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Electrocardiographic abnormalities… 2024 JAVMA article

Title: Electrocardiographic abnormalities are associated with seropositive Trypanosoma cruzi infection status using a simplified cardiac diagnostic evaluation in dogs

Authors: Kendra A. Zelachowski, Stephanie Collins, Marty Henderson, Lisa D. Auckland, Sukjung Lim, Nicholas D. Jeffery, Sarah A. Hamer, and Ashley B. Saunders

Journal/Date of Publication: Journal of the American Veterinary Medical Association, 2024

DOI: 10.2460/javma.24.05.0328

Objective: To describe associations between cardiac abnormalities and Trypanosoma cruzi serostatus by use of a simplified diagnostic evaluation in dogs at risk for T. cruzi infection.

Type of Study: Prospective, cross-sectional study

Conclusions:

  1. Seropositive dogs were more likely to show electrocardiographic conduction system abnormalities (examples: prolonged intervals, AV block, ventricular arrhythmias) than seronegative or discordant dogs.
  2. Echocardiographic findings did not clearly distinguish T. cruzi infection status in this group of dogs. Many dogs had age related myxomatous mitral valve disease.
  3. ECG abnormalities (examples: splintered QRS complexes, prolonged PR intervals) were key indicators of potential T. cruzi infection.
  4. Elevated cardiac troponin I was observed in some infected dogs, indicating myocardial damage.

Clinical Application:

  1. Electrocardiography can be used to screen for early signs of T. cruzi-related cardiac disease in high-risk dogs.
  2. Monitoring for conduction system abnormalities (prolonged intervals, AV blocks, splintered QRS complexes) can aid in identifying infected dogs.
  3. Cardiac troponin I concentrations may serve as a useful marker for myocardial damage, especially in acute or active infections.
  4. Echocardiography is useful but may not always distinguish T. cruzi-related abnormalities, especially when myxomatous mitral valve disease is present.
  5. Regular monitoring of seropositive or discordant dogs with ECG and cardiac assessments is recommended to detect and manage progression of Chagas disease.
two-panel ECG figure with notations as described in caption
Figure 2.
Lead II ECG recordings obtained in 2 dogs that were seropositive for T cruzi with splintered (asterisk) QRS complexes (panel A) and prolonged P and PR durations (panel B). Paper speed = 50 mm/s; 0.5 cm = 1 mV.

Positive clinical outcome… 2024 JVIM article

Title: Positive clinical outcome using a modified dosing regimen of benznidazole in dogs at high risk for infection or acutely infected with Trypanosoma cruzi

Authors: Sukjung Lim, Stephanie Collins, Sarah A. Hamer, Rick L. Tarleton, and Ashley B. Saunders

Journal/Date of Publication: Journal of Veterinary Internal Medicine, 2024

DOI: 10.1111/jvim.17028

Objective: The study focuses on the prevention and management of Trypanosoma cruzi (Chagas disease) infection in dogs, particularly the effects of a modified benznidazole regimen.

Type of Study: Prospective

Conclusions:

  1. Prophylactic benznidazole prevented T. cruzi infection and cardiac disease in two dogs monitored over a 2-year period.
  2. One dog without prophylaxis died from acute Chagas-related myocarditis, while another developed severe arrhythmias but showed improvement with higher-dose benznidazole treatment.
  3. Though the sample size was small, these findings suggest potential clinical benefits from prophylactic and early benznidazole use, reducing morbidity from cardiac damage.

Clinical application:

  1. Prophylactic BNZ: Modified dosing of benznidazole may prevent T. cruzi infection in some high-risk dogs.
  2. Early treatment benefit: Higher benznidazole doses (17.5 mg/kg, twice weekly) in acutely infected dogs reduced cardiac biomarker (cardiac troponin I) concentrations and arrhythmias, even without total parasitological cure.
  3. Cardiac troponin I as a marker: Monitoring levels can help track cardiac damage and recovery during treatment.
  4. Prevention in endemic areas: Some dogs in areas with high vector exposure may benefit from prophylactic treatment during peak transmission seasons.
  5. Potential for reduced mortality: Early intervention with benznidazole could reduce sudden death risk from Chagas disease in dogs.
  6. No major adverse effects: Modified benznidazole dosing was well-tolerated in these dogs, with no reported adverse effects.
scatter plot of results from study as described in caption
Figure 1.
Serum cardiac troponin I results for the 4 dogs. Dogs 1 and 2 were in the prophylaxis group, dog 3 was in the nonprophylaxis group with death after visit 2 and dog 4 was in the nonprophylaxis group and subsequently started on a modified treatment dose regimen of benznidazole. The upper limit of the reference range (0.128 ng/mL) is represented by the dotted line.

