WORM CONTROL IN SMALL RUMINANTS L.H. Williamson, DVM, MS, DACVIM

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1 WORM CONTROL IN SMALL RUMINANTS L.H. Williamson, DVM, MS, DACVIM Haemonchus contortus, better known by producers as the barber pole worm, is a major health threat to goats, sheep, llamas and alpacas living in temperate parts of the United States. Haemonchus contortus is a massive egg producer, and it can go from being in an egg to being an egg layer in as little as three weeks. These advantages enhance this parasite s remarkable genetic adaptability in response to selection pressures from anthelmintic administration. When susceptible worms are removed by treatment, only resistant worms to rapidly repopulate. The problem is magnified when the whole herd is treated with anthelmintics, followed by movement to a field with little parasite contamination. Since the resistant worms are the only contributors to the next generation, anthelmintic resistance is ensured. In many endemic areas around the world, treatment failure with conventional anthelmintics is now the rule rather than the exception. Resistant parasites can be created on the farm through frequent, non-selective administration of anthelmintics. Another way resistant parasites are acquired is within animals that are purchased or borrowed, and put on pastures without any biosecurity protocol. Many sheep and goat producers are struggling with multi-drug resistant Haemonchus contortus populations on their farms. Total drug resistance, defined as resistance to all three major drug classes (avermectins, benzimidazoles, membrane depolarizers), and the most potent avermectin, moxidectin, is on the rise. For example, a study conducted in the southeastern United States showed that Haemonchus contortus isolates from 46 sheep and goats were resistant to benzimidazoles, ivermectin, levamisole and moxidectin on 98%, 76%, 54%, and 24% of the farms, respectively. Resistance to benzimidazoles, ivermectin and levamisole were noted on 48% of the farms, and total anthelmintic resistance was found on 17% of the farms (Howell, JAVMA 2008). The situation has already worsened. Camelid H. contortus isolates are showing similar drug-resistant trends. Larval developmental assays (LDA) performed on Haemonchus contortus isolates from 34 camelid farms in the southeastern United States demonstrated resistance to the benzimidazoles, ivermectin, levamisole, and moxidectin on 100%, 91%, 18%, and 26% of the farms, respectively (WAAVP 2011; updated 2015). Fortunately, healthy, immunocompetent sheep and goats can cope with nematode burdens when infection intensity is low-to-moderate. Worm burdens stimulate an immune response, which results in varying levels of acquired resistance. Resistant animals are able to limit establishment of new infections, and expel established worms more quickly than less resistant sheep and goats. Since resistance is a genetic trait, it can be selected for in a herd or flock. The individual fecal egg count (in the face of moderate worm challenge) is an excellent marker of resistance. Resilience in the face of worm challenge is another highly desirable trait. Resilient animals develop minimal morbidity in response to moderate worm challenge Resilience is partially genetically determined, but management factors also play a big role. Excellent nutrition, and control of environmental stress factors promote resilience. The old adage, you can feed your way out of a worm problem but you cannot worm your way out of a feed problem, holds true in many situations. Body condition score, and FAMACHA scores are useful markers of the resilience trait. Recognition of resistance and resilience traits in a herd or flock provides producers with useful culling and retention information. Retention of breeding animals with demonstrated resistance and resilience will make worm control easier subsequent generations. The benefit is quite meaningful within 5 years (Bath, 2011).

2 Small ruminants are most likely to develop signs of parasitism when they are immunecompromised, and when they are subjected to such high infection intensity that acquired immune advantages are overwhelmed. Kids and lambs in their first grazing season, and pregnant and lactating females are high-risk populations. Further, suboptimal nutrition reduces immune capability, and therefore makes animals less capable of coping with parasite challenge. High infection intensity is most often encountered on permanent pastures that are over-stocked. As a rule of thumb, no more than 5-7 small ruminants should be stocked per acre of pasture. If the animals are primarily browsing, the stocking rate can be increased to 10 per acre. Areas of worm hyper-transmission can develop where animals congregate (night-time or milker holding pens, water or feeding areas), and in areas that remain moist. If not recognized and remedied, these hot spot areas can undermine worm control strategies. Dry lots and wooded areas can be used to break the parasitic life cycle when pasture intensity is high. The clinical disease associated with heavy Haemonchus contortus infections is referred to as haemonchosis. Severely affected animals show signs of weight loss, ill thrift, soft stool and anemia. The fecal egg count is often high (> 1,000 eggs per gram trichostrongyles), and can exceed 30,000 eggs per gram. The packed cell volume and total proteins are both reduced, and the blood loss can be fatal levels. Small ruminants suffering from haemonchosis must be treated with a combination of anthelmintics, each from a different chemical class, to maximize treatment efficacy. For example, full doses of levamisole, oral moxidectin, and a benzimidazole can be given sequentially. It is important to treat goats with 1.5-2X the label dose for sheep. If the affected animal is still ambulatory and appetent, a blood transfusion might not be necessary. However, weak, anorexic animals with packed cell volumes below 12% will benefit from transfusion of whole blood (1-2% of recipient s body weight). This amount of blood will not normalize the packed cell volume, but will often adequately restore function until the patient can rebuild red blood cells. A transfusion can be safely performed without first cross matching the donor and recipient as long as neither has received a previous blood or plasma transfusion. A subsequent transfusion is risky without prior testing. Whole blood (up to 1 liter per 75 kg body weight) is collected from a large, healthy, non-anemic donor into an empty one liter IV fluid bags to which 100 mls of acid citrate dextrose solution has been added, or into commercially available transfusion bags. The blood is administered using a filtered IV blood set and indwelling intravenous catheter. Initially (first minutes), drip the blood at one drop per 3 seconds. If no reaction is seen, the flow rate can be increased. The entire transfusion is given over 1-2 hours. Additional support includes excellent nutrition, and housing the recovering animal in a clean non-stressful, noncompetitive environment. Parenteral thiamine supplementation is also beneficial. Generally speaking, when a few animals in a herd or flock are showing signs of parasitism, it is warranted to assess the rest of the herd or flock. Decisions regarding which animals to treat and which to leave untreated are made based on clinical signs such as body condition score, fecal consistency, and ocular membrane color. Well-fleshed small ruminants, on average, have lower fecal egg counts than thin animals. Pallor of the conjunctiva is an excellent indicator of the severity of H. contortus infection; it is the basis principle of the FAMACHA system. Since introduction of the FAMACHA system in 2004, thousands of FAMACHA cards have been distributed in the United States, and numerous workshops have been conducted to teach small ruminant and camelid producers how to implement the concepts in their herds and flocks. FAMACHA ocular assessment

3 should be conducted in bright natural light, using the FAMACHA card as a color reference. The upper eyelid is held over the globe, then the index finger is used to gently retropulse the globe through the upper eyelid. The thumb of the same hand is used to evert the lower eyelid. The FAMACHA card is held beside the eye with the opposite hand. The color of the lower eyelid conjunctiva is compared with the FAMACHA card over a 1-2 second period, and assigned a score. Both lower eyelid conjunctiva are scored, and if variation is noted between the 2 eyelid scores, the more anemic (higher) score is assigned. Treat camelids and small ruminants that score in categories 4 or 5 with an effective anthelmintic. Animals scoring in categories 1 or 2 are not anemic and therefore do not need treatment. Animals that receive a FAMACHA score of 3 should be handled based on the individual and herd situation. For instance, young animals, and animals in herds or flocks where the majority of the animals have anemic scores and/or poor body conditions should be treated, particularly during periods of high H. contortus transmission (warm, moist conditions). Since many animals that score as a 3/5 are not anemic, more animals will be treated than actually need it. However, many less animals will be treated than when nonselective methods are used, so adequate refugia is maintained. FAMACHA examinations should be conducted every 2-3 weeks during periods of high H. contortus transmission, and less frequently during times of the year when transmission is typically low. It must be stressed that the FAMACHA system is not intended as a management tool for other types of internal parasites, only H. contortus. Assessing Treatment Efficacy The adult burdens of Haemonchus contortus and Trichostrongylus colubriformis often correlate well with a fecal egg count. The modified McMaster technique is a popular quantitative technique that can easily and quickly performed with minimal equipment. A known volume of floatation solution is mixed with a weighed amount of feces, strained, and then pipetted into the chambers of the McMaster slide. Trichostrongyle eggs in both chambers are counted under 100x magnification using a compound microscope. The number of ova seen is multiplied using a dilution factor to arrive at the eggs per gram. Depending on the amount of feces used, the lower level of detection is either 25 or 50 eggs per gram. Quantitative centrifugation methods such as the modified Wisconsin and Stoll test, require more time and equipment, but detect ova down to 5 eggs per gram. These methods can detect larger numbers of heavier parasitic ova, such as large coccidians and Nematodirus. Non-trichostrongyle eggs, such as whipworms, Nematodirus, tapeworms, and coccidian oocysts are not counted, only reported. Fecal egg counts are useful to assess which animals are harboring the most worms in the herd or flock, and to assess the types of worms present. One of the most useful applications of the fecal egg counts is to assess treatment efficacy. Pre-treatment fecal egg counts are compared with post treatment fecal egg count days after the animal was treated with an anthelmintic or combination of anthelmintics. The fecal egg count reduction test (FECRT) can be performed in herds or flocks to assess the efficacy of one or more anthelmintics. The accuracy of the results is improved by having at least 6 animals, preferably animals in each group, and by having pre-treatment fecal egg counts of at least 200 eggs per gram, preferably higher (Kaplan, 2015). The animals used in the test should not have been treated with any anthelmintics for at least 8 weeks. If testing more than one anthelmintic, the test animals can be assigned to treatment groups and treated as they go through the chute based on FAMACHA scores so that each group has a mixture of non-anemic, mildly anemic and more anemic in them. This strategy should ensure that there are enough parasitic eggs

4 in the groups to make the test meaningful. To reduce error, weigh animals and use a dosing chart (go to wormx.info for free downloads) when administering treatments. Pre-treatment fecal egg counts are calculated using the quantitative methodology of choice. However, if pre-treatment fecal egg counts are fairly low, it is a good idea to use more a test with a low sensitivity end point such as the Stoll or modified Wisconsin. Ten to 14 days later, post treatment fecal egg counts are collected from the same animals, and quantitated using the same methodology used for the pretreatment fecal egg counts. The mean pre and post treatment (tx) fecal egg counts (FECs) for each group are calculated and used in this formula: % FECR = pre tx mean FEC post tx mean FEC pre tx mean FEC 100 Highly effective drugs will have FECRT results of 97% or greater, whereas drugs with poor efficacy will test as less than 60% on the FECRT. At points in between, the reliability of the results will depend on whether or not sufficient numbers of animals with adequate pre-treatment fecal egg counts were used in the analysis. The larval developmental assay (DrenchRite assay; Horizon Technology, 1996) is another way to assess anthelmintic sensitivity. Only a few laboratories around the world offer this test, and it is expensive (estimated $450). This in vitro test detects resistance to benzimidazoles, levamisole, and the macrocylic lactone class from a single pooled fecal sample that contains sufficient numbers of viable parasite eggs (> 350 epg). Sensitivity or resistance to moxidectin can be determined based on the ivermectin dose response. Inquiries about the larval developmental assay should be directed to Sue Howell at jscb@uga.edu. Selected References Howell S, Burke J, Miller JE, et al. Prevalence of anthelmintic resistance on sheep and goat farms in the southeastern United States. J Am Vet Med Assoc 233: , 2008 Williamson LH, Storey B, Kaplan RM. Evaluation of the FAMACHA system in South American camelids. Proc 22 WAAVP: 84 (abstract), 2009 Riley DG, Van Wyk JA. Genetic parameter for FAMACHA score and related traits for host resistance/resilience and production at differing severities of worm challenge in a Merino flock in South Africa. Vet Parasitol 164: 44-52, Bath GF. Non-pharmaceutical control of endoparasitic infections in sheep. Vet Clin N Am Food Anim Pract 27: , Kaplan RM. Determining the level of efficacy of anthelmintics. Proceedings of, What Works With Worms Congress, Pretoria, South Africa, May 2015.

5 EMERGING NOVEL WORM CONTROL STRATEGIES L.H. Williamson, DVM, MS, DACVIM Management of gastrointestinal parasitism in small ruminants is a major challenge in many parts of the world, largely due to the steady worsening of multi-drug anthelmintic resistance. Haemonchus contortus, a blood feeding gastrointestinal nematode, has garnered substantial notoriety for it s pathogenicity, and for it s propensity to rapidly magnify anthelmintic resistance in offspring of worms that survived exposure to treatment. In response to the failure of conventional anthelmintics, alternative anti-parasitic strategies, such as feeding condensed tannins, and administration of copper oxide wire particles, are gaining popularity in the United States. Other strategies, such as feeding nematophagous fungi, and administration of Haemonchus contortus vaccines are currently not commercially available in this country, so the focus of this discussion will be on condensed tannins, and copper oxide wire particle administration. Condensed Tannins Plants such as sulla, sainfoin, birdsfoot trefoil, big trefoil, chicory and Sericea lespedeza contain condensed tannins, a substance with known anti-parasitic effects. 1 Tannins are plant polyphenols that are divided into 2 groups: hydrolysable, and condensed tannins. Hydrolyzable tannins are degraded in the ruminant digestive tract to absorbable, and potentially toxic metabolites. In contrast, condensed tannin metabolites are poorly absorbed, so they remain in the ingesta bound to macromolecules such as protein and polysaccharides. Consumption of low to moderate concentrations of condensed tannins has nutritional benefit because the protein-binding effect allows some dietary protein to bypass the rumen, and undergo digestion in the small intestines. However, consumption of high levels of condensed tannins can negatively impact rumen microbiota, and reduce appetite. Beneficial effects of feeding condensed tannins at optimal concentrations include decrease in bloat and methane gas formation. Condensed tannins are believed to damage parasites by binding to the protein-rich parasitic cuticle. 1 Anti-parasitic benefits include reduction in adult nematode numbers, reduced worm fecundity, and decreased fecal egg output. 1 Sericea lespedeza (SL), a non-bloating perennial legume that is rich in condensed tannins, has received a great deal of research attention recently. Sericea lespedeza is well adapted to the southeastern United States, and it grows in a variety of soils, including otherwise infertile acidic soils. 2 In addition, SL is also drought tolerant and insect resistant. For the past century, SL has mainly been used for soil stabilization, and as a livestock forage. 3 Many SL cultivars exist, but AU Grazer (Auburn, Alabama, 1997) is the primary cultivar used in the United States for feeding livestock. The anti-parasitic benefits of sericea lespedeza were only recently discovered. Min et al. noted that parasitized goats on SL-rich pasture had had a 57% reduction in fecal egg count (FEC) compared to goats grazing grass pasture. 4 In a subsequent experiment, Angora does that grazed on SL pasture for 81 days had a 76% reduction in their total adult worm burden compared to controls on crabgrass/fescue pasture. 5 Adult Haemonchus contortus were reduced by 94%, Teladorsagia circumcincta by 100%, and Trichostrongylus colubriformis populations by 45% in goats grazing SL pasture. 5 Min s research group later demonstrated that goats ingesting SL

6 pasture not only had decreased FEC, but parasitic larval development was also impaired. In addition, goats grazing SL had higher packed cell volumes (PCV), and improved immunologic function, compared to goats on crabgrass/tall fescue pasture. 6 Lambs grazing SL pasture also had lower FEC than their counterparts on Bermudagrass pasture. 7 Unlike goats, sheep appear to require an adjustment period to acclimate to the astringency of fresh sericea lespedeza. 7 Further studies showed that the condensed tannins in SL retained anti-parasitic benefits when fed as hay and as pellets, and that these formulations were highly palatable to both goats and sheep. 8,9,10,11 A titration study conducted in goats concluded that 75% of the diet needed to be comprised of SL hay to achieve the greatest benefit, but feeding it as 50% of the diet also reduced FEC compared to controls. 10 Recent research demonstrated that feeding Sericea lespedeza also has significant anti-coccidial benefit in kids and lambs. 12,13,14 Lambs naturally infected with nematodes and coccidia that received SL pellets 30 days before and 21 days after weaning, had lower FEC, and shed up to 98% less Eimeria oocysts than controls on a conventional creep feed. 12 The lambs on the SL pelleted rations did not need conventional treatment for clinical coccidiosis, whereas 33% of controls had symptoms significant enough to warrant treatment. 12 Similarly, feeding SL leaf meal pellets to recently weaned goats significantly reduced both the FEC (66%) and FOC (91%). 13 Interestingly, the FOC did not increase when the SL feeding was discontinued, indicating a direct and permanent effect on the coccidian parasites. 13 In summary, Sericea lespedeza is a non-bloating legume that can provide substantial benefit for control of gastrointestinal nematodes and coccidia in small ruminants. Sericea lespedeza effectively reduced gastrointestinal nematodes when fed fresh, as hay, or as a pelleted preparation. For control of H. contortus, and to a lesser extent, other gastrointestinal nematodes, SL should be fed at approximately 50% (or more) of the diet in any of it s various forms (fresh forage, hay, pellets, silage) during periods of high risk. Once SL feeding is discontinued, small ruminants should be closely monitored for signs of gastrointestinal parasitism. When using it for natural coccidian control, SL can be fed to youngsters as 50% or more of the diet, 2 weeks before weaning. The SL creep feed can be continued for up to 6 weeks after weaning, but not indefinitely, as micronutrient deficiencies have been noted in youngsters with long-term feeding. 3 Micronutrient issues has not been noted in adults on long term SL supplementation. 3 Practical obstacles to feeding SL are availability as well as cost. Sericea lespedeza grows well in warm climates, and it can be grown separately, or mixed with other forages. Certified AU Grazer sericea lespedeza seed and pellets are commercially available from Sims Brothers (Union Springs, Alabama). Demand for the products continues to increase, so manufacturer supplies are often limited. Copper Oxide Wire Particles Copper oxide wire particles (COWP) are marketed as 12.5g boluses for cattle, and as 2 and 4g boluses for small ruminants to treat copper deficiency. Over 15 years ago, researchers noted that administration of COWP had an anthelmintic effect, and that the impact was most significant against Haemonchus contortus. 14 Administration of 5 grams of COWP to 10 week old lambs five days prior to inoculation with either H. contortus, T. circumcincta, and T. colubriformis reduced parasitic establishment by 96, 56, and zero percent, respectively. 14

7 After administration, copper oxide wire particles mix with ingesta in the forestomachs, and then they subsequently lodge in the abomasal mucosa. Copper dissolves from the particles in the acidic environment. Dissolved copper interacts with susceptible parasites, causing expulsion or death. If abomasal ph is raised to 3-4 by Teladorsagia circumcincta infection, dissolution of copper from COWP is significantly decreased. 15 Ionic copper released from COWP is absorbed in the small intestine. Copper concentration peaks at day 4 in the proximal duodenum, and after 10 days, concentration steadily declines. 15 Research on dairy goats demonstrated that COWP (2 and 4g) reduced experimentally established H. contortus infections by 75%, and lowered fecal egg counts up to 95%. 16 Teladodorsagia circumcincta and Trichostrongylus colubriformis burdens were only reduced by 28% and 15%, respectively, at necropsy. 16 Copper oxide wire particle treatment was not very effective at preventing establishment of new H. contortus infections, however. 16 Similarly, COWP treatment (either 2.5 or 5g) significantly reduced established H. contortus infections in yearling sheep, but did not effectively limit establishment of experimental new infections over the 8 week study period. 17 In a subsequent experiment on 4 month old Zulu goat kids, neither a 2 or 4g COWP treatment prevented establishment of new H. contortus infections. 18 These findings indicate that COWP treatment is most effective against established H. contortus infections, and that it has minimal prophylactic benefit. Anthelmintic benefit of COWP only persists for 28 days. 19 Administration of copper can increase the risk of copper toxicity in small ruminants, particularly sheep. 20 Sheep are more prone to copper toxicity than goats because they are less efficient at eliminating stored hepatic copper. Hepatic copper is normally stored in hepatic lysosomes, which slowly release copper into bile for excretion in feces. If the liver becomes overloaded with copper, any stressor can cause copper to be released from lysosomal storage. Unbound copper wreaks oxidative damage on the liver and other tissues, and causes hemolysis in in circulation. 20 In order to reduce the risk of copper toxicity, several research efforts focused on identifying the lowest COWP dose that would provide anthelmintic benefit in sheep and goats. Burke et al. administered 0, 2, 4, or 6g COWP to 6 month-old lambs, 28 days after administration of H. contortus third stage larvae. 21 All doses of COWP resulted in much lower FEC, higher PCV, and a significant reduction in abomasal worms at necropsy compared to untreated controls. 21 Liver copper concentrations 28 days after COWP administration were 62.2, 135.7, 161.1, and ppm (wet matter basis) in the 0, 2, 4, and 6 g groups respectively. 21 Although none of treated lambs showed signs of copper toxicity, their hepatic copper was twice as high as control lambs at 28 days, and above the normal hepatic copper reference levels. A subsequent study in weaned lambs showed that even lower doses (0.5 and 1g COWP) had anti-parasitic benefit. 22 Further, these lower doses were safely administered 3 times, at 6 week intervals to lambs within the same grazing season. 22 In goat kids, 0.5 and 1g COWP improved FEC and PCV, compared to untreated controls. 23 The 0.5g dose was considered the optimal dose for goat kids. 23 A COWP dose titration trial was performed in mature ewes with natural parasite infections (70% H. contortus) to determine the lowest, effective dose. 24 The ewes received either 0, 0.5,

8 1, or 2g doses of COWP 60 days after lambing. 24 Seven days after administration, ewes treated with 1 or 2g COWP had lower FEC than ewes treated with either 0 or 0.5g COWP. Although PCV declined in all groups, ewes that received either the 1 or 2g COWP bolus were less anemic than the sheep in the control and 0.5g dose groups. Hepatic copper concentrations were not measured; aspartate aminotransferase activity did not differ among groups. The 0.5g COWP dose had little anti-parasitic effect in the ewes. The 1 and 2g COWP doses were deemed effective, but the 2g dose gave slightly better results. 24 Unfortunately, extensive dose titration studies have not been performed in mature goats. Interestingly, Chartier et al was one of the few researchers to take body size into account when dosing COWP. In his study, mature Saanen goats weighing kg received 4g COWP, and goats weighing kg received 2g COWP; both doses achieved anthelmintic benefit. 16 Copper oxide wire particles are typically administered within a gelatin capsule, using a balling gun. However, administration of 2g COWP in feed was as effective at reducing FEC in goats as administering it in a gelatin capsule. 25 If administered in feed, animals need to be fed individually rather than free choice to avoid inadvertent over-dosing or under-dosing. This more convenient route of administration could be particularly advantageous to handlers of exotic hoof stock that are susceptible to H. contortus. Copper oxide wire particle treatment of oryx, roan antelope, blackbuck, and blesbok reduced FEC by over 90% for up to 28 days. 26 In summary, copper oxide wire particle treatment effectively reduces established H. contortus infections in sheep and goats, based on decrease of FEC of up to 97%. However, it does not have much activity against other abomasal or intestinal parasites. Benefit appears to persist only about 28 days, and treatment does not effectively limit re-establishment of new infections. Treatment with COWP appears to have greater anti-parasitic benefit in lambs and kids than in mature sheep and goats, for reasons that are unclear. 23 Even though copper is released slowly and incompletely released from copper oxide wire particles, studies demonstrated that treatment elevates hepatic copper concentration. Although clinical copper toxicity was not induced in test subjects by COWP administration in any of these published studies, use of COWP in client-owned animals should be undertaken carefully. Assessment of copper and other minerals in hepatic tissue submitted from healthy animals, or from animals that die suddenly on farms, is recommended to determine if COWP benefits outweigh potential risks. The lowest effective dose of COWP should be used, and repeated dosing within the same grazing season should be discouraged if the micronutrient status of the herd or flock is unclear. Research supports the use of 0.5 to 1g COWP in lambs and kids for anthelmintic effect. In adult sheep, doses of 1 to 2g COWP appear sufficient. Doses of 2 to 4g COWP are indicated for use in mature goats. The lower end of the dosage range can be used for smaller breeds, and for animals where risks for copper toxicity are unknown. Treatment efficacy can be assessed using a fecal egg count reduction test. Researchers currently recommend selective (rather than whole herd or flock) use of COWP for anthelmintic purposes. 28 Since some worms survive exposure, it is possible that resistance to COWP treatment (as has been seen with conventional anthelmintic treatment) could develop. 23 Use of COWP can be combined with an anthelmintic to make treatment more broad-spectrum when infections are mixed. References

9 1. Hoste H, Jackson F, Athanasiadou S, Thamborg S, Hoskin S. The effecs of tannin-rich plants on parasitic nematodes in ruminants. Trends in Parasitol 2006; 22: Terrill TH, Miller JE, Burke JM, Mosjidis JA, Kaplan RM. Experiences with integrated concepts for the control of Haemonchus contortus in sheep and goats in the United States. Vet Parasitol 2012; 186: Terrill TH, Mosjidis JA. Smart man s lucerne and worm control, in Proceedings. What Works With Worms Congress 2015; Min, BR, Pomroy W, Hart S Sahlu T, The effect of forage condensed tannins on gastrointestinal parasite infection in grazing wether goats. J Anim Sci 2002; 80 (Suppl. 1): Min, BR, Miller D, Hart SP, Tomita GM, Loetz E, Sahlu T. Direct effects of condensed tannins on gastrointestinal nematodes in grazing Angora goats. J Anim Sci 2003; 81 (Suppl. 2): Min, BR, Hart SP, Miller D, Tomita GM, Loetz E, Sahlu T. The effect of grazing forage containing condensed tannins on gastrointestinal parasite infection and milk composition in Angora goats. Vet Parasitol 2005; 130: Burke JM, Miller JE, Terrill TH. Grazing sericea lespedeza for control of gastrointestinal nematodes in lambs. Vet Parasitol 2012; 186: Shaik SA, Terrill TH, Miller JE, Kouakou B, Kannan G, Kaplan RM, Burke JM, Mosjidis JA. Sericea leaspedeza hay as a natural deworming agent against gastrointestinal nematode infections in goats. Vet Parasitol 2006;139: Lange KC, Olcott DD, Miller JE, Mosjidis JA, Terrill TH, Burke JM, Kearney MT. Effect of sericea lespedeza, fed as hay, on natural and experimental Haemonchus contortus infections in lambs. Vet Parasitol 2006; 141: Terrill TH, Dykes GS, Shaik SA, Miller JE, Kouakou B, Kannan G, Burker JM, Mosjidis JA. Efficacy of sericea lespedeza hay as a natural dewormer in goats: dose titration study. Vet Parasitol 2009; 163: Terrill, T.H., Mosjidis, J.A., Moore, D.A., Shaik, S.A., Miller, J.E., Burke, J.M., Muir, J.P., Wolfe, R. Effect of pelleting on efficacy of sericea lespedeza hay as a natural dewormer in goats. Vet. Parasitol 2007; 146: Burke JM, Miller JE, Terrill TH, Orlik ST, Acharya M, Garza JJ, Mosjidis JA. Sericea lespedeza as an aid in the control of Eimeria spp. in lambs. Vet Parasitol 2013; 193: Kommuru DS, Barker T, Desai S, Burke JM, Ramsay A, Mueller-Harvey I, Miller JE, Mosjidis JA, Kamisetti N, Terrill TH. Use of pelleted sericea (Lespedeza cuneata) for natural control of coccidia and gastrointestinal nematodes in weaned goats. Vet Parasitol 2014; 204: Bang KS, Familton AS, Sykes AR. Effect of copper oxide wire particle treatment on establishment of major gastrointestinal nematodes in lambs. Res Vet Sci 1990; 49(6): Bang KS, Familton AS, Sykes AR. Effect of ostertagiasis on copper status in sheep: a study involving use of copper oxide wire particles. Res Vet Sci 1990; 49(3): Chartier C, Etter E, Hoste H, Pors I, Koch C, Dellac B. Efficacy of copper oxide needles for control of nematode parasites in daiy goats. Vet Res Commun 2000; 24:

10 17. Knox MR. Effectiveness of copper oxide wire particles for Haemonchus contortus control in sheep. Aust Vet J 2002; 80: Vatta AF, Waller PJ, Githiori JB, Medley GF. The potential to control Haemonchus contortus in indigenous South African goats with copper oxide wire particles. Vet Parasitol 2009; 162: Vatta AF, Waller PJ, Githiori JB, Medley GF. Persistence of the efficacy of copper oxide wire particles against Haemonchus contortus in grazing South African goats. Vet Parasitol 2012; 190: Van Saun RJ. Understanding copper nutrition in small ruminants, in Proceedings. Am Assoc Bov Pract 2012; ; Burke JM, Miller JE, Olcott DD, Olcott BM, Terrill TH. Effect of copper oxide wire particles dosage and feed supplement on Haemonchus contortus infection in lambs. Vet Parasitol 2004; 123: Burke JM, Miller JE. Evaluation of multiple low doses of copper oxide wire particles compared with levamisole for control of Haemonchus contortus in lambs. Vet Parasitol 2006; 139: Burke JM, Terrill TH, Kallu RR, Miller JE, Mosjidis J. Use of copper oxide wire particles to control gastrointestinal nematodes in goats. J Anim Sci 2007; 85: Burke JM, Morrical D, Miller JE. Control of gastrointestinal nematodes with copper oxide wire particles in a flock of lactating polypay ewes and offspring in Iowa, USA. Vet Parasitol 2007; 146: Burke JM, Soli F, Miller JE, Terrill TH, Wildeus S, Shaik SA, Getz WR, Vanguru M. Administration of copper oxide wire particles in a capsule or feed for gastrointestinal nematode control in goats. Vet Parasitol 2010; 168: Fonttenot DK, Kinney-Moscona A, Kaplan RM, Miller JE. Effects of copper oxide wire particle bolus therapy on trichostrongyle fecal egg counts in exotic artiodactylids. J Zoo Wildlife Med 2007; 39: Burke JM, Miller JE, Terrill TH, Smyth E, Acharya M. Examination of commercially available copper oxide wire particles in combination with albendazole for control of gastrointestinal nematodes in lambs. Vet Parasitol 2016; 215:1-4.

