IN-DEPTH: NEONATOLOGY


rected toward epidemiological aspects in order to reduce the likelihood of coinfections. Clearly, ad- ditional studies are needed to determine equine coronavirus virulence factors and the relative im- portance as a coinfecting agent to contribute to GI disease in foals.


Diagnosis


Diagnosis can be made using polymerase chain re- action, virus isolation, or electron microscopy.


Treatment Refer to the Rotavirus section for treatment. Cur- rently there is an ultra-purified Bentonite clay that is available for the use in horses that has the same composition as a product being investigated for hu- man rotavirus or coronavirus.d,11


4. C. difficile


C. difficile is the agent that causes pseudomembra- nous colitis associated with antibiotics in humans. It is now being identified in recent years as a signif- icant nosocomial pathogen for equine as well as hu- man patients. First described in 1935 by Hall and O’Toole, this gram-positive anaerobic bacillus was named “the difficult clostridium” because it resisted early attempt at isolation and grew very slowly. The organisms were found in stool specimens from healthy human neonates (up to 50%), which led to its classification as a commensal and was subse- quently ignored as a potential pathogen. In the 1960s and 1970s, antibiotic-associated pseudomem- branous colitis became a major clinical problem, which was attributed to mucosal ischemia or viral infection. In 1977, Larson et al16 reported that stool specimens from affected patients contained a toxin that produced cytopathic changes in tissue culture cells. C. difficile was identified as the source of the cytotoxin. It is now clear that C. dif- ficile is responsible for virtually all cases of human pseudomembranous colitis and 20% of the cases of antibiotic-induced colitis.


Pathogenesis


Pathogenesis of antibiotic-associated diarrhea/ colitis begins with a disruption of colonization resis- tance (disruption of the normal colonic flora) of C. difficile. Colonization occurs by the oral-fecal route. C. difficile forms heat-resistant spores that can persist in the environment for years. These spores can survive the acid environment of the stom- ach and convert to vegetative forms in the colon. Environment contamination by C. difficile is partic- ularly common in human hospitals that have re- ported isolation rates of 11.7% to 29%.17 Health care personnel may carry bacteria on their hands, under rings, or on stethoscopes, but fecal carriage by staff is rare. High rates of infection can be isolated from stalls (hospital rooms), scales, thermometers, and surgical preparation room.17 C. difficile has also been implicated in an outbreak of colitis.17,18


218 2020  Vol. 66  AAEP PROCEEDINGS When established in the colon, pathogenic strains


of C. difficile produce toxins that cause diarrhea and colitis. Strains that do not produce toxins are not pathogenic. Two large exotoxins, toxin A (en- terotoxin) and toxin B (cytotoxin) are produced by C. difficile. Toxins A and B appear to act synergisti- cally which cause fluid secretion, mucosal damage, and intestinal inflammation. Toxin A is also a che- moattractant for human neutrophils in vitro.19 A third toxin, an actin-specific ADP-robosyltrans- ferase (binary toxin), has been identified in certain strains of C. difficile isolated from human patients. The role and the pathogenesis of binary toxin is unclear, but it may act synergistically with toxins A and B.20,21 The toxic effects appear to follow bind- ing of toxins to membrane receptors. After binding to its intestinal receptor, Toxin A enters the cell and alters the actin cytoskeleton, leading to cell round- ing. Toxin B causes the identical rounding. In human medicine, difficile is generally acquired


in the hospital setting. Neonatal colonization is common but almost invariably asymptomatic de- spite stool cytotoxin levels may be similar to those in adults with severe colitis. Over 50% of healthy hu- man infants have transient colonies of toxicogenic C. difficile. Baverud et al22 demonstrated that nei- ther C. difficile or cytotoxin B was found in the fecal flora of 56 healthy foals (14 days to 4 months of age) not being treated with antibiotics. Similarly, a small percentage of foals are reported to be asymp- tomatic carriers with reported rates ranging from 0% to 3%. Reported rates of asymptomatic carriers in adult horse populations are very similar to that of humans (1% to 15% of healthy adults) range from 0% to 4%.6,20 This organism, therefore, is most likely a minor and uncommon component of the usual gastrointestinal tract flora. Diarrhea and fa- tal hemorrhagic necrotizing enterocolitis have been reported to occur in neonatal foals infected with toxigenic strains of C. difficile, and C. difficile may be a primary pathogen in foals, not requiring prior antimicrobial use for development of the disease.20


Clinical Presentation


Clinical presentation of C. difficile in foals range from low-grade diarrhea to fulminate colitis with ileus. The foals with severe colitis become anorexic and dehydrated. In addition to the diarrhea, foals become tachypneic, which may be, secondary to dis- comfort associated with the enteritis, pyrexia, met- abolic acidosis, or the anxiety of being in the hospital. Hypoproteinemia is also a feature of C. difficile secondary to the effects of toxins A and B leading to extravasation of plasma proteins. Met- abolic acidosis is also consistent with clostridial en- terocolitis and hypovolemia or gastrointestinal tract loss of bicarbonate. Hyponatremia may also be at- tributable to the gastrointestinal tract losses, as well as to an excess of free water associated with water consumption by these foals.


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