Infectious diseases of domestic rabbits

Abstract

16.1 Parasites of rabbits Wild rabbits are host to a variety of parasites that can be transmitted to domestic rabbits. The type and species of parasite varies throughout the world and it is beyond the scope of this book to describe them all. A detailed, illustrated description is given by Hofing and Kraus (1994). The parasites that affect domestic rabbits are described in detail by Owen (1992). This is the major reference source for the parasite section of this chapter. 16.2 Ectoparasites 16.2.1 Fleas Spilopsyllus cuniculi is a common flea that infests wild rabbits in Europe. It does not occur in the USA (Kraus et al., 1984). The fleas have a predilection for the ears where they can be found in clusters along the edges of the pinnae. The fleas are mobile and move between the environment and the host. Wild rabbit fleas are not usually found on pet rabbits. Spilopsyllus cuniculi is a small flea whose life cycle is influenced by the reproductive status of the host. Egg maturation is dependent on female reproductive hormones. Successful reproduction of the rabbit flea requires contact with a rabbit in late pregnancy or with a newborn nestling. Increased blood corticosteroid concentrations in late pregnancy attract fleas, which attach firmly to the doe to feed. Within a few hours of parturition, fleas move from the doe to the newborn babies to feed, copulate and lay eggs in the nest. The eggs hatch and the larvae feed on flea dirt deposited in the nest by the adult fleas feeding on the pregnant doe. In this way, fleas are spread from one generation to the next and are an important vector of disease, especially myxomatosis. Ctenocephalides canis or felis, the common cat and dog flea, is the usual flea that is found on pet rabbits. Infestation results from rabbits living in a house inhabited by dogs and cats. Infestation causes intense pruritus and allergic dermatitis can develop. Fleas and flea dirt can be found on the rabbit by combing the coat with a fine-toothed comb. 16.2.2 Lice Haemodipsus ventricosus is a sucking louse that affects wild rabbits and may act as a vector for myxomatosis. It is a large louse 1.5-2.5 mm in length. It is occasionally found on pet rabbits (Owen, 1992). 16.2.3 Mites Psoroptes cuniculi is the common ear mite of rabbits that causes crusting and ulceration of the external ear canal. The mites are large and active and are just visible to the naked eye. They are surface dwellers that cause intense irritation when they are present in large numbers (see Figure 16.1 ). Occasionally they are found in other areas of the body such as the perineal skin folds (see Section 9.14.2.1). Figure 16.1 Psoroptes cuniculi (Image supplied by Dr Sheelagh Lloyd, Division of Animal Pathology, University of Cambridge). The rabbit ear mite, Psoroptes cuniculi causes crusting and inflammation of the external ear canal, which often extends up the pinna (see Plate 4). Lesions are sometimes found on other parts of the body such as the perineal skin folds. Mites can just be seen with the naked eye in exudate from the lesions. Large numbers of Psoroptes cuniculi are visible on microscopic examination of the exudate, which can be softened in liquid paraffin before placing on a glass slide. Cheyletiella parasitovorax is a fur dwelling mite that can be found in large numbers in pet rabbits (see Section 9.14.2.3). Areas of dense, flaky, encrusted skin are found along the back especially above the tail base and on the neck. The mites are easily identified by microscopic examination of skin brushings or pluckings (see Figure 16.2 ). Infestation with cheyletiella is often associated with obesity, spinal disorders or dental disease. Cheyletiella parasitovorax is zoonotic and can cause erythema and pruritus in man. Pruritic lesions are found on the forearm or neck of humans that have handled infested rabbits. The lesions regress over 24 h. Figure 16.2 Cheyletiella parasitovorax. This mite can be found in the fur of healthy rabbits. It is not always associated with skin lesions. In large numbers, Cheyletiella parasitovorax mites cause pruritus and areas of white, flaky skin. Heavy infestation is usually linked to some underlying problem with grooming, such as dental disease, obesity or spinal disorders. Mites may be seen moving among skin flakes that are combed out and placed under a bright light. Cheyletiella parasitovorax can also be detected by combing out the flakes and applying acetate strips to the exposed underlying skin. The acetate strip is placed on a microscope slide and examined on low power. In heavy infestations a variety of nymphal stages, eggs and adult mites are seen. Leporacus gibbus (formerly known as Listrophorus gibbus) is the common fur mite of rabbits (see Section 9.14.2.4). Infestation is normally asymptomatic and is not significant, except that large numbers can indicate some underlying disease. The mite is usually found attached to the hair shaft where it feeds on sebaceous gland secretions (see Figure 16.3 ). The mites are just visible to the naked eye especially on light coloured rabbits when infestation gives the coat the appearance of being sprinkled with pepper. This effect is more obvious when the coat is wet. Figure 16.3 Leporacus gibbus (formerly Listrophorus gibbus). Leporacus gibbus can be found in the fur of many pet rabbits. Infestation is usually asymptomatic. Like Cheyletiella parasitovorax, heavy infestation is linked to some underlying problem with grooming, such as dental disease, obesity or spinal disorders. The mite is just visible to the naked eye, especially in light-coloured rabbits. A simple method of detecting Leporacus gibbus is to comb through the fur with a fine-toothed flea comb and place the combings in a small, clear plastic bag. The contents of the bag are viewed microscopically under low power and the mites are seen moving along hair shafts. Eggs and empty egg cases can be seen attached to hair shafts. Immature and adult mites are visible. There are morphological differences between male (a) and female mites (b). Notoedres and Sarcoptes have been described as causes of mange in rabbits. 16.2.4 Warble flies Cuterebra horripilum and C. buccata are warble flies that affect rabbits in the USA but do not occur in the UK. 16.3 Endoparasites 16.3.1 Intestinal worms There is a range of nematodes that affect wild rabbits in various parts of the world. With the exception of Passalurus ambiguus, infestations in domestic rabbits are rare, especially in pets and are unlikely to be encountered. Passalurus ambiguus is an oxyurid that is found in the caecum and large intestine. The adult worms measure 5-10 mm and are not pathogenic in the adult animal. Heavy infestations in young rabbits can be a contributory factor to the enteritis complex of diseases that occur around weaning (see Section 10.2). The small, thread-like worm is seen in the faeces of affected animals. The life cycle is direct. Passalurus ambiguus is susceptible to most anthelmintics, e.g. piperazine and fenbendazole. Ivermectin is ineffective (Morrisey, 1996). There are other helminth parasites that principally affect wild rabbits and are not found in the domestic pet. They include Graphidium strigosum and Trichostrongylus retortaeformis (Allan et al., 1999). Obeliscoides cuniculi occurs in wild rabbits in various parts of the world and in domestic rabbits in the USA (Hofing and Kraus, 1994). Obeliscoides cuniculi has been used as a laboratory model of Trichostrongylus and Ostertagia species of ruminants. No species of trematode has been reported in rabbits (Kraus et al., 1984). 16.3.2 Tapeworms The rabbit is the intermediate host for several tapeworms that affect dogs and cats. Pet rabbits that graze in gardens inhabited by pet dogs or visited by foxes can become infected. The incidence of these parasites is not high as most pet owners now worm their dogs with preparations that are effective against tapeworms. Cysticercus pisiformis is the larval stage of Taenia pisiformis, which is a tapeworm that affects dogs and foxes with rabbits acting as the intermediate host. Tapeworm segments packed with eggs are shed in faeces and contaminate pasture. Grazing rabbits ingest eggs that pass into the small intestine where the onchosphere emerges and migrates to the peritoneal cavity via the liver. Multiple oval cysts are found in the mesentery (see Plate 36). The cysts contain the inverted scolex of the tapeworm. Heavy infections cause abdominal discomfort and distension. In severe cases, they can cause intestinal obstruction. Migration through the liver results in the development of fibrous tracks and necrotic foci. Coenurus serialis is the larval stage of Taenia serialis, which is a tapeworm that affects dogs and foxes. A variety of mammals can act as intermediate hosts, usually wild rabbits and hares, but primates and even man can host the intermediate stage. Onchospheres from this tapeworm migrate to the subcutaneous tissue where they form cysts that are palpated as soft swellings under the skin. The cyst contains fluid and inverted secondary buds, each containing a scolex. Occasionally a cyst may be found in the orbit where it causes a retrobulbar swelling (Wills, 2001). Echinococcus granulosus affects dogs and foxes. Most mammalian species, including man and rabbits, can act as intermediate hosts. The adult tapeworm is small in comparison to other tapeworms. It measures 2-9 mm. Onchospheres from ingested eggs migrate to the liver or the lung via the mesenteric blood vessels. The onchosphere then develops into a huge cyst that is able to produce secondary buds, each with an inverted scolex that can produce daughter cysts. The daughter cysts can, in turn, produce daughter cysts with the result that a huge cyst full of smaller cysts develops. Rupture of the cyst seeds the surrounding tissues with smaller cysts, all of which are capable of developing. The rabbit can also be a primary host for tapeworms. The cestode species varies in wild rabbits from different parts of the world. An example is Cittotaenia ctenoides that has a free-living mite as its intermediate host. Key points 16.1 • There is a wide range of infectious diseases that affect rabbits throughout the world • Infectious and parasitic diseases are common in wild rabbits and colonies of commercial or laboratory rabbits but relatively rare in the individual pet • In pet rabbits, flea infestations are usually transmitted from other household pets such as dogs or cats • The rabbit louse Haemodipsus ventricosus can be found in wild rabbits and is occasionally found in domestic rabbits • Several mites affect rabbits. Psoroptes cuniculi, Cheyletiella parasitovorax and Leporacus gibbus are the most common in domestic rabbits • The warble flies, Cuterebra horripilum and C. buccata that affect rabbits do not occur in the UK • With the exception of cestodes and Passalurus ambiguus, endoparasite infestations in domestic rabbits are rare • Passalurus ambiguus is a small, thread-like worm that can be seen in the faeces of affected animals. It inhabits the caecum and colon. It is not usually pathogenic. The life cycle is direct • Obeliscoides cuniculi occurs in wild rabbits in various parts of the world and in domestic rabbits in the USA • The rabbit is the intermediate host for several tapeworms that affect dogs and cats. Pet rabbits that graze in gardens inhabited by pet dogs or visited by foxes can become infected • Multiple oval cysts of Cysticercus pisiformis may be found in the mesentery • Onchospheres from Coenurus serialis migrate to the subcutaneous tissue where they form cysts that may be palpated as soft swellings under the skin • Onchospheres from Echinococcus granulosus can develop into huge cysts in the liver that are able to produce secondary buds, each with an inverted scolex that can produce daughter cysts • In some parts of the world rabbits are the primary hosts to some tapeworms. Infection is unlikely in domestic rabbits in the UK. 16.4 Protozoa 16.4.1 Coccidiosis There are as many as 14 species of Eimeria which affect rabbits and vary in pathogenicity. Coccidiosis can be a serious problem of rabbit colonies. The disease is described in Section 10.10.1. Eimeria magna and Eimeria irresidua are the two most pathogenic species that affect the intestine. Other less pathogenic species include E. perforans, E. media, E. elongata, E. neoloporis, E. intestinalis, E. caecicola and E. piriformis. Eimeria steidae causes hepatic coccidiosis and has a slightly different life cycle from the intestinal Eimeria species. Oocysts can survive for many years in the environment but are susceptible to dry conditions. Recovered rabbits become immune to infection. 