2010's Top Equine Medicine Studies (AAEP 2010)
What would be your pick for the most groundbreaking news in equine veterinary internal medicine for 2010? Not sure? Read on to find out what Steve Reed, DVM, Dipl. ACVIM, of Rood & Riddle Equine Hospital in Lexington, Ky., deemed the most important news in equine internal medicine in 2010. He presented this discussion during the Kester News Hour session to help kick off the 2010 American Association of Equine Practitioners Convention, held Dec. 4-8 in Baltimore, Md.
Metabolic Syndrome, Cushing's Disease, and Laminitis
Metabolic syndrome is a widespread problem in horses, as is the laminitis that's often associated with it.
"Laminitis is one of the most important issues facing all of us in veterinary practice," said Reed. He discussed several studies and scientific communications related to metabolic syndrome and Cushing's disease, starting with a consensus statement from the American College of Veterinary Internal Medicine (published in the Journal of Veterinary Internal Medicine, JVIM) covering characteristics, diagnosis, and management of equine metabolic syndrome (EMS).
"Equine metabolic syndrome is characterized by regional adiposity (fat deposits), insulin resistance, and a predisposition to developing laminitis," summarized Reed. "Insulin resistance is characterized by hyperinsulinemia (high levels of insulin in the blood) and abnormal response to glucose/insulin testing. These horses have hyperinsulinemia in the absence of stress, pain, or recent feeding; sometimes the blood samples even look different grossly (to the naked eye). Dietary management includes reducing the energy provided in the diet, feeding lower levels of nonstructural carbohydrates (NSC), limiting access to pasture grass. Increasing physical activity is critical."
Veterinarians on a JVIM study compared the composition of fat in different places on EMS-affected horses' bodies, and they found that fat in the nuchal ligament (in the neck) had higher levels of pro-inflammatory cytokines (mediators of inflammation) than fat in other locations, and that these levels seemed unaffected by the horse's systemic (body-wide) level of insulin resistance. Reed commented that horses with large crests of fat on their necks were at higher risk for insulin resistance, and that this area of the horse seems to adopt an inflammatory state more quickly than other areas.
One issue with studying metabolic syndrome is that it can be hard to differentiate from pituitary pars intermedia dysfunction (also called Cushing's disease), noted Reed. While discussing two JVIM studies on hormone testing in horses presumed to have Cushing's disease, he commented that Cushing's disease often affects older horses than EMS does, and diagnosis can be difficult due to seasonal variations in the hormone levels used for diagnosis. However, insulin levels did not vary by season, so high levels "should raise suspicion of EMS, ECD, or both," wrote the study authors.
Cushing's horses "have cresty necks, long coats that fail to shed properly, polyuria (excessive urination) and polydypsia (excessive thirst), ravenous appetites, are prone to laminitis, and may or may not be obese," Reed noted.
Back to insulin resistance, another study in this area (in the American Journal of Veterinary Research, or AJVR) found that pre-treatment of horses at risk for endotoxemia (such as those with colic or carbohydrate overload) with levothyroxine could inhibit laminitis caused by endotoxemia-induced insulin resistance. "Figuring out ways to prevent secondary laminitis is critical," Reed commented.
Metformin is one medication that's sometimes recommended for treating insulin resistance. However, researchers on a study published in AJVR reported that metformin has low bioavailability in horses, which could be why it sometimes garners poor long-term results.
Investigators completing an AJVR study on the effects of weight gain on hormone profiles found, unsurprisingly, that feeding horses double the calories recommended resulted in increased insulin resistance that was compensated for by increased insulin secretion (hyperinsulinemia). Hyperleptinemia (high levels of leptin hormone, which reduces appetite) was also observed.
"Preventing obesity is a potential strategy to help avoid insulin resistance, hyperinsulinemia, and hyperleptinemia in horses," wrote the study authors.
Finally, Reed touched on a paper published in Equine Veterinary Journal regarding equine clinical genomics, or study of the horse's genetic code and inherited diseases. "Several groups are using the horse's genetic sequence to study diseases such as hyperkalemic periodic paralysis (HYPP), and people are also interested in using this to investigate EMS," said Reed. "We can submit blood samples to Dr. Molly McCue at Minnesota for horses that have the characteristic EMS phenotype, so perhaps they can identify a genetic marker for the disease."
