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

Trypanosoma cruzi naturally infects a broad range of mammalian species and frequently results in the pathology that has been most extensively characterized in human Chagas disease. Currently employed treatment regimens fail to achieve parasitological cure of T. cruzi infection in the majority of cases. In this study, we have extended our previous investigations of more effective, higher dose, intermittent administration protocols using the FDA-approved drug benznidazole (BNZ), in experimentally infected mice and in naturally infected dogs and nonhuman primates (NHP). Collectively, these studies demonstrate that twice-weekly administration of BNZ for more than 4 months at doses that are ~2.5-fold that of previously used daily dosing protocols, provided the best chance to obtain parasitological cure. Dosing less frequently or for shorter time periods was less dependable in all species. Prior treatment using an ineffective dosing regimen in NHPs did not prevent the attainment of parasitological cure with an intensified BNZ dosing protocol. Furthermore, parasites isolated after a failed BNZ treatment showed nearly identical susceptibility to BNZ as those obtained prior to treatment, confirming the low risk of induction of drug resistance with BNZ and the ability to adjust the treatment protocol when an initial regimen fails. These results provide guidance for the use of BNZ as an effective treatment for T. cruzi infection and encourage its wider use, minimally in high value dogs and at-risk NHP, but also potentially in humans, until better options are available.

The Use of a Modified Script Concordance Test in Clinical Rounds to Foster and Assess Clinical Reasoning Skills.

The development of clinical reasoning skills is a high priority during clinical service, but an unpredictable case load and limited time for formal instruction makes it challenging for faculty to foster and assess students' individual clinical reasoning skills. We developed an assessment for learning activity that helps students build their clinical reasoning skills based on a modified version of the script concordance test (SCT). To modify the standard SCT, we simplified it by limiting students to a 3-point Likert scale instead of a 5-point scale and added a free-text box for students to provide justification for their answer. Students completed the modified SCT during clinical rounds to prompt a group discussion with the instructor. Student feedback was positive, and the instructor gained valuable insight into the students' thought process. A modified SCT can be adopted as part of a multimodal approach to teaching on the clinic floor. The purpose of this article is to describe our modifications to the standard SCT and findings from implementation in a clinical rounds setting as a method of formative assessment for learning and developing clinical reasoning skills.

Correlations between age, body size, sex, and conformation and ultrasound-measured femoral vessel diameter in the dog, with implications for transvascular procedural planning.

Transvascular interventional radiology procedures have advanced in veterinary medicine, but basic knowledge about expected vascular size and vascular imaging requires further exploration. A prospective analytical study of 230 client-owned dogs was carried out to investigate correlations between ultrasound-measured femoral artery (FA) and femoral vein (FV) diameter and various morphometric and demographic dog variables, compare ultrasound-measured femoral vessel diameter to diameter predicted by body weight, compare right- and left-sided femoral vessel diameter, and assess measurement repeatability. Internal diameter of the FA and FV was measured with ultrasound bilaterally. Allometrically scaled body weight had the strongest correlation with FA and FV diameter (correlation coefficients: 0.92 and 0.80, respectively), although thigh circumference (FA: 0.89; FV:0.78) and withers height (FA: 0.84; FV: 0.76) were also strongly correlated. Within the entire population, males had a smaller FA (P = .005), but not FV (P = .278), than females and age was negatively associated with FA (P = .031) and FV (P < .001) diameter. Compared to ultrasound-derived measurements, body weight-predicted diameter overestimated by at least one French gauge in 32.6% and 35.2% of dogs for the FA and FV, respectively. Comparison of left and right FA and FV diameter revealed minimal mean differences, though limits of agreement could encompass multiple French gauge sizes: (Mean difference [limits of agreement]: FA = 0.00 mm [0.85-0.84 mm]; FV = 0.04 mm [1.92-1.99 mm]). Intra- and interoperator repeatability coefficients of variation were <9%. Femoral vessel diameter in dogs is influenced by multiple factors, with potential for clinically relevant differences between right- and left-sided vessels. Ultrasound measurement of femoral vessels could improve transvascular preprocedural planning.

The Creation of a Collaborative, Case-Based Learning Experience in a Large-Enrollment Classroom.

Numerous educational studies have shown that passive learning methods are frequently associated with disappointing learning outcomes, yet many faculty instructors continue to rely on passive didactic lectures. This article describes the creation of an active learning teaching approach-referred to as the collaborative, case-based classroom-that combines three pedagogical strategies: peer-assisted learning, case-based learning, and just-in-time teaching. Data from student surveys of a third-year cardiology elective showed a preference for this teaching approach compared with a case-based lecture. Six major themes emerged from survey analysis: engagement/interactivity, instructional benefit, clinical reasoning, clinical relevance, peer-assisted learning, and timely feedback. Although detailed here in the context of a cardiology elective, the collaborative, case-based classroom is a teaching approach that could be modified to fit a variety of other teaching environments.

