The Modern
Equine Vet www.modernequinevet.com
Vol 11 Issue 8 2021
Do HighPowered Lasers Work? Last Installment of a 4-Part Series on EPM: Prevention Tools by Dr. Nicola Pusterla Stealthy Stem Cells Better for Tendon Injuries Does Barometric Pressure Cause Colic?
TABLE OF CONTENTS
COVER STORY
4 High-Quality Data to
Power High-Powered Lasers Cover: Shutterstock/Makarova Viktoria
LAMENESS
Stealthy Stem Cells Better for Treating Tendon Injuries.................................................8 COLIC
Does Barometric Pressure Cause Colic?................................................................................10 Can Probiotics Prevent Gastric Ulcers?..................................................................................12 INFECTIOUS DISEASES
Tools Available to Prevent EPM..........................................................15 NEWS NOTES
Can the Gut Improve Performance?...................................................3
ADVERTISERS Shanks Veterinary Equipment..........................................................................3 Arenus Animal Health/Assure Gold.................................................................5 Merck Animal Health..........................................................................................7 American Regent/Adequan ..............................................................................9
Arenus Animal Health/Aleria..........................................................................11 American Regent/BetaVet...............................................................................13 Arenus Animal Health/Releira........................................................................17 Arenus Animal Health/Assure Gold...............................................................19
The Modern
Equine Vet SALES: Matthew Todd • Matthew Gerald EDITOR: Marie Rosenthal ART DIRECTOR: Jennifer Barlow CONTRIBUTING WRITERS: Paul Basillo • Adam Marcus COPY EDITOR: Patty Wall Published by PO Box 935 • Morrisville, PA 19067 Marie Rosenthal and Jennifer Barlow, Publishers PERCYBO media publishing
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Issue 8/2021 | ModernEquineVet.com
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NEWS NOTES
Can the Gut Improve Performance? A horse's gut microbiome communicates with its host by sending chemical signals to its cells, which helps the horse extend its energy output. “Certain types of equine gut bacteria produce chemical signals that communicate with the mitochondria in the horse's cells that regulate and generate energy,” said Eric Barrey, PhD, DVM, HVR, the integrative biology and equine genetics team leader at the National Research Institute for Agriculture, Food and Environment, in France. “We believe that metabolites—small molecules created by breaking down bigger molecules for food or growth—produced by these bacteria have the effect of delaying low blood sugar and inflammation in the cells, which in turn extends the horse's athletic performance,” Mitochondria, which provide energy to the cells, have been shown in recent studies to be interdependent with gut bacteria, and there are many studies looking at the effect of the gut microbiome on the body. “Studying horses is a good way to assess the link between gut bacteria and mitochondria, because the level of exercise, and thereby mitochondrial function, performed by a horse during an endurance race is similar to that of a human marathon runner,” said Nuria Mach, PhD, also based at the National Research Institute for Agriculture, Food and Environment. For this study they took blood samples from 20 healthy horses of similar age and performance level at the start and end of the International Endurance Competition of Fontainebleau, an 8-hour horse race in France. “These samples provided information about the chemical signals and expression of specific genes, which is the process by which DNA is converted into instructions for making proteins or other molecules. To understand the composition of the horse's gut bacteria metabolites, we obtained fecal samples at the start of the race,” she said. The researchers found that certain bacteria in the gut were linked to the expression of genes by the mitochondria in the cells. Furthermore, the genes that were expressed were linked to activities in the cell that helped it to adapt to metabolism. “Improving our understanding of the intercommunication between the horse and the gut microbiome could help enhance their individual per-
formance, as well as the method by which they are trained and their dietary composition intake. Manipulating the gut microbiota with probiotic supplements as well as prebiotics, to feed the good bacteria, could be a way for increasing the health and balance of the microbiome in horses, to better sustain endurance exercise,” Dr. Mach said. MeV
For more information: Mach N, Moroldo M, Rau A, et al. Understanding the holobiont: Crosstalk between gut microbiota and mitochondria during long exercise in horse. Front Mol Biosci. 2021 08 Apr https://doi.org/10.3389/fmolb.2021.656204
Lifting Large Animals Since 1957 www.shanksvet.com
LAMENESS
High-Quality Data to
POWER HIGH-POWERED LASERS P a u l
B a s i l i o
High-power laser therapy is often used to treat soft-tissue injuries in humans and horses, but there are few controlled studies looking at its safety and efficacy. Anecdotal data seem promising, but will lasers hold up to rigorous study? “A lot of therapy modalities are used before they are actually tested in a standardized, controlled study,” admitted Mathilde Pluim, DVM, MSc, of Tierklinik Luesche, Germany, and Ghent University in Belgium. In 2018, Dr. Pluim and her colleagues published a single-center retrospective study in Veterinary Science that included 150 horses with lesions in the superficial deep digital flexor tendon, the suspensory ligament, and the suspensory branches. The horses received high-power (15 W) laser therapy for 2 consecutive weeks, and data were logged pre-treatment, directly after treatment, and at 4 weeks post-treatment. Long-term results were also obtained up to 2 years later.
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Issue 8/2021 | ModernEquineVet.com
Shutterstock/Perkus
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LAMENESS
There was significant improvement directly after laser treatment.
“We found significant improvement directly after laser therapy,” she explained during a virtual presentation for the 66th Annual AAEP Convention. “Reinjury rate after 2 years was pretty low at 18%. The horses started controlled exercise—trotting under saddle—after 4 to 7 weeks, and they were back at their previous performance level between 4.7 and 6.1 months later. This is quite fast.” There was no sign of improved outcomes among horses that also received plateletrich plasma (PRP) or stem cells in addition to the laser therapy over those treated with laser therapy alone. However, horses with acute injuries tended to have better prognoses than horses with chronic injuries. The results of this retrospective study also showed a much sooner return-to-work when compared with other studies on equine tendon and ligament injuries. But there was one caveat. “That study had flaws because there was no control group,” Dr. Pluim said. “There was also a diverse group of horses with diverse lesions.” As a result, Dr. Pluim and her team set out to perform a study using a standardized lesion induction model.
