Conference 15 - 2015 Case: 03 20160121

Signalment:

Three-year-old female green iguana / common iguana (Iguana iguana)The owner raises green iguanas as well as multiple other species of iguanas. The three green iguanas consisted of two females and a male that were housed together. The green iguanas would fight amongst themselves with two of the iguanas developing cutaneous abscesses. The female iguana presented for necropsy became acutely ill and was dead on arrival at the submitting veterinary clinic.

Gross Description:

The iguana was in good body condition with mild postmortem decomposition. There was a 1.8 x 1.8 cm subcutaneous abscess on the chin. The liver was enlarged and slightly pale. The spleen was enlarged. The urinary bladder contained large amounts of urates. The lungs contained a few multifocal pinpoint to 0.3 cm white foci. The pericardial sac contained moderate amounts of slightly cloudy light yellow fluid that contained free floating clots of fibrin. The pericardial sac was focally adhered to the epicardium of the left ventricle. The endocardium associated with the pericardial adhesion was thick and white. The lumen of the right ventricle was almost completely filled with a large, friable, yellow, fibrinopurulent exudate that was attached to the endocardium and multifocally extended into the myocardium. The endocardium of the right ventricle was thickened and white.

Histopathologic Description:

Heart: The lumen of the right ventricle contains a large thrombus consisting of fibrin, cellular debris, and rare macrophages and heterophils that is multifocally attached to the mural and valvular endocardium. The thrombus contains moderate numbers of small gram-negative cocci. The thrombus is surrounded by numerous epithelioid macrophages and multinucleated giant cells with lesser numbers of heterophils and lymphocytes. The endocardium of the right ventricle is markedly thickened by fibrous tissue that contains small numbers of granulomas characterized by a center of fibrin, necrotic debris and small cocci surrounded by epithelioid macrophages, multinucleated giant cells, heterophils, and lymphocytes. There are a few similar granulomas in the myocardium of the right ventricle. The epicardium is multifocally thickened by fibrous tissue, macrophages, heterophils, and lymphocytes.

Morphologic Diagnosis:

1. Heart, right ventricle: Mural and valvular vegetative endocarditis with heterophilic and granulomatous inflammation and intralesional small gram-negative cocci; etiology, Neisseria iguana
2. Heart, right ventricle: Myocardial granulomas

Lab Results:

Neisseria iguana was cultured from the subcutaneous abscess and the exudate in the right ventricle of the heart.

Condition:

Vegetative endocarditis, Neisseria iguanae, iguana

Contributor Comment:

Neisseria sp. are gram-negative bacteria that typically grow as diplococci in culture.(5,7) The most well-known species of Neisseria are N. gonorrheae and N. meningitidis. Neisseria gonorrhea is a venereal disease of humans. Neisseria meningitidis causes meningitis in people. However, most Neisseria species are commensal bacteria that are part of the normal oral and nasopharyngeal flora of mammals and the intestinal tract of birds.

In the 1980s, a syndrome of abscesses and septicemia in rhinoceros iguana and common iguana was identified at the National Zoological Park.(7) The causative agent of the disease was classified as a new bacterium called Neisseria iguanae.(1) The bacterium was also isolated from the oral cavity from healthy animals in the collection. The cutaneous abscesses were believed to be the result of N. iguanae infection of the skin following bite wounds. One of the iguanas developed N. iguanae septicemia manifested as a liver abscess. In this case, the intraspecies aggression between the three common iguanas most likely resulted in the cutaneous abscess and mural and valvular endocarditis caused by Neisseria iguanae in this case.

The pathogenesis of bacterial endocarditis (also classified as infective endocarditis) is complex.(4,8,9,10) The formation of infective endocarditis lesions involves the preparation of the endothelial layer for colonization, adherence of bacteria to the endothelial surface and survival of the bacteria with propagation of the thrombus.(8) Intact endothelium is believed to be resistant to bacterial colonization.(4,8,9,10) The resistant endothelial layer has to be disturbed in order for bacteria to adhere. The disturbance of the endothelial layer can be the result of mechanical forces or due to endothelial cell activation and damage as the result of local proinflammatory molecules such as IL-1.(10) The endothelial cell damage causes activation of the coagulation cascade through the activity of tissue factor resulting in what is termed nonbacterial thrombotic endocarditis (NBTE). The resulting thrombus is colonized by bacteria that can adhere to damaged endothelial cells, platelets and adhesive extracellular matrix molecules such as fibrin and fibronectin. The bacteria adhere to the matrix molecules of the clot using a variety of surface molecules collectively called microbial surface component reacting with adhesive matrix molecules (MSCRAMMs).(10) The proliferation of the thrombus of infective endocarditis involves the interaction of bacterial pathogens and the host immune and coagulation systems. Infective endocarditis in the right side of the heart can result in emboli showering the lungs.(9) Infective endocarditis in the left side of the heart can result in systemic embolism.