16.4.2 Encephalitozoon cuniculi Encephalitozoon is an obligate intracellular protozoan parasite. It belongs to the Microsporidia genus that is a member of the subphylum Sporozoa. Microsporidia are characterized by having small spores and one polar capsule. There are several Encephalitozoon species (e.g. E. intestinalis, E. hellum, E. bieneusi, E. septata) most of which are opportunist pathogens in immunocompromised humans. Diarrhoea, renal disease and keratoconjunctivitis are among the diseases that have been associated with encephalitozoonosis in humans. In animals, Encephalitozoon cuniculi is the most important member of the Microsporidia genus. E. cuniculi primarily affects rabbits but can be found in other species. Microsporidia are unusual in that they lack mitochondria, presumably gaining their nutrition from the host cells (Pakes and Gerrity, 1994). They are characterized by a firm capsule that is strongly gram-negative (Owen, 1992). A long polar filament is neatly coiled within it. The spore has a polar cap. Infection of the host usually occurs by oral ingestion of food contaminated with infected urine. Once in the alimentary tract, the spore comes in close contact with the mucosa and infects a host cell by extruding the polar filament. Sporoplasm is transferred through the polar filament into a vacuole in the host cell where multiplication takes place. Dividing organisms are lined up along the vacuolar membrane that is thought to be of host origin (Pakes and Gerrity, 1994). The cells of the reticuloendothelial system are among those that are invaded and they distribute the parasite around the body. Eventually the organisms develop into mature spores that are oval in shape and measure approximately 2.5 × 1.5 μm with a thick cell wall (Pakes and Gerrity, 1994). The vacuole becomes distended and the cell eventually ruptures releasing spores that invade new cells. Rupture of the cells is associated with an inflammatory response (Pattison et al., 1971). Chronic inflammation results in the development of granulomatous lesions in target organs, primarily the kidney and brain, although the liver may be involved (see Plates 26 and 31). Myocarditis has also been reported (Pakes and Gerrity, 1994). Clinical signs are associated with granulomatous encephalitis or nephritis, notably vestibular disease and chronic renal failure. E. cuniculi can also cause lens rupture, pyogranulomatous uveitis and cataracts in rabbits (see Section 11.7.3.1 and Plate 24). In utero infection of the lens in the developing embryo occurs and causes the lens to rupture in later life (Stiles et al., 1997). Spores of E. cuniculi are shed in the urine of infected rabbits and transmit infection between individuals. The infection can be experimentally transmitted to rabbits by both the oral and tracheal route and young rabbits can be infected by their dam in the first few days of life. There appears to be maternal transfer of immunity to newborn rabbits (Bywater and Kellett, 1979; Lyngset, 1980). It has been suggested that ecto- and endoparasites also play a role in the transmission of E. cuniculi (Pakes and Gerrity, 1994). Following ingestion or inhalation, spores pass via infected mononuclear cells into the systemic circulation. Initially, target organs are those of high blood flow, such as the lungs, liver and kidney (Percy and Barthold, 1993) with infection of nervous tissue taking place later on in the course of the disease. An antibody response is initiated soon after infection. Antibodies to E. cuniculi can be demonstrated at least 2 weeks before intracellular organisms are demonstrated and 4 weeks before histopathological changes are seen in the kidney or organisms in the urine. Histopathogical changes in the brain are observed over 8 weeks after seroconversion (Cox and Gallachio, 1978). In vitro studies of the effects of immune and non-immune rabbit serum on E. cuniculi suggest enhanced phagocytosis of the parasite by macrophages in immune animals (Niederkorn and Shaddock, 1980). Serum antibody levels become detectable 3-4 weeks after infection, reaching high titres 6-9 weeks post-infection. Spores can be seen in the urine 1 month after infection and are excreted in large numbers up to 2 months post-infection. Shedding of spores is essentially terminated by 3 months post-infection (Percy and Barthold, 1993). Spores of E. cuniculi survive for less than 1 week at 4°C but remain viable for at least 6 weeks at 22°C. 16.4.2.1 E. cuniculi in other species E. cuniculi can infect a number of mammalian species with predilection sites and disease variation between hosts. Infections have been reported in rabbits, mice, guinea pigs, hamsters, dogs, cats, monkeys and man. There are no morphological or immunological differences between strains of E. cuniculi affecting laboratory animals. A serological survey of stray dogs showed antibodies in 13.3% (Hollister et al., 1989). Encephalitozoonosis has also been reported in birds (Poonacha and Stamper, 1985). Guinea pigs housed with infected rabbits were found to be at more risk than those housed separately in a survey by Gannon (1980). Nephritis was common but cerebral granulomas were not seen in the guinea pigs. E. cuniculi has been described in a wild rabbit in 1955 (Pakes and Gerrity, 1994) but more recent serological surveys have failed to find evidence of infection in wild rabbits, although they can be infected experimentally (Cox et al., 1980; Cox and Ross, 1980). It has been suggested that the natural hygiene habits of wild rabbits significantly decrease post-natal infection. 16.4.2.2 Zoonotic potential of E. cuniculi Although E. cuniculi can infect a range of hosts, severe systemic disease is rare in other species except in athymic or immunosuppressed mice and neonatal dogs or foxes. Athymic mice do not develop a cellular or humoral response to the parasite and masses of spores are found in the liver and other viscera (Gannon, 1980). E. cuniculi has been recognized as an opportunistic pathogen in human patients with acquired immunodeficiency syndrome (AIDS) in which it can cause interstitial pneumonitis, diarrhoea and wasting (Deplazes et al., 1996; Joste et al., 1996). Experimental infection of rabbits with E. cuniculi cultures administered into the rectum with a catheter after weeks of repeated colonic enemas resulted in E. cuniculi infection with hepatic lesions predominating rather than the typical brain and kidney changes (Fuentealba et al., 1992). 16.4.2.3 Clinical signs associated with E. cuniculi infection in rabbits E. cuniculi was first described in 1922 in rabbits exhibiting hind leg paralysis and other neurological signs. Kimman and Akkermans (1987) described an outbreak in a colony of laboratory rabbits that resulted in heavy losses. Affected animals showed muscular weakness, emaciation, polydypsia, polyuria and occasional neurological signs. Other texts describe encephalitozoonosis as a chronic, latent disease of rabbits that is significant because of its effects on experimental results. Infection with E. cuniculi in laboratory rabbits has caused many problems to scientific studies. Subclinical infection has vitiated experimental results and lesions caused by the parasite have been wrongly attributed to a number of other ailments (Wilson, 1979). Encephalitozoonosis can interfere with test results. Blood samples of rabbits with spontaneous encephalitozoonosis have been shown to have significantly lower levels of catecholamines than healthy rabbits (Levkut et al., 1997). Nowadays, laboratory rabbits are screened for E. cuniculi and seropositive animals eliminated. Encephalitozoonosis is widespread in pet rabbits. There is a range of manifestation signs from acute neurological disaster to latent infections that do not exhibit clinical signs of disease. In Germany, a serological survey of 277 pet rabbits showed that 41% were seropositive (Ewringmann and Göbel, 1999). Of the seropositive rabbits, 51 (40.8%) showed clinical signs of encephalitozoonosis. In the UK, a random survey of 30 pet rabbits revealed eight seropositive individuals (Carmichael, Idexx and Harcourt-Brown, unpublished data). After the animals had been found to be seropositive, the owners were questioned and four reported vague symptoms such as head nodding or swaying at rest, deafness or impaired mental ability. When clinical signs occur, they are usually associated with granulomatous lesions in the brain, kidney or lens although the liver, heart and other organs can be affected. In the German survey of 277 rabbits, 51 (40% of the seropositive animals) showed signs relating to infection. Twenty-three rabbits suffered from CNS disorders, 16 from renal disease and seven with uveitis. Two rabbits had both CNS and renal disease and three animals had CNS symptoms, renal disease and uveitis (Ewringmann and Göbel, 1999). Renal disease associated with E. cuniculi is described in Section 14.5.1 and ocular disease in Section 11.7.3.1. 