibroma virus: observations on the cultural and histopathologic characteristics of a new virally-induced rabbit tumor. JNCI 71:91- 104. Strayer DS et al. 1985. In vitro growth of two related leporipoxviruses in lymphoid cells. Virology 145:330-334. Strayer DS et al. 1985. Malignant rabbit fibroma syndrome. A possible model for acquired immunodeficiency syndrome (AIDS). Am J Pathol 120:170-171. Strayer DS et al. 1986. Inhibition of virus replication does not alter malignant rabbit fibroma virus-induced immunosuppression. Clin Exp Immunol 66:25-36. Strayer DS, Sell S. 1983. Immunohistology of malignant rabbit fibroma virus--a comparative study with rabbit fibroma virus. JNCI 71:105-110. Upton C, McFadden G. 1986. Tumorigenic poxviruses: analysis of viral DNA sequences implicated in the tumorigenicity of Shope fibroma virus and malignant rabbit virus. Virology 152:308-321. Yamamoto H, Fujishiro K. 1989. Pathology of spontaneous malignant fibrous histiocytoma in a Japanese white rabbit. Jikken Dobutsu 38:165-169. Fibromatosis 1. Agent: A Leporipoxvirus first isolated by Shope in 1932. 2. Epizootiology: Sylvilagus floridanus (Eastern cottontail) is considered the natural host, but other Sylvilagus spp. are resistant. Mode of transmission probably is principally via arthropods. O. cuniculus is susceptible but natural disease is rare. 3. Clinical: In cottontail, usually 1-3 subcutaneous masses on legs and feet, in some cases on muzzle or around eyes, usually ó 7 cm across and ó 2 cm thick. Masses may persist for several months but eventually regress. Rabbits remain otherwise healthy. Similar in O. cuniculus but masses regress more quickly in adults. However, neonates can develop severe generalized form, as can rare adult. Newborn cottontails also experimentally susceptible to generalized fibromatosis but this is not known to occur naturally. 4. Pathology: Lesions begin as acute inflammatory response followed by fibroblastic proliferation and resemble myxomatosis lesions except that they tend to be more cellular and contain less mucinous matrix. Some cells can have cytoplasmic inclusions. Epidermal ulceration can occur but is secondary to protrusion of the mass. 5. Diagnosis: Myxomatosis is the primary differential, but can usually be distinguished via clinical signs. If not, inoculate tumor suspension into young O. cuniculus rabbits. Also virus isolation and identification--grows in embryonated eggs and various cell lines. 6. Control: As for myxomatosis. 7. References: Ahlstrom CG. 1938. The histology of the infectious fibroma in rabbits. J Path Bact 46:461-472. Duran-Reynolds F. 1945. Immunological factors that influence the neoplastic effects of the rabbit fibroma virus. Cancer Res 5:25-29. Joiner GN et al. 1971. An epizootic of Shope fibromatosis in a commercial rabbitry. J Am Vet Med Assoc 159:1583-1587. Kilham L, Dalmat HT. 1955. Host-virus mosquito relations of Shope fibromas in cottontail rabbits. Am J Hyg 61:45-54. Kilham L, Fisher ER. 1954. Pathogenesis of fibroma in cottontail rabbits. Am J Hyg 59:104-112. Kilham L, Woke PA. 1953. Laboratory transmission of fibromas (Shope) in cottontail rabbits by means of fleas and mosquitoes. Proc Soc Exp Biol Med 83:296-301. Pogo BGT et al. 1982. Shope fibroma virus I. Biological and molecular properties of a cytocidal and a noncytocidal strain. J Virol 41:97-103. Pulley LT, Shively JN. 1973. Naturally occurring infectious fibroma in the domestic rabbit. Vet Pathol 10:509-519. Raflo CP, et al. 1973. Characterization of a fibroma virus isolated from naturally- occurring skin tumors in domestic rabbits. Lab Anim Sci 23:525-532. Shope RE. 1932. A filterable virus causing a tumor-like condition in rabbits and its relationship to virus myxomatosum. J Exp Med 56:803-822. Shope RE. 1932. A transmissible tumor-like condition in rabbits. J Exp Med 56:793-802. Strayer DS et al. 1984. Strain differences in Shope fibroma virus. An immunopathologic study. Am J Pathol 116:342-358. Upton C, McFadden G. 1986. Tumorigenic poxviruses: analysis of viral DNA sequences implicated in the tumorigenicity of Shope fibroma virus and malignant rabbit virus. Virology 152:308-321. Yiull TM, Hanson RP. 1964. Infection of suckling cottontail rabbits with Shope's fibroma virus. Proc Soc Exp Biol Med 117:376-380. Rabbit Pox 1. Agent: An Orthopoxvirus; therefore not closely related to myxomatosis and fibromatosis viruses. 2. Epizootiology: Only 6 outbreaks reported since 1930, all in laboratory rabbits, all in U.S. and Netherlands. Transmission is probably via nasal secretions and spread is rapid. Neither carriers nor reservoir hosts have been demonstrated; source of infection is a mystery. 3. Clinical: Oculonasal discharge; lymphadenopathy; crusty macules, papules, or even nodules up to 1 cm across in skin and oronasal membranes; facial edema; focal necrosis of hard palate and gums; cutaneous hemorrhages; orchitis with severe scrotal edema; vulvar edema. Death may occur in 5 days to several weeks. In some outbreaks, rabbits died rapidly and did not develop skin lesions ("pockless" rabbit pox). 4. Pathology: Multifocal to diffuse epidermal and dermal proliferation and necrosis with cutaneous and subcutaneous edema; multifocal necrosis and edema of mucous membranes and serosal surfaces, liver, spleen, ovaries, uterus, lymph nodes, adrenals, thyroid, parathyroid, et al. The testicles may be completely necrotic. Depending on duration, necrotic foci may have mononuclear cell reaction. Inclusion bodies are few. 5. Diagnosis: Signs and lesions, FA, virus isolation and identification. 6. Control: Source unknown; no specific measures. 7. Reference: Christensen LR et al. 1967. "Pock-less" rabbit pox. Lab Anim Care 17:281-286. Papillomatosis 1. Agent: Shope papilloma virus first reported in 1933. Genus Papillomavirus, family Papovaviridae. 2. Epizootiology: Natural disease in cottontail rabbits (the natural hosts) is most common in Midwest and Great Plains states. Jackrabbits (Lepus sp.) are also susceptible. Natural disease in domestic rabbits has been reported only from Southern California. Natural transmission probably occurs mostly via the rabbit tick Haemaphysalis leporis-palustris. Mosquitoes and reduviid bugs can also transmit and are a more likely source of infection in commercial rabbitries. 3. Clinical: Typical papillomas ("warts") on neck, shoulders, or abdomen. Early lesions are rough but rounded; these may develop into large horn-like growths. In about a third of cases, papillomas spontaneously regress after several months. However, about 25% of naturally infected cottontails eventually develop squamous cell carcinomas, and as many as 75% of experimentally infected domestic rabbits may do so. Lesions do not occur on the mucous membranes. 4. Pathology: Lesions are histologically typical papillomas and squamous cell carcinomas. 5. Diagnosis: Signs and lesions. Virus can be difficult or impossible to demonstrate in tumors. 6. Control: Vector control. 7. References: Giri I et al. 1985. Genomic structure of the cottontail rabbit (Shope) papillomavirus. Proc Natl Acad Sci USA 82:1580-1584. Hagen KW. 1966. Spontaneous papillomatosis in domestic rabbits. Bull Wildl Dis Assoc 2:108-110. Kidd JG, Rous P. 1940. Cancer deriving from virus papillomas of wild rabbits under natural conditions. J Exp Med 71:469-493. Larson CL et al. 1936. Transmission of rabbit papillomatosis by the rabbit tick, Haemaphysalis leporis-palustris. Biol Med 33:536-538. Phelps WC et al. 1985. Shope papillomavirus transcription in benign and malignant rabbit tumors. Virology 146:120-129. Rous P, Beard JW. 1934. Carcinomatous change in virus-induced papillomas of the skin of the rabbit. Proc Soc Exp Biol Med 32:578-580. Rous P, Beard JW. 1935. The progression to carcinoma of virus-induced rabbit papilloma. J Exp Med 62:523-548. Shope RE. 1935. Serial transmission of the virus of infectious papillomatosis in domestic rabbits. Proc Soc Exp Biol Med 32:830-832. Shope RE. 1937. Immunization of rabbits to infectious papillomatosis. J Exp Med 65:607-624. Shope RE, Hurst EW. 1933. Infectious papillomatosis of rabbits. J Exp Med 58:607-624. Syverton JT. 1952. The pathogenesis of the rabbit papilloma-to-carcinoma sequence. Ann NY Acad Sci 54:1126-1140. Oral Papillomatosis 1. Agent: A papillomavirus distinct from Shope papilloma virus. 2. Epizootiology: Cottontail and domestic rabbits susceptible, but disease mostly recognized in domestic rabbits in Northeast. Probably transmitted by contact. 3. Clinical: Lesions occur most commonly on the under surface of the tongue, and are pale, sessile when small, rough and pedunculated when larger, and rarely exceed 5 mm in diameter. Lesions do not occur outside the mouth. Animals remain healthy and papillomas usually regress within weeks. 4. Pathology: Lesions are typical papillomas. 5. Diagnosis: Distribution and morphology of lesions. 6. Control: Measures to prevent exposure to more serious infectious agents should be effective. 7. References: Dominguez JA et al. 1981. Oral papillomatosis in laboratory rabbits in Mexico. Lab Anim Sci 31:71-73. Mews AR et al. 1972. Detection of oral papillomatosis in a British rabbit colony. Lab Anim 6:141-145. Parsons RJ, Kidd JG. 1943. Oral papillomatosis of rabbits: a virus disease. J Exp Med 77:233-250. Rdzok EJ et al. 1966. Rabbit oral papillomatosis--ultrastructure of experimental infection. Cancer Res 26:160-165. Richter WR et al. 1964. Oral papillomatosis of the rabbit: An electron microscopic study. Lab Invest 13:430-___. Sundberg, JP et al. 1985. Oral papillomatosis in New Zealand white rabbits. Am J Vet Res 46:664-668. Sundberg JP, Everitt JI. 1986. Diagnostic exercise: lingual growths in rabbits. Lab Anim Sci 36:499-500. Weisbroth SH, Scher S. 1970. Spontaneous oral papillomatosis in rabbits. J Am Vet Med Assoc 157:1940-1944. Rotavirus 1. Agent: Family Reoviridae. 2. Epizootiology: Not well studied and not experimentally proven to be capable of causing disease. Isolated from many healthy rabbits. However, in Tennessee outbreak, high morbidity and mortality among susceptible rabbits. Those 1-3 weeks old were affected, about 2/3 died. This was probably an epizootic among susceptible animals not previously exposed to rotavirus, and probably was complicated by other, unidentified, agents. In colonies with enzootic infection, disease is mild or subclinical. Infection is probably common among conventional rabbits. Not known if present among wild rabbits, but serologic test results indicate that it probably is. 3. Clinical: Diarrhea, dehydration, death. Adults may have transient anorexia but no other signs. 4. Pathology: Fluid-filled small intestine. Microscopically, typical villous atrophy and fusion, which in Tennessee rabbits was readily evident only in acutely affected rabbits. Disease is thought to be exacerbated by other enteric pathogens, so one should look carefully for other lesions. 5. Diagnosis: EM of intestinal contents, Rotazyme diagnostic kit, virus isolation. 6. Control: Good barrier technique. 