The Modern
Equine Vet www.modernequinevet.com
Vol 9 Issue 11 2019
Reproduction
Advancing the First Ovulation of the Year
Ask the Nutritionist? Ideal Body Condition for a Breeding Mare Increasing the Odds for Assisted Reproduction Handling Endocrine Laminitis Zimeta Approved for Fever Diastema Management
NEW FEATURE: ASK THE NUTRITIONIST? YOUR NUTRITION QUESTIONS ANSWERED
TABLE OF CONTENTS
COVER STORY
4 Advancing the First
Ovulation of the Year Cover photo: Shutterstock/Lasse Ansaharju
ASK THE NUTRITIONIST?
What’s the Ideal Body Condition for a Mare Preparing to be Bred? .............................. 3 REPRODUCTION
Increasing the Odds for Assisted Reproduction..................................................................... 8 LAMENESS
Cooling, Confinement and Support .....................................................10 DENTISTRY
Mind the Gap: Decision-Making in Diastema Management ........14 NEWS
FDA Approves Zimeta for Equine Fever............................................12 Particularly Deadly Year for EEE Human Cases..............................18
ADVERTISERS Purina Sponsored Content.........................................3 Merck Animal Health..................................................5 AVMA | PLIT....................................................................7 American Regent Animal Health/Adequan...........9
Stokes Pharmacy........................................................10 Heska............................................................................13 American Regent Animal Health/BetaVet...........15 AAEVT............................................................................19
The Modern
Equine Vet SALES: Matthew Todd • Lillie Collett 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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Ask the
Nutritionist
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ANNA C. PESTA, MS, PHD NUTRITIONIST, EQUINE TECHNICAL SOLUTIONS, PURINA ANIMAL NUTRITION
Ask the Nutritionist is a new monthly column featuring questions answered by PhD equine nutritionists and sponsored by Purina Animal Nutrition. Have a nutrition question you want to see featured? Email the Editor. For clinics looking for specific nutritional advice, visit purinamills.com/ask-an-expert.
What’s the ideal body condition for a mare preparing to be bred? Are there any specific nutrient requirements or suggestions to optimize fertility? Body condition score (BCS) is the variable most likely to impact reproductive efficiency. Success depends on what shape mares enter the breeding season in. Evaluation of BCS should occur at least 90 days ahead of breeding to allow time to make progress, either in weight gain or loss, toward an ideal BCS of 5–7. Mares bred at a BCS of 5–7 have an advantage in many aspects of reproductive efficiency when compared to those entering breeding season too thin (BCS < 4) or too fat (BCS > 7). Mares at BCS 5–7 will: • Come into season earlier • Have a decreased interovulatory interval • Have decreased incidence of early embryonic loss, resulting in higherpregnancy rates • Have more optimal milk production • Be less likely to have foals predisposed to certain health conditions Open mares and mares in early to mid-gestation have similar energy and nutrient requirements to a horse at maintenance. Good quality forage should meet daily calorie requirements and be paired with an appropriate concentrate or balanced vitamin and mineral supplement to supply nutrients not present in forages. If forages have low protein content, a ration balancer like Purina® Enrich Plus® is a good option to provide the correct quantity and balance of amino acids, along with essential vitamins and minerals. For over-conditioned mares, restricting daily forage intake to 1.5–2% of body weight per day or utilizing slightly lower quality forages can lead to moderate weight loss. Mares that need to gain weight will benefit from the addition of a highcalorie concentrate in addition to high-quality forage. The sooner the weight gain program starts before breeding, the better, since even an ambitious
weight gain program might result in just 1–2 pounds of gain per day, depending on the size of the horse. A weight gain of approximately 50 pounds is needed to cause a one-point increase in BCS. Therefore, it may take up to 50 days to see a one-point increase in BCS. The best approach is to provide a quality, balanced ration at a rate that meets the required daily calorie level to ensure the mare is at the ideal 5–7 BCS coming into the breeding season.
