Strangles (Proceedings)

Strangles

Streptococcus equi, subsp equi

• First reported in 1251

• Gram + coccus

• Biochemically different from S. zooepidemicus

Sweeney, et al, JVIM, 2005:19:123-134

• Streptococcus equi infections in horses: guidelines for treatment, control and prevention of strangles

• Consensus statement of the American College of Veterinary Internal Medicine

Pathogenesis

S. equi enter horse via mouth or nose

• Attach to cells in lingual/palatine tonsils & epithelium of pharynx

• Translocates within hours to mandibular and suprapharyngeal lymph nodes that drain the pharynx and tonsillar areas

Molecular pathogenesis

• Neutrophils fail to phagocytose & kill bacteria

• Hyaluronic acid capsule

• Antiphagocytic SeM protein

• Mac protein

• Bacteria accumulate extracellularly in lymph nodes

• Streptolysin S & streptokinase damage cell membranes and activate proteolytic properties of plasminogen

• Contributes to abscess formation

Pathogenesis

Bacteria spread via blood or lymphatics

• Metastatic abscesses in thorax, abdomen, or other lymph nodes

• "Bastard strangles"

• Bacteremia occurs during days 6-12 in experimentally infected horses

• First clinical sign = fever

• 3 to 14 days after exposure

• Increase in WBC, neutrophils, fibrinogen

• Abscess development is rapid

• Nasal shedding begins at 2-3 days after onset of fever and persists for 2-3 weeks in most animals

• New cases can be isolated before they shed.

Chronic Shedders

• Guttural pouch infection ± chondroids

• Persistent/intermittent shedding for months-years

• Uncommon

Post-infection immunity

• Systemic & mucosal immunity is apparent 2-3 weeks after infection

• 75% of horses develop enduring immunity following recovery

Colostral immunity

• Milk from mares that have recovered from strangles contains IgGb & IgA that protect foal

• Foals that suckle immune mares are resistant until weaning.

Epidemiology

• Highly contagious

• Occurs in outbreaks

• Morbidity = 30 - 100%

• Mortality = 0 - 10%

• Morbidity highest in young (1-5 yo) horses

Transmission

Transmitted via purulent discharges from active & recovering cases

• Direct horse-to-horse contact

• Indirect contact (fomites)

• Contaminated housing

• Water buckets

• Feed utensils

• Twitches

• Tack

• Caretakers / veterinarians

Transmission originating from outwardly healthy appearing horses

• Incubating disease

o Prior to clinical signs

• Recovering from recent disease

o Still harboring & shedding bacteria

o Potential source of infection for 6 weeks after recovery

• Fully recovered from disease

o Chronic asymptomatic shedders

Long-term, subclinical S. equi carriers

• ~10% of affected horses

• Can be source of infection for susceptible animals

• Even in closed herds w/o active cases

• Efficacy of control must include recognition of these shedders

• Guttural pouch

• Location of subclinical infection

• Rupture of retropharyngeal abscesses

• Chronic empyema or "chondroid"

• Persistent or intermittent shedding

Environmental persistence of S. equi

No evidence of prolonged environmental persistence

• Survived for 63 days on wood

• Survived for 48 days on glass

• Does not readily survive in soil

• More study needed

Clinical signs

• Incubation period = 3 to 14 days

• Variable severity of clinical signs

• Dependent on immune status of animal

• Sudden onset of fever

• Catarrh of URT

• Bilateral MP nasal discharge

• Acute swelling

• Abscess formation

o Retropharyngeal and submandibular LN

• Anorexia or painful swallowing

• Stand with neck extended

• Depression / listlessness

• Pharyngitis, laryngitis / rhinitis

• dysphagia

• Upper airway snuffling / rattling sounds

• Nasal / ocular hyperemia

Clinical signs

Lymphadenopathy

• Most frequently submandibular and retropharyngeal

• Parotid LN, cranial cervical LN, other LN

• Start out as hot, painful edema of LNs

• LNs become swollen & painful

• LN abscesses mature (days - weeks)

• Abscesses rupture - drain tenacious creamy pus

• Non-odiferous

• Retropharyngeal LN abscessation not always apparent externally

• drain into guttural pouch causing empyema

• LN abscesses often exert pressure on larynx, pharynx, trachea, esophagus resulting in:

• Upper respiratory tract obstruction

• Respiratory distress

• Respiratory noise / stridor

• Asphyxiation

• Death

• Dysphagia

• Temporary left laryngeal hemiplegia

• May require temporary tracheostomy

Diagnosis

• History

• Clinical signs

• Culture of nasal swabs, nasal washes, or pus from abscesses

• Isolation of Strep equi = GOLD STANDARD OF DIAGNOSIS

Nasal Washes

• More sensitive than nasal swabs

• Instill 50 ml saline via 15 cm tubing

• Collect effluent

• Centrifuge

• Culture pellet

• May get negative cultures during 1st 24-48 hours after onset of fever

PCR

• Detects DNA sequence of SeM

• SeM = gene for antiphagocytic M protein

• Rapid results

• Adjunct to culture for detection of S. equi

• Does not distinguish b/w live and dead organisms

• PCR is ~3x more sensitive than culture

PCR is useful to:

• Detect asymptomatic carriers

• Detects DNA for weeks after disappearance of live bacteria

• Establish S. equi infection status prior to transport

• Establish S. equi infection status following transport prior to co-mingling

• Determine the success of elimination of S. equi from guttural pouch.

Serology

• ELISA to detect antibodies to SeM

• IDEXX

• SeM = virulence factor and protective immunogen

• Diagnose recent exposure/infection

• Serum titres peak 5 weeks after exposure & remain high for 6 month

• Sequential titres indicate exposure

• Determine need for booster vaccination

• Aid in diagnosis of purpura

• Does not distinguish b/w natural infection and vaccination immunity

• Vaccination - peak titres at 2 weeks and remain high for 6 months

Interpretation of SeM ELISA

• Negative

• No antibodies detected

• No immunity

• Can occur in horse with recent exposure (<7 days)

• Weak Positive

• 1:200 - 1:400

• Low level of antibody

• Repeat in 7-14 days to confirm exposure

• Moderate Positive

• 1:800 - 1:1600

• Intermediate level of antibody

• May occur 2-3 weeks post-exposure or 6 months to 2 years post-exposure

• High Positive

• 1:3200 - 1:6400

• High level of antibody

• 4-12 weeks post-exposure

• 1-2 weeks post-injectable vaccine

• 2-4 weeks post-intranasal vaccine

• Vaccination is contraindicated

• Very High Positive

• >1:12,800

• Very high level of antibodies

• Often found in horses with metastatic abscess

• Often found in horses with purpura hemorrhagica following exposure to S. equi or vaccine

Treatment

Depends on stage and severity of disease

• Stages

• Horses exposed but not showing signs

• Horses with early clinical signs

• Horses with LN abscessation

• Horses with partial URT obstruction

• Horses with strangles-associated complications

Horses exposed but no clinical signs

• Antibiotics may prevent seeding of pharyngeal LN

Horses with early clinical signs

• Fever, lethargy, anorexia

• Isolate horse

• Antibiotics may be curative and arrest clinical signs

• Inhibits protective immunity

• If horse is still exposed, is susceptible to re-infection once treatment is stopped.

Horses w/ lymph node abscessation

• Isolate horse

• Antibiotics may prolong maturation/rupture of abscess

• Promote maturation & drainage of abscess

• Local hot packs or poultice

• Surgical drainage

• Lavage w/ 3% povidone-iodine

• NSAIDs reduce fever and pain

Horses w/ guttural pouch empyema

Horses w/ partial URT obstruction

• Antibiotics are indicated to decrease size of abscess and prevent complete obstruction

• May require tracheostomy, IV fluids, NG tube feeding, surgical drainage

Horses w/ complications from Strangles

• Antibiotics are indicated

• Treatment is aimed at specific complication

Antimicrobials of Choice

• Penicillin is drug of choice

• Cephalosporins

• Macrolides

• Doxycycline

Vaccination

• Natural exposure provides protective immunity up to 5 years in 75% of horses

• Resistance is associated with antibodies to SeM

• Systemic and mucosal immunity

• Extracts of S. equi

• Intranasal vaccine

• Animals with SeM antibody titre >1:1600 should not be vaccinated

• During outbreak, only horses with no exposure should be vaccinated

Live, attenuated S. equi (Pinnacle)