7. References: Bryden AS et al. 1976. Rotavirus in rabbits. Vet Rec 99:323. Castrucci G et al. 1984. Comparative study of rotavirus strains of bovine and rabbit origin. Comp Immunol Microbiol Infect Dis 7:171-178. Castrucci G et al. 1985. Isolation and characterization of cytopathic strains of rotavirus from rabbits. Brief report. Arch Virol 83:99-104. Conner ME et al. 1988. Rabbit model of rotavirus infection. J Virol 62:1625-1633. Cromein JL et al. 1987. Evaluation of a new commercial enzyme immunoassay for rotavirus detection. J Clin Microbiol 25:2359-2362. DiGiacomo RF, Thouless ME. 1984. Age-related antibodies to rotavirus in New Zealand rabbits. J Clin Microbiol 19:710-711. DiGiacomo RF, Thouless ME. 1986. Epidemiology of naturally occurring rotavirus infection in rabbits. Lab Anim Sci 36:153-156. Iwai H et al. 1986. Prevalence of antibodies to Sendai virus and rotavirus in laboratory rabbits. Jikken Dobutsu 35:491-494. Peeters JE et al. 1982. Rotavirus in commercial suckling rabbits: Some preliminary observations. Vet Rec 52:724. Peeters JE et al. 1984. Infectious agents associated with diarrhoea in commercial rabbits: A field study. Ann Rech Vet 15:335-340. Petric M et al. 1978. Lapine rotavirus. Preliminary studies on epizootiology and transmission. Can J Comp Med 42:143-147. Sato K et al. 1982. Isolation of lapine rotavirus in cell cultures. Brief report. Arch Virol 71:267-271. Schoeb TR et al. 1986. Rotavirus-associated diarrhea in a commercial rabbitry. Lab Anim Sci 36:149-152. Takahashi E et al. 1979. Antibody to rotavirus in various animal species. Natl Inst Anim Health Qtly 19:72-73. Thouless ME et al. 1977. Serological relationships between rotaviruses from different species as studied by complement fixation and neutralization. Arch Virol 53:287-294. Thouless ME et al. 1988. Pathogenicity of rotavirus in rabbits. J Clin Microbiol 26:943-947. Corona-like Viruses Three syndromes have been reported. None have yet been recognized in U.S. (i) "Pleural effusion disease," a fatal disease resembling feline infectious peritonitis and characterized by fever, lymphocytopenia, leukocytosis, anemia, hypergammaglobulinemia, iridocyclitis, proteinaceous pleural effusion, and multifocal necrotizing inflammation of liver, kidneys, lungs, lymph nodes, and other organs. To date, this has been recognized only in Europe and has always been associated with experimental inoculation of certain strains of Treponema pallidum. The potential for natural disease, if any, is not known. One report indicates that the virus should not be classified in the Coronaviridae. (ii) Cardiomyopathy. Preliminary studies indicate that the causative coronavirus is the same as PEDV. (iii) Diarrhea, sometimes fatal. Recognized so far only in Europe and Canada, but potentially a significant cause of disease. 2. References: Christensen N et al. 1978. Pleural effusion disease in rabbits. Acta Pathol Microbiol Scand [A] 86:251-256. Descoteaux JP et al. 1985. An enteric coronavirus of the rabbit: detection by immunoelectron microscopy and identification of structural polypeptides. Arch Virol 84:241-250. Eaton P. 1984. Preliminary observations on enteritis associated with a coronavirus-like agent in rabbits. Lab Anim 18:71-74. Fennestad KL. 1985. Pathogenetic observations on pleural effusion disease in rabbits. Arch Virol 84:163-174. Fennestad KL, MacNaughton MR. 1983. Pleural effusion disease in rabbits. Properties of the aetiological agent. Arch Virol 26:179-187. Fennestad KL et al. 1975. Pleural effusion disease in rabbits, clinical and postmortem observations. Acta Pathol Microbiol Scand [B] (Suppl) 83:541-548. Lapierre J et al. 1980. Preliminary report on the observation of a coronavirus in the intestine of the laboratory rabbit. Can J Microbiol 26:1203-1208. Osterhaus ADME et al. 1982. Coronavirus-like particles in laboratory rabbits with different syndromes in the Netherlands. Lab Anim Sci 32:663-665. Small JD et al. 1979. Rabbit cardiomyopathy associated with a virus antigenically related to human coronavirus strain 229E. Am J Pathol 95:709-730. Herpesvirus cuniculi 1. Agent: Syn. "Virus III" 2. Epizootiology: Obscure. Prevalence unknown. No known natural disease; not known whether it doesn't occur or just not identified. 3. Clinical: Keratitis, orchitis, generalized erythematous and papular rash with fever can be induced experimentally. 4. Pathology: Edema and mononuclear cell infiltration in experimental orchitis, dermatitis, keratitis, myocarditis, etc. 5. Diagnosis: As with other herpesviral diseases. 6. Control: Unknown until epizootiology better understood. 7. References: Nesburn AB. 1969. Isolation and characterization of a herpes-like virus from New Zealand albino rabbit kidney cell culture: A probable reisolation of virus III of Rivers. J Virol 3:59-69. Rivers TM, Tillett WS. 1924. The lesions in rabbits experimentally infected by a virus encountered in the attempted transmission of varicella. J Exp Med 40:281-287. Herpesvirus sylvilagus Syn. cottontail virus. Not antigenically related to H. cuniculi. Only Sylvilagus spp. susceptible to infection. Prevalence unknown. No natural disease. Experimental inoculation results in chronic cell-associated viremia and a lymphoproliferative condition characterized by lymphocytosis (ó15,000/mm3 total WBC, ó95% lymphocytes with many large abnormal cells); and nodular to diffuse lymphoid proliferation in lymph nodes and spleen, with infiltration of the kidneys, liver, myocardium, and, less consistently, other organs. Whether or not this condition is true lymphosarcoma is not clear. Hinze HC. 1971. New member of the herpesvirus group isolated from wild cottontail rabbits. Infect Immun 3:350-354. Hinze HC. 1971. Induction of lymphoid hyperplasia and lymphoma-like disease in rabbits by Herpesvirus sylvilagus. Int J Cancer 8:514-522. Hinze HC, Chipman PJ. 1972. Role of herpesviruses in malignant lymphoma in rabbits. Fed Proc 31:1639-1642. Kramp WJ et al. 1985. Herpesvirus sylvilagus infects both B and T lymphocytes in vivo. J Virol 56:60-65. Lapine Parvovirus Lapine parvovirus infection originally was recognized in Japan. Limited serologic data indicate that it may be common in the United States, and it has been isolated from kidney cells of neonatal rabbits from a Pennsylvania rabbitry. It has not been associated with any naturally occurring disease, but it does cause cytopathic effects in cell culture and could therefore complicate studies in which rabbit cell cultures are used. Matsunaga Y, Chino F. 1981. Experimental infection of young rabbits with rabbit parvovirus. Arch Virol 68:257-264. Matsunaga Y, Matsuno S, Mukoyama J. 1977. Isolation and characterization of a parvovirus of rabbits. Infect Immun 18:495-500. Matsunaga Y, Matsuno S. 1983. Structural and nonstructural proteins of a rabbit parvovirus. J Virol 45:627-633. Metcalf JB et al. 1989. Natural parvovirus infection in laboratory rabbits. Am J Vet Res 50:1048-1051. "Viral Hemorrhagic Disease" VHD was first recognized in 1984 in China. It has since occurred in several European and Asian countries and in Mexico. (In Italy, 32 million rabbits are said to have died in 1986-1988.) Many other names have been used, such as "rabbit viral hemorrhagic fever," "viral hemorrhagic pneumonia," "infectious hepatic necrosis," etc. Disease is characterized by acute onset with fever, rapid respiration, and sudden death; spread is rapid and morbidity and mortality are high (ó80% and ó100%, respectively). The incubation period is very short, 24 to 72 hours. It is highly transmissible, so outbreaks in other parts of the world are possible. Lesions are not well described, but consist of widespread hemorrhage, especially in the lungs (necrotizing & hemorrhagic pneumonia), necrotizing hepatitis, lymphoid depletion, and encephalitis. Fibrin thrombi in many organs also has been reported and suggests that DIC may be an important pathogenetic process. A virus is consistently found in the blood and tissues of affected rabbits and probably is the etiologic agent. It is non-enveloped, icosahedral, and about 30 nm in diameter; contains RNA; and replicates in the cytoplasm. Some workers think it might be a picornavirus, but it has not been classified. Large numbers of viral particles are found in the liver, lung, kidney, and spleen. The virus agglutinates sheep, chicken, and human type O erythrocytes; thus hemagglutination inhibition can be used for a simple serologic test. Rabbit meat imported into this country is not subject to USDA inspection (or wasn't as of 1988), which may increase the probability of accidental importation of the disease into the US. Smid B et al. 1989. Experimental transmission and electron microscopic demonstration of the virus of haemorrhagic disease of rabbits in Czechoslovakia. Zentralbl Veterinarmed [B] 36:237-240. Xu ZJ, Chen WX. 1989. Viral haemorrhagic disease in rabbits: a review. Vet Res Commun 13:205-212. Rabbit Kidney Vacuolating Virus A polyomavirus, causes CPE in cell culture but not known to be pathogenic for domestic or wild rabbits. Crawford LV, Follett EAC. 1967. A study of rabbit kidney vacuolating virus and its DNA. J Gen Virol 1:19-24. Hartley JW, Rowe WP. 1964. New papovavirus contaminating Shope papillomata. Science 143:2588-261. Clostridiosis (Enterotoxemia) 1. Agents: Clostridium difficile and Cl. spiroforme (Cl. spiroforme appears to be more common). 2. Epizootiology: Cl. difficile is a ubiquitous anaerobe and may be carried in low numbers by normal rabbits. Cl. spiroforme is reported not to be part of normal flora, but may colonize if flora upset (e.g., by antibiotic treatment). 3. Clinical: Diarrhea and death in young or lactating rabbits and hares. Abdomens may be enlarged by gas-filled intestines. 4. Pathology: Necrotizing enterocolitis, often with extensive edema and hemorrhage. 5. Diagnosis: Lesions, gram-stained fecal smear, anaerobic culture, toxin demonstration. Toxins can be demonstrated by cytotoxicity assay, ELISA, CIE (counter immuno- electrophoresis), and latex immunoassays. Latex immunoassays are to be fastest and cheapest, and results agree well with those of ELISA tests (at least in the case of Cl. difficile toxin). Both tests offer positive and negative predictive values approaching or exceeding 90%. This is better than the cytotoxicity assay, which is not very good at detecting low concentrations of toxin. We have done cytotoxicity assays in several rabbit diarrhea outbreaks, but have not yet found an unequivocal case of clostridiosis. 6. Control: Unknown. 7. References: Anon. 1982. Lincomycin-associated diarrhea. Lab Anim Care 11:12. Borriello SP, Carman RJ. 1983. Association of iota-like toxin and Clostridium spiroforme with both spontaneous and antibiotic-associated diarrhea and colitis in rabbits. J Clin Microbiol 17:414-418. Carman RJ, Borriello SP. 1982. Clostridium spiroforme isolated from rabbits with diarrhea. Vet Rec 111:461-462. Carman RJ, Borriello SP. 1982. Observation on an association between Clostridium spiroforme and Clostridium perfringens type E enterotoxemia in rabbits. Eur J Chemother Antibiot 2:143-144. Carman RJ, Borriello SP. 1983. Laboratory diagnosis of Clostridium spiroforme mediated diarrhoea (iota enterotoxemia) of rabbits. Vet Rec 113:158. Carman RJ, Boriello SP. 1984. Infectious nature of Clostridium spiroforme-mediated rabbit enterotoxemia. Vet Microbiol 9:497-502. Carman RJ, Evans RH. 1984. Experimental and spontaneous clostridial enteropathies of laboratory and free living lagomorphs. Lab Anim Sci 34:443-452. Clark GF et al. 1987. Toxin A from Clostridium difficile binds to rabbit erythrocyte glycolipids with terminal Gal alpha 1-3 Gal beta 1-4 GlcNAc sequences. Arch Biochem Biophys 257:217-229. Dabard J et al. 1979. Experimental reproduction of neonatal diarrhea in young gnotobiotic hares simultaneously associated with Clostridium difficile and other Clostridium strains. Infect Immun 24:7-11. Dubos F et al. 1984. Immediate postnatal inoculation of a microbial barrier to prevent neonatal diarrhea induced by Clostridium difficile in young conventional and gnotobiotic hares. Am J Vet Res 45:1242-1244. Eaton P, Fernie DS. 1980. Enterotoxemia involving Clostridium perfringens iota toxin in a hysterectomy-derived rabbit colony. Lab Anim 14:347-351. Fekety R. Antibiotic-associated colitis. In Infectious Diarrheal Diseases: Current Concepts and Laboratory Procedures, ed. Ellner PD, Marcel Dekker Inc., New York, 1984, pp. 77-92. Fernie DS et al. 1984. Rabbit enterotoxemia: Purification and preliminary characterization of a toxin produced by Clostridium spiroforme. Fed Eur Microbiol Soc Microbiol Lett 21:207-211. Fernie DS, Eaton P. ____. The demonstration of a toxin resembling Clostridium perfringens iota toxin in rabbits with enterotoxemia. FEMS Microbiol Lett 8:33-35. Fesce A et al. 1977. Ecophylaxis: Preventive treatment with gentamicin of rabbit lincomycin-associated diarrhea. Folia Vet Lat 7:225-242. Gray JE, Lewis C. 1966. Enigma of antibiotic-induced diarrhea in the laboratory rabbit. Toxicol Appl Pharmacol 8:342. Harris IE, Portas BH. 1985. Enterotoxaemia in rabbits caused by Clostridium spiroforme. Aust Vet J 62:342-343. Holmes HT, Sonn RJ, Patton NM. 1988. Isolation of Clostridium spiroforme from rabbits. Lab Anim Sci 38:167-168. Hughes S et al. 1983. Clostridium difficile toxin-induced intestinal secretion in rabbit ileum in vitro. Gut 24:94-98. Katz L et al. 1978. Experimental clindamycin-associated colitis in