Panleukopenia in a 9-Week-Old 
Scottish Fold Kitten

Stephanie Shapiro
Clinical Advisor: Dr. Gretchen Schoeffler
Basic Science Advisor: Dr. Paul Maza

Senior Seminar Paper
Cornell University, College of Veterinary Medicine
February 8, 2017






Key Words: panleukopenia, parvovirus, feline, kitten

Abstract:
	The following report describes a 9-week-old Scottish fold kitten that was presented to the Cornell University Hospital for Animals in May of 2016 for depression, diarrhea, inappetence, and lethargy. On presentation, the kitten was in hypovolemic shock. Initial diagnostics did not confirm a cause for illness, so the kitten was treated supportively with fluids, antibiotics, nutritional support, and parasiticides. Sequential blood work revealed anemia, leukopenia, and neutropenia. PCR confirmed infection with feline panleukopenia virus, despite previous vaccination and three negative Parvo SNAP tests. The kitten was successfully treated and discharged to the care of his owners one week post-presentation. This report describes the clinical features, etiology and pathophysiology of feline panleukopenia virus. 

Introduction:
	Panleukopenia is a disease caused by a parvovirus specific to felines, raccoons, and various other carnivores. It attacks rapidly dividing cell lines, primarily localizing to the intestinal crypts and bone marrow. Affected animals often present with diarrhea, depression, and dehydration, ultimately leading to death in the majority of untreated cases. Clinical signs and leukopenia are highly characteristic of the disease process and polymerase chain reaction techniques (PCR) can be used for definitive diagnosis. Vaccination is highly effective in preventing the disease, but maternal antibody interference may occur in kittens. This report describes the clinical features of an affected 9-week-old Scottish fold kitten, as well as the etiology and pathophysiology of feline panleukopenia virus.


Signalment & Case History:
	A 9-week-old intact male Scottish fold kitten had been purchased as a seemingly healthy animal from a breeder near New York City. His queen and sire tested negative for feline immunodeficiency and feline leukemia virus prior to mating and he had one other female littermate. The kitten had received two combination vaccinations against feline viral rhinotracheitis, calici, and panleukopenia viruses at 6 weeks and 8 weeks of age. At those times he had also been treated with an unknown deworming medication.
	Shortly after adoption, the kitten had an episode of diarrhea. The following day, he was dull, lethargic, and inappetent. The owners brought him to their primary care veterinarian, who assessed the kitten to be 7% dehydrated and ataxic. The primary care veterinarian performed a complete blood count, chemistry panel, urinalysis, fecal flotation, abdominal ultrasound, and thoracic radiograph. Abnormalities in the laboratory tests included a left shift, lymphocytosis, hypoalbuminemia, hyponatremia, hypophosphatemia, hypocalcemia, and ketonuria. The fecal examination was negative for parasites and the imaging was reportedly unremarkable. No definitive diagnosis was made, but the kitten was treated supportively with intravenous fluids, antibiotics, and oral parasiticides. Overnight, no improvement was observed so the kitten was referred to the Cornell University Hospital for Animals.

Presentation & Clinical Findings: 
	The kitten was presented to the Emergency Service for the complaints of lethargy, inappetence, diarrhea, and dullness nonresponsive to the referral veterinarian’s supportive care. On physical exam he was tachycardic (210 bpm) and hypothermic (95.1˚F). His mentation was dull and he appeared disoriented. He had pale pink and tacky mucous membranes, a prolonged capillary refill time (2-3 seconds), and weak pulses. He was 10% dehydrated based on sunken eyes and delayed skin tent. This combined with his poor perfusion status was consistent with hypovolemic shock. His body condition score was a 2 out of 9 and he weighed 410g (average weight of a 9-week-old kitten ~1000g). Abdominal palpation caused excretion of some diarrhea, and there was wet fecal staining around his rectum.
	Point of care assessment tests were performed. His packed cell volume (PCV) was 33% (reference interval 32.6-34.0%), total solids (TS) 6.6 g/dL (reference interval 4.1-6.2 g/dL), Azostix 50-80 mg/dL (reference interval 5-15 mg/dL), and blood glucose 110 g/dL (reference interval 94-143 g/dL). On venous blood gas, he had a metabolic acidosis, hyponatremia, and hypochloremia. A blood smear revealed poikilocytosis, adequate numbers of segmented neutrophils, and a few band neutrophils. A fecal smear did not show any obvious parasites and a Parvo SNAP test was negative. 