11 DIGNOSIS AND TREATMENT OF COMMON DISEASES IN SHEEP AND GOATS L.H. Williamson, DVM, MS, DACVIM Enterotoxemia Enterotoxemia is a common cause of unnatural death in small ruminants of all ages. Clostridium perfringens type D is a normal inhabitant of the gut flora. When it rapidly proliferates in response to overconsumption of simple sugars and starches, the bacteria elaborate epsilon toxin, which causes systemic vascular permeability, and lesions in the heart, lungs, kidneys, brain, and gastrointestinal tract. Enterotoxemia can present as an acute, sub-acute, or chronic disease. The acute form occurs most commonly in young, unvaccinated lambs and kids. Gastrointestinal pain, subnormal temperature, scleral injection, vocalization, tachycardia, frothing at the mouth, neurologic signs, shock, and sudden death are common clinical signs. The sub-acute form is more frequently seen in adults, vaccinated or not, and is characterized by profuse diarrhea (possibly bloody), abdominal pain, shock, and neurological abnormalities. Death often occurs within four days of onset, but recovery is possible. Some vaccinated adult goats manifest a chronic form of the disease that can last for days to weeks. The chronic form is characterized by watery diarrhea, abdominal pain, lethargy, and anorexia. The end result is either recovery or death. Postmortem examination often reveals fibrin in the pericardium, reddened fluid filled loops of bowel, and focal brain lesions. Observation of numerous Gram-positive rods in the intestinal lumen supports the diagnosis, but oftentimes enterotoxemia is a diagnosis of exclusion. Some diagnostic facilities offer toxin analysis on bowel contents. Treatment consists of parenteral penicillin or tetracycline, flunixin meglumine, thiamine hydrochloride, Clostridium perfringens type C and D antitoxin, and fluid therapy (oral or intravenous). Vaccination of pregnant ewes and does, with approved C&D/T products, thirty days prior to parturition is highly recommended to protect neonatal lambs and kids. Neonates whose dams were not vaccinated prepartum can be vaccinated in the first week of life, and boostered at 5 and 9 weeks of age. Lambs and kids from vaccinated dams can be started on a vaccination program art 4-6 weeks of age; two boosters are given at monthly intervals. Adult breeding animals, especially dairy does and ewes that are fed concentrates to support heavy lactation, should be vaccinated every 4-6 months. Research has shown that vaccine-induced antibodies last 6 months or less, especially in goats. Breeding bucks and rams need to be vaccinated prior to breeding season, and boostered every 6 months. Non-breeding adult small ruminants on foragebased diets can be vaccinated annually. Urolithiasis Urolithiasis can affect both sexes, but the male s long narrow urethra is more prone to obstruction than the short, wide female urethra. Urinary calculi typically lodge in the sigmoid flexure, and proximal to the urethral process. The incidence of obstructive struvite-based uroliths is highest in heavily grain fed animals due to the high phosphorus content in cereal grains. Dietary phosphorus precipitates with magnesium and ammonium in alkaline urine to form calculi. Obstructive calcium-based uroliths also commonly occur in small ruminants. Although diet probably plays a role in formation of these

12 uroliths, the association is less clear than it is with struvite uroliths. Individual factors regarding calcium metabolism are suspected. The classic presentation is stranguria, characterized by posturing to urinate, vocalizing, and dribbling a small amount of urine. However, vague signs of depression, anorexia, and mild bloat are also common, especially in chronic cases. External palpation of an enlarged bladder is sometimes possible, but trans-abdominal ultrasonography is the best way to evaluate the size of the urinary bladder in sheep and goats. Normally the bladder is kept fairly empty. Visualization of a round (6-8 cm plus diameter) bladder is good evidence the animal cannot void properly. Bladder decompression via cystocentesis is necessary if the urinary obstruction is not relieved quickly by other means. Ruminants with chronic, partial, or intermittent obstruction of the urinary tract can develop hydronephrosis, which if bilateral, has a poor prognosis. An animal with complete urinary tract obstruction will ultimately rupture the urinary bladder or urethra in 2-5 days. Urethral rupture results in ventral abdominal swelling along prepuce, sometimes called "water belly". The subcutaneous tissue and skin will become necrotic, and slough. Urinary bladder rupture causes progressive abdominal distension, and depression. Uremia can lead to pulmonary edema and respiratory compromise. Initial evaluation necessitates examination of the distal penis. In some instances, the obstruction can be relieved through removal of the urethral process. Exteriorization of the penis is most easily accomplished in intact males, and wethers that were castrated later than 3 months of age. Sedation with midazolam ( mg/kg) will make the patient more compliant, without increasing urinary output. Use of xylazine and detomidine are contraindicated because these sedatives dramatically increase urinary output. The animal can be positioned on it s rump, leaning backwards, with it s back legs pulled up around the head to put pressure on the lower abdomen. Clip hair or wool around the penis to avoid entanglement during exteriorization. The sigmoid flexure is grasped through the skin and straightened while the prepuce is retracted. Lidocaine solution can be splashed on the penis to decrease discomfort. As the penis exteriorizes, it can be secured with gauze, or grasped with an atraumatic instrument (Allis, Babcock or Vulsellum forceps). If a urolith is present in the distal penis, the urethral process can be snipped off obliquely after it has been desensitized. If urine flow is established, owners must be warned that reobstruction is possible, as the bladder is most likely full of other potentially obstructionforming calculi. If urethral process amputation results in complete resolution of the obstruction, and the animal is not severely metabolically compromised, then everyone (patient, owner, veterinarian) is relieved. However, in most cases, further intervention (surgical and medial is necessary. Patients with azotemia and electrolyte abnormalities need intravenous fluid therapy to improve their chances for full recovery. Cystocentesis, followed by a surgical procedure such as a tube cystotomy or marsupialization is the most common curse of action. Perineal urethrostomy has been associated with a poor longterm outcome so is not a good recommendation in pet animals. Dissolution of cystic calculi is feasible only with phosphatic calculi. The calcium carbonate uroliths will not dissolve in acidic solutions. Preventative strategies include increasing roughage intake and decreasing grain intake. Provide a 2:1 calcium-to-phosphorus ratio in the total ration. Salt can be added to the ration (2% of ration on dry matter basis) to increase water intake. Supply fresh water at

13 all times. Urinary acidifiers can be fed to keep urine ph < 6.8 (to prevents struvite formation), but this strategy works better in theory than in reality. Caseous lymphadenitis Corynebacterium pseudotuberculosis causes external abscesses in the skin and lymph nodes, and internal abscesses in the lungs and abdomen. The disease is called caseous lymphadenitis (CL) in small ruminants, and it can become an endemic problem in a flock or herd. Abscesses form slowly 1-3 months after exposure. Occasionally, this organism causes abscesses in people. The organism persists in the environment for 8 months or more). It gains access into the body through skin wounds, or following ingestion. Abscesses anywhere on body should be considered as caseous lymphadenitis until proven otherwise by culture. External abscesses most commonly occur in association with the parotid and mandibular nodes in goats, but can be associated with any external nodes. Spread through contaminated lung secretions and shearing occurs more commonly in sheep than in goats. Small ruminants with internal abscesses can present primarily with symptoms of weight loss and ill thrift. Small ruminants with caseous lymphadenitis should be considered infected for life. The organism persists in the body because it has potent virulence factors that allow the organism to evade host defense mechanisms and spread through tissues. Recurrent abscess formation is common in affected animals. Abscesses should be cultured to confirm the diagnosis. A synergistic hemolysin inhibition test (SHI- Test) that detects CL-associated antibodies is available through UC Davis' Diagnostic Laboratory. The main drawbacks of the SHI-Test test are it will not distinguish a vaccinated animal from a naturally infected animal, and the test is fraught with false positive and false negative results. When in doubt, repeat the titer in suspect animals in 2-4 weeks. If titers are rising, and abscesses are present, then it is a safe assumption that CL is in the herd. Symptomatic commercial animals should be culled. It treatment is the preferred option, isolate the animal, and lance, drain and lavage external abscesses into leak proof disposable containers. Maintain isolation until the surgical wound has healed. This approach will not prevent recurrence of the disease, or reliably prevent the animal from contaminating the environment upon return to the herd or flock. Long-term (4-6 weeks) systemic antibiotic therapy (penicillin and rifampin) can be used to treat internal abscesses, but results are inconsistent. Tulathromycin been studied as an antibiotic choice for CL, but in vivo activity is poor in extra-pulmonary tissues. Commercial bacterin vaccines such as Case-Bac (Colorado Serum) are labeled for sheep. Lambs are vaccinated prior to co-mingling them with the adult infected flock. The initial dose is given subcutaneously followed by a booster in 4 weeks. Adults are given annual boosters. Case-Bac has been used extra-label in goats, but anecdotal reports suggest that more adverse reactions occur in this species. Texas Vet Lab markets a Corynebacterium pseudotuberculosis bacterin for goats; approval for use is on a state-by-state basis. Contagious Ecthyma or sore mouth This zoonotic parapox virus causes self-limiting scabby sores in the mouth and ears of lambs and kids. Udder lesions can occur in ewes and does. Some animals will maintain chronic lesions for years, but they are the exception and not the rule. If affected youngsters are able to eat, the owner should be advised to let the disease run it's course, and advised

14 to avoid handling lesions with their bare skin. People most commonly develop blisters on their hands when contracting orf, but deep, long-lasting ulcerative skin lesions occur in some individuals. Kids and lambs are at risk of starving if their mouth lesions are severe, or if the dam s udder becomes so painful that she will not allow them babies to nurse. These babies will need to be bottle or bucket fed. The lesions should not be debrided. Typically, lesions heal within 6 weeks time. Topical application of DW40 has been suggested as a way to dissolve the viral lipid coating, thereby enhancing lesion resolution (source: AASRP listserve). A live virus vaccine (labeled for sheep) is commercially available. The vaccine is administered to 7-30 day old lambs and extra-label in kids. The vaccine is brushed onto scarified skin. Scab formation several days later indicates the vaccine took effect. Avoid handling the live vaccine without protective gloves. Neurologic Listeriosis The zoonotic bacteria, Listeria monocytogenes, is known to cause encephalitis, abortion and septicemia in small ruminants. The bacteria can survive for an extended period of time in the environment, and can be shed intermittently in the feces, milk, semen, and uterine secretions of carrier animals. The disease is associated with silage feeding, but also with ingestion of woody browse. Small ruminants with encephalitic listeriosis initially exhibit depression and anorexia. Fever is an inconsistent finding. As the disease progresses, multifocal, and typically lateralizing signs of cranial nerve involvement arise, such as dropped jaw, salivation, tongue protrusion, strabismus, dysphagia, circling, and head tilt. Untreated cases, and cases where therapeutic intervention occurs late in the course of the disease, have a high mortality rate. Diagnosis is often made presumptively based on clinical observation of multifocal brainstem disease. A cerebrospinal fluid aspirate obtained from the lumbosacral space typically has an elevated protein concentration (> 40 mg/dl), an elevated WBC (> 5 cells/ul) and a white cell differential with over 50% mononuclear cells; neutrophils make up the remainder of the differential. The CSF can be submitted for culture, but more rapid antemortem results can be obtained by submitting the sample for PCR or a florescent antibody (FA) test. Culture, PCR and FA can also be performed on postmortem central nervous system tissues. Histopathology reveals micro-abscessation, focal necrosis, and nonsupperative perivascular inflammation of the brain stem and cranial spinal cord. Antibiotic therapy is the mainstay of treatment. Traditional antibiotic choices include tetracycline (10 mg/kg every 12 hours IV), and penicillin 22,000-44,000 units/kg every 6 hours IV). Intravenous therapy is not feasible outside a critical care setting, however. Subcutaneous procaine penicillin (10 mls per 50 kg once daily) and florfenicol (6 mls per 50 kg SQ every 3 days) can be used extra-label, with a post-treatment withdrawal time of 90 days. Treatment length is generally 2-3 weeks. Flunixin meglumine (1-2 mg/kg SQ or IV) or meloxicam (0.5-1mg/kg orally) can be used to manage inflammation. Patients that are unable to eat and drink will need ongoing fluid therapy to maintain hydration, acidbase and electrolyte concentrations. Positional support is needed for weak and recumbent patients. Transfaunation is beneficial to promote rumen function. Polioencephalomalacia (PEM)

15 Normal rumen microflora produce enough thiamine to meet the animal s needs. Thiamine deficiencies result from excessive production of thiaminases by rumenal bacteria in response to excessive carbohydrate consumption and low forage diets. Diets high in molasses and urea also promote development of PEM. Outbreaks of PEM have occurred after switching animals from a poor to a lush pasture. Amprolium administration can cause PEM if given for a prolonged period of time. Increased thiaminase activity has been also associated with administration of anthelmintics. Pre-ruminant animals can develop thiamine deficiency due to inadequate thiamine levels in milk replacers. Another form of PEM results from excessive ingestion of sulfur containing substances. Sources of dietary sulfur include calcium sulfate (gypsum), and water or forages with high sulfur content. The pathogenesis of sulfur related PEM is incompletely understood, and response to thiamine supplementation is poor. Clinical signs of PEM include a sudden onset of cortical blindness, stargazing, miosis, dorsal medial strabismus, incoordination, muscle tremors, disorientation, head pressing, excitation, excessive chewing, and facial twitching. The disorder progresses over several hours to days. Terminally, animals become recumbent, convulse and exhibit opisthotonos. Most cases of PEM occur in 6-18 month old sheep and goats, but it can occur occasionally in older animals. Diagnosis is often made presumptively based on clinical signs, and treatment response. Laboratory findings in thiamine dependent PEM cases include increased blood pyruvate concentration and decreased RBC transketolase activity. On necropsy, the brain is grossly moist and swollen, and the cortical gyri are soft and have a yellow discoloration. Ultraviolet light (Wood s lamp) will illuminate patchy areas of the cerebral cortex because lipofuscin is present in necrotic brain cells. Treatment consists of thiamine, 6-10 mg/kg body weight, given either IV or IM every 6 hours for the initial 2-3 days of treatment. As symptoms regress, thiamine treatment intervals are decreased. In critical care settings, intravenous DMSO and anticonvulsants have been used to manage brain swelling and to control seizures, respectively. Transfaunation can help restore rumen function and stimulate appetite. Client education includes dietary advice to feed more roughage and decreased concentrate feeding. If clinical signs suggest PEM, but the patient does not respond to thiamine treatment, food and water sources need to be tested for excessive sulfur concentrations. Cerebrospinal Nematodiasis ( Deerworm Disease, Meningeal Worm Disease ) Parelaphostrongylus tenuis rarely causes disease in the definitive host, the white tailed deer. Adult worms reside in the meninges of the deer, and deposit eggs in the venous sinuses and veins. The embryonated eggs travel to the lungs, where they hatch into first stage larvae. The larvae penetrate into the airways, are coughed into the pharynx, and swallowed. Eventually, the larvae pass in the feces where they are available to infect snails and slugs. The larvae develop into infective third stage larvae (L3) over a period of 3-4 weeks. New hosts become infected when they accidentally ingest infected snails and slugs. The infective third stage larvae are released from the intermediate host in the abomasum. The larvae then migrate to the spinal cord and meninges. In an aberrant host such as a small ruminant or a camelid, P. tenuis larvae penetrate the gut wall, and migrate to the central nervous system where they wander aimlessly. The resulting inflammation and destruction within the central nervous system causes clinical

16 signs. It can take days from the time the larvae are ingested until the onset of neurologic signs. The disease occurs in the late summer through winter in cooler parts of the country, but year round in the southeastern United States. Cases can arise sporadically, or as a herd outbreak. Clinical signs are often mixed (upper and lower motor neuron), and asymmetric. The most common presentation is rear limb ataxia that progresses to involve the forelimbs. Typically, affected small ruminants remain bright and alert, and maintain a normal appetite. However, when the parasites migrate through the brain, neurologic symptoms can mimic listeriosis and rabies. Diagnosis is often presumptive. However, finding an inflammatory response, with an increased proportion of eosinophils (5-97%) in the cerebrospinal fluid is highly significant. In small ruminants, the infection is not patent, so fecal exam is not a useful diagnostic tool. On postmortem examination, CNS lesions consist of irregular necrotic tracts in the spinal cord and brain. Microscopic evaluation reveals lymphocytic and eosinophilic perivascular cuffing. Sections of larvae are occasionally seen associated with areas of myelitis and meningitis, infiltratrated by inflammatory cells. Treatment consists of oral fenbendazole (20-50 mg/kg PO for 5-7 consecutive days), parenteral ivermectin (0.4 mg/kg/sq) to kill extra larvae, and anti-inflammatory therapy. Corticosteriods (dexamethasone; 0.1 mg/kg IV, IM, SQ once a day for 3-5 days, followed by a decreasing dosage of 0.05 mg/kg for 3-4 additional days) can be used in animals that are not pregnant. Alternatively, flunixin meglumine (2.2 mg/kg IV or SQ once a day for 3-5 days), or oral meloxicam (1.0 mg/kg orally once a day for first few days followed by doses of 0.5 mg/kg once daily) can be used. Recovery is dependent on the site of the lesion(s), and the onset of treatment with respect to the occurrence of clinical signs. Animals present recumbent and unable to stand have a guarded to poor prognosis. Preventative strategies include preventing the herd or flock s access to areas most likely to have high concentrations of infected intermediate hosts, such as shaded, low lying damp areas near natural water. Exposure to deer can be limited by using guardian dogs, and high barrier fences. In endemic areas, administration of subcutaneous ivermectin or doramectin at 4 and 6 weeks intevals, respectively, are the only useful strategy. However, this approach is labor intensive, and impractical in large herds and flocks. To date, efforts to develop a vaccine haven t been successful. Rabies Fortunately, rabies is not a common disease, but it has been included in this discussion because it is an important zoonotic differential for any patient exhibiting neurologic signs. The rhabdovirus is typically inoculated through bite wounds. Rabies can present as an ascending paralysis that first appeared as lameness, or as severe depression or aggression. Once symptoms begin, the disease rapidly progresses to fatality in 7 to 10 days. Diagnosis is made on postmortem tissues. The brain should be carefully harvested to avoid contamination, and sent chilled, to the diagnostic facility by overnight delivery. A fluorescent antibody test is performed within 24 hours on tissue from the hippocampus, cerebellum, or medulla. Histopathology reveals a nonsupperative encephalomyelitis. Rabies vaccines are approved for sheep. They are used extra-label in goats and camelids; vaccinate animals over 3 months of age, and booster annually.

17 Developing High Health Calves W. Mark Hilton, DVM, PAS, DABVP (beef cattle) Senior Technical Consultant, Elanco Animal Health West Lafayette, Indiana Cattle that stay healthy in the feedlot produce greater revenue than those that become sick. Data from the Texas Ranch to Rail Program on over 16,000 calves showed healthy cattle returned $67.32 per head while calves treated one or more times returned -$20.28 per head (Lalman). In the 2004 Tri-County Steer Carcass Futurity (TCSCF) in Iowa calves that were treated once netted $85.02 less than their non-treated contemporaries while calves treated two or more times netted $ less than nontreated calves (Busby, 2010). In 2014 these numbers ballooned to $ and $ less for calves treated once and two or more times respectively (Busby 2015, personal communication). The 2014 numbers show the tremendous influence on calf value when relating health to overall profitability. Let s start at the beginning and examine factors that affect health in the feedlot. Fetal programming We are just beginning to examine this fascinating area of health and productivity. The nutrition of the dam during fetal development impacts the offspring s health and development. The bottom line is that anytime we short the cow, it could have negative effects on her and potentially negative effects on her developing fetus. Dr. Rick Funston with the University of Nebraska, West Central Research and Education Center at North Platte, Nebraska is one of the pioneers in this developing field and I would encourage you to read his papers. We ve all heard for years that 75% of the growth of the developing fetus happens during the last 2 months of gestation (Ferrell, et al. 1976). That does not mean the first 7 months are unimportant. During early gestation the placenta and organs are formed with the placenta playing a major role in fetal growth. Since we are early in the evolution of research in fetal programming, there is much we still do not understand. With organogenesis and, in particular, development of the cardiopulmonary system, early gestational nutrient deficiency could increase the susceptibility of that developing fetus to respiratory disease later in life (Funston et al. 2010). We ve known for years that underfeeding energy to a cow in the last trimester of gestation increases morbidity and mortality in her offspring. Colostrum quantity and quality may be decreased and calf vigor is impaired in underfed dams. Steer calves from cows that were protein supplemented during late gestation while grazing protein deficient crop residue (5.2% CP) or stockpiled pasture (6.8% CP), had heavier carcasses, more IM fat and higher % overall body fat (Funston et al. 2010). It

18 appears that adequate nutrition of the dam allowed the offspring to express their genetic capability while the underfed dams produced calves with reduced ability to rise to their genetic potential. At all times of her life from about 14 months of age until she goes to market, the cow is eating for two or three. Watch for continued research from this exciting area of fetal programming. Calving time and environment When is the ideal time to calve? is a question I ve received throughout my career and my response is always, I ll tell you a month after the fact. It is my belief that beef cows need to be low-input and low-maintenance along with highly productive and highly profitable. I think we can have all four. If this is the goal, calving in the middle of winter in northern climates or in the middle of summer most places in North America makes little sense. Calving season is a balancing act of weather at calving time balanced with weather and forage supply at rebreeding. The issue of labor at calving time should be a minor factor because low-maintenance cows that calve on their own need little labor. Tag the calf, castrate the bulls and record the data in your IRM book. Calves born in weather conducive for a neonate to be born outside have many health advantages compared to calves born in a more confinement setting. Calving ease in heifers With the nearly industry-wide acceptance of Expected Progeny Differences (EPDs), rates of dystocia in beef heifers have decreased substantially over the past 30 years. The ideal situation is to breed heifers for at least one cycle via AI to highly proven (CED EPD >.70 accuracy) Angus or Red Angus bulls with CED EPDs in the top 5-10% of the breed (Angus > 12; Red Angus > 15). Heifers experiencing dystocia have calves with decreased vigor at birth and decreased colostrum intake which is a risk factor for increased morbidity and mortality throughout life, even though the feedlot stage. Calf vigor Calf vigor at birth is influenced by birth weight, calving ease score, sex of calf, age of dam and breed of calf. Producers don t need to use calving ease bulls on cows but need to be reasonable with regard to birthweight (BW) EPD. While the goal is not to produce 120# calves, it is also not to produce 60# calves from mature cows. In a study in Nebraska with over 4000 calves born out of 2 year-old heifers, calf mortality was increased with calves that were significantly heavier or significantly lighter at birth than the mean (Gregory et al. 1991). Selecting for extremely low birth weight does not appear to be a sound production practice as both very heavy and very light calves at birth have reduced vigor and increased mortality from birth to weaning. Crossbreeding/hybrid vigor will improve calf vigor, so cows should be mated to produce a crossbred calf. Cartwright et al. (1964) reported 6.1% heterosis for calf vigor at birth.

19 That compares to 3.9% heterosis for weaning weight. One of the best ways to improve calf vigor is to crossbreed. Colostrum Colostrum production is influenced by dam age, genetics and nutrition. Cows should be in BCS and heifers at calving time to optimize colostral production while also enhancing herd fertility. Cows produce a finite amount of immunoglobulin (Ig) and as milk EPD rises, colostral Ig concentration will decrease as the Ig will be diluted out in a greater volume of colostrum. If the calf can nurse all the colostrum, it will still receive all of the Ig. If colostrum production is in excess of the calf s ability to ingest it, the calf will have less Ig absorption. Is this a major issue? Probably not, but it is a potential concern. Higher and higher milk EPDs are not positive in my opinion. Research by Wittum and Perino (1995) showed that calves that had inadequate colostrum intake based on serum total protein 4.8 not only had increased sickness and death loss preweaning but also had 3.0 greater risk of feedlot morbidity. Colostrum intake and absorption of Ig is not just a neonatal calf health concern. Sandhills Calving System An attainable goal for many cow-calf herds is a 95% calf crop with 100% of those calves being healthy each year. One key is to allow all calves to be born into a clean environment. The definition of clean is no cattle for 2 or more months. The Sandhills Calving System (SCS) has been well researched and adapted to herds across the country (Smith et al. 2004). It is important to understand that it is the system that is important, not the sand. The system works in every state in the US and surely around the world. In the SCS, all pregnant, adult cows are placed in a large calving lot (paddock #1) approximately 7-10 days before calving is to start. After two weeks all cows that have already calved remain in paddock #1 with their calves while all cows yet to calve are moved to paddock #2. This allows those cows that have not yet calved to calve over the next 7 days in a new clean environment. After a week, cows yet to calve are moved to paddock #3, pairs remain in #2 and the process is repeated every week until calving has concluded. Bred heifers are put in a system similar and separate from the adult cows. Calf diarrhea in herds that adopt the SCS plummets to zero in many instances. Medicine and veterinary expenses disappear and calf weaning weights improve. Calves that stay healthy on the farm or ranch of origin have a greater likelihood of health in the feedlot compared to calves that have neonatal disease (Wittum). Basics of treatment of morbid calves Neonatal Diarrhea Since the majority of neonatal calf diarrhea occurs in approximately 7 14 day old calves, getting the etiological diagnosis is relatively unimportant. There are three main

20 causes of scours at that age, rotavirus, coronavirus and cryptosporidiosis and the treatment of each disease is identical. Calves with any of these diseases are dehydrated and acidotic. The primary treatment is fluid therapy. If the calf is scouring and listless but ambulatory, it is likely less than 8% dehydrated and can receive an oral rehydration solution (ORS) that corrects the acidosis and dehydration. A standard treatment is 2 quarts of ORS twice daily for 2-3 days. Because no ORS is adequate to supply the daily energy requirement of the calf, milk (via nursing the dam, bottle or esophageal tube) is also fed at 2 quarts twice daily. Goef Smith, DVM, PhD reviewed the electrolytes currently on the market in the US at the 2017 AABP annual meeting and his findings are included as Table 1 in these proceedings. If calves are down and unable to rise due to the effects of dehydration and metabolic acidosis then IV treatment is necessary. The use of hypertonic sodium bicarbonate at approximately 250ml for a neonatal calf has proven to be a rapid and effective method to correct the acidosis and dehydration in these calves. (Trefz) If calves have diarrhea at less than 5 days of age the most likely diagnosis is E. coli and systemic antibiotics need to be given in addition to oral or IV fluids. Pneumonia in the nursing calf This disease is a multifactorial disease complex just like BRD in the weaned calf. Prevention is directed toward improving calf immunity, nutrition and environment while limiting exposure to pathogens associated with the disease complex. Treatment is generally with an approved, long-lasting antimicrobial that has been successful in resolving previous cases of calf pneumonia on the farm of origin. Navel infection Prevention of disease is always superior to treatment and this is especially true for navel infections. Navel infections can become a systemic disease that infects the liver via the umbilical vein. Treatment with systemic antibiotics needs to be aggressive and prompt. Prewean/precondition/weaning Preconditioning calves = win-win-win-win. Calves are healthier with improved animal welfare; cow-calf producers enjoy improved income; feedlot buyers see decreased morbidity and mortality with improved profits and consumers get an improved product. Keys include: timely vaccinations low-stress weaning proper nutrition targeted marketing feedlot acclimation

21 Benefits include: less antibiotic use improved beef quality assurance (BQA) decreased labor improved carcass quality Data from the Ranch to Rail (TX) and Tri-County Steer Carcass Futurity (IA) shows the benefit of using two doses of MLV BRD vaccine well before feedlot entry (Lalman and Mourer 2012); (Busby 2010). Timing of doses should be at least 3 weeks apart with the initial dose at least 9 weeks preweaning and the second dose at least 3 weeks before feedlot entry. A study in Oklahoma by Kirkpatrick et al. (2008) showed the initial MLV can be given at a normal calf processing time (~ 2 months of age) with the second dose at weaning. The study showed equivalent outcomes to the more traditional 3-4 weeks prewean and at weaning with reduced labor. Do you want to know how to make the sale of high-risk calves extinct in less than 6 months time? Today, every buyer of feeder cattle agrees that they will only buy PC calves and no one will bid on high-risk (unweaned/unvaccinated) calves at any price for the next month. I think the news of the auctioneer crying No Sale! Take them back home! on a group of 500# bawling calves with no vaccinations would spread like wildfire across the plains when the lot of PC calves selling before them brought $900 each. While this surely will not happen, I do foresee the day that a major retailer may say We are only buying beef from feedlots that purchase 100% PC calves ; and that will change our industry. Feedlot entry To have the greatest chance for success in the feedlot, calves need proper nutrition, environment, immunity and animal handling. The majority of calves entering the feedlot have not had access to a high starch diet so feeding a high fiber diet that more closely resembles their nutrition on the ranch upon entry to the feedlot seems prudent. Utilizing a professional nutritionist for balancing cost-effective rations is the norm in the wellmanaged feedlot. Many smaller feedlots may not feel they can afford nutritional consultation, but experience working with producers proves otherwise. With nutrition being upwards of 70% of the cost of finishing a calf, spending a relatively small amount to get the best advice is money well spent. The ideal feedlot environment is dry but not dusty and protects against weather extremes. Shades and wind breaks should be standard features in feedlots. The use of bedding in cold and/or wet (and even extremely hot/sunny) environments has proven to be a cost-effective investment. Cattle comfort needs to have an increased focus in the feedlot.

22 The concept of low-stress cattle handling is gaining tremendous momentum and becoming the standard in many areas. The term running and cattle should never be used in the same sentence. The concept of low-stress cattle handling that may have seemed a bit trivial only years ago has become the standard of care and it is simply the right way to treat our animals. The cattle deserve the best we have at all times. If you are the producer of calves, look how you can sell a premium product through improvements in: fetal programming/nutrition of the dam calving time and calving environment calving ease in heifers calf vigor with crossbreeding colostrum using the Sandhills Calving System prewean/precondition/weaning feedlot entry If you are the buyer of feeder calves, find suppliers of calves that do all of the above so that you can feed a healthy, profitable calf that will produce the best possible product for the consumer.