rabbits. Evidence for toxin-mediated mucosal damage. Gastroenterology 74:246-252. Ketley JM et al. 1987. The effects of Clostridium difficile crude toxins and toxin A on ileal and colonic loops in immune and non immune rabbits. J Med Microbiol 24:41-52. Kim P-H, Iaconis JP, Rolfe RD. Immunization of adult hamsters against Clostridium difficile-associated ileocecitis and transfer of protection to infant hamsters. Infect Immun 55:2984-2992, 1987. LaMont JT et al. 1979. Role of clostridial toxin in the pathogenesis of clindamycin colitis in rabbits. Gastroenterology 76:356-361. Libby JM et al. 1982. Effects of the two toxins of Clostridium difficile in antibiotic- associated cecitis in hamsters. Infect Immun 36:822-829. Lyerly DM et al. 1983. Enzyme-linked immunosorbent assay for Clostridium difficile toxin A. J Clin Microbiol 17:72-78. Maiers JD, Mason SJ. 1984. Lincomycin-associated enterocolitis in rabbits. J Am Vet Med Assoc 185:670-671. McDonel JL, Duncan CL. 1975. Histopathologic effect of Cl. perfringens enterotoxin in the rabbit ileum. Infect Immun 12:1214. Mitchell TJ et al. 1986. Effect of toxin A and B of Clostridium difficile on rabbit ileum and colon. Gut 27:78-85. Mitchell TJ et al. 1987. The effects of Clostridium difficile crude toxins and purified toxin A on stripped rabbit ileal mucosa in Ussing chambers. J Med Microbiol 23:199-204. Patton NM et al. 1978. Enterotoxemia in rabbits. Lab Anim Sci 28:536-540. Peeters JE et al. 1986. Significance of Clostridium spiroforme in the enteritis complex of commercial rabbits. Vet Microbiol 12:25-31. Popoff MR. 1987. Purification and characterization of Clostridium sordellii lethal toxin and cross-reactivity with Clostridium difficile cytotoxin. Infect Immun 55:35-43. Rehg JE, Pakes SP. 1982. Implication of Clostridium difficile and Clostridium perfringens iota toxins in experimental lincomycin-associated colitis of rabbits. Lab Anim Sci 32:253-257. Stephen J et al. 1984. Clostridium difficile enterotoxin (toxin A): New results. Biochem Soc Trans 12:194. Taylor NS et al. 1981. Comparison of two toxins produced by Clostridium difficile. Infect Immun 34:1036-1043. Thilsted JP et al. 1981. Fatal diarrhea in rabbits resulting from the feeding of antibiotic-contaminated feed. J Am Vet Med Assoc 179:360-361. Triadafilopoulos G et al. 1987. Differential effects of Clostridium difficile toxins A and B on rabbit ileum. Gastroenterology 93:273-279. Vesely DL et al. 1981. Purified Clostridium difficile cytotoxin stimulates guanylate cyclase activity and inhibits adenylate cyclase activity. Infect Immun 33:285-291. Wexler H. 1989. Diagnosis of antibiotic-associated disease caused by Clostridium difficile. Clin Microbiol Newsletter 11:25-29. Wilkins T et al. Clostridial toxins active locally in the gastrointestinal tract. In Microbial Toxins and Diarrheal Disease (Ciba Foundation Symposium 112), Pittman, London, 1985, pp. 230-241. Yonushonis WP et al. 1987. Diagnosis of spontaneous Clostridium spiroforme iota enterotoxemia in a barrier rabbit breeding colony. Lab Anim Sci 37:69-71. Tyzzer's Disease 1. Agent: "Bacillus" piliformis, a gram-negative, filamentous sporeformer of uncertain classification. It has not been grown on artificial medium although it can be cultivated in eggs. 2. Epizootiology: Not often recognized, but possibly widespread; many cases probably misdiagnosed. Transmission thought to occur via fecal contamination. Infections are thought to be subclinical parasitism of small numbers of enterocytes unless animals are stressed or predisposed to disease by other unknown factors. Morbidity can be sporadic with only a few rabbits affected, or outbreaks can be severe with 50% or more affected. Mortality is near 100%. 3. Clinical: Acute onset of profuse watery diarrhea, depression, dehydration, death in a day or two. 4. Pathology: Primarily the cecum is affected and sometimes the distal ileum and proximal colon. Serosal surfaces are reddened and sometimes petechiated. The wall is edematous. Contents are brown, flocculent, and watery and the mucosa is rough and granular with adherent exudate or necrotic debris. Lesion is necrotizing and multifocal to diffuse. Multifocal necrotizing hepatitis is common; usually the foci are small (up to 2-3 mm). A few rabbits may have myocarditis. 5. Diagnosis: Morphology; silver impregnation (Warthin-Starry) to demonstrate intracellular bacilli. 6. Control: Closed colony established with Cesarean-derived stock. 7. References: Ononiwu JC, Julian RJ. 1978. An outbreak of Tyzzer's disease in an Ontario rabbitry. Can Vet J 19:107-109. Peeters JE et al. 1985. Naturally occurring Tyzzer's disease (Bacillus piliformis infection) in commercial rabbits: a clinical and pathological study. Ann Rech Vet 16:69-79. Waggie KS et al. 1987. An enzyme linked immunosorbent assay for detection of anti Bacillus piliformis serum antibody in rabbits. Lab Anim Sci 37:176-179. Salmonellosis 1. Agent: Various serotypes of Salmonella enteritidis, usually typhimurium or enteritidis. 2. Epizootiology: Rarely recognized in U.S. today, but potential exists especially where husbandry poor. Morbidity and mortality can be high. Transmission is via fecal contamination from carriers or affected animals. Potentially zoonotic. 3. Clinical: Usually nonspecific, many are found dead. Some have diarrhea, some abort. Disease may spread rapidly, with many cases appearing in a short time. 4. Pathology: Rabbits dying of peracute septicemic disease may have no lesions or only a few petechial hemorrhages. Those living a little longer may have multiple pinpoint foci of hepatic necrosis, splenomegaly, lymphadenopathy, and ulceration of Peyer's patches. In some cases there is fibrinous enteritis. 5. Diagnosis: Morphology, culture, serotyping. 6. Control: Good husbandry. Feed and bedding contaminated by vermin are a potential source of infection. Human carriers also are a possible, though unlikely, source. 7. References: Newcomer CE et al. 1984. The pathogenicity of Salmonella mbandaka in specific pathogen free rabbits. Lab Anim Sci 34:588. Onyekaba CO. 1985. Salmonella ochiogu: Experimental infection of laboratory rabbits (Oryctolagus cuniculus). Lab Anim 19:32-34. Wallis TS et al. 1986. The nature and role of mucosal damage in relation to Salmonella typhimurium induced fluid secretion in the rabbit ileum. J Med Microbiol 22:39-49. Colibacillosis 1. Agent: Escherichia coli. 2. Epizootiology: Fecal-oral transmission. Prevalence of disease and of E. coli strains pathogenic for rabbits is unknown. 3. Clinical: Diarrhea and acute death. Morbidity may be sporadic or epizootic and mortality is high. 4. Pathology: Pathogenic E. coli often are classified according to pathogenetic mechanism. Certain O:H (somatic:capsular) serotypes are characteristic of each type of organism. Classical enteropathogenic E. coli (EPEC) adhere to and destroy the microvilli of small intestinal enterocytes. (Some such strains have been called attaching-effacing E. coli, or AEEC.) Enterotoxigenic E. coli (ETEC) also adhere to the enterocyte surface, but cause disease by producing either or both a heat labile toxin (LT), which is similar to cholera toxin, and a heat stable toxin (ST). Adherence is mediated by fimbriae (pili) of several antigenic types; they are coded for by plasmids, which also encode LT and ST. Enteroinvasive E. coli (EIEC) are much less common. They resemble Shigella sp. in that they invade, multiply in, and kill epithelial cells; usually cause mucinous, bloody, or suppurative colitis like that of shigellosis; produce a cytotoxin similar or identical to Shiga toxin of Shigella dysenteriae type 1; and usually are nonmotile and non-lactose-fermenting. The Shigella-like properties, including several outer membrane proteins needed for invasion, also are coded for by plasmids. A few strains have been isolated recently that appear to lack most or all of these virulence properties, yet may still be able to cause diarrhea. Such strains are not well documented or studied. The role of E. coli in rabbit diarrhea is poorly understood. Large numbers (ó109 CFU/g) are present in the cecal contents in many cases; this is clearly abnormal, inasmuch as gram-negative organisms normally constitute only a small proportion of the enteric flora. However, it is unclear in most cases whether E. coli is a primary pathogen or merely proliferates in response to altered conditions in the intestine. (It is common to have large numbers of E. coli in the cecum in clostridiosis, for example.) There does not appear to be any prevalence of any particular serotype in cases of rabbit diarrhea, although more data is needed in this regard, and isolates usually are not tested for exotoxin production. Only AAEC strains have been shown to cause natural disease in rabbits. They attach to the surfaces of enterocytes in the distal small intestine, cecum, and colon, resulting in loss of the microvillous border and sloughing of enterocytes. Enterotoxigenic serotypes would not cause lesions, but also would be found attached to the microvillus border. Invasive strains would be expected to cause cecocolitis. 5. Diagnosis: Morphology, culture, serotyping, toxin demonstration, eliminate other diseases. 6. Control: Good sanitation and husbandry. 7. References: Camguilhem R, Milon A. 1989. Biotypes and O serogroups of Escherichia coli involved in intestinal infections of weaned rabbits: clues to diagnosis of pathogenic strains. J Clin Microbiol 27:743-747. Cantey JR, Blake RK. 1977. Diarrhea due to Escherichia coli in the rabbit. A novel mechanism. J Infect Dis 135:454-462. Cantey JR et al. 1981. Attachment of bacteria to intestinal epithelial cells in diarrhea caused by Escherichia coli strain RDEC-1 in the rabbit: Stages and role of capsule. J Infect Dis 143:219-230. Cantey JR, Inman LR. 1981. Diarrhea due to Escherichia coli strain RDEC-1 in the rabbit: The Peyer's patch as the initial site of attachment and colonization. J Infect Dis 143:440-446. Cleary TG et al. 1985. Shiga-like toxin production by enteropathogenic Escherichia coli serogroups. Infect Immun 47:335-337. Cohen MB et al. 1987. Association and dissociation of Escherichia coli heat-stable enterotoxin from rat brush border membrane receptors. Infect Immun 55:329-334. Coussement W et al. 1984. Pathology of experimental colibacillosis in rabbits. Zentralbl Veterinarmed [B] 31:64-72. Griffiths SL et al. 1986. Characterization of the receptor for cholera toxin and Escherichia coli heat labile toxin in rabbit intestinal brush borders. Biochem J 238:313-322. Hinson G et al. 1987. Adherence to human colonocytes of an Escherichia coli strain isolated from severe infantile enteritis: Molecular and structural studies of a fibrillar adhesin. Infect Immun 55:393-402. Inman LR, Cantey JR. 1983. Specific adherence of Escherichia coli (strain RDEC-1) to membranes (m cells) of the Peyer's patch in Escherichia coli diarrhea in the rabbit. J Clin Invest 71:1-8. Inman LR, Cantey JR. 1984. Peyer's patch lymphoid follicle epitherlial adherence of a rabbit enteropathogenic Escherichia coli (strain RDEC-1): Role of plasmid-mediated pili in initial adherence. J Clin Invest 74:90-95. Inman LR et al. 1986. Colonization, virulence, and mucosal interaction of an enteropathogenic Escherichia coli (strain RDEC-1) expressing shigella somatic antigen in the rabbit intestine. J Infect Dis 154:742-751. Karch H et al. 1987. A plasmid of enterohemorrhagic Escherichia coli O157:H7 is required for expression of a new fimbrial antigen and for adhesion to epithelial cells. Infect Immun 55:455-561. Kennedy DG et al. 1984. Effects of Escherichia coli heat-stable enterotoxin on intestines of mice, rats, rabbits, and piglets. Infect Immun 46:639-643. Levine MM. 1987. Escherichia coli that cause diarrhea: Enterotoxigenic, enteropathogenic, enteroinvasive, enterohemorrhagic, and enteroadherent. J Infect Dis 155:377-389. Masure HR et al. 1987. Mechanisms of bacterial pathogenicity that involve production of calmodulin-sensitive adenyl cyclases. Moon HW et al. 1983. Attaching and effacing activities of rabbit and human enteropathogenic Escherichia coli in pig and rabbit intestines. Infect Immun 41:1340-1351. Nakajima Y et al. 1987. The effects of Escherichia coli endotoxin