Comparing microbiotas of foals and their mares' milk in the first two weeks after birth.

BACKGROUND: The mare-foal relationship is essential for the well-being and growth of a foal. Mare's milk provides a foal with nutrients, protective immunity, and microbes. Within the first two weeks of life, there is a risk for a foal to suffer from diarrhea, particularly "foal heat diarrhea" which happens at about the time of a mare's estrus cycle but is more likely due to transitions in the microbiota in the foal's gastrointestinal (GI) tract. We hypothesized that this GI microbiota transition could be caused by changes in lysozyme and microbial populations in the mare's milk. To test this hypothesis, fifteen mare-foal pairs were followed in the first 15 days post-foaling. Every other day milk was collected from mares and rectal swabs were collected from foals. Lysozyme activity in the mare's milk was measured using a fluorescence assay. Microbial DNA was isolated from the milk and swabs and the V4 domain of 16 S rRNA genes were PCR amplified and sequenced using Illumina MiSeq technology. Microbial populations were analyzed using DADA2 and phyloseq within R. RESULTS: Mare's milk lysozyme activity peaked for samples at Day 1 and levels dropped to 72.5% of Day 1 activity by Day 15; however, microbial populations in the mare's milk did not vary significantly over the two weeks. Furthermore, levels of microbial diversity found in foal rectal swabs were initially similar to microbial diversity seen in mare's milk; however, over the first fifteen days, diversity increased for the foal rectal swab microbiota and swab microbial populations differed from milk microbes. A transition occurred shifting from microbes from the phylum Proteobacteria early in rectal swabs to those primarily from the phyla Firmicutes and Bacteroidota after the first few days post-foaling. These phyla contained several families and genera of microbes that promote utilization of milk components in healthy gut transition. Microbial abundance levels correlated more with days post-parturition than with lysozyme activity and mare's milk microbial populations. CONCLUSIONS: The findings suggest that much of the microbial populations responsible for the transition of the foal's gut comes from sources outside of mare's milk species and levels of lysozyme activity.

Tetanus prophylaxis in horses: guidelines for New Zealand and Australia based on a critical appraisal of the evidence.

Horses are exquisitely sensitive to tetanus neurotoxin and are exposed to the risk of infection with Clostridium tetani throughout life. The vaccine against tetanus is highly effective at preventing disease, whereas tetanus in unvaccinated populations is associated with high mortality rates. Current guidelines in New Zealand and Australia for the available vaccine contain contradictions and limitations surrounding the optimal tetanus immunisation protocols for both adult horses and foals. This review critically evaluates the scientific literature on tetanus prophylaxis in horses within the context of equine practice and available products in New Zealand and Australia. The review was conducted by a panel of industry and specialist veterinarians to obtain agreement on nine equine tetanus prophylaxis guidelines for practising veterinarians. The primary protocol for tetanus toxoid (TT) immunisation consists of a three-dose series IM for all horses ≥ 6 months of age, and a four-dose series IM is proposed if commencing vaccination in foals between 3 and 6 months of age. Tetanus prophylaxis in foals < 3 months of age relies on passive immunity strategies. Following the completion of the primary protocol, a TT booster dose IM should be administered within 5 years, and every 5 years thereafter. When followed, these protocols should provide adequate protection against tetanus in horses. Additional tetanus prophylaxis guidelines are provided for veterinarians attending a horse experiencing a known "risk event" (e.g. wound, hoof abscess, surgery, umbilical infection). When a correctly vaccinated horse experiences a risk event, pre-existing immunity provides protection against tetanus. When an unvaccinated horse or one with unknown vaccination status, or a foal born to an unvaccinated dam, experiences a risk event, TT IM and tetanus antitoxin (TAT) 1,500 IU SC should be administered simultaneously at separate sites, and the TT primary immunisation protocol should subsequently be completed for the horse's respective age. In previously immunised pregnant broodmares, a TT booster dose administered 4-8 weeks prior to parturition optimises the transfer of passive immunity against tetanus to the newborn foal via colostrum; provided that post-natal IgG concentration in serum is > 800 mg/dL (8 g/L), such foals should be passively protected against tetanus up to 6 months of age. Survivors of clinical tetanus must still receive the primary protocol for vaccination against tetanus. In summary, all horses in New Zealand and Australia should be vaccinated against tetanus with protection maintained throughout life via TT booster doses, facilitated by accurate medical record keeping and client education.