ABOUT THE AUTHOR Dr. Anna Pesta is a Nutritionist, Equine Technical Solutions, with Purina Animal Nutrition. She helps bring innovative solutions from the research team to horse owners. Most of her time is spent providing technical consultations and support to the sales team on the East Coast. She also speaks at veterinary and horse-owner meetings and professional conferences. SPONSORED BY PURINA ANIMAL NUTRITION
ModernEquineVet.com | Issue 11/2019
3
REPRODUCTION
Advancing the
FIRST OVULATION B y
4
M a r i e
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R o s e n t h a l ,
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BVetMed, CertAVP(ESM), MRCVS, reminded her colleagues that there is no one-size-fits-all method for advancing the first ovulation of the year. Each option depends on the individual mare and her situation, as well as the desires of the manager and owner. Thoroughbred breeders have always wanted to produce the most mature yearlings for sales or racing, or, in sports breeding, to achieve multiple embryos from the same mare in one season. Photoperiod manipulation is the most common method of advancing estrus through the regulation of the hormone melatonin, which inhibits gonadotropin releasing hormone (GnRH) and subsequently follicle stimulating hormone (FSH) and luteinizing hormone (LH), according to Dr. Moore who spoke at the 2019 BEVA Congress in Birmingham, U.K. Mares, which are seasonally polyestrus, are long-day breeders, and exposure to longer levels of light during anestrus induces estrus. In the natural annual cycle, longer periods of darkness through
Shutterstock/Lasse Ansaharju
OF THE YEAR
As we move into breeding season, Sarah Moore,
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REPRODUCTION
the winter stimulate the pineal gland and the release of melatonin, which inhibits the release of GnRH from the hypothalamus, and therefore, the production of FSH and LH, resulting in a period of anestrus. “Manipulation of the photoperiod does not shorten the process of transition,” explained Dr. Moore, an equine stud veterinary reproduction specialist at Rossdales Hertfordshire, U.K. “It merely moves it earlier in the year. The average time from the first day of light exposure to a first ovulation is 60 days.” That means that a light regimen usually begins on Dec. 1 to have Thoroughbred mares cycling around Feb. 14, the official start of the Thoroughbred breeding sea-
Winter Solstice January February
December Anestrus
November Transitional
April Breeding Season Regular recurring estrus cycles
September
August
The exact mechanism of action of dopamine is unknown, but it is believed to inhibit prolactin, which is suppressed in the autumn and winter and increases with increasing follicular activity. In the spring, it is hypothesized that prolactin increases the sensitivity of the follicle to LH, although use of dopamine antagonists has been shown to have no effect on FSH levels and only an indirect effect on LH prolactin. Therefore, some degree follicular activity is required for antagonists to have any effect.
PROGESTERONE Progesterone is ineffective at advancing or synchronizing estrus in mares that are in deep anestrus, but it can normalize transitional estrous cycles. It is useful for synchronizing the cycles of all the mares for breeding.
GNRH OR ITS AGONISTS GNRH or its agonists have been used to induce ovulation in transitional mares, either through daily injections or infusion. As with a dopamine antagonist, results were less successful when the mare was in deep anestrus with little follicular activity. Dose rate also affects success. However, cessation of GnRH treatment after ovulation can result in low progesterone levels and a high chance of pregnancy loss. This suggests that GnRH, cannot override the inherent seasonal suppression of ovarian activity.
FSH OR RECOMBINANT FSH + LH Treatment with recombinant FSH (reFSH) or a combination of reFSH + LH has been shown to advance the estrus in mares without the need of artificial lights. In a study, 30 mares confirmed in anestrus through ultrasonography were placed into 3 groups. The control mares were maintained under artificial lights from Dec. 1. The other 2 groups started treatment on Feb. 6. One group was given solely reFSH + hCG as an induction agent once a 35 mm follicle was reached, and the second group was given reFSH until the follicle of 29 mm was reached. Then received reFSH and LH until follicles reached 32 mm and then reLH until the 35 mm follicle was achieved and then hCG as an induction agent. All of the unestrus mares in the reFSH or reFSH + LH showed marked follicular development within 5 to 6 days of starting treatment and ovulated within 8 to 10 days when compared with 15 to 18 days for control mares. They also showed a greater number of developing follicles and the higher percentage of ovulations. However, more anovulatory follicles were seen in the treated groups compared with the controls.
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Transitional
October
Dopamine antagonists
6
March
May
June July son. Aim for approximately 15 to 16 hours of light, given by a 100 watt bulb in a 12 x 12 stable, she recommended. For any lighting regimen to be effective, mares should be exposed to a period of short day-length prior to initiating a lighting regime. Studies have shown that mares should be exposed to extra light in the evening, rather than another part of the day. Night interruption or pulse lighting also can be used to advance estrus. This was effective when 1 hour of light exposure was used 9½ to 10½ hours after darkness. “It's important to remember that light needs to be received by the mare's eye and overhead lighting may not always be the most efficient although it is often the most practical,” she said. Equilume offers a mask developed as a variation of the traditional barn lighting regime. The mask delivers 50 Lux of blue lights to 1 eye for 4 hours after dusk.