16.4.2.4 Diagnosis of E. cuniculi The definitive diagnosis of E. cuniculi as a cause of disease can be problematical. In the live animal, evidence of uveitis can be seen in rabbits that have been infected in utero. At post-mortem examination, kidneys from infected rabbits show an obvious pitted appearance on gross examination due to areas of fibrosis (see Plate 31). There are no macroscopic lesions in the central nervous system, even on gross examination of the brain. Microscopic examination of tissues is required to confirm the diagnosis. Characteristic granulomatous lesions are seen in the brain, kidney and, occasionally, the liver. The microsporidial parasite may or may not be evident. Many diagnostic tests have been developed to detect antibodies to E. cuniculi in the live animal, including intradermal and a range of serological tests. Serological screening is used by some laboratories to identify and cull potentially infected animals to reduce interference with experimental results (Pakes and Gerrity, 1994). In the pet rabbit, a humoral response to E. cuniculi infection cannot be relied upon for accurate diagnosis. In laboratory rabbits, serum antibodies develop after 3 weeks and excretion of the parasite occurs 6 weeks after experimental infection with E. cuniculi (Cox et al., 1979). Passive immunity is transferred from infected dams to their offspring, which can have titres of 1:25 to 1:800 that last until they are about 4 weeks old. After a seronegative period, young rabbits seroconvert at 8-10 weeks of age in response to natural infection (Lyngset, 1980). Therefore the presence of antibodies only indicates exposure to the organism and does not confirm E. cuniculi as a cause of disease. The antibody titre or type of immune response could be helpful in deciding whether a positive result is indicative of disease but these tests are not available in the UK at the present time. Experimentally, high antibody titres have been found in rabbits showing signs of chronic infection (Pye and Cox, 1977). IgG titres reached a level of 160-2560 after a latent phase of 13-28 days in a study of rabbits experimentally infected with E. cuniculi (Kunstyr et al., 1986). Some of the rabbits showed an episodic humoral response and became seronegative after a few weeks. There was wide individual variability in antibody response but the authors suggested that differences in IgM and IgG could distinguish between recent and chronic infection. IgM seroconversion occurs at the beginning of the antibody response and simultaneous IgG and IgM detection suggest recent infection. E. cuniculi organisms can be found in the urine of infected animals (Pye and Cox, 1977). The spores are evident as ovoid, gram-positive organisms approximately 1.5-2.5 μm in size. Staining procedures using carbol fuchsin will stain the organisms a distinct purple colour (Percy and Barthold, 1993). Theoretically, urine examination is a means of confirming the presence of antigen in the live animal, although it is impractical as a routine diagnostic technique in general practice. Organisms are intermittently excreted and urine collection can be difficult. Normal rabbit urine often contains sediment. In humans, microsporidia can be detected by centrifuging urine and resuspending the sediment in sterile non-bacteriostatic saline (De Groote et al., 1995). The suspension is smeared on a slide and stained with Weber's chromotrope-based stain. A polymerase chain reaction (PCR) test has been used for detecting encephalitozoon DNA in human samples but is not available for veterinary use at the present time (De Groote et al., 1995). 16.4.2.5 Treatment of encephalitozoonosis Although the incidence and pathogenesis of E. cuniculi has been extensively reviewed in the scientific literature, there is a dearth of information about treatment. In colonies that screen for the disease, affected animals are culled and in colonies that do not screen, infection can be subclinical with no obvious sign of disease. It is for the individual pet rabbit that treatment is usually sought. Observant owners may notice clinical signs that would be overlooked in the colony situation and are reluctant to have their animals euthanased. Several treatment protocols have been suggested based either on basic principles of therapy for granulomatous encephalitis or on in vitro susceptibility of E. cuniculi organisms to various therapeutic agents. Some cases appear to improve spontaneously without treatment, presumably due to the host's immune response. In the absence of a simple diagnostic test for the presence of the antigen in the live animal, it is difficult to monitor the efficacy of therapeutic agents in eliminating the parasite. Antibody titres have been used as a guide to the progress of the disease but controlled studies are needed to evaluate their significance as prognostic indicators. Clinical signs are not only associated with the presence of the parasite but also the associated inflammatory response that persists after the organism is eliminated. Some data have been obtained from the treatment of AIDS patients who are able to describe their symptoms and can therefore be assessed more easily than pet rabbits. Parasite excretion has been monitored using PCR assays that are not generally available for pet rabbits. In general, E. cuniculi in pet rabbits is either treated with corticosteroids to suppress the inflammatory reaction or with albendazole or oxytetracycline, both of which kill the organism in vitro. The effect of various antimicrobial agents on E. cuniculi has been studied in vitro. One technique involves incubating infected fibroblasts with various drugs for 3 days before counting the parasitic foci. Albendazole was found to inhibit 90% of microsporidial growth using this technique, which led to the use of albendazole to treat infected human AIDS patients. A wide range of other drugs was also tested, including some that are available in veterinary medicine. Metronidazole, doxycycline, sulphonamides and itraconazole could not be evaluated because of their toxic effects on the fibroblast tissue culture (Beauvais et al., 1994). Fumigallin, an agent used to treat bees for nosematosis, was found to be effective against E. cuniculi as well as albendazole. Franssen et al. (1995) found that toltrazuril, metronidazole and itraconazole were ineffective in preventing spore formation in tissue cultures of E. cuniculi and confirmed the efficacy of albendazole and fumigallin. Thiabendazole and oxbendazole were also found to be effective against the organism in vitro. Albendazole is a benzimidazole anthelmintic available as an oral preparation for cattle and sheep. It has been used to eliminate the Encephalitozoon spp. from human AIDS patients, sometimes with dramatic success (De Groote et al., 1995). Elimination of the parasite is accompanied by relief of clinical symptoms in humans. Eradication of the parasite has been confirmed at autopsy (Sobottka et al., 1995; Joste et al., 1996). Albendazole has also been used to treat clinical cases of E. cuniculi in pet rabbits with no reports of adverse effects and apparent improvement in clinical symptoms. The pharmacokinetic effects of the agent have been tested on rabbits (Li et al., 1995). An empirical course of 3-10 days treatment appears to be beneficial. In-contact rabbits should be treated as a precaution although albendazole is potentially teratogenic and is not advisable in breeding females. Oxytetracycline has also been used to treat clinical cases of encephalitozoonosis (Ewringmann and Göbel, 1999). Fenbendazole is effective against Encephalitozoon species in vitro. Fenbendazole has been shown to be effective in preventing experimental infection of E. cuniculi in laboratory rabbits and for eliminating the spores from the central nervous system of naturally infected rabbits (Suter et al., 2001). Fenbendazole was given at a dose rate of 20 mg/kg daily for up to 4 weeks. 16.4.3 Toxoplasma gondii In common with all mammals, rabbits can be infected with Toxoplasma gondii although infection is usually subclinical. Ingested sporulated oocysts hatch in the duodenum. Sporozoites invade neighbouring cells and are dispersed throughout the body via the blood and lymphatics. Once the host immune responses are established, the organisms can be found as cysts in various tissues where they can remain for years (Owen, 1992). The source of infection for rabbits is feed contaminated by cat faeces and symptoms have been described in rabbits that grazed an area frequented by cats. Clinical signs are most common in the acute phase in young rabbits. Sudden anorexia, pyrexia and death are the usual signs, although CNS symptoms such as posterior paralysis or seizures can also occur (Leland et al., 1992). Outbreaks have been described in commercial rabbits (1Harcourt, 1967; Okerman, 1988). High antibody titres have been found in wild rabbits collected from sewerage farms in Australia (Cox et al., 1981). Positive serology only indicates exposure to infection. Gustaffson et al. (1997) compared the difference in susceptibility to toxoplasmosis between two lagomorphs; the mountain hare (Lepus timidus) and the domestic rabbit (Oryctolagus cuniculus). Domestic rabbits were found to be resistant to toxoplasmosis in comparison with the mountain hare. In the mountain hare, toxoplasmosis is acutely fatal and characterized by necrosis and tissue damage in the small intestine, mesenteric lymph nodes and liver. In the domestic rabbit, lesions are mild consisting of focal accumulations of mononuclear cells, mainly in the liver and heart. Histopathology is diagnostic. Antibodies are detected early as 7-8 days post-infection (Gustaffson et al., 1997). Key points 16.2 • Domestic rabbits are susceptible to a variety of protozoan diseases including coccidiosis, Encephalitozoon cuniculi, Toxoplasma gondii, Cryptosporidia, Giardia and Sarcocystis • E. cuniculi is an intracellular protozoan parasite. It is spread through urine • Sporoplasm from ingested spores is transferred to cells of intestinal mucosa. The parasite is then distributed throughout the body by the reticuloendothelial system • The predilection sites for E. cuniculi are the brain and kidney. In utero, the lens is another predilection site • Granulomatous encephalitis, chronic renal insufficiency and phacoclastic uveitis are among the clinical syndromes associated with encephalitozoonosis. Vestibular disease is the most commonly recognized manifestation • Multiplication of spores within infected cells takes place until, eventually, the cell ruptures releasing spores that can invade neighbouring cells • Cell rupture is associated with an inflammatory response and the development of granulomas • In the kidney, spores are released into the urine to infect other animals • E. cuniculi is uncommon in wild rabbits. It can affect other mammals and birds, especially if they are immunosuppressed. Serological studies have demonstrated antibodies to E. cuniculi in dogs • E. cuniculi is potentially zoonotic although there are no reports of infections in healthy individuals. Immunosuppressed humans such as AIDS patients are susceptible • An antibody response occurs in rabbits and infected animals become immune. Serological testing can be used to detect exposure to infection • E. cuniculi is susceptible to a range of drugs in vitro. Albendazole has been used to treat human patients with success in eliminating the parasite • Albendazole is available and safe for use in rabbits although there are no data available at the present time about its efficacy. Dosage and duration of treatment is empirical. It is indicated to limit spread of infection to other rabbits • Oxytetracycline has been used to treat encephalitozoonosis in rabbits • Toxoplasmosis is rare in rabbits, but does occasionally occur • Although toxoplasmosis is potentially zoonotic, toxoplasma is only transmissable from rabbits to humans who handle or eat undercooked rabbit meat. Infection is not spread through rabbit faeces. Although toxoplasmosis is potentially zoonotic, toxoplasma is only transmissible from rabbits to humans who handle or eat undercooked rabbit meat. Infection is not spread through rabbit faeces. 