Internal Medicine/Reproduction Proceedings 2015

Internal Medicine and Reproduction 2015 Program Proceedings

Seventh Annual Symposium From Our Practice to Yours

September 23rd - September 26th, 2015

Northeast Association of Equine Practitioners

1 NEAEP Mission Statement

The mission of the NEAEP is to improve the health and welfare of horses byproviding state- of-the-art professional education and supporting the economic security of the equine industry by complementing established local associations and giving equine veterinarians, farriers, technicians, veterinary students and horse owners a unified voice at the state and regional levels.

2 2015 Internal Medicine/Reproduction

Table of Contents

New Strategies For Managing Neonatal Maladjustment Syndrome. Peter R. Morresey...... 4

Update on Anaplasmosis – Made No Better by a Name Change. Peter R. Morresey...... 10

Head Shakers – Is There Anything New Under The Sun? Peter R. Morresey...... 14

Managing Strangles Outbreaks Ashley G. Boyle...... 21

Strangles- Unusual Cases and Effective Treatments Ashley G. Boyle...... 25

Diagnosis and Management of the Sick Foal in the Field Ashley G. Boyle...... 28

Treating Colitis In The Field. Rose D. Nolen-Walston...... 30

Clenbuterol – The Good, The Bad, And The Ugly Rose D. Nolen-Walston...... 37

Equine Blood Transfusion - What You Need To Know To Get The Job Done. Rose D. Nolen-Walston...... 41

Guttural Pouch Disease- More Than Strangles Rachel Gardner...... 46

New Thinking on Gastric Ulcer Diagnosis and Treatment Rachel Gardner...... 50

Evaluation and Management of the Recumbent Horse Rachel Gardner...... 54

Nonexertional Rhabdomyolysis Stephanie J. Valberg ...... 56

Exertional Rhabdomyolysis - Causes of Poor Performance Stephanie J. Valberg...... 65

Equine Genetic Diseases - Genetic Testing: What Is Available And When To Use It Stephanie J. Valberg...... 71

The Pleurals and the Peritoneals: Body Cavity Cytology Tracy Stokol...... 78

A Case-Based Approach to Equine Blood Tracy Stokol...... 83

The ABCs of Acid-Base Analysis or the View from the Eye of a Clinical Pathologist Tracy Stokol...... 96

Non-traditional therapies for endometritis: science or voodoo? Charles F. Scoggin...... 102

The impact of aging on fertility, pregnancy, and offspring vigor in broodmares Charles F. Scoggin...... 108

The benefit of routine monitoring and supplementation of progesterone in early pregnancy Charles F. Scoggin...... 114

Management of mares for breeding with frozen semen: pre- and post-insemination considerations for maximum fertility Kristina Lu...... 118 How to successfully integrate assisted reproductive techniques in your busy practice Kristina Lu...... 124 Diagnostic methods and interpretation for endometritis Kristina Lu...... 129

3 New Strategies For Managing Neonatal Maladjustment Syndrome. Peter R. Morresey BVSc MACVSc DipACT DipACVIM (LA) Rood and Riddle Equine Hospital, PO Box 12070, Lexington, KY 40580

Introduction Neonatal Maladjustment Syndrome, Hypoxic-Ischemic Encephalopathy, or Perinatal Asphyxia Syndrome: foals poorly adapted to extrauterine life have been categorized in many ways. Clinical manifestation can be subtle or profound. This talk will summarize current literature explaining what is happening in these foals, provide insights into the things we can change and those we can’t, and walk through the author’s approach to these cases.

Pathophysiology of Neonatal Maladjustment Syndrome Cerebral ischemia may result from systemic hypoxemia depressing myocardial performance. Reduced cerebral blood flow results in decreased delivery of oxygen and energy substrates to the brain resulting in a combined hypoxic-ischemic insult. Anaerobic metabolism depletes the brain’s stores of glucose and high energy phosphates (ATP and phosphocreatine) with resulting accumulation of lactate and inorganic phosphate. (Yager, 1992) Energy failure impairs glutamate uptake resulting in extracellular accumulation leading to tonic overstimulation of postsynaptic excitotoxic amino acid receptors (excitotoxicity). Reperfusion and reoxygenation in the early post-ischemic recovery period following this insult is itself harmful. Maternal infection has been shown strongly associated with neonatal brain injury. (Willough- by, Jr., 2002) Intrauterine infection may indirectly injure the brain via the induction of sepsis and poor perfusion, or directly by the production of inflammatory mediators that devitalize neurons. (Eklind, 2001) The neonatal brain has been experimentally shown as highly susceptible to free radical-mediated injury. (Edwards, 1997) Under normal conditions, mitochondrial function generates low concentrations of the superoxide anion and hydrogen peroxide. These are scavenged by multiple enzyme systems including superoxide dismutase, catalase, and glutathione peroxidase. Other nonenzymatic antioxidants include a-tocopherol (vitamin E) and ascorbic acid (vitamin C). During reperfusion following ischemia, oxygen free radicals react with membrane phospholipids to form oxidized lipids with pro-inflammatory actions. (Grow, 2002) Regardless of the inciting cause, neural injury results in increased release of neurotrans- mitters that in turn generates an excess of second messengers, apoptosis and increases in intracellular sodium and calcium. (Grow, 2002) Accumulation of sodium concurrent with failure of energy dependent cell membrane ion pumps (e.g. Na+-K+ ATPase) leads rapidly to cell swelling. Accumulation of calcium due to glutamate excess and mediated by NMDA receptors can lead to activation of calcium-dependent phospholipases, nitric oxide synthase, and proteases. Increased activation of phospholipase A2 (PLA2) in postsynaptic neurons results in increased free arachidonic acid and PAF, enhancing glutamate-mediated neurotransmission and further potentiating NMDA receptor activity, while decreasing glutamate reuptake. Cerebral ischemia induces cyc- lo-oxygenase-2 (COX-2) expression facilitating metabolism of arachidonic acid to inflammatory lipid mediators. A self-reinforcing cycle is therefore initiated. (Arundine, 2004;Bazan, 1995)

A number of equine neonatal studies have shown the presence of intracranial hemorrhage associated with neurological compromise. Compared to a control group, convulsive foals showed hemorrhage in various locations of the brain. (Palmer, 1975) Also present was necrosis of the

4 cerebral cortex, diencephalon and brain stem. Minimal hemorrhage occurred in the brains of control foals. In another study, central nervous system hemorrhage was found more frequently in premature foals when compared to those born at full term, in foals born dead compared to live births, and in foals born following assisted delivery compared to foals born without intervention.

Clinical presentation of Neonatal Maladjustment Syndrome The most common neurological problems of foals include depression, seizure activity, abnormal behavior, loss of affinity for the mare and loss of the suckle reflex. All these signs are referable to dysfunction of the brain. Expression of neurological lesions will be dependent on the stage of development which the inciting damage occurred. The result of cerebral hypoxic or ischemic insult to the neonate, NMS/HIE/PAS is arguably the most common seizure precipitating syndrome faced by the equine clinician. The diagnosis is dependent upon a compatible history and clinical examination findings while ruling out other conditions. (Green and Mayhew, I. G., 1990) Excitatory amino acids, calcium ions, free radicals, nitric oxide, pro-inflammatory cytokines and products of lipid peroxidation are all thought to contribute to the syndrome, with the neonatal brain having an increased susceptibility to damage by these agents compared to adults. (Anderson, 1988;Arango, 2006;Arundine, 2004) In addition to neurological manifestations respiratory compromise, renal insufficiency, and gastrointestinal ileus with or without mucosal compromise can occur. Aberrant pulmonary function can result in abnormal gas exchange, in particular decreased ventilation leading to retention of carbon dioxide. As a result, central depression and abnormal blood acid base balance may result. Renal compromise leads to electrolyte and fluid balance derangements. With the loss of normal gastrointestinal function, diarrhea and sepsis can result from intestinal bacterial over- growth.

