Intestinal infection with Salmonella is most commonly associated with the development of acute diarrhea in horses. However, Salmonella can induce a spectrum of intestinal disease in horses from a mild self-limiting diarrhea, to impaction of the small colon, to acute fulminant colitis with hemorrhagic diarrhea and endotoxemia. Foals are susceptible to serious consequences from intestinal infection with Salmonella, including septicemia and osteomyelitis. Salmonella poses a small but serious risk to hospitalized horses and is of significant concern to equine hospitals, as outbreaks of Salmonella-induced colitis can occur.
Introduction and Nomenclature Surrounding Salmonella and Horses
Salmonella is a large group of Gram-negative, rod-shaped bacilli, and a member of the Enterobacteriaceae family. The nomenclature of Salmonella is complex and continuously changing. For example, the serotype that commonly affects horses is Salmonella enterica subspecies Enterica serotype Javiana, which is generally abbreviated to Salmonella Javiana (USDA National Veterinary Services Laboratory). S. enterica ser. Typhimurium is the second most common type to affect horses, but probably the more recognized name. There are many other serotypes that cause intestinal disease in horses.
An interesting historical detail: Salmonella was named after an American veterinarian, Daniel E. Salmon, who in 1884 cultured the bacteria from pigs with hog cholera.
Epidemiology of Salmonella in Horses
Salmonella is a widespread organism that is commensal to the intestinal tract of many animals. Horses, however, do not harbor any host-adapted enteric strains of Salmonella, and are therefore susceptible to most serotypes of Salmonella (Lester 2003).
A variety of horse populations have been studied, both healthy and diseased, to establish the likelihood of fecal shedding of Salmonella. The occurrence is usually low, around 1% of the population, but can sometimes be up to 8%. One study found that Warmbloods and Arabs with colic symptoms had increased odds for Salmonella shedding (Dallap Schaer, B.L. et al. 2012).
Horses can acquire Salmonella in many settings. Salmonella can be accessed anywhere birds, and particularly poultry, are present– on pastures, in feeding bins, water troughs or stagnating creeks. Rodents, cattle, wildlife and many other animals can be carriers of Salmonella as well.
The virulence of the Salmonella strain and the dose ingested by the horse will influence the severity of disease, along with the horse’s immune status, systemic health and nutritional status.
Clinical cases of Salmonella colitis in horses tend to occur more frequently in the warmer months of the year.
Hospitalized horses are at risk of infection with Salmonella. Predisposing factors include dietary changes, any form of stress, gastrointestinal disease, anesthesia, surgery, and antimicrobial use.
Pathophysiology of Salmonella in Horses
The mechanism for Salmonella-induced intestinal disease is still being researched. What is known is that some serotypes of Salmonella have virulence factors that have a variety of effects on the intestinal mucosa, including assisting the bacteria to invade the intestinal mucosa.
The inflammatory response of the host to this invasion plays an important role in triggering hypersecretion by the enterocytes, which leads to diarrhea.
If the bacterial invasion and subsequent inflammation are severe enough, the mucosa becomes permeable to toxins, which, if they bypass or overwhelm the capacity of the liver, can induce a systemic response that results in endotoxemia and potentially systemic inflammatory response syndrome (SIRS).
Proteins, particularly albumin, will leak from the inflamed and damaged mucosa. This leads to a decrease in the colloid oncotic pressure, and subsequent tissue edema, including intestinal edema, which further exacerbates the intestinal dysfunction. Villous blunting and loss of absorptive surfaces can be severe and result in malabsorption.
Necrotizing enterocolitis is the terminal outcome of severe disease.
Clinical Signs of Salmonella Colitis in Horses
Clinical signs may be restricted to a mild self-limiting diarrhea, often with a fetid odor. In more severe acute cases, colic is the first clinical sign, which generally subsides as the diarrhea develops. Hematochezia is a rare, but highly concerning sign (Lester 2003).
Intestinal sounds are often fluidy and overactive, but can vary depending of the type and severity of the condition.
In acute cases of colitis, the horse may develop endotoxemia with a fever, elevated heart and respiratory rates, and congestion of the mucous membranes.
If the disease progresses, or is acutely severe, further complications can arise such as hypercoagulation (causing venous thrombosis), laminitis, and edema of the distal limbs and other ventrally dependent areas of anatomy.
Necrotizing enterocolitis is the most severe form of the disease and presents with an acute, brief clinical course with profound metabolic abnormalities and terminal severe abdominal pain that is refractory to analgesics. One study found the median time to death in these cases was 45.5 hours (Saville, W. et al. 1996).
Salmonella infections can be particularly severe in foals, as along with the diarrhea they can develop septicemia, osteomyelitis, synovitis, arterial thrombosis, laminitis, meningitis, abscesses, pyelonephritis, pneumonia and ocular infections.