16.4.4 Other protozoan parasites of rabbits Cryptosporidia species have been described in rabbits but not as a major cause of disease. Giardia duodenalis has also been reported in rabbits, although it does not appear to be pathogenic. A single outbreak of catarrhal enteritis in rabbits has been attributed to giardiasis. There is no evidence of transmission to humans (Pakes and Gerrity, 1994). Sarcocystis cuniculi affects rabbits although it is rarely reported in the European rabbit (Oryctolagus cuniculus). It is more commonly encountered in the cottontail (Sylvilagus floridanus). Sarcocystis forms cysts in skeletal and cardiac muscle. The source of infection is believed to be cats. 16.5 Bacterial diseases 16.5.1 Pasteurellosis Pasteurella multocida is a very small, non-motile, gram-negative, ovoid, coccoid or short rod that shows bipolar staining. It is aerobic and facultatively anaerobic. The organism forms circular, convex smooth colonies on blood agar after 24 h incubation. The colonies are generally 2-2.5 mm in diameter and slightly iridescent, although variations can occur. The colonies are mucoid in appearance. There are multiple antigenic strains of P. multocida associated with different species of animal. The organism is potentially pathogenic to a variety of animals. It can also be found as a commensal organism, for example P. multocida has been isolated from the tonsils of healthy dogs and from the respiratory tract in humans. In rabbits, P. multocida can reside in the nasal cavity without causing disease. In pet rabbits that are kept individually or in small numbers, P. multocida seldom causes primary disease, although the bacterium is often found as a secondary pathogen in any purulent or suppurative condition. In colonies of rabbits kept for breeding, meat and fur production, or for laboratory purposes, pasteurellosis is a serious, infectious disease. Disease occurs when predisposing factors give the bacteria the opportunity to multiply uncontrollably and overwhelm the physiological and immunological defences of the respiratory tract. During these episodes, clones of virulent bacteria increase which are easily transmitted to neighbouring animals. The protein pattern of the outer membrane of P. multocida shows a relationship between the protein type and the animal host. Bacterial capsular polysaccharides inhibit phagocytosis. Bacterial lipopolysaccharides confer resistance to complement and bactericidal activity of serum (Deeb, 1993). There are several capsular and somatic serotypes of P. multocida that are pathogenic for domestic livestock and poultry, but only a few are pathogenic for rabbits. Serotyping entails the identification of the capsular antigen and serotypes. In rabbits, serotypes 12:A, 3:A and 3:D are the usual types identified (Percy and Barthold, 1993). Snuffles is most frequently associated with 12:A, whereas 3:A and occasionally 3:D are more frequently associated with disease of the lower respiratory tract. Virulence of infection varies between serotypes. Pasteurella multocida produces an endotoxin that varies with serotype. The role of the endotoxin in clinical disease is unclear, although it may be significant in septicaemic cases. The bacteria also produce adhesins which adhere the bacteria to epithelial tissue. Filamentous appendages elaborated by the bacteria may help P. multocida colonize mucous membranes (Deeb, 1993). The adhesive properties vary with different serotypes of P. multocida and could be important in the pathogenesis of the disease (Manning et al., 1989). Mucosal antibodies (IgA) inhibit growth of bacteria and are produced in response to exposure to P. multocida. High humoral (IgG) antibody levels are associated with chronic infection and have been used to identify infected rabbits in laboratory colonies (Deeb, 1993). 16.5.1.1 Epidemiology When sufficient numbers of P. multocida bacteria are transmitted between rabbits, a subclinical infection is established in the upper respiratory tract. Bacteria become abundant in the mucous film covering the mucous membranes but are scarce in the sinuses (Whittaker, 1989). Clinical disease occurs when there is disruption of the balance between mucociliary clearance and bacterial proliferation. Pregnancy, parturition, lactation, poor husbandry, overcrowding, stress, nutritional deficiencies, genetic predisposition and bacterial serotype can affect the course of the disease which tends to be a greater problem in the colony rabbit than in the adult pet rabbit. P. multocida is spread to newborn rabbits shortly after birth from infected does that harbour infection in their nasal cavity. There are many predisposing factors in young rabbits, including the age of weaning, the presence of vaginal infection and the prevalence of infection within the colony. There appears to be genetic susceptibility to pasteurellosis. For example, Chinchilla rabbits appear to be more susceptible than Blue Beverans (Manning et al., 1989). The incidence of disease increases with age up to about 5 months of age. After colonization of the upper respiratory tract, infection extends to the rest of the respiratory tract and tympanic bulla and can cause clinical rhinitis, conjunctivitis, pneumonia, tracheitis, dacryocystitis or otitis media. Some rabbits remain asymptomatic despite the presence of P. multocida in the nares. Such individuals are carriers and infective to contact animals. Other animals are negative on nasal culture but harbour P. multocida in the tympanic bulla. Transmission of disease can occur between rabbits by direct contact and by airborne spread. Uninfected rabbits in direct contact with infected rabbits contract pasteurellosis within 8 days to 3 weeks (Manning et al., 1989). Physical separation of rabbits by a distance of a few feet will delay transmission of infection (Lelkes and Corbett, 1983). Fomite spread has been demonstrated and contaminated water supplies have been suggested as a source of infection (Whittaker, 1989). 16.5.1.2 Clinical signs of pasteurellosis P. multocida infection can be acute, subacute or chronic. There are several clinical syndromes associated with pasteurellosis. Surveillance of rabbits for pasteurellosis at a laboratory animal facility revealed the following syndromes in a decreasing order of magnitude: rhinitis, conjunctivitis, abscesses and otitis media (DiGiacomo et al., 1983) 16.5.1.3 Rhinitis (‘snuffles’) The colloquial term ‘snuffles’ refers to upper respiratory tract infections manifested by a serous followed by purulent discharge from the nose. Affected rabbits sneeze and cough and may have an audible upper respiratory noise or ‘snuffle’. ‘Snuffles’ is usually associated with P. multocida infection although other infectious agents such as Staphylococcus aureus can be involved. In pet rabbits, dental disease and nasal foreign bodies can cause similar signs (see Section 13.2.3). The thick sticky white discharge from the nose is wiped away with the forelegs leading to a yellow staining and matting of the fur. Poor husbandry, overcrowding, poor ventilation, dust conditions and ammonia buildup exacerbate the disease. Investigations of rhinitis in laboratory rabbits have shown that some rabbits can have rhinitis for up to 2 weeks before P. multocida is isolated from nasal swabs. Clinical signs wax and wane but symptoms often persist despite treatment. 16.5.1.4 Pneumonia P. multocida is a cause of pneumonia in rabbits. The disease can be acute and rapidly fatal. Chronic or subacute infections also occur in rabbits with no clinical signs. It is not unusual to find incidental pneumonic lesions during post-mortem examination of apparently healthy rabbits. Large abscesses can be present in the thoracic cavity. 16.5.1.5 Genital infection P. multocida can be recovered from the vagina in a relatively high percentage of carrier animals (Percy and Barthold, 1993) and the organ can act as a reservoir of infection. P. multocida can be spread during mating. Bucks may harbour infection in their genital tract. Orchitis, pyometra and genital infections can be manifestations of pasteurellosis. 16.5.1.6 Wound infections and abscesses P. multocida is often isolated from abscesses and infected bite wounds. The organism is present in the nasal cavity of many rabbits and can contaminate tissues during licking and grooming. It can also be spread haematogenously. P. multocida may be isolated from post-surgical wound breakdowns and can cause osteomyelitis after orthopaedic surgery (Leibenberg and Badger, 1984). P. multocida can be isolated from facial abscesses that result from periapical infection or tissue damage caused by elongated crowns in rabbit with dental disease. 16.5.1.7 Dacryocystitis P. multocida can cause dacryocystitis (Petersen-Jones and Carrington, 1988). The organism may be isolated from purulent infections of the nasolacrimal duct which can result from spread of infection from the nasal cavity or as secondary infections in ducts blocked by elongated tooth roots especially of the maxillary incisors. 16.5.1.8 Otitis media P. multocida can spread from the nasal cavity to the tympanic bulla via the eustachian tube. A common post-mortem and radiographic finding is the presence of inspissated pus in the deeper structures of the ear (see Plate 27). Infection can spread along the vestibulocochlear nerve and cause vestibular disease resulting in neurological signs such as rolling and nystagmus. 16.5.1.9 Detection of pasteurellosis Confirmation of pasteurellosis in rabbit colonies is required to limit the spread of disease. Clinical signs are indicative of infection but diagnostic tests are required to isolate the organism and detect subclinical carriers. A deep nasal swab is required for bacteriology. It can be difficult to obtain satisfactory swabs in the conscious animal and sedation or anaesthesia is required. Bacterial culture cannot always be relied upon. Infection can be deep within the nasal passages or in the paranasal sinuses and false negative results can occur. Some rabbits have already been treated with antibiotics. Pasteurella multocida does not survive well in transport media (Sanchez et al., 2000). It survives for less than 24 h at room temperature. Some strains of P. multocida grow best at 34–35°C, which is lower than most routine cultures. Serological tests and a polymerase chain reaction (PCR) test are available in the USA. A rising titre demonstrates exposure to infection. However, the presence of antibodies does not confirm the presence of active infection. Sanchez et al. (2000) conducted a study of a combination of bacterial culture, serology and PCR testing in rabbits with clinical signs suggestive of pasteurellosis. They found that the combination of PCR and serology was more useful than culture from nasal swabs. The authors concluded that there are other organisms, such as Bordetella, Pseudomonas and Staphylococcus spp. that cause clinical signs similar to those of pasteurellosis. 