THE MERCK VETERINARY MANUAL
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Bacterial and Mycotic Diseases of Rabbits

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Pasteurellosis

Pasteurellosis is common in domestic rabbits. It is highly contagious, and is transmitted primarily by direct contact, although aerosol transmission may also occur. The etiologic agent is Pasteurella multocida, a gram-negative, nonmotile coccobacillus. In conventional colonies, 30–90% of apparently healthy rabbits may be asymptomatic carriers. Several barrier colonies of laboratory rabbits have been established as Pasteurella-free.

Pasteurellosis presents with a variety of clinical symptoms including rhinitis, pneumonia, abscesses, reproductive tract infections, torticollis, and septicemia.

Rhinitis (snuffles or nasal catarrh) is an acute, subacute, or chronic inflammation of the mucous membranes of the air passages and lungs, induced primarily by Pasteurella, but Pseudomonas, Bordetella bronchiseptica, Staphylococcus, and Streptococcus have also been isolated. The initial sign is a thin, serous exudate from the nose and eyes that later becomes purulent. The fur on the inside of the front legs just above the paws may be matted and caked with dried exudate or this area may be clean with thinned fur as a result of pawing at the nose. Infected rabbits usually sneeze and cough. In general, snuffles occurs when the resistance of the rabbit is low. Recovered rabbits are likely carriers. Pneumonia can ensue.

Pneumonia is common in domestic rabbits. Frequently, it is a secondary and complicating factor in the enteritis complex. The cause is typically P multocida but other bacteria such as Klebsiella pneumoniae, Bordetella bronchiseptica, Staphylococcus aureus, and pneumococci may be involved. Upper respiratory disease (snuffles, see above) is often a precursor of pneumonia. Inadequate ventilation, sanitation, and nesting material are predisposing factors. The number of cases of pneumonia is directly proportional to the level of ammonia in a rabbitry. Rabbits usually succumb within 1 wk after signs appear. Affected rabbits are anorectic, listless, dyspneic, and have a fever. Necropsy reveals bronchopneumonia, pleuritis, pyothorax, or pericardial petechiae. Diagnosis depends on signs, lesions, and culture results. Antibiotic treatment often fails because the pneumonia is advanced before it is detected.

Otitis media or interna (“wry neck” or head tilt) results from P multocida or Encephalitozoon cuniculi infection. An accumulation of pus or fluid in the middle or inner ear causes the rabbit to twist its head, eg, “wry neck” or torticollis. However, not all rabbits with middle ear infections show torticollis. Longterm antibiotic treatment is required for drug penetration into the affected area. Antibiotic therapy may only prevent worsening of clinical signs and, as the prognosis is guarded, most colony rabbits with this condition are culled.

Mature bucks and young rabbits seem particularly susceptible to conjunctivitis, (weepy eye) caused by P multocida or S aureus; however, the incidence is low. Transmission is by direct contact or fomites. Affected rabbits rub their eyes with their front feet. Ophthalmic ointments containing sulfonamides, antibiotics, or antibiotics and a steroid are satisfactory for treatment, but recurrence is common. Flushing the lacrimal duct with an antibiotic solution is often beneficial in chronically affected show rabbits. Conjunctivitis also accompanies rabbitpox (see Rabbitpox) and myxomatosis (see Myxomatosis).

Subcutaneous and visceral abscesses caused by Pasteurella may be clinically silent for long periods and spontaneously rupture. When bucks penned together fight, their wounds frequently develop abscesses. Abscesses in rabbits are treated differently than feline abscesses; rupture or drainage via Penrose is not the recommended course. Thick-walled abscesses should be surgically excised en bloc if possible. Open wounds should be debrided or curetted and left for second intention healing. Facial abscesses are often related to dental disease (see Dental Disease). With colony rabbits, it is usually advisable to eliminate rather than to treat the affected rabbit; with pet rabbits, drainage of the abscess accompanied by antibiotic therapy based on culture and sensitivity tests has been successful, although recurrence of signs is common.

Pasteurella often causes genital infections, but several other organisms also may be involved. They are manifest by an acute or subacute inflammation of the reproductive tract, and most frequently are found in adults, more often in does than bucks. If both horns of the uterus are affected, the does often become sterile; if only one horn is involved, a normal litter may develop in the other. The only sign of pyometra may be a thick, yellowish gray vaginal discharge. Bucks may discharge pus from the urethra or have an enlarged testicle. Chronic infection of the prostate and seminal vesicles is likely, and because venereal transmission may ensue, it is best to cull the animal in a production rabbitry colony. Surgical removal of the infected reproductive organs in conjunction with antibiotic therapy is indicated for pet rabbits. The contaminated hutch and its equipment should be thoroughly disinfected.