Alloimmune Conditions in the Neonatal Foal.

Alloimmune disorders occur in foals when pregnant mares produce antibodies against antigens on the foal's cells or tissues, and concentrate them within colostrum. Once foals nurse and absorb colostral antibodies, they can develop hematologic or cutaneous manifestations that can occur individually or in combination. These include neonatal isoerythrolysis, a hemolytic anemia directed against factors on the foal's erythrocytes, alloimmune thrombocytopenia when the antibodies are directed against platelet antigens, alloimmune neutropenia when they are directed against neutrophil antigens, and a combination of suspected alloimmune ulcerative dermatitis, neutropenia and thrombocytopenia. Foals can also develop neutrophilic dermatitis which is suspected to be alloimmune.

The relationship between Th1/Th2 cytokine polarization and milk composition in the postnatal period in Kyrgyz mares and foals.

Immune compatibility between mare and foal is one of the important topics of reproductive immunology. At this point, although there are many studies on antibodies, there are not many publications on the relationship between the cytokine levels of mare, foal and milk and the effects of milk composition on this relationship. Here we investigate the relationship between Th1/Th2 cytokine balance and milk composition in Kyrgyz mares and foals. Samples were taken soon after the foal was born and on days 5, 10 and 20 after birth. Th1 (IFN-γ, IL-2, TNF-α) and Th2 (IL-4, IL-5, IL-10) cytokine levels in blood samples were measured using a commercial ELISA kit. Dry matter, fat, protein and non-fat dry matter ratios were determined in the mare's milk and colostrum. We detected no Th1/Th2 polarization in the mare's milk on the day of the foal's birth (day 0) and day 10, but there was Th1 polarization on day 5 and Th2 cytokine polarization on day 20. There was no polarization in the blood sera of the mares on days 0, 5, and 10, and Th1 cytokine polarization was also detected on day 20. We detected no Th1/Th2 cytokine polarization in the blood sera of the foals on any of the days. Dry matter (19.66 ± 0.39%), protein (16.56 ± 0.18%), fat (2.13 ± 0.17), and non-fat dry matter (17.59 ± 0.44%) were higher in colostrum than the other days. When the correlations between cytokine levels in milk samples and milk composition were examined, there was a positive correlation between IL-5 level and protein ratio on day 10. We detected a positive correlation between IL-2 level and the fat rate on day 20. There was a positive correlation between the IL-2 level and the non-fat dry matter ratio on day 20. Further studies are now needed to determine the relationship between the changes in the composition of mare's milk in the postnatal period and Th1/Th2 cytokine polarization in mares and foals at the time of birth and in the postnatal period. Our finding that protein and fat ratios in mare's milk in the postnatal period are positively correlated with IL-2 levels should be considered in terms of foal and human nutrition.

Equine Rotaviral Diarrhea.

Equine rotavirus is one of the most common causes of infectious diarrhea in foals. Although the infection itself is self-limiting, the resulting diarrhea is due to multiple mechanisms and can be severe, requiring supportive care including fluid and electrolyte support. Prompt diagnosis is important for treatment and biosecurity decisions and can be achieved by several means. Prevention, while imperfect, currently relies on vaccination of pregnant mares before parturition, ingestion of adequate colostrum from vaccinated mares and biosecurity measures.

Rhodococcus equi-What is New This Decade?

Foals become infected shortly after birth; most develop subclinical pneumonia and 20% to 30% develop clinical pneumonia that requires treatment. It is now well established that the combination of screening programs based on thoracic ultrasonography and treatment of subclinical foals with antimicrobials has led to the development of resistant Rhodococcus equi strains. Thus, targeted treatment programs are needed. Administration of R equi-specific hyperimmune plasma shortly after birth is beneficial as foals develop less severe pneumonia but does not seem to prevent infection. This article provides a summary of clinically relevant research published during this past decade.

Neonates and Periparturient Mares: Tips and Tricks for Diagnosis and Management.

Colic is a common presenting complaint in foals. Unfortunately, evaluation of foals with colic can be difficult due to the common clinical presentation of acute abdominal pain attributable to a wide variety of disorders and a broad range of etiologies. Similar to foals, colic is one of the most common diseases of pregnant and periparturient mares. Several conditions are unique or occur more commonly in broodmares. This article reviews the most commonly encountered types of colic events in neonatal foals and periparturient mares, how to correctly diagnose these conditions, as well as details concerning appropriate medical management and/or surgical intervention.