16.5.1.10 Control of pasteurellosis in rabbit colonies Pasteurellosis is a major problem in breeding, laboratory or commercial colonies of rabbits. The disease also presents problems in multi-rabbit households or in sanctuaries and rescue centres that house several rabbits in a small space. Stress, intercurrent disease, overcrowding, and poor air quality can trigger the flare up of latent infection. As with any infectious disease in an intensive situation, good husbandry is important in the control of the disease. Affected animals should be isolated and treated promptly or even culled, as they are a source of infection to other stock. Keeping the numbers down and minimizing contact between batches of rabbits reduces transmission of disease. In infected colonies, clinical disease can be minimized by separating newly weaned rabbits from adults and by carefully controlling the environment and reducing stress factors. A clean, dry, well-ventilated environment is required with no draughts. Rabbits can withstand cold but become stressed by high temperatures. Closed stuffy sheds increase the risk of disease especially if the air quality is poor due to ammonia buildup. Fluctuations of temperature should be avoided with an optimum temperature maintained at 16–20°C and humidity of 50-70% (Whittaker, 1989). Air quality should be good with around 20 air changes per hour and preferably a filter system. 16.5.1.11 Prevention of pasteurellosis Over the years, several control strategies for pasteurellosis have been tried in rabbit colonies with varying degrees of success. Many laboratory colonies are now disease free and are vigilantly barrier-housed to prevent the introduction of infection. Pasteurella-free stock is selected by placing rabbits in isolation for 2-4 weeks and repeatedly culturing the nasal passages. Rabbits with positive cultures or signs of rhinitis are culled. Surviving rabbits are bred from and after 3 years, the colony is considered to be disease free. Other methods of producing disease-free rabbits involve caesarean derivation with hand-rearing (Manning et al., 1989) or the transfer of fertilized ova to Pasteurella-free does. Early weaning and the use of antibiotics can increase the number of disease-free stock. To ensure an uninfected status, periodic serological testing for antibodies to pasteurella is necessary. Recently a polymerase chain reaction test has been developed that can be used to detect infection (Sanchez et al., 2000). Antibiotics have also been used prophylactically in an attempt to prevent pasteurellosis by administering them either in the feed or drinking water to pregnant does. There appears to be genetic resistance to pasteurella and attempts have been made to produce disease-free strains of rabbit. Vaccines against P. multocida are used successfully in other species such as sheep and attempts have been made to produce an effective vaccine against pasteurellosis in rabbits. Both live and dead vaccines have been used and found to be effective in reducing mortality and clinical disease caused by a homologous strain of the bacteria. Most pathogenic strains from rabbits carry somatic antigens 3 and 12 and are capsule type A or D. Cross-immunity is higher between strains of the same serotype. However, despite promising results in laboratory rabbits (DiGiacomo et al., 1987), protection against nasal colonization and clinical disease caused by heterologous strains is incomplete and the results of field trials using an intranasal vaccine against A:12 have been disappointing (DiGiacomo and Deeb, 1989). There is a belief among some rabbit breeders that vaccination is feasible with either an autogenous vaccine or a vaccine produced for use against pasteurellosis in other species such as sheep or cattle. Claims of success with these vaccines are difficult to evaluate. 16.5.1.12 Treatment of pasteurellosis Treatment of pasteurellosis depends on the clinical symptoms and the type and emotional or financial value of the rabbit that is suffering from the disease. The treatment of abscesses, respiratory tract infections, dacryocystitis and vestibular disease is covered in other chapters. 16.5.2 Staphylococcus aureus Staphylococcus aureus causes suppurative inflammation. The organism is frequently isolated from infected sites in rabbits. It can also cause a fatal septicaemia. Like P. multocida, healthy rabbits can carry S. aureus in the nasal cavity. It can also be isolated from the conjunctiva and skin of healthy rabbits. S. aureus may be isolated from cases of mastitis, ulcerative pododermatitis, rhinitis, conjunctivitis, dacryocystitis, abscesses and skin infections. It is often a secondary invader in tissues damaged by trauma or some other predisposing cause. The severity of disease is governed by host resistance and bacterial virulence (Delong and Manning, 1994). In rabbit colonies, staphylococcosis can cause serious losses. 16.5.3 Bordetella bronchiseptica Bordetella bronchiseptica has been isolated from a variety of animal species including pigs, rats, dogs, cats, guinea pigs and rabbits. In rabbits, B. bronchiseptica appears to be relatively non-pathogenic although it has caused localized suppurative bronchopneumonia in laboratory rabbits treated with cortisone prior to nasal inoculation of the organism. B. bronchiseptica can cause serious upper respiratory tract infection in guinea pigs. Isolates of B. bronchiseptica from different species have been typed according to their bacterial sensitivity and investigations suggest that infected rabbits and guinea pigs can infect each other (Boot et al., 1995). Many texts recommend that the two species should not be housed together because of the risk of cross-infection although actual reports of this are rare. 16.5.4 Tyzzer's disease Tyzzer's disease is caused by a large pleomorphic, gram-negative, spore forming, obligate intracellular bacterium that is flagellate and therefore motile (Delong and Manning, 1994). The bacterium cannot be grown in vitro but can be grown in tissue culture. The bacterial genome is closely related to Clostridium species and, in recent years, the organism has been reclassified as Clostridium piliforme rather than Bacillus piliformis (Besch-Williford, 1997). Tyzzer's disease can affect a wide range of animals including rodents, cats and monkeys (Delong and Manning, 1994). The disease affects the caecum, intestine and liver causing acute diarrhoea and sudden death in the acute stage and intestinal fibrosis, stenosis and liver necrosis in chronic cases. The myocardium can also be affected. The disease usually occurs in weanling rabbits 6-12 weeks old but can occur at any age and is often predisposed by stress. Recent advances in tissue culture have led to development of diagnostic tests and serological testing is now possible in some countries. The presence of antibody in apparently healthy animals suggests latent infection of the intestinal tract. Stress or immunosuppression can precipitate overt disease (Delong and Manning, 1994). Transmission occurs by ingestion of spores that can survive in the environment for some time after an infected animal has been removed. Overcrowding, stress, low dietary fibre and transport predispose to clinical disease. Supportive treatment and antibiotic therapy are generally unrewarding. 16.5.5 Salmonellosis Salmonella organisms can be carried by wild rodents that contaminate food and water. The clinical signs can range from asymptomatic carriers to diarrhoea, emaciation and death. No successful treatment has been described. 16.5.6 Escherichia coli Escherichia coli is generally absent from the gut flora in rabbits. However, E. coli can cause enteritis, especially in suckling rabbits, and is an important cause of enteritis and death in rabbit colonies. An association has been made between colibacillosis and intestinal coccidiosis, which enhances E. coli proliferation. There is variation in pathogenicity between strains of E. coli and a large number of strains have been isolated from outbreaks of enteritis. An ‘attaching and effacing’ strain has been identified in the UK with reported mortality rates of 25-75% (Dannatt et al., 2000). This organism attaches closely to caecal epithelial cells. 16.5.7 Clostridial enterotoxaemia Clostridia are anaerobic gram-positive bacilli capable of producing powerful enterotoxins which can produce severe enteric disease. Clostridial enterotoxaemia is usually fatal. Small numbers of Clostridia spp. are normal inhabitants of the gut flora of rabbits. Clostridium spiriforme, Clostridium difficile and Clostridium perfringens can cause enterotoxaemia in rabbits (see Section 10.10.2). Weanling rabbits are most commonly affected. Clostridium spiriforme produces an iota toxin. Glucose is required as a substrate for iota toxin formation. High dietary starch levels are believed to predispose to enterotoxaemia by causing ‘carbohydrate overload’ of the caecum. Residual starch that reaches the caecum can be broken down to release glucose as a substrate for iota toxin formation. This situation is more likely to occur in juvenile rabbits rather than adults. Immature rabbits do not digest starch efficiently in the small intestine, but in adult animals starch is broken down and absorbed before it reaches the caecum. In adults, enterotoxaemia is usually related to other factors such as stress or antibiotic therapy, which disrupt the caecal microflora and allow Clostridia spp. to proliferate. 16.5.8 Other causes of bacterial enteritis Vibriosis and Campylobacter have been reported as causes of enteric disease in rabbits. A syndrome known as ‘histiocytic enteritis’ has been reported in Japan. Adenoviruses, parvoviruses, rotaviruses, coronaviruses and Herpes-like viruses have been isolated from outbreaks of enteric diseases of rabbit colonies. These infections are unlikely to be encountered in the adult pet rabbit. Percy and Barthold (1993) and DiGiacomo and Mare (1994) give detailed accounts of these infections. 16.5.9 Treponematosis Treponema cuniculi is a specific pathogen of rabbits. It is a spirochaete that causes crusty, inflammatory lesions on the genitalia and face (see Plate 10). It is sexually transmitted (see Section 9.13). Young rabbits can be infected during their passage through the birth canal. The disease is also known as venereal spirochaetosis or ‘rabbit syphilis’. Treponematosis is endemic in some breeding colonies and is occasionally encountered in the pet rabbit. 16.5.10 Listeriosis Listeria monocytogenes infection is uncommon in rabbits. It is characterized by abortion and sudden death. Contaminated feed can cause outbreaks in breeding colonies. L. monocytogenes has a predilection for the gravid uterus in advanced pregnancy. Infection can cause abortion, stillbirths and death of the doe. Post-mortem signs include straw-coloured fluid in the peritoneal cavity, disseminated pale miliary foci on the liver and visceral congestion. Fibrinous exudate and ecchymosis can be seen on the serosal surface of the uterus. 