The Controlled Study
Twelve Warmblood horses (5 geldings and 7 mares) were included in the study. Six were evaluated for 4 weeks, and 6 had extended follow-up at 6 months. Lesions were induced in the lateral suspensory branch of all 4 limbs, and laser therapy was performed in 2 limbs. Healing was evaluated through medical imaging, monitoring for lameness, and histopathologic examination. Laser therapy was performed daily for 4 weeks with a class-4 laser that emits 4 different wavelengths simultaneously. The laser penetrates up to 7.2 cm. “There were preset treatment protocols available with the device,” she added. “Depending on the
depth of penetration and the effect you want to achieve [i.e., biostimulation, anti-inflammatory or analgesic], you can pick a preset protocol suited to the type of lesions and the lesion site. One day after inducing the lesions, no heat, swelling, pain, or lameness were noted. Analgesics were initiated. The team began to walk and trot the horses for 10 minutes a day, slowly increasing to 30 minutes after 1 week. “After 1 week, we did see clear signs of [equine suspensory] desmitis,” Dr. Pluim said. “The horses in the long-term group were handwalked up to 3 months, and after that trotting and cantering exercise were slowly increased up to a full workload after 6 months.”
Results
Dr. Pluim found enlargement of the lesions in the treated and control limbs through the first 4 weeks. However, the lesion was not as clear on imaging in the treated limbs, and tissue began filling in already after 4 weeks in the treated limb. “On ultrasound, enlargement was significantly lower in the laser-treated lesions in both circumference and surface area,” she explained. The Doppler signal on ultrasonography was significantly higher in the treatment group for the first 4 weeks. Overall on MRI, the surface area of the treated lesions was significantly lower than that of the control limbs. “The mean MRI signal was also significantly lower in the treatment group,” Dr. Pluim added. “After 6 months, the signal was significantly lower in both groups when compared with 4 weeks. However, the signal was significantly lower in both the short- and long-term laser treated lesions.” Dr. Pluim and her team are now hard at work studying histopathological findings of these types of treated lesions, to analyze the quality of the healing tissue. MeV
For more information: Pluim M, Martens A, Vanderperren K, et al. Short- and long-term follow-up of 150 sports horses diagnosed with tendinopathy or desmopathy by ultrasonographic examination and treated with high-power laser therapy. Vet Sci. 2018;119(8):232-238. https://www.sciencedirect.com/science/article/abs/pii/S0034528818302455?via%3Dihub Pluim M, Martens A, Vanderperren L, et al. High-power laser therapy improves healing of the equine suspensory branch in a standardized lesion model. Front Vet Sci. 2020 Sept 3. doi.org/10.3389/fvets.2020.00600. https://www.frontiersin.org/articles/10.3389/fvets.2020.00600/full
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Issue 8/2021 | ModernEquineVet.com
Get the scoop on EPM RECOVERY
Effectively treating Equine Protozoal Myeloencephalitis (EPM) doesn’t have to be difficult. Reach for PROTAZIL® (1.56% diclazuril) Antiprotozoal Pellets • Goes to work fast (within 12 hours) — no loading dose required1 • The only FDA‑approved alfalfa‑based top dress treatment for EPM, proven safe and effective • No mess, no fuss ‑ easy to administer and highly palatable
Ask your Merck Animal Health Equine representative about PROTAZIL® or call 800-521-5767. IMPORTANT SAFETY INFORMATION: Use of PROTAZIL® (1.56% diclazuril) Antiprotozoal Pellets is contraindicated in horses with known hypersensitivity to diclazuril. Safe use in horses used for breeding purposes, during pregnancy, or in lactating mares has not been evaluated. The safety of PROTAZIL® (1.56% diclazuril) Antiprotozoal Pellets with concomitant therapies in horses has not been evaluated. For use in horses only. Do not use in horses intended for human consumption. Not for human use. Keep out of reach of children. 2 Giralda Farms • Madison, NJ 07940 • merck-animal-health-usa.com • 800-521-5767 Copyright © 2021 Intervet Inc., d/b/a/ Merck Animal Health, a subsidiary of Merck & Co., Inc. All rights reserved.
1
Hunyadi L, Papich MG, Pusterla N. Pharmacokinetics of a low‑dose and DA‑labeled dose of diclazuril administered orally as a pelleted top dressing in adult horses. J of Vet Pharmacology and Therapeutics (accepted) 2014, doi: 10.111/jvp.12176. The correlation between pharmacokinetic data and clinical effectiveness is unknown
FOR ORAL USE IN HORSES ONLY CAUTION Federal ( U.S.A.) law restricts this drug to use by or on the order of a licensed veterinarian. NADA #141-268 Approved by FDA DESCRIPTION Diclazuril, (±)-2,6-dichloro-α- (4chlorophenyl)-4- (4,5-dihydro-3,5-dioxo1,2,4-triazin-2(3H )-yl)benzeneacetonitrile, has a molecular formula of C 17 H 9 CI 3 N 4 O 2 , a molecular weight of 407.64, and a molecular structure as follows:
Diclazuril is an anticoccidial (antiprotozoal) compound with activity against several genera of the phylum Apicomplexa. PROTAZIL® (diclazuril) is supplied as oral pellets containing 1.56% diclazuril to be mixed as a top-dress in feed. Inert ingredients include dehydrated alfalfa meal, wheat middlings, cane molasses and propionic acid (preservative). INDICATIONS PROTAZIL® (1.56% diclazuril) Antiprotozoal Pellets are indicated for the treatment of equine protozoal myeloencephalitis ( EPM) caused by Sarcocystis neurona in horses. DOSAGE AND ADMINISTRATION Dosage: PROTAZIL® (1.56% diclazuril) is administered as a top dress in the horse’s daily grain ration at a rate of 1 mg diclazuril per kg (0.45 mg diclazuril/lb) of body weight for 28 days. The quantity of PROTAZIL® necessary to deliver this dose is 64 mg pellets per kg (29 mg pellets/lb) of body weight. Administration: To achieve this dose, weigh the horse (or use a weigh tape)). Scoop up PROTAZIL® to the level (cup mark) corresponding to the dose for the horse’s body weight using the following chart: Weight Range mLs of Weight Range mLs of of Horse (lb) Pellets of Horse (lb) Pellets 275 - 524 20 1275 - 1524 60 525 - 774 30 1525 - 1774 70 775 - 1024 40 1775 - 2074 80 1025 - 1274 50 -
