Diarrhea in horses and foals (Proceedings)

Causes of Diarrhea in Adult Horses

Clostridial Diarrhea

Clostridium difficile is the most common cause of antibiotic-associated diarrhea and pseudomembranous colitis in humans and horses. Risk factors in man include systemic antimicrobial use, gastrointestinal surgery, proton pump inhibitors (like omeprazole), chemotherapy, increasing age, and lack of immune competence. The primary risk factor in horses is the use of antimicrobials which results in disruption of the normal gastrointestinal microflora, allowing proliferation of the pathogenic C. difficile organisms. With reduced colonization resistance, the overgrowth may be associated with toxin elaboration, and subsequent disease, ranging from mild diarrhea to severe, life-threatening colitis. Toxins include enterotoxin (Toxin A) and cytotoxin (Toxin B), which act synergistically to induce mucosal permeability, inflammatory cell chemotaxis, and epithelial cytotoxicity. The d PCR can be applied to isolates once cultured to evaluate for the presence of Toxin A and B genes. Diagnosis of the disease relies on positive fecal cultures and identification of toxins in fecal samples. Immunoassays (ELISA) are rapid, technically easy to perform, and readily available at most commercial laboratories; they are a means of directly identifying the presence of toxins in stool samples, however they may lack sensitivity. PCR can also be applied to isolates once cultured to evaluate for the presence of Toxin A and B genes. Specific treatment is with metronidazole, smectite adsorbents, and supportive care (described below). Because of its ability to form resistant spores, the microbe may survive in the environment for prolonged periods. Most disinfectants are ineffective against spores, however peroxygen compounds and bleach can be used to decrease spore concentrations.

Salmonellosis

Infections with Salmonella sp are clinically indistinguishable from clostridial colitis. Many serotypes of salmonellae affect horses, including S. anatum and S. krefeld (belonging to the antigen group E), and the more invasive S. typhimurium and S. agona (group B). In addition to diarrhea, salmonellae may produce septicemia, particularly in foals. As for clostridia, colic, gastrointestinal surgery, anorexia and antimicrobial agents predispose horses to the development of clinical disease. Following adherence to the gastrointestinal epithelium, salmonellae produce exotoxins, leading to ion and fluid flow from the cell, with subsequent invasion of the cell. Salmonellae are intracellular pathogens. Once there, the bacteria result in death of the cell through cytotoxin-induced inhibition of protein synthesis. Treatment is primarily supportive. Systemic antimicrobials do not change the course of the GI infection. However, neonatal foals should always be covered with antimicrobials to prevent secondary bacteremia. If kidney function is normal, amikacin should be used. If foals are azotemic, ceftiofur or other 3rd-4th generation cephalosporin should be administered. Adult horses should be protected from bacteremia with antimicrobials (aminoglycoside or enrofloxacin) if they are markedly neutropenic (< 1000/µl) or febrile.

Other causes

Equine monocytic ehrlichiosis (Potomac horse fever) is caused by Neorickettsia risticii, an important cause of diarrhea in the east, as well as along the Oregon border (Shasta river) and Grass Valley in California. In addition to its geographic restrictions, the disease occurs with summer and fall seasonality. The resulting colitis and endotoxemia are clinically similar to that of other etiologies; however, laminitis appears to have a higher prevalence with this disease. In addition, abortion may occur in pregnant mares. Treatment is with oxytetracycline (can be followed with doxycycline) and supportive care, although horses must be kept well hydrated while on oxytetracycline.

Larval cyathostomiasis occurs when large numbers of small strongyle L4 larva undergo arrested development within the wall of the gastrointestinal tract. This usually leads to chronic weight loss and diarrhea, but occasionally horses present with acute diarrhea. Young horses housed on pasture with poor deworming histories are at highest risk. The diarrhea is often associated with marked protein loss, leading to hypoalbuminemia. Treatment is with larvicidal doses (10 mg/kg, PO) of fenbendazole daily for 5 days.

Newer agents currently under investigation as to their role in equine colitis include Aeromonas sp. One study found a prevalence of 55 % of this microbe in the feces of horses with diarrhea (n=40), as compared to 0 % in those without diarrhea. However, many of the horses in that study were concurrently infected with Salmonellae, intestinal parasites, or viruses (Hathcock, 1999). Lawsonia intracellularis has been receiving attention recently as a cause of diarrhea and protein losing enteropathies in foals 2-18 months of age. This disease should be suspected in foals with weight loss, hypoalbuminemia, colic, and diarrhea, or with ultrasonographic evidence of small intestinal thickening. Antemortem diagnosis can be difficult, but may be attempted with serology (titers) and fecal PCR (several pooled samples).