Diagnostics in neurological conditions Complete blood count (CBC) and serum chemistry A CBC aids in the diagnosis of systemic infection that may have spread to the CNS. Serum chemistry assays major organ system function, chiefly liver (removal of blood borne toxins) and kidney (assessment of electrolyte homeostasis). Immunoglobulin G (IgG) levels following colostrum are a direct measure of immune sufficiency in the previously hypogammaglobulinemic neonatal foal. Blood gas evaluation assesses pulmonary gas exchange and acid-base status of the foal.

Cerebrospinal fluid (CSF) analysis Cytology and microbiological culture of the CSF aids diagnosis, antimicrobial selection and prognosis in suspected cases of meningitis. Total protein concentration, nucleated cell count and RBC count should be routinely performed. Where increased intracranial pressure is suspected aspiration of CSF should be avoided as herniation of the brain through the foramen magnum may occur.

Radiography, computed tomography (CT) and Magnetic resonance imaging (MRI) Congenital malformations, disruption of bony structures and deviation of neural tissue by trauma can be visualized with radiography and CT. Both plain and contrast radiographic studies are possible. Soft tissue masses, foci of infection or vascular disruption are more readily imaged with MRI.

5 Treatment goals Once a diagnosis of a neurological disorder has been made, the treatment plan should seek to achieve the following clinical goals: • Manage seizure episodes and any neurologic dysfunction • Restore cerebral perfusion and oxygenation if compromised • Control cerebral edema • Control cerebral inflammation • Provide metabolic requirements of the debilitated patient • Address concurrent physical injuries and medical conditions if present

• Manage seizure episodes and any neurologic dysfunction Drugs for seizure control readily accessible to the practicing equine veterinarian are limited. Therapeutic targets include glutamate accumulation, aberrant calcium fluxes due to excessive activation of the N-methyl-D-aspartate (NMDA) glutamate receptors, free radical formation, lipid peroxidation, and generation of arachidonic acid metabolites. (Lipton, 1994;Nilsson, 1996)

• Restore cerebral perfusion and oxygenation if compromised Fluid therapy In addition to meeting the metabolic needs of the patient, appropriate fluid therapy is essential to ensure adequate cerebral perfusion which may have been compromised by a cerebral insult. The brain controls its own perfusion rate and pressure despite fluctuations in arterial blood delivery by autoregulation, the loss of which has been reported after cerebral ischemia and reperfusion or traumatic brain injury. Systemic dehydration has not been shown to decrease existing cerebral edema, and a negative fluid balance has been proven to be detrimental to overall patient outcome. (Clifton, 2002) Supplemental oxygen An appropriate fluid balance maintains cerebral perfusion and oxygenation while avoiding increased intracranial pressure. In situations where cerebral insult has occurred, judicious use of supplemental oxygen may of further benefit as the avoidance of hypoxemia improves neurological outcome following traumatic brain injury. (Chesnut, 1993)

•Control cerebral edema Edema of the brain decreases perfusion and oxygenation, along with causing cerebral compression against bony confinement and further trauma. Edema may be due to disruption of the blood brain barrier (BBB), cellular disruption causing intracellular water collection, or osmotic imbalances between blood and tissue. Iatrogenic over-hydration potentiates CNS edema following cranial trauma and exacerbates pulmonary edema in recumbent patients (affecting ventilation and oxygenation). Current information suggests elevation of the head during recumbency pre- vents cerebral edema and improves survival, although the mainstay of edema control has tradi- tionally been the use of hyperosmolar agents. (Feldman, 1992)

•Control cerebral inflammation Non-steroidal anti-inflammatory drugs (NSAIDs) attenuate arachidonic acid metabolites that promote platelet aggregation, and facilitate inflammatory and immune reactions. Experimentally, COX inhibitors improve cerebral blood flow, decrease edema, protect COX-2–expressing neurons, and attenuate microglial activation.

6 Glucocorticoids are immunosuppressive, diminish upregulation of pro-inflammatory cytokines and reduce monocyte infiltration following cerebral ischemia. Glucocorticoids downregulate cytokine-mediated COX-2 expression by monocytes and astrocytes and inhibit phospholipase A2, attenuating release of arachidonic acid from the cell membrane. The use of glucocorticoids in cases of cerebral insult is controversial however benefit in cases of acute bacterial meningitis has been shown. (van de Beek, 2007)

• Address concurrent physical injuries and medical conditions if present Wounds, contusions and decubital ulceration require topical treatments and dressings, and if sufficiently extensive concurrent systemic antimicrobials to counter bacterial dissemination in the compromised neonate. Leg wraps will avoid distal limb edema and secondary limb injury. Head protection ‘bumpers’ minimize secondary neurologic injury from repeated cranial trauma in recumbent or seizing foals. Corneal ulceration secondary to abrasion or exposure keratitis can be prevented by regular application of ophthalmic lubricants. If recumbent, the foal requires a supportive bed and a means to cleanly eliminate body waste. Elevation of the head (up to 30 degrees) minimizes cerebral edema. Sedation of the seizing patient may be required to minimize self-trauma. Options are limited however a2 adrenergic agonists and benzodiazepines possess favorable qualities including the added benefit of muscle relaxation which decreases overall energy requirements. Contraindi- cated drugs include butorphanol (may increase CSF pressure) and acepromazine (lowers the seizure threshold).

• Neurosteroids: their function and role in NMS Recent developments in perinatal endocrinology have indicated that neurosteroids are inte- gral to the transition to extrauterine life (Diesch, 2013). These progestagen compounds cross the blood-brain barrier and have neuromodulatory effects, inducing a syndrome of depression compatible with NMS but in the absence of hypoxic-ischemic insult. This syndrome has been experimentally reproduced in healthy foals by the administration of allopregnanolone (Madigan, 2012). Treatment of the reversion to fetal consciousness has been reported by the use of a ‘squeeze technique’, whereby the foal is restrained by ropes applying pressure to the mid-thorax region for a time period sufficient to mimic vaginal delivery (Madigan and ALEMAN, M. R., 2014;Toth, 2012).

Reference List Anderson DK, Waters TR and Means ED. Pretreatment with alpha tocopherol enhances neurologic recovery after experimental spinal cord compression injury. J Neurotrauma 1988;5(1):61-7. Arango MF and Mejia-Mantilla JH. Magnesium for acute traumatic brain injury. Cochrane Database Syst Rev 2006;(4):CD005400. Arundine M and Tymianski M. Molecular mechanisms of glutamate-dependent neurodegeneration in ischemia and traumatic brain injury. Cell Mol Life Sci 2004;61(6):657-68. Bazan NG, Rodriguez de Turco EB and Allan G. Mediators of injury in neurotrauma: intracellular signal transduction and gene expression. J Neurotrauma 1995;12(5):791-814. Chesnut RM, Marshall LF, Klauber MR, et al. The role of secondary brain injury in determining outcome from severe head injury. J Trauma 1993;34(2):216-22. Clifton GL, Miller ER, Choi SC, et al. Fluid thresholds and outcome from severe brain injury. Crit Care Med 2002;30(4):739-45.

7 Diesch TJ and Mellor DJ. Birth transitions: Pathophysiology, the onset of consciousness and possible impli- cations for neonatal maladjustment syndrome in the foal. Equine Vet J 2013;45(6):656-60.

Edwards AD, Yue X, Cox P, et al. Apoptosis in the brains of infants suffering intrauterine cerebral injury. Pediatr Res 1997;42(5):684-9.

Eklind S, Mallard C, Leverin AL, et al. Bacterial endotoxin sensitizes the immature brain to hypoxic--isch- aemic injury. Eur J Neurosci 2001;13(6):1101-6.

Feldman Z, Kanter MJ, Robertson CS, et al. Effect of head elevation on intracranial pressure, cerebral perfusion pressure, and cerebral blood flow in head-injured patients. Journal of Neurosurgery 1992;76(2): 207-11.

Green S, Mayhew IG. Neurologic disorders. In: Koterba A, Drummond W, Kosch P, editors. Equine Clinical Neonatology. 1 ed. Philadelphia: Lea and Febiger; 1990. p. 496-530.

Grow J and Barks JD. Pathogenesis of hypoxic-ischemic cerebral injury in the term infant: current concepts. Clin Perinatol 2002;29(4):585-602.