Rabbits may develop Pasteurella septicemia and die acutely without any clinical signs. Septicemia necropsy findings may reveal only congestion and petechial hemorrhages in multiple organs.

Diagnosis of pasteurellosis is based on clinical signs and isolation of P multocida. Carriers can be identified by an indirect fluorescent antibody test on nasal swabs. A technique that uses small, saline-moistened, pediatric nasopharyngeal swabs has proved superior to the standard, larger nasal swab. The swab is directed medially through the external nares past the turbinates and onto the dorsal surface of the soft palate; sedation is recommended. The swab is then retracted and can be used in the fluorescent antibody test or plated onto a culture medium. An ELISA test for detecting antibodies against P multocida may also prove beneficial in detecting carriers. PCR can discriminate between different isolates, but it is not commercially available.

Treatment is difficult and may not eradicate the organism. Antibiotics seem to provide only temporary remission, and the next stress (eg, kindling) may cause relapse. Enrofloxacin (200 mg/L of drinking water for 14 days or 5–10 mg/kg parenteral, bid for 14 days) is effective for upper respiratory P multocida infections. Tilmicosin (25 mg/kg, SC) has been reported as an effective treatment for pasteurellosis. Procaine penicillin (60,000 IU/kg, IM for 10 days) was recommended for individual rabbits, but its use should be cautioned as deaths from enterotoxemia often follow penicillin administration.

An effective intranasal vaccine is in development, but is not commercially available; therefore, the best method of control in large rabbitries is strict culling. Two methods to free a production colony of Pasteurella have been reported. The first involves culture and culling of positive animals; once the colony is Pasteurella-free, it must be maintained in isolation. In the second method, pregnant does past kindling are treated with enrofloxacin. While does remain Pasteurella-culture positive the kits remain Pasteurella-culture negative. Carriers can be identified by an indirect fluorescent antibody test on nasal swabs.

Listeriosis

Listeriosis, a sporadic septicemic disease characterized by sudden deaths or abortions, is most common in does in advanced pregnancy. Poor husbandry and stress may be important in initiating the disease. Clinical signs are variable and nonspecific and include anorexia, depression, and weight loss. In contrast to the disease in cattle and sheep, listeriosis seldom affects the CNS in rabbits. The causal agent, Listeria monocytogenes, spreads via the blood to the liver, spleen, and gravid uterus. At necropsy, the liver consistently contains multiple, pinpoint, gray-white foci. Because diagnosis is rarely made premortem, treatment is seldom attempted. L monocytogenes can infect many animals, including humans. It is difficult to isolate with normal methods, and special techniques are often required.

Intestinal Diseases

Intestinal disease is a major cause of death in young rabbits. Although most diarrheal diseases were once lumped together (as the enteritis complex) or simply called mucoid enteritis, specific diseases are being delineated. Diet, antibiotic treatment, and other factors create disturbances of the GI microflora and may predispose rabbits to dysbiosis and intestinal disease. For discussion of GI stasis due to hairballs, see Hair Chewing and Hairballs.

Enterotoxemia is an explosive diarrheal disease, primarily of rabbits 4–8 wk old. It occasionally affects adults and junior stock. Signs are lethargy, rough coat, a perineal area covered with greenish brown fecal material, and death within 48 hr. Often, a rabbit looks healthy in the evening and is dead the next morning. Necropsy reveals the typical lesions of enterotoxemia, ie, a fluid-distended intestine with hemorrhagic petechiae on the serosal surface. The primary causative agent is Clostridium spiroforme, which produces an iota toxin. Little is known about transmission of the organism; it is assumed to be a commensal that is normally present in low numbers. The type of diet seems to be a factor in development of the disease; enterotoxemia is seen less often when high-fiber diets are fed. Because lincomycin, clindamycin, and erythromycin induce Clostridium-related (eg, C difficile) enterotoxemia due to their selective effect on normal gram-positive bacteria, they are contraindicated in rabbits. Enterotoxemia is a consideration for most antibiotic therapy, and it has been seen after administration of penicillins and cephalosporins. The incidence rate is 40–80% after oral penicillin therapy, which should be considered contraindicated in rabbits. These diarrheas are remarkably similar to those that occur naturally (described above as enterotoxemia). Treatment of colony rabbits is seldom attempted because of the rapidity of death. However, when population size permits, cholestyramine has been used with promising results, both as a preventive and a treatment. Reducing stress of the young rabbits (weaning, etc) and ad lib feeding of hay or straw are helpful in prevention. Adding 250 ppm of copper sulfate to the diet of young rabbits also helps prevent enterotoxemia. Individual animal treatment for enterotoxemia should include supportive fluid therapy. There is little evidence that antibiotics are helpful. Diagnosis depends on history, signs, lesions, and demonstration of C spiroforme. Centrifugation of intestinal contents at 20,000 g for 15 min followed by culture of the supernatant-pellet interface will reveal the organism. For a definitive diagnosis, the presence of iota toxin in the supernatant of centrifuged cecal contents can be demonstrated by in vivo or in vitro assays.

