Antiparasitic treatment with itraconazole and amiodarone in 2 dogs with severe, symptomatic Chagas cardiomyopathy

Malcolm, Elizabeth; Saunders, Ashley B.; Vitt, Jordan P; Boutet, Bruno G; Hamer, Sarah A.

doi:10.1111/jvim.16422

Cited by 8 publications

(5 citation statements)

References 37 publications

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“…In the Tc /BNZ and Tc/ UNT groups, the abnormalities were poorly differentiated bundle branch block with intraventricular conduction defect. All findings are consistent with what has been reported in dogs with CD [ 4 , 6 , 42 , 60 , 61 , 62 ]. There is a possibility that NTZ may have caused cardiotoxicity, as reported by Gong et al, who observed that exposure to the drug affected the embryonic heart development of zebrafish, significantly inhibited cardiomyocyte proliferation, and promoted apoptosis, ultimately leading to cardiac tissue injury [ 63 ].…”

Section: Discussionsupporting

confidence: 93%

Effectiveness of Nitazoxanide and Electrolyzed Oxiding Water in Treating Chagas Disease in a Canine Model

Rodríguez-Morales,

Mendoza-Téllez,

Morales-Salinas

et al. 2023

Pharmaceutics

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Chagas disease (CD) is caused by the protozoan Trypanosoma cruzi, and affects seven million people in Latin America. Side effects and the limited efficacy of current treatment have led to new drug research. The objective of this work was to evaluate the effectiveness of nitazoxanide (NTZ) and electrolyzed oxidizing water (EOW) in a canine model of experimental CD. Náhuatl dogs were infected with the T. cruzi H8 strain and NTZ- or EOW-treated orally for 10 days. Seronegativity was shown at 12 months post-infection (mpi) in the NTZ-, EOW-, and benznidazole (BNZ)-treated groups. The NTZ and BNZ groups had high levels of IFN-γ, TNF-α, IL-6, IL-12B, and IL-1β at 1.5 mpi and low levels of IL-10. Electrocardiographic studies showed alterations from 3 mpi and worsening at 12 mpi; NTZ treatment produced fewer cardiac pathomorphological changes compared to EOW, similar to BNZ treatment. There was no cardiomegaly in any group. In conclusion, although NTZ and EOW did not prevent changes in cardiac conductivity, they were able to avoid the severity of heart damage in the chronic phase of CD. NTZ induced a favorable proinflammatory immune response after infection, being a better option than EOW as a possible treatment for CD after BNZ.

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Section: Discussionsupporting

confidence: 93%

Effectiveness of Nitazoxanide and Electrolyzed Oxiding Water in Treating Chagas Disease in a Canine Model

Rodríguez-Morales,

Mendoza-Téllez,

Morales-Salinas

et al. 2023

Pharmaceutics

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“…Dogs are natural hosts of T. cruzi and have been traditionally considered adequate models of Chagas disease, with an electrocardiographic and myocardial pathology that reflects human disease. 109,[131][132][133] In particular, dogs can develop a form of the disease that resembles the chronic phase of Chagas disease more closely, with changes in response outcomes following treatment with benznidazole in these animals also matching those observed in human clinical trials. 109,133,134 Nonetheless, differences in the half-life of certain drugs in dogs and humans can limit the translational potential of results obtained in this species.…”

Section: Canine Modelsmentioning

confidence: 87%

State-of-the-Art in the Drug Discovery Pathway for Chagas Disease: A Framework for Drug Development and Target Validation

Gabaldón-Figueira,

Martinez-Peinado,

Escabia

et al. 2023

RRTM

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Chagas disease is the most important protozoan infection in the Americas, and constitutes a significant public health concern throughout the world. Development of new medications against its etiologic agent, Trypanosoma cruzi , has been traditionally slow and difficult, lagging in comparison with diseases caused by other kinetoplastid parasites. Among the factors that explain this are the incompletely understood mechanisms of pathogenesis of T. cruzi infection and its complex set of interactions with the host in the chronic stage of the disease. These demand the performance of a variety of in vitro and in vivo assays as part of any drug development effort. In this review, we discuss recent breakthroughs in the understanding of the parasite’s life cycle and their implications in the search for new chemotherapeutics. For this, we present a framework to guide drug discovery efforts against Chagas disease, considering state-of-the-art preclinical models and recently developed tools for the identification and validation of molecular targets.

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“…Echo derived RV S’ correlates with reduced RV ejection fraction in infected humans, and RV systolic dysfunction is associated with worse prognosis [ 56 ]. In dogs, RV enlargement has been associated with a worse prognosis and can be an indicator of end-stage disease [ 25 , 57 ]. Advanced echocardiographic imaging with regional speckle tracking of both ventricles may provide earlier detection of wall-motion changes and myocardial damage [ 56 , 58 ].…”

Section: Discussionmentioning

confidence: 99%

Cardiac Magnetic Resonance Imaging Detects Myocardial Abnormalities in Naturally Infected Dogs with Chronic Asymptomatic Chagas Disease

Matthews

Fries

Jeffery

et al. 2023

Animals

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Trypanosoma cruzi infection causes inflammation and fibrosis, resulting in cardiac damage in dogs. The objectives of this study were to describe cardiac magnetic resonance imaging (CMR) in naturally infected dogs with chronic Chagas disease and the frequency of abnormalities for CMR and cardiac diagnostic tests. Ten asymptomatic, client-owned dogs seropositive for T. cruzi were prospectively enrolled in an observational study evaluating echocardiography, ECG (standard and ambulatory), cardiac troponin I (cTnI), and CMR. Standard ECG measurements (3/10) and cTnI concentration (1/10) outside the reference range were uncommon. Ambulatory ECG abnormalities were documented more frequently (6/10 dogs) than with standard ECG and included ventricular arrhythmias (4), supraventricular premature beats (3), second-degree atrioventricular block (2), and sinus arrest (1). Echocardiographic abnormalities were documented in 6/10 dogs including mildly increased left ventricular internal dimension in diastole (1) and decreased right ventricular (RV) systolic function based on reductions in tricuspid annular plane systolic excursion (3) and RV S’ (4). Abnormalities were detected with CMR in 7/10 dogs including delayed myocardial enhancement in 5 of which 2 also had increased extracellular volume, abnormal wall motion in 5, and loss of apical compact myocardium in 1. In conclusion, CMR abnormalities were common, and the results of this study suggest CMR can provide useful information in dogs with T. cruzi infection and may support naturally infected dogs for future clinical investigation as an animal model for Chagas disease.

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Antiparasitic treatment with itraconazole and amiodarone in 2 dogs with severe, symptomatic Chagas cardiomyopathy

Cited by 8 publications

References 37 publications

Effectiveness of Nitazoxanide and Electrolyzed Oxiding Water in Treating Chagas Disease in a Canine Model

Effectiveness of Nitazoxanide and Electrolyzed Oxiding Water in Treating Chagas Disease in a Canine Model

State-of-the-Art in the Drug Discovery Pathway for Chagas Disease: A Framework for Drug Development and Target Validation

Cardiac Magnetic Resonance Imaging Detects Myocardial Abnormalities in Naturally Infected Dogs with Chronic Asymptomatic Chagas Disease

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