Lipton SA and Rosenberg PA. Excitatory amino acids as a final common pathway for neurologic disorders. N Engl J Med 1994;330(9):613-22.

Madigan JE, Aleman MR, inventors. Methods of diagnosing and treating neonatal reversion to fetal consciousness. 2014; US 20140213563 A1.

Madigan JE, Haggett EF, Pickles KJ, et al. Allopregnanolone infusion induced neurobehavioural alterations in a neonatal foal: Is this a clue to the pathogenesis of neonatal maladjustment syndrome? Equine Vet J 2012;44:109-12.

Nilsson P, Laursen H, Hillered L, et al. Calcium movements in traumatic brain injury: the role of glutamate receptor-operated ion channels. J Cereb Blood Flow Metab 1996;16(2):262-70.

Palmer AC and Rossdale PD. Neuropathology of the convulsive foal syndrome. J Reprod Fertil Suppl 1975;(23):691-4.

Toth B, Aleman M, Brosnan RJ, et al. Evaluation of squeeze-induced somnolence in neonatal foals. American journal of veterinary research 2012;73(12):1881-9.

van de Beek D, de Gans J, McIntyre P, et al. Corticosteroids for acute bacterial meningitis. Cochrane Data- base Syst Rev 2007;(1):CD004405.

Willoughby RE, Jr. and Nelson KB. Chorioamnionitis and brain injury. Clin Perinatol 2002;29(4):603-21.

Yager JY, Brucklacher RM and Vannucci RC. Cerebral energy metabolism during hypoxia-ischemia and early recovery in immature rats. Am J Physiol 1992;262(3 Pt 2):H672-H677.

8 Sedation

Xylazine 0.02-1 mg/kg IV or IM Short acting, may promote seizures Detomidine 0.005-0.04 mg/kg IV or IM Long acting Anti-inflammatories Flunixin 0.5-1 mg/kg IV q12h Ketoprofen 1-2 mg/kg IV q12h Firocoxxib 0.1 mg/kg IV q24h Dimethyl sulfoxide 1 g/kg IV q12h Administer as 10% solution

Seizure control medications Diazepam 0.05-0.4 mg/kg IV Short-acting. Midazolam 0.2 mg/kg bolus IV Maintain with 0.1-0.2 mg/kg/h constant rate infusion. Phenobarbital 4-10 mg/kg IV over 15 min Long-acting. Maintain long term 5-10 mg/kg PO bid Pentobarbital 3-5 mg/kg IV May induce severe respiratory depression. Use only when non-re sponsive to other agents. Potassium bromide 10 mg/kg PO q 8 h. Useful adjunct therapy or may be used as the sole agent for long- term management.

Control cerebral edema Hypertonic saline Up to 7 ml/kg IV q12h IV as 3% solution Mannitol 1 mg/kg iv q12h IV as 20% solution

Miscellaneous Magnesium sulfate 0.05 mg/kg IV over 30 min. Control excitotoxic glutamate neurotransmitter cascade. Vitamin C 100 mg/kg IV q12h Anti-oxidant Vitamin E 10-20u/kg PO q24h Lipid peroxidation Thiamine 10 mg/kg iv q24h 9 Update on Anaplasmosis – Made No Better by a Name Change. Peter R. Morresey BVSc MACVSc DipACT DipACVIM (LA) Rood and Riddle Equine Hospital, PO Box 12070, Lexington, KY 40580

Introduction Formerly called equine granulocytic ehrlichiosis, anaplasmosis (Anaplasma phagocytophilum) is an infectious disease with a seasonal occurrence. While predominantly seen in northern California, cases have been reported in numerous states and other countries. The disease is known to be tick-borne and not transmissible between horses and humans although the same bacterial strains are responsible for the infection. This talk will summarize manifestation, diagnosis and treatment of this condition.

Epidemiology The first case of equine granulocytic anaplasmosis was described in California in 1969 (Grib- ble, 1969). Anaplasma phagocytophilum frequently infects horses in North America (Madi- gan, 2000) within the range of its tick vector (Ixodes sp). Areas include the northeast, midwest, northwest and southeast. Infection has also been documented in Canada, Scandinavia, Europe (Dzi-Ögiel, 2013), Great Britain, North Africa (M’ghirbi, 2012), and South America. A seasonal occurrence is noted: late fall through spring. As no effective transovarial transmission has been shown, a reservoir animal is necessary for the maintenance in nature (Woldehiwet, 2006). In California, knowledge of natural reservoirs of A. phagocytophilum is limited. Immature I. pacificus commonly feed on small reptiles and mammals, birds, deer and wild carnivore. Once adult, I. pacificus infests dogs, coyotes, horses, deer, wild mammals, several rodent species and cattle predominantly. Persistent bacteremia, particularly during the summer may facilitate maintenance reservoir of A. phagocytophilum in California. Detection of concurrent Bartonella henselae, Borrelia burgdorferi, and A. phagocytophilum infection of I. pacificus ticks has been demonstrated in California (Holden, 2006). In the eastern US, A. phagocytophilum has been documented in mice, chipmunks, and voles (Telford, 1996;Tyzzer, 1938;Walls, 1997), however the most significant reservoir forA. phagocytophilum is the white-footed mouse with a seroprevalence ranging between 1-50% (Nicholson, 1998;Telford, 1996). Severity of clinical disease of A. phagocytophilum varies widely between locations. In the United States, human disease manifestations are more severe when compared to disease in Eu- rope where it is relatively mild. However in the US cattle disease is rare yet cattle and sheep in Europe have significant signs of disease (Woldehiwet, 2006). Cross species reactivity occurs. Seroconversion in horses with the absence of disease has been documented following inoculation with the bovine variant of A. phagocytophilum (Pusterla, 1998). Experimental infection with the human adapted strain however caused clinical disease indistinguishable from natural infection in one study (Barlough, 1995), and was fatal to one horse in another study (Franzen, 2007). Persistence of A. phagocytophilum has been detected in the bloodstream of horses following experimental infection. This was unrelated to the occurrence of clinical disease, suggesting persistence may occur with natural infection during an acute outbreak (Franzen, 2009). Cyclic bacteremia has also been documented following experimental infection of lambs (Granquist, 2010).

10 Pathogenesis In the horse, A. phagocytophilum infection has an incubation period of approximately 10 days (range 1-3 weeks) post introduction via a tick-bite (Dzi-Ögiel, 2013). The pathogenesis of disease is poorly understood. Once inoculated through the dermis by the bite of a tick, lymphatic spread or dissemination via the bloodstream is likely. Thereafter cells of the lymphoreticular and hemopoietic systems are invaded leading to the characteristic clinical signs. Replication occurs within vacuoles of professional phagocytes. It is thought that following invasion of the liver, spleen, lungs and other organs, localized inflammatory reactions are initiated and inflammatory cell accumulation is promoted. Inflammatory mediators IL-1ß, TNF-a, and IL-8 are thought responsible (Kim, 2002). Pancytopenia is thought to result from peripheral sequestration, consumption and lysis of cellular blood constituents. Host immunological defense dysfunction or suppression appears to result from A. phagocytophilium infection. Affected horses can develop a wide range of opportunistic infections with bacteria, fungi and viruses. Both humoral and cell-mediated immunity are affected, with phago- cytic and migratory functional deficits present.

Clinical disease Clinical signs initially include fever (101.5-106°F) and mild depression. As disease progresses, fever becomes undulating (101.5-106°F). Anorexia may occur. Petechiation and ecchymoses can occur. Edema develops in the subcutaneous tissue and fascia. Regional vasculitis is common, with the limb subcutaneous tissue and fascia predominantly affected. This leads to reluctance to move. In many cases ataxia develops. Icterus is often seen. Cardiac arrhythmias (ventricular tachycardia and premature ventricular contractions) may be heard. A transient systolic heart murmur has been reported in experimentally infected horses, being ascribed to physiologic turbulence (Franzen, 2005;Madigan, 1993).

Subclinical infections are frequent, therefore many A. phagocytophilum infections are likely undetected, this being exacerbated by many of the symptoms appearing rather nonspecific for any particular disease (Madigan, 2000).

