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Clostridium difficile and C perfringens Infection

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Clostridium difficile is a large, gram-positive, anaerobic, spore-forming motile rod and is the major cause of antibiotic-associated colitis in people. C difficile–associated diarrhea and disease develops spontaneously in a variety of other species including horses, pigs, calves, dogs, cats, hamsters, guinea pigs, rats, and rabbits. C difficile produces protein toxins A, B, and/or the binary toxin CDT in the intestine. Toxin A is an enterotoxin that causes hypersecretion of fluid into the intestinal lumen and also causes tissue damage. Toxin B is a potent cytotoxin that induces inflammation and necrosis. The mechanism of action of CDT is not known. Disruption of colonic microflora together with the presence of toxigenic C difficile strains that overgrow in the intestines are the prerequisites for disease. Diagnostic tests for C difficile toxins include cell cytoxicity assays and ELISA on fecal samples, anaerobic culture, and PCR to discriminate between toxigenic and nontoxigenic strains. C perfringens is widely distributed in the soil and the GI tract of animals and is characterized by its ability to produce potent exotoxins, some of which are responsible for specific enterotoxemias. Five types (A, B, C, D, and E) have been identified and produce one or more of four major toxins (alpha, beta, epsilon, and iota). C perfringens type A is most common and the most variable strain in toxigenic properties. Alpha toxin production is associated with gas gangrene, traumatic infections, avian and canine necrotic enteritis, colitis in horses, and diarrhea in pigs. C perfringens types B and C cause severe enteritides, dysentery, toxemia, and high mortality in young lambs, calves, pigs, and foals (beta toxin). Type C causes enterotoxemia in adult cattle, sheep, and goats. The diseases are listed below, categorized as to cause and host.

Clostridia-associated Enterocolitides in Horses

Clostridium difficile and C perfringens have been implicated in this acute, sporadic disease of horses characterized by diarrhea and colic. Because of uncertainty about the etiology, the condition has also been referred to as idiopathic colitis, but there is now good evidence that these organisms are responsible for enterocolitis in horses in approximately 20%–30% of cases of acute diarrhea. (See also Clostridia-associated Enterocolitis in Horses.)

C difficile may be found in low concentrations in the feces of as many as 10% of healthy horses. C difficile and C perfringens organisms may be present in soil or the environment and be ingested by horses. The factors that trigger disease are not well known, but it is presumed that some alteration in the normal flora permits excessive multiplication of the bacteria, which produce toxins capable of causing intestinal damage and systemic effects.

Predisposing factors that have been suggested include change in diet and antibiotic therapy. Other host factors that may determine whether disease develops include age, immunity, and presence or absence of intestinal receptors for the clostridial toxins. Recent antibiotic therapy is a common feature of the history of horses with C difficile–induced diarrhea. Certain antibiotics, notably macrolides and especially erythromycin ethylsuccinate, β-lactam antibiotics, and trimethoprim/sulfonamide, are more likely than others to be associated with C difficile colitis. Mares with foals that are being treated with erythromycin ethylsuccinate appear to be at high risk. Elimination of roughage from the diet before surgery is also reported to predispose to C difficile colitis. Acute diarrhea has been reproduced in healthy neonatal foals using C difficile spores and vegetative cell forms. Acute anterior enteritis (duodenitis jejunitis, see Clostridia-associated Enterocolitis in Horses) has also been associated with C difficile in a case-control study.

C perfringens type A is believed to cause diarrhea by elaboration of an enterotoxin (CPE), which is released during sporulation and stimulates intestinal epithelial cells to secrete excess fluid into the lumen. A novel necrotizing toxin, called β2, produced by some strains of C perfringens, has recently been strongly associated with colitis in horses.

Foals and adult horses may be affected. Typically, there are signs of abdominal pain and diarrhea with or without blood. There may be abdominal distention, especially in cases of C difficile–induced diarrhea. Dehydration, toxemia, and shock may develop, and the mortality rate is variable. One or several animals on a farm may be affected. Horses with anterior enteritis have associated severe recurrent nasogastric reflux, fever, and malaise.