Body Condition
Other factors including age, body weight, nutrition and proximity to
DECEMBER
Increased hypothalamic GnRH
MARCH
Sequential anovulatory follicles
JANUARY
Increased FSH secretion
FEBRUARY
Onset of follicular development
APRIL
MAY
Follicular steroidogenesis begins
1st ovulation of the year
LH secretion begins
Failure of LH secretion Failure of follicular steroidogenesis
the stallion will affect the mare's response to both the photoperiod and pharmacological manipula-
tion. “Various studies have discussed the stimulatory effective [on] mares introduced to lush
grass and high-quality protein,” Dr. Moore said. “The current recommendation is that the mare enter the breeding season with a body condition score of over 5 out of 9 and a body fat content of over 15%.” Some mares need a bit more help, and there are a number of pharmacologic agents that can help manipulate anestrus (see box). Agent choice depends on the mare, the cost and the ability of the client to remain adherent with the regimen. And all of the regimens require some degree of follicular activity, she warned. “Unfortunately, there is currently no drug program that has any effect without some degree of follicular activity as much as it would make our lives a lot easier,” Dr. Moore said. MeV
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REPRODUCTION
Increasing the Odds for Assisted Reproduction By Adam Marcus A new method for assisted reproduction in horses could save time and money, while significantly increasing the odds of a successful procedure. The approach allows breeders to use eggs from fertile mares, fertilize them using intracytoplasmic sperm injection (ICSI) and then reimplant them into the same mares’ uteruses during the same ovulation cycle. For the study, researchers at Colorado State University in Fort Collins gave ovulation-inducing drugs to mares. Once the oocytes had matured, the researchers removed them from the ovarian follicles and fertilized them using ICSI, then transferred the blastocysts back
ing to the investigators. “Following this synchronization regime, ICSI-produced embryos can be transferred into oocyte donors’ uteri during the same cycle, allowing donors to carry pregnancies after assisted fertilization,” according to the researchers, who reported their findings in a recent issue of Reproduction, Fertility and Development. Elaine Carnevale, DVM, PhD, a professor of Biomedical Sciences at Colorado State, and the senior author of the study, noted that the new method can be used when sperm is only available for ICSI. “Transferring the embryo back into the egg donor’s uterus eliminates the costs associated with the lease and
into the mares’ uteruses after roughly 1 week. The researchers aspirated 20 follicles from 9 mares, harvesting 12 oocytes that underwent ICSI. Of those, 10 (83%) cleaved, and 8 (67%) developed into blastocysts, they reported. The 8 blastocysts progressed into 5 pregnancies, resulting in a pregnancy rate of 62% per transferred embryo and 42% per sperm-injected egg, accord-
maintenance of a recipient,” she told the Modern Equine Vet. “The egg donor mare can carry its own offspring, which some owners prefer to a surrogate mare.” Katrin Hinrichs, DVM, PhD, the regents professor and Patsy Link Chair in Mare Reproductive Studies at the Texas A&M University College of Veterinary Medicine and Biomedical Sciences, in College Station, said the new approach “has value especially for small breeders, who might not want to buy or maintain an extra mare as a recipient; or owners of less valuable mares, that are not in work, but from which the owner would like a foal.” MeV
For more information: Rossini JB, Rodriguez J, Carnevale EM. Autogenous transfer of intracytoplasmic sperm injection-produced equine embryos into the uterus of the oocyte donor during the same oestrous cycle. Reprod Fertil Dev. 2019 Oct 4 (Online ahead of print). https://pubmed.ncbi.nlm.nih.gov/31581979-autogenous-transfer-of-intracytoplasmic-sperm-injection-produced-equineembryos-into-the-uterus-of-the-oocyte-donor-during-the-same-oestrous-cycle/ 8
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Shutterstock/Emma Hicks Photography
A new method for assisted reproduction allows breeders to use eggs from a fertile mare, fertilize them using ICSI and then reimplant them into the same mare's uterus during the same ovulation cycle.