Severity of disease and duration of clinical signs appears age related. In adults, disease progresses with signs characteristic of disease: fever, anorexia, edema, reluctance to move and ataxia. Horses under 4 years of age develop milder disease with signs similar to older horses, while those under 1 year of age may present with only fever.

Neither laminitis nor abortion have been reported subsequent to A. phagocytophilium infection, in contrast to many differential diagnoses.

Differential diagnosis As the clinical signs of anaplasmosis are many and varied in the horse, a number of differential diagnoses need to be considered as they can result in more serious pathology should they not be ruled out by physical or laboratory examination: • Borreliosis: Lyme disease can also present with vague signs of fever, depression and lame- ness. Vector range is similar to anaplasmosis.

11 • Encephalitis (Equine viral encephalitides): Acute onset of high fever, ataxia and severe depression. • Purpura hemorrhagica: High fever, vasculitis, limb edema, petechiation and laminitis potential. • Equine infectious anemia: High fever, depression, anemia, and petechiation. • Equine viral arteritis: High fever, limb edema and depression. • Potomac Horse Fever (Neorickettsia risticii): Similar vector range. High fever and malaise, with diarrhea and usually profound leukopenia. Rapid onset of laminitis. • Equine protozoal myeloencephalitis Insidious or sometimes rapid onset of ataxia. • Equine herpesvirus-1: High fever, depression and ataxia. • West Nile virus: High fever, depression, muscle fasciculations and ataxia. • Liver disease: Icterus, moderate to severe depression, anorexia, weakness, ataxia, edema, hemorrhage, diarrhea and anemia. Leptospirosis: Fever, depression and multiple organ dysfunction may result.

Diagnosis Anaplasmosis presents with a range of non-specific signs, however fever, anemia, icterus, a reluctance to move and swollen legs are generally seen, and highly suggestive in areas known to be prone to infection. Laboratory findings include thrombocytopenia, anemia and leucopenia. These abnormalities have been shown both in natural and experimental infections (Bermann, 2002;Franzen, 2009;Reubel, 1998). The diagnosis is made by detection of typical inclusions (morulae) in neutrophil granulo- cytes and from EDTA-blood by PCR or later by antibody seroconversion with an IFA test. It can be detected in buffy coat blood smears early in the course of clinical infection and illness as morula in neutrophils, with increasing numbers visible in a Giemsa-stained blood smear after the first few days of pyrexia (peak ehrlichemia days 3-5). Between 0.5-16% of neutrophils may be affected, appearing 2.6±1.5 days post onset of fever (Franzen, 2005). Detection of A. phagocytophilum DNA by PCR of EDTA whole blood samples (EDTA blood) is consistently positive 2-3 days before appearance of clinical signs, and persists 4-9 days following resolution of clinical signs. The PCR has been shown to be much more sensitive than microscopic investigation (Franzen, 2005). This is especially useful both early and late in the course of infection where the number of morulae are low and make cytological diagnosis difficult. Serology is of marginal utility as in the acute phase of the infection horses are usually sero- negative (Franzen, 2005). Isolated serum samples do not differentiate between current or past infection. Experimentally, seroconversion has been demonstrated between 12-16 days post inoculation. Maximum IFA titers are found within 3-7 days subsequent to the onset of positivity (Franzen, 2005). A fourfold increase in titer confirms recent exposure. A positive IFAT persists for up to 300d post inoculation with the organism (Nyindo, 1978).

Treatment The administration of oxytetracycline (7mg/kg iv q 24h) is an effective treatment (Madigan, 1993), However, experimental infection has revealed some horses can make a full recovery without treatment (Franzen, 2009). This may account for the relatively high seropositivity re-

12 ported in European studies (Hansen, 2010;Passamonti, 2010). Seroprevalence between horses with or without likelihood of vector-borne diseases was similar, indicating subclinical infections were likely to be commonplace (Passamonti, 2010). Prognosis Complete recovery from clinical signs of disease, including neurological symptoms, occurs within 2 to 3 weeks of onset (Franzen, 2005;Madigan, 1993). Recovered horses are solidly immune for in excess of two years and are not believed to develop a carrier state. Persistence of infection has been suggested with some European strains, but further verification is required. Tick control measures are mandatory for control of disease. There is no vaccine.

Reference List

Barlough JE, Madigan JE, DeRock E, et al. Protection against Ehrlichia equi is conferred by prior infection with the human granulocytotropic Ehrlichia (HGE agent). J Clin Microbiol 1995;33(12):3333-4.

Bermann F, Davoust B, Fournier PE, et al. Ehrlichia equi (Anaplasma phagocytophila) infection in an adult horse in France. Vet Rec 2002;150(25):787-8.

Dzi-Ögiel B, Adaszek L, Kalinowski M, et al. Equine granulocytic anaplasmosis. Research in Veterinary Science 2013;95(2):316-20.

Franzen P, Aspan A, Egenvall A, et al. Acute clinical, hematologic, serologic, and polymerase chain reaction findings in horses experimentally infected with a European strain ofAnaplasma phagocytophilum. J Vet Intern Med 2005;19(2):232-9.

Franzen P, Aspan A, Egenvall A, et al. Molecular evidence for persistence of Anaplasma phagocytophilum in the absence of clinical abnormalities in horses after recovery from acute experimental infection. J Vet Intern Med 2009;23(3):636-42.

Franzen P, Berg AL, Aspan A, et al. Death of a horse infected experimentally with Anaplasma phagocytophilum. Vet Rec 2007;160(4):122-5.

Granquist EG, Bårdsen K, Bergström K, et al. Variant -and individual dependent nature of persistent Ana- plasma phagocytophilum infection. Acta Vet Scand 2010;52(1):25.

Gribble DH. Equine ehrlichiosis. J Am Vet Med Assoc 1969;155(2):462-9.

Hansen M, Christoffersen M, Thuesen L, et al. Seroprevalence of Borrelia burgdorferi sensu lato and Anaplasma phagocytophilum in Danish horses. Acta Vet Scand 2010;52(1):1-6.

Holden K, Boothby JT, Kasten RW, et al. Co-detection of Bartonella henselae, Borrelia burgdorferi, and Anaplasma phagocytophilum in Ixodes pacificus Ticks from California, USA. Vector-Borne and Zoonotic Diseases 2006;6(1):99-102.

Kim HY, Mott J, Zhi N, et al. Cytokine gene expression by peripheral blood leukocytes in horses experimentally infected with Anaplasma phagocytophila. Clinical and diagnostic laboratory immunology 2002;9(5):1079-84.

Head Shakers – Is There Anything New Under The Sun?

13 Head Shakers – Is There Anything New Under The Sun? Peter R. Morresey BVSc MACVSc DipACT DipACVIM (LA) Rood and Riddle Equine Hospital, PO Box 12070, Lexington, KY 40580

Introduction Head shaking in horses is a syndrome of many alleged causes and numerous touted treatments. It is a source of frustration to owners, trainers and veterinarians alike. Often a diagnosis of exclusion, a systematic and comprehensive work-up is necessary to eliminate treatable organic disease that may manifest as shaking of the head. Contemporary theories on pathophysiology, diagnostic approaches, and current treatment of head shaking are discussed. Signalment The mean age at onset (or recognition) of headshaking has been reported in various studies, both clinical and owner observational, as 7.3, 7.5, and 9 years (Lane, 1987;Madigan, 2001;Mills, 2002). Geldings in these studies were over-represented (63–78%) however breed predilection was detected. In the populations studied, many affected horses were acquired by the current owner in late autumn or winter when headshaking was not present or apparent to the new owner (Lane, 1987;Madigan, 2001). Clinical syndrome Headshaking syndrome is commonly seen during exercise, particularly at a trot when the head is held relatively stationary. However, it can also occur at rest or during other gaits. Affect- ed horses display a characteristic headshaking or head-tossing in a vertical plane. Other signs include snorting, rapid movements of the upper lip, nasal discharge, lacrimation, and rubbing or striking the nares or side of the face with a foreleg or fixed object. The majority of affected horses have a seasonal worsening of signs. Onset occurs in spring with signs continuing until late summer or autumn. This suggests photoperiod associated neuro- humoral changes, changes in temperature and humidity, allergen exposure or unknown environmental factors contribute to the onset of the headshaking syndrome. Pathophysiology of head shaking Shaking of the equine head can be associated with frustration or anticipation of activity. It is also a response to noxious stimuli – insects, poorly fitting tack and restraint. While there is a long list of potential causes of headshaking, many are not amenable to treatment. Those amenable to medical or surgical treatment in include temporohyoid osteoarthropathy, trigeminal neuralgia and allergic reactions. Other causes include hormonal imbalances and vascular changes. Temporohyoid osteoarthropathy (THO) Headshaking with or without deficits of the facial and/or vestibular nerves has been attributed to bony proliferation of the temporohyoid joint and proximal shaft of the stylohyoid bone. While some reports indicate an infectious etiology (recovery of bacteria via tympanocentesis or nec- ropsy (Blythe, 1997;Power, 1983), others have not (Naylor, 2010). The predilection for Quarter horses, Paints and Appaloosas also speaks against an infectious etiology. Affected horses are most commonly presented when neurological deficits develop. Bony proliferation leads to impingement of either or both of the facial and vestibular nerves in the area of the acoustic meatus. The onset of neurologic signs may be acute (vestibular ataxia, facial