23 References Busby, D. (2015) personal communication. Busby, D., (2010). Tri-county steer futurity data. Proceedings. Am Assoc Bov Pract Conf Cartwright, T. C., Ellis Jr, G. F., Kruse, W. E., & Crouch, E. K. (1964). Hybrid vigor in Brahman- Hereford crosses. Tech. Monogr. 1. Texas Agric. Exp. Stn., College Station. Ferrell, C. L., Garrett, W. N., & Hinman, N. (1976). Growth, development and composition of the udder and gravid uterus of beef heifers during pregnancy. Journal of Animal Science, 42(6), Funston, R. N., Larson, D. M., & Vonnahme, K. A. (2010). Effects of maternal nutrition on conceptus growth and offspring performance: Implications for beef cattle production. Journal of Animal Science, 88(13 electronic suppl), E205-E215. Gregory, K. E., Cundiff, L. V., & Koch, R. M. (1991). Breed effects and heterosis in advanced generations of composite populations for birth weight, birth date, dystocia, and survival as traits of dam in beef cattle. Journal of animal science, 69(9), Kirkpatrick, J. G., Step, D. L., Payton, M. E., Richards, J. B., McTague, L. F., Saliki, J. T.,... & Wright, J. C. (2008). Effect of age at the time of vaccination on antibody titers and feedlot performance in beef calves. Journal of the American Veterinary Medical Association, 233(1), Lalman, D., & Mourer, G. (2012) Effects of preconditioning on health, performance and prices of weaned calves. Oklahoma Cooperative Extension Service, Fact Sheet F Available at Accessed October 4, Smith, D. R., Grotelueschen, D. M., Knott, T., & Ensley, S. (2004). Prevention of neonatal calf diarrhea with the sandhills calving system. In Proc Am Assoc Bov Pract (Vol. 37, pp ). Smith, G. W. " Myth: One Oral Electrolyte is Just as Good as Another." AABP Conference Proceedings. Vol In Press. Trefz, F. M., P. D. Constable, and I. Lorenz. "Effect of Intravenous Small Volume Hypertonic Sodium Bicarbonate, Sodium Chloride, and Glucose Solutions in Decreasing Plasma Potassium Concentration in Hyperkalemic Neonatal Calves with Diarrhea." Journal of Veterinary Internal Medicine 31.3 (2017): Wittum, T. E., & Perino, L. J. (1995). Passive immune status at postpartum hour 24 and longterm health and performance of calves. American journal of veterinary research, 56(9),

24 PREVENTION OF DYSTOCIA AN EASIER WAY TO HANDLE BOVINE DYSTOCIAS W. Mark Hilton, DVM, PAS, DABVP (beef cattle) Senior Technical Consultant, Elanco Animal Health West Lafayette, Indiana Dystocia continues to be an important issue for the cow calf industry despite an apparent decrease in incidence during the last 20 to 30 years. 1 Genetics The most common cause of a dystocia is a fetal-dam disparity and first calf heifers are the most likely animal in the herd to experience dystocia. 2 The most successful way to prevent dystocia in heifers is to breed them to highly proven sires that have high calving ease direct expected progeny differences (CED EPD) and are from breeds known to have acceptable calving ease. 3 Each breed association publishes CED EPDs for bulls in their respective breeds and it is important to note that some breeds have improved calving ease compared to others. Breeds that excel in calving ease include Angus and Red Angus where breeds like Charolais and Shorthorn would have very few calving ease bulls. At this time there is not across breed EPD adjustment factors for calving ease as there is for traits like birth weight. Birth weight EPDs can be used to assess the relative calving ease of different bulls if CED EPDs are not available. The correlation between birth weight and calving ease is strong, but it is not a direct correlation. Studies show that for each kilogram increase in birthweight there is a % increase in dystocia rate 4,5. When selecting bulls to use on heifers it is ideal to use an artificial insemination (AI) sire that has high accuracy for calving ease. Many AI sires are available that have an accuracy of over 0.80 for calving ease and this would be considered a highly proven bull to sue on heifers. Yearling bulls are frequently used via natural service and most will have very low accuracies, sometimes as low as The service sire that is selected to be used on a group of yearling heifers is the most important factor in limiting the dystocia rate the following year. But, we must remember that the dam supplies half of the genetic material to the calf so selecting heifers with moderate birthweights or high maternal calving ease EPDs is also very important. Pelvic area Since the primary cause of dystocia in beef cattle is due to a fetal-dam disparity, numerous researchers have looked at pelvic measurements of the yearling female to predict subsequent risk of dystocia. Unfortunately, heifers with larger pelvic openings tend to be larger in frame score, and also have calves with heavier birth weights. Therefore, selecting for larger pelvic openings does not lead to a reduction in rate of dystocia 6.

25 Nutrition Numerous trials have been conducted to examine the relationship between precalving nutrition, calf birth weights and incidence of dystocia. In nine trials where precalving nutrition was influenced to cause heifers to calve from BCS 4-6, calf birth weight increased from 0-3 kg as BCS increased. 7 In these same studies, the incidence of dystocia was unchanged in seven trials and increased in two. When protein levels were increased, similar results were produced. While increasing precalving nutrition generally had no effect on dystocia rate, it had a profound effect on subsequent reproduction. In one study, two-year-old heifers nursing their first calf that calved in BCS 4 had a pregnancy percentage of 56% in a 60-day breeding season where heifers calving at BCS 6 had a 96% pregnancy percentage in the same timeframe. 8 It is clear that restricting feed intake to below NRC guidelines is not an effective way to reduce dystocia rates in heifers. TREATMENT OF DYSTOCIA: TEACHING THE BEEF PRODUCER: WHEN TO CHECK/WHEN TO CALL FOR HELP My experience working with producers for over 30 years is that all the timing data we give them for the different stages of labor is confusing and leads to them calling too late on many dystocias. When we started emphasizing PROGRESS EVERY HOUR to our clients in newsletters and at producer meetings, our success rate on being called early enough to deliver a live calf soared. For even more precise timing information, a heifer should make progress every hour while a cow should make progress every 30 minutes. This makes sense in that a multiparous animal nearly always delivers more quickly than a primiparous animal. Common problems that lead to more problems Many heifers and some cows with a dystocia have an incompletely dilated birth canal (vagina and/or vulva). After you clean the cow up, place both gloved and lubed arms into the birth canal, interlock your fingers and expand your arms outward. Do this for about 1-2 minutes. Many times manual dilation of the vagina is necessary and will greatly ease delivery (very important!!) Have the owner dilate while you go to truck to get something. This way you are not worn out when the real work begins. Do not use J-lube if there is any chance of a Caesarian Section. If any of the product spills into the abdomen it will likely cause death due to the overwhelming inflammatory response. 9 Definitions Presentation what part of the calf is entering the birth canal first? Normal is head first or anterior presentation Position where is calf s back in relation to the cow s back? Normal is dorsal/sacral. Posture where are front legs and head in relation to the trunk of the body? Normal is front legs extended and head/neck forward, resting on legs.

26 Obstetrical Technique If the calf is in an abnormal presentation, position or posture, you must have the cow standing to effectively manipulate the calf. When the cow is lying down the weight of her rumen is pushing on the uterus and the calf and it makes manipulation nearly impossible. To aid in relaxing the uterus when you have to manipulate the calf, give the cow 10ml Epinephrine (1:1000) IM in the neck and in about 2 minutes, the uterus will be relaxed. This relaxation will allow you to push the calf farther into the uterus and make the malpresentation much easier to resolve. This technique is most effective with a live calf. Once the calf is in normal presentation, position or posture, lay the cow down on her side using a long rope. The half hitch method of rope placement is depicted in figure 1. Lying down is the natural position of the cow during labor and our goal is to mimic nature. In addition, in recumbency, the unburdened pelvic floor is pulled forward to functionally increase the vertical diameter of the pelvis. 10 When the cow is standing, the pelvic floor is unable to move. It is also my experience that once the cow is in lateral recumbency she increases the force of her abdominal contraction. To deliver the calf, only pull when the cow pushes. 11 This is true if using manpower or the calf jack. When the cow rests, you should also rest. The goal is not to launch the calf out of the cow. When the calf is delivered to the hips, take a break and the cow will generally rest and then push the calf a bit more. Because of the short rest, the calf will generally rotate about 45 to 90 so that he slides right out. If we pull too quickly, we can wedge the calf s hips into the cow s pelvis before the calf has a chance to rotate. Keys to Success lay the cow down on her side only after the calf is in the correct position for delivery use a maximum force of one man per leg, pull lower leg first, walk shoulders out, pull straight out to get shoulders past pelvis of cow, then gently pull on both legs to get calf s hips up to cow s pelvis. (I nearly always use the jack. First, it teaches the owner the correct use of this equipment and second it is easier on my back.) STOP pulling at this point and allow cow to rest. The cow will usually rotate the calf into her pelvis so that the calf does not become hiplocked. after delivery, put calf in dog sitting position so lungs inflate equally; never hang calf upside down stick a clean straw in calf s nostril to stimulate breathing check the cow for additional calves get the cow up so she begins licking the calf place calf out of the wind, be sure calf is up in 30 minutes and nursing colostrum 30 minutes after standing dip navel with tincture of iodine if indicated, put cow and calf into a clean environment

27 Teach your Clients When to Call for Assistance 11 Owners should be taught to call when they: 1. Don t know what the problem is 2. Know the problem, but don t know the solution 3. Know the problem, know the solution, but unable to make progress. If you make no progress in 30 minutes, call for assistance. Video clip demonstrations at Click on Video demonstrations. Figure 1

28 References 1. United States Department of Agriculture (USDA), Beef Part V: reference of beef cow calf management practices in the United States ; p.16. Available at: V.pdf. Accessed September 14, Waldner CL. Cow attributes, herd management and environmental factors associated with the risk of calf death at or within 1h of birth and the risk of dystocia in cow calf herds in Western Canada. Livest Sci 2014;163: Hilton, W. Mark, and Danielle Glynn. "Management to Prevent Dystocia." Bovine Reproduction (2015): Gregory K, Cundiff L, Koch R. Breed effects and heterosis in advanced generations of composite populations for birth weight, birth date, dystocia, and survival as traits of dam in beef cattle. J Anim Sci 1991;69: Smith G, Laster D, Gregory K. Characterization of biological types of cattle. I. Dystocia and preweaning growth. J Anim Sci 1976;43: Laster D. Factors affecting pelvic size and dystocia in beef cattle. J Anim Sci 1974;38: Funston R. Nutrition and reproduction interactions. In:Proceedings, Applied Reproductive Strategies in Beef Cattle, 2010, pp Available at Nutrition.pdf 8. Spitzer J, Morrison D, Wettemann R, Faulkner L. Reproductive responses and calf birth and weaning weights as affected by body condition at parturition and postpartum weight gain in primiparous beef cows. J Anim Sci 1995;73: Frazer GS, Beard WL, Abrahamsen E, et al. Systemic effects of peritoneal instillation of a polyethylene polymer based obstetrical lubricant in horses. In: Wolfe D, editor. Proceedings of the Annual Conference of the Society for Theriogenology. Lexington (KY): p Schuijt, G. "Dystocia in the cow. The Utrecht way of physical examination, diagnosis, obstetrical approach and delivery." Proc Annu Meet Soc Theriogenology Mortimer RG. Calving and handling calving difficulties. In: Calving management manual Available at: neonatal/calving%20and%20handling%20calving%20difficulties.pdf. Accessed September 14, 2015.

29 ACHIEVING BEEF HERD REPRODUCTIVE EFFICIENCY W. Mark Hilton, D.V.M., PAS, DABVP (beef cattle) Senior Technical Consultant, Elanco Animal Health West Lafayette, IN Abstract Excellent reproductive efficiency can be achieved in a beef herd by using a multifaceted approach focusing on herd production and management issues. Numbers that would define reproductive efficiency for most herds would include a 90-95% pregnancy rate, less than 2% abortion rate with 65, 88 and 100% of the calves born by days 21, 42 and 65 of the calving season respectively. Heritability of reproductive traits tends to be low and disease causing reproductive failure in beef herds is uncommon in many parts of North America. Heifer selection and development, nutrition and utilizing heterosis are some of the keys to success. Efficiency is not synonymous with maximums, but rather is more closely aligned to optimums. Recent research with cost control as the core of heifer development shows that heifers can be developed more efficiently than previously thought. Introduction Having a large percentage of beef calves born in a relatively short period of time will decrease labor, enhance marketing opportunities, improve herd health and enhance overall herd income. Herds with acceptable pregnancy rates and a short, defined calving season have achieved these results with a disciplined, deliberate plan for reproductive success. Because beef cattle are raised across vastly different environments, specific definitions of reproductive efficiency can be quite varied. Specific questions and concerns for a given environment should be addressed with individuals who are deemed to be experts in these geographic locations. The universal concepts of reproductive efficiency are the focus of this paper. The National Animal Health Monitoring System (NAHMS) data from revealed that 91.5% of exposed females calved in each year. 1 While this number may seem to be acceptable for some regions of North America, when it is coupled with the fact that 34% of all herds had no defined calving season and only 50.4% of herds had calves born in three or fewer months, the numbers show reason for concern. 1 A well-managed herd should be able to achieve a 90-95% pregnancy rate with only a 1-2% abortion rate in 65 days. 2 Reproductive concerns tend to be an accumulation of errors, 3 and solving these concerns is rewarding for both the herd owner and the veterinarian. Utilizing the techniques discussed in this paper should provide a template to preventing and/or solving reproductive concerns in a beef herd. 1

30 Heifers Selection Building a beef herd that excels in fertility should start with the selection of heifer calves that will breed early, calve yearly on schedule, and remain in the herd for 12 to 15 years. Since reproductive traits tend to be of low heritability, (10% or lower) selection for fertility cannot be the primary focus of ensuring reproductive success. 4-6 Heifers selected as potential replacements need to be able to thrive in their given environment. If a highly fertile, low maintenance herd is desired, females with excessive nutrient demands will not allow the herd to reach its goals. Extreme milk production, mature body weight and frame score must not compromise the overall goal of having a herd that excels in fertility as extremes in any or all can diminish herd fertility. Recent work from Australia indicates that Angus heifers selected for low residual feed intake (RFI) calved 8.1 days later than high RFI females across two calving seasons. 7 Conversely, some other studies with similar parameters have shown no difference in fertility among females of differing RFI. While low RFI will improve the efficiency of our industry, we must be cautious not to use single-trait selection and suffer some unintended consequences. Economics Reproductive efficiency is about optimums and not maximums. The law of diminishing marginal returns states that in all productive processes, adding more of one factor of production, while holding all others constant, will at some point yield lower per-unit returns. 8 Adding more costs, e.g. generally feed, to the group to get one or more or even all the heifers pregnant is generally not cost-effective when the initial pregnancy rate is already quite acceptable. Recommended guidelines for heifer development have generally been to target a weight of 60%- 65% of mature body weight at the time of breeding. Recent work from Nebraska that targeted heifers to weigh 55%-60% of mature body weight at breeding showed a feed cost savings of $22 per heifer when heifers were bred at 53% vs. 58% of mature body weight. 9 Developing spring-born heifers to calve at 53% of mature body weight did not affect reproductive success, dystocia rate or calf performance compared to heifers at 58% of mature body weight. We must be aware, though, that targets are not always met, as was the case in this study. Heifers developed to weigh 53% of mature weight may in fact reach a weight below this target and cause reproductive rate to fall below an acceptable rate. Leaving some room for error seems to be a prudent tactic. Heifers can be developed to gain steadily from weaning to breeding, or the growth rate can be variable across this time frame. The path to puberty is unimportant so long as the heifer attains puberty before breeding Records from the American Angus Association in 2013 showed that the average sevenyear-old cow weighed 1394 pounds (634 kg) so a heifer in this average herd needs to 2

31 weigh 740 to 900 lbs ( kg) at breeding if she is to weigh 53%-65% of her mature body weight. 14 While 1,394 pounds is the average weight of a registered Angus cow, this figure can be highly variable across herds in North America. For our example, we will use this weight as the mature weight of the cows. If a heifer born on March 23 is weaned 190 days later on September 19 and weighs 475 lbs (216 kg), a gain of 324 lbs (147 kg) is needed to reach the target breeding weight of 800 lbs (364 kg) used 59% for example by May 23 of the following year. This will give a calving date of March 1 the following year, which equates to calving at approximately 23 months of age. To gain 325 lbs (148 kg) over 246 days, a gain of 1.32 lbs (0.60 kg) per day is necessary. An example ration of 16 lbs hay and 4 lbs dry corn gluten with appropriate vitamins and minerals would cost $1.15 per head per day. A more cost-effective option would be to allow a 30-day backgrounding ration where heifers gain 1.5 lbs (0.68 kg) per day followed by 60 days of grazing cornstalks (cost $0.00-$3.60 for 60 days) or stockpiled grass ($21.00 for 60 days). An expected gain of 0-30 lbs in this 60-day period would be reasonable. 15 Now the heifers have 155 days to gain 280 lbs (127 kg) and a growing ration containing a higher percentage of a coproduct feed like corn gluten feed or distiller s grains with solubles would be a reasonable choice that would also cost less than the $1.15 per day ration. Crossbreeding The major benefit of heterosis is in strengthening lowly heritable traits. 5,16 In a commercial herd, all potential replacement heifers should be crossbreeds, with no more than 75% of one breed making up the cross. Research published from a ten year study in 1994 at Montana State University showed that crossbred cows had 1.2 years longer productive lives and weaned 74 lbs (34 kg) more calf/cow exposed each year compared to the straightbred cows. The financial benefit was nearly $70 per cow per year for the crossbred cows compared to their straightbred counterparts. 17 Breed Heifers Early In most beef herds, getting nursing two-year-olds bred back is the biggest fertility challenge. As we examine herd nutrient needs, this female is still growing and requires additional energy and protein compared to a mature cow. 18 One technique is to breed heifers two to three weeks before the cow herd so that this high-risk group has additional days from calving to rebreeding. At times, the environmental stress that could be associated with earlier calving is not worth the benefit of the increased lag time before breeding, so this needs to be addressed before this recommendation is made. Shortened Breeding Season for Heifers A late calving heifer becomes a late calving cow or an open cow. 7,19-21 The way to keep this negative from happening is to not allow any heifers to calve late. If the cow breeding season is 65 days, the heifer season should be only 30 to 42 days. If the adult cows calve March 21 to May 25 and the heifers calve March 1 to April 11 (21 days ahead of cows and for only 40 days), even the last heifer to calve is exposed to the bulls from day 62 to 127 post-calving which should give the heifer an excellent chance to rebreed. If, however, a heifer calves on May 25, she is only exposed to the bull from day 18 to 82 3

32 post-calving. This will likely give her only one opportunity for rebreeding. Do not start with a problem; breed heifers for a shorter time than cows. Exposing about 10% more heifers to the bull should produce a similar number of pregnant heifers if breeding is reduced from 65 to 40 days. Pregnancy Exam Heifers Early Another advantage to breeding heifers for a reduced time is that these heifers can be pregnancy checked early so that all open heifers can move to the feedlot. If heifer breeding is from May 22 to July 1, they can be examined for pregnancy around August 10. In the Upper Midwestern and Great Plains regions of the U.S. most pastures are in the summer slump and a non-productive animal is better to be off the pasture and in the feedlot. The economics of having a heifer at 16 months of age and open is less favorable than having a bred heifer, but with current prices, it is still profitable to feed and sell the open heifer as a feedlot animal. Herd Health Every herd owner needs a herd-health veterinarian to guide them on health decisions A proper vaccination protocol melded with biosecurity and parasite control programs is a must. The veterinarian must also be knowledgeable in areas of nutrition or work with a nutrition consultant, as this is a key component of a healthy herd. A sample herd health protocol is included. Nutrition Priority of Energy Use by the Cow Reproduction is a luxury to all animals, and females must intake enough energy or have enough energy reserves to initiate cyclicity. According to Short et. al, a cow needs to meet each of these needs before the next one is met Basal metabolism 2. Physical activities including grazing 3. Growth 4. Supporting basic energy reserves 5. Maintaining an existing pregnancy 6. Milk production 7. Adding to energy reserves 8. Estrous cycling and initiating pregnancy 9. Storing excess energy The list makes it very apparent that estrous cycling and initiating a pregnancy is not a high priority to the cow, and adequate nutrition must be supplied if the cow is going to maintain a yearly calving interval. 4

33 Table 1. Energy requirements during the last month of gestation in cow 18 Body Condition Score Body Condition Score (BCS) at calving is the single most important factor in rebreeding success. 9 Since heifers have an increased requirement for energy and protein compared to mature cows, heifers should calve in a BCS greater than cows. 18 Most studies show a BCS of 5.5 to 6.0 out of 9 is optimum for cows, 23,24 so heifers should calve in BCS 6.5 to 7.0. This is especially true with the increased mature size and increased milk production of today s females. A study done from showed that a BCS of 6.0 at calving was superior to BCS of 5.0 or 4.0 in terms of rebreeding success (96 vs. 80 vs. 56) in a 60-day breeding season. 25 The heifers in the study weighed 933 lbs (424 kg) for BCS 6.0 and 744 lbs (338kg) for BCS 4.0 so they were significantly lighter than a typical two-year-old today. In addition, the average expected progeny difference (EPD) for milk in the Angus breed was +2 in 1986 and in 2017 it is Other breeds have seen similar increases in milk production, and increased milk production demands increased energy intake and increased pre-calving BCS. The most cost-effective time to add BCS to a cow is in the period immediately postweaning. If cows are thin at weaning time and calves are weaned at seven months of age or older, cows have little chance to regain BCS before the next calving season. This factor is compounded if the cows are under environmental stress during this time. If a cow that calves in March has her calf weaned in November in the northern half of North America, adding BCS from November to March is nearly impossible or very expensive. If instead these calves are weaned in September at 5.5 to 6 months of age, cows have time to regain BCS during a time of the year with little or no weather stress. Herd fertility will ultimately be improved because cows go into the winter and calve in a higher BCS. Herd profitability will also increase, as it is cheaper to feed the calf directly than to feed the cow to feed the calf. 5

34 Table 2. Relationship of body condition score (BCS) to beef cow performance and income 24 BCS a Preg rate % b Calving interval, days Wean age, days c Calf ADG (lbs) d Calf WW (lbs) e Calf value, $/cwt. f Gross income g Cow income h a Body Condition Score: scale of 1 (thin) to 9 (obese). b Pregnancy rates averaged across trials in Texas, Oklahoma, and Florida when BCS was assessed at calving, breeding, and pregnancy testing. c Weaning Age; 240 days for cows in BCS of 5 and 6 and decreases as calving intervals increase. d Average daily gain. e Adjusted weaning weight; calculated as calf age times calf gain plus birth weight (70 lb). f Average price for similar weight calves April 28, g Calculated as calf weight times calf price. h Calculated as income/calf times pregnancy rate times 0.92 (% calves raised as those pregnant). In seven of nine trials where high-energy rations were compared to moderate and lowenergy rations, dystocia rate was unchanged even though birth weights were altered in some experiments. In four of the five trials where protein levels were varied, highprotein rations again did not increase dystocia rates. It appears that heifers need to calve in a BCS of >7 to decrease fertility and increase dystocia rates. 27 While BCS at calving has the highest correlation to rebreeding success, heifers and cows must be fed a balanced ration post-calving if cows are expected to become pregnant in a timely manner. Micronutrient nutrition Numerous studies have looked at the role of micronutrient deficiencies on herd reproductive status. While the roles of copper, selenium, manganese, Vitamin A and Vitamin E have been studied in herd reproductive problems, the results have been inconsistent. Recently a study of 771 cows in 39 herds in western Canada showed a significant (P < 0.001) association between serum copper concentrations and pregnancy status in cows less than 10 years of age. The strongest association with nonpregnancy was for cows with serum copper concentrations less than 0.40 ppm. 28 Remedies for an Extended Calving Season Even utilizing the recommendations for producing fertile, early-calving heifers, herds with an extended calving season will need to either add a secondary calving season to the herd management plan or cut days from the single breeding season each year and cull all open cows. It is unrealistic to assume a producer can move from a 180-day calving season, where 25% of the calves are born in the first 21 days of the calving season, to a 65-day season in one year. 6

35 If a herd is located in an area where two separate calving seasons are environmentally sustainable, this is an easy and quick fix to an extended calving season. For example, if a herd currently calves year-round and a April 15 to June 20 season is ideal, with a secondary season of August 15 to October 15 also acceptable, this extended season can be remedied in just over a year by timely pulling of the bulls, pregnancy testing cows, and culling all open females. I have developed a spreadsheet for use in the timing of various events and it can be downloaded from If the herd has only one time of year that is conducive to calving, the following strategies can be used: Keep significantly more heifers than the normal 8% to 20% replacement rate Select, develop and breed heifers as outlined earlier Cut 30 to 60 days off the breeding season each year until the herd is at the desired calving season. Sell all open cows. For this system to work, the owner cannot have favorite cows that are immune from culling. Bulls Fertile Bulls Every bull should have a complete breeding soundness examination (BSE) before being turned out with cows. A spreadsheet has been developed by Dr. Tom Kasari that assesses the cost-effectiveness of performing a BSE on beef bulls before the breeding season. With 475-lb feeder calves valued at $ per cwt. and cost of $75 for a BSE, the benefit-to-cost ratio for doing a BSE is $18.57:1. So, the producer realizes a gain of $18.57 for every dollar spent on doing BSEs on his bulls. Numerous charts are available for producers to use when determining how many cows a fertile bull can service in a 65-day breeding season. While helpful, the numbers are difficult to remember. We proposed a rule of thumb in our practice over 25 years ago that recommends that a bull be placed with one cow per month of age of the bull up to 50. So, a 38-month-old bull should be able to service 38 cows in a 65-day breeding season. Multiple bulls of similar age would also fit our criteria, so three bulls with ages of 25, 28 and 29 months would be able to service 82 cows in a 65-day breeding season. There are breed differences in regard to fertility and these differences need to be taken into consideration. A published research summary on the use of crossbred or composite sires showed that crossbred Bos Taurus x Bos Taurus bulls had calves born an average of 10 days earlier than comparable purebred bulls, while Bos Taurus x Bos Indicus bulls sired calves that were born 7.8 days earlier than the purebred bulls. 29 7

36 Bull Exposure Exposing females to a herd bull or surgically altered teaser bull 20 to 30 days before the start of the breeding season will induce an earlier estrus as compared to females without bull exposure. 30,31 If a herd bull is used and females get bred before the earliest desired service date, exposed females can be given an injection of prostaglandin the day the bulls are turned out. This will abort any females more than five days pregnant, and most should recycle soon after the injection. Additional Reproductive Aids Reproductive tract scoring: In herds with poorer than anticipated pregnancy rates in yearling heifers, the use of reproductive tract scoring (RTS) can be beneficial. Heifers should be palpated 30 to 60 days before the anticipated breeding season so that if a larger than expected number of heifers are found to be in scores 1 to 3, appropriate management changes can be addressed so a majority of heifer s are at RTS 4 to 5 at the time of breeding. 32,33 Reduced suckling: Once or twice-daily nursing 34 and 48-hour calf removal 35 are both short-term fixes to a potentially long-term problem. Each has been used to salvage a breeding season, but should not become standard procedure (see heifers, selection ). Ionophores: Feeding heifers monensin or lasalocid will increase the percent of heifers cycling before and during the breeding season due to improved feed efficiency when fed ionophores. Only monensin is approved for females after breeding for improvement in feed efficiency. Although monensin has no label claim for reducing post-partum interval, it would be expected that this could be a derived benefit of the improvement in feed efficiency. In five trials where monensin was fed to mature beef cows the result was an average decrease in the postpartum interval of 18.8 days. 36 Induction of estrus with hormones: It is the opinion of the author that jump starting heifers to induce them to cycle may be counter-productive. Do we have trials that show that anestrus heifers that were hormonally induced to cycle have equal stability as compared to heifers that had cycled naturally prior to the breeding season? If these induced heifers have fewer productive years due to lower inherent fertility, we are better served to have them be open as yearlings. Fertility is a lowly heritable trait, but most studies do show some degree of heritability. 4-6 Conclusions Assisting a herd owner in achieving reproductive efficiency is a long-term endeavor that will improve herd uniformity, marketing, health, and herd profitability while decreasing labor. If a herd has underperformed with regard to herd fertility, a multifaceted, deliberate approach to improving nutrition, genetics, health, record keeping and herd management is the key to success. 8

37 References 1 UDSA Beef Part II: Reference of beef cow-calf management practices in the United States. Accessed 5/12/17. < 708_dr_PartII.pdf>. 2 Hilton, W. M Achieving reproductive efficiency in beef cow herds. Proceedings of the 44 th annual conference of the American Association of Bovine Practitioners, pp Dr. Brad White, personal communication. 4 Cammack, K. et al Review: reproductive traits and their heritabilities in beef cattle. Prof Anim Sci 25: Martin, L. et al Genetic effects on beef heifer puberty and subsequent reproduction. J Anim Sci 70: Milagres, J. et al Heritability estimates for some measures of reproduction in Hereford heifers. J Anim Sci 49(3): Donoghue, K. et al Onset of puberty and early-life reproduction in Angus females divergently selected for post-weaning residual feed intake Anim Prod Sci 51: Wikipedia. Diminishing returns. Accessed 5/12/17. < 9 Funston, R. et al Comparison of target breeding weight and breeding date for replacement beef heifers and effects on subsequent reproduction and calf performance. J Anim Sci 82: Freetly, H. et al Production performance of beef cows raised on three different nutritionally controlled heifer development programs. J Anim Sci 79: Lynch, J. et al Influence of timing of gain on growth and reproductive performance of beef replacement heifers. J Anim Sci 75: Patterson, D. et al Management considerations in heifer development and puberty. J Anim Sci 70: Roberts, A. et al Effects of restricted feeding of beef heifers during the postweaning period on growth, efficiency, and ultrasound carcass characteristics. J Anim Sci 85: Northcutt, S What does an Angus cow weigh? Angus Beef Bulletin.Accessed 5/2/17 < ml#.wqh9nu2gotv >. 15 Poore, M. et al Production and use of stockpiled fescue to reduce beef cattle production costs. Proc Am Soc Anim Sci.79: Cundiff, L. et al Effects of heterosis on reproduction in Hereford, Angus and Shorthorn cattle. J Anim Sci 38(4): Davis, K. et al Life cycle evaluation of five biological types of beef cattle in a cowcalf range production system: II. Biological and economic performance. J Anim Sci 72: Caton, J. et al Nutritional management during gestation: impacts on lifelong performance. Proceedings of the Florida Ruminant Nutrition Symposium, January Gainsville, Florida. Accessed 4/411. < 19 Burris M. and Priode B Effect of calving date on subsequent calving performance. J Anim Sci 17:

38 20 Lesmeister, J. et al Date of first calving in beef cows and subsequent calf production. J Anim Sci 36(1): Wiltbank, J Research needs in beef cattle reproduction. J Anim Sci 31: Short, R. et al Physiological mechanisms controlling anestrus and infertility in postpartum beef cattle. J Anim Sci 68: Houghton, P Effects of body composition, pre- and postpartum energy level and early weaning on reproductive performance of beef cows and pre-weaning calf gain. J Anim Sci 68: Kunkle, W Effect of body condition on productivity in beef cattle, in Fields MJ, Sand RS Factors Affecting Calf Crop. Boca Raton, CRC Press LLC, Spitzer, J. et al Reproductive responses and calf birth and weaning weights as affected by body condition at parturition and postpartum weight gain in primiparous beef cows. J Anim Sci 73: Genetic trends. Accessed 5/12/17. < 27 Funston R Nutrition and reproduction interactions. Proceedings, Applied Reproductive Strategies in Beef Cattle. Accessed 4/4/11. < 28 Van De Weyer, L. et al Associations between pre-breeding serum micronutrient concentrations and pregnancy outcome in beef cows. J Am Vet Med Assoc 238(10): Thrift, F. and Aaron, D The crossbred sire: experimental results for cattle. J Anim Sci 65: Alberio, R Effect of a teaser bull on ovarian and behavioral activity of suckling beef cows. Anim Reprod Sci 14: Zalesky, D. et al Influence of exposure to bulls on resumption of estrous cycles following parturition in beef cows. J Anim Sci 59: LeFever, D., and Odde, K Predicting reproductive performance in beef heifers by reproductive tract evaluation before breeding. 33 Holm, D et al, The value of reproductive tract scoring as a predictor of fertility and production outcomes in beef heifers. J Anim Sci 87: Randel, R.D Effect of once-daily suckling on postpartum interval and cow calf performance of first-calf Brahman Hereford heifers. J. Anim. Sci. 53, Smith, M. F., et al "Hormone treatments and use of calf removal in postpartum beef cows." J. Anim. Sci 48.6: Funston, R. Optimizing reproductive performance. Accessed 4/4/11. < Elanco is a trademark of Eli Lilly and Company or its affiliates Eli Lilly and Company or its affiliates. nchlth

39 2/24/2018 Implant Hormone Facts Economics of Using Implants and Ionophores in Beef Production W. Mark Hilton, DVM, PAS, DABVP (beef cattle) Technical Consultant, Elanco Animal Health USBBUMUL Loy, D Understanding hormone use in beef cattle Q&A. Iowa State University Extension. 2 Soy Isoflavones Overview. Micronutrient Information Center, Linus Pauling Institute, Oregon State University. Accessed Nov. 16, USBBUMUL Grazing Implant Dose (mg): Estimated Days of Activity 1,2 Total dosage, mg d d d 25.7a 36 c a b 8 a 20 b 20b a Estradiol; b Estradiol benzoate; c Estrogen-like (zeranol). 1 Tatum, J. D Pre-harvest cattle management practices for enhancing beef tenderness. Executive summary: prepared for the National Cattlemen s Beef Association. p McCollum, F. T. III. Implanting beef calves and stocker cattle. AgriLife Extension Texas A&M System. L d Compudose Ralgro Encore Component E C Component TE G Component E SComponent E H Estrogen Progesterone Testosterone Propionate TBA USBBUMUL Component E-C with Tylan in Suckling Steer Calves 1 (13 Trial Average) Average Daily Gain (ADG), lbs Control 0.11 lb/d 2.09 Component E-C/Synovex C Control Component E-C/Synovex C 1 Selk, G. E Implants for suckling steer and heifer calves and potential replacement heifers. In: proc. Impact of Implants on Performance and Carcass Value of Beef Cattle, Oklahoma Agric. Exp. Sta., Oklahoma State Univ., Stillwater. P-957: USBBUMUL Improvement in ADG with Component E-C in Suckling Steer Calves 1, Increase in ADG, % Component E-C/Synovex C Dollar Return with Component EC 5.4% in ADG = 0.11 lbs in gain / day 155 d period x 0.11 lb / d = 17 lbs 17 lbs x $1.50 / lb = $ Selk, G. E Implants for suckling steer and heifer calves and potential replacement heifers. In: proc. Impact of Implants on Performance and Carcass Value of Beef Cattle, Oklahoma Agric. Exp. Sta., Oklahoma State Univ., Stillwater. P-957: Duckett, S. K. and J. G. Andrae Implant strategies in an integrated beef production system. J. Anim. Sci. 79: E110-E117. USBBUMUL Stocker Producer 2008 Product Use Survey 1 60% 50% 40% 30% 20% 10% 0% Implants Ionophores Use technology Non-use National Stocker Survey sponsored by Kansas State, Elanco & BEEF magazine, and other data on file. USBBUMUL W. Mark Hilton, DVM 1

40 2/24/2018 Benefits of Grazing-phase Implants Implanting Stocker Cattle = $$$ in the Bank 1 One of the most profitable management tools available to stocker producers 1 Implants improve weight gain by lbs 1 Grazing implants provide a substantial return on investment as much as 17:1 2 1 Kuhl, G. L Abstract: Stocker cattle responses to implants. Oklahoma State University Symposium: Impact of implants on performance and carcass value of beef cattle. p Duckett, S. K. & J. G. Andrae Implant strategies in an integrated beef production system. J. Anim. Sci. 79:e110 e117. USBBUMUL Duckett, S. K. & J. G. Andrae Implant strategies in an integrated beef production system. J. Anim. Sci. 79:E110 E117. USBBUMUL Implant Mode of Action Active Compounds Commonly Used in Implants Estrogenic compounds Estradiol Estradiol benzoate Progesterone Zeranol (estrogen-like activity) Androgenic compounds Testosterone propionate Trenbolone acetate (TBA) USBBUMUL USBBUMUL Grazing Implant Dose (mg): Estimated Days of Activity 1,2 Direct Changes in Implanted Cattle Affecting Growth 1,2 a Estradiol. b Estradiol benzoate. c Estrogen-like (zeranol). 1 Tatum, J. D Pre-harvest cattle management practices for enhancing beef tenderness. Executive summary: prepared for the National Cattlemen s Beef Association. p McCollum, F. T. III. Implanting beef calves and stocker cattle. AgriLife Extension Texas A&M System. L USBBUMUL Effect on bovine skeletal muscle Estradiol increases IGF-1 mrna TBA stimulates growth through enhanced proliferation & differentiation of satellite cells as a result of increased sensitivity to IGF-1 & fibroblast growth factor (FGF) 1 Adapted from Metabolic modifiers: effects on the nutrient requirements of food-producing animals. National Research Council, Pages Adapted from D. Griffin & T. Mader. June Beef cattle implant update. University of Nebraska. NebGuide G USBBUMUL W. Mark Hilton, DVM 2

41 2/24/2018 Summary of Effects of Implants on Growth & Composition 1,2 Increased growth rate is usually accompanied by an increase in feed intake Increased rates of protein synthesis with lesser reductions in protein degradation Limited data indicates little direct effect on lipid metabolism & associated fat deposition Implant Mode of Action 1,2 Protein synthesis Protein degradation Fat utilization Fat synthesis 1 Adapted from Metabolic modifiers: effects on the nutrient requirements of food-producing animals. National Research Council, Pages Adapted from D. Griffin & T. Mader. June Beef cattle implant update. University of Nebraska. NebGuide G USBBUMUL Adapted from Metabolic modifiers: effects on the nutrient requirements of food-producing animals. National Research Council, Pages Adapted from D. Griffin & T. Mader. June Beef cattle implant update. University of Nebraska. NebGuide G USBBUMUL Component with Tylan Grazing Implants Implant Performance USBBUMUL Tatum, J. D Pre-harvest cattle management practices for enhancing beef tenderness. Executive summary: prepared for the National Cattlemen s Beef Association. p McCollum, F. T. III. Implanting beef calves and stocker cattle. AgriLife Extension Texas A&M System. L USBBUMUL Performance Benefit of Stocker-phase Implants Compared to Non-implanted Controls by Implant Type 1 Oklahoma State University 1 Stockerphase Implant Compared to Nonimplanted Cattle Implants increase ADG by 12-16% over non-implanted controls 1 Duckett, S. K. & J. G. Andrae Implant strategies in an integrated beef production system. J. Anim. Sci. 79:E110 E117. USBBUMUL Gill, D. R., S.C. Smith, W. Nichols, and M.R. Montague. July Performance of stocker steers implanted with Ralgro, Synovex-S or Revalor-G Animal Science Research Report. Oklahoma Agriculture Experiment State Division of Agriculture Science and Natural Resources Oklahoma State University. P-943. USBBUMUL W. Mark Hilton, DVM 3

42 2/24/2018 Oklahoma State University Stocker Cattle Implant Study (2010) 1 Total ADG days Oklahoma State University Stocker Cattle Implant Study (2010) 1 Total ADG days Component TE-G with Tylan increased ADG 9% versus control (no implant) & 4.5% compared with Ralgro. 1 McMurphy, C. P., E. D. Sharman, D. A. Cox, G. W. Horn & D. L. Lalman Effects of implant type and protein source on growth of steers grazing summer pasture. Proc. Western Sections ASAS. J. Anim. Sci. p. 61:100. USBBUMUL Component TE-G with Tylan outperformed Ralgro by 11% during the last month of the study. Ralgro performance during this period was no better than a non-implanted control. 1 McMurphy, C. P., E. D. Sharman, D. A. Cox, G. W. Horn & D. L. Lalman Effects of implant type and protein source on growth of steers grazing summer pasture. Proc. Western Sections ASAS. J. Anim. Sci. p. 61:100. USBBUMUL Component TE-G with Tylan Benefits Summary One implant for both steers & heifers Better performance than Ralgro or no implant in an Oklahoma State Study * Effective under a wide range of pasture conditions Tylan protects your implant investment by reducing implant defects 1 Stacked Studies *For references, see slide Elanco Study No. T1EUS USBBUMUL USBBUMUL The Original Elanco Stacked Technologies Research (5-Trial Pasture Summary) 1 Treatment * Increase in ADG over control, lbs % Improvement over control P-value Control Supplement Rumensin Compudose < 0.01 Rumensin + Compudose Current Stacked Technologies Pasture Research Study site Oklahoma State University 1 University of Arkansas 2 Noble Foundation 3 Forage (days) Winter wheat (112) Winter wheat (87) Cereal rye (84) Cattle type (n) Crossbred steers (207) Crossbred steers (180) Crossbred steers (90) Main plot: supplement treatments Energy supplement or Energy supplement + Rumensin Non-medicated loose mineral or Rumensin loose mineral or Rumensin protein blocks White salt blocks or non-medicated mineral blocks or Rumensin mineral blocks Split plot: implant treatments None or Component with Tylan None or Component with Tylan None or Component with Tylan * No interaction was observed between treatments (P > 0.22); therefore, treatment responses were additive. 1 Wagner et al J. Anim. Sci. 58:1062. USBBUMUL Sharman et al J. Anim. Sci. Vol. 90 (Suppl. 3): Beck et al J. Anim. Sci. Vol. 90 (Suppl. 1):27. 3 Reuter et al J. Anim. Sci. Vol. 91 (Suppl. 1):16. USBBUMUL W. Mark Hilton, DVM 4

43 2/24/2018 Current Stacked Technologies Pasture Research Results * Study site Additional lbs from Rumensin Additional lbs from Component with Tylan Additional lbs from Rumensin & Component with Tylan P- value Oklahoma State University University of Arkansas Noble 3 Foundation Busting Implant Myths * Interactions between treatments were not significant; therefore, the technologies are additive. 1 Sharman et al J. Anim. Sci. Vol. 90 (Suppl. 3): Beck et al J. Anim. Sci. Vol. 90 (Suppl. 1):27. 3 Reuter et al J. Anim. Sci. Vol. 91 (Suppl. 1):16. USBBUMUL USBBUMUL Myth Implanted cattle will receive a discount at the sale barn compared to their nonimplanted counterparts. Superior Livestock Data 1 The effect of implant status on the sale price of beef calves sold through Superior Livestock video auctions in Factor # of Lots LSM of sale price ($/cwt) Regression coefficient P-value 2010: Were calves in the lot implanted?.54 Yes 1, No 4, : Were calves in the lot implanted?.20 Yes 1, No 4, : Were calves in the lot implanted?.72 Yes 1, No 3, : Were calves in the lot implanted?.32 Yes 1, No 4, Superior livestock auction data: 2010 to Data on file. USBBUMUL USBBUMUL Myth Cattle implanted in pre-feedlot production phases will perform more poorly in the feedlot. Review of Feedlot Performance from Pre-Feedlot Implanting Research cited Implant program Pre-feedlot implant's effect on feedlot Investigator(s) Suckling Stocker Feedlot ADG FE Performance Year George et al Y Y No impact Paisley et al. 1, Y Y Y No impact Brazle Y Y No impact Kuhl, G. L Y Y Improved No impact Schaneman & Pritchard Y No impact Y Fankhauser et al. 1,2* 1997 Y Trended lower Y Trended lower Kuhl et al. 1, Y Y No impact No impact No impact Brandt et al Y Y No impact Mader et al. 1, Y Y No impact No impact Y Coffey et al. 1** 1992 Y Y Reduced McCann et al Y Y No impact Rush et al Y Y Improved No impact Grigsby et al Y Y Improved No impact Simms et al. 1, Y Y No impact Y Hutsheson & Roquette Y Y No impact Mader et al Y Y Reduced Laudert et al Y Y No impact Laudert et al Y Reduced Y Kunkle et al Y Y Y No impact *Especially when feedlot reimplantation program was not used. **Two successive Synovex -S implants were administered during the grazing phase and an additional two Synovex-S at finishing. USBBUMUL J. S. Drouillard & G. L. Kuhl Effects of previous grazing nutrition and management on feedlot performance and cattle. J. Anim. Sci. 77( E. Suppl): E Duckett, S. K. & J. G Andrae Implant strategies in an integrated beef production system. J. Anim. Sci. 79(E. Suppl.):E USBBUMUL W. Mark Hilton, DVM 5

44 2/24/2018 Myth Cattle implanted in pre-feedlot production phases will have reduced carcass quality. Review of Carcass Impacts from Pre-feedlot Implanting Research cited in reviews Implant program Pre-feedlot implant effect on carcass Investigator(s) Year Suckling Stocker Feedlot HCW QG Quality Traits George et al Y Y No impact No impact Paisley et al. 1, Y Y Y Improved Slight impact* Brazle, F. K Y Y No impact Kuhl, G. L Y Y No impact Schaneman & Pritchard Y Y No impact Fankhauser et al. 1, Y Y No impact Kuhl et al. 1, Y Y Improved No impact No impact Mader, T. L Y Y Little impact Brandt et al Y Y Improved No impact Mader et al Y Y No impact Rush et al Y Y No impact Grigsby et al Y Y No impact Simms et al. 1, Y Y Y No impact Hutsheson & Roquette Y Y Trended higher Mader et al. 1, Y Y Y No impact Kunkle et al Y Y Y Improved *Steers produced carcasses with increased skeletal and overall maturity. USBBUMUL Drouillard & Kuhl JAS 77: Duckett, S. K. & J. G Andrae Implant strategies in an integrated beef production system. J. Anim. Sci. 79(E. Suppl.):E USBBUMUL Effects of Implanting with Component TE-G with Tylan 1 Lifetime Implanting Pays USBBUMUL Study design: 193 steers randomly allotted by BW to 1 of 12 pastures Pastures were randomly assigned to 1 of 3 treatments for fall/winter grazing Control: high calcium, non-medicated, free-choice mineral mix Midd-Corn: 2 lbs/steer/day of corn-wheat middlingbased energy supplement Midd-DDGs: 2 lbs/steer/day of energy supplement containing 65% DDGs Both energy supplements contained 160 g/ton of monensin 1 Sharman, E. D., P. A. Lancaster, G. W. Horn & G. D. Hufstedler. Effects of energy supplements and a combination grazing implant on performance and carcass characteristics of growing cattle on wheat pasture Plains Nutrition Council Proceedings. AREC pp USBBUMUL Effects of Implanting with Component TE-G with Tylan 1 Study design, continued: On day 0, half of the steers in each pasture were implanted with Component TE-G with Tylan Steers grazed wheat pasture until first hollow stem (111 days) Following the fall-winter grazing phase, steers were commingled for a 37-day graze-out period at a stocking rate of 2.15 steers/acre Steers were transported to a commercial feedlot after graze-out, implanted upon arrival with Component TE-S with Tylan & fed in a single pen for 130 days prior to harvest Effects of Implanting with Component TE-G with Tylan Grazing Phase 1 1 Sharman, E. D., P. A. Lancaster, G. W. Horn & G. D. Hufstedler. Effects of energy supplements and a combination grazing implant on performance and carcass characteristics of growing cattle on wheat pasture Plains Nutrition Council Proceedings. AREC pp USBBUMUL Sharman, E. D., P. A. Lancaster, G. W. Horn & G. D. Hufstedler. Effects of energy supplements and a combination grazing implant on performance and carcass characteristics of growing cattle on wheat pasture Plains Nutrition Council Proceedings. AREC pp USBBUMUL W. Mark Hilton, DVM 6

45 2/24/2018 Effects of Implanting with Component TE-G with Tylan Subsequent Feedlot & Carcass Performance 1 Effects of Implanting with Component TE-G with Tylan 1 Key points: Component TE-G improved ADG by 15% during winter grazing (P = 0.001) The additional weight gain resulting from the grazing implant was carried through the finishing phase Implanting with Component TE-G with Tylan during winter grazing increased (P < 0.001) HCW & had no impact on marbling deposition No negative impact on carcass quality characteristics was observed 1 Sharman, E. D., P. A. Lancaster, G. W. Horn & G. D. Hufstedler. Effects of energy supplements and a combination grazing implant on performance and carcass characteristics of growing cattle on wheat pasture Plains Nutrition Council Proceedings. AREC pp USBBUMUL Sharman, E. D., P. A. Lancaster, G. W. Horn & G. D. Hufstedler. Effects of energy supplements and a combination grazing implant on performance and carcass characteristics of growing cattle on wheat pasture Plains Nutrition Council Proceedings. AREC pp USBBUMUL Lifetime Implanting Performance Benefits Implanting increases rate of weight gain, live weight & market value in each phase of beef production. 1 * Average market price ( ; CattleFax, 1995) = $2.04/lb for 500-lb steer calves, $1.68/lb for 802-lb steers, $2.49/lb for Choice, and $2.38/lb for Select carcasses (assuming a 15% reduction in percentage Choice with implanting from a base of 75% Choice for unimplanted cattle and a 62% dressing percentage). Stocker steer calves implanted with Component E-C with Tylan/Synovex-C or Ralgro at 2 mo of age. Stocker steers implanted with Ralgro, Component E-S with Tylan/Synovex S or Component TE-G with Tylan/Revalor-G at the start of the grazing season. Feedlot steers implanted with implants containing estrogenic hormones only or both estrogenic and androgenic hormones (EA) at the start or midpoint of the finishing period. Implanted in each phase (suckling, stocker and feedlot). 1 Duckett, S. K. & J. G. Andrae Implant strategies in an integrated beef production system. J. Anim. Sci. 79:E110 E117. USBBUMUL Lifetime Implanting Performance Benefits Summary 1,2 Increased gains in the stocker phase are often additive to feedyard gains Appropriate grazing implant strategies result in little or no impact on feedlot performance & carcass quality Grazing implants allow stocker producers to add weight at a lower cost of gain than in the feedlot, improving efficiency & reducing overall cost of production 1 Kuhl, G. L Abstract: Stocker cattle responses to implants. Oklahoma State University Symposium: Impact of implants on performance and carcass value of beef cattle. p Duckett, S. K. & J. G. Andrae Implant strategies in an integrated beef production system. J. Anim. Sci. 79:E110 E117. USBBUMUL Response to Implanting Implant Quality: Importance of a Local Antibacterial At the site, every animal mounts an inflammatory response to implanting 1 Dirt, manure & bacteria present on the ear can increase the inflammatory response 1 When cattle were implanted under dirty conditions, there were fewer abscesses when Component with Tylan was used compared to an implant not containing Tylan (P < 0.05) 2 USBBUMUL Loughin, M Evaluation of implant site characteristics. Elanco Reference No Data on file. 2 Elanco Study No. T1EUS USBBUMUL W. Mark Hilton, DVM 7

46 2/24/2018 Implant Site Quality Localized Antibacterial Protection Component with Tylan implants include a Tylan pellet (tylosin tartrate) as the first pellet in each dose The blue Tylan pellet dissolves, releasing antibacterial protection throughout the implant site USBBUMUL USBBUMUL Localized Antibacterial Protection Compudose & Encore both include a coating of oxytetracycline on each implant as a localized antibacterial. Impact of Component TE-S with or without Tylan on Implant Defects & Performance (2010) 1 Study conducted at the University of Illinois Objective: Determine the effect of a Tylan pellet on implant defects & the resulting performance in finishing steers 1 Elanco Study No. T1EUS USBBUMUL USBBUMUL Impact of Component TE-S with or without Tylan 1 Study design: 320 yearling crossbred steers (698-lb initial weight) Implant treatments: Control no implants Component TE-S without Tylan Component TE-S with Tylan Sanitation procedures: Clean manufacturer s recommendation Dirty needle dragged through manure slurry, no sanitation Note: During the two-day initiation period, more than one inch of rain fell per day resulting in cattle being wet Impact of Component TE-S with and without Tylan 1 Live & carcass-adjusted performance* (122 days on feed) *Performance adjusted to 63.5% yield. 1 Elanco Study No. T1EUS USBBUMUL Elanco Study No. T1EUS USBBUMUL W. Mark Hilton, DVM 8

47 2/24/2018 Impact of Component TE-S with and without Tylan 1 Impact of Component TE-S with and without Tylan 1 Carcass parameters (122 days on feed) Calculated economic impact* 1 Elanco Study No. T1EUS USBBUMUL Elanco Study No. T1EUS USBBUMUL Component EZ Implanter Implanting Devices For use with Component with Tylan implants TE-G, E-S & E-H Durable & easy to use 20-dose belt for improved implanting efficiency USBBUMUL USBBUMUL Compudose & Encore Implanter For use with Compudose & Encore implants Durable & easy to use 20-dose wheel for improved implanting efficiency The label contains complete use information, including cautions and warnings. Always read, understand and follow label and use directions. Implants: Administer one dose in the ear subcutaneously according to label directions. Rumensin: Growing cattle on pasture or in drylot (stockers, feeders, and dairy and beef replacement heifers) For increased rate of weight gain: Feed 50 to 200 mg/hd/d of monensin in at least 1.0 lb of Type C medicated feed. Or, after the 5th day, feed 400 mg/hd/d every other day in at least 2.0 lbs of Type C medicated feed. The Type C medicated feed must contain 15 to 400 g/ton of monensin (90% DM basis). For the prevention and control of coccidiosis: Feed at a rate to provide 0.14 to 0.42 mg/lb of body weight/d of monensin up to a maximum of 200 mg/hd/d. The Type C medicated feed must contain 15 to 400 g/ton of monensin (90% DM basis). Free-choice supplements: Approved supplements must provide not less than 50 nor more than 200 mg/hd/d of monensin. Ralgro is a registered trademark of Merck Animal Health, its affiliates and/or its licensors. Synovex is the property of Zoetis Inc., its affiliates and/or its licensors. Revalor is a registered trademark of Merck Animal Health, its affiliates and/or its licensors. Rumensin is a trademark for Elanco s brand of monensin. Tylan is a trademark for Elanco s brand of tylosin. Elanco, Rumensin, Compudose, Component, Encore, Component EZ, Full Value Beef and the diagonal bar are trademarks owned or licensed by Eli Lilly and Company, its subsidiaries or affiliates Eli Lilly and Company, its subsidiaries or affiliates. NCFD USBBUMUL USBBUMUL W. Mark Hilton, DVM 9

48 2/24/2018 What Is Rumensin? Impact of Rumensin in Stocker Cattle & the Production Beef Herd [insert meeting name] [insert date] USBBUMUL Ionophore classified by FDA as a non-medically important antimicrobial that is used exclusively in animals, NOT human medicine A fermentative by-product derived from soil-borne bacteria (Streptomyces spp.) 1 Feed additive that increases average daily gain (ADG) by improving the energy utilization of feedstuffs 2 1 Elanco manufacturing data on file. 2 USBBUMUL01392 Bergen and Bates J Anim Sci 58: Rumensin for Stocker Cattle: A Proven Management Tool 1-3 Works throughout the supplementation period Rumensin in Stocker Cattle = More Pounds to Sell with an Investment of Pennies/Head/Day Results of Rumensin supplementation: + Improves energy utilization + Improves nitrogen metabolism 4 + Prevents & controls coccidiosis Improved ADG & more lbs to market 1 Twenty-four Trial Pasture Summary, Rumensin 0 vs. 200 mg/hd/day. Elanco Animal Health. Data on file. 2 Potter et al., J Anim Sci 62: Rumensin (monensin sodium) Freedom of Information Summary (NADA ). 4 USBBUMUL01392 Bergen and Bates J Anim Sci 58: USBBUMUL01392 *Twenty-four Trial Pasture Summary, Rumensin 0 vs mg/hd/day. Elanco Animal Health. Data on file. 58 Value of Additional Gain in a 100-Day Grazing Program Assumptions: 100 days; $0.02 cents/hd/day Rumensin cost; 0.2 * lb/day increased ADG Net value of increased ADG at different values of gain ($/lb) Rumensin No. hd cost, $ $0.50 $0.75 $1.00 $1.25 $ ,300 1,800 2,300 2, ,000 4,000 6,500 9,000 11,500 14,000 1,000 2,000 8,000 13,000 18,000 23,000 28,000 5,000 10,000 40,000 65,000 90, , ,000 10,000 20,000 80, , , , ,000 Rumensin Mode of Action ROI% 400% 650% 900% 1,150% 1,400% Example: [100 hd x 0.2 lb ADG x 100 days x $0.50/lb] - Rumensin cost = $800 USBBUMUL USBBUMUL01392 * Twenty-four Trial Pasture Summary, Rumensin 0 vs mg/hd/day. Elanco Animal Health. Data on file W. Mark Hilton, DVM 10

49 2/24/2018 Rumen Bacterial Population Shift While Feeding Rumensin 1 Volatile Fatty Acids (VFA) Effects of Rumensin on VFA Percentages in Fistulated Cattle on Pasture (Molar Percent in Rumen) Acetic Monensin, mg/hd/d Propionic Monensin, mg/hd/d Butyric Monensin, mg/hd/d 1 Richardson et al., J. Anim. Sci. 43:657. USBBUMUL Adapted from Dawson and Boling Appl Environ Microb 46:160. USBBUMUL Carbohydrate Digestion by Rumen Microbes & VFA Efficiency 1 Efficiency of Energy Conversion with Rumensin 1 Carbon atoms are conserved resulting in more energy for the cattle to utilize. 1 Adapted from Nagaraja, T. G., C. J. Newbold, C. J. Van Nevel & D. I. Meyer Manipulation of Rumen USBBUMUL01392 Fermentation. The Rumen Microbial Ecosystem, 2 nd edition. Ed: Hobson & Stewart. pp Supplementing with an ionophore enables the nutritionist/producer to increase the net energy for maintenance (NEm) value of the diet by 12%. 2 1 Adapted from Nagaraja, T. G., C. J. Newbold, C. J. Van Nevel & D. I. Meyer Manipulation of Rumen Fermentation. The Rumen Microbial Ecosystem, 2 nd edition. Ed: Hobson & Stewart. pp USBBUMUL Nutrient Requirements of Beef Cattle. National Academy Press. 64 Rumensin Mode of Action Influence on Energetics Feeding Rumensin causes a shift in rumen bacterial populations This increased population of gram negative bacteria produce more propionate Propionate is a more energyefficient fuel source for cattle Rumensin Can Be Delivered in Energy, Protein and/or Mineral Supplements Energy Grains Grain by-products Protein Meals/by-products Cubes/blocks Mineral Loose mineral Mineral blocks USBBUMUL USBBUMUL W. Mark Hilton, DVM 11

