Streptococcal toxic shock syndrome in a captive kinkajou (Potos flavus)

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Streptococcal toxic shock syndrome in a captive kinkajou (Potos flavus) Alan R. Glassman DVM , Akhilesh Ramachandran BVSc&AH, PhD, DACVM , Shane D. Lyon DVM, MS, DACVIM , Jessica Robertson DVM , ˜ Brandao ˜ LMV, MSDECZM (Avian) Ian Kanda RVT , Joao PII: DOI: Reference:

S1557-5063(20)30019-7 https://doi.org/10.1053/j.jepm.2020.02.012 JEPM 50283

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Journal of Exotic Pet Medicine

Please cite this article as: Alan R. Glassman DVM , Akhilesh Ramachandran BVSc&AH, PhD, DACVM , Shane D. Lyon DVM, MS, DACVIM , Jessica Robertson DVM , Ian Kanda RVT , ˜ Brandao ˜ LMV, MSDECZM (Avian) , Streptococcal toxic shock syndrome in a captive kinkajou Joao (Potos flavus), Journal of Exotic Pet Medicine (2020), doi: https://doi.org/10.1053/j.jepm.2020.02.012

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Case Report

Streptococcal toxic shock syndrome in a captive kinkajou (Potos flavus) Alan R. Glassmana1, DVM; Akhilesh Ramachandranb, BVSc&AH, PhD, DACVM; Shane D. Lyona, DVM, MS, DACVIM; Jessica Robertsonc, DVM; Ian Kandaa, RVT; João Brandãoa, LMV, MS, DECZM (Avian).

Departments of aVeterinary Clinical Sciences and bOklahoma Animal Disease Diagnostic Lab, College of Veterinary Medicine, Oklahoma State University, 2065 W Farm Rd, Stillwater, OK 74078, USA c

William R. Pritchard Veterinary Medical Teaching Hospital, School of Veterinary Medicine,

University of California – Davis, 1 Shield Ave, Davis, CA 95616, USA

1 Present

address: Department of Veterinary Programs, Brevard Zoo, 8225 N Wickham Rd,

Melbourne, FL 32940, USA

Address correspondence to Dr. Alan Glassman ([email protected])

Abstract: Background A clinical diagnosis of streptococcal toxic shock syndrome requires isolation of streptococci from a normally sterile site, hypotension, and two or more of the following; evidence of hepatic or renal involvement, coagulopathy, acute respiratory distress, or extensive soft tissue necrosis.

Case Description An approximately 5-year-old intact, male, captive-raised kinkajou (Potos flavus) was evaluated for severe respiratory distress and obtunded mentation. On presentation, the kinkajou was nonresponsive, laterally recumbent, hypothermic, tachypneic, and had marked upper respiratory sounds. Thoracic radiograph findings included pneumothorax, most severe in the left hemithorax, and pulmonary atelectasis. Bloodwork revealed neutrophilia with a left shift, azotemia, thrombocytopenia, and liver enzyme elevations. On the blood smear, a low number of neutrophils exhibited phagocytized cocci bacteria indicative of bacteremia. The animal died shortly after presentation.

Conclusions and Case Relevance On necropsy, pneumothorax was confirmed, and the lungs were severely atelectatic with bullae. Histopathology revealed septic thrombi within pulmonary arteries and meningeal vessels. Streptococcus canis was cultured from lung samples and a Lancefield Group G Streptococcus was cultured from the blood. Oral swabs of one cagemate and one new individual acquired by the same owner both cultured S. canis. This report describes streptococcal toxic shock syndrome, previously unreported in kinkajous or any non-domestic species.

Keywords: Kinkajou; Potos flavus; Streptococcal toxic shock syndrome; Lancefield Group G Streptococcus

Abbreviations:

STSS Streptococcal toxic shock syndrome RR Reference range

Acknowledgements: This case was partially supported by the Oklahoma State University Dr. Kristie Plunkett Fund in Exotic Animal Medicine. Introduction: Streptococcal toxic shock syndrome (STSS) has been previously reported in humans [1], dogs [2-4], cats [5,6], and a horse [7]. The case definition of STSS requires three components: isolation of streptococci from a normally sterile site, hypotension, and two or more of the following: renal impairment, coagulopathy (thrombocytopenia or disseminated intravascular coagulation), liver abnormalities, acute respiratory distress (pulmonary capillary leakage, edema), extensive soft-tissue necrosis such as fasciitis, myositis, gangrene and/or erythematous rash [8].