There’s nothing else like it. Over the past 30 years, Adequan® i.m. (polysulfated glycosaminoglycan) has been recommended millions of times1 to treat degenerative disease, and with good reason. From day one, it’s been 2, 3 the only FDA-Approved equine PSGAG joint precription available, and the only one proven to. Restore synovial joint lubrication Repair joint cartilage Reverse the disease cycle Reduce inflammation When you start with it early and stay with it as needed, horses may enjoy greater mobility 2, 4, 5 over a lifetime. Discover if Adequan is the right choice. Talk to your American Regent Animal Health sales representative or call (800) 458-0163 to order. 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 (800) 734-9236 or email pv@americanregent.com. Please see Full Prescribing Information at 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. Adequan and the Horse Head design are registered trademarks of American Regent, Inc. © 2019, American Regent, Inc. PP-AI-US-0222 2/2019
LAMENESS
Cooling, Confinement and Support How to Handle Endocrinopathic Laminitis
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cally apparent, the damage is likely already done. The basement membrane can repair itself, but the architecture will never return to normal; the changes are irreversible. “With that in mind, we need to decide where we can intervene and what the best intervention might be,” said Andrew van Eps, BVSc, PhD, DACVIM (Large Animal), at the 2019 BEVA Congress in Birmingham, England, UK. “Prevention is where it's at. It's where we have to focus our efforts.” Endocrinopathic lameness is one of the problems that could benefit from intervention. The key for these horses is early diagnosis, as they may have advanced pathology prior to showing outward signs, he said. In fact, a recent study showed that 50% of horses with radiographic evidence of laminitis on admission had no history of owner or veterinary recognition of the
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signs of disease. “I think it’s reasonable to do screening radiographs, particularly in horses and ponies that are considered at risk,” he said. “We should also look for the presence of divergent rings that are further apart at the heel and closer together at the toe.”
Prevention
Targeting insulin dysregulation or interfering with the effects of insulin on the horse’s feet are 2 areas to target. Early diagnosis using dynamic testing—particularly oral sugar testing—and then medically managing the insulin response to ingested carbohydrates are promising strategies. “If we’re going to interfere with the effects of insulin on the feet, then we need to know how insulin actually affects the feet,” said Dr. van Eps, who is associate professor of Equine Musculoskeletal Research at the University of Pennsylvania School
of Veterinary Medicine. “That is where our challenge is at the moment. Our best evidence points to the fact that even though insulin has vascular effects, the effects are probably not causing the issue.” Current research is pointing to a growth factor (IGF-1R) signaling problem. In other words, insulin is directly affecting the growth factor signaling pathways in the feet. The effects are similar to cell transformation in certain cancers, he explained. While the similarities are mostly academic, additional research has shown that cooling the feet can prevent this type of laminitis. “It wasn't just a mild effect,” Dr. van Eps said. “Cooling had a marked effect in the insulin model. As we cooled the feet, the architecture was preserved.
Acute Management
What constitutes rational first aid for acute cases? First, start with
the underlying cause. “I used to feel that we shouldn’t measure insulin levels or test for Cushing’s in a horse with an active bout of laminitis because of the stress involved, but now I’ve gone the opposite way,” Dr. van Eps said. “I test for underlying endocrinopathy, and I treat aggressively to try
to reduce its effects.” Other goals include minimizing further lamellar damage, providing anesthesia, and monitoring progression. To limit damage in these horses, anti-inflammatories may be helpful, but they typically don’t make a drastic difference. To make a bigger dent, Dr. van Eps
looks to mechanical manipulation of the feet—either with foot support or a specialized surface—and confinement and restriction of activity. “Mechanically, our elements are the weight of the horse pushing down on the ground, the pull of the deep flexor tendon, and the lever action of the hoof wall—not
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LAMENESS
What’s New in Chronic Laminitis? For management of chronic cases, there haven’t been too many recent breakthroughs. “We’re still battling the lamellar wedge,” Dr. Andrew van Eps said. “We’re also battling the misalignment of the coronary papillae.” The exact sources of pain caused by laminitis are starting to come into better focus. There is pain from the lamellae themselves, but there is also a significant component of pain coming from the bone, due to the loss of the suspensory function of lamellae. The bone now presses on the sole, which it simply is not designed to do. With the advent of 3D imaging, veterinarians are getting a better picture of the bone pathology and resorption of bone involved in laminitis. “The combination of pain and bone resorption has parallels with cancer-induced bone pain and complex regional pain syndrome in people,” Dr. van Eps said. “In those cases, the only thing that improves pain levels are bisphosphonates. Opioids are not particularly helpful, but bisphosphonates improve pain in people with these problems, so it’s something to consider.” Perhaps one of the biggest advancements is the use of clogs. “I’m a clog convert,” Dr. van Eps said. “You can move the breakover back quite drastically, and in all directions. Sometimes you get miraculous results just by putting clogs on.” just of the toe but also around its perimeter,” he said. “These forces are counteracted by the lamellae, and there are only a limited number of ways to manipulate this.” Raising the heel and reducing the pull of the deep flexor tendon is one
way, as is trimming some of the hoof wall and reducing the lever arm. “The only other thing we can do is transfer some of that load from the wall on to the sole and frog,” he said. “We can achieve that with an impression material.”