One 2.4-lb bucket of PROTAZIL® will treat one 1274-lb horse for 28 days. One 10-lb bucket of PROTAZIL® will treat five 1100-lb horses for 28 days. CONTRAINDICATIONS Use of PROTAZIL® (1.56% diclazuril) Antiprotozoal Pellets is contraindicated in horses with known hypersensitivity to diclazuril. WARNINGS For use in horses only. Do not use in horses intended for human consumption. Not for human use. Keep out of reach of children. PRECAUTIONS The safe use of PROTAZIL® (1.56% diclazuril) Antiprotozoal Pellets in horses used for breeding purposes, during pregnancy, or in lactating mares has not been evaluated. The safety of PROTAZIL® (1.56% diclazuril) Antiprotozoal Pellets with concomitant therapies in horses has not been evaluated. ADVERSE REACTIONS There were no adverse effects noted in the field study which could be ascribed to diclazuril. To report suspected adverse reactions, to obtain a MSDS, or for technical assistance call 1-800-224-5318. CLINICAL PHARMACOLOGY The effectiveness of diclazuril in inhibiting merozoite production of Sarcocystis neurona and S. falcatula in bovine turbinate cell cultures was studied by Lindsay and Dubey (2000).1 Diclazuril inhibited merozoite production by more than 80% in cultures of S. neurona or S. falcatula treated with 0.1 ng/mL diclazuril and greater than 95% inhibition of merozoite production (IC 95 ) was observed when infected cultures were treated with 1.0 ng/mL diclazuril. The clinical relevance of the in vitro cell culture data has not been determined. PHARMACOKINETICS IN THE HORSE The oral bioavailability of diclazuril from the PROTAZIL® (1.56% diclazuril) Antiprotozoal Pellets at a 5 mg/kg dose rate is approximately 5%. Related diclazuril concentrations in the cerebrospinal fluid (CSF) range between 1% and 5% of the concentrations observed in the plasma. Nevertheless, based upon equine pilot study data, CSF concentrations are expected to substantially exceed the in vitro IC 95 estimates for merozoite production (Dirikolu et al., 1999) 2. Due to its long terminal elimination half-life in horses (approximately 43-65 hours), diclazuril accumulation occurs with once-daily dosing. Corresponding steady state blood levels are achieved by approximately Day 10 of administration. EFFECTIVENESS Two hundred and fourteen mares, stallions, and geldings of various breeds, ranging in age from 9.6 months to 30 years, were enrolled in a multi-center field study. All horses were confirmed EPM-positive based on the results of clinical examinations and laboratory testing,
LAMENESS
including CSF Western Blot analyses. Horses were administered PROTAZIL® (1.56% diclazuril) Antiprotozoal Pellets at doses of 1, 5, or 10 mg diclazuril/kg body weight as a top-dress on their daily grain ration for 28 days. The horses were then evaluated for clinical changes via a modified Mayhew neurological scale on Day 48 as follows: 0. Normal, neurological deficits not detected. 1. Neurological deficits may be detectable at normal gaits; signs exacerbated with manipulative procedures (e.g., backing, turning in tight circles, walking with head elevation, truncal swaying, etc.). 2. Neurological deficit obvious at normal gaits or posture; signs exacerbated with manipulative procedures. 3. Neurological deficit very prominent at normal gaits: horses give the impression they may fall (but do not) and buckle or fall with manipulative procedures. 4. Neurological deficit is profound at normal gait: horse frequently stumbles or trips and may fall at normal gaits or when manipulative procedures were utilized. 5. Horse is recumbent, unable to rise. Each horse’s response to treatment was compared to its pre-treatment values. Successful response to treatment was defined as clinical improvement of at least one grade by Day 48 ± conversion of CSF to Western Blot-negative status for S. neurona or achievement of Western Blot-negative CSF status without improvement of 1 ataxia grade. Forty-two horses were initially evaluated for effectiveness and 214 horses were evaluated for safety. Clinical condition was evaluated by the clinical investigator’s subjective scoring and then corroborated by evaluation of the neurological examination videotapes by a masked panel of three equine veterinarians. Although 42 horses were evaluated for clinical effectiveness, corroboration of clinical effectiveness via videotape evaluation was not possible for one horse due to missing neurologic examination videotapes. Therefore, this horse was not included in the success rate calculation. Based on the numbers of horses that seroconverted to negative Western Blot status, and the numbers of horses classified as successes by the clinical investigators, 28 of 42 horses (67%) at 1 mg/kg were considered successes. With regard to independent expert masked videotape assessments, 10 of 24 horses (42%) at 1 mg/kg were considered successes. There was no clinical difference in effectiveness among the 1, 5, and 10 mg/kg treatment group results. Adverse events were reported for two of the 214 horses evaluated for safety. In the first case, a horse was enrolled showing severe neurologic signs. Within 24 hours of dosing, the horse was recumbent, biting, and exhibiting signs of dementia. The horse died, and no cause of death was determined. In the second case, the horse began walking stiffly approximately 13 days after the start of dosing. The referring veterinarian reported that the horse had been fed grass clippings and possibly had laminitis. ANIMAL SAFETY PROTAZIL® (1.56% diclazuril) Antiprotozoal Pellets were administered to 30 horses (15 males and 15 females, ranging from 5 to 9 months of age) in a target animal safety study. Five groups of 6 horses each (3 males and 3 females) received 0, 5 (5X), 15 (15X), 25 (25X) or 50 (50X) mg diclazuril/kg (2.27mg/ lb) body weight/day for 42 consecutive days as a top-dress on the grain ration of the horse. The variables measured during the study included: clinical and physical observations, body weights, food and water consumption, hematology, serum chemistry, urinalysis, fecal analysis, necropsy, organ weights, gross and histopathologic examinations. The safety of diclazuril top-dress administered to horses at 1 mg/kg once daily cannot be determined based solely on this study because of the lack of an adequate control group (control horses tested positive for the test drug in plasma and CSF). However, possible findings associated with the drug were limited to elevations in BUN, creatinine, and SDH and less than anticipated weight gain. Definitive test article-related effects were decreased grain/top-dress consumption in horses in the 50 mg/kg group. In a second target animal safety study, PROTAZIL® (1.56% diclazuril) Antiprotozoal Pellets were administered to 24 horses (12 males and 12 females, ranging from 2 to 8 years of age). Three groups of 4 horses/sex/group received 0, 1, or 5 mg diclazuril/kg body weight/day for 42 days as a top-dress on the grain ration of the horse. The variables measured during the study included physical examinations, body weights, food and water consumption, hematology, and serum chemistry. There were no test article-related findings seen during the study. STORAGE INFORMATION Store between 15°C to 30°C (59°F to 86°F). HOW SUPPLIED PROTAZIL® (1.56 % diclazuril) Antiprotozoal Pellets are supplied in 2.4-lb (1.1 kg) and 10-lb (4.5 kg) buckets. REFERENCES 1. Lindsay, D. S., and Dubey, J. P. 2000. Determination of the activity of diclazuril against Sarcocystis neurona and Sarcocystis falcatula in cell cultures. J. Parasitology, 86(1):164–166.