16.5.11 Paratuberculosis (Johne's disease) Paratuberculosis, caused by Mycobacterium paratuberculosis, affects many species, especially ruminants. It is characterized by diarrhoea, emaciation and loss of bodily condition and most animals become infected as neonates through the ingestion of contaminated milk or water. Clinical infection becomes apparent after a prolonged subclinical phase that can last for several years. Although the disease is most often reported in ruminants, monogastric animals have been infected experimentally without evidence of clinical disease. Oral infection of newborn rabbits can produce intermittent diarrhoea and granulomatous enteritis similar to that observed in cattle. In Scotland, the high incidence of paratuberculosis in wild rabbits has been linked with a high prevalence of infection in cattle. A survey of wild rabbits revealed that 67% were infected with Mycobacterium paratuberculosis (Greig et al., 1997). Epidemiological studies found an association between the infection in wild rabbits and a history of Johne's disease on the farms where the rabbits were caught (Greig et al., 1999). Mycobacterium avium subspecies paratuberculosis was also isolated from foxes and stoats collected from affected farms (Beard et al., 1999). In the wild rabbits affected with paratuberculosis, general body condition was good although a proportion of them had thickened areas of intestinal mucosa with occasional granuloma. Large numbers of intracellular acid-fast bacilli were present in the lesions. 16.5.12 Pseudotuberculosis Pseudotuberculosis, caused by Yersinia pseudotuberculosis, is a common infection in rodents, especially guinea pigs. In rabbits, the disease is usually encountered in wild animals although it has been described in captive ones. Affected rabbits suffer from a wasting disease, a dull coat and occasional diarrhoea. Nodular swelling of the liver may be detected on abdominal palpation (Wood, 1978). Yersinia pseudotuberculosis can be isolated from faeces or caecal contents. Lesions of pseudotuberculosis include large areas of caseous necrosis in the mesenteric lymph nodes, liver and spleen. Necrosis of Peyer's patches in the small intestine and caecum may be found. The disease may also involve other organs such as the liver and spleen (DeLong and Manning, 1994). Yersiniosis is associated with vermin and control of mice and rats is required (Okerman, 1988). 16.5.13 Tularaemia Tularaemia is an acute septicaemic disease caused by Francisella tularensis. It is common in wild rabbits and hares but is seldom encountered in domestic rabbits. The organism can affect many vertebrate species and has zoonotic potential. Most human cases that have been linked to rabbits have followed exposure to the cottontail (Sylvilagus floridanus). According to Delong and Manning (1994), there have been no reported human cases of tularaemia acquired from Oryctolagus cuniculus. 16.5.14 Lyme disease Lyme disease is an acute, often recurrent polyarthritis of dogs and humans caused by a spirochaete Borrelia burgdorferi. It is a tick-borne disease. Cottontail rabbits (Sylvilagus floridanus) have been shown to have antibodies to Borrelia burgdorferi in areas where rabbit-feeding Ixodes are abundant (Telford and Speilman, 1989). Key points 16.3 • Pasteurella multocida is a very small non-motile, gram-negative, ovoid, coccoid or short rod that shows bipolar staining. It is aerobic and facultatively anaerobic • P. multocida forms circular, convex smooth colonies on blood agar after 24 h incubation. The colonies are generally 2-2.5 mm in diameter and slightly iridescent although variations can occur. The colonies may be mucoid in appearance • There are several serotypes of P. multocida that are pathogenic for rabbits. Snuffles is most frequently associated with 12:A, whereas 3:A and occasionally 3:D are more frequently associated with disease of the lower respiratory tract • Clinical disease occurs when there is disruption of the balance between mucociliary clearance and bacterial proliferation • Pregnancy, parturition, lactation, poor husbandry, overcrowding, stress, nutritional deficiencies, genetic predisposition and bacterial serotype can affect the course of pasteurellosis, which tends to be a greater problem in the ‘colony’ rabbit rather than in the adult pet rabbit • Physical separation of rabbits by a distance of a few feet will delay transmission of infection. Fomite spread can occur • P. multocida can be isolated from a number of clinical conditions of rabbits. Rhinitis, sinusitis, dacrocystitis, pneumonia, otitis media, otitis interna, abscesses and genital tract infections are all manifestations of pasteurellosis • A deep nasal swab is required for bacteriology. Bacterial culture cannot always be relied upon because of false negative results and presence of antibiotics in rabbits that have already been treated • Serological tests for pasteurellosis and a polymerase chain reaction (PCR) test are available in the USA • Pasteurellosis is a major problem in colonies of rabbits. Affected animals are a source of infection to other stock. Keeping the numbers down and minimizing contact between batches of rabbits reduces transmission of disease. Stress can trigger latent infections to flare up • Clinical disease can be minimized in infected colonies by separating newly weaned rabbits from adults and by carefully controlling the environment and reducing stress factors • Fluctuations of temperature should be avoided with an optimum temperature maintained at 16–20°C and humidity of 50-70%. Air quality should be good with around 20 air changes per hour and preferably a filter system • Other bacterial infections of rabbit colonies include Staphylococcus aureus, Bordetella bronchiseptica, Clostridium piliformis (Tyzzer's disease), Salmonella, E. coli, clostridial enterotoxaemia, Campylobacter, Treponema cuniculi, Listeria monocytogenes, Pseudomonas, Fusiformis and Corynebacterium spp • Wild rabbits can be infected with Mycobacterium paratuberculosis (paratuberculosis, Johne's disease), Yersinia pseudotuberculosis (pseudotuberculosis), Francisella tularensis (tularaemia) and Borrelia burgdorferi (Lyme disease). 16.5.15 Non-specific bacterial infections There are many other bacterial infections of rabbits. They are associated with stress, overcowding, injuries, reproduction, poor husbandry and intercurrent disease. Examples include Pseudomonas, Fusiformis and Corynebacterium. 16.6 Viral diseases 16.6.1 Myxomatosis Myxomatosis is a fatal disease of the European rabbit (Oryctolagus cuniculi). It is characterized by subcutaneous swellings that exude a mucoid secretion when sectioned. Lesions occur around body orifices and on the face especially on the eyelids. Pet rabbits can contract the disease by direct contact with infected wild rabbits or via insect vectors. The disease is mainly spread by arthropods, especially the European rabbit flea Spilopsyllus cuniculi. In wild rabbits, outbreaks of myxomatosis wax and wane according to the virulence of the strain and the immune status of the native rabbit population. 16.6.1.1 History of myxomatosis Myxoma virus was one of the first viruses to be discovered. It affected a group of laboratory rabbits in Uruguay in 1896 (Fenner and Fantani, 1999). In 1927, Aragao recognized virus particles in stained smears and called attention to its close resemblance with smallpox and fowlpox. Myxoma virus was later classified as a pox virus (Fenner and Ross, 1994). Brazilian workers found that the virus is transmitted mechanically by fleas and mosquitoes. Myxomatosis is now an endemic disease of wild rabbits throughout Europe. It was first recognized in England in 1953 after it crossed the channel from France where it was illegally introduced in 1952. Prior to this, in 1952, infected rabbits had been released into the Heisker Islands in the Outer Hebrides as a deliberate experiment in pest control. Two years later, in 1954, the rabbit population was as large as ever despite the considerable mortality that resulted from myxomatosis (Fenner and Fantani, 1999). Although there were efforts to eradicate myxomatosis in the UK, the disease spread rapidly through the wild rabbit population in the summer of 1953 and was endemic by the late 1950s. The attitude to myxomatosis in the UK was different from other parts of the world. Rabbits were frequently kept as pets and there was outcry at the sight of blind, sick rabbits stumbling along roads or on commons and other public places. As a result, in 1954, it became an offence knowingly to use or permit the use of an infected rabbit to spread the disease into an uninfected population. This law was difficult to enforce. 16.6.1.2 Epidemiology of myxomatosis Myxoma virus causes a trivial infection in its natural host, either Sylvilagus brasiensis (Tapeti, Forest rabbit, found in Mexico or Argentina) or Sylvilagus bachmani (Brush rabbit) which is native to California. In the European rabbit Oryctolagus cuniculi, myxoma virus causes a serious and life-threatening disease. Myxomatosisis can occur in hares but infection is rare and usually mild. There are different strains of myxomatosis that affect wild rabbits, e.g. the Standard Laboratory (Moses) strain and the Lausanne strain, which is more virulent. The Standard Laboratory strain produces relatively flat skin lesions in contrast to the protuberant lesions produced by the Lausanne strains (Fenner and Ross, 1994). Some variants are associated with fewer and smaller skin lesions but cause massive pulmonary oedema. In field conditions, myxomatosis is spread by insect vectors especially fleas and mosquitoes, although any insect that penetrates the skin will transmit the disease. The disease can also be spread directly between rabbits by contact or inhalation. The virus persists in hutches that have been contaminated with fluid from lesions from infected rabbits and will infect unvaccinated rabbits that are put into them. Cheyletiella parasitovorax can act as a vector in the spread of disease (Fenner and Fantani, 1999). The life cycle of the insect vector affects the pattern of disease outbreaks and epidemiology of myxomatosis. Mosquitoes are the main vectors in many parts of the world. In those countries where myxomatosis is transmitted by mosquitoes, the disease spreads rapidly and is frequently encountered in pet rabbits housed in hutches. There is a high seasonal incidence. In the UK, disease outbreaks tend to remain localized with isolated pockets of infection and the disease is only sporadically encountered in pet rabbits. The difference in epidemiology is attributed to the difference in the life cycle of insect vectors. In the UK, the European rabbit flea, Spilopsyllus cuniculi, is the major insect vector rather than mosquito species Aedes and Anopheles spp. Even in the absence of the host, fleas can maintain infectivity throughout the winter and act as a reservoir of infection for the following year. Fleas are an effective means of transmission due to their life cycle that is synchronized with the reproductive status of the doe and results in heavy flea infestations of susceptible neonates. Different strains of the myxoma virus show a variation in virulence. Rabbits infected with highly virulent strains die so quickly that the disease is not transmitted as readily as the less virulent strains. Environmental temperature also has an effect on mortality rates with the disease being more lethal at low temperatures. There is a genetic resistance to myxomatosis in some individuals. 