Clostridium difficile is a large, gram-positive, anaerobic, spore-forming motile rod and is the major cause of antimicrobial-associated colitis in humans. 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 (microbiota) together with the presence of toxigenic C difficile strains that overgrow in the intestines are prerequisites for disease.
Diagnostic tests for C difficile toxins include cell cytotoxicity assays and ELISA on fecal samples, anaerobic culture, and PCR assay 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 regarding its 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 by 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 strong evidence that these organisms are responsible for enterocolitis in horses in approximately 20%–30% of cases of acute diarrhea.
Etiology of Clostridia-Associated Entercolitides 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 may include change in diet and antimicrobial 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 antimicrobial therapy is common in the history of horses with C difficile–induced diarrhea. Certain antimicrobials, notably macrolides and especially erythromycin ethylsuccinate, beta-lactam antimicrobials, 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) 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, beta-2, produced by some strains of C perfringens, has recently been strongly associated with colitis in horses.
Clinical Findings of Clostridia-Associated Entercolitides in Horses
Foals and adult horses may be affected. Typically, clinical signs include 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 exclusively have hemorrhagic duodenitis.
Diagnosis of Clostridia-Associated Entercolitides in Horses
Fecal culture and toxin detection
Toxin gene identification by PCR ribotyping
Clinical signs of the disease are similar to those of acute salmonellosis, Potomac horse fever, or monocytic ehrlichiosis. The identification of C perfringens as the cause of diarrhea in horses depends on detection 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 notable. The diagnosis of C difficile diarrhea is suggested by a history of recent treatment with antimicrobials and is supported by detection 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.
Control of Clostridia-Associated Entercolitides in Horses
Adequate isolation procedures and disease control in high-risk horses
Proper and judicious antimicrobial use
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 being administered antimicrobials. 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. No control measures are available for prevention of C perfringens–induced diarrhea. Administration of oral metronidazole (15 mg/kg, every 8 hours) 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 was 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 have 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 pathogenic strains in humans.
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 decade, 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 clostridia are recovered in most cases. The clinical course is peracute, with anorexia, colic, drop in milk production, 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.