• Provides immunity at the pharyngeal and tonsillar regions

• 2 doses at 2-3 week intervals followed by annual booster

• Adverse effects include abscesses, MP nasal discharge, and purpura

• Do not give concurrent injectable vaccinations

IM Vaccination

Extracts of S. equi

• Takes 2 weeks to develop protective immunity

• 2-3 doses at 2 week intervals followed by annual booster

• Booster pregnant mares 1 month prior to foaling

Prevention

• Difficult at training barns, sales barns, breeding farms, racetracks

• Quarantine of incoming horses for 3 weeks

• Screening of incoming horses to identify shedders

• Culture and PCR of 3 weekly nasal washes

• Guttural pouch endoscopy / lavage / culture

• High standards of hygeine

• Disinfect fomites

• Protective clothing

• Avoid indirect transmission b/w resident horses and quarantined horses

Control of Outbreaks

• Stop movement of horses on/off farm

• Quarantine horses with strangles and contact horses in quarantined areas

• Employ proper hygeine principles

• Prevent direct / indirect exposure to unexposed horses

• Keep unexposed horses in clean areas

• Screen all convalescing cases for carriers following clinical recovery using nasal swab/lavage

• Test nasal washes via culture and PCR

• Weekly for at least 3 weeks

• Endoscope and lavage guttural pouches of positive horses to detect long-term carriers

• Culture and PCR of GP lavage samples

Treatment of Carriers with Guttural Pouch Infections

• Repeated lavage

• Systemic penicillin

• Topical penicillin into pouches

Penicillin Gel

• Verheyen et al, EVJ, 2000

• 2 g gelatin + 40 ml sterile water

• Heat to dissolve gelatin

• Cool gelatin to 50C

• Add 10 ml sterile water to 10 MU sodium benzylpenicillin

• All penicillin solution to cooled gelatin

• Dispense into syringes and allow to cool

Complications from Strangles

20% of horses -Mortality is higher in horses with complications

• Complications associated with metastatic spread of infection

• Complications associated with immune-mediated processes

• Agalactia in lactating mares

Bastard Strangles

• Metastatic spread

• Potentially can infect any site

• Lung, mesentery, liver, spleen, kidneys, brain

• Cranial mediastinal LN abscess

• Pneumonia, pleuropneumonia

Sinuses, guttural pouches

Myocarditis / endocarditis

Panopthalmitis / periorbital abscess / ulcerative keratitis

Paravertebral abscess

Septic arthritis

Tenosynovitis

Clinical signs, diagnosis and treatment are dependent on organ system affected

Weight loss, anorexia, lethargy, fever

Can be challenging cases to diagnose

SeM titers > 1:12,800 are suggestive

Radiography, ultrasound, rectal, abdominocentesis, MRI, CT

Guttural pouch empyema and chondroids

Diagnosis: endoscopy

• Lymphadenopathy & empyema

• Flush and culture/PCR

Diagnosis: radiography

• Fluid line in GP

• Tracheal compression

Guttural Pouch Empyema and Chondroids

Treatment: lavage

Chondroid removal

• Fragmentation and lavage

• Basket retrieval

• Surgical approach

Mesenteric Abscesses

Myocardial Abscesses

Brain Abscesses

Immune-mediated sequelae to strangles

• Purpura hemorrhagica

• Infarctive purpura hemorrhagica

• Acute rhabdomyolysis

• Immune mediated myopathy

Purpura hemorrhagica

Immune mediated vasculitis

• Type III hypersensitivity response characterized by antibody-antigen complex deposition in blood vessel walls

• Immune complexes stimulate complement activation and chemoattractants stimulate neutrophil infiltration

• Neutrophils release proteolytic enzymes result in vessel wall damage and edema formation

• Leukocytoclastic vasculitis

• Petechia and ecchymosis result from RBC leakage into extravascular tissues

• Clinical signs

• Stiff gait

• Anorexia, lethargy

• Tachycardia / tachypnea

• Colic / diarrhea

• Laminitis

• Respiratory distress

Sweeney, JAVMA, 1987

• 74 cases of strangles on a farm

• 4 had purpura hemorrhagica

• All 4 were male yearlings

• All 4 had been vaccinated for strangles 2-16 weeks earlier

Pusterla, Vet Rec, 2003

• 53 cases of purpura over 20 years

• Mean age = 8.4 years

• All had dependent edema

• 43 of 53 had petechiae or ecchymosis

• 32% had concurrent S. equi infection or "exposure"

• 9% occurred post S. equi M protein vaccination

• 17% had concurrent C. pseudotuberculosis infection

• 9% diagnosed with unknown respiratory infection

• 28% were idiopathic

Diagnosis

• History

• Clinical signs

• Petechiae/ecchymosis often better visualized via endoscopy

• Hematology

• Leukocytosis and mature neutrophilia

• Hyperfibrinogenemia

• Hypoalbuminemia

• Hyperglobulinemia

• Normal platelet counts

• Skin biopsy

• Leukocytoclastic vasculitis

• Marked elevations in SeM titers

• >1:12,800

• Response to therapy

Therapy

• Immunosuppressive therapy

• Dexamethasone (0.04-0.2 mg/kg IM, IV, PO, q 24h)