16.6.1.3 Clinical signs of myxomatosis The pathogenesis of myxomatosis follows the same pattern as other pox virus infections (Fenner and Ross, 1994). Sequential replication of the virus takes place at the inoculation site and the regional lymph node. It is followed by cell-associated viraemia and generalized infection throughout the body. The disease starts with a skin lesion, which typically develops 4-5 days after inoculation of the virus and enlarges to become about 3 cm in diameter 9-10 days after infection. The rabbit is viraemic, with virus replication taking place throughout the lymphoid system. The eyelids become thickened and eventually the eyes are completely closed by the ninth day with a semipurulent ocular discharge. Secondary lesions develop throughout the body, typically on the nares, lips, eyelids and base of the ears and on the external genitalia and anus. Aerosol infection can result in pneumonic signs, which is a feature of outbreaks in intensive farmed rabbits. This syndrome is characterized by a longer incubation period (1-3 weeks) and accompanied by lacrimation and mucopurulent nasal discharge (Fenner and Fantani, 1999). Myxomatosis is accompanied by sterility and abandonment of litters. Myxomatosis is usually fatal due to inanation, secondary bacterial infection or in wild rabbits, predation. In rabbits that recover, inflammation of the testicles renders a buck infertile for up to 12 months (Fenner and Fantani, 1999). Very young rabbits are particularly susceptible to infection and die more rapidly than adult animals unless they have some passive immunity. Several factors determine whether rabbits survive or die from myxomatosis and how long they live after infection. Infected rabbits mount an immune response that can be detected by in vitro tests about 7 days after infection and reach peak levels by about 28 days (Fenner and Ross, 1994). Antibodies persist for prolonged periods and give absolute immunity for many months. Maternal transfer of antibodies takes place and immunity lasts for 4-5 weeks in baby rabbits. Some rabbits have a genetic resistance to infection, which has limited mortality rates in outbreaks in wild rabbits. Genetic resistance to infection varies between rabbit populations and countries. British rabbits were slow to develop resistance in comparison with Australian rabbits (Fenner and Ross, 1994). A phenomenon known as ‘paternal resistance’ is also described. It has been discovered that bucks mating within 7 months of infection sometimes confer partial resistance to progeny born to the mated doe within the following 7 months. Speculation about some immunogenic factor in semen has been made (Fenner and Ross, 1994). 16.6.1.4 Relationship of myxomatosis with Shope fibroma virus The viruses that cause myxomatosis are members of the Leporipoxvirus genus that cause fibromas in their natural hosts. The natural host of myxoma virus is not the European rabbit (Oryctolagus cuniculi) but the Forest rabbit (Sylvilagus brasiensis) or Brush rabbit (Sylvilagus bachmani) that are native to North or South America. Another important member of the Leporipoxvirus genus is rabbit fibroma virus (Shope fibroma virus), which naturally affects the cottontail (Sylvilagus floridanus). In the European rabbit (Oryctolagus cuniculi) Shope fibroma virus causes a benign fibroma. Shope fibroma virus is endemic in cottontails in the Eastern USA. It causes fibromas that remain localized but can persist for months. In newborn or immunocompromised individuals, generalized fibromatosis can occur (Fenner and Fantani, 1999). Like myxomatosis, Shope fibroma virus is spread by insect vectors. Transmission by mosquitoes occurs more readily than in the European rabbit. In situations where cottontails and mosquitoes are common, generalized fibromatosis can occur in adults because multiple mosquito bites produce a fibroma at each site (Fenner and Fantani, 1999). In the European rabbit (Oryctolagus cuniculi), fibromas caused by Shope fibroma virus regress within 3 weeks of inoculation. Abundant virus can be found in the superficial layers of fibromas caused by Shope fibroma virus in the natural host, Sylvilagus floridanus, in comparison with fibromas in the European rabbit (Oryctolagus cuniculi). Shope fibroma cannot be established as an enzootic disease in European rabbits but cross-immunity between Shope fibroma virus and myxomatosis occurs and European rabbits that have recovered from infection with Shope fibroma virus are immune to myxomatosis. 16.6.1.5 Immunization In common with other pox viruses, dead vaccines are unlikely to be effective and so a live vaccine is required to confer resistance to myxomatosis. Live attenuated strains of myxoma virus have been used for vaccination but problems have occurred with virulence and possible immunosuppression (Fenner and Fantani, 1999). The discovery of Shope fibroma virus and its cross-immunity with myxomatosis led to the development of a live vaccine containing Shope fibroma virus. The present day vaccine that is available in the UK (Nobivac Myxo, Intervet) is a live, attenuated freeze-dried virus vaccine containing Shope fibroma virus grown in cell-line tissue culture. Key points 16.4 • Myxomatosis is characterized by subcutaneous swellings that exude a mucoid secretion when sectioned. Lesions occur around body orifices and on the face especially the eyelids • The disease is mainly spread by arthropods, especially the European rabbit flea Spilopsyllus cuniculi. Mosquitoes are vectors in many parts of the world • In wild rabbits, outbreaks of myxomatosis wax and wane according to the virulence of the strain and the immune status of the native rabbit population • Myxomatosisis can occur in hares but is rare and usually mild • Environmental temperature has an effect on mortality rates with the disease being more lethal at low temperatures • Myxomatosis starts with a skin lesion at the site of inoculation. The rabbit becomes viraemic with virus replication taking place throughout the lymphoid system. Secondary lesions develop throughout the body, typically on the nares, lips, eyelids and base of the ears and on the external genitalia and anus • Aerosol infection can result in pneumonic signs, which may be a feature of outbreaks in intensive farmed rabbits • Myxomatosis is accompanied by sterility and abandonment of litters • Myxomavirus is a member of the Leporipoxvirus genus. It causes a trivial infection in its natural host, either Sylvilagus brasiensis (Tapeti, Forest Rabbit, found in Mexico or Argentina) or Sylvilagus bachmani (Brush Rabbit) which is native to California. In the European Rabbit (Oryctolagus cuniculi), myxomavirus causes a serious life-threatening disease • Another important member of the Leporipoxvirus genus is rabbit fibroma virus (Shope fibroma virus), which naturally affects the Cottontail (Sylvilagus floridanus) and causes a benign fibroma in European rabbits. Attenuated Shope fibroma virus is used to manufacture vaccine against myxomatosis • It is possible, on rare occasions, for rabbits to recover from myxomatosis. Ambient temperature affects the course of the disease with high environmental temperature increasing recovery rate (85°C) • Antibiotics, a warm environment, good nursing and non-steroidal analgesics can be used treat myxomatosis. Corticosteroids are contraindicated due to their immunosuppressive effects. Opioid analgesics are ineffective in ameliorating signs of pain. 16.6.1.6 Recovery from myxomatosis It is possible for rabbits to recover from myxomatosis. Apart from the virulence of the virus strain, certain environmental factors affect the resistance of the rabbit to myxomatosis, i.e. intercurrent infection and environmental temperature. Ambient temperature affects the course of the disease with high environmental temperature increasing recovery rate (85°C). Antibiotics, a warm environment and good nursing can be successful and some pet rabbits have survived myxomatosis although their chances are not good. The risk of secondary problems such as gastrointestinal stasis or pasteurellosis is ever present. Non-steroidal analgesics are useful but the use of corticosteroids is contraindicated due to their immunosuppressive effects. Opioid analgesics do not appear to be effective in ameliorating signs of pain. In a study of the effect of buprenorphine on the course of myxomatosis in laboratory rabbits, there was no difference in survival time. Treated rabbits refused food and water a day earlier than untreated rabbits and had lower rectal temperatures immediately prior to death (Robinson et al., 1999). 16.6.2 Viral haemorrhagic disease (VHD) Viral haemorrhagic disease (VHD) is a highly infectious lethal disease of rabbits with a high mortality rate. It is caused by a host-specific calicivirus. VHD only affects the European rabbit Oryctolagus cuniculi. The disease may be called ‘rabbit haemorrhagic disease’ (RHD) and the virus known as ‘rabbit haemorrhagic disease virus’ (RHDV). Sometimes the term ‘rabbit calicivirus disease’ (RCD) is used. VHD originated in 1984 in the People's Republic of China that, at that time, was the world's largest exporter of rabbit meat. A disease broke out in a colony of Angora rabbits that had recently been imported into Germany (Fenner and Fantani, 1999). Except for the suckling rabbits, all the rabbits died within a week and in less than 9 months the disease had spread over 50 000 square kilometres and reached Italy and Europe. By 1988, VHD had been reported in commercial rabbits in many countries worldwide, probably introduced through rabbit meat. In Europe, the disease spread into the wild rabbit population. In 1990, VHD reached Scandinavia. Wild rabbits in the densely populated island of Gotland became nearly extinct within 1 week (Gavier-Widén, 1996). Hundreds of rabbits were seen dead in the fields and many more died in their burrows. Pet rabbits that had been kept indoors and fed on commercial food started dying indicating that humans can act as vectors for VHD. Coincidentally, another disease, European Brown Hare Syndrome (EBHS) was sweeping through Europe. EBHS is caused by a distinctly different calicivirus. In 1996, a non-pathogenic calicivirus was recovered from breeding rabbits in Italy that produced seroconversion and was found to protect rabbits against VHD. The virus has been isolated and identified as a calicivirus. There is evidence that this virus existed before the onset of VHD (Capucci et al., 1997). 16.6.2.1 Pathogenesis of VHD VHD is caused by a calicivirus that has a predilection for hepatocytes and replicates within the cytoplasm of these cells. Experimentally infected rabbits die 3-4 days after infection. VHD is essentially a necrotizing hepatitis, often associated with necrosis of the spleen (see Plate 35). Disseminated intravascular coagulation produces fibrinous thrombi within small blood vessels in most organs, notably the lungs, heart and kidneys resulting in haemorrhages. Death is due to disseminated intravascular coagulopathy or to liver failure. 