For specialized surfaces, Dr. van Eps is still a big fan of sand, even though it won’t win him many friends among the people who actually have to deal with the cleanup, he joked. “It reduces the leverage of breakover in every direction,” he said. “It allows the feet to pivot without grabbing, and it supports the sole and frog. For a horse that’s suffering from an acute laminitic episode. I think sand is ideal, but there's a lot of maintenance involved.” Cooling the feet with ice and water is one of the mainstays of treatment, regardless of the type of laminitis. There is evidence that cooling makes a difference even after lameness has started. While there is no standard length of cooling therapy, Dr. van Eps said that longer is not necessarily better. Any therapeutic gains tend to drop off after several days. MeV
FDA Approves Zimeta for Equine Pyrexia The FDA approved dipyrone injection (Zimeta, KindredBio) for the control of equine pyrexia. Pyrexia is associated with a number of underlying diseases and can result in significant negative outcomes, including dehydration, laminitis, muscle wasting, weight loss and in some cases—death. Among performance horses, fever can also lead to loss of training and competition days. There are more than 8 million horses in the United States, and more than 1 million are seen by a veterinarian for fever annually. Dipyrone belongs to the pyrazolone class of nonsteroidal anti-inflammatory (NSAID) drugs and is the first injectable dipyrone product to receive FDA approval for equine use. Dipyrone is intended for IV injection once or twice daily (every 12 hours) for up to 3 days. The overall number of doses and duration of treatment depends on the response observed. Dipyrone has been shown to cause gastric ulcers, abnormal feces and prolongation of coagulation parameters in horses. Horses on dipyrone should be monitored for signs of lack of appetite, diarrhea, or unexplained bleeding. In addition, caution should be used in horses 12
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at risk for hemorrhage. The safe use of dipyrone in horses younger than 3 years of age, horses used for breeding, or in pregnant or lactating mares has not been evaluated. Dipyrone is not for use in food animals. Direct contact with the skin should be avoided. Practitioners should take precautions when handling and using loaded syringes to prevent accidental selfinjection, as studies have indicated that dipyrone can cause agranulocytosis in humans. In 1977, the FDA formally withdrew the approval of all dipyrone-containing drugs for humans use, after becoming aware of the adverse event. However, the data generated to support the approval of dipyrone did not indicate that agranulocytosis occurred in horses treated with the drug. Following the removal of the human drug product from the U.S. market, sales of an unapproved equine dipyrone product continued. However, in 1996, the FDA removed the unapproved equine dipyrone product from the market due to concerns about its use in food-producing animals. Subsequently, the FDA noted increased distribution of compounded dipyrone sold for use in horses. MeV
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Imaging the Possibilities
DENTISTRY
Mind the Gap:
Decision-Making in Diastema Management of horses have diastema—abnormal spaces between the teeth that can trap food—and most of them are in pain, according to Neil Townsend, MSc, BVSc, DipECVS, DipEVDC (Equine), MRCVS, of Three Counties Equine Hospital, Gloucestershire, England, United Kingdom. Each diastema offers its own challenges, so a thorough, proactive plan is important, according to Dr. Townsend.