Stealthy Stem Cells Better for Treating Tendon Injuries Treating equine donor stem cells with a growth factor called TGF-β2 may allow them to avoid triggering an immune response in recipients, according to new research from North Carolina State University. The work could simplify the stem cell treatment process for ligament and tendon injuries in horses, and may also have implications for human stem cell therapies. Mesenchymal stem cell therapy is a promising avenue for treating musculoskeletal injuries—particularly tendon and ligament injuries—in horses. Found in bone marrow, mesenchymal stem cells act as repair directors, producing secretions that recruit paracrine, or healing, factors to the site of injury. Just as blood cells have types that depend on which antigens are on the blood cell's surface, mesenchymal stem cells have differing sets of major histocompatibility complex molecules (MHCs) on their surfaces. If the MHCs of donor and recipient aren't a match, the donor's stem cells cause an immune response. In organ transplants, MHCs are carefully matched to prevent rejection. “These treatments aren't like a bone marrow transplant or an organ transplant,” explained Lauren Schnabel, DVM, PhD, Dip. ACVS, Dip. ACVSMR, associate professor of equine orthopedic surgery at NC State and corresponding author of the work. “Since the mesenchymal stem cells are being used temporarily to treat localized injury, researchers once thought that they didn't need to be matched—that they wouldn't cause an immune response. Unfortunately, that isn't the case.” Dr. Schnabel and Alix Berglund, DVM, PhD, research scholar at NC State and lead author of the paper describing the work, wanted to find a way to use mesenchymal
For more information:
2. Dirikolu, L., Lehner, F., Nattrass, C., Bentz, B. G., Woods, W. E., Carter, W. E., Karpiesiuk, W. G., Jacobs, J., Boyles, J., Harkins, J. D., Granstrom, D. E. and Tobin, T. 1999. Diclazuril in the horse: Its identification and detection and preliminary pharmacokinetics. J. Vet. Pharmacol. Therap. 22:374–379. Intervet Inc d/b/a Merck Animal Health 2 Giralda Farms, Madison, NJ 07940 Copyright © 2021 Intervet Inc. a subsidiary of Merck & Co. Inc. All rights reserved. 07-2014 211.x.3.0.3
stem cell therapy without the time, effort and additional cost of donor-recipient matching. “Since these cells don't have to be in the body as long as an organ does, 'hiding' them from the immune system long enough for them to secrete their paracrine factors could be a way around donorrecipient matching,” Dr. Berglund said. “Downregulating expression of the MHC molecules could be one way to do this.” The researchers cultured stem cells and lymphocytes, or T cells, from 8 horses, cross-pairing them in vitro so that the stem cells and lymphocytes had differing MHC haplotypes. In 1 group, stem cells had been treated with transforming growth factor beta (TGF-β2) prior to being added to the lymphocytes in the culture media; the other group was untreated. TGF-β2 is a cell-signaling molecule produced by white blood cells that blocks immune responses. Cultures with treated stem cells had a 50% higher stem cell survival rate than untreated cultures. “We use mesenchymal stem cells to treat musculoskeletal injuries—particularly tendon injuries—in horses very effectively,” Dr. Schnabel said. “And while you can extract the secretions from the stem cells, you get better results with the cells themselves. Stem cells aren't just a reservoir of secretions, they're a communications hub that tells other cells what they should be doing. So finding a way to utilize these cells without stimulating immune response gives us better treatment options.” Dr. Berglund called this pilot study promising, adding, “Our next steps will be to further explore the immune response in vivo, and to look at human cells in vitro, as this work has excellent potential to help humans with these injuries as well.” MeV
Berglund AK, Long JM, Robertson JB, et al. TGF-β2 reduces the cell-mediated immunogenicity of equine MHCmismatched bone marrow-derived mesenchymal stem cells without altering immunomodulatory properties. Front Cell Dev Biol. 2021 Feb. 4 DOI: 10.3389/fcell.2021.628382 https://www.frontiersin.org/articles/10.3389/fcell.2021.628382/full
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Issue 8/2021 | ModernEquineVet.com
There’s nothing else like it. For more than 30 years, Adequan® i.m. (polysulfated glycosaminoglycan) has been administered millions of times1 to treat degenerative joint disease, and with good reason. From day one, it’s been 2, 3 the only FDA-Approved equine PSGAG joint treatment available, and the only one proven to. Reduce inflammation Restore synovial joint lubrication Repair joint cartilage Reverse the disease cycle When you start with it early and stay with it as needed, horses may enjoy greater mobility over a 2, 4, 5 lifetime. Discover if Adequan is the right choice. Visit adequan.com/Ordering-Information to find a distributor and place an order today. BRIEF SUMMARY: Prior to use please consult the product insert, a summary of which follows: CAUTION: Federal law restricts this drug to use by or on the order of a licensed veterinarian. INDICATIONS: Adequan® i.m. is recommended for the intramuscular treatment of non-infectious degenerative and/or traumatic joint dysfunction and associated lameness of the carpal and hock joints in horses. CONTRAINDICATIONS: There are no known contraindications to the use of intramuscular Polysulfated Glycosaminoglycan. WARNINGS: Do not use in horses intended for human consumption. Not for use in humans. Keep this and all medications out of the reach of children. PRECAUTIONS: The safe use of Adequan® i.m. in horses used for breeding purposes, during pregnancy, or in lactating mares has not been evaluated. For customer care, or to obtain product information, visit www.adequan.com. To report an adverse event please contact American Regent, Inc. at 1-888-354-4857 or email pv@americanregent.com. Please see Full Prescribing Information at www.adequan.com.