50 2/24/2018 Rumensin Studies Across Multiple Forage Types 24-Trial Summary 1,2 Oklahoma Wheat Pasture Rumensin Mineral Study Supplementation Cost Summary 1 Year 1 ( ) ADG, lbs Improvement, lbs/hd/d (%) Range in improvement, lbs/hd/d (%) With no ionophore 1.23 a With Rumensin * 1.43 b 0.20 (16.3%) ab Means within a column without a common superscript differ (P < 0.01) (5.7%) 0.36 (29.3%) Mineral cost, $/ton Mineral intake, oz/hd/d Ionophore, mg/hd/d Cost, $/hd Nonionophore a $10.31 Rumensin b 83 c $2.66 ab Means within a row without a common superscript differ (P < 0.002). cd Means within a row without a common superscript differ (P < 0.001). Bovatec a 258 d $9.18 *200 mg monensin/hd/d/ 1 Twenty-four Trial Pasture Summary, Rumensin 0 vs. 200 mg/hd/day. Elanco Animal Health. Data on file. USBBUMUL Potter, et al., J. Anim. Sci.62: Horn, G., C. Gibson, J. Kountz & C. Lundsford Two-Year Summary: Effect of Mineral Supplementation With or Without Ionophores on Growth Performance of Wheat Pasture Stocker Cattle. Proceedings from the USBBUMUL01392 Wheatland Stocker Conference. pp. A1-A19. (Elanco Trial No. T1FB50002). 68 Oklahoma Wheat Pasture Rumensin Mineral Study Economic Analysis 1 Year 1 ( ) Oklahoma Wheat Pasture Rumensin Mineral Study Weekly Consumption 1 Year 2 ( ) Initial wt, lbs Final wt, lbs Daily gain, lbs Total mineral intake, lbs Mineral costs, $/hd Control Nonionophore Rumensin Bovatec Intake, oz/hd/d Non-ionophore Rumensin Bovatec Selling price, $/cwt Profit, $/hd Value vs. control, $/hd $ $ $ Week of trial Mineral consumption measured weekly. Cattle placed on native pasture from 1/30 to 2/7 due to ice storm. 1 Horn, G., C. Gibson, J. Kountz & C. Lundsford Two-Year Summary: Effect of Mineral Supplementation 1 Horn, G., C. Gibson, J. Kountz & C. Lundsford Two-Year Summary: Effect of Mineral Supplementation With or Without Ionophores on Growth Performance of Wheat Pasture Stocker Cattle. Proceedings from the With or Without Ionophores on Growth Performance of Wheat Pasture Stocker Cattle. Proceedings from the USBBUMUL01392 Wheatland Stocker Conference. pp. A1-A19. (Elanco Trial No. T1FB50002). 69 USBBUMUL01392 Wheatland Stocker Conference. pp. A1-A19. (Elanco Trial No. T1FB50002). 70 Rumensin in Stocker Cattle Summary 1-3 What Will Rumensin Do for Stocker Cattle? Rumensin-supplemented pasture cattle consistently gained 0.20 lbs/hd/d more than cattle not receiving Rumensin For pennies per head per day, stocker operations can produce 20 more pounds of additional selling weight per head in a 100-day grazing season Effective across a wide range of forage types, growing seasons & supplementation methods Prevents & controls coccidiosis Increase the energy available for production from any feed or forage source 1 Twenty-four Trial Pasture Summary, Rumensin 0 vs. 200 mg/hd/day. Elanco Animal Health. Data on file. 2 Potter et al., J. Anim. Sci. 62:583. Rumensin (monensin sodium) Freedom of Information Summary (NADA ). USBBUMUL USBBUMUL W. Mark Hilton, DVM 12

51 2/24/2018 Rumensin in Replacement Heifers Rumensin in the Beef Production Herd Replacement Heifers Increases weight gain 1 when fed during development resulting in fewer days to first estrus; heifers that breed earlier in their first breeding season generally breed earlier throughout their lifetime 2 Prevents & controls coccidiosis USBBUMUL Ten-Trial Summary, Effect of Rumensin on Average Daily Gain of Replacement Heifers. Elanco Animal Health. Data on file. 2 Patterson D. J., R. C. Perry, G. H. Kiracofe, R. A. Bellows, R. B. Stagmiller and L. R. Corah Management USBBUMUL01392 considerations in heifer development and puberty. J. Anim. Sci. 70: Rumensin for Replacement Heifers Across Multiple Forage Types 5-Trial Reproductive Safety Study & 10-Trial Performance Summary Monensin (mg/hd/day) Avg. day of trial at first estrus 1 ADG, lbs 2 Improvement lbs/hd/d (%) a 1.43 a b 1.57 b 0.14 (9.8%) Rumensin in the Beef Production Herd Mature Beef Cows ab Means within a column without a common superscript differ (P < 0.001). 1 Five Trial Reproductive Data Summary in Replacement Heifers. Elanco Animal Health. Data on file. 2 Ten Trial Summary, Effect of Rumensin on Average Daily Gain of Replacement Heifers. Elanco Animal Health. USBBUMUL01392 Data on file. 75 USBBUMUL Rumensin for Mature Beef Cows Only ionophore approved for use in mature, reproducing beef cows Improves feed efficiency, which helps maximize profitability Maintains body weight on 5% to 10% less feed Prevents & controls coccidiosis Rumensin in the Cow Herd Rumensin (monensin) is approved for the prevention & control of coccidiosis & the improvement of feed efficiency in mature reproducing beef cows. Summary of Rumensin in the cow herd (n = 415) ab Means within a row without a common superscript differ (P < 0.01). USBBUMUL USBBUMUL Rumensin for Beef Cows 4-Trial Dose Titration Summary. Elanco Animal Health. Data on file 78 W. Mark Hilton, DVM 13

52 2/24/2018 Effect of Supplement on ADG 1* The Value of Supplementation Total feed cost savings per cow with Rumensin during a 112-day supplementation period to increase BCS from 4 to 5 1 Kg Control Treatment Monensin *P-value = J.D. Sparks, A.J. Sexten, C.P. McMurphy, G.L. Mourer, M.A. Brown, C.J. Richards, & D.L. Lalman. Effects of bale feeder type and supplementation of monensin on hay waste, intake, and performance of beef cattle. Oklahoma State University. USBBUMUL Lalman, OSU Cowculator v 2.0. Beef Cow Nutrition Evaluation Software. Oklahoma Cooperative Extension Service. CR Feed requirement data to generate the values in chart are based on the example calculations from the Cowculator. Hay and supplement prices reflect past, present and future cost per ton held at a constant ratio of hay to supplement cost. USBBUMUL Rumensin for Mature Beef Cows Reproductive Safety 1 4-Trial Summary Safety Information for Beef Cows Rumensin is proven to be safe for use in reproducing cattle Avg. days on study at calving Days from calving to conception No. cows bred No. cows conceived Monensin, mg/hd/d a b b 100 Percent conception ab Means within a row without a common superscript differ (P < 0.04). 97 USBBUMUL USBBUMUL Rumensin for Beef Cows 4-Trial Dose Titration Summary. Elanco Animal Health. Data on file. 82 Rumensin for Mature Beef Cows Reproductive Safety Trial Monensin, mg/hd/d No. pastures * Conception date ** 161 a 155 b Calf to conception, days 90 a 85 b Calving percentage (%) 80.7 a 91.9 b ab Means within a row without a common superscript differ (P < 0.01). For all products: The label contains complete use information, including cautions and warnings. Always read, understand and follow the label and use directions. For Rumensin: Consumption by unapproved species or feeding undiluted may be toxic or fatal. Do not feed to veal calves. * Pasture was the experimental unit, and each pasture contained 9 to 11 cow-calf pairs. ** Julian calendar date. Logistic regression analysis. 1 USBBUMUL01392 Bailey et al., Can. J. Anim. Sci. 88: USBBUMUL W. Mark Hilton, DVM 14

53 2/24/2018 Rumensin: Growing cattle on pasture or in drylot (stockers, feeders, and dairy and beef replacement heifers) For increased rate of weight gain: Feed 50 to 200 mg/hd/d of monensin in at least 1.0 lb of Type C medicated feed. Or, after the 5th day, feed 400 mg/hd/d every other day in at least 2.0 lbs of Type C medicated feed. The Type C medicated feed must contain 15 to 400 g/ton of monensin (90% DM basis). For the prevention and control of coccidiosis: Feed at a rate to provide 0.14 to 0.42 mg/lb of body weight/d of monensin up to a maximum of 200 mg/hd/d. The Type C medicated feed must contain 15 to 400 g/ton of monensin (90% DM basis). Free-choice supplements: Approved supplements must provide not less than 50 nor more than 200 mg/hd/d of monensin. Rumensin: Mature reproducing beef cows For improved feed efficiency when receiving supplemental feed: Feed continuously at a rate of 50 to 200 mg/hd/d of monensin. Cows on pasture or in drylot must receive a minimum of 1.0 lb of Type C medicated feed/hd/d. Do not self-feed. For the prevention and control of coccidiosis: Feed at a rate of 0.14 to 0.42 mg/lb of body weight/d of monensin up to a maximum of 200 mg/hd/d. Economics of Using Implants and Ionophores in Beef Production Implants Administer one dose in the ear subcutaneously according to label directions. Bovatec and Deccox are the property of Zoetis Inc., its affiliates and/or its licensors. Corid is a registered trademark of Merial. Elanco, Component, Rumensin,Tylan and the diagonal bar are all trademarks owned or licensed by Eli Lilly and Company, its subsidiaries or affiliates Eli Lilly and Company, its subsidiaries or affiliates. NCFD USBBUMUL W. Mark Hilton, DVM, PAS, DABVP (beef cattle) Technical Consultant, Elanco Animal Health USBBUMUL W. Mark Hilton, DVM 15

54 Pruritus in Horses: Diagnosis and Management Susan L. White DVM, MS, DACVIM College of Veterinary Medicine University of Georgia, Athens, GA Pruritus often leads to self-inflicted trauma, alopecia, and moderate to severe secondary skin lesions resulting in horses which are visually disfigured and/or unsound for work. Because of the many possible diagnosis of a pruritic skin disease the history, especially the environment, seasonality, age of onset and progress of the disease, previous treatment modalities and response, is very important in making a diagnosis. Time spent obtaining a detailed, complete history is rewarding and often equally as important as the examination and diagnostic tests. Insect Bite Hypersensitivity (IBH) A large percentage of horses affected with seasonal pruritic dermatitis are hypersensitive to the bites of insects. Any biting insect, including Culicoides spp. (No-see-ums, midges, punkies), stable flies (Stomoxys calcitrans), horn flies (Hematobia sp), black flies or "buffalo gnats" (Simulian spp.), horse and deer flies (Tabanidae and Chrysops spp.), mosquitoes (primarily Culex and Aedes spp.), can cause insect hypersensitivity dermatitis. "Chiggers" (Trombiculids) and ticks can also lead to hypersensitivity reactions. Insect bite induced hypersensitivities are characterized by intense pruritus which often leads to excoriation, extensive hair loss, secondary infections and chronically to hyperkeratosis and lichenification. Several different clinical syndromes have been associated with hypersensitivities to different insects. Queensland or Sweet Itch, initiated by the bites of hematophagous Culicoides species, is classically characterized by a diffuse dorsal distribution with severe involvement of the mane and tail area. However, there are several species of Culicoides in different geographic areas and different species have different preferred areas of feeding, with some species having a predilection for biting the ventral aspect of the body. The only region generally not affected by Culicoides is the flank. A hereditary predisposition to develop hypersensitivity to Culicoides spp. has been shown in some breeds of horses and clinical evidence supports a familial tendency for hypersensitivity in many, if not all, breeds. Although Culicoides spp gnats are the most common and consequently the most studied, there are a wide variety of gnats in certain regions of the country (such as the southeast) that occur in great numbers, can be found almost anytime of the day, and cause annoyance, irritation and serve as atopenes contributing to hypersensitivity reactions. Simulian flies are blood suckers and bites are covered with small accumulations of dried blood. In mass attacks urticaria and angioedema may occur and can be associated with systemic signs of weakness with an increased pulse and respiratory rate, particularly in small young animals. Bites of Simulian spp. are most commonly associated with lesions on the head and within the inner pinnae, but in "swarm attacks" may bite any region of the horse. A generalized ventral distribution of lesions may also be caused by black flies. Bites of horn flies (Haematobia irritatins) have been implicated in Ventral Midline Dermatitis, characterized by sharply demarcated focal lesions which often ooze serum. Horn flies prefer shade, and thus a few flies on a horse in the sunshine will be found on the ventral midline. In

55 areas of heavy horn fly populations, these flies may be found everywhere on the body surface, including the body, legs and face. Horn flies breed only in cattle manure, thus most severe infestations are within a quarter of a mile of cattle farms. However, these flies may travel farther on wind currents, as they have been found on horses without nearby cattle. Stable flies (Stomoxys calcitrans) are vicious biters (as opposed to house flies (Musca spp) that feed on body secretions) that cause pain and may be accompanied by blood drops, especially on the legs and lower abdomen. Initial lesions may consist of erythema, wheals, and raised nodules with a central crust. Exudative dermatitis of the legs due to reactions to extensive stable fly bites and/or urticaria and large nodules that are pruritic characterize hypersensitivity to stable flies. Mosquito bites produce wheals and papules that are variably pruritic and are often painful. The lesions do not have a central crust as the bites of other insects. Most individual lesions resolve in 1-2 days, however larger persistent nodules may develop in certain individuals. Chiggers and harvest mites (trombiculids) are free living and are found in undeveloped or overgrown fields and wooded areas. Adults are plant parasites, but the 6-legged larval form requires blood or tissue fluids for further development. Mites are non host specific and normally feed on small rodents. Infestations of horses may occur if horses are pastured or ridden in contaminated areas and are most prevalent in the summer and fall. Feeding larvae cause papules with 1-2mm crusts and can be intensely pruritic. Larvae remain on the host for 2-7 days before dropping off to molt and are often absent by the time the horse is presented for examination. The larvae are mm long and yellow-orange to red in color and, if found, confirm the diagnosis. Horses may develop hypersensitivities to ticks, either larvae ("seed ticks") or adults. Bites may induce individual large nodules with a central crust and/or ulcer. Multiple bites may induce generalized edema, multiple nodules or ulcerated crusted areas. Very small larvae are easily overlooked even in massive infestations. Pruritus may be extreme, resulting in severe secondary lesions. Ticks are most commonly found on the legs, tail, head and ears. Allergic diseases involve the interaction of three major factors: genetic constitution, exposure to allergens, and a dysregulation of the immune response determined by genetic predisposition and degree of exposure to allergens. However, other environmental factors such as infectious disease, contact with endotoxin and degree of infestation of endoparasites may also influence the prevalence of allergic diseases. Insect hypersensitivities are characterized by a Type I reaction. Type I hypersensitivity reactions develop in genetically programmed susceptible individuals and is mediated by IgE antibodies and some subtypes of IgG, which are produced by plasma cells near epithelial surfaces and are specific to individual antigens. Specific antibody binds to the surface receptors of tissue mast cells and blood basophils, and, when cross linked by specific antigen, causes degranulation of and release of inflammatory and vasoactive mediators from mast cells. Horses with IBH have been shown to have a strong Th2 type immune response with the relative overproduction of IL-4, IL-5, IL-6, IL-13 and IL-31. Lack of suppression of the TH2 response by T regulatory cells further enhances the immune response. A compromise in skin barrier function has been demonstrated in atopic humans and dogs and is thought to occur in horses. Irregular or patchy components that form the tight junctions between epithelial cells

56 allow for allergen entry, which is exacerbated by secondary skin infections. Furthermore, IL-31 binds directly to receptors on nerve fibers and promotes the sensation (along with other inflammatory mediators) of itch. Other allergies of the horse are atopic dermatitis, food allergies or contact allergies. Atopy is defined as a genetically programmed disease in which the patient becomes sensitized to environmental antigens that in a nonatopic animal creates no disease. Human and canine atopy has been proven to be genetically programmed and there is reasonable evidence that atopy of horses is also genetically determined. Atopic reactions are a Type I hypersensitivity to allergens (termed atopenes) that are absorbed percutaneously, inhaled or ingested. The hypersensitivity is not solely IgE and IgGd dependent and is a complex disorder of the immunologic system that results in a perturbation of many aspects of the immune response. Environmental factors, such as horses stabled most of the time early in life, may be sensitized at an early age to molds found in barns. Early high challenge with insect bites, parasitism, viral infections and vaccination with modified live virus vaccines, may all influence the onset and occurrence of clinical disease in atopic individuals. Atopic animals often exhibit clinical signs of disease much earlier than horses with acquired insect hypersensitivities. Atopic horses may present between 1-4 years of age, although clinical signs may first appear as old as 7. Clinical signs may be seasonal or persistent year round, dependent on the atopene. Many atopic horses' clinical signs will progress from seasonal to year round over time. The primary clinical signs are pruritus and urticaria that are generally symmetric. Regions of the body such as the face, ears, neck and legs may be affected or a more dorsal distribution of lesions on the mane, back and tail may occur. Atopic horses may also present with sterile eosinophilic folliculitis or tufted papules that become crusted and alopecic. It is important to remember that allergic reactions develop to common environmental antigens and that no new substances need be introduce to initiate the clinical disease. Secondary lesions caused by self inflicted trauma due to pruritus often result in more extensive lesions and secondary superficial infections. It is not unusual for atopic horses (particularly in the southeast) to have concurrent insect hypersensitivities, or, more rarely, a food allergy. Recently horses with IBH, atopy, or RAO have been shown to be more likely to develop another clinical manifestation of allergic response. Food allergies are relatively rare and are poorly documented in the literature. Food allergies may be presented as persistent or recurrent urticaria or pruritus with accompanying secondary lesions. Food allergies are best diagnosed by limiting the diet to one forage for 4 weeks and then adding back one foodstuff per week. Most authors prefer grass hay as high protein hays such as alfalfa or peanut hay may contain the inciting agent. Soy, a common ingredient in any commercial concentrate feed, is also a relatively common allergen. In the author's experience the most common offending feed is sweet feed or any other feed with molasses. An alternative to limiting the diet to just one forage is to eliminate molasses based feeds, commercial grain mixes or pellets and supplements containing alfalfa for 3-4 weeks, then challenge the horse with the eliminated feed to determine the response to the feed. Contact dermatitis is characterized clinically by hyperemia, papules, and vesicles and may appear like urticaria. It is generated by the percutaneous absorption of a substance which acts as a hapten and combines with a cutaneous protein. A T-cell response occurs against both hapten and protein. Once sensitized, lesions may be seen as early as 5-6 hours or as late as hours

57 after contact with the offending substance. Pruritus may be a component of the clinical response. Secondary skin changes associated with prolonged and/or repeated exposure include hyperpigmentation, lichenification, ulceration, and secondary pyoderma and mimic lesions associated with chronic insect allergies. Ingredients of many topical medications and insect repellents can produce contact allergies. Consequently care must be used in the selection and use of topical medications in other allergic dermatosis. Skin lesions due to agents producing irritation alone may also resemble contact allergies. Removal of the offending material as both diagnostic and curative and, although time consuming, offers the best solution. Diagnosis Diagnosis is made from the signalment, history, clinical signs and ruling out other possible diagnoses. IBH typically improves and exacerbates seasonally, whereas atopy may occur at any time of the year. Urticaria, commonly found in atopy, is not a diagnosis but a cutaneous reaction pattern that may be induced by a wide variety of causes, both immunologic and nonimmunologic. Rule outs for urticaria include drug and vaccine reactions, stinging and biting insects (such as wasps) and arachnids, infections, contacts, vasculitis, and cold, stress or exercise induced lesions. The distribution of lesions on an affected horse with IBH is dependent on the biting characteristics of the insect responsible. Since there is still much to be learned about the identification and feeding habits of many of the insects implicated in allergic dermatoses, it may not be possible to identify the exact etiological agent. Intradermal Allergy Testing Intradermal skin testing (IDT) is not used to make a definitive diagnosis but to identify allergens that can be avoided or used in allergen specific immunotherapy (ASIT). Fifty percent or more of clinically normal horses in past reports have been found to respond positively to intradermal skin testing, although clinically normal horses generally respond to fewer antigens. Nevertheless, intradermal skin testing with currently available antigens on selected cases may provide identification of reactive antigens and guide part of therapeutic management. Antigens should be chosen from the environment of the horse, including insects, plants (grasses, weeds and trees), grains and forages. Both regional and seasonal variations in allergens exist, thus knowledge of the prevalence of plants and pollens help determine antigen selection. The optimal concentration of antigens in test solutions is variable and is still an active area of investigation. False negative reactions may occur if the horse has received glucocorticoids, antihistamines or progestagens. There is no reliable information on withdrawal times of these medications prior to skin testing. Anecdotal withdrawal times, developed by individual clinicians, are: 3 weeks for oral or topically administered corticosteroides, 8 weeks for injectable corticosteroides, and 10 days for antihistamines and products and diets containing omega 3/omega 6 fatty acids. Phenothiazine tranquilizers and excessive excitement may also result in false negative reactions. Detomidine sedation is useful for testing excitable horses. False positive reactions may occur if the allergen is innately irritant to the horse or if the allergen vial has become contaminated by bacteria or fungi. Occasionally horses may have "irritable skin" where large positive reactions are seen at all injection sites, including the saline control. Despite

58 the number of difficulties and inexact science of IDT, it remains the preferred test for identifying allergens for avoidance and ASIT, particularly for atopy. A positive ID skin test means a horse has skin sensitizing antibody; it does not mean clinical disease is present. Size of the reaction site does not necessarily correlate with the clinical importance of the allergen. Positive reactions can occur in clinically normal horses. The frequency of positive reactions to molds and insects in clinically normal horses tends to increase with the age of the horse. Thus the results of ID test must be evaluated in concert with the historical and clinical findings. Serologic tests for circulating IgE In the ELISA, or enzyme linked immunosorbent assay, the antigen to be tested is attached to a solid substrate and are exposed to the patient's serum. Specific antibody binds to the antigen on the solid surface which is subsequently washed. The amount of bound IgE is determined by the addition of a labeled antiglobin with an indicator attached. There is, however, poor correlation between the results obtained by serology and intradermal skin testing. Increased concentration of IgE in heavily parasitized animals may give false positive reactions. IgGd may also contribute to allergic dermatoses and is not detected by any of the serologic tests for IgE. Current methodology to overcome some of the limitations of serologic testing include prior absorbance of test serum for helminth associated and nonspecific IgE. Investigation of the correlation between ID testing, RAST, and 2 ELISAs for circulating IgE concentrations in horses with atopic dermatitis, recurrent urticaria, and normal horses showed none of the 3 serum allergy tests detected allergen hypersensitivity with any reliability. Furthermore, IDT determines tissue fixed IgE and the entire inflammatory cascade. Since augmentation of the B cell response occurs in tissues, IDT remains the test of choice. As with IDT, a positive serologic test means a horse has circulating antibody; it does not mean clinical disease is present. Control of atopy and insect-mediated hypersensitivities Control of insect-mediated hypersensitivities by avoidance is the primary therapy. However complete avoidance can be difficult to impossible since several different insects with different feeding patterns may be involved. (Table 1) However, stabling of horses during peak feeding times of biting insects identified in clinical disease can substantially reduce the antigenic load. Stabling horses in barns with clock operated mist sprayers of nonresidual pyrethrins may offer the best overall protection. Because some horses may develop a contactant or hypersensitivity response to repellants, strategic use of fans to prevent insects from landing on the horse are advisable in stalls and loafing sheds. Screens used to exclude insects must have 60 squares per square inch of screen to exclude Culicoides spp. Permethrin products, which can be applied at less frequent intervals, may aid in protecting horses at pasture. Several spot on permethrin products with 44% - 64% permethrin are marketed specifically for horses. These products are applied to the poll, withers, tail head, and upper legs every 1-4 weeks (read labels). Topical permethrin sprays (look for > 2% concentration of permethrin or cypermethrin) can be used for other areas of the body on a daily basis. The use of petroleum jellies and oils as a mechanical barrier may decrease the occurrence of bites, especially when isolated areas of the body, such as the inside of the ears, are affected. Pyrethrin impregnated plastic mesh stable sheets are available and have been found useful by some owners as have "body suits" of light weight fly sheets and fine mesh.

59 The use of corticosteroids in topically applied creams or leave on rinses is helpful. Systemic corticosteroids remain the best overall palliative therapy for generalized intense pruritus. Treatment should be initiated with mg/kg prednisolone orally/day in the morning until the pruritus and secondary skin trauma are under control. The dose is then tapered to the least amount that will control the clinical signs. Every other day administration (0.5 mg/kg PO) is desirable for long term use. Prednisone may be used in some cases, but, because of its limited and variable oral bioavailability, not all horses will respond to its use. In severe nonresponsive cases dexamethasone at mg/kg parenterally or orally may interrupt the inflammatory response. Once the pruritus and skin lesion development is under control, prednisolone or prednisone may be substituted. A combination of the best managerial practices possible and oral every other day administration of prednisone or prednisolone often will provide adequate control, however the long term aim is to control pruritus without the use of steroids. The author uses systemic steroids to put a wedge in the itch-scratch cycle, with the goal of eventually stopping parenteral administration of steroids. Antihistamines, particularly hydroxyzine hydrochloride, can be used at a dose of mg/kg every 8-12 hours orally. Hydroxyzine is more effective in controlling urticaria than pruritus, but is a useful part of the management strategy. Other antihistamines that may offer some benefit are: cetirizine ( mg/kg BID); chlorpheniramine (0.25 mg/kg BID); diphenhydramine ( mg/kg BID); pyrilamine maleate (1 mg/kg BID). Some authors also recommend tricyclic antidepressants doxepin hydrochloride ( mg/kg BI or amitriptyline (1-2 mg/kg BID). Allergen specific immune therapy (ASIT) consists of a series of injections with increasing concentrations of antigens identified by IDT given over several weeks followed by maintenance injections given every days. Improvement is gradual and generally recognized after 6-12 months of treatment. If used as part of the therapy for IBH the injection series should be timed such that the maintenance dose is achieved prior to the onset of the insect exposure. Experience with ASIT in horses has show % of cases improve with therapy. Many horses with chronic insect hypersensitivities have a type IV (delayed) allergic response to insect bites as well as an immediate of type I response. Since delayed hypersensitivity is not immunoglobulin mediated, response to ASIT regimen is less likely. It is important to remember that ASIT begun during the middle of the insect season and height of the horse s cutaneous response is very unlikely to improve the horse during the current season. Atopic horses are the most likely to respond favorably to ASIT. Atopic horses improve at least 50% to 100% with partial improvement in 80% of atopic horses with concurrent insect allergies. A recent retrospective study reported that 84% of owners reported a good response in horses treated with immunotherapy. Of these, 93% of owners of horses that improved reported that their horses needed treatment with parenteral steroids prior to immunotherapy, and after 1 year of immunotherapy 59% were managed with immunotherapy alone. Systemic corticosteroids may be used as in insect hypersensitivities and, in cases of recurrent or persistent urticaria, hydroxyzine orally every 12 hours may control reoccurrence of hives. Hydroxyzine will not resolve existing urticaria. Doxipen, a tricyclic antidepressant that also has antihistaminic effects, has been used for atopy ( mg/kg orally every 12 hours), however this author has no experience with it.

