Myocarditis in a Dog Positive for Brucella canis
ABSTRACT
A 1 yr old female spayed dog presented for evaluation of lethargy, hyporexia, and left hind limb lameness. On presentation, she was tachycardic and febrile. Echocardiogram revealed pericardial effusion and evidence of pericarditis and myocarditis, and electrocardiogram showed underlying sinus rhythm with complex arrhythmias. Cardiac troponin-I level was markedly elevated. The dog was hospitalized for 6 days on IV fluid therapy and treated with ampicillin/sulbactam and enrofloxacin. She was discharged on amoxicillin-clavulanic acid and maropitant citrate. Within 24 hr, the dog returned because of progressive clinical signs. It was revealed that two of her littermates had tested positive for Brucella canis, so antimicrobial therapy was switched to enrofloxacin and doxycycline. Six days later, the dog developed worsening clinical signs and was euthanized. Postmortem examination was performed. Blood cultures and brucellosis testing were positive for B canis. Two other dogs and two humans in the household were ultimately diagnosed with brucellosis. To our knowledge, infection with B canis has not been reported in dogs diagnosed with myocarditis. However, myocarditis is a rare clinical manifestation of brucellosis in humans. Depending on patient history, clinical signs, and diagnostic findings, brucellosis is a zoonotic disease that may be a differential diagnosis in dogs with suspected myocarditis.
Introduction
Myocarditis is an uncommon, inflammatory disease of the myocardium that is caused by numerous infectious and noninfectious agents.1,2 Endomyocardial biopsy is routinely performed in humans to acquire an antemortem diagnosis; however, this procedure is less common in dogs, and antemortem diagnosis of myocarditis is often based on clinical evaluation.1 Myocarditis is a rare complication of brucellosis in humans,3 but myocarditis associated with brucellosis has not been reported in dogs.
Brucellosis is a zoonotic disease caused by gram-negative bacteria belonging to the genus Brucella.4 Brucella canis is the species of bacteria known primarily for causing brucellosis in dogs. Infection with B canis is often considered an underdiagnosed disease in both dogs and humans, owing to the wide variety of possible clinical signs and to false-negative test results.5,6 The bacteria are difficult to eradicate in dogs, and euthanasia is often the recommended treatment.4,6 Alternatively, treatment with antimicrobials can be considered. Combination antimicrobial therapy has historically been favored over a single-agent treatment plan. The use of tetracyclines, aminoglycosides, enrofloxacin, and rifampin has been reported, and prolonged treatment and monitoring is often necessary.4,6
The objective of this case report is to describe the clinical presentation, evaluation, outcome, and zoonotic relevance of a dog diagnosed with myocarditis and B canis.
Case Report
A 20.3 kg 1 yr old spayed female mixed-breed dog was presented for evaluation of a 1 wk history of lethargy, hyporexia, and left hind limb lameness. The dog had been transported from Texas at 8 wk of age, after being discovered with littermates in a dumpster. One week before presentation, she had been prescribed carprofen by her primary care veterinarian for left hind limb lameness, after which the lameness improved but appetite and energy level worsened. Informed consent was obtained from the owners before any diagnostics or treatment, and the dog was clinically managed according to contemporary standards of care.
Initial physical examination findings included tachycardia with an irregular rhythm, pyrexia (39.4°C), and moderate generalized muscle wasting with a body condition score of 3/9. Findings prompted the use of point-of-care ultrasound, which revealed mild pericardial effusion. Initial laboratory testing was performed, including a complete blood count, serum chemistry panel, and urinalysis. The white blood cell count was moderately elevated (33,550 cells/µL; reference interval [RI] 4400–15,100 cells/µL) with a moderate neutrophilia (26,505 cells/µL; RI 2800–11,500 cells/µL) and a moderate monocytosis (3360 cells/µL; RI 100–1500 cells/µL). Serum chemistry profile revealed hyperglobulinemia (5.7 g/dL; RI 2.3–4.2 g/dL), hypoalbuminemia (2.5 g/dL; RI 2.8–4.0 g/dL), and elevated alkaline phosphatase (365 U/L; RI 12–127 U/L) and aspartate aminotransferase (126 U/L; RI 9–54 U/L). Urinalysis showed rare white blood cells and trace protein; urine culture was negative. Cardiac troponin-I was elevated at 8.0 ng/mL (RI <0.08 ng/mL). Thromboelastography performed on day two of hospitalization was normal. Antibody and polymerase chain reaction for Trypanosoma cruzi testing was submitted on day two of hospitalization, and results were negative when received 2 wk later.
Thoracic radiographs performed on the day of admission showed a mildly enlarged cardiac silhouette, a mild diffuse interstitial pattern, and spondylosis of T12-L2 with radiolucent regions within the endplates of T13-L2. Abdominal ultrasound showed an enlarged spleen with irregularly shaped, hypoechoic foci. The medial iliac and pancreaticoduodenal lymph nodes were mildly enlarged. Fine needle aspirate of the splenic foci yielded no cytologic abnormalities.