Problem List & Differential Diagnoses:
	The kitten’s dull mentation status, poor circulatory function, and hypothermia were attributed to hypovolemic shock. The hypovolemia was secondary to severe dehydration that resulted from decreased fluid intake and increased fluid loss (diarrhea). Differential diagnoses for diarrhea included infectious, which may be viral: coronavirus enteritis, panleukopenia; bacterial: clostridia, campylobacter, salmonella; or parasitic: roundworms, hookworms, whipworms, and developmental or congenital, which may include an inborn error of metabolism such as a storage disease or a blood dyscrasia.
	The abnormalities detected on the point of care assessment tests were relatively mild and likely related to the two previously identified problems, hypovolemic shock and diarrhea. Given the patient’s young age, infection was prioritized as the most probable cause of his clinical signs. 
  
Prognosis & Treatment: 
 	The kitten was given a 50% chance of survival due to its compromised status upon intake. Treatments included intravenous fluid administration (Lactated Ringers, 25 ml/kg, over 15 minutes followed by a continuous rate infusion at 10 ml/kg/hr), heat support, intravenous antibiotic therapy (ampicillin/sulbactam 22 mg/kg every 8 hours, metronidazole 10 mg/kg every 8 hours), antiemetic (ondansetron 0.2 mg/kg every 8 hours), and oral antiparasitic (fenbendazole 50 mg/kg every 24 hours). The kitten’s caloric requirements were satisfied with a combination of oral and parenteral nutrition (Hill’s A/D and Aminosyn 8.5%). As his condition was classic for FPV, a repeated Parvo SNAP test was evaluated; this again had a negative result. The kitten was considered an infectious disease suspect, which meant using isolation protocols and proper personal protective equipment to prevent potential disease transmission to other hospitalized patients.
	Over the next several days, serial complete blood counts were monitored. The kitten’s hematocrit continued to decline and hit a nadir of 21% (reference interval 32.2-34.3%).  Though initial white blood cell values were at the low end of the normal interval the kitten quickly became leukopenic. The white blood cell nadir was 1.7 thou/uL (reference interval 5.1-16.2 thou/uL) and neutrophils dropped to zero (reference interval 2.3-11.6 thou/uL). Due to concern about the potential for sepsis, the kitten’s antimicrobial spectrum was expanded (enrofloxacin 5 mg/kg every 24 hours IV, and sulfadimethoxine 12.5 mg/kg every 12 hours PO). Additionally, a fecal sample was submitted for a parvovirus PCR test. The parvovirus PCR was positive, confirming the suspicion of panleukopenia despite multiple negative SNAP tests. 

Outcome:
 	Eight days after presentation, the kitten was given a fair prognosis and discharged to the care of his owners. At this time, the kitten was still leukopenic at 2.9 thou/uL (reference interval 5.1-16.2 thou/uL) and neutropenic at 1.0 thou/uL (reference interval 2.3-11.6 thou/uL). He was clinically brighter than on admission and was willing to eat canned food on his own. He was discharged with three antibiotics (amoxicillin/clavulanate 17.5 mg/kg every 12 hours PO, metronidazole 11.5 mg/kg every 12 hours PO, and enrofloxacin 4.2 mg/kg every 24 hours PO), along with the coccidiostat (sulfadimethoxine 10.2 mg/kg every 12 hours PO).  Two days later, the primary care veterinarian reported the kitten to be bright, alert, and responsive; much improved since the last visit. Five days post-hospitalization, the kitten had resolution of his leukopenia and neutropenia, with only a very mild anemia. Eight months following initial presentation, the kitten was reported to be healthy and doing very well at home.  

Discussion – Panleukopenia:
Introduction
	Feline panleukopenia virus is a highly infectious, environmentally stable parvovirus of felines, raccoons, and various other carnivores. Initially known as “cat plague” in the 1800s, the causative virus was not identified until the 1960s. During the late 1960s and early 1970s, both inactivated and modified live vaccines for FPV were created, substantially decreasing the incidence of FPV (1).

Etiology
	The specific term FPV refers to a single parvovirus serotype, unlike canine parvovirus (CPV), which has mutated over the years into many distinct strains (2). FPV requires rapidly dividing mitotic cells for replication and, as a single stranded DNA virus, produces Cowdry Type A intranuclear inclusions (3). The virus can survive for up to a year on surfaces, but is susceptible to disinfection with sodium hypochlorite (bleach), peracetic acid, formaldehyde, or sodium hydroxide (4). 