Right dorsal colitis secondary to phenylbutazone and other NSAID intoxication may result in diarrhea, as well as hypoproteinemia, colic, and signs of endotoxemia. Young performance horses, ponies, and dehydrated horses appear to be at highest risk. Inhibition of PGE, with a subsequent reduction in perfusion of the gastrointestinal mucosa, a decrease in mucus and bicarbonate secretion, and a delay in migration of basal epithelial cells towards the lumen, result in gastrointestinal injury. Treatment is with Misoprostol, sucralfate, and pelleted feed. Colloids are optimal fluids, when fluid therapy is necessary.

Horses can develop diarrhea from dietary causes, such as moldy feed, or toxins such as blister beetle or oleander.

Enterocolitis and diarrhea in neonatal Foals

1. Viral Causes

Rotavirus is a common cause of diarrhea and enteritis in foals up to a few months of age. It is a distinct genus of viruses that belong to the family Reoviridae (dsRNA, nonenveloped). It affects the small intestinal microvilli, leading to maldigestion and malabsorption. Lactase deficiency is a common sequel to rotaviral infection. Some hypersecretion also occurs. Clinical signs are similar to those seen with other causes of diarrhea – the foals are depressed, have a decreased appetite, and are febrile. Diarrhea then follows within 12-24 hours, and affected foals may develop hyponatremia, hypochloremia, and acidosis as with other causes of enterocolitis. Rotaviral diarrhea may occur as an outbreak or as sporadic cases, and many foals (particularly older foals) may be subclinical. Shedding may occur for several days after clinical signs resolve, but intermittent shedding has been reported for as long as 8 months. The organism may persist in the environment for many months under the right conditions. The diagnosis is based on enzyme-linked imunosorbent assay (ELISA) or electron microscopy of feces. Treatment is supportive. Exogenous lactase enzyme should be provided (3000-6000 IU/average size foal PO, q 3-6 h). For severe cases that are non-responsive to supportive care, extra label use of nitazoxanide has been tried as this drug is used in humans with rotaviral diarrhea. A vaccine for broodmares is available in Kentucky where outbreaks are common. The vaccine confers partial immunity to the foal through colostrum – ie, it reduces the severity of disease and the prevalence. Control measures include good hygiene on farms as well as phenolic agents as disinfectants (the virus is resistant to many other disinfectants such as bleach or quaternary ammonium compounds).

Other viruses that have been associated with diarrhea in foals include Coronavirus, Adenovirus, and Parvovirus, although they are considered far less common than Rotavirus and their role in equine diarrhea remains to be studied.

2. Clostridial Enterocolitis in Neonatal Foals

Neonatal foals are susceptible to Clostridium perfringens and Clostridium difficile.

Clostridium perfringens: types A and C can affect foals, leading to diarrhea, colic, and death. Type A is most common, while type C is most fatal. The disease usually affects foals less than seven days of age-especially those three days and younger although older animals can be affected less severely. Colic and bloating may be the only signs evident before death ensues, particularly with type C. Hemorrhagic diarrhea may be present, especially with type C. Diagnosis is based on culture of the organism while ruling out other pathogens, as the organism can be found in normal animals. New ELISAs are available to detect clostridial toxins, and are available at the California Animal Health and Food Safety Laboratory, San Bernadino. Alternatively, once cultured, the isolate could be evaluated for the presence of toxin genes via PCR, in order to identify the type and establish pathogenicity. Treatment involves metronidazole – early treatment of suspect cases is the key. Presumptive, empirical treatment is key; in other words, colic, gas distention, and diarrhea in a young foal should raise the suspicion of Clostridium perfringens, especially if leukopenia is evident. This should warrant metronidazole therapy until diagnostics are completed. Hyperimmune plasma with types C and D antitoxin has been tried. One thing to note is that foals with high levels of IgG appear to be at risk for clostridiosis. It is thought that colostral trypsin inhibitors (that are meant to inhibit degradation of colostral IgG by the gastric pH) may protect the clostridial toxins from gastric degradation and allow them to survive through to the small intestine where they cause enteritis.

Clostridium difficile: Clostridium difficile can affect neonates without prior antibiotic use, very different to what occurs in adult horses (i.e., it can infect neonates as a primary pathogen). Clostridium difficile can cause watery diarrhea or severe, hemorrhagic diarrhea. It can also lead to lactase deficiency, with a secondary osmotic effect. Treatment is with metronidazole, lactase enzyme, smectite and supportive care. There is some evidence that NZT may be effective against Clostridium difficile in humans.