All three presenters acknowledged the difficulty in managing and feeding horses with EMS. Palmer commented, "Owner compliance can be a real problem; they might say, 'Doc, he only gets a handful of this or that, so how do you restrict them further?' ""It's very difficult," admitted Reed. "Owners need to be aware that you're not being kind to these horses when you put them outside at certain times of the year. Even pasture is not always your horse's friend, because grass at certain times of the year can be a big predisposing factor to developing laminitis."
- Frank N, Geor RJ, Bailey SR, Durham AE, et al. Equine metabolic syndrome ACVIM consensus statement. J Vet Intern Med 2010;24:467-475.
- Burns TA, Geor RJ, Mudge MC, McCutcheon LJ, et al. Proinflammatory cytokine and chemokine gene expression profiles in subcutaneous visceral adipose tissue depots of insulin-resistant and insulin-sensitive light breed horses.J Vet Intern Med 2010;24:932-939.
- Tinworth KD, Edwards S, Harris PA, Sillence MN, et al. Pharmacokinetics of metformin after enteral administration in insulin-resistant ponies. Amer J Vet Res 2010;71(10):1201-1206.
- Frank N, Elliott SB, Chameroy KA, Toth F, et al. Association of season and pasture grazing with blood hormone and metabolic concentrations in horses with presumed pituitary pars intermedia dysfunction. J Vet Intern Med2010;24:1167-1175.
- Place NJ, McGowan CM, Lamb SV, Schanbacher BJ, et al. Seasonal variation in serum concentrations of selected metabolic hormones in horses. J Vet Inter Med 2010;24:650-654.
- Toth F, Frank N, Geor RJ, Boston RC. Effects of pretreatment with dexamethasone or levothyroxine sodium on endotoxin-induced alterations in glucose and insulin dynamics in horses. Amer J Vet Res 2010;71(1);61-68.
- Carter RE, McCutcheon LJ, George LA, Smith TL, et al. Effects of diet-induced weight gain on insulin sensitivity and plasma hormone and lipid concentrations in horses. Amer J Vet Res 70;(10)2009:1250-1258.
- Brosnahan MM, Brooks SA, Antzak DF. Equine clinical genomics: A clinician's primer. Equine Vet J2010;42(7)658-670.
Equine herpesvirus (EHV) can cause respiratory disease, neurologic disease, or abortion. It can become dormant in the horse's body but recrudesce (reactivate) when the horse is stressed, which has been suspected to cause outbreaks of associated disease. In one JVIM study, investigators infected horses with EHV, then stressed them four months later with dexamethasone (a corticosteroid, which reduces immune function and can be used to treat allergic reactions and other inflammatory conditions). The virus reactivated and subsequently was detected in blood and nasal secretions of all horses, and one developed a fever, but uninfected horses placed in contact with those horses did not become ill.
Another JVIM study on EHV highlighted the extremely contagious nature of the virus in the context of a nosocomial (hospital-acquired) outbreak of the disease at a university equine hospital following admission of an infected horse. The index case was handled with "strict infection control procedures," yet six other horses became infected and two caused outbreaks at their home farms afterward.
"We must have preplanned infection control programs and the virus may still move from horse to horse, so early detection and isolation with a strict protocol is essential," Reed commented.
- Pusterla N, Hussey SB, Mapes S, Johnson C, et al. Molecular investigation of the viral kinetics of equine herpesvirus-1 in blood and nasal secretions of horses after corticosteroid-induced recrudescence of latent Infection. J Vet Intern Med 2010;24:1153-1157.
- Goehring LS, Landholt GA, Morley PS. Detection and management of an outbreak of equine herpesvirus type 1 infection and associated neurological disease in a veterinary teaching hospital. J Vet Intern Med. 2010;24:1176-1183.
Lawsonia intracellularis can cause weight loss, loose feces, edema, and hypoproteinemia (low protein levels) in foals. Reed discussed a JVIM study that confirmed foals could acquire the disease from ingesting feces or food contaminated with feces from infected foals. The infected foals began shedding L. intracellularis in their feces 12-18 days after infection and shedding lasted for seven to 21 days.