Abundant triatomines… 2024 Acta Tropica article

Title: Abundant triatomines in Texas dog kennel environments: Triatomine collections, infection with Trypanosoma cruzi, and blood feeding hosts

Authors: R.E. Busselman, R. Curtis-Robles, A.C. Meyers, I.B. Zecca, L.D. Auckland, C.L. Hodo, D. Christopher, A.B. Saunders, and S.A. Hamer

Journal/Date of Publication: Acta Tropica, 2024

DOI: 10.1016/j.actatropica.2023.107087

Objective: Triatomines were collected across central and south Texas to identify their primary bloodmeal hosts, T. cruzi status, and the T. cruzi discrete typing units (DTUs) present. 

Type of Study: Prospective

Conclusions:

  1. Triatomine insects are common in Texas dog kennels, with high infection rates of T. cruzi.
  2. Dogs are the primary blood meal host, indicating a significant risk of Chagas disease transmission in kennels.
  3. T. cruzi was found with multiple DTUs, mainly TcI and TcIV.
  4. Scent detection dogs were effective in identifying cryptic triatomine habitats.

Clinical application:

  1. Risk Assessment: Dog kennels, particularly those with outdoor exposure, are high-risk environments for Chagas disease.
  2. Detection and Surveillance: Using scent detection dogs can enhance triatomine detection in difficult-to-reach areas.
  3. Vector Control: Dogs in high-risk areas may benefit from insecticide treatments to reduce triatomine bites.
  4. Disease Prevention: Preventative measures should focus on reducing kennel exposure to triatomines, including structural modifications and pesticide application.
  5. Host Management: Since dogs are primary hosts, vector control strategies should prioritize interventions that limit dog-triatomine interactions.
three-panel graphical abstract with a map, photos and graphs depicting the written abstract from the article
Graphical Abstract.
Panel 1: 550 triatomines collected from 10 kennels throughout southern Texas
Panel 2: Triatomines tested for Trypanosoma cruzi using qPCR; Triatomines tested for bloodmeal hosts using series of cytB-targeting PCRs
Panel 3: 47.8% Trypanosoma cruzi infection prevalence (n=157); 53 bloodmeal hosts identified – dogs were the predominant host

Frequency Variation… 2023 Antimicrobial Agents and Chemotherapy article

Title: Frequency Variation and Dose Modification of Benznidazole Administration for the Treatment of Trypanosoma cruzi Infection in Mice, Dogs, and Nonhuman Primates

Authors: Juan M. Bustamante, Brooke E. White, Gregory K. Wilkerson, Carolyn L. Hodo, Lisa D. Auckland, Wei Wang, Stephanie McCain, Sarah A. Hamer, Ashley B. Saunders, and Rick L. Tarleton

Journal/Date of Publication: Antimicrobial Agents and Chemotherapy, 2023

DOI: 10.1128/aac.00132-23

Objective: Treatment of chronic Trypanosoma cruzi (Chagas disease) infections in animals, with a focus on the effectiveness of higher dose, intermittent benznidazole treatment protocols.

Type of Study: Prospective

Conclusions:

  1. Twice-weekly high-dose benznidazole treatment over several months led to parasitological cures in some animals (mice, dogs, and macaques), though results varied.
  2. Shorter or less frequent treatment regimens were less effective.
  3. Parasites did not develop resistance to benznidazole even after failed treatment regimens, and re-treatment was still effective.
  4. The protocol has potential applications for high-risk animals (example: working dogs, zoo animals), but its utility in humans remains uncertain due to the risk of adverse effects.

