History
A 4-year-old castrated male Mastiff died on the way to Louisiana State University Veterinary Teaching Hospital Emergency Services. The dog had been in distress for an hour and had a swollen wound on the right front paw which the owner had discovered a day prior and treated with over-the-counter topical medications. The body was submitted for postmortem examination to the Louisiana Animal Disease Diagnostic Laboratory. Two years prior, the dog had severe injuries from a car accident, including pneumothorax and nerve damage to the right forelimb.
Gross Findings
On postmortem examination, the pericardial sac had a tear at the base of the heart, with herniation of the right auricle (Figure 1). The herniated right auricle was markedly enlarged and filled with clotted blood. The heart was markedly enlarged, weighing 370 g (0.71% of body weight; reference interval, 0.43% to 0.99%). The right ventricle was severely dilated with significant thinning of the wall. The right ventricular free wall (RV) was 0.2 cm thick; the left ventricular free wall (LV) was 1.2 cm thick; and the interventricular septum was 1.2 cm thick (RV:LV ratio = 1:6; reference interval, 1:2 to 3). Multiple pale streaks were visible on the surface of the heart. The lungs were mottled pink to dark red, wet, and failed to collapse. There was mild hepatomegaly and a small amount of serosanguinous abdominal effusion. The fifth digit of the right forelimb was swollen and firm with ulceration.
A—Necropsy image of the body cavity of a 4-year-old castrated male Mastiff that died suddenly. The right auricle is dark red, enlarged, and herniated out of the pericardial sac (white asterisk). The lungs are mottled pink to dark red, wet, and fail to collapse. The liver is dark red and slightly enlarged. Mild serosanguineous effusion is present in the abdominal cavity (white arrowhead). B—The heart of the Mastiff removed from the body cavity. The right ventricle of the heart is markedly enlarged (curved arrow) as well as the right auricle (asterisk). Pale tan streaks are visible in the myocardium (arrowheads).
Citation: Journal of the American Veterinary Medical Association 263, 3; 10.2460/javma.24.08.0525
Histopathological Findings
Affecting 50% to 70% of the right ventricular free wall and interventricular septum as well as 30% of the left ventricular free wall in the examined sections, there was multifocal to coalescing myocarditis consisting of lymphocytes, macrophages, and plasma cells (Figure 2). The myofibers were atrophied and degenerated at the sites of inflammation with replacement fibrosis. No infectious agents were identified histologically. The liver had changes consistent with chronic passive congestion. Other findings included pulmonary edema, gallbladder edema, and pancreatic hemorrhage, indicating shock. The fifth digit of the right forelimb had chronic ulcerative dermatitis with bone remodeling.
Photomicrograph of the myocardium of the animal from Figure 1. Subgross picture of the right ventricle. Affecting approximately 50% to 70% of the right ventricular free wall and interventricular septum, the myocardium is replaced by inflammation (dark blue areas; arrow) and fibrosis (pale pink areas; circled). H&E stain; bar = 1,600 µm.
Citation: Journal of the American Veterinary Medical Association 263, 3; 10.2460/javma.24.08.0525
Molecular Diagnostic and Immunohistochemistry Findings
Immunohistochemistry for Trypanosoma cruzi, the causative agent of Chagas disease (American trypanosomiasis) labeled T cruzi antigen within the sarcoplasm of cardiomyocytes and cytoplasm of macrophages in areas of myocarditis (Figure 3). Trypanosoma cruzi was also confirmed via PCR testing. PCR testing for Bartonella henselae was negative.
Photomicrographs of the myocardium of the animal from Figure 1. A—The myocardium is infiltrated by large numbers of lymphocytes, histiocytes, and plasma cells, with fibrosis (asterisks) and cardiomyocyte atrophy (arrowheads). H&E stain; bar = 50 µm. B—Immunohistochemistry for Trypanosoma cruzi. The antigen is highlighted in red within presumptive macrophages and cardiomyocytes. Chromogen: Fast Red; bar = 50 µm.
Citation: Journal of the American Veterinary Medical Association 263, 3; 10.2460/javma.24.08.0525
Morphologic Diagnosis and Case Summary
Morphologic diagnoses: Myocarditis, lymphoplasmacytic and histiocytic, multifocal to coalescing, severe, chronic with intralesional T cruzi antigen and replacement fibrosis.
Case summary: Myocarditis and sudden death attributable to T cruzi infection (“Chagas disease”) in a dog.
Comments
The dog died suddenly, and postmortem examination revealed cardiomegaly. Based on the myocarditis noted microscopically and T cruzi antigen and nucleic acid detection by IHC and PCR, Chagas disease was diagnosed as the primary cause of death. The myocarditis led to heart failure, evidenced by chronic passive congestion in the liver, and cardiogenic shock, evidenced by pulmonary edema, gallbladder edema, and pancreatic hemorrhage. The pericardial tear was likely from a previous car accident, and the herniation of the right auricle could have occurred at that same time or afterward as the heart enlarged due to the chronic myocarditis. It is possible that the right auricular herniation also contributed to the cardiogenic shock. The initial complaint of a digit wound was irrelevant to the dog’s death.
Other possible differential diagnoses for an adult dog with cardiomegaly and sudden death include heartworm (Dirofilaria immitis) disease, dilated cardiomyopathy, or Bartonella henselae infection. Heartworm disease is diagnosed by the presence of heartworms in the pulmonary artery and characteristic endoarteritis. dilated cardiomyopathy, which is considered a genetic disease, is identified by eccentric ventricular dilation and histologic fibrofatty change or attenuated wavy myofibers with lack of significant inflammation. Bartonella henselae, the causative agent of cat scratch fever, is also a cause of myocarditis and can be confirmed by PCR testing.