Case Report: An approximately 5-year-old intact, male, captive-raised kinkajou (Potos flavus) was presented to Oklahoma State University Boren Veterinary Medical Teaching Hospital (Stillwater, OK) after being found obtunded in severe respiratory distress. The kinkajou was reportedly normal 12-hours prior and had no past medical history. The patient shared an outdoor enclosure with two non-affected kinkajous. Three days prior to presentation the patient developed a raised mass over the right mandible and generalized facial swelling. The owner suspected a tooth root abscess and

administered one 22.7 mg tablet of enrofloxacin once a day for three days in the food, without veterinarian consultation. Since the patient shared the outdoor enclosure with other kinkajous, it was unclear if the patient ingested the medication. On presentation, the patient was laterally recumbent and non-responsive, weighed 1.8-kg with a body condition score of 3/5. Rectal temperature was below the range of the thermometer (< 92°F). Respiratory rate was 70 breaths per minute, there were marked upper respiratory sounds, and cardiac and lung auscultation were inaudible. Femoral pulses were weak, and mucous membranes were dark red to purple, and injected with a capillary refill time greater than 3 seconds. The patient was suspected to be approximately 10% dehydrated. A right-sided swelling was present along the maxillary arcade and zygomatic arch. Bilateral mydriasis was present and palpebral reflex was weak on the left medial canthus, but otherwise absent bilaterally. A thick, serosanguineous to bloody discharge was noted in the oral cavity and nares, and a gag reflex was absent. Initial stabilization included heat support, flow-by oxygen, and subcutaneous fluids while permission for further treatments and diagnostics were obtained. Indirect oscillometric blood pressure (VetGard+, Vmed Technology, Mill Creek, WA) was measured with a #2 cuff placed at the base of the tail. Mean arterial blood pressure ranged from 70 to 80 mmHg. Once the owner approved further procedures, blood was collected, and intravenous fluid resuscitation was initiated. Blood gas analysis revealed hyponatremia (126mEq/L [RR 133-151 mEq/L]) and azotemia (blood urea nitrogen [BUN]: 89mg/dL [RR 2.1-27.4 mg/dL] and creatinine 1.7mg/dL [RR 0.2-0.9 mg/dL]) [9]. Hematology revealed leukocytosis (38.7x103/µL [RR 2.920.8x103/µL]), with a degenerate left shift (neutrophils (5.805 x 103/µl; [RR 1.13- 8.99x103/µL])

band neutrophils [23.7x103/µl]) as well as monocytosis (4.26 x103/µL [RR 0-1.448 x103/µL]) [9]. The majority of both mature and immature neutrophils exhibited toxic changes, such as Döhle bodies and foamy cytoplasm, and low numbers of neutrophils were observed with phagocytized cocci bacteria indicative of bacteremia (Figure A). Thrombocytopenia (86 x103/µL [RR 107-766 x103/µL]) was suspected although occasional small platelet clumps and giant platelets were present on the blood smear [9]. There was an average of 2 platelets per 1,000X field. Plasma biochemistry revealed hyperproteinemia (10.8 g/dL [RR 6.2-9 g/dL]), hyperglobulinemia (7.5 mg/dL [RR 1.9-5.1 mg/dL]), azotemia (BUN 59 mg/dL [RR 2.1-27.4 mg/dL] and creatinine 1.6 mg/dL [RR 0.2-0.9 mg/dL]), hyperphosphatemia (13 mg/dL [RR 3.78.7 mg/dL]), hyponatremia (125mEq/L [RR 133-151 mEq/L]) and hypochloremia (85mEq/L [RR 96-112 mEq/L]) [9]. Aspartate aminotransferase (AST) (739IU/L [RR 94-300 IU/L]) and creatinine phosphokinase (CPK) were both elevated (6,394 IU/L [RR 88-1145 IU/L]) [9]. Thoracic radiographs revealed a pneumothorax most severe in the left hemithorax, and pulmonary atelectasis. The cardiac silhouette was elevated on the lateral views and there was retraction of the lung lobes (Figure B and C). Prior to therapeutic thoracocentesis the patient developed cardiac arrest and was pronounced dead. The owner consented for necropsy. On gross necropsy, pneumothorax was confirmed by lack of negative pressure within the thoracic cavity. The lungs were small and collapsed bilaterally, and the tip of the left caudal lung lobe was expanded up to 1 x 3 cm by an air-filled bulla. Histopathology revealed pulmonary arteries and meningeal vessels occluded by fibrin thrombi admixed with myriad hazy bacterial colonies. Arteriolar walls were largely replaced by fibrinoid necrosis with large numbers of macrophages, neutrophils, lymphocytes, mineralization, and fibrin. Alveoli were closely apposed (atelectasis) and contained low amounts of eosinophilic proteinaceous fluid admixed with