Clinical application:

  1. Higher benznidazole doses, administered intermittently, can cure T. cruzi in mice, dogs, and macaques.
  2. The twice-weekly regimen is promising for chronically infected dogs and non-human primates, providing an alternative to daily dosing protocols.
  3. Retreatment is viable if initial protocols fail, as parasites did not exhibit resistance.
  4. Dogs showed declining antibody levels, suggesting effective parasite clearance.
  5. The protocol could be especially beneficial for high-value animals in endemic regions.
  6. Long-term, high-dose benznidazole treatment shows limited toxicity in dogs and non-human primates, making it a potential option in veterinary settings.
  7. The absence of uniform outcomes suggests treatment duration may need to be tailored to individual cases.
Schematic representation of the study in chronically infected macaques treated weekly and biweekly with BNZ as described in caption
Figure 3. (A) Schematic representation of the study in chronically infected macaques treated weekly and biweekly with BNZ. A total of 10 macaques chronically infected with T. cruzi were used in this study; eight were treated with BNZ weekly at a concentration of 37.5 mg/kg (2.5 times the standard daily dose) over 28 weeks, follow by a cessation of the treatment between week 28 and 38 due to COVID-19 research restrictions. Two animals were kept as untreated controls. At week 38, five macaques (four treated and one untreated) were necropsied to collect the tissues for assessment of parasites persistence by qPCR. With the remaining five macaques, one of them was continued untreated and the other four were treated with a second round of BNZ delivered biweekly at the same concentration as before, over a 15-week period (from week 43 to 58). At the 62-week time point, this second set of macaques (four treated and one untreated) were necropsied to collect the tissues for assessment of parasites persistence by qPCR. (B) Macaque identification, pretreatment, and end of treatment course 1 (28 weeks) blood qPCR status, and tissue PCR results at necropsy are shown. Totals for tissue PCR indicate the number of T. cruzi DNA-positive PCRs per total number of tissue specimens tested singly or in pools of five from the indicated tissues.

Trypanosoma cruzi infection… 2024 JAVMA article

Title: Trypanosoma cruzi infection diagnosed in dogs in nonendemic areas and results from a survey suggest a need for increased Chagas disease awareness in North America

Authors: Emily A. Gavic, Sarah E. Achen, Phillip R. Fox, Eduardo J. Benjamin, Jonathan Goodwin, Tamilselvam Gunasekaran, Karsten E. Schober, Sonja S. Tjostheim, John Vickers, Jessica L. Ward, Duncan S. Russell, Mark Rishniw, Sarah A. Hamer, and Ashley B. Saunders

Journal/Date of Publication: Journal of the American Veterinary Medical Association, 2023

DOI: 10.2460/javma.22.10.0445

Objective: To describe the clinical presentation and outcome in dogs diagnosed with Trypanosoma cruzi infection in non-endemic areas and to survey veterinary cardiologists in North America for Chagas disease awareness.

Type of Study: Retrospective, multicenter study

Conclusions:

  1. Dogs can be diagnosed with Chagas disease in non-endemic areas, often linked to travel or relocation from endemic regions.
  2. The study found low awareness and knowledge of Chagas disease among veterinary cardiologists in nonendemic areas, underscoring the need for enhanced education and resources.

Clinical Application:

  1. Importance of considering Chagas disease in differential diagnoses for dogs with travel history and cardiac symptoms.
  2. Increased need for diagnostic resources and knowledge sharing among veterinarians in non-endemic regions.
  3. Encouragement for thorough travel history assessments to identify potential risks of vector-borne diseases.
AI generated rendering of T. cruzi parasite in blood
Trypanosoma cruzi parasite in blood (Generated with Adobe Stock AI)

Prophylactic low-dose… 2022 PLoS Neglected Tropical Diseases article

Title: Prophylactic low-dose, bi-weekly benznidazole treatment fails to prevent Trypanosoma cruzi infection in dogs under intense transmission pressure

Authors: Juan M. Bustamante, Angel M. Padilla, Brooke White, Lisa D. Auckland, Rachel E. Busselman, Stephanie Collins, Elizabeth L. Malcolm, Briana F. Wilson, Ashley B. Saunders, Sarah A. Hamer, and Rick L. Tarleton

Journal/Date of Publication: PLoS Neglected Tropical Diseases, 2022

DOI: 10.1371/journal.pntd.0010688

Objective: The focus of the study is the prevention of Trypanosoma cruzi infection (Chagas disease) in dogs, especially in environments with high transmission pressure, such as large dog kennels in southern Texas.