Salmonella can also cause other forms of intestinal disease such as impaction of the small colon and cecum, as well as diffuse or localized small intestinal inflammation. If colic pain is persistent and diarrhea is not evident, then the horse should be checked for gastric reflux by nasogastric intubation, and for an impaction with a rectal exam. The rectal exam can irritate an already inflamed small colon and rectal mucosa, so the exam should be as gentle as possible, and the rectum infused with lidocaine prior, to minimize inflammation and straining.
Hematology and Biochemistry
A neutropenia with a shift to immature neutrophils and toxic changes is common in the acute phase. As the disease progresses, this may change to a mature neutrophilia with elevated fibrinogen.
Electrolyte derangements will likely occur and include hyponatremia, hypochloremia and decreased bicarbonate.
If the horse is dehydrated or has circulatory problems due to endotoxemia, the lactate will be elevated, as will the blood urea nitrogen (BUN) and creatinine. These derangements should resolve within 24-48 hours with appropriate fluid therapy, unless there is a secondary problem.
Hypoproteinemia can be profound, and progressively worsen. The severity can be masked if the horse is dehydrated.
Liver enzymes may show mild elevations secondary to endotoxemia or ascending infections.
Diagnosing Salmonella Colitis
The gold standard for Salmonella testing is aerobic culture of five fecal samples collected at 24 hours intervals. Early diarrhea tends to be watery and dilute, so the likelihood of positive culture will improve as the fecal consistency becomes more solid; however, this often means a significant delay before diagnosis is confirmed.
More rapid methods of testing include:
- Lateral Flow Immunoassays (LFI), such as Reveal® for Salmonella Test System, and RapidChek® SELECTTM for Salmonella. These tests offer the advantage of rapid point-of-care testing, and have a low occurrence of false positives, however the sensitivity is not high and repeat testing may be required. Also, the accuracy of the test varies with the strain and/or serotype. The test takes at least 18 hours to complete, as an enrichment period is required prior to running the test.
- Real-time PCR (qPCR) and DNA hybridization assays (DNAH). These tests can be highly sensitive, however they are more likely to provide a false positive as they can detect DNA of non-viable bacteria. Many diagnostic laboratories are now running PCR diagnostic profiles for diarrhea that include Salmonella.
Fecal aerobic culture is still recommended, as phenotypic and genotypic information is often useful for determining epidemiology, and in some cases antimicrobial selection.
Treatment for Salmonella Colitis in Horses
Treatment is generally supportive, as the Salmonella infection is usually self-limiting, and treatment is aimed at minimizing the systemic effects of endotoxemia.
- Intravenous fluids. Maintaining circulation and hydration is important particularly for kidney function, bowel function, circulation to the laminae of the hooves, and to dilute endotoxins.
- Plasma therapy. Commercial hyperimmune plasma contains antibodies and important proteins, including albumin, that help maintain circulation, minimize edema, and minimize the effects of endotoxemia. Non-commercial fresh frozen plasma can also be appropriate, if from a reliable source. 6-8 L of either product is recommended.
- Colloid therapy. The less expensive synthetic colloids have been used to support the circulation in the face of hypoproteinemia. Hetastarch (Hydroxyethyl starch) is commonly used, however the benefits of synthetic colloids are coming under debate. Plasma is preferable.
- Nonsteroidal anti-inflammatories (NSAIDs) and Polymixin B administration can also minimize the effects of endotoxemia, and NSAIDs may help with abdominal discomfort.
- Cryotherapy for the hooves and distal limbs has been shown to reduce the incidence of laminitis in horses with colitis (Kullman et al. 2014).
- Heparin may be required if a coagulopathy occurs.
- Antidiarrheal preparations such as activated charcoal and bismuth salicylate may help absorb luminal intestinal toxins.
- Antibiotics may not be required. Salmonella are intracellular pathogens that can thrive inside enterocytes, making antibiotic treatment extremely challenging. Antibiotics should be avoided in uncomplicated cases. Antimicrobials may even cause salmonellosis by inhibiting competitive microbes (Feary, D. et al. 2006). Lester (2003) suggests consideration of antibiotic use in the following situations:
- Evidence of extraintestinal infection
- Foals younger than 90 days
- Chronic recurrent enteric disease
The presence of severe leukopenia, neutropenia or septicemia.
Preventing Salmonella Infection
A vaccine is available for pregnant mares and foals, Vetivax Equine Salmonella Vaccine®.
Disinfectants that are active against Salmonella include accelerated Hydrogen Peroxide (i.e. Accel®), diluted 1:16; or 2% Peroxymonosulfate (i.e. Virkon-S®).
Most equine hospitals have stringent infectious disease protocols in place to prevent outbreaks of Salmonella and other diseases.
New and Alternative Treatment Options to Consider
Ongoing research in other species as well as some new research in equines shows the potential utility of some other substances for managing GI health in horses.
Glutamine
Glutamine helps to heal the mucosa and strengthen tight junctions between enterocytes. In several animal models, when salmonella infections start, enterocyte usage of glutamine immediately increases (Posho, L. et al. 1998). Treatment with glutamine in farmed animals has shown that, although there is little effect on fecal shedding, there is improvement of gut integrity and weight gain (Fasina, Y. et al. 2010) as well as mucosal healing (Kaya, E. et al. 2007).