as a trigger for hepatic infection of rabbits with Fusobacterium necrophorum. J Comp Pathol 97:207-215. O'Brien AD et al. 1982. Production of Shigella dysenteriae type 1-like cytotoxin by Escherichia coli. J Infect Dis 146:763-769. O'Brien AD et al. 1984. Shiga-like toxin-converting phages from Escherichia coli strains that cause hemorrhagic colitis or infantile diarrhea. Science 226:694-696. Okerman L, Devriese L A. 1985. Biotypes of enteropathogenic Escherichia coli strains from rabbits. J Clin Microbiol 22:955-958. Pai CH et al. 1986. Experimental infection if infant rabbits with verotoxin-producing Escherichia coli. Infect Immun 51:16-23. Peeters JE et al. 1984. Infectious agents associated with diarrhea in commercial rabbits. A field study. Ann Rech Vet 15:24-29. Peeters JE et al. 1984. Pathogenicity of attaching effacing enteropathogenic Escherichia coli isolated from diarrheic suckling and weanling rabbits for newborn rabbits. Infect Immun 46:690-696. Peeters JE et al. 1984. Pathogenic properties of Escherichia coli strains isolated from diarrheic commercial rabbits. J Clin Microbiol 20:34-39. Peeters JE et al. 1985. Scanning and transmission electron microscopy of attaching effacing Escherichia coli in weanling rabbits. Vet Pathol 22:54-59. Potter ME et al. 1985. Diarrhea due to Escherichia coli O157:H7 in the infant rabbit. J Infect Dis 152:1341-1343. Prescott JF. 1978. Escherichia coli and diarrhea in the rabbit. Vet Pathol 15:237-248. Rose R et al. 1987. Effects of Escherichia coli heat stable enterotoxin b on small intestinal villi in pigs, rabbits, and lambs. Vet Pathol 24:71-79. Takeuchi A et al. 1978. Scanning and transmission electron microscopic study of Escherichia coli O15 (RDEC-1) enteric infection in rabbits. Infect Immun 19:686-694. Wachsmith K. Laboratory detection of endotoxins. In Infectious Diarrheal Diseases: Current Concepts and Laboratory Procedures, ed. Ellner PD, Marcel Dekker Inc., New York, 1984, pp. 77-92. Campylobacterosis 1. Agent: An unidentified Campylobacter-like organism is almost certainly either the primary cause or a secondary one, although this has not yet been proven experimentally. Immunologic cross-reactivity with monoclonal antibodies and polyclonal antisera indicate that the intracellular organisms in rabbits are related, or perhaps identical, to the ones in swine, hamsters, and ferrets. Immunologic studies and protein electrophoretic patterns indicate that although the intracellular organisms may be related to Campylobacter spp., they are not a known species of Campylobacter. (For a review, see Schoeb and Fox.) C. jenuni has been isolated from rabbits, but has not been shown to cause disease. 2. Epizootiology: One report cites low but persistent morbidity (< 10%); mortality was high among affected rabbits. In rabbits from Tennessee, we have seen some sporadic cases and others associated with epizootics of diarrheal disease. Dr. James Fox at MIT has been consulted regarding cases in Massachusetts and Michigan, and I've heard of cases in Missouri. 3. Clinical: Moon et al. reported fulminating diarrhea, sometimes with mucus and blood, among weanlings, but many were found dead without observed diarrhea. Our cases have been in sucklings to young adults. Some of them have had fulminating diarrhea, but most have had less severe signs. 4. Pathology: The pattern described by Moon et al. is multifocal to diffuse, suppurative and superficially necrotizing cecocolitis. We have seen a few cases like this; most were associated with the epizootic of rotavirus infection we reported. Organisms were demonstrable in Warthin-Starry-stained sections within epithelial cells in areas of degeneration and necrosis. We also have seen a different pattern, not previously reported in rabbits, in which there is multifocal to diffuse, mild to moderate hyperplasia of mucosal epithelium in the small intestine, cecum, and colon, with numerous organisms demonstrable within the apical cytoplasm of epithelial cells in Warthin-Starry-stained sections. Dr. Fox found that these organisms react with monoclonal antibody against "omega" antigen of intracellular Campylobacter-like organisms extracted from intestines of pigs with proliferative ileitis and with polyclonal antisera against the pig organisms, as do the intracellular bacteria in proliferative ileitis of hamsters and proliferative colitis of ferrets. Organisms in the Moon et al. report had morphologic features of Campylobacter sp.; our findings have been similar. Umemura et al. describe "histiocytic enteritis," in which the distal small intestine was thickened with accumulations of macrophages in the lamina propria and the epithelial cells contained Campylobacter-like bacteria. They didn't mention epithelial hyperplasia in their description, but it is evident in the illustration. A few of our rabbits had similar lesions, with "omega" antigen in macrophages, so it seems likely that "histiocytic enteritis" is the same disease. 5. Diagnosis: Lesions, demonstration of organism (Warthin-Starry, immunofluorescence), rule out other causes. Use caution--Campylobacter has been isolated from rabbits without disease. We have not been able to isolate the causative organism from any of our cases. 6. Control: Specific measures not known. 7. References: Blaser MJ. Campylobacter enteritis. In Infectious Diarrheal Disease: Current Concepts and Laboratory Procedures, ed. Ellner PD, Marcel Dekker Inc., New York, 1984, pp. 1-12. Caldwell MB, Walker RI. 1986. Adult rabbit model for Campylobacter enteritis. Am J Pathol 122:573-576. Fox JG, Lawson GHK. 1988. Campylobacter-like omega intracellular antigen in proliferative colitis of ferrets. Lab Anim Sci 38:34-36. Lawson GHK, Rowland AC, MacIntyre N. 1985. Demonstration of a new intracellular antigen in porcine intestinal adenomatosis and hamster proliferative ileitis. Vet Microbiol 10:303-313. McOrist S, Boid R, Lawson GH. 1989. Antigenic analysis of Campylobacter species and an intracellular Campylobacter-like organism associated with porcine proliferative enteropathies. Infect Immun 57:957-962. McOrist S et al. 1987. Monoclonal antibodies to intracellular campylobacter-like organisms of the porcine proliferative enteropathies. Vet Rec 121:421-422. McOrist S et al. 1989. Early lesions of proliferative enteritis in pigs and hamsters. Vet Pathol 26:260-264. McOrist S, Lawson GH. 1987. Possible relationship of proliferative enteritis in pigs and hamsters. Vet Microbiol 15:293-302. Moon HW et al. 1974. Intraepithelial vibrio associated with acute typhlitis of young rabbits. Vet Pathol 11:313-326. Prescott JF, Bruin-Mosch CW. 1981. Carriage of Campylobacter jejuni in healthy and diarrheic animals. Am J Vet Res 42:164-165. Schoeb TR, Fox JG. Proliferative enteritis associated with intraepithelial Campylobacter-like bacteria in rabbits (Oryctolagus cuniculus). Vet Pathol, in press. Stills HF Jr, Hook RR Jr, Sprouse RF. 1987. Utilization of monoclonal antibodies to evaluate the involvement of Campylobacter jejuni in proliferative ileitis in Syrian hamsters (Mesocricetus auratus). Infect Immun 55:2240-2246. Stills HF Jr, Hook RR Jr. 1989. Experimental production of proliferative ileitis in Syrian hamsters (Mesocricetus auratus) by using an ileal homogenate free of Campylobacter jejuni. Infect Immun 57:191-195. Umemura T et al. 1982. Histiocytic enteritis of rabbits. Vet Pathol 19:326-328. Mucoid Enteropathy 1. Cause: Unknown. Pathologic features suggest it is an enterotoxin-induced secretory diarrhea, and some evidence suggests that ME is infectious and transmissible, but no consistent association with any particular organism has been found. Some experimental results suggest that ME may be related to reduced intestinal motility. Lelkes proposes that ME results from imbalances in cecal microflora. It is uncertain even that ME is a distinct disease. However, there is a syndrome or set of signs and lesions that until further information becomes available can be recognized as ME (see below). 2. Epizootiology: Unknown. ME is widely distributed in U.S. One of the most common causes of mortality in production colonies. 3. Clinical: Anorexia, polydipsia, subnormal temperature, depression, mucinous or fluid diarrhea. Usually in weanling (7-10 weeks old) rabbits. 4. Pathology: Distention of the stomach and small intestine with fluid and gas. The cecum can be impacted with pasty or dry contents. The colon characteristically contains casts of clear gelatinous mucus. Microscopically there may be increased mucus secretion (goblet cell hyperplasia) but there is no inflammation. 5. Diagnosis: Signs and lesions. 6. Control: Unknown. Antibiotics may reduce mortality. 7. References: Lelkes L. 1987. A review of rabbit enteric diseases: A new perspective. J Appl Rabbit Res 10:55-61. McLeod CG, Katz W. 1986. Opportunistic bacteria isolated from the caecum of rabbits with mucoid enteritis. Br Vet J 142:177-188. Toofanian F. 1985. Intestinal disaccharidase and alkaline phosphatase activities in experimental rabbit mucoid enteropathy. Lab Anim Sci 35:624-626. Toofanian F, Targowski S. 1983. Experimental production of rabbit mucoid enteritis. Am J Vet Res 44:705-708. Toofanian F, Targowski S. 1986. Stimulation of colonic goblet cells by cecal filtrates from rabbits with experimental mucoid enteropathy. Lab Anim Sci 36:157-160. Toofanian F, Hamar DW. 1986. Cecal short chain fatty acids in experimental rabbit mucoid enteropathy. Am J Vet Res 47:2423-2425. van Kruiningen HJ, Williams CB. 1972. Mucoid enteritis of rabbits. Comparison to cholera and cystic fibrosis. Vet Pathol 9:53-77. Vetesi F, Kutas F. 1973. Mucoid enteritis in the rabbit associated with E. coli. Changes in water, electrolyte, and acid-base balance. Acta Vet Acad Sci Hung 23:381-388. Yersiniosis 1. Agent: Yersinia pseudotuberculosis (possibly also Y. enterocolitica). 2. Epizootiology: An uncommon disease, transmitted by fecal contamination and ingestion, therefore probably would not be seen in well managed rabbitry. Potentially zoonotic. 3. Clinical: Chronic weight loss with or without diarrhea, perhaps palpable abdominal masses. 4. Pathology: Most consistently, enlargement and caseous necrosis of mesenteric lymph nodes. Caseous necrotizing lesions can also occur in Peyer's patches, appendix, liver, spleen, lungs, kidneys, peripheral nodes, bones, heart, etc. 5. Diagnosis: Lesions, culture. 6. Control: Prevent access of vermin to rabbitry. 7. Reference: Pai CH et al. 1980. Experimental Yersinia enterocolitica enteritis in rabbits. Infect Immun 28:238-244. Pasteurellosis 1. Etiology and pathogenesis: Pasteurella multocida, a short gram-negative bipolar bacillus, is the causative organism. Isolates may produce smooth, rough, or mucoid colonies; those producing mucoid ones are thought to be the most pathogenic. Various serotypes exist which may vary in virulence. Some recent evidence suggests that virulence may be related to adherence to respiratory epithelium and may not be due, as previously suggested, to ability to resist phagocytosis and killing by neutrophils. Commonly isolated serotypes include 12:A, 3:D, and 3:A (somatic:capsular antigens). Several organisms other than P. multocida have been isolated from pyogenic respiratory lesions in rabbits, particularly Bordetella bronchiseptica and Staphylococcus aureus. However, only P. multocida causes significant disease experimentally. Still, other factors must be involved because the response to experimental inoculation varies considerably. These factors remain to be elucidated, but likely possibilities include variation in organism virulence and factors affecting host resistance, such as concurrent disease and stress associated with experimentation, parturition and lactation, shipping, bad weather, and so forth. Further, clinically normal rabbits can harbor the organism in the nasal passages, and the extent to which the respiratory tract and other organs are affected also is probably affected by many variables. Currently, it is generally thought that the major route of infection is via the upper respiratory tract from which infection may spread distally to the lungs, to the eyes via the nasolacrimal duct or from the front paws contaminated with nasal exudate, to the middle ears via the auditory tubes, and into the blood resulting in acute death or in localization in other organs. P. pneumotropica has been isolated from "Pasteurella-free" rabbits. It did not cause any disease. 