3. Salmonellosis:

This is similar to what occurs in adults, only more severe. Neonates should always be covered with broad-spectrum antibiotics to protect against bacteremia, particularly with enteroinvasive pathogens such as Group B salmonellae.

4. Parasitic causes:

Cryptosporidium parvum: This protozoal agent can cause outbreaks of diarrhea in foals. The organism invades the microvillous portion of the epithelium, just under the cell membrane – it is intracellular, but extra-cytosolic. It causes blunting of the villi and malabsorption with a secondary osmotic pull. Healthy foals and adults may shed the organism subclinically. Diarrhea is usually evident at 5 days of age or older, although younger foals may be affected with heavy contamination. Detection of oocysts via fecal flotation, acid-fast staining, or immunofluorescence is diagnostic. Treatment primarily consists of supportive care. Paromomycin is an experimental drug used in calves and human AIDS patients with cryptosporidial enteritis. Azithromycin and nitazoxanide (NZT) also have some activity, but these require further study and should only be used if supportive care is unsuccessful in severe cases. Cryptosporidium is zoonotic and oocysts can remain viable in the environment for months. Formalin, peroxide, ammonia, and undiluted bleach have some efficacy against the agent.

Strongyloides westeri ("Threadworm") : This worm is an unusual cause of diarrhea in neonates. The route of infection is ingestion of milk that contains larvae. Patent infections can be diagnosed via fecal flotation with salt or sugar solutions. The egg is embryonated and approximately half the size of a Strongyle egg. The prepatent period is 8-14 days. Foals may be infested subclinically and heavy infestations can result in diarrhea. Prevention is through anthelmintic treatment of the dam shortly before or after foaling. Effective anthelmintics include ivermectin, benzimidazoles, and febantel. These agents may be used to treat infected foals as well.

5. Other causes of diarrhea in foals–

     • Foal Heat diarrhea – 5-14 d of age; b. Pica – ingesting dirt, sand, hair, feedstuffs; c. gastroduodenal ulceration; d. overfeeding or milk substitutes; f. hypoxemia or hypoperfusion to the gut – part of sepsis, hypoxic encephalopathy, or necrotizing enterocolitis

Diarrhea in Suckling/Weanling Age Foals:

In addition to the diseases adult horses are susceptible to, as well as some of the agents neonates get, older foals also develop diarrhea from the following two agents:

1. Rhodococcus equi : Can cause granulomatous enterocolitis and diarrhea in foals 1-5 months of age. They may have pyogranulomas in the lungs, colon, and mesenteric lymph nodes. Diagnosis is by exclusion of other agents, the presence of R. equi in the lungs, and fecal PCR or fecal culture. Treatment: macrolide and rifampin. Recently, azithromycin or clarithromycin has been used in place of erythromycin as the macrolide.

2. Lawsonia intracellularis: Proliferative enteropathy in 2-18 month old foals. Clinical signs include lethargy, weight loss, diarrhea, poor hair coat, potbelly, colic, and edema. Ultrasonography shows markedly thickened small intestinal walls, similar to R. equi. Marked pan-hypoproteinemia is evident. Diagnosis: Antemortem= serology (titer > 1:30) and fecal PCR. Postmortem=histopathology, silver stains. Treatment is with oxytetracycline, doxycycline, azithromycin +/- rifampin, clarithromycin, or chloramphenicol. Renal function should be monitored in foals on oxytetracycline. Macrolides can cause enterocolitis.

Treatment of Colitis

Treatment of horses with colitis is largely supportive. Specific therapy may be directed toward particular agents. For example, clostridial (ie, C. difficile and C. perfringens) enterocolitis is treated with metronidazole (15 mg/kg PO q 8 h for adults, and 10 mg/kg PO q 8-12 hours for foals). Neorickettsia risticii is treated very effectively with oxytetracycline (6.6 mg/kg IV diluted in 5 % dextrose in water, once daily for 3-7 days) or oral doxycycline (10 mg/kg PO, BID). Lawsonia intracellularis is treated with oxytetracycline (6.6 mg/kg IV, q 24 h (monitor kidneys!) followed by 10 mg/kg PO q 12 h doxycycline), oral azithromycin (10 mg/kg PO, q 24h for 5 days, then every other day) +/- rifampin (5 mg/kg PO, BID), or chloramphenicol (50 mg/kg PO, q 6-8 h). Rhodococcus equi is treated with azithromycin, clarithromycin or erythromycin and rifampin. Colitis induced by NSAIDs may be treated with antiulcer medication (if gastric ulcers are present), as well as synthetic PGE1 (Misoprostol). Dietary adjustments are very important in the therapy of right dorsal colitis, including a pelleted diet (a low-bulk diet to 'rest' the colon), psyllium, and corn or canola oil to provide short chain fatty acids that are beneficial for colonic healing. Larval cyathostomiasis is treated with moxidectin (labeled dose) or high dose fenbendazole (most effective treatment-10 mg/kg PO, q 24 h for 5 days). Sand impactions are treated with psyllium and IV or oral hydration, and surgery in severe cases.