60 Urticarial reactions may be associated with antigen exposure by systemic administration, inhalation, or ingestion. Definitive diagnosis of the etiologic agent is accomplished by removal and challenge. All possible antigens in the environment must be tested as hypersensitivity may develop to an antigen that has been present for a prolonged period of time. Recurrent urticaria can occur to common environmental antigens such as straw, blankets, tack as well as hay and grains. Differential Diagnoses Other dermatoses that may have also exhibit pruritus are onchocerciasis, oxyuriasis, dermatophytois, pemphigus foliaceus, pediculosis and chorioptic mange. Onchocerciasis, a hypersensitivity to the microfilaria of Onchocerca cervicalis, has a lesion distribution that can mimic Culicoides allergic dermatitis. Since Culicoides spp. are the major vector of Onchocerca, differentiation between the two can be difficult. Finding large numbers of microfilaria in the skin of clinically affected horses is helpful but not diagnostic, an inflammatory reaction to the larvae on histopathological examination is necessary. Ivermectin and moxidectin kill microfilaria in the skin within 14 days but do not eliminate adult Onchocerca in the ligamentum nuchae. Clinically, the incidence of onchocerciasis has decreased with the common and frequent use of ivermectin or moxidectin for internal parasite control. However, strategic use of anthelmintics for gastrointestinal parasite control may result in more frequent occurrence of onchocerciasis. Infestations with Oxyuris equi are characterized by tail rubbing with loss of tail hairs and excoriations of the underlying skin. Diagnosis is made by examining an acetate tape that has been applied to the anal region for Oxyuris ova. Early infestations of dermatophytes may appear as localized wheals. Some infestations may be accompanied by a marked response to fungal products and have a more generalized edema, particularly on the legs which may be painful and/or prutitic. Pemphigus foliaceus may also be pruritic, particularly when horses are exposed to sunlight, as solar radiation exacerbates pruritus. In cool weather lice and chorioptes mange are common conditions exhibiting pruritus. Chorioptes mites affect the lower limbs and are most frequently found on horses with large amounts of lower limb hair (draft breeds, Andalusians). Skin scrapings for diagnosis of chorioptes should be mixed with an insecticide as the mites move very fast and may crawl off the slide before examination. Although sucking lice (Haematopinus asini) are controlled with avermectins, biting lice (Bovicoli (Damalinia) equi, Wenedkiella equi equi) and chorioptic mites feed on epithelial tissue debris and are poorly controlled by parenterally administered avermectins. These parasites are most effectively treated with topical agents such as lyme sulfur or permethrin. Persistence of parasite populations occur in low numbers often on asymptomatic animals, thus all in contact animals and common tack or grooming equipment should be treated. Secondary skin infections with Staphylococcus sp or Malassezia sp may occur concurrently in atopic horses. It is well documented that atopic dogs are prone to both bacterial pyoderma and Malassezia infections. Staphylococcal infections may be an impetigo characterized by an accumulation of neutrophils on the skin surface or may act as superantigens which enhance the activation of large numbers of T cells and contribute to the inflammatory reaction in the skin. In this case small groups of stapholococci may be seen adherent to keratinocytes without the presence of neutrophils. Malassezia sp are considered to be commensal surface organisms in dogs but in one study were not demonstrated on normal horses. Clinical infections of Malassezia

61 infections are characterized by greasy to waxy foul smelling variably pruritic dermatitis in the axillae, groin, udder and prepuce. Superficial overgrowth of staphylococcal organisms and Malassezia infections may be treated topically with shampoos and antibiotics and antifungal agents respectively. Staphylococcal impetigo responds best to systemic antimicrobial treatment. In all cases of pruritic dermatitis managerial procedures to decrease exposure to exciting agents as well as symptomatic therapy to reduce pruritus is warranted. All avenues available to decrease exposure to insects should be fully implemented. Heat, humidity and solar radiation exacerbate pruritus thus the provision of shade and wind currents by fans can provide relief. Simple feeds and whole grains are better than mixed multiple grain sweet feeds. Cold water rinses and shampoos can rehydrate dry skin and reduce the amount of topical allergens on the skin. Colloidal oatmeal, pramoxine (a topical anthesthetic) and 1% hydrocortisone shampoos or leave on rinses (hydrocortisone is not absorbed) may reduce pruritus and minimize or reduce the amount of systemic antipruritics needed. A complete and detailed investigation into the etiology of the disease should occur simultaneously with general symptomatic care. The client must understand that hypersensitivities and atopy are life long and the horse will need continuous management and or therapy. Often a patient may be symptom free with low exposure to inciting antigens and symptomatic as the antigen "load" increases. Antigen exposure is additive, thus comprehensive management is needed to best control clinical disease. Table 1 Insect Breeding area Feeding times Stable flies Manure, rotting vegetation Daytime Horn flies Cattle manure Daytime Horse & Deer flies Vegetation close to water water Daytime Culicoides Standing water & manure Twilight to dawn Simulian (Black) flies Running water Morning & evening Mosquitoes Water Dusk to 2 hours past sunset Suggested Reading (free site) Proceedings of the 8 th World Congress of Veterinary Dermatology (2016)

62 Skin Infections in Horses Susan L. White DVM, MS, DACVIM Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens GA Bacterial folliculitis may present as a superficial pyoderma to deep ulcerated lesions. The causative agent is usually a coagulase positive Staphylococcus aureus or S. intermedius, although Corynebacterium pseudotuberculosis and occasionally other organisms may also cause folliculitis. Mild lesions may be characterized by alopecia and exfoliation which may be regional or generalized. The lesions may be circular with crusts and epidermal collarettes that must be differentiated from dermatophytosis. The lesions may present as a few papules with crusts to a more generalized military dermatitis. Lesions are often found associated with tack and other equipment (blankets, fly masks), particularly on young horses, or horses kept in unclean conditions, or horses with suboptimal nutrition, and/or immuno-compromised horses. Staphylococcal dermatitis is often alone or one of multiple inciting agents in pastern dermatitis. The lesions may begin with multiple encrusted papules that enlarge and coalesce. Lesions generally begin on the plantar surface but may spread to encircle much of the leg and migrate proximally to include the fetlock and lower cannon bone. Staphylococcal granulomas or botryomycosis are most frequently associated with improper castration technique, but may be found anywhere on the body and resemble fungal granulomas. Lesions may be variably pruritic and/or painful. Lesions associated with tack and pastern dermatitis are most often painful. Diagnostic tests may include cytology, culture and histopathology. Histologic evaluation of biopsy specimens shows folliculitis and or furnunculosis, however bacterial colonies are not always observed. Polymerase chain reaction determination may be made for Staphylococcal organisms, preferably on fresh tissue. Similarly, bacterial sequencing techniques can be used to identify C. pseudotuberculosis. a Methicillin resistant Staphylococcus aureus have been identified in asymptomatic and symptomatic infected horses. MRSA infections have been documented to move from horse to horse, horse to humans, humans to horses and presumably humans to humans in both hospital and farm environments. Consequently, the examining veterinarian should take appropriate precautions (barrier protection and/or hand washing) when examining and treating equine patients with bacterial folliculitis. Similar precautions should be practiced by owners when treating their horses. The severity of bacterial pyoderma is not necessarily associated with methicillin resistance. Coagulase positive S. aureus have several properties that evade the defense systems of the body. In addition, horse neutrophils have been shown to lack efficiency in killing staphylococcal organisms. Young horses that suffer recurrent bacterial pyoderma should be evaluated for the presence of a partial immunodeficiency. Selective IgM deficiency, B cell deficiency, and transient hypogammaglobulinemia may be associated with recurrent pyoderma. b Local lesions may be treated with gentle cleansing (2-4% chlorhexidine shampoo, ethyl lactate shampoo, or Tricide cleansing solution c ) and topical treatment (generic mupirocin ointment,

63 2% silversulfadiazine, or Tricide-Neo d ). Deeper or more generalized lesions may be treated with oral trimethoprim sulfa (30 mg/kg q 12 hours). For organisms resistant to TMS, and not methicillin resistant ceftiofur ( 2.2 mg/kg ceftiofur Na IM or IV q 12 hrs or ceftiofur crystalline free acid 6.6 mg/kg IM q 4 days) may be used. Enrofloxacin may be use (7.5 mg/kg PO q 24 hours) in horses older than 2 years. However, staphylococcal organisms develop resistance to enrofloxicin quickly, thus it is not an optimum choice for initial therapy. Use of Tricide potentiated antimicrobials will often decrease or eliminate the need for systemic antimicrobials. Pastern folliculitis should be treated by gentle cleansing. In many instances over zealous cleaning (including harsh disinfectants and scrubbing) exacerbate lesions and prevent healing. Topical antimicrobial therapy, applied after thorough drying of the lesions, and an appropriate dry wrap (sheet cottons with polo wraps) are often all that is necessary. DERMATOPHILOSIS Dermatophilosis is a common superficial crusting and pustular dermatitis which is not pruritic. It is caused by Dermatophilus congolensis, an actinomycete (gram positive), branching filamentous organism, which forms spores. Synonyms used by horsemen for this condition are rain scald, rain rot, cutaneous streptothricosis and winter fungus. It occurs worldwide and there is a high association with rain, poor grooming, poor nutrition, ticks and lack of sunlight. Consequently the disease is usually a fall and winter disease but can occur any time when significant prolonged wet conditions prevail. The organism may be maintained on carrier animals, both domestic and wild, and zoospores may survive for prolonged periods in the environment. Certain farms, even under good management, have a high incidence of dermatophilosis in resident horses. Conversely, certain horses are more susceptible to dermatophilosis than others, often exhibiting severe disease where herd mates kept in identical conditions do not. To establish an infection there must be skin damage, either from maceration of the epidermis due to prolonged wetting, bites of insects and arthropods, or minor skin injuries from vegetation (briars and other brush). In hot humid environments horses may develop dermatophilosis under the saddle area due to repeated sweating and lack of cleanliness. In the most common presentation of the disease lesions are found over the dorsum of the back as scab-like, exudative crusts which coagulate, causing the hair to stick together. The hair tufts stand erect as a paint-brush effect. In early infections the lesions may be felt better than seen by running your hand over the hair, the underlying scabs will be evident. In more advanced infections the hair tuffs stand up. By pulling out the hair tufts, the underlying skin is moist, raw, and may be hemorrhagic. The hair roots extend through the scab in the characteristic paint brush effect. Untreated severe lesions may result in deep ulcers that extend into the subcutaneous tissues or, in extreme cases, deeper. In the active stage, the lesions are painful. Dermatophilosis may also present with extensive epidermal thickening and alopecia. Lesions may be found on the lower legs if horses are kept in moist pasture conditions, particularly in deep grass and are often a component of pastern dermatitis. Foals may have lesions on their legs, ventral abdomen and sides of the trunk and hindquarters from lying in wet pastures. Regardless of the form, this disease is the only exudative, painful, non-pruritic common disease in clinical practice. Diagnosis is often made on clinical presentation and can be confirmed by cytology, biopsy and culture. Cytological preparations of crusts soaked in saline and minced may be stained with Diff

64 Quik, Gram s stain of new methylene blue. If exudate is present on the underside of the crusts simple impression smears can be used for cytological examination. D. congolensis appears as gram positive branching multiseptate hyphae with cuboidal packets of coccoid cells in parallel rows (railroad track appearance). Recently a reverse transcriptase quantitative PCR (RT-qPCR) has been shown to be superior to cytological examination and may be mused to confirm dermatophilosis when cytology is unrewarding. Histological evaluation of biopsies show thick crusts with alternating layers of parakeratotic stratum corneum and dried serum and degenerate neutrophils. Superficial folliculitis is also present and branching organisms may be seen in crusts and follicles. In most cases the disease can be treated with crust removal and sufficient housing to keep the horse dry. In early superficial infections the crusts can be removed by grooming. The zoospores in the crusts are resilient and thus should be disposed of rather than left in the environment of the horse. Likewise any grooming equipment, tack and blankets should be thoroughly cleaned and confined to individual horses. Crusts can also be removed by bathing. Any appropriate equine shampoo is adequate, although most references suggest biocidal shampoos or rinses (2% - 4% chlorohexidine). Crust removal may take days to weeks, depending on the severity of the disease and the degree of pain exhibited by the patient. Warm water soaks prior to active scrubbing help soften crusts and ease removal. Horses may be treated with parenteral penicillin or oral trimethoprim potentiated sulfonamides, particularly when the lesions are deep and generalized. Future cases can be prevented by optimizing nutrition, cleanliness of the horse and keeping the horse dry. In some situations (pasture maintained horses) provision of a run in shed may be sufficient to avoid further infections. DERMATOPHYTOSIS Dermatophytosis is a superficial contagious and zoonotic fungal skin disease spread by direct contact and fomites. It can be spread from host to host, soil to host and host to man to host. Trichophyton equinum is the most common cause of dermatophytosis in horses. Other dermatophytes are T. mentagrophytes, T. verrucosum, Microsporum equinum (M. canis) and M. gypseum. M. gypseum is the only dermatophyte that is normally a soil inhabitant (the others are zoophilic and have adapted to animals) and produces more severe cases of dermatophytosis. Transmission can be by direct contact but is often transmitted by contaminated objects. In many clinical situations, there will be no evidence of transmission to other animals in contact with the affected one. Young animals are most susceptible. Lesions usually begin as focal lesions with initial urticaria. Central alopecia, scaling and crusting appears; pruritus is variable. The usual distribution is in the saddle and girth area especially in large training stables where more than one horse affected. Atypical forms can include extensive crusting and scaling with little alopecia, or in the case of M. gypseum severe inflammatory reaction with suppuration crusts and ulceration and, if on the lower limbs, edema. Lesions may be confined to the posterior aspect of the pastern and heel and present as pastern dermatitis, or more rarely be confined to the coronary band. Lesions may wax and wane dependent on environmental conditions and are often self limiting.

65 Diagnosis is by fungal culture. Hair should be plucked from the periphery of active nonmedicated lesions and gently pressed into Dermatophyte Test Media (DTM) or Sabouraud s agar. Because the surface of the horse normally has large numbers of saprophytic fungi and bacterial, gentle cleansing of the area prior to sampling may reduce the number of contaminants and aid diagnosis. Cultures should be incubated at room temperature and protected from light. DTM contains a ph indicator, phenol red, which is red at alkaline ph. Pathogenic dermatophytes metabolize protein first, turning the media red in 5-7 days as colonies first appear. Green or black colonies are contaminants. All contaminant fungi will metabolize protein eventually (and turn the media red) thus if cultures are not examined every day between incubations days 1-10, the diagnosis may be erroneous. Trichophyton equinum may have a niacin requirement not found in DTM, therefore it has been recommended that 1-2 drops of a vitamin B solution be added to the media before inoculation. T. verrucosum had been reported not to grow on DTM, thus Sabouraud s agar may be appropriate. In all cases, colonies should be examined cytologically to confirm their identification. Two dermatophytes, M. canis and T. mentagrophytes may be identified psot culture with a one step PCR and may be available in some diagnostic laboratories. Aspergillus and other species may metabolize proteins, mimicking dermatophyte growth on DTM. Adhesive tape collection of affected hair for direct microscopic evaluation may be helpful in diagnosis. Clear packing tape (such as 3M ScotchPad PackagingTape) is preferable to regular clear Scotch tape as it has a stronger adhesive and will collect fragile infected hairs. The tape is transferred to a glass slide and examined under low power (4X 10X) for ectothrix. Skin biopsy from the periphery of a lesion may also confirm the presence of dermatophytes. Because Trichophyton may cause acantholysis, biopsy specimens may look like pemphigus on histological evaluation. 11 Spontaneous regression of most cases occurs in 3 weeks to 3 months. Therapy may shorten the course and reduce spread and environmental contamination. Sunlight, good nutrition (including adequate vitamin A) and decontamination of environment, including all objects (tack, brushes etc) as they are often the source of infection help speed resolution of the disease. Although repeated bathing with idodine or chorhexidine shampoos is discouraged (they have no residual action and physical act of bathing may result in further hair loss and disperse infective spores in the coat) the author believes an initial gentle shampoo to remove surface dirt and crusts is beneficial. Shampoos containing ketaconazole may also be used. After that rinses may be applied with a very soft brush daily for 5-7 days. The act of gently brushing on rinses encourages the medication to get close to the opening of hair follicles, where the infection resides. Economical topical rinses are Captan (rose fungicide, 50% powder in most garden stores, mix 1 oz. (2 tbsp) per gallon of water) and Lime sulfur (LymDyp, DVM, 1 cup to 1 gallon of water). Topical sprays appropriate for rinsing large areas of the horse are available. e Spot treatment of isolated lesions with antifungal agents may also be used. Systemic therapy with griseofulvin (Fulvicin ) is not recommended by the author. The drug has a very poor and erratic oral bioavailabilty and is likely completely ineffective in some, if not most, horses. It must be given daily over 2-3 weeks to the horse (single mass dose not effective) and the effective dose unknown. Reports of cures with griseolfulvin may be due to spontaneous regression of the infection.

66 a S Sanchez, Athens Diagnosic Laboratory, College of Veterinary Medicine, University of Georgia, Athens GA 30602, personal communication b S L White, unpublished data c,d Molecular Therapeutics, LLC, 111 Riverbend Rd, Suite 166, Athens, GA e Equishield CK Rinse. Kinetic Vet, P.O. Box Lexington, KY Suggested reading Weese SJ and Yu A. Infectious Folliculitis and Dermatophytosis. Vet Clin N Am, Equine, 2013, 29;3: or go to and select proceedings WVDC proceedings 2016 from the drop down menu (free site) page 322

67 IMMUNE MEDIATED DISEASES IN HORSES: DIAGNOSIS AND THERAPY Susan L. White DVM, MS, DACVIM College of Veterinary Medicine University of Georgia, Athens, GA BULLOUS AUTOIMMUNE SKIN DISEASES Bullous autoimmune skin diseases, characterized by the formation of bullae or vesicles, are divided into two groups dependent on the location of clefts and the formation of bullae within the skin. In the pemphigus group of diseases the vesicles form intradermally; in pemphigoid the clefts occur at the dermal epidermal junction. The primary lesion of pemphigus is acantholysis in which the epidermal cells loose their adhesion, separate from one another and become rounded. The loss of cellular adhesion is due to autoantibody directed to one or more of the cell adhesion proteins, particularly the desmosomal antigens of the keratinocytes of stratified squamous epithelium. Antibody binding results in activation of keratinocyte proteolytic enzymes in the intercellular space. The desmosome is hydrolyzed and intercellular cohesion is lost. Marked heterogeneity of desmosomal antigens of squamous epithelium occurs dependent on the degree of maturation and differentiation of the keratinocytes within the epithelium. In vitro studies of cultured keratinocytes have shown differences in antigenic expression dependent on culture conditions. Thus antigen expression in vivo, may also depend on the location and function of squamous epithelium in different areas of the body. The two distinct disease entities of pemphigus are distinguished by the site of epidermal clefting. Antibody in pemphigus foliaceous is bound primarily to desmoglein 1 of more mature cells in the subcorneal or granular layer resulting in superficial vesicles. Antibody in pemphigus vulgaris binds to desmoglein 3 of basal cells and sometimes one or two suprabasal cell layers forming suprabasilar clefts. Additionally, pemphigus may be drug induced or occur secondarily to primary neoplasia (paraneoplastic pemphigus). Pemphigus foliaceus is the most common form of pemphigus in the horse. It affects horses of all ages, breeds and sex. Because of the superficial nature the primary lesions of vesicles and pustules are often not clinically recognized and the presenting signs are of an exfoliative dermatitis with crusts, scales, erosions, epidermal collarettes and alopecia. Many horses are painful and approximately 50% are pruritic, especially in hot, humid weather and/or when exposed to intense solar radiation. Pain and pruritis often cause self inflicted trauma which result in numerous secondary lesions. Lesion distribution varies considerably. Lesions may initially occur in a generalized distribution. Lesions may begin on the dorsal body surface of the neck and back and spread ventrally or they may begin ventrally and spread dorsally. Horses with lesions that begin on the limbs generally have lesions associated with the coronary bands, pasterns and fetlocks which are often confluent. In other cases that begin with a dorsal distribution, lesions may be found over the entire dorsum, sparing the limbs and head, on the head only or regionally on the neck. Lesions may be confined to the axillary and perineal areas and the head. Lesions may rapidly generalize in 2 to 4 weeks or remain localized for months. In general, lesion distribution is symmetric, chronic and progressive.

68 Horses may have concurrent clinical and laboratory signs of systemic illness. Clinical signs include depression, decreased appetite, weight loss, ventral and limb edema, and pyrexia. Abnormal laboratory findings include a mild normocytic normochromic anemia, neutrophilia, mild hypoalbuminemia and hypergammaglobinemia. In our clinic it is common for the client to report some degree of depression (mild behavior change) and slight decrease in appetite. The number and severity of other systemic signs generally correlate with the severity of the skin lesions (generalized vs. localized) and their duration. Differential diagnosis includes dermatophytosis, dermatophilosis, parasitic dermatitis including onchocerciasis, culicoides hypersensitivity and other insect bite hypersensitivities, seborrhea complex, bacterial folliculitis, contact dermatitis, drug eruptions, equine exfoliative dermatitis and sarcoidosis. Definitive diagnosis is made from the history, physical examination, cytologic evaluation of direct smears, and skin biopsies for histologic evaluation. Laboratory evaluation of direct smears and skin biopsies is dependent on proper sampling of primary lesions. Because of the transient nature of vesicles and pustules the horse may have to be carefully examined for several days to ensure sampling of newly formed lesions. Microscopic examination of cytologic preparations of lesions usually reveal numerous acanthocytes (large, rounded darkly staining epithelial cells), nondegenerate neutrophils and/or eosinophils with no intracellular bacteria. Skin biopsies for histological evaluation are generally most successfully obtained by an elliptical biopsy across an intact lesion that is pinned to heavy paper or cardboard prior to fixation in 10% buffered neutral formalin. Because of the superficial nature of the bullae and associated crusts, surgical preparation of the biopsy site should not be done. Histopathologic changes include acantholysis within the stratum corneum or granulosum with clefts, vesicles or pustules. Hair follicles may be similarly affected. Acantholytic cells may be found singularly or in clusters with neutrophils and/or eosinophils within the lesions or on the surface of erosions. Trichophyton equinum infections may have crusts and acantholytic cells and mimic the cytologic and histologic findings of pemphigus, thus fungal stains should be performed on all biopsies taken to rule out pemphigus. The importance of correlating historical, physical and laboratory findings to diagnose pemphigus is emphasized by a group of horses seen in our clinic that suffered from Culicoides spp. and other insect hypersensitivities for 1-3 years prior to the onset of pemphigus foliaceous. The history typically reveals a seasonal pruritic dermatitis that responds to insect avoidance management that becomes progressively worse each season. Clinical presentation at the time of positive direct immunofluorescent testing and characteristic histopathologic changes of the skin usually occurs in the winter. Recent history from the client complaint notes that the pruritus and/or lesion development do not subside with cooler temperatures and decrease in the insect population. Careful examination of the horse will usually reveal characteristic new lesions often in locations not typical of insect hypersensitivity. The pathogenesis of pemphigus foliaceous subsequent to insect hypersensitivity is unknown. A human variant of pemphigus foliaceous, Brazilian pemphigus, occurs in well defined areas of unimproved jungle of South America and is associated with a particular species of Simulian flies. Passive antibody studies have shown Brazilian pemphigus to be a true autoimmune disease. The incidence is higher in certain families of genetically related people and is not contagious. Although controversy exists on the presence

69 or absence of a viral agent the current hypothesis is against an infectious agent. Chronic inflammation may result in transformation of epidermal cell antigens or antibodies to components of insect saliva may cross react with epidermal cell antigens. Although some cases of pemphigus resolve spontaneously most require substantial doses of systemic corticosteriods with or without the use of other immunosuppressive drugs. Since treatment may result in severe adverse side effects it is important to fully evaluate the patient prior to treatment. Supportive care, particularly in hot humid climates, will help speed the response to therapy. Affected horses should be protected from sunlight as ultraviolet light is known to aggravate lesions and often produces an intense burning sensation in humans. Gentle cleansing of the skin, particularly in hot weather when sweating occurs, will minimize pruritus. Minimal topical agents such as commercial horse shampoos and fly repellents should be used as these compounds often aggravate skin lesions. Fly control is best provided by strategically placed fans to prevent insects from landing. Initial treatment with mg/kg of prednisone or prednisolone per os once daily will usually result in a cessation of new lesions and improvement in skin condition in days. Because of the limited and variable bioavailability of prednisone, some horses may not respond to this drug. Once remission has occurred, the total dose of prednisone or prednisolone may be decreased by 50 mg every 5-7 days until a maintenance level is reached. Alternate day therapy can then be initiated with the lowest effective dose. Horses not controlled by prednisone may be controlled with mg/kg of dexamethasone given in a similar regimen. Many horses do not respond to corticosteroid treatment alone. Multimodal treatment with one or a combination of therapies will often give more favorable results. Adjunctive therapy with essential fatty acids (fresh ground flaxseed, Omega Horse Shine, Omega Fields, info@omegafields.com or Omega Max, Triple Crown Nutrition, Inc. and vitamin E (13 IU/kg/day PO) often work well with steroid therapy. Pentoxyfyline (8-10 mg/kg PO 2-3 times/day) may decrease the production of inflammatory cytokines and modulate the immune response. Azothioprine (2-3 mg/kg PO q 24 hrs for 3-4 weeks and then every other day) is an immune suppressive drug and can be used as a steroid sparing drug when adverse effects of steroids are anticipated or occur. Alternatively gold salt therapy (aurothiomalate) may be used. Patients are given 2 test doses of 20 mg and 40 mg/im one week apart and then 1 mg/kg weekly until remission. Concurrent use of corticosteriods during the first 3 to 6 weeks of gold salt therapy may help resolution of lesions. Once remission occurs maintenance therapy consists of injections of 1 mg/kg every 3-6 weeks. Although side effects of gold therapy are common in other species (dermatitis, stomatitis, proteinuria, blood dyscrasias) adverse reactions have not been reported in the horse. It is advisable, however, to monitor patients with biweekly CBC s and weekly urinalysis during initial therapy and then every 2-3 months during maintenance therapy. (Note: Currently aurothiomalate is only available in Canada.) Many cases treated for 3-6 months and then removed from therapy remain in remission for weeks to years. Reoccurrence has occurred as long as 2.5 years after cessation of therapy. In general the sooner reoccurrence occurs or if reoccurrence occurs on maintenance therapy the harder it is to control the disease in the future. Many horses with pemphigus foliaceous are not alive one year after diagnosis. Although successful medical management the majority of cases is possible, many owners become discouraged and frustrated at the expense and inexact

70 science of managing chronically affected cases. Pemphigus vulgaris with suprabasilar vesicle formation, although common in the dog and man, is not common in the horse. Two cases have been diagnosed in our clinic in the last 25 years and few reports are found in the literature. Bullous pemphigoid, characterized by clefting at the dermal epidermal junction and the deposition of immunoglobulins and complement in the basement membrane of the basal epithelial cells, is also rare. Antibodies in pemphigoid are directed against the basilar surface of the epithelial cells and, on direct immunofluorescent testing, are found in a linear deposit along the basal cell basement membrane. The 4 cases documented in the literature and the 3 cases diagnosed in our clinic have been characterized by large lesions and prominent Nikolsky s sign, in which new clefts are easily formed by the application of digital shearing force to the skin. All of the horses were severely systemically ill and were nonresponsive to therapy. Two cases had corneal lesions and one case at the University of Georgia had immunoglobulin deposits within the kidney. No single concept has emerged concerning the cause of bullous autoimmune skin diseases. Experimental animal studies infer that the diseases result from a range of genetic and immunological abnormalities which may be influenced by environment that differ from one individual to the next. Because some cases remain in remission without continuous therapy and others do not, there are likely many predisposing causes. Drug-induced and paraneoplastic pemphigus resolve (with therapy) once the inciting cause is removed. Other predisposing factors may include systemic diseases, stress and allergies. ALOPECIA AREATA Alopecia areata is a rare autoimmune disease that can have a variety of presentations and clinical progression that occurs in humans, dogs and equids. T lymphocytes directed against antigens of the hair matrix and root sheath epithelium result in hair loss. Autoantibodies directed against hair follicle antigens have also been demonstrated in cases of alopecia areata in the horse, however their significance is not yet known. Hereditary factors may be important in pathogenesis. Diffuse thinning of the mane and tail, formerly known as idiopathic dystrophy of the mane and tail, frequently found in Appaloosas, is now considered a form of alopecia areata. Alopecia areata also occurs as one or more circumscribed to patchy areas of alopecia on the body. The onset of alopecia may be gradual or rapid. Clinical signs may wax and wane in a synchronous (i.e. be more severe in summer or winter) or asynchronous fashion. Periods of spontaneous remission may occur or affected areas of the skin may recover while other areas become affected. In most cases visual examination of the skin appears normal and the horse is not pruritic, although some cases with pathohistologic findings consistent with alopecia areata may have crusts, pruritus and/or pain. Alopecia areata should be considered as a rule out in cases where patchy, nonpruitic, apparently noninflammatory alopecia occurs. Diagnosis is confirmed by biopsy and histologic evaluation of newly affected areas of skin. Lymphocytic bulbitis is the pathognomonic finding with accumulations of lymphocytes in a "swarm of bees" pattern around hair bulbs in the anagen phase. Lymphocyte invasion of the of the matrix of the bulb and outer root sheath may also be seen, however these lesions often difficult to demonstrate and multiple biopsies may be needed.

71 Treatment is most effective with either topical or systemic cortiocosteroids. However, many, if not most, cases respond poorly or not at all. Long term immunosuppressive doses are needed in those cases that do respond. Thus, treatment may not be justified in every case, particularly if a prospective treatment trial is not effective. Suggested reading (free site) or go to and select proceedings WVDC2016 from the drop down menu page 335

72 DIAGNOSTIC PROCEDURES IN DERMATOLOGY: BEST PRACTICES * Susan L White DVM, MS, DAVCIM College of Veterinary Medicine University of Georgia, Athens, GA Dermatologic disease is a common client complaint yet veterinarians often have difficulty in establishing a definitive diagnosis. Techniques for sampling dermatologic lesions to aid in diagnosis are simple and require limited equipment. Sample selection site, sample collection procedures and sample submission (when using a veterinary diagnostic laboratory) all influence the quality of results obtained. CYTOLOGY Specimens for cytological examination can be collected in a variety of ways. Impression smears are obtained by pressing firmly one or more times on a lesion that is wet or moist. Alternatively, the slide can be pulled across a lesion once. Rubbing the slide back and forth may disrupt cells and interfere with evaluation. Impression smears may also be made from the underside of crusts (for example when looking for Dermatophilus), from the cut surfaces of excised masses (such as tumors) or from extirpated nodules. Alternatively scrapings may be used to sample underneath crusts, vesicles or peeling stratum corneum. Intact pustules can be opened with the tip of a small needle and contents applied to a slide and subsequently smeared. Cotton or nylon tipped swabs are usually used when imprints, scrapings or aspirates cannot be obtained, such as collecting samples from draining tracts. The swab should be pre-moistened with isotonic fluid to minimize cell damage during sample collection and slide preparation. The swab should be rolled onto the slide in a single line to distribute the acquired material. Fine needle aspirates can be obtained using gauge needle and a 6-10 cc syringe. Enough suction should be applied to aspirate tissue into the needle, but not so much that red cell contamination occurs. The syringe should be removed from the needle and air drawn into the syringe and to expel the contents of the needle onto a slide. Very thick samples can be gently squashed. The top slide is then pulled off the end of the sample slide to smear the material. The objective, regardless of acquisition method, is to obtain a single layer of cells on the slide. Ideally several slides are made. Slides should be rapidly and completely air dried. If the material collected is greasy or waxy, or if the slide is made from a moistened swab the slide should be heat fixed prior to staining. Heat fixation can be done with a blow dryer directly on the slide from a distance of about 10 inches, a cigarette lighter or a match. The slide should be held over the flame for 5 seconds without burning the slide or damaging the sample by overheating. If soot accumulates on the slide it should be wiped off either before or after the slide is stained. To collect hair for suspected dermatophytosis hairs should be plucked from the leading edge of a lesion. Alternatively hair and crusts may be collected by brushing with a clean small stiff brush (such a toothbrush) or scraped with a scalpel at a lesion edge. Collected material should be placed in a test tube with a cotton plug or in a paper envelope. Moisture in a sealed tube may

73 result in a proliferation of saprophtytic fungi. These samples may be used for both cytology and culture. MICROBIOLOGY Bacteriologic culture and sensitivity testing is necessary when initial therapy doesn t work, in deep skin infections with draining tracts or granulomas, when other bacteria besides cocci are seen on skin cytology, or if methicillin-resistant staphylococcus is suspected. Any moist lesion will contain bacteria after 24 hours, therefore attempt to culture lesions as soon as they occur or by opening a closed pustule. Samples may be obtained with a moistened cotton or nylon tipped swab, by aspiration or from a tissue biopsy. Sterile equipment and aseptic technique should be used. Swabs or tissue samples should be obtained from the tissue exudate interface where the proliferation of organisms occur. Aspirated samples of purulent exudate generally are sparsely populated or devoid of live organisms. Multiple swabs should be obtained from the lesion site as the laboratory will often set up a number of different tests on day 1 based on the information provided by the clinician. Swabs should be immediately placed in a non-nutritive transport media (such as a commercial culturette, and kept cool, as microorganisms die rapidly in dry conditions. Whenever possible submit tissue rather than tissue swabs. Tissue samples should be aseptically collected, wrapped in sterile gauze moistened with saline or LRS and placed in an airtight sterile container. A ring block or regional anesthesia is preferred when obtaining a biopsy for culture, as lidocaine and epinephrine inhibit the growth of many gram positive and gram negative bacteria, mycobacteria and fungi. An unstained air dried and or fixed slide for a Gram stain should accompany the samples for microbial propagation. Samples should be transported to the laboratory as rapidly as possible; ice packs and overnight shipping are recommended. Limitations of bacterial culture are an over growth of contaminating organisms, organisms that don t grow or are slow growing, deficient culture technique, delayed shipping of the sample, and concurrent antibiotic therapy at the time of sampling. Organisms that are hard to grow may be identified by molecular techniques from tissue samples. If a deep fungal infection is suspected a tissue sample is best for culture and molecular diagnostic techniques. A sample of tissue for histopathological evaluation should also be submitted to confirm that fungal isolates are pathogenic. BIOPSY Skin biopsies are best obtained from early developing lesions and not chronic ulcerated lesions. This step may require a careful complete examination of skin, especially if there is a generalized distribution of lesions. Biopsies from excoriated or traumatized lesions, found in many pruritic conditions, are not likely to be informative. Anti-inflammatory medications, especially corticosteroids, will alter an inflammatory disease process, rendering a biopsy less informative. Most authors recommend discontinuation of oral corticosteroids 2-3 weeks prior to a biopsy, and 4-6 weeks in long acting corticosteroids given parenterally, even if new lesions are occurring. Lesions which are secondarily infected with bacteria or yeast should be treated prior to biopsy so the primary disease process may be identified.