"At least this disease is treatable with simple antibiotics, usually oxytetracycline," Reed commented.
- Pusterla N, Wattanaphansak S, Mapes S, Collier J, et al. Oral infection of weanling foals with an equine isolate of Lawsonia intracellularis, agent of equine proliferative enteropathy. J Vet Intern Med 2010;24:622-627.
Authors of another hospital infection report described an outbreak of Salmonella newport that affected 61 animals in a veterinary teaching hospital, killing 36% of them and necessitating closure of the hospital for thorough decontamination and remediation of biosecurity. Study authors estimated the costs of the outbreak at $4.12 million.
"The biggest benefits of rigorous infection control and surveillance strategies are earlier detection (of highly infectious organisms like Salmonella), earlier cessation (shorter outbreaks), and improved ability for aggressive intervention," said Reed.
- Dallap-Schaer BL, Aceto H, Rankin SC. Outbreak of salmonellosis caused by Salmonella enterica serovar Newport MDR-AmpC in a Large Animal Veterinary Teaching Hospital. J Vet Intern Med 2010; 24: 1138-1146.
Piroplasmosis, caused by the organisms Babesia caballi and Theileria equi, is a disease found worldwide that causes anorexia, anemia, fever, malaise, and icterus (jaundice) in horses. "This disease recently re-emerged in the United States; it's a persistent infection but often clinical signs are nonspecific," said Reed. Following discussion of a Parasitology Research paper, he added, "Serologic tests are useful for detecting latent infection."
- Jaffer O, Abdishakur F, Hakimuddin F, et al. A comparative study of serological tests and PCR for the diagnosis of equine piroplasmosis. Parasitol Res 2010;106:709-713.
- Traub-Dargatz JL, Short M, Pelzel A, Norman T, et al. In-depth Session: Equine Piroplasmosis AAEP Sunday December 5, 2010 Baltimore, MD.
Antibiotic-Resistant Rhodococcus equi
Rhodococcus equi causes sometimes-fatal pneumonia in foals, and is a "big problem in foals three weeks to five months of age," said Reed. In this study (published in the Journal of the American Veterinary Medical Association, JAVMA), researchers found that while infection with antibiotic-resistant R. equi was not common (3.7% of submitted R. equi samples), 63.2% of those resistant isolates were resistant to more than one antimicrobial, and foals infected with those strains were nearly seven times more likely to die from their infections. The study authors emphasized the value of culturing the causative organism in foal pneumonia cases, and determining susceptibility of the organism to antibiotics to treat the disease successfully.
- Giguère S, Lee E, Williams E, Cohen N, Chaffin K, Halbert N, Martens R, Franklin R, Clark C, Slovis N. Determination of the prevalence of antimicrobial resistance to macrolide antimicrobials or rifampin in Rhodococcus equi isolates and treatment outcome in foals infected with antimicrobial-resistant isolates of R equi. J Am Vet Med Assoc 2010; 237:74-81.
Heart Problems in Racehorses
Reed discussed three studies on cardiac (heart) function in racehorses, starting with one JVIM article in which veterinarians sought to investigate heartbeat variations in healthy racing Standardbreds. The researchers found that "arrhythmias occur frequently in racing Standardbreds during cardiac deceleration (when slowing down after a race). ... Circumstances imposing unusual demand and racing at the trot appear to predispose (horses to arrhythmia). These findings provide insight into possible mechanisms of sudden death."
Researchers on a second JVIM study with a similar goal used a sophisticated treadmill evaluation along with echocardiography, Doppler imaging, and speckle tracking to investigate left ventricular function (activity of the left lower chamber of the heart) in healthy horses. "This is important because if we could learn about stress echocardiography in horses, we could target certain diseases and investigate medications that are important in management and performance issues," explained Reed.
Lastly, investigators on an AJVR study evaluated the use of a horse-side analyzer for cardiac troponin I, a protein involved in heart muscle contraction. The authors found that the horse-side analyzer compared well against a laboratory test, but Reed commented that it took significant induced cardiac disease to detect differences in cardiac troponin I levels.
- Physick-Sheard and M.K.J. McGurrin. Ventricular Arrhythmias during Race Recovery in Standardbred Racehorses and Associations with Autonomic Activity. J Vet Intern Med 2010;24:1158-1166.