JPC Diagnosis:

Heart: Endomyocarditis, granulomatous and heterophilic, focally extensive, marked with ventricular thrombosis and numerous bacterial colonies.

Conference Comment:

Neisseria spp. are generally classified as obligate human pathogens, commensal organisms in humans and mammals and/or organisms that may cause opportunistic human infections. As mentioned above by the contributor Neisseria spp. bacteria are common oral flora of many mammals including N. canis, which has been isolated from the throats of cats and can be present in cat bite wound infections, and N. weaver, N. zoodegmatis, N. animaloris which are normal oral flora of dogs and can be present in dog bite wound infections and in some cases can result in systemic infections in humans. Other species have been isolated from the oral cavity of guinea pigs, cows and rhesus monkeys. Neisseria spp. have also been isolated from the duodenum of healthy cats. Pathogenic Neisseria spp. utilize a number of adhesins, most commonly referenced with regard to human infections, and one of the best known is the type IV pilus which imparts twitching motility and facilitates uptake of foreign DNA. Most of the Neisseria spp. causing significant disease also possess a polysaccharide capsule, enabling avoidance of complement mediated killing and phagocytosis. Another feature which aids in resistance to antibody and complement mediated killing includes lipooligosaccharide (LOS), which is a membrane structure composed of lipid and oligosaccharide which is structurally different from lipopolysaccharide (LPS).3

Conference participants described this lesion as a severe granulomatous endocarditis with granuloma formation and fibrosis. The ventricle was described as being 100% occluded by a large, dense fibrin thrombus which contains numerous bacterial colonies as well as erythrocytes and necrotic debris, and is multifocally attached to the markedly thickened endocardium. Multiple granulomas are present in the superficial myocardium, near the epicardialmyocardial junction. Granulomas contain a dense core of eosinophilic debris (characteristic of reptile granulomas) surrounded by multiple macrophages with the presence of many multinucleate giant cells as well. The abundant white space surrounding the dense central core of debris is likely the result of retraction artifact. The granulomas most peripheral layer is composed of dense fibrous connective tissue. The differential diagnosis discussed includes mycobacterial and fungal infections.

The moderator briefly discussed the structure of reptile hearts as there are significant differences with mammalian hearts. Most reptiles have a single common ventricle and two atria. Three cavities or divisions are present in the ventricle, termed the cavum pulmonale, cavum arteriosum and cavum venosum and are partially separated by muscular septa. Blood flows from the right atrium, through the cavum venosum and into the cavum pulmonale and then enters the pulmonary circulation. Oxygenated blood flows from the pulmonary veins and reenters the heart through left atrium, flows into the cavum arteriosum during diastole, which channels blood into the cavum venosum which then flows into the aorta. Oxygenated and deoxygenated blood is separated by pressure differences, outflow resistance and differential flow. Shunting and mixing of oxygenated and deoxygenated blood is variable depending on the reptile species and activity level. Nonetheless, blood flows are described as well separated within the ventricle (due to septa) and mixing of oxygen-poor and oxygen-rich blood is minimized.(4)

References:

1. Barrett SJ, Schlater LK, Montali RJ, Sneath PHA. A new species of Neisseria from iguanid lizards, Neisseria iguanae sp. nov. Lett Appl Microbiol. 1994; 18:200-202.

2. Freedman LR. The pathogenesis of infective endocarditis. J Antimicro Chemother. 1987; 20(Suppl. A): 1-6.

3. Hung MC, Christodoulides M. The biology of Neisseria adhesins. Biology. 2013; 2(3):1054-1109.

4. Jensen B, van den Berg G, van den berg R, Oostra RJ et al. Development of the hearts of lizards and snakes and perspectives to cardiac evolution. PLoS One. 2013; 8(6):e63651.

5. Liu G, Tang CM, Exley RM. Non-pathogenic Neisseria: members of an abundant, multihabitat, diverse genus. Microbiology. 2015; 161(7):1297-312.

6. Markey B, Leonard F, Archambault M, Cullinane A, Maguire D. Glucose nonfermenting, Gram-negative bacteria. In: Clinical Veterinary Microbiology. 2nd ed. London, UK: Mosby Elsevier; 2016: 375-379.

7. Plowman CA, Montali RJ, Phillips LG, Schlater LK, Lowenstine LG. Septicemia and chronic abscesses in iguanas (Cyclura cornuta and Iguana iguana) associated with Neisseria species. J Zoo Anim Med. 1987; 18(2-3): 86-93.

8. Sullman PM, Drake TA, Sande MA. Pathogenesis of endocarditis. Am J Med. 1985; 78 (Suppl. 6B): 110-115.

9. Thiene G, Basso C. Pathology and pathogenesis of infective endocarditis in native heart valves. Cardiovasc Pathol. 2006; 15: 256-263.

10. Widmer E, Que Y-A, Entenza JM, Moreillon P. New concepts in the pathophysiology of infective endocarditis. Curr Infect Dis Rep. 2006; 8(4): 271-279.