14 nerve deficits), chronic (persistent corneal ulceration resulting from diminished tear production or blinking), or initially subtle but progressive (as with the onset of a head tilt, trouble with the bit, or difficulty chewing) (Blythe, 1997;Walker, 2002). Trigeminal neuralgia/neuropathy (TN) In the horse, TN triggers include bright light or sunshine (photic headshaking), touch, auditory and olfactory stimuli (Madigan, 1995;Madigan, 2001;Mills, 2002). Also, exercise-induced increases in airflow through the nasal passages, blood flow to nasal and turbinate mucosa, and maxillary arterial pulse profile (Newton, 2000). As a cause of headshaking, TN was first considered over a century ago (1899) following successful treatment by infraorbital neurectomy (Williams, 1899). Further supporting evidence has been provided more recently, as perineural anesthesia of branches of the trigeminal nerve has led to transient improvement, with lasting improvement reported following neurectomy, chemical sclerosis, or coil compression of the infraorbital or maxillary nerves (Mair, 1999;Mair, 1992;New- ton, 2000;Roberts, 2009;Roberts, 2013). Paralleling TN as a cause of headshaking in horses, TN in humans can cause a shooting or burning sensation across the face. The maxillary branch is most often affected with right-sided disease more prevalent (considered due to a narrower right foramen rotundum and foramen ovale through which the nerve passes). In people with classical TN (parallels idiopathic headshaking in horses) is partial demyelination of the trigeminal nerve is the only pathological finding, and is thought to be associated with vascular compression. It is considered that the resulting demyelination disturbs trigeminal nerve electrophysiology, resulting in ectopic electrical impulses that precipitate facial pain (Zakrzewska, 2002). Histopathology of trigeminal nerve, the ganglion and several branches from headshaking horses has not revealed demyelination or other pathology (Newton, 2001). However, increased excitability of the nerve has been demonstrated following stimulation of the trigeminal nerve in four horses with headshaking syndrome (Pickles, 2011b). Trigeminal ganglion infection with latent EHV-1 has been investigated as a cause of altered trigeminal nerve function. However, latent EHV-1 as detected by real-time PCR, was recovered from only one of eight geldings with headshaking syndrome (Aleman, 2012). Luteinizing hormone (LH) Headshaking syndrome is observed most frequently in geldings and displays a seasonal occurrence. Increased activity of gonadotropin releasing hormone (GnRH) leading to increased cir- culating concentrations of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), could lead to seasonal changes in trigeminal nerve excitability in affected geldings (Pickles, 2011a). However, GnRH vaccine was administered to geldings with headshaking syndrome decreased LH and FSH concentrations but did not ameliorate signs of headshaking (Pickles, 2011a). Allergy As headshaking has a seasonal prevalence, it has been hypothesized that headshaking syndrome may be initiated by allergic reactions (LANE, 1987). Cough (27% of cases evaluated) and excessive tracheal mucus (32% of horses examined by airway endoscopy) in keeping with recurrent airway obstruction (RAO or ‘heaves’). Allergic rhinitis associated with these conditions in humans, affecting up to 30% of adults and 40% of children, may trigger headshaking syndrome. Serous nasal secretions, congestion, sneezing, and airflow obstruction present in humans with allergic rhinitis can be associated with facial pain. However investigation in horses (nasal mucosal biopsies, gross and microscopic examination of the head and nasal passages), of headshakers

15 has not supported this hypothesis. Vasomotor rhinitis Non-allergic rhinopathy (vasomotor rhinitis) has been documented to cause headshaking syndrome (Lane, 1987;McGorum, 1990). Being non-seasonal and non-allergic in origin, it is considered that altered autonomic control of nasal mucosal blood flow and secretions precipitates the condition. With increased airflow during exercise, clinical signs that are indistinguishable from allergic rhinitis may develop. Vasoconstrictive drugs (i.e. decongestants) and intranasal corticosteroids can alleviate signs. Photic headshaking In humans, photic stimulation via the optic nerve leads to a tickling sensation in the nasal mucosa (Whitman, 1993). This may be the result of light stimulation of the optic nerves causing activation of the maxillary branch of the trigeminal nerve, or regional parasympathetic branches (Everett, 1964). It has been postulated that the photic trigger is present in some horses with headshaking similar to this human photic sneeze (Madigan, 1995). Clinical signs of photic headshakers are indistinguishable from those of non-photic headshakers (Madigan, 2001;Newton, 2000). This suggests multiple triggers activate the same final effector trigeminal response. Such stimuli include sound (metal sound, clap), eating (hard carrots, fibrous hay), and nasal mucosal stimulation via diagnostic nasal swabbing (Aleman, 2014).

Diagnosis History and characteristics of headshaking A detailed history should be taken from the owner. This can include management procedures, diet, exercise and environmental changes. When investigating idiopathic headshaking following exclusion of other diseases, the characteristic head motion (rapid downward motion of the nose followed by upward flinging of the head) should be present. Physical examination In addition to a complete general examination which includes the oral cavity, ophthalmic and otoscopic examinations are needed. Endoscopy of the upper airway, including the guttural pouches, and radiography of the head and throatlatch region are indicated. Computed tomography (CT) and magnetic resonance imaging (MRI) improve visualization of both bone and soft tissue. Local anesthesia of the infraorbital nerve Used as an aid to diagnosis but reported success is low. Infraorbital anesthesia with 2% mepivacaine improved 3/19, had no effect on 8/19, and worsened 8/19 horses (Mair, 1999). In another study only 1/8 horses improved and only by 50% however the volume of mepivacaine was lower (Newton, 2000). A higher volume of local anesthetic infiltration may however affect adjacent nerves. Bilateral anesthesia of the posterior ethmoidal nerve (maxillary nerve) improved 13/17 horses (Newton, 2000) and 23/27 horses (Roberts, 2013) with headshaking. However the location of the nerve requires an extended period for diffusion of the anesthetic to achieve a full effect (Aleman, 2014;Newton, 2000).

16 Treatment Headshaking may be a response to a noxious stimulus, whether physiological or behavioral. Removal of the source of discomfort or treatment of the underlying organic disease is necessary in all cases. However, since the etiology of idiopathic headshaking is unknown, there are no specific or demonstrably curative treatments currently. The basis of control is therefore management (where possible) and not cure. Currently reported treatments have a low success rate, and do not correct the underlying abnormal trigeminal neurophysiology. As some horses have been noted to go into spontaneous remission, it seems possible that the aberrant trigeminal nerve physiology and activity might be reversible. Ameliorating the disturbed nerve function appears to hold promise as the key to successful treatment. Environmental management to avoid established precipitating stimuli is central to control. This may involve riding at night or in low light situations, but this is impractical especially for competition horses. Nose nets and face masks have enjoyed some success, with up to 75% of owners reporting measurable improvement with appliances ranging from full coverage of the muzzle and lips, to coverage of only the nostrils and upper lip (Mills, 2003). Medication usage is commonplace, with a number of compounds reported to be at least par- tially effective in reducing severity of presentation (Table 1). As with all pharmaceutical usage, deleterious effects and tendency to overuse are of concern, as is violation of regulations relating to competition withdrawal times. Surgical approaches have been reported. Infraorbital neurectomy first appeared in the veterinary literature in the late 1800s (Williams, 1899). Response is minimal and a high post-surgical complication rate suggests this procedure is contraindicated (Mair, 1999). Chemical sclerosis of the posterior ethmoidal nerve similarly suffers from a lack of efficacy with a high rate of reoccur- rence reported (Newton, 2000). The placement of platinum coils to compress the caudal infraorbital nerve has been reported used in horses unresponsive to medical therapy, with up to 50% success achieved however multiple surgeries were required in some horses due to repeated re- occurrence of headshaking (Roberts, 2009;Roberts, 2013). Due to post-operative complications including increased severity of nose rubbing progressing to self-trauma, surgical interventions should be considered salvage procedures for horses non-responsive to other modalities and at risk of euthanasia.

