Feline Panleukopenia Virus

Tonya McNinch, DVM; Perry J. Bain, DVM, PhD; Kenneth S. Latimer, DVM, PhD; Melanie Johnson, DVM; Heather L. Tarpley, DVM; Bruce E. LeRoy, DVM, PhD

Class of 2005 (McNinch) and the Department of Pathology (Bain, Latimer, Johnson, Tarpley, LeRoy) College of Veterinary Medicine, University of Georgia, Athens, GA 30602-7388

Introduction

Feline panleukopenia virus (FPV) is an autonomous parvovirus belonging to the family Parvoviridae and in the subgroup feline parvovirus.¹ FPV, also known as feline parvoviral enteritis, feline distemper virus and feline infectious enteritis, is closely related to canine parvovirus type 2 (Merck). FPV, like other parvoviruses, is a non-enveloped, single-stranded DNA virus with an established tropism for cells undergoing mitosis (cellular division).² All members of the family Felidae are susceptible to FPV infection and subsequent disease, as are representatives of the related families Procyonidae (coatimundis and raccoons), Viverridae and Mustelidae (minks). The virus does appear to replicate to some extent in dogs; however, dogs do not appear to shed the virus or develop clinical signs of infection. FPV infection among the dog population is an area of ongoing research and debate.^3,4

Incidence and Transmission

FPV is a severe, highly contagious disease that is oftentimes fatal. Feline panleukopenia occurs worldwide, but is rarely seen as a clinical entity due to the effectiveness of vaccination in preventing the disease. Young, unvaccinated kittens present most commonly with this disease. Unvaccinated feral cat colonies and other wild felids also serve as reservoirs of infection for the domestic cat population.²

FPV exposure and infection can occur in several ways. The major route of transmission is direct contact between a susceptible host and an infected animal or its secretions. The virus is shed in all body secretions of infected animals for up to six weeks. Once introduced into the environment, the virus is very hardy and can persist for years. Treatment of fomites (inantimate objects) and other contaminated materials for ten minutes with bleach, 4% formaldehyde or 1% gluteraldehyde is necessary to inactivate the virus. Fomites, including contaminated instruments, cages and bedding, are also an important route of viral exposure. Mechanical transmission of FPV via arthropod vectors is probable as well. Lastly, this virus also can cross the placenta to infect the fetuses in utero.³

Pathogenesis

When a susceptible host is exposed to an infected animal or its secretions (the most common mode of transmission), FPV enters the oropharynx and replicates in regional lymphoid tissues. Hematogenous spread then accounts for viral entry into other tissues and organs.² The pathogenesis of feline panleukopenia from this point is directly related to the tropism of parvoviruses for rapidly dividing cells. Parvoviruses need to infect cells in the S phase of the cell cycle for viral replication to occur, so rapidly dividing cell populations are most susceptible to infection. In adult cats, FPV replicates mainly in lymphoid and myeloid precursor cells in the bone marrow, lymph nodes, thymus and spleen, as well as in the epithelial cells of the intestinal crypts.^3,4,5 In utero infections due to exposure of a pregnant queen to FPV have a variety of outcomes dependent upon the stage of gestation during which the fetuses are infected. The virus will replicate in the rapidly dividing cells of the fetus. Whether the infection is widespread or is localized to the central nervous system (CNS) and/or bone marrow is dependent on the developmental stage of the fetuses at the time of infection. Infection very early in gestation leads to widespread infiltration of fetal cells by the virus, while exposure in late gestation or in the early neonate results in infections of the CNS or bone marrow and lymphoid organs. Common neurologic tissues affected include the cerebellum, cerebrum, retina and optic nerve.³ The virus has been found to replicate to some extent in the thymus, bone marrow and spleen of the dog but not the small intestine or mesenteric lymph nodes.⁴

Once FPV virus infects a cell, the cell is prevented from entering mitosis regardless of the cell type. Viral replication within the cell leads to eventual cell death and tissue necrosis, possibly due to viral induction of apoptotic pathways.⁵ The virus replicates for approximately five to seven days within the body before there is notable cell destruction, resulting in an incubation period of about one week between exposure to the virus and presentation with clinical signs.