2. Epizootiology: Infection is essentially ubiquitous among conventional colonies. Prevalence of infection within colonies varies widely but can be 70% or more. Transmission is primarily by contact or aerosol, although venereal transmission also can occur. Asymptomatic carriers are important as disseminators of infection. 3. Clinical: Respiratory signs predominate: Mucopurulent nasal discharge, sneezing, coughing, or "snuffling." In a few cases in which otitis extends into the inner ear, torticollis or "wryneck" may occur. Sterility in does and orchitis or balanoposthitis are major manifestations of genital infection. Most deaths result from septicemia and pneumonia. Usually these animals are found dead; premonitory signs are seldom observed. Subcutaneous abscesses and mucopurulent conjunctivitis also occur. 4. Pathology: Chronic suppurative rhinitis, in some cases with grossly visible exudate. Pneumonia is usually typical airway-centered fibrinopurulent bronchopneumonia, sometimes accompanied by pleuritis. In otitis media, exudate usually is visible grossly. Abscesses are typical and not microscopically distinctive. They can occur in the subcutis, lungs, brain, heart, muscle, testicles, uterus, and other organs. Chronic suppurative endometritis with pyometra can occur. Rabbits dying of sep- ticemia may have no lesions or only a few petechiae. 5. Diagnosis: In live rabbits, by culture of nasal swabs. Diagnoses in necropsy cases are made by culturing affected organs and by demonstration of appropriate lesions. Septicemia is difficult to diagnose. The blood, bone marrow, spleen, and liver may be cultured, but Pasteurella septicemia probably is blamed for the deaths of many rabbits that actually are due to other, unknown causes. 6. Control: Good barrier technique, begin colony with Cesarean-derived SPF stock. 7. References: Al-Lebban ZS, Corbeil LB, Coles EH. 1988. Rabbit pasteurellosis: induced disease and vaccination. Am J Vet Res 49:312-316. Cary CJ et al. 1984. Serological analysis of five serotypes of Pasteurella multocida of rabbit origin by use of an enzyme-linked immunosorbent assay with lipopolysaccaride as antigen. J Clin Microbiol 20:191-194. Deeb BJ et al. 1989. Field trial of a live streptomycin dependent Pasteurella multocida serotype A:12 vaccine in rabbits. Lab Anim Sci 39:229-233. DiGiacomo RF et al. 1983. Natural history of infection with Pasteurella multocida in rabbits. J Am Vet Med Assoc 183:1172. DiGiacomo RF et al. 1987. Safety and efficacy of a streptomycin dependent live Pasteurella multocida vaccine in rabbits. Lab Anim Sci 37:187-190. DiGiacomo RF et al. 1989. Atrophic rhinitis in New Zealand white rabbits infected with Pasteurella multocida. Am J Vet Res 50:1460-1465. Glass LS, Beasley JN. 1989. Infection with and antibody response to Pasteurella multocida and Bordetella bronchiseptica in immature rabbits. Lab Anim Sci 39:406-410. Hofing EL et al. 1979. In vitro killing of Pasteurella multocida: The effect of rabbit granulocyte and specific antibody source. Am J Vet Res 40:679-683. Holmes HT et al. 1986. Serologic methods for detection of Pasteurella multocida infections in nasal culture negative rabbits. Lab Anim Sci 36:640-645. Hwang EJ et al. 1986. Characterization of an antigen purified from type 3 strains of Pasteurella multocida and its use for an enzyme-linked immunosorbent assay. Lab Anim Sci 36:633-639. Jones SM, Carrington SD. 1988. Pasteurella dacryocystitis in rabbits. Vet Rec 122:514-515. Kirchner BK et al. 1983. Pasteurella pneumotropica in rabbits from a "Pasteurella-free" production colony. Lab Anim Sci 33:461-462. Klaassen JM et al. 1985. Enzyme linked immunosorbent assay for immunoglobulin G antibody to Pasteurella multocida in rabbits. J Clin Microbiol 21:617-621. Kunstyr I, Naumann S. 1985. Head tilt in rabbits caused by pasteurellosis and encephalitozoonosis. Lab Anim 19:208-213. Liebenberg SP, Badger VM. 1984. Suppurative osteomyelitis in the foot of a rabbit. J Am Vet Med Assoc 185:1382. Lu YS, et al. 1983. Capsular and somatic serotypes of Pasteurella multocida isolates recovered from healthy and diseased rabbits in Texas. J Clin Microbiol 18:292-295. Lu YS et al. 1987. A potassium thiocyanate extract vaccine prepared from Pasteurella multocida 3:A protects rabbits against homologous challenge. Infect Immun 55:2967-2976. Lu YS et al. 1988. Distribution of a monoclonal antibody-recognized protective protein immunogen on the outer membranes of Pasteurella multocida rabbit isolates. J Clin Microbiol 26:1326-1330. Lukas VS et al. An enzyme linked immunosorbent assay to detect serum IgG to Pasteurella multocida in naturally and experimentally infected rabbits. Lab Anim Sci 37:60-64. Manning PJ et al. 1986. Pasteurellosis in laboratory rabbits: characterization of lipopolysaccharides of Pasteurella multocida by polyacrylamide gel electrophoresis, immunoblot techniques, and enzyme linked immunosorbent assay. Infect Immun 53:460-463. Manning PJ. 1982. Serology of Pasteurella multocida in laboratory rabbits: A review. Lab Anim Sci 32:666-671. Manning PJ. 1984. Naturally occurring pasteurellosis in laboratory rabbits: Chemical and serological studies of whole cells and lipopolysaccharides of Pasteurella multocida. Infect Immun 44:502-507. Murray KA et al. 1985. Acute meningoencephalomyelitis in a rabbit infected with Pasteurella multocida. Lab Anim Sci 35:169-171. Nakagawa M et al. 1986. Bacteriological and serological studies on Pasteurella multocida infection in rabbits. Jikken Dobutsu 35:463-469. Percy DH et al. 1984. Characterization of Pasteurella multocida isolated from rabbits in Canada. Can J Comp Med 48:162-165. Percy DH et al. 1985. Pasteurella multocida infection in the domestic rabbit: immunization with a streptomycin dependent mutant. Can J Comp Med 49:227-230. Percy DH et al. 1986. Experimental pneumonia in rabbits inoculated with strains of Pasteurella multocida. Can J Vet Res 50:36-41. Rimler RB, Brogden KA. 1986. Pasteurella multocida isolated from rabbits and swine: Serologic types and toxin production. Am J Vet Res 47:730. Ringler DH et al. 1985. Protection of rabbits against experimental pasteurellosis by vaccination with a potassium thiocyanate extract of Pasteurella multocida. Infect Immun 49:498-504. Rush HG et al. 1981. Resistance of Pasteurella multocida to rabbit neutrophil phagocytosis and killing. Am J Vet Res 47:1760-1768. Scharf RA et al. 1981. A modified barrier system for maintenance of Pasteurella-free rabbits. Lab Anim Sci 31:513-515. Scher S et al. 1969. The establishment of a specific pathogen-free rabbit breeding colony. I. Procedure for establishment and maintenance. Lab Anim Sci 19:610-799. Sokkar SM et al. 1987. Pathogenesis of Pasteurella multocida in experimentally infected rabbits. Arch Exp Veterinarmed 41:516-521. Ward GM. 1973. Development of a Pasteurella-free rabbit colony. Lab Anim Sci 23:671-674. Welch WD et al. 1987. Pharmacokinetics of penicillin G in serum and nasal washings of Pasteurella multocida free and infected rabbits. Lab Anim Sci 37:65-68. Staphylococcosis 1. Agent: Staphylococcus aureus. 2. Epizootiology: S. aureus is very widespread and is carried in the upper respiratory tracts of many animals and people. Transmission readily occurs via fomites, contact, and aerosol. 3. Clinical: Subcutaneous and mammary gland abscesses and necrotizing dermatitis are most common. Septicemic rabbits are usually just found dead. Lesions can be chronic and exudative, but extensive necrotizing lesions leading to death also occur. In very young rabbits, outbreaks of exudative staphylococcal dermatitis can cause high morbidity and mortality. 4. Pathology: Suppurative to necrotizing dermatitis and mastitis. Rabbits dead of peracute septicemia will probably have no lesions, but those surviving a few days can develop multifocal suppurative lesions in the heart, kidneys, lungs, liver, spleen, testicles, epididymides, joints, and bones. 5. Diagnosis: Culture. 6. Control: Difficult to exclude from colony. Can treat with antibiotics but some will die of enteric complications of therapy. Autogenous bacterin may help control. 7. References: Adlam C et al. 1977. Natural and experimental staphylococcal mastitis in rabbits. J Comp Pathol 86:581-593. Carolan MG. 1986. Staphylococcosis in rabbits [letter]. Vet Rec 119:412. Cohen JO. 1987. Veterinary medicine today: Staphylococcosis. J Am Vet Med Assoc 190:151-153. Devriese LA. 1984. A simplified system for biotyping Staphylococcus aureus strains isolated from animal species. J Appl Bacteriol 56:215-220. Millichamp NJ, Collins BR. 1986. Blepharoconjunctivitis associated with Staphylococcus aureus in a rabbit. J Am Vet Med Assoc 189:1153-1154. Okerman L et al. 1984. Cutaneous staphylococcosis in rabbits. Vet Rec 114:313-315. Snyder SB et al. 1976. Disseminated staphyloccal disease in laboratory rabbits (Oryctolagus cuniculus). Lab Anim Sci 26:86-89. Tularemia 1. Agent: Francisella tularensis (gram-negative and aerobic). 2. Epizootiology: Although numerous species, including laboratory rabbits, are susceptible, from a practical standpoint the disease is important mostly as a zoonotic hazard associated with wild rabbits (Sylvilagus spp.) and hares (Lepus spp.). Direct contact and wound entry or penetration of intact skin are most common means of transmission to man, but transmission by inhalation or ingestion also occurs. Among wild animals, infection is spread primarily by blood-sucking or biting arthropods, which may be merely mechanical or true biological vectors. Human infections also have resulted from tick bites. 3. Clinical: Affected animals usually are found dead; signs when observed are nonspecific. In man, fever and lymphadenopathy with or without abscess or phlegmon at initial site. Can be fatal if untreated, but responds well to antibiotics. 4. Pathology: Multifocal necrotizing and suppurative lesions in many organs: liver, spleen, lungs, lymph nodes, bone marrow, et al. 5. Diagnosis: Lesions, culture. 6. Control: Prevent vectors from entering colony. Use care when dressing wild rabbits. 7. References: Evans ME et al. 1985. Tularemia: A 30-year experience with 88 cases. Medicine (Baltimore) 64:251-269. Gordon JR et al. 1983. Tularemia transmitted by ticks (Dermacentor andersoni) in Saskatchewan. Can J Comp Med 47:408-411. Morner T et al. 1988. Infections with Francisella tularensis biovar palaearctica in hares (Lepus timidus, Lepus europaeus) from Sweden. J Wildl Dis 24:422-433. Rohrbach BW. 1988. Zoonosis update. Tularemia. J Am Vet Med Assoc 193:428-432. Treponematosis 1. Agent: Treponema cuniculi, a spirochete. 2. Epizootiology: Disease is rare, although serologic evidence indicates that infection may be rather more common than disease. Transmission is by contact during breeding. 3. Clinical: Lesions usually are on the genitalia but can also affect the anus and the skin of the perineum. A few rabbits develop lesions on the face. Lesions begin as reddened swellings which exude serum, become crusty and ulcerated, and eventually become dry and scaly and heal, with mild scarring. The course is usually several weeks. Affected rabbits are otherwise healthy. Females are reported to be less severely affected than males. 4. Pathology: Epidermal acanthosis and hyperkeratosis with dermal infiltration by lymphocytes and plasma cells, or ulceration with chronic suppurative reaction; there may be dermal or subcutaneous focal granulomas with necrotic centers. Spirochetes demonstrable in skin with Warthin-Starry stain. 5. Diagnosis: Lesion morphology, Warthin-Starry stain, dark field microscopy, serologic tests for syphilis including VDRL (Venereal Disease Research Laboratory), RPR (rapid plasma reagin), and FTA-ABS (fluorescent treponemal antibody-absorbed) tests. FTA-ABS antibodies appear to be the most persistent after treatment. 6. Control: No unusual measures needed. Treat with penicillin (lesions can still take 1 to 4 weeks to heal completely). 