Selected cardiac abnormalities in Trypanosoma cruzi serologically positive, discordant, and negative working dogs along the Texas-Mexico border.

BACKGROUND: Chagas disease is increasingly recognized in the southern U.S., where triatomine vectors transmit Trypanosoma cruzi among wildlife and domestic dogs with occasional vector spillover to humans. As in humans, clinical outcome in dogs is variable, ranging from acute death to asymptomatic infections or chronic heart disease. In order to characterize cardiac manifestations of T. cruzi infections, we tracked a cohort of naturally-infected dogs and a matched cohort of uninfected dogs. We hypothesized that selected measures of cardiac disease (abnormal rate, abnormal rhythm, and elevated cardiac troponin I (cTnI; a biomarker of cardiac injury)) would occur more commonly in infected than uninfected dogs matched by age, breed, sex and location. In addition to the clearly positive and negative dogs, we specifically tracked dogs with discordant test results across three independent serological assays to gather clinical data that might elucidate the infection status of these animals and inform the utility of the different testing approaches. RESULTS: We placed an ambulatory ECG monitor (Holter) on 48 government working dogs and analyzed 39 successful recordings that met length and quality criteria from 17 T. cruzi-infected, 18 uninfected dogs and 4 dogs with discordant results. Overall, 76.5% of positive, 100.0% of discordant, and 11.1% of negative dogs showed > 1 ECG abnormality (p < 0.0001), and positive and discordant dogs had a higher mean number of different types of ECG abnormalities than negative dogs (p < 0.001-0.014). The most common cardiac abnormalities included supraventricular and ventricular arrhythmias and atrioventricular block. Positive dogs had higher serum concentrations of cTnI than both negative dogs (p = 0.044) and discordant dogs (p = 0.06). Based on dog handler reports, nearly all (4/5; 80%) dogs with reported performance decline or fatigue were T. cruzi-infected dogs. CONCLUSIONS: Further understanding cardiac manifestations in dogs naturally infected with T. cruzi is critical for prognostication, establishing a baseline for drug and vaccine studies, and better understanding of zoonotic risk.

Echocardiographic values and prevalence of cardiac abnormalities in clinically healthy adult Borzoi dogs.

OBJECTIVE: To develop breed-specific echocardiographic values for normal Borzoi and to report the prevalence of structural cardiac abnormalities. ANIMALS: 146 clinically healthy, adult Borzoi dogs. METHODS: Cardiac auscultation and standard echocardiograms were performed. Longitudinal follow-up was described in a subset of dogs (n = 25). RESULTS: Most Borzoi were structurally normal (119/146, 81.5%), with breed-specific echocardiographic values generated independently for each sex, as females weighed significantly less than males (30.4 ± 3.8 kg vs 38.3 ± 4.1 kg, respectively; P < .001), and a significant impact of sex was found on most measurements. Physiologic heart murmurs were identified in 64/119 (53.8%) normal dogs. Thirty-six (30.2%) structurally normal dogs had trace or mild mitral regurgitation, and 43 (36.1%) had trace or mild tricuspid regurgitation. Structural cardiac disease was identified in 21 dogs (14.4%), including 9 dogs (6.2%) with dilated cardiomyopathy (DCM), 9 dogs (6.2%) with stage B1 myxomatous mitral valve disease (MMVD), and 3 (2.1%) dogs with congenital abnormalities. Seven dogs (4.8%) had equivocal abnormalities. During follow-up, new dogs were diagnosed with occult DCM (n = 3), equivocal DCM (1), and stage B1 MMVD (2). Two dogs originally diagnosed with DCM (1 occult and 1 equivocal) normalized after diet change. CLINICAL RELEVANCE: Borzoi dogs commonly have physiologic heart murmurs and mild atrioventricular valve regurgitation. Both DCM and MMVD were identified at similar frequencies in healthy Borzoi, although dogs with MMVD all had normal heart sizes. Echocardiographic screening for DCM in Borzoi should be considered, with breed-specific echocardiographic values now available for improved diagnostic confidence.

Electrocardiographic abnormalities are frequently detected in healthy adult Borzoi with a normal echocardiogram.