Clinical Signs

Systemic clinical signs usually are seen in kittens between the ages of four and six months of age that have not been vaccinated, but feline panleukopenia can be seen in older, immunologically naïve cats. These patients generally have inappetance, lethargy, and fever that become apparent between two and seven days after initial exposure. Vomiting begins a few days after the fever develops, may contain bile and is unrelated to eating. Diarrhea is the last symptom to present; the feces may range from mucoid to bloody. Combined vomiting and diarrhea lead to rapidly progressive dehydration.⁶ Thickened intestinal loops may be noted and a pain response may be elicited upon abdominal palpation. The gastrointestinal signs are from viral destruction of intestinal crypt epithelium and the inability to effectively replace sloughed villous cells. Clinical signs appear acutely and death can occur within twelve hours. It is important to note that FPV is not responsible for chronic signs, as the disease is acutely self-limiting. The presence of a chronic condition should increase suspicion of an etiologic agent other than FPV.³

Exposure of a pregnant queen to the FPV during early gestation can result in fetal death and resorption (which may be mistaken for infertility), production of mummified fetuses, or abortion. Late gestational or early neonatal exposure to FPV results in CNS infection. Kittens affected during this timeframe may exhibit a cerebellar ataxia as they become ambulatory. FPV destroys the external germinal cell layer of the cerebellum, resulting in hypoplasia of the granular cell layer and Purkinje cells. Classical signs of cerebellar ataxia include intention tremors, a wide- based stance, and a hypermetric uncoordinated gait. Infections involving the optic nerve or retina may present as clinical blindness, but cerebellar lesions are much more common.³

Laboratory and Pathological Findings

The hallmark of FPV infection is a marked leukopenia, consisting mainly of neutropenia, but involving all white blood cells. The leukocyte count may be as low as 50 cells /m l. The degree of clinical disease generally correlates with the severity of the leukopenia.³ Patients with a leukocyte count < 2,000 cells /m l often have a guarded to poor prognosis.⁶ Lymphocytes are depleted in lymphoid tissues accompanied by subsequent atrophy of these tissues. A rebound neutrophilic leukocytosis is typical in recovering patients. Thrombocytopenia may occur as the virus is replicating in bone marrow. Anemia is uncommon due to the relatively long lifespan of the red blood cells and the acute progression of the disease.³ Bone marrow aspiration may reveal decreases in erythroid and myeloid precursors. Prerenal azotemia is usually present from severe dehydration.

Pathological findings at necropsy include hyperemic, thickened small intestinal bowel loops and enlarged mesenteric lymph nodes. Intestinal lesions predominantly are found in the jejunum and ileum. Kittens affected in utero may have cerebellar atrophy, hydrocephalus or hydrancephaly.³ Grossly, the bone marrow may appear fatty and gelatinous to semi fluid. Organs such as the spleen, liver and kidneys also may be enlarged and somewhat edematous.⁶ Histological examination of the small intestinal epithelium reveals dilated, necrotic crypts and shortened, blunt villi. Necrotic debris and sloughed epithelial cells are abundant in the intestinal lumen. Basophilic intranuclear inclusion bodies may be present in some of the remaining crypt cells. Lymphoid organs show obliteration of lymphoid cells; some inclusion bodies may be observed in the nuclei of any remaining cells.²

Diagnosis

Differential diagnoses for acute, severe gastroenteritis include (but are not limited to) FPV infection, salmonellosis, campylobacteriosis, toxoplasmosis, cryptosporidiosis, enteric toxicosis, pancreatitis, other viral enteritides, acute bacterial sepsis with endotoxemia, gastrointestinal foreign body with perforation and peritonitis, feline immunodeficiency virus infection, and feline leukemia virus infection.^3,6

Generally, a presumptive diagnosis of FPV infection can be made based on the acute onset of panleukopenia with gastrointestinal signs in a susceptible cat. However, fecal examination and culture may be warranted to exclude some of the aforementioned diseases. Feline leukemia virus and feline immunodeficiency virus infections are more chronic and persistent diseases than FPV infection. However, these diseases can occur concurrently and should be excluded by appropriate laboratory testing.³

Due to the prevalence of FPV in the environment and common vaccination practices, most cats possess serum antibodies to FPV. Demonstrating a rising antibody titer over a period of time or the presence of viral antigens or DNA in a sample suggests active ongoing infection. A fourfold rising titer of virus-neutralizing antibodies in the serum indicates active FPV infection, as does detection of the virus in biological samples using fluorescent antibody tags. ELISA, monoclonal antibodies, PCR and virus isolation techniques also can be used to detect the FPV in various biologic samples.³ The CITE^® canine parvovirus test is a widely available and effective in-house test to cross-detect FPV in feces in the acute phase of infection.⁶

Potential Sequelae of Viral Infection

Although FPV infection can be a fatal primary disease, there are often complications that increase the probability of mortality. Extreme thrombocytopenia can lead to disseminated intravascular coagulation (DIC) TCP occurs in DIC but usually does not cause the syndrome. Sloughing of the intestinal lumen allows for bacteria and bacterial endotoxins to enter the bloodstream, predisposing the patient to bacteremia and endotoxemia.³ The animal’s severe leukopenia results in acquired immunodeficiency. Secondary bacterial, viral or fungal infections are not uncommon. Severe dehydration, electrolyte disturbances, hypoglycemia and hypoproteinemia may develop due to vomiting, diarrhea and gastrointestinal leakage (Merck). Even if the animal survives initial FPV infection, complications such as cardiomyopathy may develop later in life.⁷