Primary diastema are the result of dental buds that have developed too far apart or from insufficient angulation of the 06s, 10s, or 11s. These are typically seen in younger horses. “Secondary diastema are generally next to displaced or supernumerary cheek teeth,” Dr. Townsend said. The teeth of geriatric horses begin to taper toward their apex, they’re not quite as compressed as they had been, and they develop shallow pockets. “These can be more significant than deeper pockets in younger horses because there’s no level of reserve crown in these teeth, and they’re more likely to have significant attachment loss,” Dr. Townsend said here at the 2019 BEVA Congress in Birmingham, England, UK. Diastema are further classified as open- or valve-type. Open diastema are typically less problematic than valve diastema, but the presenting signs for each are equally recognizable. Quidding, halitosis and poor performance on the bit are the telltale signs. “Some of these horses won’t
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show signs at all,” he said. “I recently saw a horse that had some of the worst periodontal disease I’ve seen in a while, but it was showing absolutely no clinical signs. In other horses, they may have minor periodontal disease with marked pain.” Regardless, treating the diastema before secondary effects (eg, swelling of the jaw, draining tracts, sinusitis) show up is important. Once those stages begin, treatment becomes more difficult.
Diagnosis
Mirrors and endoscopes are a must, but Dr. Townsend emphasized that old-fashioned palpation is still a valuable tool. “Older horses in particular will have slightly mobile teeth, but you won’t be able to detect how mobile they are if there are diastema,” he said. “Don’t forget to have a feel in there as well. You must have a well-sedated horse for this; the diastema are usually at the very back of the mouth, so push that tongue out of the way and have a good look in.” For radiographs, a standard oblique view will show you the mandibular teeth, and aiming down at 30 degrees will give you a good visualization of the apical regions. For visualization of the interdental bone, an open-mouth
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The link between RAPID ONSET and LONG-ACTING RELIEF of pain & inflammation1 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 ® 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 cleft palate in offspring and 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. 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) 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. DOSAGE AND ADMINISTRATION: Shake well immediately before use. Use immediately after opening, then discard any remaining contents. RX ONLY 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. © 2019 American Regent, Inc. PP-BV-US-0027 5/2019
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.
PP-BV-US-0027_FullPg_Ad.indd 2
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 customer care or to obtain product information visit www.betavetequine.com or call 1-800-458-0163. To report an adverse event please contact American Regent Animal Health at (800) 734-9236 or email pv@americanregent.com.
A Division of American Regent, Inc. 5 Ramsey Rd. | Shirley, NY 11967
5/17/2019 9:15:15 AM
DENTISTRY
oblique projection while angling up or down 10 to 15 degrees should be sufficient.
Treatment
On the human side, the literature is packed with studies evaluating the gold-standard treatments. Unfortunately, there are only a few in equine medicine. “We then have to look at the treatment similarities between horses and humans,” Dr. Townsend said. “The inflammatory response that we get in a periodontal pocket is similar. Plaque is the substrate in humans, and while there is plaque in equine teeth, the most common part is the trapped food material between the teeth. Flushing the periodontal pocket and mechanically removing the food is part of the ultimate aim of reducing the bacterial load in those tissues.” Dr. Townsend uses a headstand and a lavage system for a flushing. Nowadays he wears a pair of goggles for this part, after his optometrist was appalled at the state of his contact lenses following a particularly intense flushing, he said. He employs a regular dental syringe to flush out loose food material, then pushes the tongue to one side and uses a pair of straight forceps to pick out the food on the sides. At this point, he’s staying out of the periodontal pockets. “I don’t use nerve blocks for this—I tend to use topical local anesthetic, such as prilocainelidocaine gel,” he said. “It comes with an applicator, but I prefer drawing it up into a standard 5-mL syringe, then dribbling it over the periodontal pocket. Then I can really get into the bottom of that pocket with lavage and rightangled forceps.” After flushing, Dr. Townsend will repeat the mirror or oral endoscope exam to make sure he
hasn’t missed any food, and then it’s on to assessment of the pocket depth with a periodontal probe. Examine the conformation of the diastema—whether it is open or valve-type, and then make sure none of the teeth are loose or in need of extraction.
Flushing the periodontal pocket and removing the food mechanically is part of reducing the bacterial load in these tissues. Packing
Before packing a diastema, Dr. Townsend recommended asking whether you’ve got the space clean enough. “I think it’s relatively safe to put packing material in some of the open diastema where you can see all the way to the bottom,” he explained. “However, I don’t think we can truly say that we're fully able to evaluate the depth of some of these periodontal pockets.” The aim of diastema packing is to protect the gingival tissues from the oral environment. One of the more common packing materials is polyvinyl siloxane, although Dr. Townsend noted that alarms are starting to be raised about the material. “Recent in vitro evidence suggests that it is toxic to periodontal
fibroblasts,” he explained. “The one we tend to use most was effective at killing these periodontal cells. That being said, it is an in vitro study, but it has made me think about what we’re putting into these spaces.” Non-permanent packing materials, such as crushed metronidazole tablets, adhesive dental paste, calcium hydroxide, and doxycycline gel are often employed as well. “For me, getting the food out is the most important thing,” Dr. Townsend said. “If it’s a deep periodontal pocket I will protect it with a [gelatin sponge containing colloidal silver] so food doesn’t make its way to the bottom, and it will slowly dissolve over time.” With valve diastema, packing may just be treating a single symptom while leaving the underlying problem untouched, he added.