Epidemiology
	Feline panleukopenia virus is observed worldwide, most prominently in unvaccinated populations. There is a subset of young vaccinated felines susceptible to FPV due to maternal antibody interference during an “immunity gap” period (2). In older, properly vaccinated felines, FPV is extremely rare. The occurrence of FPV is higher in late summer, as correlates with the increase in queening during this time period (5). Kittens between 8 and 16 weeks are most susceptible to FPV, followed by cats under one year of age. There is no correlation between sex and susceptibility (6).

Transmission
	Feline panleukopenia virus is most commonly transmitted via fecal – oral route. This may occur by direct contact with the feces of an infected feline, contact with improperly sanitized fomites, or via human interaction due to unclean hands, clothing, or shoes carrying the virus (7). In utero transmission may also occur if the queen has an acute infection late in gestation (6). Cats do not appear to maintain a carrier state of the virus post infection, though may shed viral particles in feces for up to one month after clinical resolution of infection (7).  

Pathogenesis
	Once ingested, FPV locates to rapidly dividing cells. This initially begins in intestinal crypts, where the virus’s cytolytic action causes destruction of the stem cells, leading to crypt ectasia and short, fused, blunted villi. The disrupted mucosal integrity prevents osmotic regulation, resulting in diarrhea, and allows for endotoxin uptake, resulting in increased susceptibility to secondary bacterial infections and septicemia. FPV also infects leukocyte and erythrocyte progenitor cells in the bone marrow, resulting first in panleukopenia and shortly thereafter anemia. Lymphoid tissue elsewhere in the body is affected similarly, severely immunocompromising the host. If infection occurs in utero or as a neonate, the Purkinje cells in the cerebellum and retinal cells are destroyed, resulting in cerebellar hypoplasia and retinal dysplasia, respectively (1, 8).

Clinical Signs
	Infection with FPV may result in five different clinical syndromes (1). The peracute syndrome often has no clinical signs other than sudden death. The acute syndrome is more common. These cats exhibit clinical signs including depression, diarrhea, dehydration, vomiting, anorexia, and fever which then progresses to hypothermia and death. A milder clinical syndrome of FPV exists as well; these cats have clinical signs of mild gastroenteritis, fever, depression, and inappetence, along with a mild leukopenia. Many of these cats will recover from this form without treatment. A subclinical form of FPV infection may occur in adult cats. These cats appear to be normal, but have a fever and leukopenia. These cats actively shed the virus during the infection, and thus can be a source of contamination. They, too, will recover without treatment. Lastly, when infected in utero, if the kitten survives to birth it may have cerebellar hypoplasia, retinal dysplasia, and hydrocephalus. These kittens can often have a normal lifespan but will have lifelong deficits (1, 8).

Diagnosis
	Diagnosis of FPV is often made on the basis of history and presentation. Signalment is important, as an unvaccinated cat or a cat last vaccinated prior to 16 weeks of age are much more likely to be infected with FPV. Kittens from shelter environments have a higher risk of exposure (1). Clinically the classic presentation of an FPV infected cat includes sudden onset of depression, lethargy, diarrhea, vomiting, dehydration, anorexia, and fever. On blood work, the most prominent abnormality is leukopenia, present in all FPV infected cats at some point during the course of the disease (1). 
	The in-house Parvo SNAP test originally created for canine parvovirus has also been shown to correlate with FPV infections in felines; however, false negatives are common (9). The gold standard for detection is PCR of FPV antigen from fecal matter (9). Additional diagnostic methods include viral isolation, immunofluorescent assay of small intestinal tissue, electron microscopy, or serological assays such as virus neutralization (2).  Diagnosis may also be based on post-mortem findings. Gross pathology includes a rough hair coat, emaciation, dehydration, evidence of diarrhea and/or vomiting, edematous small intestines with petechial or ecchymotic hemorrhages, thymus atrophy, and cerebellar hypoplasia in neonates (1). 