- Schefer KD, Bitschnau C, Weishaupt MA, Schwarzwald CC. Quantitative analysis of stress echocardiograms in healthy horses with 2-dimensional (2D) echocardiography, anatomical M-mode, tissue doppler imaging and 2D speckle tracking. J Vet Intern Med 2010;24;918-931.
- Kraus MS, Jesty SA, Gelzer AR, Ducharme NG, et al. Measurement of plasma cardiac troponin 1 concentration by use of a point-of care analyzer in clinically normal horses and horses with experimentally Induced Cardiac Disease.Am J Vet Res January 2010;71(1):55-59.
To study treatments for a disease, one must be able to first induce the disease. Reed described one study from AJVR in which researchers found that a combination of certain fungal spores, lipopolysaccharide, and silica microspheres worsened recurrent airway obstruction (RAO) in susceptible horses.
"This appears to provide a useful model for future research," he commented.
A research team on another RAO study, this article from JVIM, reported an association between RAO and increased parasite resistance. A third study (from EVJ) was the first to show improvement in RAO-affected horses with oral prednisolone medication, and also found that low-dose oral dexamethasone was effective (even more so than prednisolone).
Researchers also investigated genetic markers for a form of RAO known as summer pasture-associated obstructive pulmonary disease (striking horses on summer pasture rather than those in dusty barn environments), and reported that the disease was a "multifactorial, complex form" with several genes involved."
Lastly, Reed discussed an EVJ study in which veterinarians compared horse owner-assessed respiratory signs (RAO-affected horses' clinical signs graded by owners on a scale of 1-4) with thorough veterinary examination of the lower respiratory tract. The researchers reported that horse owners' assessment of their horses' respiratory disease correlated well with the veterinary evaluation.
"Listen to owners--they know their horses," commented Reed.
- Beeler-Marfisi J, Clark ME, Wen X, Sears W, et al. Experimental induction of recurrent airway obstruction with inhaled fungal spores, lipopolysaccharide and silica microspheres in horses. Amer J Vet Res 2010;71(6):682-689.
- Neuhaus S, Bruendeler P, Frey CF, Gottstein B, et al. Increased parasite resistance and recurrent airway obstruction in horses of a high prevalence family. J Vet Intern Med 2010;24:406-413.
- Leclere M, Lefebvre-Lavoie J, Beauchamp G, Lavoie JP. Efficacy of oral prednisolone and dexamethasone in horses with recurrent airway obstruction in the presence of continuous antigen exposure. Equine Vet J 2010;May 42(4):316-321.
- Venugopal CS, Mendes LC, Piero JR, Laborde SS, et al. Transcriptional changes associated with recurrent airway obstruction in affected and unaffected horses. Am J Vet Res 2010 Apr 71;(4):476-482.
- Christmann U, Hite RD, Tan RH, Thatcher CD, et al. Surfactant alterations in horses with recurrent airway obstruction at various clinical stages. Am J Vet Res 2010 Apr 71;(4):468-475.
- Laumen E, Doherr MG, Gerber V. Relationship of horse owner assessed respiratory signs index to characteristics of recurrent airway obstruction in two warmblood families. Equine Vet J 2010 Mar;42(2):142-148.
"I couldn't be here without talking a little about neurologic problems," said Reed--known for his interest in neurologic disease--with a smile as he began his final Kester News Hour segment. First, he described an EVJ study in which researchers described in detail the anatomy of the articular process joints in the neck, which had not previously been described. This has bearing on evaluation of horses with neurologic problems that could be attributed to compression of the spinal cord in the neck.
"By taking variations of straight lateral and angled radiographs of the neck, one could see bone changes (potential joint problems) and identify which side of the neck they were on," explained Reed.
- Claridge HAH, Piercy RJ, Parry A, Weller R. The 3D anatomy of the cervical articular process joints in the horse and their topographical relationship to the spinal cord. Equine Vet J 2010;42 (8):726-731.