Widening
For select cases with valve diastema, widening the space can be a useful treatment. However, there is the potential to do some harm. “I start out with a high-speed handpiece and small fissure bur to create a groove between the teeth, and then I use a slightly larger bur to extend the groove through,” Dr. Townsend said. “You’re looking to take off more of the rostral aspect of the caudal tooth instead of caudal aspect of the rostral tooth.” The next step is to use an IC300 handpiece and a carbide bur to make a straight gap across. This is an aggressive setup, so proper technique is crucial. “I usually try to see these horses again in 3 to 4 weeks,” he said. “I flush the periodontal pockets, and then assess in another 3 to 4 weeks. I’ll also change the horse’s diet to avoid short, chopped fiber that tends to preferentially get stuck in between the teeth.” MeV ModernEquineVet.com | Issue 11/2019
17
NEWS NOTES
Particularly Deadly Year for EEE Human Cases
Images courtesy of National Institutes of Health
This year has brought home the fact that eastern equine encephalitis (EEE) affects more than horses; 2019 was a particularly deadly year for the disease in the United States, according to a new report by the National Institute of Allergy and Infectious Diseases. As of Nov. 12, 36 confirmed cases of EEE had been reported by 8 states; 13 of these cases were fatal. In a recent commentary, public health officials described the current research efforts to address EEE, and the need for a national strategy to address the growing threat of EEE virus and other emerging and re-emerging arboviruses.
There were 12 documented human EEE epidemics between 1831 and 1959 in the United States. The virus is spread among Culiseta melanura mosquitoes and various tree-perching birds found in forested wetlands. Occasionally, other mosquito species transmit the virus to people and other mammals.
In people, EEE virus takes roughly 3 to 10 days to cause symptoms. The virus initially causes fever, malaise, intense headache, muscle aches, nausea and vomiting; specific diagnostic testing may not reveal EEE because the virus is difficult to isolate from clinical samples and testing for EEEV antibodies may be negative. Neurologic signs of EEE, which may appear within 5 days of infection, initially are nonspecific but rapidly progress. Most people (96%) infected with the virus do not develop symptoms; however, of those who do, onethird or more die, and the others frequently suffer permanent and severe neurologic damage. So far, no antiviral drug has proven safe and effective against EEE, but many compounds are being assessed. Monoclonal antibodies have been found effective in an experimental animal model but only when given prior to infection. Patients with EEE are treated with supportive care, which often includes intensive care in a hospital and ventilator assistance. Patients with EEE are not infectious, and social support and counseling for both the patient and the family are vitally important given the seriousness of the disease, the authors wrote. Several EEE vaccine candidates are in development but may have trouble reaching advanced development and licensure, because human EEE outbreaks are rare, brief and focal, and occur sporadically in unpredictable locations, making it difficult to identify an appropriate target population for vaccination. Efforts to develop mosquito-saliva vaccines that would be effective against multiple mosquito diseases, including EEE, are in early stages. In the absence of effective EEE vaccines and treatments, state and local health departments can provide an early warning of imminent human infections by surveilling horses, birds and mosquitoes, but these efforts are threatened by insufficient funding. Although outbreaks of EEE disease are infrequent and focal, the spike in cases in 2019 and the looming presence of other, potentially deadly arboviruses in the United States demand a national defense strategy for arboviruses and other vector-borne diseases, the authors wrote. MeV
For more information: Morens DM, Folkers GK, Fauci AS. Eastern Equine Encephalitis Virusâ&#x20AC;&#x201D;Another Emergent Arbovirus in the United States. N Engl J Med. 2019;381:1989-1992. DOI: 10.10561/NEJMp181166. https://www.nejm.org/doi/full/10.1056/NEJMp1914328?query=featured_home 18
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