17 Table 1

Treatment Dose/frequency Comments

Cyproheptadine 0.3mg/kg po q12h Moderate improvement. Lethargy

Carbamazepine 2-8mg/kg po q6h-q12h Moderate improvement. (may be used in combination Unpredictable efficacy with cyproheptadine).

Hydroxyzine 1mg/kg po q12h Moderate improvement.

Fluphenazine 50mg im. Repeat 1-4 monthly Neurological dysfunction.

Phenobarbital 3-6mg/kg po q12h Calmative. Sedation.

Gabapentin 5-20 mg/kg po q12h-q24h Anecdotal reports, variable.

Corticosteroids Standard dosage, also Variable success pulse therapy reported.

Magnesium Variable Calmative.

Melatonin 15-18mg po q24h Dose 5pm. Altered hair shedding.

Sodium cromoglycate eye drops Apply OU q6h Seasonal head shakers.

Adapted from: (Madigan, 2001) (Mair, 1999) (Madigan, 1995) (Newton, 2000) (Pickles, 2014) (Stalin, 2008) (Tomlinson, 2013)

Reference List

Aleman M, Pickles KJ, Simonek G, et al. Latent Equine Herpesvirus-1 in Trigeminal Ganglia and Equine Idiopathic Headshaking. J Vet Intern Med 2012;26(1):192-4.

18 Aleman M, Rhodes D, Williams DC, et al. Sensory Evoked Potentials of the Trigeminal Nerve for the Diag- nosis of Idiopathic Headshaking in a Horse. J Vet Intern Med 2014;28(1):250-3.

Blythe LL. Otitis media and interna and temporohyoid osteoarthropathy. The Veterinary clinics of North America Equine practice 1997;13(1):21-42.

Everett HC. Sneezing in response to light. Neurology 1964;14(5):483.

Lane JG and Mair TS. Observations on headshaking in the horse. Equine Vet J 1987;19(4):331-6.

Madigan JE, Kortz G, Murphy C, et al. Photic headshaking in the horse: 7 cases. Equine Vet J 1995;27(4):306- 11.

Madigan JE and Bell SA. Owner survey of headshaking in horses. Journal of the American Veterinary Medical Association 2001;219(3):334-7.

Mair TS. Assessment of bilateral infra-orbital nerve blockade and bilateral infra-orbital neurectomy in the investigation and treatment of idiopathic headshaking. Equine Vet J 1999;31(3):262-4.

Mair TS, Howarth S and Lane JG. Evaluation of some prophylactic therapies for the idiopathic headshaker syndrome. Equine Vet J 1992;24(S11):10-2.

McGorum BC and Dixon PM. Vasomotor rhinitis with headshaking in a pony. Equine Vet J 1990;22(3):220-2.

Mills DS, Cook S, Taylor K, et al. Analysis of the variations in clinical signs shown by 254 cases of equine headshaking. The Veterinary record 2002;150(8):236-40.

Mills DS and Taylor K. Field study of the efficacy of three types of nose net for the treatment of headshaking in horses. The Veterinary record 2003;152(2):41-4.

Naylor RJ, Perkins JD, Allen S, et al. Histopathology and computed tomography of age-associated degeneration of the equine temporohyoid joint. Equine Vet J 2010;42(5):425-30.

Newton SA. The fuctional anatomy of the trigeminal nerve of the horse University of Liverpool; 2001.

Newton SA, Knottenbelt DC and Eldridge PR. Headshaking in horses: possible aetiopathogenesis suggested by the results of diagnostic tests and several treatment regimes used in 20 cases. Equine Vet J 2000;32(3):208-16.

Pickles KJ, Berger J, Davies R, et al. Use of a gonadotrophin-releasing hormone vaccine in headshaking horses. Veterinary Record 2011a;168(1):19.

Pickles KJ, Gibson TJ, Johnson CB, et al. Preliminary investigation of somatosensory evoked potentials in equine headshaking. The Veterinary record 2011b;168(19):511.

Pickles K, Madigan J and Aleman M. Idiopathic headshaking: Is it still idiopathic? The Veterinary Journal 2014;201(1):21-30.

Power HT, Watrous BJ and de Lahunta A. Facial and vestibulocochlear nerve disease in six horses. Journal of the American Veterinary Medical Association 1983;183(10):1076-80.

Roberts VLH, Mckane SA, Williams A, et al. Caudal compression of the infraorbital nerve: A novel surgical technique for treatment of idiopathic headshaking and assessment of its efficacy in 24 horses. Equine Vet J 2009;41(2):165-70.

19 Roberts VLH, Perkins JD, Skärlina E, et al. Caudal anaesthesia of the infraorbital nerve for diagnosis of idiopathic headshaking and caudal compression of the infraorbital nerve for its treatment, in 58 horses. Equine Vet J 2013;45(1):107-10.

Stalin CE, Boydell IP and Pike RE. Treatment of seasonal headshaking in three horses with sodium cromoglycate eye drops. The Veterinary record 2008;163(10):305-6.

Tomlinson JE, Neff P, Boston RC, et al. Treatment of Idiopathic Headshaking in Horses with Pulsed High-Dose Dexamethasone. J Vet Intern Med 2013;27(6):1551-4.

Walker AM, Sellon DC, Comelisse CJ, et al. Temporohyoid Osteoarthropathy in 33 Horses (1993-2000). J Vet Intern Med 2002;16(6):697-703.

Whitman BW and Packer RJ. The photic sneeze reflex Literature review and discussion. Neurology 1993;43(5):868.

Williams LW. Involuntary shaking of the head and its treatment by trifacial neurectomy. American Veterinary Review 1899;23:321-6.

Zakrzewska JM. Diagnosis and Differential Diagnosis of Trigeminal Neuralgia. The Clinical Journal of Pain 2002;18(1).

20 Managing Strangles Outbreaks Ashley G. Boyle, DVM, DACVIM Assistant Professor of Medicine, Section Field Service Department of Clinical Studies, New Bolton Center, University of Pennsylvania 382 West Street Rd. Kennett Square, PA [email protected] Pathophysiology

S. equi subsp equi is inhaled or ingested after direct contact with mucopurulent discharge from infected horses or contaminated equipment. The bacterium attaches to the crypts and epithelium of the lingual and palatine tonsils. The organism enters the mandibular and pharyngeal lymph nodes. Clinical signs develop 3 to 14 days after exposure. 1,2 Clinical Signs

The first clinical sign of strangles is acute-onset fever (often >103°F), followed by lethargy, depression, bilateral mucopurulent nasal discharge, lymphadenopathy, and abscessation of the retropharyngeal and mandibular lymph nodes. Occasionally, the parotid and cranial cervical lymph nodes are affected. Retropharyngeal lymph node enlargement can lead to narrowing of the pharynx, resulting in upper respiratory noise, dysphagia, and neck extension. Empyema results when the retropharyngeal lymph nodes drain pus into the guttural pouches. Horses may develop respiratory distress due to retropharyngeal abscesses that are not externally mature. Clinical signs are more severe in immunologically naïve (1 through 5 years of age), geriatric (older than 20 years), and immunocompromised horses.1,2,3 Some horses may develop complications such as metastatic abscessation, purpura hemorrhagica, and myositis. Transmission

