ACVP 2017: Clostridium difficile Infection - An Emerging Zoonosis?

According to Francisco A. Uzal, DVM, PhD, DACVP, professor of veterinary diagnostic pathology at the University of California, Davis, most clostridial diseases affect both humans and animals.

Presenting at the American College of Veterinary Pathologists 2017 Annual Meeting in Vancouver, British Columbia, Canada, Dr. Uzal emphasized that “Clostridium difficile is considered the main cause of antibiotic-associated diarrhea in humans and in most animals.” However, he noted that antibiotic administration is not an important risk factor for development of C. difficile—associated disease (CDAD) in piglets and foals, for reasons that are poorly understood.

Nevertheless, in most species, antimicrobial administration causes disruption of the normal protective intestinal flora, said Dr. Uzal. In veterinary species, in particular, this is associated with virtually any antibiotic. Subsequent C. difficile infection then leads to germination of bacterial spores in the small intestine, colonization of the organism in the large intestine, and production of the bacterial toxins that cause characteristic intestinal CDAD lesions.

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Infection with C. difficile occurs via exogenous or endogenous routes. The exogenous route occurs most commonly and represents the traditional route of infection, he noted, involving ingestion of C. difficile spores, which are ubiquitous in the environment. In contrast, endogenous infection involves proliferation of endogenous C. difficile toxigenic strains in the intestinal tract.

The two main toxins produced by C. difficile are toxin A (TcdA, an enterotoxin) and toxin B (TcdB, a cytotoxin). Traditionally, researchers considered TcdA to be the more virulent of the two toxins, said Dr. Uzal, but experts now believe that both toxins act synergistically. “The idea is that toxin A disrupts epithelial integrity and allows toxin B into the cell,” leading to necrotizing enterocolitis, he explained.

The distribution of CDAD lesions in the intestinal tract of horses tends to be age dependent, said Dr. Uzal. Typically, foals younger than 1 month develop lesions in the small intestine, whereas older animals tend to develop lesions in the colon and cecum. Although necrotizing enterocolitis in horses is not specific for CDAD, Dr. Uzal stressed that it should lead diagnosticians to at least consider CDAD high on the list of diagnostic differentials.

In pigs, C. difficile infection causes mesocolonic edema in addition to necrotizing enterocolitis. However, mesocolonic edema is also not specific for this infection in pigs, he said.

Dr. Uzal emphasized that diagnosis of CDAD relies on a combination of gross and microscopic lesions, detection of toxins, and demonstration of C. difficile by culture or DNA-based tests.

C. difficile is also the most common cause of health care—associated infections in many countries, he added. And, although there are no definitive data proving transmission of C. difficile infection to humans, increasing evidence points toward a zoonotic potential. For example, some C. difficile ribotypes that are virulent for humans, including the emerging ribotype 078, are found in high numbers in the intestinal tracts of various food animal species, such as cattle and pigs. C. difficile infection, therefore, very likely is a zoonotic infection, concluded Dr. Uzal.