Treatment
	There is no specific therapy directed towards FPV itself; rather, supportive care is aimed at restoring and maintaining hydration and nutrition and preventing secondary infections. Intravenous fluids with electrolytes as needed based on laboratory data are essential throughout treatment. Dextrose solutions can be used in severely hypoglycemic patients.  Antiemetics should be given if the patient is vomiting. Early enteric nutrition with a bland diet is suggested, as studies in dogs with canine parvovirus show beneficial effects. B complex vitamin supplementation is also recommended to prevent thiamine deficiency. Broad spectrum intravenous antibiotic therapy is critical to reducing the high risk of septicemia (4).  

Prognosis
	In kittens infected after birth but prior to 8 weeks of age, mortality is nearly 100% (10). In older kittens, negative prognostic indicators include: potassium < 4.0 mmol/L, albumin < 3.0 g/dL,  and leukocytes < 2000/uL (10). Kittens that meet all three criteria have a mortality of over 90% without supportive care, and of 50% with supportive care. Guarded prognosis is given to kittens with leukocyte counts between 2000-4000/uL (10). Adult cats tend to present with mild or subclinical infections, though in an acute infection, mortality statistics are similar to those of kittens. If the cat survives past the initial 5-7 days of an acute infection, the prognosis for full recovery increases dramatically (10). 

Prevention
	Vaccination using an inactivated or modified live subcutaneous vaccine is highly efficacious when used appropriately. Kittens should be vaccinated starting at 6-8 weeks of age and revaccinated every 3-4 weeks until they have attained a minimum age of 16 weeks (11). Some data suggests kittens up to 20 weeks of age still have circulating maternal antibodies that may prevent proper immunity development, and another vaccine booster at 20 weeks may be recommended (12). Following vaccination as a kitten, a cat should be revaccinated in one year, and then every three years (11). 

Conclusion:
	This report exemplified the classic presentation of a kitten infected with FPV, including the disease progression and treatment approach. It also illustrated the possibility of false negatives when using the Parvo SNAP test, and the importance of maintaining panleukopenia as a differential diagnosis when clinical signs and laboratory data are suggestive. In practice, it is always advisable to view the entire patient, laboratory work, and additional diagnostics with good judgment in creating a treatment plan.


References
1. Scott, Fred W. "Panleukopenia." Diseases of the Cat: Medicine and Surgery. 	Philadelphia: WB Saunders, 1987. 182-93.

2. Truyen, Uwe and Colin Parrish. “Feline panleukopenia virus: Its interesting evolution and 	current problems in immunoprophylaxis against a serious pathogen.” Veterinary 	Microbiology. 165.1-2 (2013): 29-32.

3. Csiza, C. K. et al. “Pathogenesis of feline panleukopenia virus in susceptible newborn 		kittens I. Clinical Signs, Hematology, Serology, and Virology.” Infection and Immunity 	3.6 (1971):833–37.

4. Truyen, Uwe, et al. "Feline Panleukopenia. ABCD guidelines on prevention and 	management." Journal of Feline Medicine & Surgery 11.7 (2009): 538-46.

5. Reif, John S. "Seasonality, natality and herd immunity in feline panleukopenia." 	American Journal of Epidemiology 103.1 (1976): 81-87.

6. Parrish, Colin R. “Pathogenesis of feline panleukopenia virus and canine parvovirus.”; 	Parvoviruses. New York: Oxford University Press, 2006. 429-34.

7. Bloom, Micheal E. and Jonathan R. Kerr. “Pathogenesis of parvovirus infections.”; 	Parvoviruses. New York: Oxford University Press, 2006. 323-41.

8. Gaskell, Rosalind M., Susan Dawson, and Alan Radford. “Other feline viral diseases.” 	Textbook of Veterinary Internal Medicine. St. Louis: Elsevier Saunders, 2010. 949-950.

9. Abd-Eldaim, Mohamed M, Melissa J. Beall, & Melissa Kennedy. “Detection of feline 	panleukopenia virus using a commercial ELISA for canine parvovirus.” Veterinary 	Therapeutics: Research in Applied Veterinary Medicine 10.4 (2009).

10. Kruse, B.D., et al. "Prognostic factors in cats with feline panleukopenia." Journal of 	Veterinary Internal Medicine 24.6 (2010): 1271-276. 

11. Richards, James R. et al. "The 2006 American Association of Feline Practitioners 	feline vaccine advisory panel report." Journal of the American Veterinary Medical 	Association 229.9 (2006): 1405-441.

12. Jakel, Verena et al. "Vaccination against feline panleukopenia: implications from a field 	study in kittens." BMC Veterinary Research 8.1 (2012): 62. 
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