16.6.2.2 Epidemiology of VHD The calicivirus that causes VHD is antigenically similar to the virus that causes European Brown Hare Syndrome. Attempts to cross-infect rabbits and hares with heterologous virus have failed to induce disease. VHD only affects the European rabbits, not cottontails or other small mammals such as chinchillas, guinea pigs, rats and mice. VHD calicivirus can survive for long periods outside the host. Viable virus has been detected for as long as 105 days on a cloth (Fenner and Fantani, 1999). Environmental temperature is an important factor in the survival of the virus which can remain viable for 22-35 days at 22°C but only for 3-7 days at 37°C. VHD virus is spread by oral, nasal and parenteral transmission and is present in urine and faeces from infected rabbits. Contaminated foods can be a source of infection. When VHD is introduced into a susceptible population, the mortality rate is high and can be 90-100% in rabbits over 2 months of age. Infected young rabbits survive and become immune so when the disease becomes endemic the morbidity and mortality rate falls. In wild rabbits, the disease appears to break out every second year. Insects mechanically transmit the virus in viraemic blood from one animal to another. VHD virus can survive for several weeks in carcasses and skin. Fleas, blowflies and mosquitoes are known to spread the disease (Fenner and Fantani, 1999). PCR techniques have shown that virus can be retained in the body of blowflies for up to 9 days and bushflies for 7 days. Fly ‘spots’ (faeces) are also infective and can contaminate pasture. Flies can travel long distances and be carried along by the wind and spread the disease far and wide. It has also been demonstrated that domestic and wild carnivores can play an important role in the epidemiology of VHD since virulent material can be collected from faecal material after experimental oral inoculation. The virus is very stable in carcasses even after freezing and thawing (Lumeij, 1997). Up until October 1996, VHD was a notifiable disease in Great Britain. It is now endemic and poses a real threat to the pet rabbit due to its resistance and ease of transmission. Deaths have been reported nationwide that have been confirmed at post-mortem to be due to VHD. 16.6.2.3 Clinical signs of viral haemorrhagic disease VHD has a short incubation period of 3-4 days. The disease can be peracute with animals being found dead within a few hours of eating and behaving normally. Acute cases are quiet, pyrexic with an increased respiratory rate and usually die within 12 h. A feature of the disease is a dramatic drop in blood pressure that makes it difficult to find a vein to take blood samples or set up intravenous fluids Dying rabbits are pallid, shocked and collapsed. Haematuria, haemorrhagic vaginal discharges or foamy exudate from the nostrils may be seen. Vascular infarcts can occur within the brain and occasionally convulsions or other neurological signs are seen just before death. Agonal vocalizing and cyanosis have been described (Donnelly, 1995). The ‘classic’ picture is a dead rabbit in opisthotonus with a haemorrhagic nasal discharge. The occasional rabbit can recover from the acute phase, only to develop jaundice and die a few days later. Young rabbits less than 4 weeks of age remain unaffected and develop a life-long immunity if they are exposed to the disease. Unexposed rabbits become increasingly susceptible until 6-10 weeks of age when physiological resistance to the virus disappears. The physiological age immunity of young rabbits has been ascribed to the increase in hepatic transaminase production that occurs after 5 weeks of age (Donnelly, 1995). In adult rabbits, the mortality rate is high. There is no treatment for affected rabbits. 16.6.2.4 Diagnosis of VHD VHD is suspected in any sudden death especially if more than one rabbit in the household has died. The post-mortem picture may be of a healthy rabbit with non-impacted food in the stomach and hard faecal pellets in the distal colon, suggesting that death was sudden. The liver is always affected, although the gross appearance may not reflect the severe histopathological changes. The liver is enlarged, friable and pale with a distinct lobular pattern (see Plate 35). The spleen is also enlarged. Haemorrhages can be found in any organ but are usually present in the lung. The trachea is often full of a foamy exudate. Haematologically, there are fibrin thrombi, lymphopaenia, a reduction in platelets and a failure of other blood clotting factors that result in multiple organ failure due to general circu latory dysfunction. Disseminated intravascular coagulation is a characteristic feature of the pathogenesis of VHD (Chasey, 1997). Histopathology confirms acute hepatic necrosis. There may be many other changes such as acute nephropathy or alveolar haemorrhage. Congestion and haemorrhages can occur in any organ due to terminal intravascular coagulation. The typical histopathological changes in the liver are usually diagnostic but there are a number of other tests that confirm the diagnosis, including hamagglutination tests and electron microscopy. Large numbers of characteristic calicivirus can be detected by electron microscopic examination of liver (Chasey et al., 1995). Fresh liver is required by the laboratory. ELISA tests are also available. 16.6.2.5 Vaccination Due to the devastating effects of VHD in China, a vaccine was quickly developed from inactivated virus obtained from the liver and spleens of infected rabbits. The immunological response to inactivated vaccines is good. VHD virus is difficult to grow in tissue culture so attenuated strains have not been produced. Virus antigen harvested from experimentally infected rabbits is inactivated with formalin or β-propiolactone to produce effective killed vaccines that are commercially available. Vaccination is advisable for all pet rabbits (see Section 3.2). At the present time, there is only one type of attenuated vaccine available in the UK (Cylap, Websters). Genetically engineered vaccines are being produced that insert the gene for the coat protein of the VHD virus into attenuated myxoma virus for simultaneous immunization of VHD and myxomatosis (Barcena et al., 2000). 16.6.3 Papillomatosis There are descriptions of two papillomaviruses that can affect rabbits. Shope papillomavirus causes a benign disease in cottontails (Sylvilagus floridanus) but may cause malignant neoplasms resembling squamous cell carcinomas in the European rabbit (Oryctolagus cuniculus). The disease occurs in the wild population of cottontails in the Eastern USA and in domestic rabbits in some American commercial units. Shope papillomavirus is immunologically distinct from the other papillomavirus, which causes oral papillomatosis. Oral papillomatosis is manifested by wart-like growths on the ventral aspect of the tongue and on other parts of the oral mucosa. The virus is transmitted in oral secretions containing sloughed cells from the warts. Young rabbits are most susceptible and the papillomas grow slowly over a period of 6-9 months. The animals become immune at which point the base of the papilloma becomes inflamed causing sloughing of the tumour, ulcer formation and finally re-epithelialization. Oral papillomas of rabbits are not known to undergo carcinomatous transformation (Kraus et al., 1984). 16.6.4 Coronavirus Coronavirus infection in rabbits was initially described in 1968. Affected rabbits were pyrexic, developed pulmonary oedema and pleural effusion and mortality rates were high. Iridocyclitis has been associated with the disease. An analogy with feline infectious peritonitis has been made. Coronavirus has also been implicated in outbreaks of enteric disease in weanling rabbits. The virus has not been propagated in vitro and it is unclear whether it is a naturally occurring pathogen of rabbits or a virus from another species adapted to rabbits in contaminated treponemal stocks (DiGiacomo and Mare, 1994). The disease was first recognized in the 1960s in rabbits inoculated with suspensions of rabbit testes containing Treponema pallidum (human syphilis). Subsequently the agent has been detected in T. pallidum infected rabbit tissue throughout the world. Coronavirus infection is used experimentally to produce a rabbit model of cardiomyopathy and has only been described in laboratory rabbits. Antibodies to the virus cross-react with human and other mammalian coronaviruses (DiGiacomo and Mare, 1994). 16.5 Mycotic infections 16.5.1 Dermatophytosis Dermatophytosis (ringworm) is occasionally encountered in rabbits. Trichophyton mentagro phytes and Microsporum canis are the species most commonly described (Percy and Barthold, 1993). Lesions are usually found on the base of the ears and muzzle but can involve other areas of the body such as the paws (see Section 9.15). Asymptomatic carriers can occur. Young rabbits are most likely to be affected (Vangeel et al., 2000). Dermatophilus congalensis has been isolated from rabbits. Key points 16.5 • Viral haemorrhagic disease (VHD) is a highly infectious lethal disease of rabbits with a high mortality rate. It is caused by a host-specific calicivirus. VHD only affects the European rabbit Oryctolagus cuniculi • The disease may be called ‘rabbit haemorrhagic disease’ (RHD) and the virus known as ‘rabbit haemorrhagic disease virus’ (RHDV). Sometimes the term ‘rabbit calicivirus disease’ (RCD) is used • The causative calicivirus of VHD has a predilection for hepatocytes. VHD is essentially a necrotizing hepatitis. Death is usually due to disseminated intravascular coagulopathy • VHD calicivirus can survive for long periods outside the host. Viable virus has been detected for as long as 105 days on cloth • VHD virus is spread by oral, nasal and parenteral transmission and is present in urine and faeces from infected rabbits. Contaminated foods can be a source of infection • When VHD is introduced into a susceptible population, the mortality rate is high and can be 90-100% in rabbits over 2 months of age • VHD has a short incubation period of 3-4 days. The disease can be peracute with animals being found dead within a few hours of eating and behaving normally • The ‘classic’ picture is a dead rabbit in opisthotonus with a haemorrhagic nasal discharge • Haematuria, haemorrhagic vaginal discharges or foamy exudate from the nostrils may be seen • Vascular infarcts can occur within the brain and occasionally convulsions or other neurological signs are seen just before death • There is no specific treatment for affected rabbits • Young rabbits, less than 4 weeks of age, remain unaffected and develop a life-long immunity if they are exposed to the disease. Unexposed rabbits become increasingly susceptible until 6-10 weeks of age when physiological resistance to the virus disappears • The typical histopathological changes in the liver are usually diagnostic • An effective vaccine against VHD is available in the UK • Other viruses that affect rabbits include papillomavirus, coronavirus, rotavirus, and parvovirus • Fungal infections of domestic rabbits include Trichophyton mentagrophytes, Microsporum canis, Dermatophilus congalensis and aspergillosis. 16.5.2 Aspergillosis Pulmonary aspergillotic granulomas have been described in laboratory rabbits (Percy and Barthold, 1993).