alveolar macrophages. Bronchioles and bronchi were filled with abundant mucus while the periphery of some sections contained distended alveolar spaces that coalesced (emphysema, bulla formation). Bacterial culture of the lung yielded a very large number of Streptococcus canis, moderate amounts of Citrobacter sp. and a small number of Pseudomonas plecoglossicida, Staphylococcus sciuri and Achromobacter xylosoxidans. Bacterial identification was performed by matrix assisted laser desorption/ionization – time of flight (MALDI-TOF) mass spectrometry. Blood culture grew a moderate number of beta-hemolytic Streptococcus sp. classified as a Lancefield Group G Streptococcus. Based on the clinical data and postmortem results, a diagnosis of STSS was made. Discussion: The case reported herein fulfills the STSS case definition requirements detailed above. Streptococcus canis was cultured from lung tissue and a streptococcus Lancefield group G was cultured from the blood. Lancefield serological group G contains animal source S. canis and human source Streptococcus dysgalactiae subspecies equisimilis [10]. Based on the low likelihood that of two different Lancefield Group G bacteria cultured from the same animal at the same time, the blood culture was most likely S. canis. Hypotension was subjectively considered in this case however it is difficult to assess due to the critical nature of the patient, lack of direct blood pressure determination, and limited knowledge of this specific species. An indirect blood pressure reading of 70 to 80 mmHg mean arterial pressure was taken during initial triage exam. Hypotension is defined in most mammalian species as a mean blood pressure below 60 mmHg or a systolic blood pressure below 90 mmHg [11]. Accuracy of the indirect blood pressure measurements in kinkajous is

previously unreported and its reliability and accuracy are currently unknown. Indirect oscillometric pressure also has been found to overestimate blood pressure measurements when hypotension is present in a study in dogs compared to invasive blood pressure measurements [12], so similar results may exist in kinkajous. Unfortunately, due to the critical nature of the patient and its rapid decline to cardiopulmonary arrest, an arterial line and direct blood pressure could not be performed. Systemic hypotension was not fully reflected with the indirect blood pressure measurements but suspected based on the poor pulse quality and decreased body temperature. The elevated creatinine was potentially associated with renal impairment but may also be due to the patient’s dehydration. In human STSS cases renal impairment is often noted by creatinine values on average exceeding 2.5 times normal [1]. In this case the creatinine was approximately twice the upper end of reference interval. Liver abnormalities were present with an elevation of AST. An automatic platelet count of 86 x103/µL was noted for this patient. The reference interval is extremely wide in this species making the true degree of thrombocytopenia difficult to interpret although based on comparison to mean and median levels (411 x103/µL and 388 x103/µL) [9] thrombocytopenia is still highly suspected. The presence of septic thrombi strongly supports a theory of increased platelet consumption via disseminated intravascular coagulation process. Evidence of acute respiratory distress syndrome and extensive erythematous rash or soft tissue necrosis were not appreciated in this case. Pneumothorax was suspected to be due to rupture of pulmonary bullae.

In previous cases of STSS with S. canis, the use of enrofloxacin has been believed to be associated with the progression of infection [13]. In vitro research has shown enrofloxacin causes induction of a lysogenic bacteriophage increasing expression of a superantigen gene which may explain the connection between enrofloxacin and incidence of STSS in canine patients [13]. The previous oral administration of enrofloxacin could have exacerbated progression of this case. S. canis has not been reported as normal microflora of the oral cavity in the kinkajou [14]. In an attempt to further clarify this information, the oral cavities of the cagemates, two newly acquired kinkajous in the colony, and two kinkajous from a different colony were cultured for S. canis. One cagemate and one new individual acquired by the same owner both cultured S. canis. No other instances of respiratory distress or acute death have been observed in this group of kinkajous over a period of 4 years. This report describes a case of STSS previously unreported in a kinkajou. The isolation of S. canis and a Lancefield Group G Streptococcus (which was not identified further) from the lung and the blood, respectively, presumptive hypotension, along with the hepatic disease and presumptive coagulopathy are highly suggestive of STSS. STSS should be considered in kinkajous presenting in shock. This case report also highlights the potential for STSS in nondomestic species.

Declaration of interests None

References:

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Figures legends:

Figure A: Blood smear from a kinkajou (Potos flavus) showing a neutrophil with phagocytized cocci bacteria. Romanowsky stain.

Figure B: Left lateral radiograph of a kinkajou (Potos flavus). Findings include an elevated cardiac silhouette with retraction of the lung lobes.

Figure C: Ventral-dorsal radiograph of a kinkajou (Potos flavus) showing retraction of the lung lobes and pulmonary atelectasis.