www.adequan.com 1 Data on file. 2 Adequan® i.m. Package Insert, Rev 1/19. 3 Burba DJ, Collier MA, DeBault LE, Hanson-Painton O, Thompson HC, Holder CL: In vivo kinetic study on uptake and distribution of intramuscular tritium-labeled polysulfated glycosaminoglycan in equine body fluid compartments and articular cartilage in an osteochondral defect model. J Equine Vet Sci 1993; 13: 696-703. 4 Kim DY, Taylor HW, Moore RM, Paulsen DB, Cho DY. Articular chondrocyte apoptosis in equine osteoarthritis. The Veterinary Journal 2003; 166: 52-57. 5 McIlwraith CW, Frisbie DD, Kawcak CE, van Weeren PR. Joint Disease in the Horse.St. Louis, MO: Elsevier, 2016; 33-48. All trademarks are the property of American Regent, Inc. © 2021, American Regent, Inc. PP-AI-US-0629 05/2021
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DOES BAROMETRIC PRESSURE CAUSE COLIC B y
A d a m
M a r c u s
A recent study lets the air out of the notion that barometric pressure is associated with the risk for colic in horses. Although barometric pressure was not linked to the risk for colic, the study did find an association between higher latitude and seasonal weather changes—particularly spring, summer and fall, which can be volatile in the Mid-Atlantic states—and gastrointestinal illness in horses. However, the veterinarians said this effect likely reflects the way horse owners and stables manage their animals rather than any direct impact of weather on GI health. 10
Issue 8/2021 | ModernEquineVet.com
Shutterstock/Anaite/ Victoria Antonova/ Sylvie Bouchard/ Kwadrat
COLIC
IN A WORLD OF ITS OWN
Researched Respiratory Support Researched and Proven as an aid in controlling IAD and RAO Recommended in the ACVIM Consensus Statement on Respiratory Disease (1)
(2)
Not all Omega 3’s are the same; use the Researched and Recommended 1500mg Purified DHA formulation. Your Clients Deserve The Best in a Non-Pharmaceutical Solution.
– Using the Best Matters References: [1] Nogradi N, Couetil LL, Messick J, Stochelski MA, Burgess JA. Evaluation of an Omega-3 Fatty Acid Containing Feed Supplement in the Management of Horses with Chronic Lower Airway Inflammatory Diseases. J Vet Intern Med 2015; 29:299-306. [2] Couetil LL, Cardwell J.M, Gerber V, Lavoie J.-P, Leguillette R, Richard E.A. Inflammatory Airway Disease of Horses. ACVIM Consensus Statement J of Vet Intern Med 2016; 30:503-515 p. 508-510.
Check with Arenus on how Aleira can help your equine patients effectively cope with respiratory and immune function disorders. See how Aleira can help you to reduce or eliminate pharmaceutical interventions.
Arenus Animal Health | 866-791-3344 | www.arenus.com
COLIC
“Although barometric pressure changes were not found to be significantly associated with the diagnosis of colic in our analysis, seasons with changing weather in the mid-Atlantic region were,” said Ashley Boyle, DVM, an associate professor in the School of Veterinary Medicine at the University of Pennsylvania, and leader of the study team. “We are extrapolating that human management changes may be playing a role in this, so minimizing disruptions in management of the horses is advised.” For the study, Dr. Boyle and her colleagues examined electronic veterinary records of 11,601 horses treated in the Penn system between January 2005 and January 2017. To look for an effect of barometric pressure on health outcomes, they matched pressure readings from weather stations located in the geographic region where Penn equine vets practice. Barometric pressure has been tied to certain medi-
cal problems for both people and animals, but in this study, it was not associated with the risk for colic or other health issues in horses, Dr. Boyle’s group found. But animals were significantly more likely to develop colic in the spring, fall and summer than in winter, they reported (odds ratios of 1.29, 1.72 and 1.85, and P=0.04, P<0.0001 and P<0.0001, respectively). Interestingly, the researchers found that every 1° increase in latitude was linked to a 2.4% increase in the risk for colic relative to other equine complaints, including esophageal choke, cuts, lameness and eye conditions. In the Northern Hemisphere, where the study was conducted, rising latitude generally means colder winters. Horses have been shown to drink less water during cold weather—potentially leading to dehydration, which is a known risk factor for colic, as well as reduced ileal contractility, Dr. Boyle’s group said. MeV
For more information: Cianci J et al. Lack of Association between barometric pressure and incidence of colic in equine academic ambulatory practice. J Equine Vet Sci 2021;97 February 2021, 103342 https://doi.org/10.1016/j.jevs.2020.103342 https://www.sciencedirect.com/science/article/abs/pii/S0737080620304330
Can Probiotics Help Protect Against Gastric Ulcers? By Adam Marcus Fermented rice may not sound appealing, but Japanese researchers say the product could be an effective treatment for gastric ulcers in horses. Horses with ulcers that were fed an extract of fermented rice for a month experienced significant improvement in the lesions compared with animals given tap water, the researchers reported. For the study, researchers at Yamaguchi University and their colleagues tested the effects of the rice extract in 17 horses with gastric ulcers that had been confirmed by endoscopy. Of the animals, 8 received the extract orally once a day at a dose of 0.2 mL/kg, and 9 received plain tap water. After 1 month, the animals again underwent endoscopy, and their gastric lesions were assessed for signs of change. Among the untreated horses, the ul-
cers did not appear to resolve from their baseline severity. But in the horses that received the rice extract, the ulcers shrank substantially, from a score of 4 at baseline to 1 after treatment, the researchers reported. “In this study, the administration of a rice fermented extract improved gastric mucosal lesions in horses with gastric ulcers. This may be because the rice fermented extract improved the healing of gastric mucosal epithelial cells,” according to the researchers, who published their findings in the Journal of Equine Science. “Thus, a rice fermented extract, which is stable when boiled, might be a novel alternative anti-ulcer agent that protects cells and improves wound restoration through vanilloid receptor-mediated neural systems, synthesis of prostaglandins, induction of heat shock proteins, and suppression of gastric acid [secretion],” they added. MeV
For more information: Sasaki N, et al. Effect of a novel rice fermented extract on gastric ulcers in horses. J Equine Sci. 2021;32(2):27-30. doi: 10.1294/jes.32.27. Epub 2021 Jun 18. https://www.jstage.jst.go.jp/article/jes/32/2/32_2101/_pdf/-char/en
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Issue 8/2021 | ModernEquineVet.com
The only dual ingredient injectable corticosteroid approved by the FDA for use in horses
The link between RAPID ONSET and LONG-ACTING RELIEF of pain & inflammation 1