Shedding of S. equi subsp equi begins 2 to 3 days after onset of fever. In most cases, shedding persists for a minimum of 2 to 3 weeks. Horses that have recovered from strangles have been shown to shed for an additional 6 weeks.1 If organisms are harbored in the guttural pouches, horses have been shown to shed S. equi subsp equi for up to 2.5 years. These outwardly healthy horses (i.e., carriers) that still shed organisms are a source of infection when introduced into a new population of horses.6,7,8 Transmission occurs through nose-to-nose contact; proximity; equipment (e.g., water buckets, feed buckets, tack, twitches); clothing; and equipment of owners, caretakers, farriers, and veterinarians.1 Under laboratory conditions, S. equi subsp equi has been shown to persist on wood for 63 days at 35.6°F and for 48 days on glass and wood at 68°F.9 One study modeling field conditions revealed that the organism was found to persist for less than 4 days, 23 but moist environments (e.g., water buckets) allow the organism to persist for extended periods.1,2 Seventy-five percent of horses that have been infected with S. equi subsp equi and have not been treated with antimicrobials develop lasting immunity for approximately 5 years or longer. 1,2,10,11 Diagnostic Testing

Early definitive diagnosis is essential for containing this highly infectious disease. Cytologic evaluation reveals gram-positive extracellular cocci in long chains supports a diagnosis of a ß-hemo-

21 lytic streptococcus organism. Historically, the gold standard for diagnosis is bacterial culture of abscess aspirates, nasopharyngeal swabs, nasopharyngeal revealing S. equi subsp equi. This is the preferred method on aspirates of mature abscesses, but takes a minimum of 24 hours to ob- tain results. In our clinical practice, we now use polymerase chain reaction (PCR) testing to detect the DNA of the organism as the gold standard which can also be performed on nasopharyngeal swab, nasopharyngeal wash, and guttural pouch wash samples.1 Nasopharyngeal washes are preferable to nasopharyngeal swabs due to a larger sampling area, but guttural pouch sampling is the most reliable, although more expensive and requires specialized equipment. PCR testing is more sensitive than bacterial culture22 and should always be used in combination. Treatment

The goal of treating strangles is to control transmission and eliminate infection while providing future immunity to the disease. Uncomplicated cases of strangles are often left to run their course with supportive care, providing lasting immunity. Affected horses should be isolated in a clean, dry stall and fed moist, palatable food. NSAIDs should be used judiciously to decrease swelling and promote eating. Hot compresses or topical 20% ichthammol can be used to accelerate maturation of abscessation. Mature external abscesses should be lanced to allow drainage, followed by daily lavage of open abscesses using dilute povidone iodine solution. This speeds resolution of abscessation as well as alleviation of compression of the pharynx. 2 Methods Of Outbreak Control

Most outbreaks are thought to originate from introduction of an infected horse to a naïve population. All new horses should be isolated for 3 weeks and monitored for any signs of disease, including fever. If cost is not prohibitive, horses should be screened for S. equi subsp equi infection using nasopharyngeal washes. Many farms with repeated infections have resorted to screening for infection via endoscopic evaluation and PCR testing of guttural pouch lavages. The Animal Health Trust in the United Kingdom recently developed a new serologic test that detects antigens differ- ently than the SeM ELISA. This new test appears to be more sensitive for detecting animals with recent exposure (as little as 2 weeks) to S. equi subsp equi and has been used as a screening tool to determine who needs endoscopic examinations upon arrival to a farm during quarantine prior to introduction into the herd. However, this test is currently not available in the United States and there is no way to distinguish vaccinated animals from recently exposed animals.15

Once an outbreak has occurred, twice-daily monitoring of rectal temperatures of all horses on the farm is essential to contain the outbreak. Because febrile horses do not shed disease for the initial 2 days, immediate identification of febrile horses enables caretakers to isolate these horses before shedding occurs. All movement of horses to and from the farm should be stopped until they are determined to be noninfectious. All equipment (e.g., pitchforks, buckets, grooming tools) for an affected horse should be isolated and used only for that horse. Personnel handling infected horses should wear barrier precautions (i.e., gowns, gloves, plastic boots that cover shoes) and, ideally, should not handle noninfected horses or should handle infected horses last. Water buckets should be disinfected daily. 1,8 Facilities and equipment should be cleaned first to remove all organic material and then disinfected with phenols, iodophors, or chlorhexidine compounds or steam cleaned. 1,9 Surfaces and equipment must be allowed to dry thoroughly. Paddocks that hold infected horses should be rested for 4 weeks. A minimum of two weeks after all cases of strangles have resolved, one guttural pouch lavage along with an endoscopic examination for empyema

22 or chondroids should be obtained from convalescing horses and their contacts at approximately weekly intervals and tested for S. equi subsp equi via PCR to detect carriers. This is preferable to the previously recommended three nasopharyngeal washes. Horses have been found positive in their guttural pouches despite three negative nasopharyngeal washes. 16 A series of 3 nasopharyngeal swabs, collected 1 week apart, will result in detection by a positive culture on at least one of the swabs in approximately 60% of carrier animals. Concurrent testing of these swabs by PCR increases the likelihood of detection to over 90% of carrier animals. 15 For the purpose of efficien- cy, I recommend treating each guttural pouch with penicillin at the time of endoscopic examination unless there is gross contamination of the guttural pouch which would require aggressive lavage. A minimum of three weeks should be waited prior to retesting a treated, previously positive guttural pouch via PCR . The percentage of carriers per outbreak could be as high as 10%.1,8, 12,17,18 It is important to remember that SeM ELISA does not detect carrier status.19

The use of vaccination during an outbreak is controversial. The 2005 ACVIM Consensus State- ment recommends that live vaccine should be administered only to healthy animals with no known exposure to infected horses during an outbreak, but no published data show that use during an outbreak is detrimental.1 The AAEP Infectious Disease Committee does not recommend vaccination during an outbreak.13 It is suggested that horses recovering from infection should not be vaccinated for 1-2 years. 20

Eradication of this disease will not be possible until the subpopulation of carriers is eliminated and the development of new vaccines that distinguish vaccinates from exposed are available. 21

REFERENCES

1. Sweeney CR, Timoney JF, Newton JR, Hines MT. Streptococcus equi infections in horses: guidelines for treatment, control, and prevention of strangles. J Vet Intern Med 2005:19:123-134.

2. Boyle AG. Streptococcus equi subspecies equi Infection (Strangles) in horses. Compendium Continuing Education for the Practicing Veterinarian 2011; 33:online.

3. Sweeney CR, Benson CE, Whitlock RH, et al. Description of an epizootic and persistence of Streptococ- cus equi infections in horses. JAVMA 1989;9:1281-1286.

4. Ford J, Lokai MD. Complications of Streptococcus equi infection. Equine Pract 1980;4:41-44.

5. Radostits OM, Gay CC, Blood DC, et al. Purpura hemorrhagica. In: Veterinary Medicine: A Textbook of the Diseases of Cattle, Sheep, Pigs, Goats and Horses. 8th ed. London: Balliere Tindall; 1999:1713-1714.

6. Carlson GP. Diseases of the hematopoietic and hemolymphatic systems. In: Smith BP, ed. Large Animal Internal Medicine. 3rd ed. St. Louis: CV Mosby; 2002:1043.

7. Galan JE, Timoney JF. Immune complexes in purpura hemorrhagica of the horse contain IgA and M antigen of Streptococcus equi. J Immunol 1985;135:3134-3137.

8. Newton JR, Verheyen K, Talbot NC, et al. Control of strangles outbreaks by isolation of guttural pouch carriers identified using PCR and culture of Streptococcus equi. Equine etV J 2000;32:515-526.

9. Jorm LR. Laboratory studies on the survival of Streptococcus equi on surfaces. In: Plowright W, Ross- dale PD, Wade JF, eds. Proceedings of Equine infectious Diseases VI. Newmarket, UK: R & W Publica-

23 tions;1992:39-43.