Treatment

The mainstay of treatment is supportive therapy. Careful patient monitoring and parenteral fluid administration are necessary to maintain an adequate hydration status and correct any electrolyte abnormalities. Oral food and water intake should be prohibited. Antiemetics may be given to decrease vomiting and make the patient more comfortable. Parenteral broad spectrum antibiotics may decrease the susceptibility of the patient to secondary infections. Steroid administration is contraindicated due to immunosuppressive side effects. Plasma or whole blood transfusions may be necessary to compensate for hypoproteinemia, anemia or hypotension. The patient also should be monitored and treated for any developing acidosis or hypoglycemia. Administration of parenteral nutrition should be considered in the severely emaciated patient as part of supportive therapy.^3,6

It should be noted that cerebellar problems due to in utero FPV infection are nonprogressive. As long as the affected kittens have no life-threatening deficits and can be placed in proper homes, they can make good pets.

Prevention

Since there is no specific treatment for FPV infection, prevention of viral infection by vaccination is recommended. Both inactivated and modified-live vaccines (MLVs) are commercially marketed and are effective in preventing feline panleukopenia. MLVs provide more rapid protection and only require one vaccination in the absence of maternal antibodies to afford protection to the animal. MLVs, however, should not be given to kittens under four weeks of age, pregnant queens or immunocompromised animals. Inactivated vaccines, on the other hand, pose no threat of causing actual disease or shedding of live virus. The adjuvant used with inactivated vaccines does run a higher risk of causing a vaccine reaction than the MLV. Also, more than one injection of inactivated vaccine is necessary to provide sufficient immunity. All factors should be taken into consideration when deciding upon a vaccination protocol which may change on an individual basis from patient to patient.³

General vaccinations start when a kitten is eight weeks old. Vaccination with either modified-live or inactivated product is followed by boosters given every two to three weeks until the kitten is between twelve and fourteen weeks of age. This protocol is designed to boost the kitten’s immunity as maternal immunity wanes. Colostrum-deprived kittens should receive the inactivated FPV vaccination as early as four weeks of age. Administration of hyperimmune serum can be used in cases of known exposure to other cats with feline panleukopenia. Any new cats of unknown vaccination history should be immunized with a MLV and isolated for at least two weeks before introducing them into a multicat household. Once kittens are fully vaccinated, a booster vaccination should be given at one year of age and then repeated every three years to maintain adequate FPV protection.³

In conclusion, feline panleukopenia is a severe, highly contagious, multisystemic disease that is endemic in the cat population. Prevention of disease by adequate vaccination is important because there is no specific treatment for FPV. Maintaining good hygiene, sanitation, and quarantine also are helpful in containing outbreaks of disease.

References

1. Ikeda Y, Nakamura K, Miyazawa T, Tohya Y, Takahashi E, Mochizuki, M. Feline host range of canine parvovirus: recent emergence of new antigenic types in cats. Emerg Infect Dis 2002; 8:341-346.

2. Murphy FA, Gibbs PJ, Studdert MJ, Horzinek MC: Veterinary Virology, 3rd ed. Academic Press, CITY, 1999; 348-351.

3. Greene CE (ed): Infectious Disease of the Dog and Cat, 2nd ed. W.B. Saunders Co., Philadelphia, 1998:52-57.

4. Truyen U, Parrish CR. Canine and feline host ranges of canine parvovirus and feline panleukopenia virus: distinct host cell tropisms of each virus in vitro and in vivo. J Virology 1992; 66:5399-5408.

5. Bauder B, Suchy A, Gabler C, Weissenböck, H. Apoptosis in feline panleukopenia and canine parvovirus enteritis. J Vet Med 2000; 47:775-784.

6. Aiello SE, Mays A (eds): The Merck Veterinary Manual, 8th ed. Whitehouse Station, N. J., 1998:559-560.

7. Meurs KM, Fox PR, Magnon AL, Liu S, Towbin, JA. Molecular screening by polymerase chain reaction detects panleukopenia virus DNA in formalin-fixed hearts from cats with idiopathic cardiomyopathy and myocarditis. Cardiovascular Pathol 2000; 9:119-126.

Acknowledgment

The "digital watercolor - cat" image is from the eeSmith.net website and is used under the provisions of the Creative Commons License.

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