74 All biopsies should include the dermis. Do not prepare or clip skin if the lesion is in the epidermis as preparation may remove important components of the lesion. For deeper lesions hair may be clipped with scissors. Instruments should not remove any crusts or scales and should not touch the skin. After obtaining the biopsy, specimens should be fixed in 10% buffered neutral formalin (BFN). Formalin containers should have a top as wide as the container (do not use glass), seal completely, and the formalin solution should be no older than 1 year. If any precipitates are present in the formalin it is unsuitable for use. Autolysis of biopsy samples begins in less than 5 minutes, thus biopsies should be placed in fixative immediately after they are obtained. If multiple biopsies are obtained, each biopsy should be placed in formalin in sequence, rather than waiting until all samples are collected. Punch biopsies are useful for lesions of the epidermis and dermis, but not if the disease extends into the subcutaneous tissue. A new punch biopsy should be used for each patient. A minimum of a 6 mm biopsy punch should be used, and an 8 or larger punch is preferred. When obtaining a punch biopsy only abnormal skin should be included and the punch should be centered over the lesion. Using a permanent marker (such as a Sharpie) to mark the desired biopsy site prior to acquisition ensures the biopsy contains the part of the lesion selected. The junctional edge of a lesion should not be sampled with a punch. During processing by the histopathology laboratory, the circular sample is cut down the middle and each half placed face down in the cassette. Sections for slides are made from these cut surfaces. Skin coloration or other features that may be obvious on clinical examination loose their color and distinction once fixed in formalin and cannot be used for orientation. If it is important to examine the junctional edge of a lesion then an elliptical biopsy should be obtained. If a biopsy is obtained from an area of alopecia the direction of the hair in surrounding normal skin should be marked with a permanent marker before taking the biopsy. On the submission form request the tissue be cut along the marked line. This will ensure that entire hair follicles are present in the resultant slide and avoid cross sections of hair follicles. To ensure the disease process is properly represented several punch samples should be obtained, preferably from lesions in different stages of development. A minimum of 3 samples is recommended and some authors recommend 5-8. Most diagnostic laboratories have a single charge for 3 biopsies; some laboratories do not limit the number of skin biopsies that can be submitted from a patient on one submission form. Care should be taken to ensure that local anesthetic is placed in the subcutaneous tissue under the biopsy site as infiltration of the local anesthetic into the skin will result in artifacts that can obscure pathological changes. The biopsy punch should be held perpendicular to the skin and turned in one direction while gentle pressure is applied. The biopsy should be carefully lifted using small forceps or a small needle, handling the subcutaneous tissue only, and cut by a scalpel blade (preferably) or small scissors to avoid stretching or crushing artifacts. If the crust detaches it should be wrapped in microscope lens paper and included with the biopsy. The submission form should indicate that the crust is separate and should be cut in. To avoid curling artifact punch biopsies 8mm or larger should be placed subcutaneous side down onto cardboard

75 or a piece of a tongue depressor for a few seconds prior to being placed upside down in formalin for fixation. Any wrapped crust should also be submerged into the formalin for fixation. An elliptical biopsy is preferable when there is an ulcer, or the junctional area between normal and abnormal skin and or evaluation of structures deep to the dermis is needed. The biopsy should include ~ 1/3 normal skin and 2/3 abnormal skin and be perpendicular to the lesion edge. Elliptical biopsies should be placed on a tongue depressor or cardboard, cut side down, with gentle pressure applied to adhere the biopsy. Preferably, the sample should be pinned in place (25 gauge needles work well) to avoid curling artifact. The entire unit is then placed in BFN, biopsy side down. The ratio of BNF to tissue should be 10:1 or greater to ensure complete fixation. Excisional biopsies may be preferred when a small circumscribed lesion can be completely removed. A wedge biopsy may be used when a large lesion, such as a tumor or other mass, requires deep tissue for evaluation. To avoid distortion of the tissue with local anesthetic an L or ring block or regional anesthesia should be used. Electrocautery or laser should not be used when obtaining the biopsy. Submitted tissue should be no thicker than 0.5 to 1 cm, as that is the limit of formalin penetration. If a mass larger than 1 cm has been removed, slice through most of the mass at 0.5 m 1 cm intervals to allow proper tissue fixation. If the margins of a lesion need to be examined to determine if a tumor has been completely removed the edges may be marked with india ink ( ) by first submersing the mass in ink prior to formalin fixation. The ink will dry in approximately 60 seconds and the sample is then placed in BFN. Alternatively, each border of the sample may be marked with different colors of ink ( ) or acrylic paint and a key provided on the submission form. Shave biopsies are often used on the coronary band due to concerns of subsequent abnormal hoof growth. Biopsies should be taken towards the heel bulbs. These small and fragile samples are best submitted on a sponge designed for histopathological use and placed in a cassette ( prior to immersing in formalin. Plastic cassettes and sponges may be able to be obtained from the diagnostic laboratory on request. Alternatively, the biopsy may be wrapped in lens paper. The sample should be pushed into formalin to ensure fixation. SUBMISSION OF SAMPLES TO A DIAGNOSTIC LABORATORY Evaluation of samples submitted to a diagnostic laboratory is done with consideration of the history and clinical context. Most diagnostic laboratory professionals agree that sample interpretation is 50-80% context. Thus, useful results obtained from dermatologic samples are dependent on appropriate information accompanying submitted material. Submission forms should include all patient information: owner name and animal name, species, age, sex, and breed. Submission containers should be labeled with the owner s name and sample identification. If multiple samples are submitted each container should also be labeled with the sampling location. Abbreviations or anagrams should not be used. What may be familiar among working clinicians may not be to diagnostic laboratory personal. The history should be readable and informative such that the reader has a complete understanding of the patient s circumstances and disease progress. A good way to ensure complete information is provided on a diagnostic

76 requisition form is to answer the following questions posed by DW Pinson (Writing diagnostic laboratory requisition form histories. J Am Vet Med Assoc 2014; 244: ). What is the primary reason for evaluation? This helps to define the problem for the laboratory diagnostician. Is the current skin lesion unresponsive to previous therapy? Is the lesion or disease process very unusual? What is the duration and frequency of the problem? Words such as acute, chronic, rapid or slow have no specific meaning. Be precise in describing duration, progression or growth, and/or recurrence of the lesion(s). What are the objective clinical findings? These are things that can be observed, described, measured or quantified. It is important to indicate if the disease is affecting the total health of the horse or not. This information provides the pathologist with important background information. What are your differential diagnoses? It is helpful to list these in order of probability. If the lesions are unusual, or if you have specific concerns about a possible rule out this information should also be supplied. What specifically was sampled? For example, the junctional edge of a bullous lesion, a complete excision of a closed pustule, or a shave biopsy of the coronary band provides needed contextual information. If multiple lesions in different stages of development are biopsied, this information should also be included. What is the appearance of the tissue or lesion? In addition to a precise and concise written description, photographs of the patient and close up of the lesions and or biopsy site are helpful. Photographs can be included on electronic submission forms or, should the laboratory use paper forms, the owner s name and your name can be linked to photographs submitted separately via . * abridged from White SL. How to sample dermatologic lesions for submission to a diagnostic laboratory to maximize results. Proceed Am Assoc Equine Pract Annual Convention 2015, pp

77 Updates on Equine Pituitary Pars Intermedia Dysfunction and Equine Metabolic Syndrome Sarah Reuss, VMD, DACVIM Boehringer Ingelheim Animal Health The differentiation between pituitary pars intermedia dysfunction (PPID) and Equine Metabolic Syndrome (EMS) can be a challenge for the equine practitioner. Clinical signs are similar, and while the two diseases have different pathophysiology, they can be co-expressed with some EMS-affected horses subsequently developing PPID, and some PPID-affected horses having abnormal insulin regulation. Management of one condition without addressing the other is difficult, and horses with one condition exacerbating the other are more likely to develop laminitis. Therefore, we will briefly review each focusing on practical diagnosis and management. PPID results from oxidative injury to the dopaminergic neurons in the hypothalamus resulting in a lack of inhibition of the pituitary pars intermedia and excessive secretion of the hormones derived from prohormone proopiomelanocortin (POMC). Most notably, there is increased production of adrenocorticotropin hormone (ACTH), but other POMC end-products such as α-melanocyte-stimulating hormone (αmsh), β-endorphin, and corticotrophin-like intermediate peptide (CLIP) may result in the clinical signs seen in some horses. Clinical signs of PPID result from both overaction of the pars intermedia as well as loss of function of the surrounding tissues. Early clinical signs may include changes in attitude, regional hypertrichosis, delayed shedding, regional adiposity, and loss of muscle mass over the topline. There may be a decrease in athletic performance, and investigation into musculoskeletal injuries in horses with early PPID has revealed an increased incidence of suspensory desmitis as well. Over time, advanced PPID cases may develop generalized hypertrichosis, loss of seasonal shedding, abnormal sweating, rounded abdomen, recurrent infections, infertility, laminitis, blindness, and seizure activity. EMS results from an interaction between genetics and environment, and is a group of problems composed generalized or regional adiposity, insulin dysregulation (ID- any combination of fasting hyperinsulinemia, postprandial hyperinsulinemia or tissue insulin resistance), dyslipidemia, altered adipokine concentrations and increased risk of laminitis. Most horses with EMS are obese with a body condition score >7. They also have regional adiposity like the PPID horses, but without the muscle loss. Mean neck circumference has also been negatively correlated with insulin sensitivity in obese horses. Horses with EMS often present for spontaneously occurring laminitis. Fasting hyperinsulinemia and excessive insulin response to oral sugars are they key components of EMS that are detected in equids with naturally occurring laminitis. Altered vascular dynamics and weakening of dermal-epidermal attachments may also play a role. Testing for both PPID and EMS is recommended for any horse with laminitis, but other early clinical signs of PPID such as changes in haircoat or sweating should also prompt testing. All horses being tested for PPID should also have their insulin status investigated as insulin dysregulation is common in horses with PPID and successful management of either relies upon recognition of both. Routine monitoring, especially for ID, is advisable especially in at risk breeds such as ponies, Morgan horse, Paso Finos, Arabians, and Warmbloods. It is important to remember different laboratories use different methodology and reference intervals, so use lab specific values. The following values are from the Cornell Animal Health Diagnostic Lab.

78 Testing for PPID is a common source of confusion and debate. It is important to remember that there is some seasonal variability to the HPA axis. While this used to be cited as a reason to not test horses in late summer/fall, this recommendation has changed but one must remain aware of the current consensus ( and use the values specific to each diagnostic lab and season. It should also be noted that pergolide treatment can be considered regardless of test outcome in horses with hypertrichosis, laminitis, or other strong clinical suspicion. The appropriate screening test for PPID depends on the stage of disease as well as time of year. Horses with advanced signs of PPID may be screened with a resting ACTH sample. Resting ACTH concentrations are the easiest to obtain as it is a single plasma sample, and while sample handling is important it is not as onerous as once believed. Blood can be collected into a glass or plastic ACTH tube but must be kept cool at all times. The sample should be centrifuged to separate plasma prior to freezing or shipping, but delays beyond the initially described 2 hours maximum to centrifugation appear acceptable. The sample should be shipped overnight with ice packs, and while the sample may be frozen it is not necessary. It is important to use seasonally adjusted reference intervals, recognizing that normal will be increased in the late summer/fall and the magnitude of that seasonal change may vary by breed. In general, concentrations less than 30 pg/ml are considered negative for PPID and > 50pg/mL positive from mid-november to mid-july, with pg/ml being equivocal. From mid-july to mid-november, <50 pg/ml is negative, >100 pg/ml is positive, and pg/ml is equivocal. Horses with equivocal resting ACTH or normal ACTH concentration but a strong clinical suspicion of PPID should have a TRH stimulation performed. TRH is believed to be a releasing factor for the pars intermedia, so horses with PPID show an increase in ACTH after TRH administration. The TRH stimulation test can be performed while hay is fed but not grain and should not be performed within 24 hours of an oral sugar test. The veterinarian collects a baseline ACTH, administers 1.0mg TRH intravenously, and collects a second ACTH sample 10 minutes after TRH administration. 10 minute post measurement of ACTH <110 pg/ml is considered negative for PPID, pg/ml equivocal, and >200 pg/ml positive. At this time, however, the TRH stimulation test is only validated from mid-november to mid-july. Testing for EMS involves either a resting insulin concentration or an oral sugar test (OST). The resting insulin concentration may be useful in advanced cases but has low sensitivity and may be falsely negative in a mildly affected animal. Complete fasting is neither necessary nor recommended, but no grain should be fed within 4 hours. A general cut-off value of <20 µu/ml is considered negative, while >50 µu/ml indicates insulin dysregulation. Values from uu/ml are suspect and should prompt dynamic testing. The OST is more sensitive for detection of ID. It is performed by leaving only one flake of hay with the horse after 10 PM and performing the test the next morning, or feed as normal in the morning and then fast the horse for 6-8 hours. Then administer Karo Light corn syrup at a dosage of 0.15 ml/kg PO (75 ml for a 500-kg horse), and blood samples are collected for glucose and insulin measurements 60 and 90 minutes later. It is considered negative for ID if the insulin concentration is < 45 µu/ml, and strong evidence of ID if the insulin concentration is > 60 µu/ml. Measurements between 45 to 60 µu/ml are weak evidence and should prompt appropriate management strategies and retesting at a later date. Insulin tolerance test can also be performed to assess tissue insulin sensitivity by administering 0.10 IU/kg regular insulin intravenously and measuring blood glucose 30 minutes later. A less than 50% decrease from baseline is consistent with insulin resistance. High molecular weight adiponectin testing is not currently available in the United

79 States. Leptin measurement is available however, and higher concentrations are associated with increased adiposity and metabolic derangement in adipose tissue. It appears more directly associated with obesity than ID. Hypertriglyceridemia may be a predictor of laminitis in ponies. There are several promising future tests on the horizon as well. PPID requires pharmacological treatment in addition to proper nutrition, husbandry, and treatment of concurrent health problems. Specific treatment for PPID includes the drug pergolide, a dopamine receptor agonist used to restore inhibition of melanotrophs in the pars intermedia. The FDA-approved pergolide (Prascend ; Boehringer Ingelheim) is recommended at an initial dose of approximately 2 ug/kg (1.0 mg for a 500 kg horse) once a day with dosing titrated to effect. Potential adverse reactions include decreased appetite, weight loss, and lethargy. The test used to initially diagnose the PPID (baseline ACTH or TRH stimulation) can be rechecked at 30 days to monitor response to treatment. In horses with normalization of clinical signs and laboratory testing, the dose should be held consistent with recheck monitoring done every 6 months. If clinical signs improve but laboratory tests are still abnormal, the dosage can be held the same or increased according to the veterinarian s preference but with plans of careful monitoring. If laboratory response is adequate but clinical signs recur or a new problem develops, reassess the entire patient prior to increasing pergolide dosage. In patients with both a poor clinical and laboratory response, the dosage of pergolide may be increased by 0.5 to 1.0 mg/day with a recheck after 30 days. An ongoing long-term treatment study of horses on pergolide has shown that most horses show clinical and laboratory improvement, owners are satisfied, and many horses can go years without need for progressive increase in drug dosage. Other medications have been used as well. Cyproheptadine antagonizes serotonin which is stimulatory to the pars intermedia, so it will also decrease ACTH plasma concentrations, but is less effective than pergolide alone. Trilostane inhibits cortisol synthesis at the level of the adrenal cortex by inhibiting 3β-hydroxysteroid dehydrogenase. Given that the pathogenesis of PPID in horses does not directly involve the adrenal gland, trilostane should not be a first line treatment in horses with PPID. Diet and exercise are the primary strategies to manage EMS. Obese horses should be placed on a restricted diet of hay only (with a low NSC or soaked for at least 60 minutes) and a ration balancer. Horses with ID but leaner body condition may need more calories provided, which can be done in the form of fat (up to 20% of calories) and/or a low-nsc commercial feed. To accelerate weight loss in obese animals, levothyroxine sodium may be used to induce a mild state of hyperthyroidism, but it is important to remember that this will only work in conjunction with calorie restriction. Metformin hydrochloride has limited evidence that it can limit postprandial hyperinsulinemia despite low oral bioavailability. It may be useful in animals with persistent hyperinsulinemia at a dose of 30 mg/kg given minutes before feeding, up to 3 times daily. It is well tolerated in most horses with the exception of possible oral irritation. Early recognition and appropriate treatment of horses with PPID and/or EMS should increase their quality of life and ideally keep them active well into their later years. Further information and updated recommendations can be found at

80 Fluid Therapy for Horses in the Field Sarah M. Reuss, VMD, DACVIM Boehringer Ingelheim Animal Health Fluid therapy is used in horses for a variety of reasons, but the basic goals are to replace losses, support the cardiovascular system, and maintain hydration in the face of ongoing losses. In horses with colic due to intestinal impactions, fluids are also commonly given in an effort to promote hydration of the colonic contents. While intravenous fluids can be given in the field in some circumstances, enteral fluids are generally more practical and as we will discuss, often more effective. Fluids may be given either intravenously or enterally. Intravenous fluids are more expensive, require an indwelling intravenous catheter with the associated risk of thrombophlebitis, and may be impractical on the farm. However, horses with diarrhea, signs of hypovolemic shock, or nasogastric reflux greater than 2-3L will generally necessitate IV fluids to maintain hydration. In hospital settings, high volume intravenous fluids (2 to 3 times maintenance rate or ml/kg/d) are often given under the premise that there will be net flux of fluid into the gut lumen resulting in softening of impacted material. However, there is conflicting evidence as to the effect of IV fluid volumes on fecal hydration. In one study of normal horses, 5L/h of IV fluids for 12 hours (approximately twice maintenance) did not show any effect on hydration of right dorsal colon contents or feces. In another study comparing fluid rates and means of administration to dehydrated horses, fecal and systemic hydration was restored at twice maintenance IV fluids; however there was no additional benefit seen when increasing the rate to three times maintenance. In fact, horses given three times maintenance IV fluids had increased urine production and sodium loss which could contribute to electrolyte abnormalities as well as rebound dehydration when fluids are discontinued. When giving intravenous fluids, there are two main choices: crystalloids or colloids. Isotonic crystalloids distribute amongst the extracellular fluid compartment with only 20-25% remaining within the plasma volume. Therefore, the maximum hemodynamic benefits occur early, and 3-4 times the intravascular deficit may need to be given. Several isotonic crystalloids have historically been available in 5L bags for administration to adult horses: 0.9% saline, lactated Ringer s solution (LRS), Plasmalyte A or 148, and Normosol R. Large volumes of saline can cause a hyperchloremic metabolic acidosis, which limits its usefulness in most horses. There are certain cases, however where it is indicated. These include hyperkalemia, metabolic alkalosis, hypochloremia, or hepatic encephalopathy. LRS is a very commonly used fluid. It is slightly higher in Cl relative to Na, so it is also slightly acidifying. It is buffered with lactate, so it is not a good fluid choice for horses with decreased lactate clearance due to liver dysfunction but is otherwise safe for horses with hyperlactatemia due to decreased tissue perfusion. LRS also contains calcium, so it should not be given with blood products or sodium bicarbonate. Normosol R and Plasmalyte A are the closest to equine plasma in terms of electrolyte composition. They are buffered with acetate and citrate, contain magnesium, but do not contain calcium. Therefore they are good for cardiac necrosis and brain, and chelation with blood products or sodium bicarbonate will not be encountered. Hypertonic crystalloids, namely hypertonic saline (7.4%), can be used for rapid volume expansion. It causes a shift of interstitial and intracellular fluids into the vascular space resulting in an increase in the extracellular fluid volume of 4 to 5 times the infused volume for at least 60

81 minutes after infusion. Comparing hypertonic saline with isotonic saline in the resuscitation of horses participating in an endurance event, hypertonic saline resulted in a greater decrease in PCV and total protein, shorter time to urination, and lower specific gravity. Not surprisingly, there were also greater increases in sodium and chloride. Hypertonic saline has also been shown to improve the hemodynamic derangements of endotoxemia in part by acting as a positive inotrope, decreasing endothelial edema, and decreasing neutrophil activation. It also decreases intra-cranial pressure making it a popular fluid for critical care. Doses should not exceed 4ml/kg and must always be followed with isotonic crystalloids within 2.5 hours. Colloids available for use in horses include synthetic hydroxyethyl starches, dextrans and plasma. They can be used to provide sustained volume expansion as they remain within the vascular space longer than crystalloids. Because of their persistence in the circulation, colloids will produce the same resuscitative effect as 3 to 6 times that volume of an isotonic crystalloid. Higher molecular weight colloids will persist in circulation longer while smaller molecules exert more osmotic pressure to draw fluid in from the interstitial space. Hetastarch is a heterogenous synthetic colloid. In normal ponies, a dose of 10mL/kg increases the colloidal oncotic pressure from 24 to 27 mm Hg and that effect persists for more than 120 hours. In hypoproteinemic horses, that effect is shorter lasting only 24 to 36 hours. Adverse effects of synthetic colloids include allergenicity, kidney injury, tissue accumulation, and interference with coagulation. At doses of 20 ml/kg, hetastarch was shown to cause a decrease in vwf and factor VIII activity, and prolonged bleeding times. Changes in platelet function have also been shown with 10 ml/kg doses of hetastarch in the horse. It is also worth noting that after hetastarch administration, the plasma total solids are no longer a useful guide to plasma oncotic pressure. Plasma is a natural colloid that also provides albumin, some clotting factors, and antibodies. At least 6 to 8 liters are required to treat clinically significant hypoproteinemia in adult horses, and horses should be monitored for anaphylaxis. Enteral fluid administration is less expensive and generally easier to perform on the farm. However, it requires an intact intestinal epithelium and motile small intestine. Contraindications to enteral fluids include ileus, reflux, gastric or small intestinal obstruction, severe diarrhea, or cardiovascular compromise. Enteral fluid therapy has some advantages as a treatment for colonic impactions. Fluids delivered via nasogastric tube will exit the stomach within 15 minutes and reach the cecum and large intestine within 1-2 hours in most normal horses. Intermittent bolus delivery may also result in more fluid being delivered to the colon as it will overwhelm the small intestine s capacity for absorption. Nasogastric administration may also stimulate the gastrocolic reflex, thus aiding with overall GI motility. There is evidence that leaving an indwelling nasogastric tube in place for 72 hours does delay gastric emptying, so repeat intubation may be better despite its inconvenience and behavioral effects in horses necessitating prolonged treatment. Enteral fluid therapy is slightly more forgiving than intravenous fluids in terms of rate and electrolyte composition. However, large volumes of plain water or hypotonic solutions may cause marked electrolyte abnormalities including hyponatremia, hypokalemia, and hypocalcemia. Isotonic fluids, however, are generally well tolerated with no significant effects on plasma biochemistry values except for a mild hemodilution when using a potassium rich solution with 6g NaCl and 3g KCl per liter of water. Most average size horses can tolerate 6-10L/h of intragastric fluids, however there does seem to be some individual variation. Horses with a significant amount of colonic ingesta may show signs of discomfort when large volumes (>5L) of fluid are administered. Fortunately, this generally resolves with time, walking, or

82 decompression via the nasogastric tube. Abdominal distension can also be seen with high volume enteral fluids, but is generally well tolerated by most horses. Many horses treated with enteral fluids for an impaction will develop self-limiting diarrhea due to excretion of fluids as the impaction resolves, and cecal rupture has also been reported. Administration of enteral fluids has been evaluated in several studies in normal horses. In one study of adult horses, plain water given at once (50mL/kg/day), twice (100 ml/kg/day), or three times (150 ml/kg/day) maintenance administered via nasogastric tube over 4 treatment periods every 6 hours was shown to be safe and effective at restoring intestinal hydration with a volume-dependent effect on fecal volume. In another study, a balanced electrolyte solution (135 mmol Na/L, 5 mmol K/L, 95 mmol Cl/L and 45 mmol HCO3/L) given continuously at a rate of 10L/h via nasogastric tube was shown to be more effective in hydrating ingesta that an identical rate of fluids given intravenously along with one intragastric dose of magnesium sulfate (1g/kg in 1L water). There was also a trend of more fecal production in the horses treated with enteral fluids, and there were less systemic effects. In another study, hydration was measured in the feces and right dorsal colon of normal horses with indwelling fistulas in a crossover design of 6 treatments. Intragastric balanced electrolyte solution or sodium sulfate resulted in the best hydration of RDC contents, while sodium sulfate, magnesium sulfate, and balanced electrolyte solution resulted in the most hydrated feces. Sodium sulfate caused hypocalcemia and hypernatremia, while plain water caused hyponatremia leaving the balanced electrolyte solution as the safest and most effective option. Enteral fluids have also been shown to be effective in the management of clinical cases of non-strangulating large colon lesions. In a retrospective analysis of 147 horses with large colon impactions where all were treated with IV fluids and only 49 (33.3%) received any enteral treatment, the mean time to resolution of impaction was 48 hours with a range from 1-6 days. This contrasts with the duration of medical treatment found in another study in which all horses received enteral treatment with or without concurrent IV fluids. 102 horses with large colon impactions or displacements were given either enteral fluids alone (8-10L of a potassium-rich isotonic electrolyte solution every 2 hours, n=49) or enteral fluids simultaneously with intravenous fluids (2 ml/kg/h lactated Ringer s solution, n=53). Both groups had a mean time to resolution of approximately 24 hours for impactions and 14 hours for displacements with no significant electrolyte abnormalities suggesting that the addition of enteral treatment resulted in faster resolution than the previous study. The overall success rate was 99% for impactions and 83% for displacements. Another retrospective study of 53 horses found that impactions treated with enteral fluids resolved faster, had shorter hospitalizations (4 vs 7 days), and lower mean hospital bills ( 483 vs 2006) than horses treated with intravenous fluids. The bulk of the evidence supports treatment of colic with enteral fluids whenever possible. Enteral fluids can also be used to correct mild electrolyte abnormalities. A potassium-rich balanced electrolyte solution safely corrected mild hypokalemia in horses with large colon impactions and displacements. Administration of 1g/kg body weight of NaHCO3 has been shown to increase cecal ph which may be useful in the treatment of horses with grain overload. Fluid therapy is an essential part of treating sick horses. It can serve several purposes including replacing deficits, supporting the cardiovascular system, correcting electrolyte disturbances, and hydrating gastrointestinal contents. Frequent monitoring is essential to assess hydration status and determine endpoints of fluid therapy or the need for referral and more intensive therapy.

83 Practical Pain Management in Horses Sarah M. Reuss, VMD, DACVIM Boehringer Ingelheim Animal Health Equine medicine and surgery has advanced drastically over the past several decades resulting in advanced diagnostics and therapeutics. More complex and potentially painful conditions and procedures are encountered as a result. Therefore, recognition and treatment of pain is vital for animal welfare and to improve overall outcomes. Pain can be a protective mechanism resulting in withdrawal or avoidance of harmful stimuli, but chronic pain can negatively affect healing and recovery. Before discussing how to treat pain, we must first review how to recognize it. Pain is defined by the International Association for the Study of Pain (IASP) as an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage. Therefore, it is hard to quantify in veterinary species who cannot self-report. Different types of pain (e.g., colic vs laminitis) may also require different systems to quantify it. There have been a variety of pain scales suggested over the years, but a universal one has not been adapted. To be most useful, a pain scale needs to be objective, repeatable, and usable within a busy clinical setting. It is also worth noting that pain behaviors may be altered by the presence of an observer, so video camera systems may be implemented. Specific behaviors and physiologic parameters all need to be taken into account. Behavior changes seen with pain may include reduced weight bearing, attention focused towards the abdomen, changes in facial expression and body position, changes in appetite, changes in social behavior, and changes in attitude. Recently facial features have been described more systematically in the horse grimace scale or equine pain face. These include ear position, stare, and tension around eyes, nostrils, muzzle, and chewing muscles. Physiologic parameters such as heart rate, respiratory rate, serum cortisol and noninvasive blood pressure have been studied with conflicting results. Visual analog scales have been attempted but have poor inter-observer variability. These may be useful for horse owners though to quantify changes in pain over time. Simple descriptive scales (i.e. the AAEP lameness scale or Obel laminitis scale) have been developed for some conditions, and several simple descriptive scales have been combined to make composite pain scales. These composite pain scales may include both physiologic and behavioral scores. The Equine Utrecht University Scale for Composite Pain Assessment (EQUUS-COMPASS) and Scale for Facial Assessment of Pain (EQUUS-FAP) have good inter-observer reliability, sensitivity, and specificity. Further work is needed to determine the best way to quantify pain in equine patients, but there is at least improved recognition of this need. There are a variety of analgesic agents available for use in the horse. Source of pain, animal signalment, and concurrent conditions may dictate the most appropriate first choice option. Multimodal therapy is also frequently indicated. Practical considerations in the field include method of administration, frequency of dosing, cost, and regulatory considerations. Non-steroidal anti-inflammatory drugs (NSAIDs) are the cornerstone of routine pain management in horses. They reversibly and irreversibly inhibit cyclooxygenase which has two isoforms: COX-1 and COX-2. COX-1 is constitutively expressed and is important for physiologic activities such as renal perfusion and mucosal blood flow; therefore, most of the detrimental side effects of NSAIDs are due to its inhibition. COX-2 is inducible and causes the release of pro-inflammatory prostanoids, making it the suggested preferred target of action to minimize toxic effects. Both phenylbutazone and flunixin meglumine are non-selective, while firocoxib is COX-1 sparing. Toxicity is unlikely when NSAIDs are given for short duration at appropriate doses, but repeated administration may result in serious side effects such as acute kidney injury (medullary crest necrosis) and right dorsal colitis. The role of NSAIDs in gastric ulceration is controversial. Using multiple NSAIDs concurrently is also contraindicated as it increases the risk of toxicity.