Type of study: Prospective

Conclusions: 

  1. Low-dose, bi-weekly benznidazole treatment did not prevent new T. cruzi infections in dogs under intense transmission pressure.
  2. 22.4% of dogs developed new infections, with no significant difference between the treated and control groups.
  3. More potent or frequent dosing may be necessary, and while this regimen did not prevent infections, the impact on clinical disease severity was not assessed in this study.

Clinical application:

  1. Current low-dose benznidazole regimen is ineffective in preventing T. cruzi infections in dogs in high transmission areas.
  2. More aggressive or frequent prophylactic treatment might be necessary.
  3. Prophylactic treatment did not show immediate benefits but its impact on disease severity or progression requires further study.
  4. The study highlights the risk of Chagas disease in working dogs, even under vector control measures.
  5. Regular PCR and serological monitoring can help in early detection of T. cruzi infection.
  6. Seasonal variation in transmission risk may suggest the need for earlier prophylaxis initiation.
  7. Prophylactic failure underscores the need for alternative approaches, including vaccine development or enhanced vector control.
  8. Further studies in dogs are key as they can serve as sentinels for human health because they have a similar disease progression, share the same environment, and exposure risks as humans.
multi-panel figure depicting results of serology of T. cruzi negative dogs in study as described in caption
Figure 2. Initial screening results with multiplex serology and PCR to identify T. cruzi-negative dogs to enroll in the prophylaxis study.(A) Schematic representation of dog screening and prophylaxis trial. Heatmaps of antibody levels (mean fluorescence intensity; MFI) and qPCR measurement of T. cruzi DNA in blood were used to classify dogs as uninfected (B), T. cruzi-infected (C), or seronegative but with a blood PCR result that did not reach the cut-off for being considered positive (D). Recombinant T. cruzi proteins are defined in the Materials and Methods; lysate = a sonicate of T. cruzi trypomastigotes and amastigotes; GFP = recombinant green fluorescent protein (negative antigen control); Parvo = Parvovirus vaccine antigen (positive serological control).

Prevalence of Trypanosoma cruzi infection… 2020 Veterinary Parasitology article

Title: Prevalence of Trypanosoma cruzi infection and associated histologic findings in domestic cats (Felis catus)

Authors: Italo B. Zecca, Carolyn L. Hodo, Sarah Slack, Lisa Auckland, Sandy Rodgers, Keswick C. Killet, Ashley B. Saunders, and Sarah A. Hamer

Journal/Date of Publication: Veterinary Parasitology, 2020

DOI: 10.1016/j.vetpar.2019.109014

Objective: To quantify domestic cat infection with T. cruzi using serologic and molecular approaches in a Chagas-endemic region of the southern United States, and to evaluate cardiac pathology in naturally infected versus uninfected cats.

Type of Study: Prospective, cross-sectional study

Conclusions:

  1. Seroprevalence: 11.4% of cats were seropositive.
  2. Molecular Findings: T. cruzi DNA was detected in 1.8% of cats; TcI genotype found exclusively.
  3. Histologic Findings: 42.1% of seropositive cats exhibited cardiac inflammation.
  4. Domestic cats are potential reservoirs for T. cruzi, underscoring the need for further research on their role in disease transmission and pathology.

Clinical application:

  1. Veterinarians in endemic areas should consider T. cruzi infection in cats with undiagnosed cardiac issues.
  2. Need for awareness about Chagas disease in cats, as it could signal risk to nearby humans and animals.
  3. Suggested monitoring of cats in endemic areas, especially those in rural and vector-prone environments.
photomicrograph of the left heart atrium of a cat 20x with H&E stain as described in caption
Figure 2. Left heart atrium of a cat 20x (H&E stain): Cardiac myofibers are separated by moderate numbers of lymphocytes and plasma cells, with myocyte degeneration and loss (Inflammation Score = 2/4).