• Prednisolone (0.5 – 1 mg/kg PO q 24 h)

• Taper over 2-4 weeks

• Treat any existing focus of infection

• PPG (22,000 U/kg IM q 12 h)

• NSAIDs

• Hydrotherapy

• Pressure bandages of lower limbs

• Pneumatic compression device

• Supportive care

Prognosis

• Pusterla, et al, Vet Rec, 2003

• 92% survival

• Sweeney et al, JAVMA, 1987

• 75% survival

• Most cases resolve in 4-8 weeks

• Relapses can occur

Other causes

• S. equi

• Equine influenza

• Equine herpes virus 1

• Streptococcus zooepidemicus

• Rhodococcus equi

• Corynebacterium pseudotuberculosis

• Idiopathic

Finding the cause of purpura

Rule out S. equi infection first!

• Peripheral abscesses

• Guttural pouch empyema & retropharyngeal lymphadenopathy

• Metastatic S. equi / bastard strangles

• Culture concurrent abscesses

• Upper airway endoscopy

o GP empyema, lymphadenopathy, chondroids

o Cultures/ PCR for M protein

• SeM ELISA ≥(1:12,800)

o IDEXX, Lexington, KY

Other DDX for purpura

Thrombocytopenia (IMTP)

Equine infectious anemia

• Coggins (AGID) or ELISA

Anaplasma phagocytophilum

• Inclusion bodies in neutrophils and eosinophils (Giemsa)

• Serology, IFA, PCR

• EVA

• Serology

• Virus isolation

Complications of Purpura

Secondary infections

• Secondary to skin necrosis

• Cellulitis, tenosynovitis, septic arthritis

• Chronic granulation tissue

Life threatening sequelae

• Laminitis

• Infarctions

• Multi-organ failure

• Hemorrhage

Complications of Purpura

Renal failure secondary to purpura

• Azotemia, proteinuria, isosthenuria

• Mixed membrano-mesangial proliferative glomerulonephritis

• Likely due to immune complex deposition

Infarctive purpura hemorrhagica

Less common than conventional purpura

• Severe, often fatal form of purpura

• 3-4 weeks post-infection with S. equi

• Vasculitis leads to DIC

• Muscle infarcts

Infarctive purpura hemorrhagica

Clinical features

• Lameness

• Stiffness, reluctance to move

• Muscle swellings

• Colic

• Respiratory distress

• Inflammatory leukogram

• Marked elevations in CK and AST

• Myoglobinuria

• Prolonged coagulogram

• Increased D-dimers

Infarctive purpura hemorrhagica

Treatment

Aggressive immunosuppression (dexamethasone)

IV fluids for diuresis

Antibiotics for existing infection

DMSO and Vitamin E

Anti-cogulative therapy

Heparin, low-molecular weight heparin, aspirin, plasma

Laminitis prophylaxis

Aggressive analgesics

• NSAIDs

• Lidocaine, butorphanol, ketamine CRI's

Prognosis

• Poor prognosis

• Some cases gradually recover with aggressive therapy

Acute rhabdomyolysis

Another sequelae to S. equi infection

Rare, and usually fatal

Quarter Horses younger than 7 y.o.

Stiff, stilted gait

Acute, painful firm muscle swellings

Epaxial and gluteal muscles

Signs noted within 1 week of onset of clinical S. equi infection (abscesses)

Marked elevations in CK and AST

Myoglobinuria

Sponsellor, JAVMA, 2005

Valberg, AAEP, 2006

Immune-mediated myositis

Valberg, 1996; Valberg 2006; Lewis, et al, 2007

• Stiffness

• Rapidly progressive muscle atrophy of epaxial and gluteal muscles

• Predominately QHs

• Recent history of respiratory disease or exposure to S. equi or S. zoo

• Elevated muscle enzymes (AST, CPK)

• Diagnosis – muscle biopsy

• Lymphocytes and macrophages infiltrate into muscle fibers, fiber necrosis

• Treatment = dexamethasone + antimicrobial treatment of any underlying Strep infection

• Prognosis - good

Immune-mediated myocarditis

• Non-suppurative myocarditis

• Tachycardia

• Arrhythmias

• Diagnosis

• History

• Clinical signs

• Elevated Troponin 1 levels

• Treatment

• Immunosuppressive therapy