Tyzzer disease (see Tyzzer Disease), caused by Clostridium piliforme, is characterized by profuse watery diarrhea, anorexia, dehydration, lethargy, staining of the hindquarters, and death within 1–3 days in weanling rabbits 6–12 wk old. Acute outbreaks have been associated with >90% mortality. Some rabbits may develop chronic infections that present clinically as a wasting disease. Infection occurs by ingestion and is associated with poor sanitation and stress. The lesions consist of necrotic enteritis along with multifocal necrosis in the liver and heart. Diagnosis is made histologically; special stains (eg, Giemsa or Warthin-Starry silver) show the characteristic intracellular bacterium. Culturing is impractical because the bacterium does not grow on artificial media. Serologic tests are available from laboratory animal diagnostic laboratories. Tyzzer disease affects a wide spectrum of other species but has not been reported in humans, although titers have been documented in pregnant women. Although antibiotics used in treatment of other animals have not been effective in rabbits, oxytetracycline has been of some value in limiting an outbreak. No vaccine is available. Aggressive disinfection and decontamination of the housing facility to reduce the presence of hardy spores is indicated with either 1% peracetic acid or 3% hypochlorite.

Escherichia coli as a cause of rabbit diarrhea has been confused by the circumstance that E coli often proliferate when rabbits develop diarrhea for any reason. Enteropathogenic strains of E coli (serotype O103) commonly express the eae gene, which codes for intimin, an outer membrane protein associated with the attaching and effacing lesions. Serotypes O15:H, O109:H2, O103:H2, O128, and O132 are also important. Normal healthy rabbits do not have E coli of any strain associated with their GI tract.

Two types of colibacillosis are seen in rabbits, depending on age. Rabbits 1–2 wk old develop a severe yellowish diarrhea that results in high mortality. It is common for entire litters to succumb to this disease. In weaned rabbits 4–6 wk old, a diarrheal disease very similar to that described for enterotoxemia is seen. The intestines are fluid filled, with petechial hemorrhages on the serosal surface, similar to the pathology described for both Tyzzer's disease and enterotoxemia (see Enterotoxemia). Death occurs in 5–14 days, or rabbits are left stunted and unthrifty. Diagnosis is made by isolating E coli on blood agar and then having the isolate biotyped or serotyped. Electron micrographs of E coli attached to the mucosa are also helpful. In severe cases, treatment is not successful; in mild cases, antibiotics are of value. Severely affected rabbits should be culled, and facilities thoroughly sanitized. High-fiber diets appear to help prevent the disease in weaned rabbits.

Proliferative enteropathy caused by Lawsonia intracellularis has been reported to cause diarrhea in weanling rabbits. Clinical symptoms include diarrhea, depression, and dehydration, which resolve over 1–2 wk. Disease does not cause death unless associated with a dual infection with another enteropathogenic agent. Diagnosis is based on necropsy findings of a thickened and corrugated ileum and histologic identification of the rod-shaped to curved or spiral silver-staining organism in crypt enterocytes. The organism requires cell-containing media (enterocytes) for culture. Immunohistochemistry and PCR may be useful to identify L intracellularis. Isolation of sick animals and symptomatic treatment is advised.

Mucoid enteropathy is a distinct diarrheal disease of rabbits, characterized by minimal inflammation, hypersecretion, and accumulation of mucus in the small and large intestines. While the etiology is unknown, it may occur concurrent with other enteric diseases. Predisposing factors include dietary changes, dietary fiber <6% or >22%, antibiotic treatments, environmental stress, and challenges with other bacteria. Clinical signs are gelatinous or mucus-covered feces, anorexia, lethargy, subnormal temperature, dehydration, rough coat, and often a bloated abdomen due to excess water in the stomach. A firm, impacted cecum may be palpable. The perineal area is often covered with mucus and feces. Diagnosis is based on clinical signs and necropsy findings of gelatinous mucus in the colon. Rabbits may live for ∼1 wk. Treatment is unrewarding, but intense fluid therapy, enema removal of mucus mass, antibiotics, and analgesics may be tried. Prevention is the same as for any rabbit enteropathy.