7. References: Cunliffe-Beamer T, Fox RR. 1981. Venereal spirochetosis of rabbits: Eradication. Lab Anim Sci 31:379-381. DiGiacomo RF et al. 1983. Treponema paraluis-cuniculi infection in a commercial rabbitry. Epidemiology and serodiagnosis. Lab Anim Sci 33:562-566. DiGiacomo RF et al. 1984. Clinical course and treatment of venereal spirochaetosis in New Zealand white rabbits. Br J Vener Dis 60:214-218. DiGiacomo RF et al. 1985. Chronicity of infection with Treponema paraluis cuniculi in New Zealand white rabbits. Genitourin Med 61:156-164. Gaertner DJ, Barthold SW. 1989. Diagnostic exercise: nasal mass in a rabbit. Lab Anim Sci 39:440-441. Miscellaneous bacterial conditions 1. Listeriosis Agent: Listeria monocytogenes, a small gram-positive bacillus. Listeriosis is sporadic and rarely recognized today. Transmission is poorly understood. The organism survives well in the environment, and there is some evidence for ingestion as common route; therefore, many opportunities for ingestion of contaminated feed probably occur. Clinical signs include death or abortion. Listeriosis is a septicemic disease, with cervical and mesenteric lymphadenitis, multifocal necrotizing and suppurative hepatitis, splenitis, adrenal adenitis, etc. In pregnant does, suppurative endometritis results in placentitis, abortion, and fetal or neonatal septicemia, as in other species. Watson GL, Evans MG. 1985. Listeriosis in a rabbit. Vet Pathol 22:191-193. 2. Necrobacillosis Agent: Fusobacterium necrophorum, a gram-negative anaerobe and common intestinal commensal. Disease is sporadic and usually results from fecal contamination of wounds, thus it usually occurs in situations of poor sanitation. Lesions are most commonly on the face (perhaps because of coprophagy) and feet. They are necrotizing and fetid and often ulcerative, although they may be deep, even in underlying bone. Visceral dissemination occurs in some cases. The primary characteristic of the lesions is caseous necrosis. Garibaldi BA, Moyer C, Fox JG. 1990. Diagnostic exercise: mandibular swelling in a rabbit. Lab Anim Sci 40:77-78. Nakajima Y et al. 1987. The effects of Escherichia coli endotoxin as a trigger for hepatic infection of rabbits with Fusobacterium necrophorum. J Comp Pathol 97:207-215. 3. Sylvatic plague Agent: Yersinia pestis. Not a disease of laboratory rabbits, but occasionally affects wild rabbits, and human infections have been acquired from handling wild rabbits. Transmitted naturally by arthropods, especially fleas, but people can acquire from contact with carcasses. In man, disease can be septicemic, pneumonic, or localized with lymphadenopathy. Diagnosis is by culture. 4. Cilia-associated respiratory (CAR) bacillus Rabbits are susceptible to natural and experimental infection. The prevalence of CAR bacillus in rabbits is not known. We have seen several cases here. In some, the bronchi had mild lesions similar to those observed in rats; in others, the organisms were evident only in the larynges and were associated with mild suppurative laryngitis. Lukas VS, Ruehl WW, Hamm TE Jr. 1987. An enzyme-linked immunosorbent assay to detect serum IgG in rabbits naturally exposed to cilia-associated respiratory bacillus. (Abstract) Lab Anim Sci 37:533. MacKenzie WF, Magill LS, Hulse M. 1981. A filamentous bacterium associated with respiratory disease in wild rats. Vet Pathol 18:836-839. Matsushita S et al. 1989. Transmission experiments of cilia-associated respiratory bacillus in mice, rabbits and guineapigs. Lab Anim 23:96-102. Waggie KS, Spencer TH, Allen AM. 1987. Cilia associated respiratory (CAR) bacillus infection in New Zealand White rabbits. (Abstract) Lab Anim Sci 37:533. 5. Other Srivastava KK et al. 1986. Characterization of a Haemophilus sp. isolated from a rabbit with conjunctivitis. Lab Anim Sci 36:291-293. Zarnke RL, Schlater L. 1988. Actinobacillosis in free-ranging snowshoe hares (Lepus americanus) from Alaska. J Wildl Dis 24:176-177. Mycotic diseases Fungal diseases in rabbits are uncommon to rare. Dermatophytosis should be a differential diagnosis in dermatitis. Frame SR, Mehdi NA, Turek JJ. 1989. Naturally occurring mucocutaneous histoplasmosis in a rabbit. J Comp Pathol 101:351-354. Matsui T et al. 1985. Pulmonary aspergillosis in apparently healthy young rabbits. Vet Pathol 22:200-205. Vogstberger LM et al. 1986. Spontaneous dermatophytosis due to Microsporum canis in rabbits. Lab Anim Sci 36:294-297. Encephalitozoonosis 1. Agent: Encephalitozoon cuniculi (Microsporida). The organism has been confused with Nosema sp., from which it cannot be distinguished by ordinary light microscopy, but there are distinctive ultrastructural and antigenic differences between the two. 2. Epizootiology: Natural mode of transmission not proven, but probably is via ingestion of infective spores passed in urine. Transplacental transmission also can occur. 3. Clinical: For practical purposes, none, although some older reports mention various neurological signs. 4. Pathology: Most common finding is scarring in the kidney, visible as multiple 1-2 mm pale slightly depressed areas in the capsular surface. These are confluent with radially oriented linear areas of chronic tubulointerstitial nephritis. Early lesions are granulomatous and necrotizing; older ones are fibrotic and contain many plasma cells. Gross lesions are not visible in the brain, but many, if not most, infected rabbits have some degree of multifocal granulomatous encephalitis, with mononuclear perivascular cuffing and leptomeningitis near affected areas. Lesions can occur anywhere in the brain but usually are most numerous in the cerebrum. Other organs are rarely if ever affected. Organisms are gram-positive and can be demonstrated with tissue gram stains, although they are difficult to find in many cases. 5. Diagnosis: Lesions, gram stain, serologic tests. 6. Control: Difficult, but can be done by cesarean derivation with intensive monitoring. 7. References: Ansbacher L, Nichols MF, Hahn AW. 1988. The influence of Encephalitozoon cuniculi on neural tissue responses to implanted biomaterials in the rabbit. Lab Anim Sci 38:689-695. Beckwith C et al. 1988. Dot enzyme-linked immunosorbent assay (dot ELISA) for antibodies to Encephalitozoon cuniculi. Lab Anim Sci 38:573-576. Bywater JE, Kellett. 1978. Encephalitozoon cuniculi antibodies in a specific-pathogen- free rabbit unit. Infect Immun 21:360-364. Bywater JE, Kellett. 1978. The eradication of Encephalitozoon cuniculi from a specific pathogen-free rabbit colony. Lab Anim Sci 28:402-404. Cox JC. 1977. Altered immune responsiveness associated with Encephalitozoon cuniculi infection in rabbits. Infect Immun 15:393-395. Cox JC et al. 1972. Presumptive diagnosis of Nosema cuniculi in rabbits by immunofluorescence. Res Vet Sci 13:595-597. Cox JC et al. 1977. Application of immunofluorescence to the establishment of an Encephalitozoon cuniculi-free rabbit colony. Lab Anim Sci 27:204-209. Cox JC, Gallichio HA. 1977. An evaluation of indirect immunofluorescence in the serological diagnosis of Nosema cuniculi infection. Res Vet Sci 22:50-52. Didier ES, Shadduck JA. 1988. Modulated immune responsiveness associated with experimental Encephalitozoon cuniculi infection in BABL/c mice. Lab Anim Sci 38:680- 688. Flatt RE, Jackson SJ. 1970. Renal nosematosis in young rabbits. Pathol Vet 7:492-497. Goodman DG, Garner FM. 1972. A comparison of methods for detecting Nosema cuniculi in rabbit urine. Lab Anim Sci 22:568-572. Howell JMcC, Edington N. 1968. The production of rabbits free from lesions associated with Encephalitozoon cuniculi. Lab Anim 2:143-146. Hunt RD et al. 1972. Encephalitozoonosis: Evidence for vertical transmission. J Infect Dis 126:212-214. Kellett BS, Bywater JEC. 1978. A modified india-ink immunoreaction for the detection of encephalitozoonosis. Lab Anim 12:59-60. Kunstyr I et al. 1986. Humoral antibody response of rabbits to experimental infection with Encephalitozoon cuniculi. Vet Parasitol 21:223-232. Kunstyr I, Naumann S. 1985. Head tilt in rabbits caused by pasteurellosis and encephalitozoonosis. Lab Anim 19:208-213. Pakes SP et al. 1972. A diagnostic skin test for encephalitozoonosis (nosematosis) in rabbits. Lab Anim Sci 22:870-877. Pakes SP et al. 1984. Comparison of tests for the diagnosis of spontaneous encephalitozoonosis in rabbits. Lab Anim Sci 34:356-359. Pang VF, Shadduck JA. 1985. Susceptibility of cats, sheep, and swine to a rabbit isolate of Encephalitozoon cuniculi. Am J Vet Res 46:1071-1077. Pye D, Cox JC. 1977. Isolation of Encephalitozoon cuniculi from urine samples. Lab Anim 11:233-234. Waller T. 1977. The india-ink immunoreaction: a method for the rapid diagnosis of encephalitozoonosis. Lab Anim 11:93-97. Waller T, Bergquist NR. 1982. Rapid simultaneous diagnosis of toxoplasmosis and encephalitozoonosis by carbon immunoassay. Lab Anim Sci 32:515-517. Wosu NJ et al. 1977. Diagnosis of encephalitozoonosis in experimentally infected rabbits by intradermal and immunofluorescence tests. Lab Anim Sci 27:210-216. Wosu NJ et al. 1977. Diagnosis of experimental encephalitozoonosis in rabbits by complement fixation. J Infect Dis 135:944-948. Hepatic Coccidiosis 1. Agent: Eimeria stiedae. 2. Epizootiology: Common in conventional rabbits. Transmitted by fecal-oral route. 3. Clinical: Usually none. Severely affected rabbits can lose weight, become debilitated, develop hepatomegaly and icterus. 4. Pathology: Yellow-white or yellow-tan nodules from a few mm to 1-2 cm in diameter in the liver; these are bile ducts chronically inflamed and dilated with bile and exudate. Microscopic: chronic proliferative cholangitis and cholecystitis, with numerous schizonts, microgametes, macrogametes, and developing oocysts in the epithelial cells; also, oocysts in the lumen. 5. Diagnosis: Fecal examination; lesions. 6. Control: Good barrier technique (must start with clean stock); can be controlled with sulfonamide treatment but not recommended. 7. References: Gomez Bautista M et al. 1986. The levels of total protein and protein fractions in the serum of rabbits infected with Eimeria stiedae. Ann Parasitol Hum Comp 61:393-400. Gomez Bautista M et al. 1987. The effect of the host's age on the pathology of Eimeria stiedae infection in rabbits. Vet Parasitol 24:47-57. Joyner LP et al. 1983. Eimeria stiedae in rabbits. The demonstra-tion of responses to chemotherapy. Res Vet Sci 34:64-67. Pakandl M. 1986. Efficacy of salinomycin, monensin and lasalocid against spontaneous Eimeria infection in rabbits. Folia Parasitol (Praha) 33:195-198. Patterson LT. 1987. Rabbit coccidiosis. Vet Hum Toxicol 29(Suppl 1):73-79. Peeters JE, Geeroms R. 1986. Efficacy of toltrazuril against intestinal and hepatic coccidiosis in rabbits. Vet Parasitol 22:21-35. Intestinal Coccidiosis 1. Agents: Eimeria spp. At least 10 spp., but only 3 or 4 are significant pathogens, e.g., E. magna, E. irresidua, E. intestinalis. 2. Epizootiology: Transmission is by fecal-oral route; oocysts must sporulate to become infective. Common among conventional rabbits. 3. Clinical: Varies from none to profuse watery, even bloody, diarrhea and death, depending on susceptibility of host (young or not previously exposed are more susceptible), species of causative organism, and inoculating dose. Mild or no signs are more common. Our experience has been that although infection is common in conventional rabbits, we never have seen a case in which enteric coccidiosis caused death. 4. Pathology: Most Eimeria species in rabbits affect one or more segments of small intestine; a few affect cecum or colon also. Parasitized enterocytes are lost resulting in superficially necrotizing enteritis. Severity of epithelial destruction and degree of inflammatory response vary considerably. 5. Diagnosis: Fecal examination; histopathology. 6. Control: Sanitation; barrier technique. Sulfonamides control but not recommended. 