Equine Protozoal Myeloencephalitis Testing
Reed also discussed equine protozoal myelocencephalitis (EPM), which commonly affects horses yet is not easy to definitively diagnose in living animals. Researchers on a JVIM study compared two diagnostic tests for the disease in living horses, and they found that the immunofluorescent antibody test (IFAT, or Western blot) was more sensitive for detecting the disease than the enzyme-linked immunosorbent assay (ELISA).
Also in the realm of EPM testing, a report in Veterinary Parasitology described a modification of the ELISA test to detect more surface proteins characteristic of the causative organism Sarcocystis neurona, thus making the test able to account for slight genetic variations of the organism (and, thus, more sensitive for detecting the organism).
Yet another study (from JVIM) involved testing for antibodies to EPM rather than the causative organism itself, and researchers on the paper reported good results with this method. Additionally, this testing method was not compromised when a sample of cerebrospinal fluid (CSF, which surrounds the brain and spinal cord) was contaminated with blood by the sampling process.
Finally, Reed mentioned a study discussed at the 2010 American College of Veterinary Internal Medicine conference that showed a paired ELISA test developed at the University of Kentucky's Gluck Equine Research Center, designed to be run simultaneously on blood and cerebrospinal fluid, was effective at detecting EPM. Also, the researchers found that the ratio of antibodies in serum compared to CSF was an effective indicator of EPM.
"This study verified that analysis of both serum and CSF from horses suspected to have EPM is more beneficial than examination of serum alone," wrote the authors (including Reed).
- Johnson AL, Burton AJ, Sweeney RW. Utility of 2 immunological tests for antemortem diagnosis of equine protozoal myeloencephalitis (Sarcocystis neurona infection) in naturally occurring cases. J Vet Intern Med 2010; 24:1184-1189.
- Yeargan MR, Howe DK. Improved detection of equine antibodies against Sarcocystis neurona using polyvalent ELISA based on the parasite SnSAG surface antigens. Veterinary Parasitology 2010 In Press (available on line).
- Furr MK, Howe DK, Reed SM, Yeargan MR. Antibody coefficients for the diagnosis of equine protozoal myeloencephalitis. J Vet Intern Med 2011, In Press.
- Reed SM, Howe DK, Yeargan MR, Morrow JK, et al. New quantitative assays for the differential diagnosis of protozoal myeloencephalitis (EPM), in Proceedings. Am College of Vet Int Med 2010:339.
Kester Tips of the Hat
The Kester News Hour always features Tips of the Hat, which are salutes to outstanding veterinarians, programs, etc. This year the tips of the hat included Texas A&M University volunteers and students for supporting future veterinary students with wet labs for more than 200 students (These were "arguably the most comprehensive hands-on experience for students available," commented Reed). The labs are planned by a group of 18 veterinary students, and many university staff, private vets, and sponsors donate time and materials to educate these students at minimal cost to them.
The second Tip of the Hat went to the organizers and supporters of the Opportunities in Equine Practice seminar, held in Lexington, Ky. The seminar is organized by Bill Rood, DVM, co-owner of Rood & Riddle, with support from private practitioners and the AAEP Foundation, and more than 3,500 students have attended in its eight years of existence.
"It's the largest recruitment and career forum out there," said Reed.
Additional Studies (not discussed)
- Medina-Torres CE, Weese JS, Staempfli HR. Validation of a commercial enzyme immunoassay for detection of Clostridium difficile toxins in feces of horses with acute diarrhea. J Vet Intern Med 2010;24:628-632.
- Moran G, Folch H, Araya O, Burgos R, et al. Detection of reagenic antibodies against Faenia rectivirgula from the serum of horses affected with recurrent airway obstruction by an in vitro bioassay. Vet Res Commun 2010 December 34(8);719-726.
- Withers JM, Voute LV, Hammond G, Lischer CJ. Radiographic anatomy of the articular process joints of the caudal cervical vertebrae in the horse on lateral and oblique projection. Equine Vet J 2010 42(8):726-731.
- Goehring LS, van Maanen C, Berendsen M, Cullinane A, et al. Experimental infection with neuropathogenic equid herpesvirus-1 (EHV-1) in adult horses. The Vet J 2010 186:180-187.
About the Author
Christy West has a BS in Equine Science from the University of Kentucky, and an MS in Agricultural Journalism from the University of Wisconsin-Madison.
POLL: University Equine Hospitals