Mastitis

(Blue breasts)

Mastitis is common in commercial rabbitries and is occasionally seen in smaller units. Poor sanitation enhances spread throughout the rabbitry. Mastitis affects lactating does and may progress to a septicemia that rapidly kills the doe. Generally, it is caused by staphylococci, but streptococci and other bacteria have been isolated. Initially, the mammary glands become hot, reddened, and swollen. Later, they may become cyanotic, hence the common name, “blue bag.” The doe will not eat but may crave water. Fever ≥105°F (40.5°C) is often noted. If antibiotic treatment is started early (the first day the doe goes off feed), the rabbit may be saved and damage limited to 1–2 mammary glands. If >2 glands are lost, keeping the doe may not be economical. Because penicillin often causes diarrhea in rabbits, does should be treated only after the pelleted ration has been replaced with hay or some other high-fiber diet (see Enterotoxemia). Kits should not be fostered to another doe because they will spread the infection to the foster mother. Handrearing of infected young may be attempted but is difficult. The incidence of mastitis can be reduced if nest boxes are maintained without rough edges to the entrance, which can traumatize the teats when the doe jumps in and out of the nest box. It is essential for the nest box to be sanitized both before and after use. Vaccines have not proved to be beneficial in preventing mastitis.

Treponematosis

(Vent disease, Syphilis, Spirochetosis)

Treponematosis, a specific venereal disease of domestic rabbits, is caused by the spirochete Treponema paraluis cuniculi. It occurs in both sexes and is transmitted by coitus and from the doe to offspring. Although closely related to the organism (T pallidum) that causes human syphilis, T cuniculi is not transmissible to other domestic animals or humans. The incubation period is 3–6 wk. Small vesicles or ulcers are formed, which ultimately become covered with a heavy scab. These lesions usually are confined to the genital region, but the lips and eyelids may be involved. Infected rabbits should not be mated. Diagnosis is based on the lesions and observation of the spirochete's corkscrew motility under darkfield microscopy. Serologic tests used to diagnose T pallidum, such as the VDRL slide test and the rapid-plasma regain card test are widely available and can be used to diagnose T cuniculi. Hutch burn is a differential diagnosis.

Benzathine penicillin G, 42,000 IU/kg, SC, at weekly intervals for 3 wk, is necessary to eradicate treponematosis from a herd. All rabbits must be treated even if no lesions are present. Lesions usually heal within 10–14 days, and recovered rabbits can be bred without danger of transmitting the infection. A potential side effect of penicillin treatment is diarrhea and the possibility of an enteritis outbreak due to proliferation of gram-negative bacteria in the gut. Rabbits treated with penicillin should be switched to hay and treated with antidiarrheals immediately if needed (see Enterotoxemia).

Dermatophytosis

(Ringworm)

Clinical dermatophytosis commonly affects individual rabbits, but epizootics can also occur. Ringworm is generally associated with poor husbandry, poor nutrition, and other environmental stressors. The cause is most commonly Trichophyton mentagrophytes and occasionally Microsporum canis. Transmission is by direct contact. Fomites, such as hair brushes, that evade proper disinfection can play a significant role in spreading infection. Asymptomatic carriers are very common. The lesions usually appear first on the head and may spread to any area of the skin. Affected areas are circular, raised, reddened, and capped with white, bran-like, flaky material. A negative result with a Wood's lamp illumination does not rule out dermatophytosis, as all agents do not fluoresce. Hair plucked from the edge of the lesion may be cultured on special media, such as dermatophyte test media or Sabouraud's agar. A KOH skin scraping taken from the periphery of the lesion that reveals fungal forms confirms the diagnosis. Because rabbits with active infections are infectious for humans and other animals, they should be either isolated and treated or killed. Griseofulvin at an individual dosage of 25 mg/kg body wt, sid for 2 wk or in the feed at 825 mg/kg of feed is effective but not approved for use in rabbits; it should not be used in rabbits intended for human consumption. Griseofulvin may be teratogenic and should not be used in pregnant does. Topical antifungal creams containing itraconazole (5 mg/kg, PO, sid for 4–6 wk), clotrimazole, or miconazole may be effective extra-label treatments. For rabbitries, treatment with either 1% copper sulfate as a dip or 8 oz of MECA (metabolized chlorous acid/chlorine dioxide compound, 1:1:10 mix of base:activator:water) sprayed on 6 times in a 26-day period was shown to be effective.

Tularemia

Tularemia is rare in domestic rabbits, but wild rabbits and rodents are highly susceptible and have been involved in most epizootics. Up to 90% of human cases are linked to wild lagomorph exposure. The etiologic agent, Francisella tularensis, is an aerobic nonmotile gram-negative, pleomorphic, bipolar coccobacillus that is prevalent in the south central USA. It is highly infectious and passed through the skin, through the respiratory tract via aerosols, by ingestion, and via bloodsucking arthropods. Tularemia causes an acute fatal septicemia. Diagnosis is based on necropsy findings of septicemic bacterial disease with numerous small, bright white hepatic foci, congestion, and enlargement of the liver and spleen. Treatment of the animal is not indicated. Tularemia is a reportable disease.

Last full review/revision July 2011 by Diane McClure, DVM, PhD, DACLAM

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