BetaVet® (betamethasone sodium phosphate & betamethasone acetate injectable suspension) is indicated for the control of pain and inflammation associated with osteoarthritis in horses. Learn more at www.betavetequine.com or call 1-800-458-0163. Please see Brief Summary of Full Prescribing Information on the following page. INDICATION BetaVet® (betamethasone sodium phosphate and betamethasone acetate injectable suspension) is indicated for the control of pain and inflammation associated with osteoarthritis in horses. IMPORTANT SAFETY INFORMATION For Intra-articular (I.A.) use in Horses. CONTRAINDICATIONS BetaVet® is contraindicated in horses with hypersensitivity to betamethasone. Intra-articular injection of corticosteroids for local effect is contraindicated in the presence of septic arthritis. WARNINGS: Do not use in horses intended for human consumption. Clinical and experimental data have demonstrated that corticosteroids administered orally or parenterally to animals may induce the first stage of parturition when administered during the last trimester of pregnancy and may precipitate premature parturition followed by dystocia, fetal death, retained placenta, and metritis. Additionally, corticosteroids administered to dogs, rabbits and rodents during pregnancy have resulted in congenital anomalies. Before use of corticosteroids in pregnant animals, the possible benefits should be weighed against potential hazards. Human Warnings: Not for use in humans. Keep this and all medications out of the reach of children. PRECAUTIONS: Corticosteroids, including BetaVet,® administered intra-articularly are systemically absorbed. Do not use in horses with acute infections. Acute moderate to severe exacerbation of pain, further loss of joint motion, fever, or malaise within several days following intra-articular injection may indicate a septic process. Because of the anti-inflammatory action of corticosteroids, signs of infection in the treated joint may be masked. Due to the potential for exacerbation of clinical signs of laminitis, glucocorticoids should be used with caution in horses with a history of laminitis, or horses
otherwise at a higher risk for laminitis. Use with caution in horses with chronic nephritis, equine pituitary pars intermedia dysfunction (PPID), and congestive heart failure. Concurrent use of other anti-inflammatory drugs, should be approached with caution. Consider appropriate wash out times prior to administering additional NSAIDs or corticosteroids. ADVERSE REACTIONS: Adverse reactions reported during a field study of 239 horses of various breeds which had been administered either BetaVet® (n=119) or a saline control (n=120) at five percent (5%) and above were: acute joint effusion and/ or local injection site swelling (within 2 days of injection), 15% BetaVet® and 13% saline control; increased lameness (within the first 5 days), 6.7% BetaVet® and 8.3% saline control; loose stool, 5.9% BetaVet® and 8.3% saline control; increased heat in joint, 2.5% BetaVet® and 5% saline control; and depression, 5.9% BetaVet® and 1.6% saline control. SHAKE WELL IMMEDIATELY BEFORE USE. For additional safety information, please see full prescribing information. CAUTION: Federal law restricts this drug to use by or on the order of a licensed veterinarian. References: 1. Trotter GW. Intra-articular corticosteroids. In: McIlwraith CW, Trotter GW, eds. Joint Disease in the Horse. Philadelphia: W.B. Saunders; 1996; 237–256.
BetaVet® and the Horse Head design are registered trademarks of American Regent, Inc. © 2021 American Regent, Inc. PP-BV-US-0035 3/2021
BRIEF SUMMARY OF PRESCRIBING INFORMATION (Betamethasone Sodium Phosphate and Betamethasone Acetate Injectable Suspension) 6 mg betamethasone per mL For Intra-Articular (I.A.) Use in Horses CAUTION: Federal law restricts this drug to use by or on the order of a licensed veterinarian. INDICATION: BetaVet® is indicated for the control of pain and inflammation associated with osteoarthritis in horses. DOSAGE AND ADMINISTRATION: Shake well immediately before use. CONTRAINDICATIONS: BetaVet® is contraindicated in horses with hypersensitivity to betamethasone. Intra-articular injection of corticosteroids for local effect is contraindicated in the presence of septic arthritis. WARNINGS: Do not use in horses intended for human consumption. Clinical and experimental data have demonstrated that corticosteroids administered orally or parenterally to animals may induce the first stage of parturition when administered during the last trimester of pregnancy and may precipitate premature parturition followed by dystocia, fetal death, retained placenta, and metritis. Additionally, corticosteroids administered to dogs, rabbits and rodents during pregnancy have resulted in cleft palate in offspring. Corticosteroids administered to dogs during pregnancy have also resulted in other congenital anomalies including deformed forelegs, phocomelia and anasarca. Therefore, before use of corticosteroids in pregnant animals, the possible benefits to the pregnant animal should be weighed against potential hazards to its developing embryo or fetus. Human Warnings: Not for use in humans. For use in animals only. Keep this and all medications out of the reach of children. Consult a physician in the case of accidental human exposure. PRECAUTIONS: Corticosteroids, including BetaVet®, administered intra-articularly are systemically absorbed. Do not use in horses with acute infections. Acute moderate to severe exacerbation of pain, further loss of joint motion, fever, or malaise within several days following intra-articular injection may indicate a septic process. Because of the anti-inflammatory action of corticosteroids, signs of infection in the treated joint may be masked. Appropriate examination of joint fluid is necessary to exclude a septic process. If a bacterial infection is present, appropriate antibacterial therapy should be instituted immediately. Additional doses of corticosteroids should not be administered until joint sepsis has been definitively ruled out. Due to the potential for exacerbation of clinical signs of laminitis, glucocorticoids should be used with caution in horses with a history of laminitis, or horses otherwise at a higher risk for laminitis. Use with caution in horses with chronic nephritis, equine pituitary pars intermedia dysfunction (PPID), and congestive heart failure. Concurrent use of other anti-inflammatory drugs, such as NSAIDs or other corticosteroids, should be approached with caution. Due to the potential for systemic exposure, concomitant use of NSAIDs and corticosteroids may increase the risk of gastrointestinal, renal, and other toxicity. Consider appropriate wash out times prior to administering additional NSAIDs or corticosteroids. ADVERSE REACTIONS: Adverse reactions reported during a field study of 239 horses of various breeds which had been administered either BetaVet® (n=119) or a saline control (n=120) were: acute joint effusion and/or local injection site swelling (within 2 days of injection), 15% BetaVet® and 13% saline control; increased lameness (within the first 5 days), 6.7% BetaVet® and 8.3% saline control; loose stool, 5.9% BetaVet® and 8.3% saline control; increased heat in joint, 2.5% BetaVet® and 5% saline control; depression, 5.9% BetaVet® and 1.6% saline control; agitation/anxiety, 4.2% BetaVet® and 2.5% saline control; delayed swelling of treated joint (5 or more days after injection), 2.5% BetaVet® and 3.3% saline control; inappetance, 3.4% BetaVet® and 2.5% saline control; dry stool, 1.7% BetaVet® and 0% saline control; excessive sweating, 0.8% BetaVet® and 0% saline control; acute non-weight bearing lameness, 0.8% BetaVet®and 0% saline control; and laminitis, 0.8% BetaVet® and 0% saline control.