Supportive care consists of restoration of blood volume and ultimately hydration status. This is achieved through the use of replacement crystalloids (LRS, Plasma-Lyte 148, Normosol R or 0.9% saline) and colloids (plasma, hetastarch, concentrated albumin). Hypertonic (7-7.5 % sodium chloride) saline can be used as a rapid volume expander (up to 4 ml/kg IV) in severely volume-depleted adult horses that still have some interstitial fluid to mobilize. Flunixin meglumine (banamine) should be utilized at anti-endotoxic doses (0.25 mg/kg IV, TID), aimed at reducing excessive prostaglandin production by inhibiting cyclooxygenase activity. Use of flunixin or other NSAIDS should be done with caution in neonatal foals. Low molecular heparin (such as Dalteparin 50 U/kg SQ, q 24 h) can be used to minimize thrombotic complications.

Prokinetics, particularly lidocaine (1.3 mg/kg loading dose slowly, followed by a CRI of 0.05 mg/kg/min, IV), can be used if obstructions have been ruled out and the horse has ileus with a lack or absence of fecal production. Lidocaine offers the advantages of analgesic and antiinflammatory properties. Agents used for combating endotoxemia are controversial and include pentoxyfylline, polymyxin B, and DMSO. Activated charcoal (0.5 kg for a 500 kg horse) given repeatedly may reduce the absorption of endotoxin, and may bind other toxicants as well. Antioxidants such as DMSO, vitamin E, selenium, or superoxide dismutase may be helpful for minimizing oxidative damage.

Other therapies include bismuth subsalicylate, which may reduce local prostaglandin production, reduce colonic secretion, and aid in binding endotoxin within the gastrointestinal lumen. Transfaunation with colonic or fecal contents from a normal adult horse may provide bacteria to aid in reestablishing normal GI flora, although this remains to be documented. Donor horses should be tested negative for Salmonella sp. and other pathogens. The horse should also have access to salt blocks, as well as oral electrolyte solutions and fresh water for self-regulation of hydration and electrolyte status. Anti-ulcer medication should be utilized whenever gastric ulcers are documented, or when anorexia is prolonged (anorexia alone can induce nonglandular ulcers because horses are constant acid secretors). Cimetidine (6.6-20 mg/kg PO, TID), ranitidine (8 mg/kg PO, BID-TID; 1.5-2 mg/kg IV BID), famotidine (2.8 mg/kg PO q 12 h or 0.3 mg/kg IV q 12), or omeprazole (4 mg/kg PO, q 24 h) can be utilized.

Antibiotics should be used judiciously in adult horses in order to prevent further exacerbation of the colitis through alterations in the gastrointestinal flora. Neonatal foals should be treated with broad-spectrum antibiotics because of risks of bacteria or sepsis. Whenever renal failure is not present, aminoglycosides, such as amikacin (15-21 mg/kg, IV q 24h) or gentamicin (6.6 mg/kg IV, q 24 h), can be administered whenever horses are neutropenic or febrile. The goal of this therapy is not aimed at a specific pathogen, but rather to minimize the potential for bacterial translocation of enteric organisms associated with a compromised mucosa. Aminoglycosides are considered relatively safe in regards to the normal GI flora, as they are poorly distributed to the lumen and have no anaerobic activity. Urinalyses and serial serum creatinine concentrations should be monitored closely in horses treated with aminoglycosides.

General supportive care, including good nutrition, should also be addressed. Partial or total parenteral nutrition should be supplied in anorectic horses.

Complications

Secondary complications include thromboses and infarctions due to coagulation disorders, including jugular thromboses where catheters are in place. Due to risks of thrombophlebitis, minimally thrombogenic catheters should be utilized, such as those comprised of polyurethane. Laminitis is frequently a life-threatening complication, especially when involving distal displacement of the third phalanx. Icing of the feet may be prophylactic in these endotoxic horses. Other sequelae of colitis include septicemia, peritonitis, renal or other organ failure, chronic diarrhea, weight loss, and adhesions/constrictions. Due to altered forward, progressive motility of the large and small colons, horses recovering from severe colitis should be monitored for impactions as they are recovering from the diarrhea.