Tyzzer's disease is an enterohepatic syndrome of a wide range of animals (see Rabbits: T yzzer's Disease) that is seen worldwide. Sporadic fatal infection of foals is common, and acute fatal epidemics occur in laboratory animals. The disease is rare in dogs, cats, calves, and other animals. It primarily affects young, stressed animals; however, some species appear resistant unless stressed or immunosuppressed, while others appear to be susceptible without immunosuppression. Dietary factors, including excessive nitrogenous diets, seemingly make foals more susceptible to the disease. Excessive nitrogenous compounds may cause immunosuppression. Immunosuppressive drugs and some antibacterials, especially sulfonamides, predispose animals to the disease.
Etiology and Pathogenesis
The cause is Clostridium piliforme a motile, sporeforming, rod shaped, flagellated, obligate, intracellular bacterium. It does not grow in cell-free media but can be cultured in the yolk sac of chick embryos or tissue culture cells. The vegetative phase is very labile; spores may survive in soiled bedding at room temperature for >1 yr and can also survive at ∼133°F (60°C) for 1 hr. The endospores are resistant to exposure to 70% ethanol, 3% cresol, or 4% chlorhexidine; however, they are sensitive to 0.4% peracetic acid, 0.015% sodium hypochlorite, 1% iodophor, and 5% phenol.
The pathogenesis is poorly understood. Infection most likely results from oral exposure, eg, the ingestion of spores shed in the feces of infected animals. Possible sources include infective spores from the environment, contact with carrier animals, and in neonatal foals, ingestion of feces from the dam.
Some isolates of C piliforme produce toxins, while others do not. The role of these toxins in the pathogenesis of C piliforme is unknown, but the toxic isolates are generally more virulent than nontoxic isolates. The more toxigenic strains appear more likely to induce hepatic lesions in mice, while the nontoxigenic strains do not.
Tyzzer's disease may be severe in many animal species, but infections are often subclinical or asymptomatic. There may be differences in susceptibility within animal species. B lymphocytes, T lymphocytes, and natural killer cells may play a role in mediating strain susceptibility. Seroanalysis using monoclonal antibody-based competitive inhibition ELISA suggests that Tyzzer's disease may be relatively common in horses, which are susceptible to at least 2 distinct strains.
The primary site of infection is the lower intestinal tract with subsequent dissemination via the blood or lymphatics. The bacterium has an affinity for the intestine (epithelial and smooth muscle cells), hepatocytes, and cardiac myocytes. Stress factors such as capture, overcrowding, shipping, and poor sanitation appear to be predisposing. Sulfonamide administration predisposes rabbits to the disease. Mortality is highest at weaning age except in foals, in which the disease is seen between 1 and 6 wk of age, with most cases between 1 and 2 wk. In some species, the disease has been identified concurrently with other diseases, eg, feline infectious peritonitis in cats, distemper and mycotic pneumonia in dogs, and cryptosporidial and coronaviral enteritis in calves.
The disease most often affects well-nourished animals, especially animals fed high protein diets, during periods of stress. Under laboratory conditions, stress is created by immunosuppressive drugs or other factors that can be easily identified. With many experiments, stress may be involved as part of the protocol, and when the disease develops, it is devastating.
After experimental infection, the incubation period in foals is 3–7 days; under natural conditions, the period is unknown. Most foals are found in a coma or dead. Clinical signs, if seen, are of short duration (a few hours to 2 days). Signs are variable, but may include depression, anorexia, pyrexia, jaundice, diarrhea, and recumbency. Terminally, there are convulsions and coma. Signs vary slightly between species. Laboratory animals may show depression, ruffled coat, and varying degrees of watery diarrhea; at the start of an outbreak, they often are found dead.
Clinicopathologic tests are of little value in laboratory animals because they die so rapidly. In foals, the serum enzymes sorbitol dehydrogenase, AST, alkaline phosphatase, lactate dehydrogenase, and γ-glutamyltransferase are increased. There is also hyperbilirubinemia, leukopenia, hemoconcentration, and terminally profound hypoglycemia.