Plasma melatonin concentration during the early post-partum period in Thoroughbred mares and their foals.

The authors aimed to determine the plasma melatonin concentration in mares and their new-born foals in the early post-partum period. Blood samples were collected from the jugular vein of 53 mare-foal pairs within twelve hours after parturition. Plasma melatonin levels were measured by ELISA. The melatonin concentration, adjusted for the moment of parturition using a generalised linear model, was 34.58 pg mL-1 in mares. It was significantly lower (27.63 pg mL-1) in the new-born foals. However, the melatonin concentration declined differently by the end of the twelve hours, it decreased less in the offspring than in the mothers. An artificial light supplementation at the end of gestation reduced the melatonin concentration both in mares and their foals by about 10 pg mL-1, compared to the controls. An elevated melatonin production may be related to preparation of mares for parturition and ensures the chances of survival of offspring, therefore the melatonin may reach its peak at the moment of foaling regardless of its actual time. The effect of low melatonin concentration in new-born foals might be associated with the foal's health and subsequent performance. The need to monitor the melatonin concentration in the offspring justifies further studies.

Effects of different grains on bacterial diversity and enzyme activity associated with digestion of starch in the foal stomach.

BACKGROUND: Compared with the stomach of ruminant cattle, the stomach of horse is small and mainly for chemical digestion, but the microorganisms in the stomach play an important role in maintaining the homeostasis of the internal environment. Due to the complexity of the microbes in the stomach, little is known about the diversity and structure of bacteria in the equine stomach. Grains are the main energy source for plant-eating livestock and energy is derived through enzymatic hydrolysis of grains into glucose or their microbial fermentation into Volatile fatty acids (VFA). However, the mechanism through which these ingested grains are chemically digested as well as the effect of these grains on the stomach remains elusive. This study explored the effects of feeding different grains (corn, oats, and barley) on bacterial diversity, structure, and composition in the foal's stomach content. Furthermore, the effects of different grains on the vitality of starch digestion-related stomach enzymes were investigated. RESULTS: No significant differences were observed (P > 0.05) in the bacterial rarefaction curves of Operational Taxonomic Units (OTUs) and diversity of the stomach microbiota in all foals. This study also revealed the statistical differences for Firmicutes, Cyanobacteria, Actinobacteria, Fibrobacteres, Lactobacillaceae, Streptococcaceae, Unidentified_Clostridiales, Prevotellaceae, Lactobacillus, Streptococcus, Unidentified_Cyanobacteria, Unidentified_Clostridiales, Lactococcus, Sphingomonas, Lactobacillus_hayakitensis, Lactobacillus_equigenerosi, and Clostridium_perfringens. The linear discriminant analysis effect size analysis revealed 9 bacteria at each classification level. The functional analysis of species information by using FAPROTAX software was able to predict 35 functions, and the top 5 functions were chemoheterotrophy, fermentation, animal_parasites_or_symbionts, nitrate_reduction, and aerobic_chemoheterotrophy. The study also revealed statistical differences for pH, glucose concentration, ß-amylase, maltase, and amylase. CONCLUSIONS: The different grains had no significant effect on the microbial diversity of the stomach content of the foal. However, the relative bacterial abundances differed significantly in response to different diets. Particularly, oats fed to the foals significantly increased the relative abundance of Firmicutes, Lactobacillaceae, Lactobacillus, and Lactobacillus_hayakitensis. The grain had no significant effect on the pH of the stomach content, glucose concentration, and enzyme viability in the foal.

Surgical management of a Salter-Harris type I proximal physeal fracture of the tibia in a foal: a case report.