CLINICAL PHARMACOLOGY: Betamethasone is a potent glucocorticoid steroid with anti-inflammatory and immunosuppressive properties. Depending upon their physico-chemical properties, drugs administered intra-articularly may enter the general circulation because the synovial joint cavity is in direct equilibrium with the surrounding blood supply. After the intra-articular administration of 9 mg BetaVet® in horses, there were quantifiable concentrations of betamethasone (above 1.0 ng/mL) in the plasma. EFFECTIVENESS: A negative control, randomized, masked field study provided data to evaluate the effectiveness of BetaVet® administered at 1.5 mL (9 mg betamethasone) once intra-articularly for the control of pain and inflammation associated with osteoarthritis in horses. Clinical success was defined as improvement in one lameness grade according to the AAEP lameness scoring system on Day 5 following treatment. The success rate for horses in the BetaVet® group was statistically significantly different (p=0.0061) than that in the saline group, with success rates of 75.73% and 52.52%, respectively (back-transformed from the logistic regression). ANIMAL SAFETY: A 3-week target animal safety (TAS) study was conducted to evaluate the safety of BetaVet® in mature, healthy horses. Treatment groups included a control (isotonic saline at a volume equivalent to the 4x group); 1X (0.0225 mg betamethasone per pound bodyweight; BetaVet®); 2X (0.045 mg betamethasone per pound bodyweight; BetaVet®) and 4X (0.09 mg betamethasone per pound bodyweight; BetaVet®). Treatments were administered by intra-articular injection into the left middle carpal joint once every 5-days for 3 treatments. Injection site reactions were the most common observations in all treatment groups. Injection site reactions were observed within 1 hour of dosing and included swelling at the injection site, lameness/stiffness of the left front limb, and flexing the left front knee at rest. The injection site reactions ranged from slight swelling (in many horses on multiple days in all treatment groups) to excessive fluid with swelling, pain, and lameness (4x group only). Injection site reactions were observed most commonly on treatment days, and generally decreased in number and severity over subsequent days. The incidence of injection site reactions increased after the second and third injection (number of abnormalities noted on day 10 > day 5 > day 0). In the BetaVet® treated groups the number and severity of the injection site reactions were dose dependent. The 4X BetaVet® group had the highest overall incidence of and severity of injection site reactions, which included heat, swelling, pain, bleeding, and holding the limb up at rest. The control group and 4X group (which received similar injection volumes) had a similar incidence of injection site reactions; however, the severity of reactions was greater in the 4X group. Absolute neutrophils were statistically significantly higher in the BetaVet® treated groups as compared to the control group. Trends toward a decrease in lymphocytes and eosinophils, and an increase in monocytes were identified in the BetaVet® treated groups after the initial dose of BetaVet®. Individual animal values for white blood cells generally remained within the reference range. BetaVet® treated horses also had a trend toward increased blood glucose after the initial dose. Some individual animals showed mild increases in blood glucose above the reference range. SHAKE WELL BEFORE USING NADA 141-418, Approved by FDA For For customer customer care care or or to to obtain obtain product product information information visit visit www.betavetequine.com 458-0163. www.betavetequine.com or or call call (800) 1-800-458-0163. To report an adverse event please contact American Regent Animal Health at at (888) 354-4857 email pv@americanregent.com. (800) 734-9236 or or email pv@americanregent.com.
A Division of American Regent, Inc. 5 Ramsey Rd. | Shirley, NY 11967
INFECTIOUS DISEASES
Tools Available to
Prevent EPM PART
4
B y
N i c o l a
In this four-part series, Nicola Pusterla, DVM, PhD, DACVIM, guides us through a reflective account of equine protozoal myeloencephalitis (EPM). This is our final article in the series. Don’t miss the first three, which provide a review of EPM and its causes, guidance for diagnosis and approved treatments.
P u s t e r l a ,
D V M ,
When it comes to preventing equine proto-
zoal myeloencephalitis (EPM), there is no silver bullet and there’s no vaccine. The most practical preventive measures include basic farm management practices. However, researchers are actively studying the disease on many fronts, including the effects of metaphylactic treatment for high-risk horses.
Special Considerations for High-Risk Horses
Given the total number of horses infected with Sarcocystis neurona and Neospora hughesi, it’s quite a small number that end up developing neurological deficits. However, the severity of these deficits warrants prevention as a critical goal for veterinarians and horse owners. And while the exposure rate is high for S. neurona and N. hughesi, there are multiple “risk” factors that make some horses more susceptible to clinical disease. The horse’s lifestyle and age are some of the most important risk factors to monitor regarding EPM. That is because both age and use act as primary drivers of the horse’s overall immune system response. When the young performance horse is in rigorous training, S. neurona and N. hughesi are more efficient at taking advantage of that host’s weakened immune response and invading the central nervous system.
KEY POINT: The prime candidate for EPM is a young performance horse. If exposed to infective sporocysts,
P h D ,
D A C V I M
these horses are more likely to develop EPM at a greater rate compared with their less active, nontraveling herd mates. Practices for Prevention
Even in a perfect world, where we could maintain our horses in an opossum-free environment, EPM would still exist. This is because only one of the parasites responsible for EPM—S. neurona—is transferred through opossum feces. The other responsible parasite—N. hughesi—likely has a worldwide distribution since it depends on the individual horse, not a definitive host, and is prevalent even in regions without opossums. So how can we minimize the risk? There are several practical ways: 1. Do not feed on the ground. If horses are out on pasture or in a paddock and grain is fed on the ground, wildlife will be more attracted to that area and can contaminate this environment. 2. Offer fresh water. Prevent horses from drinking from ponds and other natural water sources, which are more likely to be contaminated. Provide fresh water from a protected source. 3. Keep wildlife outside. Protect the areas where feed is stored—thus eliminating wildlife from entering the feed room and stables. 4. Minimize stress. Healthy, relaxed horses are more ModernEquineVet.com | Issue 8/2021
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INFECTIOUS DISEASES
EPM RISK FACTORS ENVIRONMENT Exposure to wildlife is perhaps the most important. Horses living on a site where previous EPM cases have been diagnosed are at higher risk. This is likely due to environmental factors regarding the facility and its contamination levels. AGE Young performance horses are more likely to contract EPM. TIME OF YEAR Summer and fall are the most prevalent seasons. HEALTH STATUS Horses experiencing immunosuppression due to stress, pain, or underlying disease, are more likely to contract EPM. CAREER/USE Horses in demanding careers (i.e., undergoing training, travel and/or competing) are more susceptible. capable of fighting off protozoal parasites than those with compromised immune systems.