10. Pusterla N, Watson JL, Affolter VK, et al. Purpura haemorrhagica in 53 horses. Vet Rec 2003;153:118- 121.

11. Freeman DE. Diagnosis and treatment of diseases of the guttural pouch (part 2). Compend Contin Educ Pract Vet 1980;2:S25-S31.

12. Newton JR, Wood JN, Dunn KA, et al. Naturally occurring persistent and asymptomatic infection of the guttural pouches of horses with Streptococcus equi. Vet Rec 1997;140:84-90.

13. AAEP. Strangles (Streptococcus equi). Accessed June 2009 at www.aaep.org/strangles.htm.

14. Waller A, Robinson C, Newton JR. Further thoughts on the eradication of strangles in equids. JAVMA 2007;231:1335.

15. http://www.aht.org.uk/cms-display/bact_bloodadvice.html Accessed January 2012.

16. Getting a grip on Strangles, Havermeyer Workshop, October 2012.

17. Newton JR, Wood JN, Dunn KA, et al. Naturally occurring persistent and asymptomatic infection of the guttural

pouches of horses with Streptococcus equi. Vet Rec 1997;140:84-90.

18. Verheyen K, Newton JR, Talbot NC, et al. Elimination of guttural pouch infection and inflammation in asymptomatic carriers of Streptococcus equi. Equine Vet J 2000;32:527-532.

19. Davidson A, Traub-Dargatz JL, Magnuson R, et al. Lack of correlation between antibody titers to fibrinogen binding protein of Streptococcus equi and persistent carriers of strangles. JVet Diagn Invest 2008;20:457-462.

20. Wilson JH. Vaccine efficacy and controversies. Proc 51st Annu Meet AAEP 2005;409-420.

21. Waller A, Robinson C, Newton JR. Further thoughts on the eradication of strangles in equids. JAVMA 2007;231:1335.

22. Boyle, AG, Boston RC, O’Shea K, Young S, Rankin SC, Optimization of an in vitro assay to detect Strep- tococcus equi subsp. equi. Vet. Microbiol. 159: 406-410, 2012.

23. Weese JS, Jarlot C, Morley PS, Survival of Streptococcus equi on surfaces in an outdoor environment. Can Vet J. 2009 Sep;50(9):968-70.

24. Boyle AG et al. J Am Vet Med Assoc 2009;235: 973.

24 Strangles- Unusual Cases and Effective Treatments Ashley G. Boyle, DVM, DACVIM Assistant Professor of Medicine, Section Field Service Department of Clinical Studies, New Bolton Center, University of Pennsylvania 382 West Street Rd. Kennett Square, PA [email protected] Usual Abscess Locations

S. equi subsp equi can infect any lymph node including and limited to periocular resulting in S. equi positive ocular discharge, parotid lymph nodes, and suprascapular. Bastard Strangles (Metastatic Abscessation)

In as many as 20% of cases, S. equi subsp equi spreads via hematogenous or lymphatic spread. This results in metastatic abscessation which can affect any organ system. Aspiration of mucopurulent discharge or hematogenous or lymphatic spread to the lungs can cause pneumonia. Abscessation in the mesentery, liver, spleen, and kidneys is common, leading to peritonitis and clinical signs of colic. Abscessation of the cranial mediastinal lymph nodes can cause tracheal compression and respiratory distress. Neurologic signs are present when abscessation occurs in the brain.1 The mortality rate of horses with strangles is less than 2%, but the presence of bastard strangles increases the mortality rate to as high as 62%. 2,4 Purpura Hemorrhagica

Purpura hemorrhagica is an aseptic necrotizing vasculitis that can occur in mature horses after repeated natural exposure to infection or after vaccination of horses that have had strangles.1,5,6,7 The actual incidence of this type III hypersensitivity response secondary to strangles or vaccination is unknown. 1,2 Clinical signs range from mild to life-threatening, including pitting edema of the head, trunk, and distal limbs as well as petechiae and ecchymoses. In some cases, antigen– antibody complexes affect other sites, including the gastrointestinal tract, muscles, lungs, and kidneys. 1,2,4,5 Guttural Pouch Empyema And Carriers

Carriers can appear outwardly healthy but harbor S. equi subsp equi in their guttural pouches. De- finitive determination of carrier status requires endoscopic examination of the guttural pouches as well as culture and PCR testing of guttural pouch lavage fluid. 1,2,7,8 Often, if there is no external abscessation, there will be internal abscessation of the retropharyngeal lymph nodes. This can recognized early by painful palpation of the throat latch region and squeezing the trachea. These horses are at high risk for rupture into the guttural pouch and asphyxiation and often require pre- sentative tracheostomies. Any horse with guttural pouch empyema is also at risk for aspiration pneumonia. Serologic Testing

Serologic testing involves the use of ELISA to detect the SeM protein. Serology is useful for detecting recent, but not current, infection; assessing the need for vaccination; identifying horses that may be predisposed to purpura hemorrhagica; and diagnosing S. equi subsp equi–associat-

25 ed purpura hemorrhagica and metastatic abscessation.1,2,6

Various authors have suggested that horses with high serum SeM-specific antibody titers may be predisposed to developing purpura hemorrhagica when vaccinated against S equi.1 A 2009 study24 identified factors associated with an increased likelihood that horses would have SeM-specific antibody titers ≥ 1:1,600. Results indicated that older horses, horses other than Thorough- breds and Warmbloods, and horses that had been vaccinated with an attenuated-live intranasal S equi vaccine between 1 and 3 years previously had an increased likelihood of having a serum SeM-specific antibody titer ≥ 1:1,600. We also found that 26/35 (74%) horses that had been vaccinated with IN strangles when their SeM titer was equal to 1:1,600 did not have any complications associated with purpura.24 Therefore, the recommendation is to not vaccinate when the titer is ≥ 1: 3,200. Treatment

While the use of antimicrobials for treating strangles is controversial, horses with complications such as metastatic disease or purpura definitely require the use of systemic antimicrobials for extended periods. In addition, horses with severely enlarged lymph nodes and dyspnea often require an emergency tracheostomy 1,2,3,7 and intensive supportive care. The preferred antimicrobial is penicillin (procaine penicillin [22,000 to 44,000 IU/kg IM q12h] or aqueous potassium penicillin [22,000 to 44,000 IU/kg IV q6h]). The use of antimicrobials during the acute phase of fever and depression may prevent abscess formation and decrease shedding but also the development of lasting immunity. Cases of purpura hemorrhagica also require the use of systemic corticosteroids (dexamethasone, 0.1 to 0.2 mg/kg IV or IM q12–24h; prednisolone, 0.5 to 1 mg/kg PO q24h) for an average of 3 weeks to reduce systemic vasculitis.2,10

Elimination of guttural pouch empyema requires repeated lavage with a solution of 20% acetylcys- teine in buffered saline via polyethylene tubing through an endoscope or via a chambers catheter. Chondroids are particularly difficult to remove, possibly requiring manual removal with endoscopic equipment such as a memory helical polyp retrieval basket, repeated lavage via indwelling cath- eters, or surgical removal.1,2,8,12,13 Successful elimination of S. equi subsp equi in these carriers requires local treatment of the guttural pouch with a penicillin gel after removal of the material within the guttural pouch.1,12,13 Repeated local treatment and systemic treatment with procaine penicillin or potassium penicillin for 7 to 10 days are necessary for refractory cases.2,8

References

1. Sweeney CR, Timoney JF, Newton JR, Hines MT. Streptococcus equi infections in horses: guidelines for treatment, control, and prevention of strangles. J Vet Intern Med 2005:19:123-134.

2. Boyle AG. Streptococcus equi subspecies equi Infection (Strangles) in horses. Compendium Continuing Education for the Practicing Veterinarian 2011; 33:online.

3. Sweeney CR, Benson CE, Whitlock RH, et al. Description of an epizootic and persistence of Streptococ- cus equi infections in horses. JAVMA 1989;9:1281-1286.

4. Ford J, Lokai MD. Complications of Streptococcus equi infection. Equine Pract 1980;4:41-44.

26 6. Carlson GP. Diseases of the hematopoietic and hemolymphatic systems. In: Smith BP, ed. Large Animal Internal Medicine. 3rd ed. St. Louis: CV Mosby; 2002:1043.