BACKGROUND: One of the traumatic fractures occurring in the hindlimb of the foals is physeal fractures of the tibia. The most common type of proximal tibial fracture in foals is reported to be Salter-Harris type II. CASE PRESENTATION: This case report describes the history, clinical signs, radiographic findings, and surgical management of a proximal physeal fracture of the tibia due to the kick trauma in a 2-weeks-old Kurdish female foal, with signs of left pelvic limb lameness, valgus deviation with non-weight-bearing, non-mobility in stifle region and crepitation in the affected area. In this case, radiography was utilized to confirm the fracture and detect the exact location of the fracture fragments. The Salter-Harris type I accompanied by tibial tuberosity fracture was diagnosed. In this case, a size 4.5 mm seven-hole, T-plate, and cortical bone screws were employed to fix the physeal fracture, and a cortical bone screw was utilized to fix the tibial tuberosity in the normal position. Case follow-up during two months showed no significant complications, and the patient was fully recovered (no lameness anymore). CONCLUSIONS: To our knowledge, this is the first report of Salter-Harris type I fracture in proximal tibia accompanied by tibial tuberosity fracture in a foal treated by a T-plate implant. A cortical screw in lag fashion for tibial tuberosity was utilized in this case for the first time, and the results were satisfying. T-Plate fixation can be recommended as an effective surgical treatment for proximal tibial fractures in foals.

Fetoplacental pathology of equine abortion, premature birth, and neonatal loss due to Chlamydia psittaci.

This report describes the fetoplacental pathology of Chlamydia psittaci-associated abortion, premature birth, and neonatal loss in 46 of 442 equine abortion investigations between 2015 and 2019. Seven abortions, 26 premature births, and 13 neonatal deaths with positive C. psittaci polymerase chain reaction (PCR) were evaluated. In 83% of cases (38/46), C. psittaci infection was considered as the primary cause of loss based on quantitative PCR (qPCR) confirmation, pathological findings, and exclusion of other causes, and was supported by Chlamydia spp immunolabeling in fetoplacental lesions. Lymphohistiocytic placentitis with vasculitis (36/38) affected the amnion, umbilical cord, and chorioallantois at the umbilical vessel insertion and/or cervical pole. Lymphohistiocytic chorionitis in the subvillous stroma extended to the allantois mostly without villous destruction. Lymphohistiocytic amnionitis and funisitis occurred at the amniotic cord attachment. Lymphohistiocytic hepatitis was observed in 19/38 cases and pneumonia was identified in 26 cases. Chlamydia spp immunolabeled in placenta, lung, liver, or splenic tissue in the cases that were tested (14/38). C. psittaci infection was not the cause of loss in 2 cases with other diseases and of uncertain significance in 6 cases with no conclusive cause of loss. immunohistochemistry (IHC) was negative for 6 of these cases (6/8). The highest Chlamydia load was detected in pooled placental tissues by qPCR. qPCR and IHC had 83% congruence at a qPCR cut-off of 1 gene copy. IHC limits of detection corresponded to infections with 2 × 102 gene copies identified by qPCR. This study confirms the etiological role of C. psittaci as a cause of naturally occurring equine reproductive loss.

Urinary Tract Disorders of Foals.

Urinary disease in the neonatal period can occur with primary congenital renal defects or as a secondary consequence of birth trauma, ischemic injury, nephrotoxic medications, or systemic illness. This article reviews the clinical evaluation of the urinary system in foals and highlights diagnostic and therapeutic features of the most commonly encountered urinary disorders of the equine neonatal patient.

Effects of steam-flaked grains on foals' growth and faecal microbiota.

BACKGROUND: There is little objective information concerning the effect of steam-flaked grains on foal's growth performance and faecal microbiota. To determine the effects of steam-flaked grains on foal's growth performance and faecal microbiota, faecal samples were collection from 18 foals which had been fed either corn, oat or barley diets over the 60 days of the experiment. Body weight and conformation measurements were collected. Next-generation sequencing of the V3 + V4 region of the 16 S rRNA gene was used to assess the microbial composition of faeces. Alpha diversity, Venn graph, Relative abundance and beta diversity are presented. RESULTS: There was a significantly higher larger increase in the body weight of those foals fed barley compared to either corn or oats. There were also significant changes in the Alpha diversity of the gut microbiota. The Shannon and Simpson indices were significantly higher in the barley fed group than those fed corn or oats. The Chao1 index was significantly higher in the oat fed group than the corn or barley fed groups. There were significant changes in the relative abundance of bacteria in the microbiota in terms of phylum, family and genus. The histogram of LDA value distribution showed that the 12 statistically different biomarkers of the bacteria were present. Tax4Fun function annotation clustering heat map showed that functional information was detected from 26 species of bacteria in faecal samples from the foals. CONCLUSIONS: Differences by starch sources were found in overall growth of the foals and in the faecal microbiota if either supplementary corn, oat or barley was fed. Further studies are required to determine the potential impact of the changes in the microbiota on the health and development of foals fed cereal starch of different sources.

