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Heartworm Disease Of the 21 st Century

Canine Chagas

Chagas DiseaseAmerican Trypanosomiasis

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Chagas Disease

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T. cruzi Trypomastigote, 15-20um T. cruzi Amastigote, 2-4um

Chagas DiseaseLouisiana

5.3% Shelter/Companion animals

Tennessee

6.4% Companion animals

Texas (~630,000 infected)

9% Shelter dogs

13.1% Companion animals San Antonio region

8% U.S. Military Working dogs

Oklahoma

3.6% Companion animals

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Preva lence

Chagas Disease

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Chagas DiseaseCl in ica l Symptoms Canine

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Acute Collapse

Arrhythmias

Lymphadenopathy/Splenomegaly

Fever

Neurological signs

Chronic Arrhythmias

Ascites

Congestive heart failure

Weight loss

Lethargy

Acute death

ASYMPTOMATIC

Chagas Disease

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Chagas Disease

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Chagas DiseaseCl in ica l Symptoms in Fe l ine and Humans

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FelineCardiovascular and gastrointestinal symptoms

In Mexico, urban domestic cats were determined to be important peridomestic reservoirs

No studies have assessed the epidemiology of Chagas disease in cats in the US

Currently assessing cohorts of Texas cats presenting to the TAMU Teaching Hospital for T. cruzi-associated cardiac disease

HumansCardiac

DCM#1 cardiomyopathy in Latin America

GastrointestinalMegaesophagusMegacolon

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Atrial arrhythmiasVentricular arrhythmias

Chagas Disease

Chagas Disease

ECGRange of arrhythmias

Arrhythmogenic antibodies

Autonomic denervation

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Diagnostic ImagingRadiographs

Echocardiogram

PathologyBlood smear

Troponin

White blood cell count

Lymph node aspirates

Necropsy

Chagas Disease

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Diagnostics• Serology (21 day post infection)

• IFA GOLD STANDARD

• Lifelong persistence likely

• Texas Veterinary Medical Diagnostic Laboratory

• ELISA

• Not FDA approved

• Western Blot

• Not commercially available

PCR• Kinetoplast DNA 121/122

• 99%+ Acute sensitivity, 100% specificity

• 51% Chronic sensitivity, 100% specificity

• Decreased parasitemia with chronicity of infection

• Serial PCR - Good for monitoring treatment efficacy

Blood Culture• Slow (2-20 weeks)

• Limited

Chagas Disease

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Case Study

Molly9 Yr Spayed Labrador Retriever

Indoor / Outdoor

200 acre ranch East Texas

Weakness

Collapse

Panting

Weight loss

Ascites

Hyporexia

Chagas Disease

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Case Study

MollyRadiographs

ECG

CBC/Chemistry

Chagas IFA

1:640PCR

Positive

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Chagas Disease

Benznidazole• Targets T. cruzi DNA via free

radical generation

• Not FDA approved in dogs

• Difficult to obtain

• Good efficacy in Acute phase (>90% efficacy)

• Poor efficacy in Chronic phase (BENEFIT study)

• Side effects common

• Efficacy is highly strain dependent

Allopurinol• Xanthine oxidase inhibitor (reduces

uric acid)

• Humans 62% reduction in parasitemia

• Unknown efficacy in dogs via purine inhibition

Other Azoles• Ketoconazole

• Fluconazole

• Posaconazole

• Ravuconazole

Chagas Disease Treatment

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Amiodarone• Class III antiarrhythmic

• Disrupts calcium homeostasis/Cruzipain

• Loading dose: 15mg/kg PO BID x 7 d,

7.5mg/kg PO BID x 14 d then….

• Maintenance: 7.5mg/kg PO SID

• Adverse events: ALT/SAP elevations,

lethargy, anorexia

Itraconazole• Triazole antifungal

• Interferes with ergosterol synthesis

• 10mg/kg PO SID with food

• Adverse events: anorexia, vomiting,

weight loss, cutaneous eruption,

ALT/SAP elevations, lethargy

Target 2-3 ug/mL

Treatment is for 12 months

Chagas Disease

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Case Study

MollyAbdominocentesis

Quadruple therapy

Itraconazole 300mg PO SID

ITZ #1: 8.2 ug/mL (2-3ug/mL)

Reduce itraconazole 100mg PO SID

ITZ #2: 2.2 ug/mL (2-3ug/mL)

Amiodarone 250mg PO SID

PCR negative @ 1 and 6 months

Chagas Disease

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Case Study

MollyQuadruple therapy

1. ACEi

Enalapril or Benazepril 0.5mg/kg PO SID

2. Pimobendan

2-3 mg/kg PO BID

Dose escalation q 8 hrs

3. Furosemide

1-3 mg/kg PO BID; caution for ascites

4. Spironolactone

RAAS inhibition, reduction of fibrosis

2 mg/kg PO SID

Chagas Disease

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Case Study

Molly

Reduction in cardiomegaly

Minimal ascites

No pleural effusion

Normal appetite

Weight gain

Normal activity

Begging for table food (again!)

Monitor PCR 1 and 2 months post tx

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