Don’t Fight Nature
Ultimately the goal for prevention is not to eliminate wildlife. Wildlife serves an important ecological purpose we must strive to sustain. (Remember, if you eliminate 1 opossum, another will simply take its place.) Rather, the goal is to discourage wildlife from scavenging for feed meant for horses.
KEY POINT: Minimizing stress and protecting feeding areas and feed are the easiest and most practical ways to prevent EPM. If that’s not enough for some high-stakes horses, what else can be done? For horses with many of the risk factors mentioned above, specifically active performance horses with high stress levels due to training and transportation, it may be beneficial to use a metaphylactic approach. This involves administering lower concentrations of an antiprotozoal drug to reach and maintain blood levels to prevent neurological invasion in susceptible horses. I’ve been involved with much of the work on diclazuril (Protazil, Merck), which has shown that using a lower daily dosing or staggering doses of diclazuril (extending the administration interval to twice a week) can lead to diclazuril blood levels that are 16
Issue 8/2021 | ModernEquineVet.com
known to be inhibitory to S. neurona. That doesn’t mean this strategy will lead to less EPM. It’s simply proof-of-concept that we can alter the dose and frequency of diclazuril drug administration to lead to blood levels that are known to potentially be effective at inhibiting apicomplexan protozoal parasites. In another study—the only 1 that looked at the long-term effects of diclazuril—we evaluated the overall seroprevalence in foals located in a geographic area with high exposure rates to S. neurona. A low dose of diclazuril (0.5 mg/kg) was administered every day from 1 month of age to 1 year of age. At the end of the year-long study, 88% of nontreated horses (control group) tested seropositive while only 6% of the treated horses did. We know that a horse must test seropositive to develop EPM, and here we saw a clear association between daily drug administration and lower seroprevalence. So, in theory, we’ve reduced the risk of the treated horses developing EPM. Further studies are needed to clearly guide best practices for our industry in terms of metaphylactic treatment; but existing research is very promising.
Is resistance a concern?
When discussing the preventive use of diclazuril, I often get asked if we’re at risk of inducing S. neurona resistance to diclazuril. In short, no. Since horses are dead-end hosts, the encysted form (sarcocyst) does not appear in horses, hence there is minimal risk that diclazuril resistance develops and that such resistant forms of S. neurona are ingested by opossums and the life cycle is completed. While EPM has been recognized and studied for more than 5 decades, it is a dynamic field with more important studies on the horizon. In fact, EPM is still being studied on several fronts—from additional blood and neurodegeneration markers to other preventive procedures and protocols and understanding why certain horses are at a higher risk of developing EPM. Many horses are exposed to S. neurona or N. hughesi, and some are more likely than others to develop EPM. Those most at risk are young performance horses. While simple management strategies can lower exposure, metaphylactic treatment may be beneficial to certain at-risk horses. Studies demonstrate the benefits of using diclazuril in reducing seroprevalence as well as the magnitude of titer in horses under high exposure to S. neurona. Focus on case definition to identify the horse that would benefit the most from a metaphylactic approach, and when it would be most helpful—when that horse is traveling, competing and most stressed. In the meantime, research continues, and our industry holds promise of new and improved ways to prevent EPM.
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INFECTIOUS DISEASES
Important Safety Information
Use of Protazil® (1.56% diclazuril) antiprotozoal pellets is contraindicated in horses with known hypersensitivity to diclazuril. Safe use in horses used for breeding purposes, during pregnancy, or in lactating mares has not been evaluated. The safety of Protazil® (1.56% diclazuril) Antiprotozoal Pellets with concomitant therapies in horses has not been evaluated. For use in horses only. Do not use in horses intended for human consumption. Not for human use. Keep out of reach of children. This concludes our four-article series on EPM. Don’t miss our first three articles providing a review of EPM and its causes, guidance for diagnosis as well as available treatments and recovery strategies. MeV
About the Author
Nicola Pusterla, DVM, PhD, DACVIM, is a professor of epidemiology and medicine at the University of California, Davis, School of Veterinary Medicine. His research focuses on infectious diseases and molecular epidemiology. Dr. Pusterla wrote this article series in partnership with Merck Animal Health. He was instrumental in setting up the Equine Respiratory Surveillance Program with Merck at UC Davis.
For more information: James et al. Seroprevalences of anti-Sarcocystis neurona and anti-Neospora hughesi antibodies among healthy equids in the United States. JAVMA 2017; 250(11):1291-1301 https://doi.org/10.2460/javma.250.11.1291 Reed SM, et al. Equine protozoal myeloencephalitis: an updated consensus statement with a focus on parasite biology, diagnosis, treatment and prevention. J Vet Intern Med 2016;30:491–502. https://onlinelibrary.wiley.com/doi/10.1111/jvim.13834 Hunyadi L, Papich MG, Pusterla N. Pharmacokinetics of a low-dose and FDA-labeled dose of diclazuril administered orally as a pelleted top dressing in adult horses. J Vet Pharmacol Ther. 2015 Jun;38(3):243-8. doi: 10.1111/jvp.12176. Epub 2014 Oct 20. https://onlinelibrary.wiley.com/doi/10.1111/jvp.12176 Hunyadi L, Papich MG, Pusterla N. Diclazuril nonlinear mixed-effects pharmacokinetic modelling of plasma concentrations after oral administration to adult horses every 3–4 days. Vet J. 2018;242:74-76. https://www.sciencedirect.com/science/article/abs/pii/S1090023318304362?via%3Dihub
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CLICK HERE TO READ PART 2 IN THE SERIES
CLICK HERE TO READ PART 3 IN THE SERIES
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