Plasma disposition of ceftazidime in healthy neonatal foals following intravenous and intramuscular administration.

Cephalosporin antimicrobials can be utilized for the treatment of sepsis in neonatal foals, particularly when an aminoglycoside is contraindicated. Some cephalosporins, however, are not utilized because of cost, sporadic availability, or uncertainty about efficacy. The plasma disposition of ceftazidime, a third-generation cephalosporin with a broad spectrum of activity against a wide variety of gram-negative bacteria and minimal renal side effects has not been reported in neonatal foals. In this study, the plasma disposition of single intravenous (IV) and intramuscular (IM) doses of ceftazidime in neonatal foals was determined. Six healthy one to two-day-old foals were given 25 mg/kg of ceftazidime by IV and IM routes in a cross-over design, with a 48-h washout period between doses. Non-compartmental analysis was used to estimate plasma pharmacokinetic parameters. Median t1/2 was 2 h and median AUC0-last was 364 µg h/ml for both IV and IM administration. Median Cmax after IM administration was 101 µg/ml, with a median Tmax of 0.7 h. Relative bioavailability of IM injection was 90%. There were no statistically significant differences between estimated IV and IM pharmacokinetic parameters. Plasma concentrations remained above the human CLSI susceptible breakpoint for Enterobacteriaceae for over 8 h following IV and IM administration.

Effects of dietary fish oil and alpha-tocopherol supplementation on selected blood parameters and fatty acid profiles in mares and their foals.

The effects of fish oil (40 ml/day) supplementation, with or without synthetic all-rac-alpha-tocopherol-acetate (2,500 IU/day), during the last 65 days before expected parturition were investigated in 15 adult mares (553 ± 24 kg BW) and their foals. Mares were assigned to one of three diets: control (n = 5), control plus fish oil and alpha-tocopherol (n = 4; FO + AT) or control with just fish oil (n = 6; FO). Blood samples were obtained from the mares before a 15-day dietary adaptation period (T1) and from mares and foals the first (T2) and fifth (T3) days post-partum. Colostrum was collected at T2 and milk at T3. Routine haematological, biochemical and alpha-tocopherol analyses were undertaken on all blood samples. Fatty acid concentrations were determined in the foal serum and alpha-tocopherol concentrations measured in the milk and colostrum. Diet had no effect on haematology or biochemistry in the mares. Alpha-tocopherol concentrations were significantly higher at T2 & T3 in the FO + AT mares. Foal WBCs were higher in FO (11.33 ± 2.59 × 109 /l), comparing to FO + AT and control groups (9.18 ± 1.24 × 109 /l and 7.26 ± 1.03 × 109 /l, respectively), at T3 (p < .05). There was no significant effect of the fish oil supplementation on the foal's serum fatty acid profile. In the FO + AT group, both colostrum and milk alpha-tocopherol concentrations (2.56 ± 0.36 and 1.36 ± 0.22 µg/ml, respectively) were higher compared than those of the FO group (1.33 ± 0.39 and 0.72 ± 0.31 µg/ml, respectively; p < .05). Additional 2,500 IU/day of synthetic alpha-tocopherol in the last 65 days of pregnancy increased alpha-tocopherol concentrations in colostrum and milk and the foal's serum. 40 ml/day fish oil, however, did not significantly increase serum eicosapentaenoic acid and docosahexaenoic acid concentrations in the foals.

Emergency Management of Equid Foals in the Field.

Foal emergencies can be intimidating to manage in the field, yet many conditions will respond well to the supportive care possible on the farm. Triage of the foal targets focused supportive care to stabilize the foal before referral to a hospital or to facilitate the management in the field. There are many diagnostic and therapeutic options available in the field setting to support a successful outcome on the farm.

Arthroscopic guided repair of a slab fracture of the fourth carpal bone in an 8-month-old thoroughbred horse.

An 8-month-old thoroughbred colt presented with sudden onset right forelimb lameness. A radiographic series of the right carpus was performed, and it revealed a slab fracture of the fourth carpal bone and fracture of the proximal part of the third metacarpal bone. Arthroscopically guided repair of the slab fracture of the fourth carpal bone with a 3.5 mm cortex screw and lag screw fixation of the fracture of the proximal part of the third metacarpal bone were performed. The horse started to race at 32 months old and started in 65 races over three years without any trouble associated with the right carpus.