7. References: Gregory MW, Catchpole J. 1986. Coccidiosis in rabbits: The pathology of Eimeria flavescens infection. Int J Parasitol 16:131-145. Ogunbiyi AO, Uche EM. 1981. Intussusception in a rabbit (Oryctolagus cuniculus) associated with coccidiosis. Lab Anim 15:129. Pakandl M. 1988. Description of Eimeria vejdovskyi sp.n. and redescription of Eimeria media Kessel, 1929 from the rabbit. Folia Parasitol (Praha) 35:1-9. Peeters JE et al. 1984. Clinical and pathological changes after Eimeria intestinalis infection in rabbits. Zentralbl Veterinarmed [B] 731:9-24. Peeters JE, Geeroms R. 1989. Efficacy of diclazuril against robenidine resistant Eimeria magna in rabbits. Vet Rec 124:589-590. San Martin-Nunez BV, Ordonez-Escudero D, Alunda JM. 1988. Preventive treatment of rabbit coccidiosis with alpha-difluoromethylornithine. Vet Parasitol 30:1-10. Varga I. 1982. Large scale management systems and parasite populations: Coccidia in rabbits. Vet Parasitol 11:69-84. Miscellaneous Protozoa 1. Cryptosporidium cuniculus. Frequency of infection not known. Probably transmitted via fecal-oral route. No clinical signs known; reported only from apparently healthy rabbits. Pathogenic in other species, however. No histologic lesions; organisms attached to enterocytes of small intestine. Inman LR, Takeuchi A. 1979. Spontaneous cryptosporidiosis in an adult female rabbit. Vet Pathol 16:89-95. Rehg JE et al. 1979. Cryptosporidium cuniculus in the rabbit (Oryctolagus cuniculus). Lab Anim Sci 29:656-660. Ryan MJ et al. 1986. Cryptosporidium in a wild cottontail rabbit (Sylvilagus floridanus). J Wildl Dis 22:267. 2. Toxoplasma gondii. Transmitted by ingestion of infective oocysts from cat feces; also transplacentally. Rare today in domestic rabbits. Clinically, fever, usually without specific signs but sometimes neurologic signs, death in a few days. Multifocal necrosis of lymph nodes, spleen, liver, lungs, heart, brain, with vasculitis; organisms parasitize endothelial cells. Chronic lesions may be granulomatous or proliferative ("reticuloendothelial" hyperplasia). Ise Y et al. 1985. Detection of circulating antigens in sera of rabbits infected with Toxoplasma gondii. Infect Immun 48:269-272. 3. Sarcocystis cuniculi. Life cycle not definitely known, but rabbit is intermediate host. Definitive host is probably cat. Transmission is by ingestion of infective oocysts. No clinical disease. Lesions: sarcocysts in skeletal and cardiac muscle. These are grossly visible as fine pale streaks. There is usually no inflammatory response but in some cases eosinophilic myositis and myocarditis may result. Psoroptic Mange (Otoacariasis) 1. Agent: Psoroptes cuniculi. 2. Epizootiology: Common among conventional rabbits. Transmitted via contact. 3. Clinical: Ears are painful and itch intensely; affected rabbits shake heads and scratch ears. Inner surface of pinna covered with brown, scaly, fetid material. Skin beneath is raw, mites are grossly visible. 4. Pathology: Chronic erosive and proliferative eosinophilic dermatitis. Mites are non- burrowing and thus are found only in exudate, not in tissue. 5. Diagnosis: Appearance is characteristic; mites easily identified microscopically. 6. Control: Barrier technique. Can treat with mineral oil with or without acaricide, but cannot eliminate from colony. 7. References: Pandey VS. 1989. Effect of ivermectin on the ear mange mite, Psoroptes cuniculi, of rabbits. Br Vet J 145:54-56. Rafferty DE, Gray JS. 1987. The feeding behaviour of Psoroptes spp. mites on rabbits and sheep. J Parasitol 73:901-906. Stewart GA, Fisher WF. 1986. Cross reactivity between the house dust mite Dermatophagoides pteronyssinus and the mange mites Psoroptes cuniculi and P. ovis. I. Demonstration of antibodies to the house dust mite allergen Dpt 12 in sera from P. cuniculi infested rabbits. J Allergy Clin Immunol 78:293-299. Wright, FC, Riner JC. 1985. Comparative efficiency of injection routes and doses of ivermectin against Psoroptes in rabbits. Am J Vet Res 46:752-754. Sarcoptic Mange 1. Agents: Sarcoptes scabei and Notoedres cati. 2. Epizootiology: Worldwide distribution. Uncommon today in domestic rabbits. Zoonotic. 3. Clinical: Lesions are pruritic, variably alopecic, and crusty or oozing; usually on the muzzle at first then spreading over the face and head. 4. Pathology: Chronic dermatitis with acanthosis, burrowing mites in epidermis. Self-trauma can result in ulcerated areas with suppurative inflammation. 5. Diagnosis: Skin scraping, histopathology. 6. Control: Barrier technique. 7. References: Arlian LG et al. 1988. Effects of S. scabiei var. canis (Acari: Sarcoptidae) on blood indexes of parasitized rabbits. J Med Entomol 25:360-369. Lin SL et al. 1984. Diagnostic exercise. Sarcoptic mange in a rabbit. Lab Anim Sci 34:353-355. Fur Mites 1. Agent: Cheyletiella parasitovorax. 2. Epizootiology: Transmitted by contact. Not common today. 3. Clinical: None with light infestation, but if severe may have alopecia with red, scaly skin, not pruritic, mainly on trunk over scapulae. 4. Pathology: Dermatitis with hyperkeratosis. Mite is non-burrowing. 5. Diagnosis: Skin scraping. Differentiate from Listrophorus gibbus, another fur mite which is considered non-pathogenic. 6. Control: Topical treatments work; good barrier better. Helminth Parasites 1. Nematodes: Many spp. are known in wild rabbits, including Obeliscoides cuniculi, Nematodirus leporis, et al. (Trichostrongylidae, found in the stomach); Protostrongylus boughtoni (Metastrongylidae, bronchi); Passaluris ambiguus et al. (Oxyuridae, cecum and colon); Trichuris leporis (Trichuridae, cecum and colon); and Dirofilaria scapiceps (Filaridae, subcutis). Recently, a filariid of wild (Sylvilagus) rabbits in Louisiana was described: Brugia lepori. Of these, only Passaluris ambiguus is found in domestic rabbits with any frequency, and it is considered non-pathogenic. Larvae of the racoon ascarid Baylisascaris procyonis can cause visceral larval migrans with necrotizing and eosinophilic encephalitis. Duwel D, Brech K. 1981. Control of oxyuriasis in rabbits by fenbendazole. Lab Anim 15:101-105. Eberhard ML. 1984. Brugia lepori sp. n. (Filaroidea: Onchocerdidae) from rabbits (Sylvilagus aquaticus, S. floridanus) in Louisiana. J Parasitol 70:576-579. Kazacos KR et al. 1983. Fatal cerebrospinal disease caused by Baylisascaris procyonis in domestic rabbits. J Am Vet Med Assoc 183:967-971. Kazacos KR, Kazacos EA. 1988. Diagnostic exercise: Neuromuscular condition in rabbits. Lab Anim Sci 38:187-189. Watkins AR et al. 1984. The effects of single and multiple doses of thiabendazole on growing and arrested stages of the rabbit stomach worm Obeliscoides cuniculi. Vet Parasitol 16:295-302. 2. Cestodes: Wild rabbits frequently harbor Cittotaenia spp. and Raillietina spp. These are very rarely found in domestic rabbits. Domestic rabbits raised under poor husbandry conditions, however, commonly harbor larvae of the dog tapeworm Taenia pisiformis as cysticerci in the mesentery and liver and of T. serialis as coenuri in the skeletal muscles. Others have been reported. Tenora F, Beranek L, Stanek M. Larvocysts of the cestode T. polyacantha (Leucart, 1856) parasitizing Oryctolagus cuniculus. Folia Parasitol (Praha) 1988; 35:21-22 3. Trematodes: Hasstilesia tricolor is common in wild rabbits but has not been reported in domestic rabbits. Miscellaneous Parasites 1. Linguatula serrata A pentastomid. Rabbits are intermediate hosts and are infected by ingesting ova coughed up or defecated by definitive host (Canidae such as dog, fox, etc. and rarely sheep and man). Common in wild rabbits but rare in domestic rabbits. No disease; usually discovered at necropsy as incidental finding. Encysted nymphs found in abdominal and thoracic viscera. About 5 mm long. 2. Haemaphysalis leporis-palustris Only tick of significance in domestic rabbits; numerous other species affect wild rabbits. All can be vectors of tularemia, probably other bacterial diseases such as staphylococcosis, and of rickettsial diseases such as Rocky Mountain spotted fever and borelliosis. H. leporis-palustris occurs throughout North America. A three-host tick; larvae and nymphs commonly attach to birds, and adults spend only short time on rabbits, so not commonly seen. Sometimes abscesses at attachment site, but usually none. Anderson JF et al. 1989. Antigenically variable Borrelia burgdorferi isolated from cottontail rabbits and Ixodes dentatus in rural and urban areas. J Clin Microbiol 27:13-20. Ciceroni L et al. 1988. Rickettsiae of the spotted fever group associated with the host-parasite system Oryctolagus cuniculi/Rhipicephalus pusillus. Zentralbl Bakteriol Mikrobiol Hyg [A] 269:211-217. Lane RS, Burgdorfer W. 1988. Spirochetes in mammals and ticks (Acari: Ixodidae) from a focus of Lyme borreliosis in California. J Wildl Dis 24:1-9. 3. Haemodipsus ventricosus Louse, order Anoplura. Transmitted by contact. Present only under conditions of poor husbandry. Potential disease vector. No disease in in light infestations, anemia if heavy. 4. Cuterebra spp. Adult flies lay eggs around rabbit burrows or housing, larvae penetrate skin and develop. Larvae encyst in subcutis; cysts communicate with skin surface. Commonly called "warbles". Baird CR. 1983. Biology of Cuterebra lepusculi Townsend (Diptera: Cuterebridae) in cottontail rabbits in Idaho. J Wildl Dis 19:214-218. 5. Cediopsylla simplex and Odontopsyllus multispinosus Fleas; numerous species can affect rabbits but these are the only ones found with any frequency on domestic rabbits. Reportedly common, but not often found as only a few fleas generally infest each rabbit. Potential disease vectors. Usually no clinical signs, possibly some scratching or dermatitis. Neoplasms 1. Oryctolagus cuniculus. Accumulation of good data is hampered by the longer generation time and life span of the domestic rabbit compared to the mouse, and by the lack of old rabbits. Most are killed before 2 years old (normal life span is 7-8 years) so few rabbits reach a tumor-prone age. However, as in mice, some strains have a greater than usual incidence of certain tumors. Survey of Reported Tumors: a. Common: Uterine adenocarcinoma, lymphosarcoma, embryonal nephroma, and biliary adenoma and carcinoma, mammary intraductal papilloma and carcinoma (in older, > 3 yrs, female rabbits). (Though not tumors, adrenal cortical hyperplastic nodules are common and could be confused with tumors.). b. Uncommon: leiomyoma and leiomyosarcoma, vaginal squamous cell carcinoma. c. Rare or very rare: Ovarian, testicular, stomach, intestine, lung, CNS, urinary bladder, skin, bone, endocrine. (i) Uterine adenocarcinoma is the most common tumor of Oryctolagus cuniculus. Reproductive problems precede clinical appearance (palpable uterine nodules) by 6-10 months, and include decreased fertility and litter size, and more stillbirths, dystocia, and other difficulties. Tumors are usually multiple. The growth rate varies considerably but a typical mass could reach 5 cm in diameter by 6 months or so; many metastasize (mostly to the lung) and cause death in 12-24 months. Thus, they are slowly developing but inexorable. Gross lesions tend to be poorly demarcated pale lumps in the uterus, and somewhat more discrete, round, sometimes confluent or umbilicated nodules in the lungs. These are characterized histologically by a tubular and papillary adenocarcinoma pattern with abundant fibrous or myoid stroma. In the uterus, any of several endometrial abnormalities usually precedes the appearance of carcinoma: Adenomyosis (internal endometriosis), endometritis, pyometra, hyperplasia or atrophy. Which, if any, of these may be regarded as "precancerous" is unknown. Etiologic factors other than age remain obscure. There is apparently no relationship to parity. There may be a breed (hereditary) predisposition, but some random bred colonies also have high incidence. Some believe that "endocrine disturbances", particularly hyperestrogenism, are important. This remains to be substantiated experimentally, but some such general effect may indeed exist; mammary gland hyperplasia, adenosis, cysts, and tumors commonly accompany uterine adenocarcinoma. The high spontaneous incidence of this tumor gives it potential value as an experimental model. Elsinghorst TA et al. 1984. Comparative pathology of endometrial carcinoma. Vet Q 6:200-208. Hughes JR et al. 1981. Cystic mammary disease in a rabbit. J Am Vet Med Assoc 178:138-139. Lansdown AB et al. 1980. Endometrial adenocarcinoma in a young rabbit. Vet Rec 107:353. (ii) Lymphosarcoma: In contrast to other species, reported features of rabbit lymphosarcoma are rather uniform. Juveniles and young adults (8-18 months) are