Chagas disease is a zoonotic disease caused by the protozoan hemoflagellate T cruzi, which is transmitted to mammalian hosts by insects of the subfamily Triatominae, commonly known as kissing bugs. Transmission of T cruzi typically occurs when the kissing bug feeds and defecates near the bite site; the mammalian host then scratches the site of the insect bite and contaminates the wound with the insect’s infective feces. Vertical transmission occurs, as well as transmission by ingestion of contaminated water or food or ingestion of the kissing bug itself.1–3 Chagas disease can be a foodborne disease in humans, and typically occurs when an infected kissing bug is accidentally processed into a tropical fruit juice that is not pasteurized.4 This results in a severe form of disease when compared to cutaneous transmission due to exposure to an increased amount of T cruzi, and because T cruzi can penetrate gastric mucosa more easily than skin.
Historically, Chagas disease has been prevalent in Latin America, but there has been a growing number of cases identified in the southern US. The wildlife reservoir of T cruzi in the US includes at least 18 species including raccoons, rats, and squirrels.3 In regions where Chagas disease is endemic, dogs serve as both domestic reservoirs and sentinels. Dogs are more likely than humans to contract the parasite due to their habit of ingesting the kissing bug and are more susceptible to infection via kissing bug bite.3 If 1 dog in the household is infected then it is likely that other dogs in the household are also infected, and the infection of dogs precedes infection of children within a household.2,3
The life cycle of T cruzi begins when a triatomine vector takes a blood meal from an infected host with parasitemia. The trypomastigotes in the blood meal enter the midgut of the insect and become noninfective epimastigotes that then multiply. Starvation is thought to be a trigger for the next stage of their life cycle where epimastigotes move to the hindgut and differentiate into infectious metacyclic trypomastigotes which are shed in the insect’s feces.1 Once inoculated into a mammalian host, the metacyclic trypomastigotes penetrate host cells and become amastigotes. Trypanosoma cruzi preferentially infects mononuclear phagocytic cells, such as macrophages, and myocytes, but can invade all cell types.1 The amastigotes then undergo a replicative cycle within the host cell and transform into trypomastigotes which enter the bloodstream. These trypomastigotes can infect additional host cells or be ingested by the Triatomine insect via a blood meal.
There are 3 stages of Chagas disease in mammals: acute, indeterminate, and chronic. In the acute stage, patients often have detectable parasitemia but are asymptomatic. Clinical signs appear 2 to 3 weeks after infection and can include generalized lymphadenopathy, lethargy, pale mucus membranes, myocarditis, ascites, hepatomegaly, splenomegaly, and sudden death. ECG abnormalities like arrythmias or conduction abnormalities may be present.3,5 In humans, red-purple, warm, areas of edema termed “chagomas” are often present at the site of vector-borne transmission, usually on uncovered skin, particularly around the eye.4 In the indeterminate stage, parasitemia decreases, clinical signs abate, and ECG abnormalities improve.5 Patients may remain in the indeterminate phase for an indefinite amount of time. In the chronic stage, ventricular arrythmias, mostly premature contractions, may precede cardiovascular problems due to ongoing myocardial degeneration leading to heart failure.2 Other clinical signs can include exercise intolerance, megaesophagus, and megacolon.3
Diagnosis of Chagas disease is difficult given the lack of distinct clinical signs and it is common for the disease to go unnoticed until the animal dies suddenly due to heart failure. Indirect hemagglutination test, indirect immunofluorescence test, ELISA, and PCR can be used for diagnosis; however, results of these tests are often variable and it is recommended that 2 different testing methods are used to confirm the diagnosis.3 In the acute stage when parasitemia is high, hemoculture and PCR are the tests of choice, and T cruzi may be seen on blood smears. In the later stages, parasitemia is lower and indirect tests like the indirect hemagglutination test, indirect immunofluorescence test, and ELISA are a better choice.3 Treatment for Chagas disease is challenging. In humans, Chagas disease can be treated with Benznidazole and Nifurtimox; however, these drugs do not consistently prevent T cruzi-induced cardiomyopathy nor are effective in established chronic T cruzi-induced cardiomyopathy.4 Treatment protocols for dogs are not well established. Preventative measures include pest control and dog collars treated with Deltamethrin to prevent triatomine bites.3
Acknowledgments
The authors thank the members of the Histology and Immunohistochemistry section at the Louisiana Animal Disease Diagnostic Laboratory/LSU Diagnostics, School of Veterinary Medicine, Louisiana State University.
Disclosures
The authors have nothing to disclose. No AI-assisted technologies were used in the generation of this manuscript.
Funding
The authors have nothing to disclose.
References
- 2.↑
Meyers AC, Hamer SA, Matthews D, Gordon SG, Saunders AB. Risk factors and select cardiac characteristics in dogs naturally infected with Trypanosoma cruzi presenting to a teaching hospital in Texas. J Vet Intern Med. 2019;33(4):1695-1706. doi:10.1111/jvim.15516
- 3.↑
Nieto P. Ecological Risk Models for Visceral Leishmaniasis in Bahia, Brazil and Diagnosis of Trypanosoma cruzi Infection in Dogs in South Central Louisiana. Dissertation. Louisiana State University; 2009.
- 4.↑
Altcheh JM, Freilij H. Chagas disease: Disease: A Clinical Approach. Springer Nature; 2019. doi:10.1007/978-3-030-00054-7
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Barr SC, Gossett KA, Klei TR. Clinical, clinicopathologic, and parasitologic observations of trypanosomiasis in dogs infected with North American Trypanosoma cruzi isolates. Am J Vet Res. 1991;52(6):954-960. doi:10.2460/ajvr.1991.52.06.954