Glutamine is a conditionally essential amino acid. During catabolic stress of the bowel, as found in infection and sepsis, glutamine is consumed at a rate exceeding its production, warranting supplementation (Rao, R. et al. 2011).
These studies come with a caveat: although they have been conducted on GI tracts in animals as varied as chickens, cows and pigs, there are as yet no similar studies in horses. However, these studies are consistent with reports of the utility of glutamine in right dorsal colitis (Rötting, A. et al. 2004) demonstrating a clear connection between glutamine and equine GI dysbiosis.
Mannan oligosaccharide
Mannan oligosaccharide (MOS) may be useful as a bacterial “sponge”, before, during and after a Salmonella infection. This complex sugar resembles the mannose sugars that coat enterocytes. These sugars are the main target of Salmonella, which binds to them with fimbrial lectins, bacterial projections which act as mannose receptors (Sharon, N. et al. 2015). Salmonella fimbria preferentially latch onto MOS instead of the mannose-coated enterocytes, and the unattached pathogen can then be shed in the feces. MOS can protect equines from most pathogens as effectively as antibiotics (Spring, P. et al. 2015).
MOS may also be useful as an emergency treatment for diarrhea in horses at a rate of 100-200 mg/kg, q8-24h (Orsini, J. et al. 2013).
Antibiotics save lives, but overuse or misuse can lead to resistant bacteria. MOS has not been shown to lead to bacterial resistance, which provides a good rationale for using MOS as a substitute for antibiotics wherever possible.
MOS has no known precautions or side effects (Orsini, J. et al. 2013).
References
- Dallap Schaer, B.L. et al. (2012) Identification of Predictors of Salmonella Shedding in Adult Horses Presented for Acute Colic. Journal of Veterinary Internal Medicine 26:1177-1185.
- Fasina, Y. et al. (2010) “Effect of Dietary Glutamine Supplementation on Salmonella Colonization in the Ceca of Young Broiler Chicks.” Poultry Science 89, no. 5 (May 2010): 1042–48. doi:10.3382/ps.2009-00415.
- Feary, D. et al. (2003) “Enteritis and Colitis in Horses.” Veterinary Clinics of North America: Equine Practice 22, no. 2 (August 2006): 437–79. doi:10.1016/j.cveq.2006.03.008.
- Kaya, E. et al. (2007) “The Effect of L-Glutamine on Mucosal Healing in Experimental Colitis Is Superior to Short-Chain Fatty Acids.” The Turkish Journal of Gastroenterology: The Official Journal of Turkish Society of Gastroenterology 18, no. 2 (June 2007): 89–94.
- Kullmann, A. et al. (2014) Prophylactic digital cryotherapy is associated with decreased incidence of laminitis in horses diagnosed with colitis. Equine Veterinary Journal 46:554-559.
- Lester, G. (2003) Salmonellosis. In: Current Therapy in Equine Medicine 5, chapter ed: AT Blikslager; book ed: N.E. Robinson. Saunders, St Louis Missouri pp. 56-59.
- Orsini, J. et al. (2013) Equine Emergencies: Treatment and Procedures. Elsevier Health Sciences.
- Posho, L. et al (1998). “Effects of Salmonella typhimuriumInfection and Ofloxacin Treatment on Glucose and Glutamine Metabolism in Caco-2/TC-7 Cells.” Antimicrobial Agents and Chemotherapy 42, no. 11 (November 1, 1998): 2950–55.
- Rao, R. et al. (2011) “Role of Glutamine in Protection of Intestinal Epithelial Tight Junctions.” Journal of Epithelial Biology & Pharmacology 5, no. Suppl 1-M7 (January 2012): 47–54. doi:10.2174/1875044301205010047.
- Rötting, A. et al. (2004) “Effects of Phenylbutazone, Indomethacin, Prostaglandin E2, Butyrate, and Glutamine on Restitution of Oxidant-Injured Right Dorsal Colon of Horses in Vitro.” American Journal of Veterinary Research 65, no. 11 (November 1, 2004): 1589–95. doi:10.2460/ajvr.2004.65.1589.
- Saville, W. et al. (1996) Necrotizing Enterocolitis: A Retrospective Study. Journal of Veterinary Internal Medicine 10:265-270.
- Sharon, N. et al. (2015) “Bacterial Adherence to Cell Surface Sugars.” Ciba Foundation Symposium 80 (1981): 119–41.
- Spearman, K. (2016) MOS supplements in for pregnant mares have been shown to significantly increase IgG, IgM and IgA levels in colostrum. Foals from mares fed MOS have a reduced incidence of diarrhea.
- Spring, P. et al. (2015) “A Review of 733 Published Trials on Bio-Mos®, a Mannan Oligosaccharide, and Actigen®, a Second Generation Mannose Rich Fraction, on Farm and Companion Animals.” Journal of Applied Animal Nutrition 3 (2015): e8 (11 pages). doi:10.1017/jan.2015.6.
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