Equine rotavirus infection.

This review briefly describes the virus classification, clinical signs, epidemiology, diagnosis, disinfection, and vaccines related equine group A rotavirus (RVA) infection. Equine RVA is one of the most important pathogens causing diarrhoea in foals. The main transmission route is faecal-oral, and the clinical signs are diarrhoea, fever, lethargy, and anorexia (decreased suckling). Some human RVA rapid antigen detection kits based on the principles of the immunochromatographic assay are useful for the diagnosis of equine RVA infection. The kits are used in daily clinical practice because of their rapidity and ease of handling. Equine RVA is a non-enveloped virus and is more resistant to disinfectants than enveloped viruses such as equine influenza virus and equine herpesvirus. Although amphoteric soaps and quaternary ammonium compounds are commonly used in veterinary hygiene, they are generally ineffective against equine RVA. Alcohol products, aldehydes, and chlorine- and iodine-based compounds are effective against equine RVA. Inactivated vaccines have been used for equine RVA infection in some countries. Pregnant mares are intramuscularly inoculated with a vaccine, and thus their colostrum has abundant antibodies against RVA at the time of birth. According to G and P classification defined in accordance with the VP7 and VP4 genes, respectively, the predominant equine RVAs circulating in horse populations globally are G3P[12] and G14P[12] equine RVAs, but the vaccines contain only the G3P[12] equine RVA strain. Ideally, a G14P[12] equine RVA should be added as a vaccine strain to obtain a better vaccine effect.

Isolation and characterization of a rare group A rotavirus G13P[18] strain from a diarrhoeic foal in Japan.

A rare genotype G13P[18] group A rotavirus (RVA/Horse-tc/JPN/MK9/2019/G13P[18]) was isolated from a diarrhoeic foal for the first time in 28 years. The genotype constellation of the virus was assigned to G13-P[18]-I6-R9-C9-M6-A6-N9-T12-E14-H11 and was the same as that of the first isolated strain, RVA/Horse-tc/GBR/L338/1991/G13P[18]. Phylogenetic analysis suggests that the virus is related to RVA/Horse-tc/GBR/L338/1991/G13P[18] and is distant from typical equine rotaviruses of the G3P[12] and G14P[12] genotypes.

Morphine plasmatic concentration in a pregnant mare and its foal after long term epidural administration.

BACKGROUND: Epidural administration of morphine has been shown to be an effective analgesic strategy in horses; however, the possible occurrence of side effects limits its usage. In order to decrease their frequency, it is important to target the minimal effective plasma concentration and avoid overdosing. As to date species-specific pharmacokinetics data are not available for epidural morphine, the dosing regimen is usually established on the basis of clinical reports and personal experience. In certain physiological conditions, like gestation, the outcome of an empirical dosing scheme can be unpredictable. The aim of this case report is to describe the pharmacological profile of morphine and its metabolites after prolonged epidural administration in a pregnant mare and her foal. CASE PRESENTATION: A 20 years old pregnant mare was presented to our hospital because of severe lameness, 2 months before delivery. Following an ineffective systemic pain treatment, an epidural catheter was inserted and morphine administered (initial dose 0.1 mg/kg every 8 h). Due to its efficacy in controlling pain, it was continued until end of gestation. Plasmatic concentration of morphine and its metabolites were assessed in the mare 6 weeks after starting the treatment, and in both the mare and foal during the first days after delivery. Plasmatic values similar to those previously reported in the literature following morphine short term administration through various routes and not accompanied by side effects were found in the mare, except during an excitatory period. Moreover, no evidence of dangerous drug accumulation or significant milk passage was noticed in the foal. Mild reduction of feces production with no signs of colic and two self-limiting episodes of excitement occurred during treatment in the mare. No side effects occurred during gestation and first phases of life in the foal. CONCLUSION: Prolonged epidural administration of morphine in a pregnant mare allowed good pain control in absence of clinically relevant side effects, in both the mare and her foal. Sudden increase in morphine plasmatic concentration can occur and side effects appear; careful treatment to the lowest effective dose and continuous monitoring of the clinical condition of the treated horse should be performed.