84 Flunixin meglumine is arguably the most frequently used analgesic in cases of colic. Dosed at 1.1 mg/kg IV, onset of action should occur in approximately 20 minutes and last for 8-12 hours. This dose should be repeated no more frequently than every 12 hours. While labeled for use either intravenously or intramuscularly, potentially fatal clostridial myositis has been reported secondary to intramuscular flunixin injection, so IV or oral use is recommended. Flunixin has variable effects on gastrointestinal permeability in ischemia-reperfusion models. Phenylbutazone is used primarily for musculoskeletal pain and is COX non-selective. There is no apparent benefit to 8.8 mg/kg/d (4g/day) over 4.4 mg/kg/d (2g/day) using force plate analysis, so the lower dose should be used to minimize side effects. Firocoxib is COX-1 sparing at its label dose and showed results similar to phenylbutazone for horses with naturally occurring osteoarthritis. With ischemic-injured jejunum, firocoxib was found to provide equivalent analgesia to flunixin meglumine based on post-operative pain scores. Firocoxib (Equioxx ) is available for intravenous or oral use as both a paste and tablet. Diclofenac is a topical NSAID that can be applied over areas of inflammation. It has been shown to improve lameness when applied over an affected joint, and may also have some disease modifying effects on cartilage. Alpha2-adrenergic agents are frequently used for both their sedative and analgesic properties. Their onset of action is more rapid and analgesia is more potent than NSAIDs. Xylazine has a short duration of action of minutes. Detomidine is 100 times more potent than xylazine and lasts for minutes. One multicenter clinical trial found that detomidine at either 20ug/kg or 40 ug/kg provided better subjective visceral analgesia than flunixin or butorphanol, but it does not provide any somatic anti-nociception. Side effects of the α2-agonists include transient hypertension followed by hypotension and bradycardia. They also cause transient ileus that lasts longer than the sedative and analgesic effects, and the sedation also outlasts the analgesia. Opioids analgesic effect is primarily at the spinal and supraspinal level. Butorphanol is the most commonly used opioid and is a mixed agonist-antagonist. It provides somatic and visceral antinociception. While butorphanol is less likely to cause excitement than other opioids, it should be administered concurrently with a α2-adrenergic agonist to minimize those effects when given intravenously. Butorphanol will also cause some ileus which can be decreased by administering it as a continuous rate infusion (23.7 ug/kg/h). Horses given a 24-hour infusion of butorphanol after colic surgery had a significant reduction in pain scores. While morphine does provide both visceral and somatic anti-nociception, it also has significant effects on gastrointestinal motility. Buprenorphine is a partial opioid agonist, acting at the µ-receptor. It provides good somatic nociception and pairs well with detomidine for clinical procedures or standing surgery. Its duration of action is 8-12 hours and may provide superior analgesia to butorphanol. While tempting based upon its transdermal delivery option, fentanyl has not been found to provide significant nociception on its own except at extremely high serum concentrations. It may have more of a clinical effect when combined with NSAIDs as pain scores (but not lameness scores) have been shown to decrease when administered together. There is individual variability in terms of peak plasma concentration and time taken to reach peak after application of fentanyl patches to horses. Application of the transdermal patch to the thorax or groin area produces the most consistent results. Tramadol has weak opioid activity as well as inhibition of neuronal reuptake of serotonin. While it has been found to be minimally bioavailable in the horse, it has been used in horses with pain refractory to other drugs. Side effects may include excitement, trembling, and decreased GI motility. Further work is needed on the use of tramadol in horses. Ketamine is a non-competitive NMDA receptor antagonist that may provide some analgesic effects at sub-anaesthetic dosages. It is also anti-inflammatory with decreased chemotactic activation of neutrophils and suppression of cytokine production. In one study it was not shown to have significant effect on somatic nociception in awake horses, but in another study provided decreased limb off-loading in laminitic horses when administered in combination with tramadol. In that study, ketamine alone was not evaluated. Gabapentin is an anti-epileptic agent that binds calcium channels in the brain. Oral

85 gabapentin has been reported to provide analgesia in individual reports of laminitis and neuropathic pain, despite showing low oral bioavailability. N-butylscopolammonium bromide (Buscopan ) blocks the muscarinic acetylcholine receptors of the gastrointestinal tract. It is frequently used for its spasmolytic effects in horses with gas colic and impactions. Effects last minutes, however it will also induce a tachycardia that may persist for 50 minutes. In a duodenal and colorectal distension model, the colorectal distension threshold did increase and there was a trend for increased duodenal distension. In an ex-vivo model, N-butylscopolammonium bromide inhibited spontaneous and cholingerically mediated contraction in ileal smooth muscle strips suggesting it might be useful in the treatment of ileal impactions, although further study is needed. Improved recognition and treatment of pain in horses will positively affect outcome. Various drug classes are available for use. Table 1. Frequently used analgesics and their recommended doses. Drug Dosage NSAIDs Flunixin meglumine mg/kg IV or PO q8-24h Phenylbutazone mg/kg IV or PO q12-24h Firocoxib 0.09 mg/kg IV or 0.1 mg/kg PO q24h α2-adrenergic Agonists Xylazine mg/kg IV, IM Detomidine ug/kg IV, IM Opioids Butorphanol mg/kg IV, IM or 23/7ug/kg/h IV CRI Buprenorphine mg/kg, IV, q4-8h Tramadol 5-10 mg/kg, PO, q6h Other Gabapentin 5-20 mg/kg, PO, q6-12h N-butylscopolammonium bromide 0.3 mg/kg IV Lidocaine 1.3 mg/kg over 5-10 minutes, then 0.05 mg/kg/min IV CRI LBK Loading dose over 15 min then CRI Lidocaine 1.3 mg/kg then 3 mg/kg/h Butrophanol mg/kg then mg/kg/h Ketamine 0.55 mg/kg then 0.5 mg/kg/h

86 Equine Equine Complementary Therapy (Acupuncture and Spinal Manipulation) 1 Carla W Pasteur DVM CVA CVSMT CERP Acupuncture in equine medicine is most commonly used for lameness, poor performance and reproduction. A practical approach to utilizing acupuncture and conventional medicine is; if the horse is lame use conventional medicine first and then after a diagnosis is made use acupuncture to support the conventional treatment. If no diagnosis is possible acupuncture gives another point of view and can be used treat the problem. The same pattern can be followed for poor performance and reproduction. Internal medicine cases can be treated with Traditional Chinese Veterinary Medicine (TCVM) as well. Many effects of acupuncture have been discovered. Acupuncture creates changes in brain function and different points have different effects. Points used to treat pain have similar fmri effects and points that are anatomically very close together have different fmri changes. Local effects include changes in mast cells and neuropeptides. Many acupuncture points are at fascial planes and stimulation of mechanoreceptors within the fascia may be part of the mechanism of action. Acupuncture has many effects and can be difficult to study in healthy subjects as it seems to work differently in heath and in disease. TCVM categorizes disease in a way that is unfamiliar to western veterinarians. Conventionally we would treat all horses with recurrent airway disease (RAO) the same way. In TCVM they are divided into many patterns and treated accordingly. A horse with a dry cough and red tongue would not be treated the same as a horse with a wet cough and a pale tongue. Tongue color is one of the clinical signs considered during a TCVM exam and is an indication of the horse s pattern or diagnosis. Research on acupuncture for specific diseases is hampered by the fact that western diagnoses don t translate directly into TCVM. Deciding on one acupuncture treatment protocol for a group of horses with RAO is like treating all equine cough with antibiotics. It would work well if the horses were coughing due to a bacterial infection but not as well if they had RAO. The results of such a study would be inconclusive. The TCVM pattern determines the treatment and is the result of a through exam. The history will provide a differential list and the clinical exam will narrow the list. The questions asked during a TCVM exam often seem odd but are looking for fine details to determine the pattern. For example: If the horse gets turnout, does he stand more in the shade or in the sun? Are the signs worse in the morning or afternoon? Does he lean into pressure or avoid it? The basic division is Excess or Deficiency. An example of an Excess pattern would be a respiratory infection. The horse is hot (has a fever), a forceful cough, the pulse is very strong and bounding and there is yellow nasal discharge. An old horse with lethargy, a poor appetite, and a pale tongue is a deficient pattern. The most common pattern in equine lameness is Stagnation. Stagnation is an Excess pattern but it can have Excess and Deficiency signs. Stagnation is like a dam on a river, it creates an excess on one side and a deficiency on the other. Stagnation is painful. Fortunately, Stagnation is easy to treat with TCVM. Points commonly used are LIV-3, ST-36 and LI-4. Herbal formulas include Liver Happy or Xiao Yao San, Double P 2, and Qi Performance (Formulas from Jing-Tang Reddick, FL). The scan is part of the equine TCVM exam. To scan we apply pressure to specific points and observe the horse s reaction. Because Stagnation is an Excess pattern the points become sensitive

87 Equine to palpation. Humans will say it feels like a bruise when touched. The reaction can be subtle, a skin twitch or it can be very clear, the horse may kick out or bite. The scan gives information about the musculoskeletal system and certain groups of point indicate specific joints or regions. For example, LI-18, SI-9 and PC-1 indicate front foot pain. It is interesting that these foot points are often reactive when the horse is due to be reset or just after it has been shod. Most internal medicine cases will not react much to scanning. One notable exception is ulcers. Reaction at ST-7, CV-12 or along the Bladder meridian in the lumbar region may indicate ulcers. A predictable pattern of pain on the body due to a musculoskeletal or internal problem is via the somato-somato or viscerosomato reflex. Another part of the TCVM exam that may seem unusual is the tongue and pulse exam. The tongue is observed for its shape, color and amount of moisture. The variation of these is surprising. A normal equine tongue is pale pink and fills the area between the dental arcades without exceeding it. Common abnormalities are pale, red or purple. A pale tongue indicates a deficiency pattern. In TCVM there are 4 main deficiency patterns; Qi, Blood, Yin or Yang. A pale tongue may be a deficiency of Qi, Blood or Yang depending on what other signs are present. A red tongue may be a deficiency of Yin or an excess of Yang or Heat. A purple tongue indicates stagnation. Pulse diagnosis palpates the rate and quality of the pulse. Like any palpation pulse diagnosis takes practice and time to perfect. Acupuncture needles are a small gauge and they are solid. They are flexible and have a short handle. Usually they come with a guide tube to help get them into the skin. It takes practice to place acupuncture needles especially in the hindquarters where the skin and fascia are very dense. Needle length varies depending on the part of the body we are needling. In the head or distal limb, a mm needle is used and they may be placed so that only part of the needle is thru the skin. For most areas, a 50mm needle is used and in the large hindquarter muscles a mm needle is used. It is important to know the depth of the point and the underlying anatomy. Many points are near joints or synovial structures which need to be avoided. The number of needles varies greatly and depends on the patient s condition and age. For a performance problem in a competing sport horse needles are used. For a geriatric or weak patient only a few needles are used, maybe as few as 4. The points chosen for treatment are based on the pattern and the site of the problem. For example, a horse that presents with lumbar back pain likely has a Stagnation pattern. The tongue would be purple and the pulse would be wiry. Reactive points would include BL-22 thru BL-26. Points to clear Stagnation LIV-3, ST-36 or LI-4 should be used along with local points and distal points. Local points are near the problem in this case a point cranial to the region of pain and a point caudal to it would be good choices, BL-20 and BL-26. Distal points in this context means points away from the problem. Distal points may be in the distal limb or for this case near the head. LIV- 3 could be used as a distal point in addition to a pattern point. Another good choice would be BL- 65. Case 1: 7 year old Paint gelding grade 4 lame RH for 4 months. Complete lameness exam repeated several times failed to reveal the cause of the lameness. TCVM exam found a purple tongue, a wiry pulse, reactivity at GB-27 and BL-28 and moderate effusion in the right stifle. Pattern diagnosis was Stagnation. Treatment at KI-1, LIV-1, ST-45right, BL-28, GB-30, SP-13, ST-36,

88 Equine BL-40 and the Eyes of Knee. Electro-acupuncture was used at BL-28 to BL-40 and SP-13 to ST- 36. Follow-up exam was scheduled in two weeks. Two weeks later his lameness was improved to a grade 2 and his tongue was pale purple pulse was not wiry and the reactive point were GB-27/29 and BL-28/54 all on the right. BL29 and BL-54 indicate hip pain. TCVM pattern was Stagnation in the right hip. Treatment points were HT-9, LU-11, LIV-3, BL-67, GB-30, BL-54 right, SP-13, BL-28, GB-29 right and BL-40. This time the treatment could be focused on the right hip. Electro-acupuncture at BL-28 to BL-40 bilateral and GB-29 to GB-30 on the right. He was sound two weeks after the second treatment and remained sound on the right hind for nine years.

89 Equine Equine Complementary Therapy (Acupuncture and Spinal Manipulation) 2 Carla W Pasteur DVM CVA CVSMT CERP Veterinary medical manipulation (VMM) is used to restore or maintain normal joint range of motion. It is used to treat restrictions. Normal range of motion is needed not only for top athletic performance but also to maintain healthy joint cartilage. Cartilage is nourished by imbibition which is greatest and maximal flexion and extension. Most lay people think that adjustments move the bones but instead the adjustments stimulate mechanoreceptors and change the soft tissue. The body is designed like a tensegrity structure; the compression elements, the bones, are floating in the tensional elements, the soft tissue. To keep the joints healthy and moving freely the soft tissue must be addressed. Injuries can occur as a result of one bad step but often they are the result of chronic insult. Many sport horse injuries are not due to one bad step but rather due to ten thousand not very good steps. VMM is one tool to keep equine athletes sound and performing well. Distal limb lameness may be due to an axial skeletal problem or may cause a compensatory axial skeletal problem. Axial restrictions can lead to distal limb lameness via changes in weight-bearing, disruption of nerve function, overloading other structures and changes in muscle tone. A restriction that interferes with left lateral bend will cause the horse to land harder on the left front when circling left. The horse will keep its head and neck straight or to the right. This could lead to an over-use injury to the left front limb. Nerve function can be affected by axial skeletal restrictions. The nerves come off the spinal cord and travel through the intervertebral foramen (IVF) and to the limbs. Likewise, sensory nerves come from the limb through the IVF to the spinal cord and brain. Restrictions can affect the nerve roots, the dorsal root ganglion and the spinal nerves by changes in the IVF. Compression of nerve roots can cause paresthesia, hyperesthesia, decreased reflexes and motor weakness. In humans, sciatic nerve pain can present as primary foot pain. All lame horses should have a VMM exam. Common owner complaints that may respond to VMM include; stiff to one side, heavy on one rein, difficulty with one canter lead, cross-cantering, difficulty with collection, a decrease in performance and back pain. It is important to consider all possible causes and treat accordingly. The best treatment is often a multi-modal approach. Horse with a history of recent trauma, neurologic signs or joint laxity should not be adjusted until a through conventional exam is completed. There are many ways to manipulate a restriction, the most important consideration is to respect the anatomy. The manipulation should not exceed the anatomic barriers. A common method is to use a High Velocity Low Amplitude (HVLA) thrust. Strength is not needed. The speed of the thrust should stimulate the golgi tendon organs to cause a reflex relaxation to the surrounding muscles. The VMM exam includes a history, static and dynamic physical exam, and motion palpation. The static exam includes evaluating the posture, stance, muscle tone and balance. Horses should stand square, hold their neck and back in a neutral, relaxed position and have good muscle tone without tension. Muscle tone without tension gives the body a smooth appearance. Sharp muscle definition is a sign of muscle tension. It is common to find muscle tension, asymmetry, atrophy and lack of development. Training and conditioning change both muscle tone and tension however, if a

90 Equine restriction is interfering with peripheral nerve function muscles cannot develop properly even with extensive training. When the restrictions are treated the muscles can quickly regain their normal mass. The equine neck and back are currently a hot topic of research and we are beginning to define normal and pathologic structure. On physical exam signs that can indicate cervical or thoracolumbar pain include; abnormal posture, muscle atrophy, changes in muscle tone and compensatory movement. Any deviation from square stance should be investigated. Obvious signs are standing with one front limb advanced, resting a hind limb or frequent weight shifting. More subtle signs may be standing with the front limbs slightly retracted, the hind limbs protracted, base wide or base narrow. Standing with the head elevated or with the limbs retracted can be a sign of cervical or back pain. Shifting weight in the hindlimbs can be bilateral limb pain, sacroiliac region pain or thoracolumbar pain. Changes in muscle mass or tone are common and may indicate restrictions or other issues of the vertebrae. In the upper cervical region, the capitis muscles may feel tense on palpation or be atrophied. A decrease in muscle mass of the paracervical muscles will allow the facets and transverse processes to be more evident. The muscle that is most obvious in the thoracolumbar region is the longissimus dorsi. Atrophy or lack of development is common. The longissimus lumborum can appear hypertrophied especially when the horse is starting to work in extreme collection but atrophy is most common. Atrophy or lack of development can also be seen in the middle gluteal and the vertebral heads of the biceps femoris, and semitendinosus with changes in the lumbar vertebrae and sacroiliac region. Asymmetry of the pelvis can cause performance issues and uneven gait. Compare the height of the tuber coxa, tuber sacrale and tuber ischium as well as the muscle mass of the left and right sides. Compensatory movement in the cervical region is easily seen in lateral bend. The horse should be able to bring the head caudal to the elbow at a neutral level without rotation. Horses that prematurely rotate are likely to have a cervical issue. Structural changes in the lower cervical facets are fairly common and increase with age. Because the facets are one of the borders of the IVF changes can cause nerve dysfunction. Humans with changes in the IVF often have pain, weakness, numbness or abnormal sensation in their hands and arms. In horses, we can see front limb lameness due to cervical issues. Compensation can be keeping the neck in extension or flexion rather than in a neutral position. Motion palpation is the cornerstone of a VMM exam and is the definitive way to diagnose a restriction. Restrictions can be at the end ranges of motion and can be subtle. Like any palpation technique practice and experience are important. Each restriction has a listing, which is a way of describing the restriction. The listing should include the bone, the reference point and the direction. For example, a T10 spinous right means that T5 spinous process is restricted to the right side and it does not have full ROM to the left. This restriction could interfere with turning to the right, saddle fit and potentially the longissimus mass or tone near the caudal aspect of the withers.

91 Equine Equine Complementary Therapy (Acupuncture and Spinal Manipulation) 3 Carla W Pasteur DVM CVA CVSMT CERP The VMM exam includes; history, static exam, dynamic exam and motion palpation. The dynamic exam is done at a walk. Movement of the axial skeleton is greatest at the walk. Horses stiffen the spine at a trot for more efficient energy transfer from the hind limbs. Stiffening the spine and the increased concussion make the trot the ideal gait to emphasize distal limb lameness but less than ideal for evaluating the axial skeleton. On a straight line at the walk the head and neck should move in a figure 8 pattern and equally to the left and right. Common abnormalities include; lack of movement to one side, holding the neck in one position only and carrying the head and neck stiff and extended. The pelvis should move not only up and down but also left and right. Lack of lateral pelvic excursion is often seen with restrictions of the lumbar, pelvis or sacrum. Horses may carry the hindquarters to one side. The hind feet should land in line with the front feet. If when watching the horse walk directly toward or away from you, you can see a hind foot land between the front feet or lateral to the front feet the horse is not moving in good alignment. The horse should be walked in a small circle, approximately 4 meters, left and right. They should walk forward in a circle not spinning around the front feet. We are looking for subtle changes in movement patterns. The most common problem seen with this test is that the horse circumducts, adducts or posts with the hind limbs. Abnormal movement of the hind limbs while circling can indicate musculoskeletal pain, weakness or poor proprioception without overt neurologic disease. The horse should be asked to back several steps and should keep the neck in a neutral ventroflexed position and take clear diagonal steps. Case 2: 2 year old Thoroughbred presented for hindquarter weakness. He has been treated with Marquis for the last 6 weeks with no improvement. Static Exam: Cranial nerve exam revealed atrophy of the masseter and temporalis on the left. Left upper eyelid was slightly drooping. Less muscle mass in right pectorals, right triceps, right longissimus dorsi, middle gluteal and hamstrings. Stance was irregular. Dynamic exam: Steps were irregular in length and hoof placement was irregular. He walked slowly and deliberately. On a circle, he abducted and abducted his hind limbs and posted on the hind limbs when asked to turn tightly. Backing was not observed. He was weak on dynamic sway test. Motion palpation: C5, C6, C7 body left, bilateral accessory carpals dorsal, sternum right, L2 and L3 spinous right, right PI ilium and sacral base ventral Acupuncture scan: reactivity at ST-10 left, BL20-24 bilateral, BL-28 right BL53/54 bilateral Tongue: pale and purple Pulse: wiry and weaker on the right Treatment: All restrictions found were adjusted. Acupuncture at BL-10, Jing-jia-ji at C3/4 thru C6/7 BL-62 SI-3, Qi-hai-shu, Shen-shu/jiao, Ba-jiao 4, BL-54, LIV-3 Electroacupuncture at Jingjia-ji cranial to caudal, Qi-hai-shu to Ba-jiao 4 at 20 Hz for 10 minutes. Plan: Continue Marquis and re-check in one week.

92 Equine The trainer felt he was stronger behind after the first treatment. He was placing his feet more accurately and was not as weak on dynamic sway. He was treated a second time and was able to continue training and progress normally. Case 3 5 year old QH mare with a history of intermittent lameness RF of one year duration. Exam done by attending veterinarian revealed moderate response to hoof testers over frog and heels of RF, negative flexion tests, inconclusive diagnostic analgesia in RF, moderate changes in RF navicular bone. Little to no response to shoeing changes or coffin joint injections. Static exam: Muscle tension lines throughout the cervical region worse on the right. Atrophy of the paraspinal muscles in the neck, longissimus dorsi bilaterally and the left middle gluteal. She stands with her hind feet protracted and her front feet close to midline. On dynamic exam she has a shortened cranial phase of stride on both front limbs, limited lateral motion of the head and neck, carries her neck slightly extended and circumducts the left hind on a right circle. When asked to step back she dragged her front limbs and lacked diagonal pairs. Restrictions found and adjusted: left TMJ dorsal compartment, right occiput ventral, C5 body left, C7 body left, left accessory carpal dorsal, T12 spinous left, left Posterior Inferior (PI) ilium. The restriction at C7 did not completely resolve. Acupuncture scan revealed reactive points at GB20, BL10, GB21 (hock or cervical), LI17/16, ST10 (lower cervical), BL20 23 (low back), BL54, Lu-gu (soft tissue hip). Acupuncture points needled were: Acupuncture treatment: BL10 for calming, Jing-jia-ji at C3/4 C4/5 and C5/6, SI3 for cervical pain and stiffness, Qian-ti-men for foot pain, Shen-shu and Yao-qian for back pain and to address potential bony issues. Electroacupuncture at Jing-jia-ji cranial to caudal and Yao-qian to Shen-shu. After the first treatment the lameness did not recur for two months. She presented 10 weeks after the first treatment and her exam was similar to the first exam but the signs were not as severe. She was treated again and again the C7 restriction did not fully resolve. One month later she was examined although she was not showing any clinical signs. The treatment was similar and the restriction at C7 was fully resolved after treatment. She was sound for the next three years and was lost to follow up.

93 Laser Therapy in Equine Practice Ronald J. Riegel DVM Introduction Laser therapy, now known as photobiomodulation therapy (PBMT), has been utilized in the equine industry since the late 1970 s. These initial therapeutic lasers emitted only 1mW of power and were used primarily for acupuncture point stimulation. Technological advances throughout the years have now made it possible to safely use therapeutic lasers emitting > 30 W. The ability to safely administer photonic energy utilizing higher levels of power, wavelengths within the therapeutic window, and at the correct dosage allows penetration to and saturation of the target tissues resulting in a physiological and biochemical cascade of events within these cells resulting in consistent therapeutic/clinical outcomes. Fundamental Information Until 2014, the nomenclature utilized within this modality was confusing and inconsistent. The first publication in 1968 used the description low power laser rays. Throughout the 1980 s up until just a few years ago inconsistent terminology was commonly used to describe the lighttissue interaction which results in a cellular physiological change. Biostiumulation, cool laser, cold laser, cold low-level laser, and soft laser terminology were proposed to distinguish this equipment from their surgical counterparts. In the early 1990 s the term low level-laser therapy (LLLT) was introduced. This term referenced the level of tissue reaction to the dose of light that it receives. Therefore LLLT, by definition, is the dose of light that is delivered to the cell below the level of the damage threshold of the cell and results in cellular photoactivation. Unfortunately, many of our colleagues in the veterinary profession interpret this as the power of the laser. It is the level of tissue reaction, not an indicator of the level of the power being emitted by the laser. All therapeutic lasers are low level-lasers regardless of the power. By 2016, the accurate and descriptive terms for the effective therapeutic application of light was finally adapted: photobiomodulation therapy (PBMT). Photobiomodulation (PBM) is the biochemical and physiological processes within the cell that result in an increase in cellular metabolism whereas, PBMT is the application of this non-thermal photonic stimulation to the cells. Learning point: Low level-laser therapy describes the dose of light delivered below the level of the damage threshold of the cell; not the level of power of the equipment. Photobiomodulaton therapy is the medically accepted nomenclature for the application of light to a cell that results in both photophysical and photobiochemical events that achieve a therapeutic outcome. There is further confusion, within our profession, by the non-standardized use of equipment parameters and treatment terms. An understanding of the following terms is essential to provide proper treatment.

94 Watt (W): Unit of power. Formula: W = J/time(t). Joule (J): Unit of work and energy. Formula: J = W x t. Dosage (J/cm 2 ): The radiant energy received by a surface per unit area. Formula: Dose = power (W) x time(seconds)/area of treatment (square centimeters) = joules per square centimeter(j/cm 2 ). The key to consistent clinical responses is the application of a sufficient number of joules (J) at a penetrating wavelength over a specific anatomical area (cm 2 ) to reach the target cells with enough energy to stimulate sufficient mitochondria resulting in a physiologic/ biochemical reaction resulting in a clinical response. Extrapolations made from the current research have resulted in the current recommended dosages. Application Recommended Dosage Wounds/dermal lesions 6 ± 4 J/cm 2 Superficial Structures (DDF, SDF) 12 ± 5 J/cm 2 Deep musculature 25 ± 10 J/cm 2 Joints 20 ± 5 J/cm 2 Large joints (stifle) 25 ± 5 J/cm 2 Unique applications: L/S, SI 30 ± 10 J/cm 2 Trigger Points 4 ± 2 J/cm 2 Acupuncture Points Superficial: J/point Deep: J/point PBMT initiates a biochemical cascade of events that clinically results in a reduction of pain, a modulation of the inflammatory reaction, and an increase in the microcirculation. These three events occur simultaneously and are well documented in the literature. The following charts simplifies these mechanisms of action.

95 Biochemical/Physiological Cascade of Events That Result in a Reduction of Pain PBMT Nitric oxide production Farvier, 2014 Beta endorphins Cidral-Filho 2014 Bradykinin levels Chow, R.T. and Barnsley, L Ion channel normalization Rosenbaum, T,PhD, et al Serotonin release Magalhaes 2015 Acetylcholine release Rochkind and Shainberg 2013 Blocked depolarization of C-Afferent Ohno T Tsuchiya K et al Wakabayashi, H., et al Action potential stabilization Rochkind S, et al Analgesia

96 Biochemical/Physiological Cascade of Events That Result in a Reduction of Acute Inflammation PBMT Cytochrome Activation ROS Production Proton Gradient Change Cell Membrane Changes ATP Increase Vasodilation IL-1 Decrease Ca, Na, K Ion Changes PG Synthesis Increase Leukocyte Activity Enhanced Lymphocyte Response Temperature Modulation Angiogenesis SOD Production Reduced Inflammation

97 Physiological Mechanisms Behind Tissue Healing PBMT Increased Leukocyte Activity Increased Macrophage Activity Increased Vascular Regeneration Increased Fibroblast Proliferation Early Cell Regeneration Enhanced Cell Differentiation Increased Tensile Strength Increased Collagen Reduced Healing Time General PBMT Therapeutic Protocols A complete and accurate diagnosis, including all secondary and tertiary involved compensatory structures, is crucial to the successful resolution of the disorder. In addition to the primary, secondary, and tertiary areas receiving treatment, photonic stimulation of the corresponding acupuncture points and trigger points related to the diagnosis completes this therapeutic strategy. Photonic administration should preferably made on-contact with the dermis. This is not always possible over wounds or extremely painful areas but should be the primary administration technique when possible. This on-contact technique provides the maximum amount of energy to enter the target tissues. Irrespective of administration being on or off-contact, the hand piece should always be perpendicular to the dermis to minimize the reflection of the energy and provide the highest power density possible through the treatment spot size.