Transthoracic echocardiography performed on day two of hospitalization revealed a moderate volume of echogenic pericardial effusion with mild cardiac tamponade. The pericardium appeared subjectively mildly thickened and the myocardium had mixed echogenicity (Figure 1). The left ventricular systolic function was subjectively reduced (Supplementary Video I). Electrocardiographic findings included an underlying sinus rhythm with intermittent sinus pauses, occasional sinus arrest, paroxysmal supraventricular tachycardia, variable first-degree atrioventricular block, and ST segment elevation on a chest lead.
Citation: Journal of the American Animal Hospital Association 61, 6; 10.5326/JAAHA-MS-7485
Pericardiocentesis was performed, and 150 mL of serosanguinous fluid was removed. Cytologic analysis revealed mixed inflammation (packed cell volume 1.0%, total nucleated cell count 18.54 K/µL with 58% nondegenerate neutrophils, 26% macrophages, 16% small, well-differentiated lymphocytes). No infectious organisms were detected. Anaerobic, aerobic, and fungal cultures yielded no growth.
Additional testing performed on day two of hospitalization included an endotracheal wash with cytology and culture. Cytology revealed suppurative inflammation with a small, mixed population of bacteria. Few organisms were found intracellularly, and no fungal elements were noted. Fungal serology panel including testing for Coccidioides (immunoglobulin G and immunoglobulin M), Blastomyces, Cryptococcus, Histoplasma, and Aspergillus was negative for all agents. The primary differential for this dog was myocarditis and pericarditis with unknown etiology.
The dog was hospitalized on continuous electrocardiogram monitoring and IV fluids. Blood cultures were submitted, and antimicrobial therapy was initiated with ampicillin/sulbactam (50 mg/kg IV q 8 hr) and enrofloxacin (10 mg/kg IV q 24 hr). Within 12 hr of initiating antimicrobials, the dog’s rectal temperature decreased to 37.5°C. Repeat cardiac troponin-I showed a reduction to 3.3 ng/dL. The dog was discharged on day six of hospitalization with amoxicillin-clavulanic acid (13 mg/kg per os [PO] q 12 hr) and maropitant citrate (2 mg/kg PO q 24 hr).
The dog returned to the hospital within 24 hr of being discharged, when the owner learned that two of the dog’s littermates had tested positive for B canis. The dog also had shown progressive lethargy and anorexia. Antimicrobial therapy was switched from amoxicillin-clavulanic acid to enrofloxacin (7 mg/kg PO q 24 hr) and doxycycline (5 mg/kg PO q 12 hr), and the zoonotic risks associated with brucellosis were discussed. The blood culture was pending, so serological testing for brucellosis was submitted.
Six days later, the dog was presented to the emergency service for worsening clinical signs. Her owner reported restlessness, tachycardia, and tachypnea. Physical examination revealed 1 kg of weight loss, tachycardia, an irregular rhythm, a new grade III/VI systolic murmur, distended jugular veins, and thready femoral pulses with pulse deficits. She was afebrile at 38.0°C. Point-of-care ultrasound showed mild pleural effusion, mild pericardial effusion, and markedly decreased systolic function. The owners elected to euthanize the dog.
A postmortem examination was performed by a board-certified pathologist. The pericardium was mildly thickened and contained approximately 5 mL of red-tinged, clear fluid. The epicardium was diffusely roughened with the apex of the heart being most affected (Figure 2A). There were extensive, multifocal to coalescing, irregular, white to tan areas on the epicardium that extended transmurally to the endocardial surface on cut section (Figure 2B). No abnormalities were noted on the heart valves. Additionally, there was pleural effusion, thickened mediastinal pleura, mildly enlarged sternal lymph nodes, and pulmonary edema.
Citation: Journal of the American Animal Hospital Association 61, 6; 10.5326/JAAHA-MS-7485
Histologically, there was severe, transmural pyogranulomatous pancarditis characterized by multifocal to coalescing separation and replacement of cardiomyocytes by an infiltrate primarily composed of neutrophils and macrophages, with fewer lymphocytes and plasma cells (Figure 2C). In the most severely affected areas, cardiomyocytes exhibited necrosis, characterized by shrinkage, fragmentation, loss of cross striations, and hypereosinophilic sarcoplasm. Extracardiac lesions included pulmonary edema, with increased numbers of alveolar macrophages containing intracytoplasmic erythrocytes (heart failure cells), and bridging spondylosis at the level of T12-L1.
The cardiac tissues were stained with Periodic acid-Schiff, Gram, and Ziehl-Neelsen. No pathologic agent was detected. The final diagnosis was severe, chronic-active, transmural pyogranulomatous pancarditis, with congestive heart failure and discospondylosis.
Blood cultures, rapid slide agglutination, and agar gel immunodiffusion were positive for B canis. The state health department was then notified, because brucellosis is considered a reportable disease. In accordance with guidance from the Centers for Disease Control and Prevention, individuals who had direct contact with the dog were also notified. Two of four household dogs and two human family members tested positive for B canis. The affected humans had mild symptoms that resolved with medical management.