most commonly affected. Clinical findings include palpable abdominal masses, peripheral lymph node enlargement, anemia, and visible invasion of the ciliary body and anterior chamber of the eye. Four gross lesions are nearly constant: pale confluent renal cortical nodules, hepatomegaly usually without discrete nodules but with lobular accentuation, splenomegaly, and enlargement of any or all lymph nodes. Lymphoid tissue in the gastrointestinal tract is commonly affected and may ulcerate; peribronchial lymphoid tissue is affected less frequently. Ovaries and adrenals can be completely destroyed. The cells resemble large lymphoblasts. In the liver they accumulate periportally and in the kidney they are mostly interstitial with little destruction of nephrons. Interestingly, there is evidence that in certain strains at least, susceptibility is conferred by an autosomal recessive gene. This gene also apparently is responsible for a disease resembling that of NZB mice, except that it is sometimes accompanied by thymomas. (Thymomas are ordinarily sporadic and usually incidental findings, though thymic hyperplasia is not uncommon.) A rare Hodgkins'- like type has been described. Cloyd GG, Johnson GR. 1978. Lymphosarcoma with lymphoblastic leukemia in a New Zealand white rabbit. Lab Anim Sci 28:66-69. Fiume JW et al. 1980. Lymphoblastic leukemia in a rabbit: a case report. Lab Anim 14:49-51. (iii) Biliary adenoma and adenocarcinoma. Adenomas of the intrahepatic ducts are single or multiple, well demarcated, and often cystic. Most have considerable fibrous or myxoid stroma. They usually are an incidental PM finding. (iv) Embryonal nephroma. All reported ones were benign and were usually incidental findings. They have been found in old as well as young rabbits and apparently are very slow growing. They are single or multiple, white, projecting, discrete cortical nodules in either or both kidneys. Microscopically they resemble the human and porcine counterpart but contain no cartilage, muscle, or other mesenchymal elements as do many Wilm's tumors, which can be highly malignant. Thus, the rabbit tumor is of little value as a model. Polycythemia can accompany these tumors. Wardrop HJ et al. 1982. Nephroblastoma with secondary polycythemia in a New Zealand white rabbit. Lab Anim Sci 32:280-282. Lipman NS et al. 1985. Polycythemia in a New Zealand White rabbit with an embryonal nephroma. J Am Vet Med Assoc 187:1255-1256. (v) Mammary carcinoma is more common in multiparous females 3 years of age or more. Resembling mammary tumors in women in many ways, carcinomas are frequently preceded by cystic hyperplasia and adenomas. Papillomas appear in cystic ducts and become progressively more aggressive and invasive with time. Widespread metastases may occur. Some believe endocrine disturbances to be of etiologic importance. There is no evidence for a rabbit mammary retrovirus. (vi) Oral papillomas are fairly common in some areas of the U.S. They are caused by DNA virus of the genus Papillomavirus, as is the Shope papilloma of Sylvilagus spp; however the viruses are antigenically distinct, and the oral papilloma does not become malignant as the Shope papilloma can. Oral papilloma occurs naturally only in Oryctolagus spp., although Sylvilagus sp. can be experimentally infected. Following a latent period of 2-4 weeks after inoculation, papillomas appear, typically on the ventrum of the tongue. They grow slowly over 3-9 months reaching a maximum height of 4-6 mm. A cell-mediated response eventually occurs, resulting in sloughing of the tumors. Basophilic intranuclear inclusions are reportedly found in affected epithelium. 2. Sylvilagus sp. The only well known tumors of wild rabbits are the Shope tumors. A very few others have been reported including cases of lymphosarcoma resembling that of Oryctolagus sp. 3. Lepus sp. Very little is known of neoplasms in hares. They presently seem similar to those in rabbits with the following exceptions: myeloid leukemia, ovarian teratomas, and hare fibromas (caused by a distinct virus of the myxoma-fibroma group of poxviruses) in European hares. Miscellaneous references--neoplasms: Altman NH et al. 1978. Trichoepithelioma in a rabbit. Vet Pathol 15:671-672. Bishop L. 1978. Intracranial teratoma in a domestic rabbit. Vet Pathol 15:525-530. Brown PJ, Stafford RA. 1989. A testicular seminoma in a rabbit. J Comp Pathol 100:353-355. Hoover JP et al. 1986. Osteogenic sarcoma with subcutaneous involvement in a rabbit. J Am Vet Med Assoc 189:1156-1157. Lichtensteiger CA, Leathers CW. 1987. Peritoneal mesothelioma in a rabbit. Vet Pathol 24:464-466. Pletcher JM, Murphy JC. 1984. Spontaneous malignant hemangioendothelioma in two rabbits. Vet Pathol 21:542-544. Walberg JA. 1981. Osteogenic sarcoma with metastasis in a rabbit (Oryctolagus cuniculus). Lab Anim Sci 31:407-408. Zwicker GM, Killinger JM. 1985. Interstitial cell tumors in a young adult New Zealand white rabbit. Toxicol Pathol 13:232-235. Ulcerative Pododermatitis ("Sore Hocks") 1. Cause: Trauma and bacterial infection (commonly Staph. aureus). Wire bottoms may traumatize feet especially if rabbits are large and heavy, if cage is poorly constructed, or if sanitation is poor. 2. Clinical: Crusty or exuding ulcers on plantar aspect of metatarsus, sometimes on front feet also. Affected rabbits can appear healthy but some can lose appetite, lose weight, and eventually die. 3. Treatment: Topical ointments with antibiotics, can put flat surface in cage or put rabbit in solid-bottom cage with soft bedding, but creates sanitation problems. Vertebral Fracture and Luxation ("Broken Back") 1. Cause: Trauma due to improper handling. 2. Clinical: Posterior paresis or paralysis. If cord is transected, rabbit will lose bladder and anal sphincter control and will have soiled fur on the hindquarters. If not recognized for several days, may develop decubital ulcers, uremia. 3. Treatment: Usually euthanasia. However, rabbits not having severe cord damage can recover various degrees of limb function over two weeks or so. Moist Dermatitis ("Slobbers," "Wet Dewlap") 1. Cause: Bacterial infection of skin kept chronically wet because of drooling (e.g., due to malocclusion), watering in pans or poor husbandry. 2. Clinical: Exudative, sometimes fetid, dermatitis affecting the folds of the dewlap. 3. Treatment: Remove cause of wetness; topical or systemic antibiotics or both. Buphthalmia 1. Cause: Hereditary, autosomal recessive with incomplete penetrance (not all bu/bu homozygotes are affected). 2. Clinical: Common in NZW rabbits raised for laboratory use. One or both eyes affected; become enlarged and protruding, and corneal opacity, ulceration, and even rupture may result. 3. Pathology: Thought to result from abnormal drainage from anterior chamber. Analogous to glaucoma, but weaker sclera of rabbit permits enlargement which is not characteristic of glaucoma. Also, atrophy of ciliary processes and excavation of optic disc. 4. Diagnosis: Characteristic morphology. Mandibular Prognathism (Malocclusion) 1. Cause: Autosomal recessive (mp/mp) mutation. 2. Clinical: Common in domestic NZW rabbits. Mandibular incisors extend past maxillary incisors so that normal wearing against one another does not occur. Maxillary incisors grow in a curve and may eventually pierce the palate. Mandibular incisors protrude from the mouth. The rabbit may be unable to eat and eventually die of starvation. 3. Treatment: Incisors of affected rabbits must be clipped frequently (they grow 2 to 2.5 mm/week). General References Lelkes L. 1987. A review of rabbit enteric diseases: A new perspective. J Appl Rabbit Res 10:55-61. Weisbroth SH, Flatt RE, Kraus AL (eds). The Biology of the Laboratory Rabbit. Academic Press, New York, 1974. Miscellaneous References Bortolotti A, Castelli D, Bonati M. 1989. Hematology and serum chemistry values of adult, pregnant and newborn New Zealand rabbits (Oryctolagus cuniculus). Lab Anim Sci 39:437-439. Broderson JR. 1989. A retrospective review of lesions associated with the use of Freund's adjuvant. Lab Anim Sci 39:400-405. Brown RL et al. 1969. Ultrastructural pathology of an acute fatal enteritis of captive cottontail rabbits. Search for an etiologic agent. Am J Pathol 57:93-107. Burgess EC, Windberg LA. 1989. Borrelia sp. infection in coyotes, black-tailed jack rabbits and desert cottontails in southern Texas. J Wildl Dis 25:47-51. Fallon MT et al. 1988. Diagnostic exercise: eye lesions in a rabbit. Lab Anim Sci 38:612-613. Filice G, Cereda PM, Varnier OE. 1988. Infection of rabbits with human immunodeficiency virus. Nature 335:366-369. Fox RR et al. 1971. Hereditary cortical cysts in the rabbit. J Heredity 62:105-109. Garibaldi BA, Goad ME. 1988. Hypercalcemia with secondary nephrolithiasis in a rabbit. Lab Anim Sci 38:331-333. Garibaldi BA, Goad ME. 1988. Lipid keratopathy in the Watanabe (WHHL) rabbit. Vet Pathol 25:173-174. Gillett NA et al. 1983. Medical and surgical management of gastric obstruction from a hair ball in the rabbit. J Am Vet Med Assoc 183:1176-1178. Green PW et al. 1984. Spontaneous degenerative spinal disease in the laboratory rabbit. J Orthop Res 2:161-168. Green RA, Baker DC. 1987. Coagulation defects of aflatoxin intoxicated rabbits. Vet Pathol 24:62-70. Hanglow AC et al. 1986. Synovitis associated with serum IgM rheumatoid factor arising spontaneously in 'Old English' rabbits. Ann Rheum Dis 45:331-338. Hill JE et al. 1988. Spontaneous storage-like disease in a rabbit. Vet Pathol 25:91-92. Hinton M. 1981. Kidney disease in the rabbit: A histological survey. Lab Anim 15:263-265. Hofmann JR Jr, Hixson CJ. 1986. Amyloid A protein deposits in a rabbit with pyometra. J Am Vet Med Assoc 189:1155-1186. Leary SL et al. 1984. Experimental and naturally-occurring gastric foreign bodies in laboratory rabbits. Lab Anim Sci 34:58-61. Lee KJ et al. 1978. Hydronephrosis caused by urinary lithiasis in a New Zealand white rabbit (Oryctolagus cuniculus). Vet Pathol. 15:676-678. Machii K et al. 1989. Infection of rabbits with Sendai virus. Lab Anim Sci 39:334-337. Mendlowsky B. 1975. Neuromuscular lesions in restrained rabbits. Vet Pathol 12:378-386. Moore CP et al. 1987. Anterior corneal dystrophy of American Dutch Belted rabbits: Biomicroscopic and histopathologic findings. Vet Pathol 24:28-33. Morrell JM. 1989. Hydrometra in the rabbit. Vet Rec 125:325. Morton D et al. 1986. Histologic alterations in the testes of laboratory rabbits. Vet Pathol 23:214-217. Ngatia TA et al. 1989. Arteriosclerosis and related lesions in rabbits. J Comp Pathol 101:279-286. Pfaffenberger GS, Valencia VB. 1988. Ectoparasites of sympatric cottontails (Sylvilagus audubonii Nelson) and jack rabbits (Lepus californicus Mearns) from the high plains of eastern New Mexico. J Parasitol 74:842-846. Port CD, Dodd DC. 1983. Two cases of corneal epithelial dystrophy in rabbits. Lab Anim Sci 33:587-588. Richter CB, Hendren RL. 1969. The pathology and epidemiology of acute enteritis in captive cottontail rabbits (Sylvilagus floridanus). Vet Pathol 6:159-175. Sebesteny A et al. 1985. Lipid keratopathy and atheromatosis in an SPF laboratory rabbit colony attributable to diet. Lab Anim 19:180-188. Shell LG, Saunders G. 1989. Arteriosclerosis in a rabbit. J Am Vet Med Assoc 194:679-680. Smith CA, Stone DM, Prieur DJ. 1989. Spontaneous profuse superovulation in association with ectopic fetuses in a rabbit. Lab Anim Sci 39:74-77. Stadler J et al. 1983. Use of the New Zealand white rabbit in teratology. Incidence of spontaneous and drug-induced malformations. Food Chem Toxicol 21:631-636. Strohlein DA, Christensen BM. 1983. Metazoan parasites of the eastern cottontail rabbit in western Kentucky. J Wildl Dis 19:20-23. Swartout MS, Gerken DF. 1987. Lead-induced toxicosis in two domestic rabbits. J Am Vet Med Assoc 191-717-719. Van Herck H et al. 1989. Prolapsus vaginae in the IIIVO/JU rabbit. Lab Anim 23:333-336. Weisbroth SH. 1975. Torsion of the caudate lobe of the liver in Oryctolagus cuniculus. Vet Pathol 12:13-15. Wilson RB et al. 1987. Liver lobe torsion in a rabbit. Lab Anim Sci 37:506-507. Yamini B, Stein S. 1989. Abortion, stillbirth, neonatal death, and nutritional myodegeneration in a rabbit breeding colony. J Am Vet Med Assoc 194:561-562.