Characteristic lesions are seen in the liver, myocardium, and intestinal tract. In the liver, white, gray, or yellowish foci of necrosis, 2 mm in diameter, are few to disseminated. The hepatic necrosis is most marked and disseminated in foals in which the multiple necrotic foci with slightly depressed hemorrhagic centers appear to infect almost every hepatic lobule. In addition, there is marked hepatomegaly, and the hepatic lymph nodes are hyperplastic. In rabbits, severe lesions develop in the intestines and heart. The terminal ileum, cecum, and proximal colon are diffusely reddened. Diffuse (“paint-brush”) hemorrhage is frequently seen on the serosa of the cecum. Patchy areas of mucosal necrosis are present in the cecum and colon, together with marked edema of the wall of the cecum. Mesenteric lymph nodes may be enlarged and edematous. White streaks in the myocardium may be present, especially near the apex. Intestinal and heart lesions are generally milder or absent in other animals.
Microscopically, randomly distributed and coalescing foci of necrosis in the liver are associated with scant to moderate infiltration of neutrophils and macrophages. The causative bacteria are found in a crisscross pattern in viable hepatocytes at the periphery of the necrotic foci. In the cecum and colon of rabbits, patchy areas of necrosis extend as deep as the muscularis externa with associated mucosal and submucosal infiltrates of neutrophils. Organisms may be found in the epithelium, muscularis mucosa, and muscularis externa of the affected intestine. When cardiac lesions are present, they consist of foci of fiber fragmentation, vacuolation, loss of cross-striations, and minimal inflammatory cell infiltration.
Serology and PCR may be used clinically to test for the disease. However, clinical signs in addition to the commonly available diagnostic methods must be interpreted together for a presumptive clinical diagnosis. A definitive clinical diagnosis is not possible due to the lack of a definitive diagnostic test. Diagnosis is based on demonstration of organisms in tissue sections with special stains. The organism stains poorly with H&E and Gram's stains. With Giemsa stain, the bacillus stains well in the liver and intestinal epithelium and in smears of infected organs but poorly in smooth muscles and cardiac muscle cells. The Warthin-Starry or Levaditi silver stains are preferable to other stains because the bacillus stains well in the cytoplasm of all infected cells.
Treatment and Control
Little is known about the effectiveness of antibiotics for treatment; some antibiotics are known to aggravate the disease. C piliforme is sensitive to tetracycline and partially sensitive to streptomycin, erythromycin, penicillin, and chlortetracycline; it is resistant to sulfonamides and chloramphenicol.
In neonatal foals, the disease seems to be nearly 100% fatal, although it is likely that some foals less severely affected survive. Once the disease is present on a farm, it may be seen sporadically year after year. Animals suspected of being infected may be treated IV initially with 50% dextrose, followed by 10% dextrose (slowly), other fluid therapy, and antibiotics. Most foals respond dramatically to the dextrose therapy but relapse into a coma and die in a few hours. Rarely, an occasional foal appears to survive the disease after prolonged treatment with dextrose given slowly IV with antibiotics.
Because the disease in foals is sporadic and not highly contagious, specific preventive measures are usually not indicated. In areas where endospores are present in the environment, many foals may be exposed; however, only a few that are immunosuppressed become acutely affected. On premises where the disease is prevalent, overfeeding of mares, especially with high protein diets, appears to enhance susceptibility in neonatal foals. Reducing the nitrogenous dietary factors that may induce immunosuppression in neonatal foals may lessen the incidence of the disease. In general, factors that cause stress and immunosuppression should also be reduced. When the disease is seen in a colony of laboratory animals, treatment is not recommended because it prolongs the disease and possibly produces carrier animals. It is best to destroy all animals in the colony, decontaminate the environment, and restock with disease-free animals.
Last full review/revision March 2012 by Thomas W. Swerczek, DVM, PhD