Lesions:

The characteristic lesion is a necrotizing enterocolitis-typhlitis. There is severe loss of colonic and cecal mucosal epithelial cells, hemorrhagic colitis and typhlitis, and thrombosis in capillaries of the intestinal mucosa. Horses with anterior enteritis will mostly have hemorrhagic duodenitis.

Clinical features of the disease are similar to those of acute salmonellosis (see Salmonellosis), Potomac horse fever (see Potomac Horse Fever), or monocytic ehrlichiosis. The identification of C perfringens as the cause of diarrhea in horses depends on demonstration of the presence of enterotoxin or the gene for CPE in the feces or intestinal fluid and the absence of other likely etiologic agents. Most C perfringens found in the intestine of horses lack the gene for CPE expression. Large numbers of C perfringens in anaerobic fecal culture of horses with diarrhea is not diagnostically significant. The diagnosis of C difficile diarrhea is suggested by a history of recent treatment with antibiotics and is supported by demonstration of the presence of C difficile toxin A and/or B in a freshly passed or frozen fecal sample submitted to a laboratory using a human ELISA validated in horses, with good sensitivity and specificity. The toxin gene may be identified by PCR ribotyping.

Steps may be taken to reduce the opportunity for C difficile infections in horses. Proper isolation procedures and infectious disease control should be applied to high-risk horses receiving antibiotics. The environmental load of C difficile spores may be reduced by surface disinfection with sporicidal disinfectants, and the spread may be reduced by hand washing and by isolation of infectious horses and foals. There are no control measures available for prevention of C perfringens–induced diarrhea. Oral metronidazole (15 mg/kg, tid) is recommended for treatment of either of these clostridial infections. Metronidazole might be teratogenic, so its use should be avoided if possible in pregnant mares.

Clostridium difficile in Swine

Clostridium difficile has emerged as an important cause of diarrhea in neonatal swine. In some studies, it has been identified as the second most frequent cause of diarrhea in 1- to 7-day-old pigs. Mesocolonic edema is a characteristic feature of the disease seen in almost all affected pigs, but this lesion is not pathognomonic. Diagnosis of the disease depends on detection of toxins as described for the disease in horses. Porcine, equine, bovine, and canine C difficile isolates may show an antimicrobial susceptibility profile overlapping that of isolates from human patients, raising the possibility for interspecies transmission of C difficile. Dormant C difficile spores have been found in meat of pigs and beef cattle. Some of the ribotypes isolated were similar or identical to human pathogenic strains.

Clostridium difficile in Dogs

Clostridium difficile has not been established as a primary pathogen in dogs. However, human toxigenic C difficile strains have been frequently isolated from rectal swabs of dogs visiting human patients in hospitals. Human ELISA for C difficile toxins does not perform well in dogs with diarrhea and has poor sensitivity and specificity. Approximately 10% of asymptomatic dogs shed toxigenic C difficile in feces.

Clostridium difficile in Calves

Clostridium difficile has been identified as a potential cause of diarrhea in young calves. The disease could not be reproduced in colostrum-deprived neonatal calves with spores or vegetative cells. C difficile has been found in high prevalence in veal calves early in the veal production process.

Clostridium perfringens in Adult Cattle

In the past few years, hemorrhagic bowel, bloody gut, or jejunal hemorrhage syndrome has emerged sporadically in individual, high-producing dairy cows in early lactation. Although no specific etiology has been established, it is assumed that Clostridium perfringens type A is involved, because large numbers of this clostridium may be recovered in most cases. The clinical course is peracute, with anorexia, colic, drop in milk yield, hemorrhage into the intestine, and sudden death despite aggressive supportive and surgical treatment. Gross postmortem findings include severe hemorrhage and necrosis in the intestines. Prevention consists of optimizing nutritional management and avoiding sudden feed changes. Autogenous vaccines in affected dairy herds have been tried with anecdotal success.

Last full review/revision March 2014 by Henry R. Stämpfli, DVM, DrMedVet, DACVIM

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