OBJECTIVE: Borzoi reportedly experience sudden death. The objective of this study was to report ECG intervals, amplitudes, and frequency of ECG abnormalities in clinically healthy Borzoi. METHODS: 98 clinically healthy Borzoi were prospectively recruited and underwent echocardiogram, ECG, and cardiac troponin I testing between October 2020 and December 2022. Standard ECG measurements were obtained. Early repolarization notches and slurs were recorded. RESULTS: Of 82 Borzoi with a structurally normal echocardiogram, ventricular arrhythmias were documented in 8 (10%) dogs, all of which had normal cardiac troponin I concentrations. Median P wave duration was 55 milliseconds (range, 45 to 70 milliseconds). Median PR interval was 125 milliseconds (range, 80 to 175 milliseconds). Thirty-one (38%) Borzoi had first-degree atrioventricular block (PR interval > 130 milliseconds). Median QRS duration was 65 milliseconds (range, 48 to 90 milliseconds). Median QT interval was 235 milliseconds (range, 185 to 275 milliseconds). Twenty-nine (35%) and 15 (18%) of 82 Borzoi had QT intervals > 240 or > 250 milliseconds, respectively. Sixty-seven of 82 (82%) Borzoi had early repolarization notches or slurs. Seventeen of 82 (21%) Borzoi had an abnormality of the ST segment, most commonly convexity/doming. Convexity of the ST segment was intermittent (n = 9) or persistent (4). CONCLUSIONS: Ventricular arrhythmias, early repolarization, prolonged QT intervals, and ST segment abnormalities are not infrequent in clinically healthy Borzoi. P, PR, and QRS durations are commonly prolonged compared to general canine reference intervals. CLINICAL RELEVANCE: Future study into heritable channelopathies in Borzoi is warranted given the frequency of ventricular arrhythmias, repolarization abnormalities, and sudden death in the breed. Breed-specific ECG reference intervals are needed.

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

Trypanosoma cruzi infection in dogs can cause heart failure and sudden death with few treatment options available. A litter of 4 dogs living in a T cruzi endemic area were randomized to prophylaxis and nonprophylaxis groups as part of a study evaluating a modified benznidazole dosing regimen administered twice weekly to prevent T cruzi infection during a vector transmission season. The 2 dogs that received prophylaxis remained healthy without T cruzi infection or cardiac disease for >2 years. One dog that did not receive prophylaxis died unexpectedly with acute T cruzi-induced pancarditis, and the second dog tested positive for T cruzi and developed complex arrhythmias with markedly increased cardiac troponin I and improved with a higher benznidazole treatment dose. Although the small sample size precludes definitive conclusions, we describe the potential clinical benefit of prophylactic and early treatment with modified benznidazole dosing regimens for dogs with T cruzi infection.

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

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. METHODS: A prospective, cross-sectional study was performed using a simplified diagnostic evaluation including high-sensitivity cardiac troponin I, 30-second ECG, and echocardiogram with 7 variables in 46 client-owned dogs from high-risk environments. Dogs were categorized as serologically positive (SP), negative (SN), or discordant (SD) by use of 2 antibody tests. Functional evaluation of cardiac health scores and blood PCR were obtained. RESULTS: Dogs were SP (n = 19), SN (17), and SD (10), with 9 PCR positive (7 SP, 1 SN, 1 SD). Troponin was above reference range in 6 of 46 (4 SP, 1 SN, 1 SD), and functional evaluation of cardiac health scores were 0 in all dogs. Conduction system abnormalities (prolonged interval durations, second-degree atrioventricular block, splintered QRS complex) and ventricular arrhythmias were documented in 8 (7 SP, 0 SN, 1 SD). Twenty-six (12 SP, 8 SN, 6 SD) had echocardiographic abnormalities, most often myxomatous mitral valve disease (MMVD) and left ventricular enlargement. Seropositive dogs were significantly older and had a higher likelihood of MMVD. Conduction system abnormalities were associated with positive serostatus. CONCLUSIONS: Echocardiographic abnormalities were complicated by MMVD and did not distinguish between serostatus. An ECG with assessment and detailed measurement of complexes and cardiac troponin I are simple tests to perform with abnormalities detected in seroreactive dogs. CLINICAL RELEVANCE: Electrocardiographic abnormalities in high-risk or seroreactive dogs should prompt further evaluation and monitoring of T cruzi infection.

An intrapericardial technique for PDA ligation: surgical description and clinical outcome in 35 dogs.

A number of surgical techniques have been reported for dissection and ligation of patent ductus arteriosi (PDAs) in dogs. The objectives of this study were to provide a detailed description of an intrapericardial technique for PDA dissection and ligation and to report the clinical outcome of that technique in dogs. Medical records of 35 dogs were retrospectively reviewed for signalment, clinical signs, echocardiographic findings, surgical time, intra- and postoperative complications, and completeness of ductal closure. Median surgery time was 60 min (range, 35-125 min). Neither intraoperative nor postoperative complications occurred. Within 48 hr of surgery, the continuous left basilar heart murmur was absent in all dogs, and complete echocardiographic closure was confirmed in 29 of 32 dogs. Residual flow was identified echocardiographically in three dogs within 48 hr of surgery. Residual flow was decreased in one dog at 1 mo, which resolved within 33 mo. One dog had mild residual flow postoperatively but did not return for follow-up. The intrapericardial technique was successful for PDA dissection and ligation and had a lower rate (6%) of echocardiographic residual flow compared with previously reported techniques.