Introduction

Tyzzer’s disease is an infectious disease caused by Clostridium piliforme. The disease is named after Ernest Tyzzer, who, in 1917, initially described this condition as a fatal epizootic diarrheal disease of Japanese waltzing mice. It affects a wide variety of domestic and non-domestic animal species, including humans. The most susceptible species are horses, rabbits, and laboratory animals. There is neither an effective treatment nor commercial vaccines available to prevent this disease.

Etiology

Clostridium piliforme is a Gram-negative, spore-forming, obligate intracellular, filamentous, pleomorphic, and motile bacterium. Vegetative organisms are 0.3 to 0.5 μm in diameter and 8 to 10 μm in length, with very thin (10–15 nm diameter) peritrichous flagella. The spores measure 0.5 to 1.0 μm in diameter, and they have thick coats (80–200 nm). This microorganism may develop subterminal spores, which are not, however, easily seen in tissue sections. The rods appear in bundles within the cytoplasm of hepatocytes and enterocytes. C. piliforme has never been cultured on artificial media and it grows only in tissue culture or in fertile eggs. It stains positively with silver, methylene blue, and thionine stains and it is PAS positive.

Although formerly known as Bacillus piliformis, 16S rRNA gene sequencing led to assignment of this microorganism to the genus Clostridium and the designation of Clostridium piliforme. The phylogenetic tree suggests that the closest relatives of this organism are Clostridium coccoides, Clostridium oroticum, Clostridium clostridiformis, Clostridium symbiosum, and Clostridium aminovalericum.

C. piliforme is relatively labile in the vegetative phase, but its spores may survive for long periods in the environment, including contaminated bedding, where it can remain infectious for at least one year, although some reports indicate that spores can remain viable in the environment for up to five years. The spores of C. piliforme are resistant to heating up to 60 °C for 30 min, 80 °C for 15 min, and to exposure to 70% ethanol, 3% cresol, 4% chlorhexidine, 0.037% formaldehyde, 0.4% peracetic acid, 0.015% sodium hypochlorite, 1% iodophol, or 5% phenol.

Epidemiology

Neonates and juvenile individuals are usually more susceptible to Tyzzer’s disease than adults. Predisposing factors such as stress, overcrowding, dietary imbalances, coprophagia, poor sanitary management, parasitism, sulfonamide and corticosteroid administration may lead to the clinical presentation of the disease.

Foals, lagomorphs, and laboratory animals appear to be the most susceptible species, presenting low morbidity and high mortality. In addition, this disease has also been reported, among others, in red pandas, white-tailed deer, cattle, dogs, cats, cotton-top tamarins, coyotes, snow leopards, gray foxes, servals, and in several avian species like weaver birds. A human case was described in an immunosuppressed patient infected with Human Immunodeficiency Virus.

The disease in horses, which is considered one of the most susceptible species, has been reported in North America, Australia, Europe, and Africa. The ingestion of spores from the environment is the most likely route of infection, although this has not been confirmed. Fecal shedding of C. piliforme in adult horses has been demonstrated, and this led to the belief that coprophagia may play an important role in the infection of foals. Vertical transmission does not occur under natural conditions, although intrauterine transmission has been demonstrated in mice and in rats treated with prednisolone during the last week of pregnancy. Colostral transfer of antibodies to C. piliforme has been demonstrated in horses.

Pathogenesis

Very little is known about the pathogenesis of C. piliforme infection. The proposed theory of mode of transmission is fecal–oral, by ingestion of spores from an environment contaminated by feces. Following oral exposure, most immunocompetent animals clear the infection within a few weeks. However, in permissive individuals, C. piliforme proliferates in the intestinal mucosa, specifically in the ileum, colon, and cecum, producing necrosis and sloughing of enterocytes. Entry to the portal circulation results in subsequent dissemination to the liver and other organs, predominantly the myocardium. The organism is shed in feces.

The incubation period of the disease may be as long as seven days. Experimentally, in hamsters inoculated with infected liver homogenates, organisms and lesions are detectable in the mucosa of the small and large intestine by three days post inoculation, and multiple lesions and bacilli may be present in the liver by day 6 to 8 post exposure. Depletion of neutrophils or natural killer cells in experimentally infected mice increases the severity of disease, but macrophage depletion does not appear to influence the susceptibility to, or the course of, the disease.

Clinical signs

The young of many animal species can contract Tyzzer’s disease, and show similar clinical signs, with only a few differences that are discussed later in this chapter. Most animal species have icterus and dehydration; fecal staining of the perineum may also be observed, although this is not a consistent finding.

In foals, Tyzzer’s disease is a fatal infection, occurring mainly between 1 and 4 weeks of age, with either no clinical signs or acute signs of enterohepatic disease. In adults, the mortality is lower. When observed, clinical signs are of short duration and include lethargy, weakness, anorexia, fever, hypothermia, varying degrees of watery diarrhea, abdominal pain, dehydration, tachycardia, vomiting, jaundice, seizures, and coma.

Sudden death or outbreaks of profuse watery diarrhea are the main clinical signs in rabbits and mice.

Gerbils and rats are very susceptible to the disease, and in addition to the clinical signs mentioned above for all species, they may show ruffled hair coat and hunched posture.

Clinical signs reported in kittens are diarrhea of approximately five days’ duration, head tilt, and vacant staring, which rapidly progress to depression and collapse.

The disease in a weaver bird consisted of incapacity to fly or perch, and neurological signs including head tilt, torticollis, and rolling onto its back.

Clinico-pathologic findings

Biochemical findings are similar in all species and include hypoglycemia, hypoalbuminemia, hypoproteinemia, hyperbilirubinemia, and elevated hepatic enzymes, such as aspartate aminotransferase (AST), alanine aminotransferase (SGPT), alkaline phosphatase, and lactate dehydrogenase (LDH). Foals may also present elevated serum fibrinogen. Non-regenerative anemia, leukocytosis, or leukopenia can be present.