Discussion
Myocarditis is an uncommon inflammatory disease of the myocardium that has been associated with cardiac dysfunction and a guarded prognosis in dogs.1 Multifocal arrhythmias, including ventricular tachycardia, supraventricular tachyarrhythmia, and atrioventricular block, and/or dilated cardiomyopathy phenotype are hallmarks of the disease.1,2 Presenting complaints often include nonspecific signs of lethargy and hyporexia. The most common physical examination and laboratory findings in dogs with myocarditis include fever, heart murmur, neutrophilia, monocytosis, evidence of decreased organ perfusion, and elevations of cardiac troponin-I. Many infectious and noninfectious causes of myocarditis have been reported in dogs.1,2
Myocarditis is a reported rare clinical manifestation of brucellosis in humans.3,7 Brucellosis is a zoonotic disease caused by gram-negative bacteria belonging to the genus Brucella.4 B canis has the lowest zoonotic potential among Brucella species and is primarily known for causing brucellosis in dogs.8 Routes of infection for B canis include oral, nasal, conjunctival, and genital mucosa. Puppies can be infected through vertical transmission and may either seroconvert or become permanent carriers of the bacteria.4,8 Once a dog becomes a permanent carrier, antimicrobial therapy is unlikely to be successful at eliminating the infection.4
Brucella canis is known for causing reproductive signs in dogs, such as epididymitis in males and abortions in females. However, the bacteria can spread to nonreproductive organs and result in diseases such as lymphadenitis, uveitis, endocarditis, and discospondylitis.4–6 Discospondylitis can manifest as lameness in dogs. This dog had severe focal discospondylosis and a history of lameness, which could have been secondary to prior discospondylitis. Other nonspecific signs of brucellosis that this dog experienced are fever, lethargy, hyporexia, and weight loss.4,8 Although the postmortem microscopic examination did not reveal the presence of bacterial organisms, the positive blood cultures and serology, in combination with clinical findings and histopathological evidence of severe myocarditis, support a diagnosis of Brucella-related myocarditis.
Treatment is often successful in humans with brucellosis, whereas euthanasia is generally recommended in dogs, because of concern for transmission to humans or other dogs.3,4,6 Dogs without clinical signs of the disease could potentially be isolated until the organism self-eliminates. However, antimicrobial treatment in persistently infected dogs, or dogs with significant illness, is often unsuccessful, with a high risk of relapse. If treatment is pursued, combination antimicrobial therapy with tetracyclines and aminoglycosides is favored.4,6 However, relapse is still considered likely and continued monitoring is necessary.4
Diagnosing both myocarditis and brucellosis can be challenging in dogs. A set of criteria to diagnose myocarditis in dogs has been proposed.1 Although this set of criteria may be helpful in diagnosing myocarditis earlier, treatment remains challenging because it is often based on the underlying etiology. Brucellosis diagnosis requires an index of suspicion based on clinical findings and close attention to signalment and history. The potential zoonotic nature of B canis necessitates careful biosecurity protocols during patient care and testing.8
Conclusion
This report describes a dog with severe myocarditis and B canis. Therefore, brucellosis may be considered as a differential diagnosis in dogs diagnosed with myocarditis, especially in young dogs with unknown backgrounds and other signs of systemic disease (i.e., discospondylitis or reproductive organ involvement). Although rare, the diagnosis of B canis has important clinical and health safety implications for owners, medical personnel, and laboratory staff, which further underscores the importance of early clinical suspicion.
The authors would like to thank the hospital technicians, students, and staff involved in this case as well as the histopathology and clinical pathology staff.
Transthoracic right parasternal long-axis 2-D echocardiographic images showing long axis (A) and short axis (B) views. There is a moderate volume of pericardial effusion (white stars) and thickened pericardium (white arrow). LA, left atrium; LV, left ventricle; RV, right ventricle.
Gross image of the intact heart (A) and a cut section through the left and right ventricle (B). Panel A demonstrates diffuse roughening of the epicardium, with the apex of the heart being most affected. Panel B demonstrates extensive, transmural, multifocal to coalescing, irregular, white to tan areas, with the left ventricle and interventricular septum being the most affected. Panel C shows a photomicrograph of the heart at 10× magnification showing severe, transmural pyogranulomatous pancarditis characterized by multifocal to coalescing separation and replacement of cardiomyocytes by an infiltrate primarily composed of neutrophils and macrophages, with fewer lymphocytes and plasma cells (asterisks). In the most severely affected areas, cardiomyocytes exhibited necrosis, characterized by shrinkage, fragmentation, loss of cross striations, and hypereosinophilic sarcoplasm. Hematoxylin and eosin stain; bar = 200 μm.
Contributor Notes
The online version of this article (available at www.jaaha.org) contains supplementary data in the form of one video.
