Feline Panleucopenia

Feline Panleucopenia (FPL) is a highly contagious disease of domestic and feral cats, caused by the feline panleucopenia virus(FPV), which is closely linked to canine Parvovirus type 2 (CPV2). The disease isoften fatal and primarily affects 3-5 month-old kittens, following the decline of maternal antibodies (Ab);  adult cats, up to 4-5 years of age, are also at risk if not correctly vaccinated.

The infection has a worldwide distribution and causes enteritis, panleucopenia, foetal death, cerebellar disease and idiopathic myocarditis and cardiomyopathy.

The use of effective vaccines has drastically reduced the incidence of the disease. However, there are some strains of FPV, more similar to CPV2, to which cats are particularly sensitive, which cause a disease with symptoms similar to those of FPV, and which can be transmitted also to dogs, causing illness also in this species.

TRANSMISSION

The disease is transmitted through direct contact with infected cats but, given the long period of environmental survival, more frequently, the infection occurs through contact with the virus present in organic material dispersed in the environment. The virus can persist in hospitalised cats for several months and in kittens infected in utero for more than a year. It is therefore extremely important to control the hygienic conditions of the environment in which the kittens are located, taking into account that the virus can also be transmitted to adults if these are not vaccinated.

The incubation period is of approximately 4-10 days. The severity of the clinical signs after infection varies based upon a series of factors, but to a lesser extent compared to infection from CPV2[4]: absence of maternal antibodies, which protect until approximately 8 weeks of age; poor hygiene conditions; overcrowding; stress; presence of other enteric pathogens such as feline Coronavirus, Salmonella and Campylobacter. Not least, another important element to be considered is the defensive capacity of the immune system, which is often unable to produce sufficient quantities of virus-neutralising Ab. The primary targets of the viral agent are the lymphoid tissues in the oropharynx; after viraemia, the virus mainly spreads to the lymph nodes, spleen, thymus, bone marrow and intestinal crypts, i.e. to tissues with a high mitotic index. In the foetus, the cerebellar tissue is mainly affected, causing cerebellar hypoplasia.

CLINICAL SIGNS

Diarrhoea is the main and best known clinical sign of panleucopenia, caused by the destruction of the intestinal villi and the reduction, sometimes disappearance, of the epithelial intestinal cells. This said, the clinical signs of the infection are in fact quite variable, ranging from forms often characterised by a rather subtle, sometimes even sub-clinical,  onset, up to forms with a hyper-acute clinical onset. The hyper-acute disease is characterised by severe depression, very low temperature and death within 24 hours. The acute form, which is the one more commonly diagnosed, is instead characterised by fever (40-41°C), anorexia, sensory depression and abdominal pain. Vomiting and diarrhoea develop 24-72 hours after the initial signs and the faeces may be extremely fluid with profuse, watery and often bloody diarrhoea. Affected cats are very thirsty but do not quench their thirst spontaneously; dehydration rapidly develops which, if not adequately supported with i.v. fluids, can  lead to a fatal outcome. Intestinal irregularities and mesenteric lymphadenopathy are detected upon palpation of the abdomen. Petechiae and ecchymosis are also present in some patients, caused by the development of disseminated intravascular coagulation(DIC). Damage to the intestinal mucosa allows bacterial overgrowth and favours a severe septicaemia. Death occurs in 90-95% of cases. At necropsy, these subjects show evidence of severe dehydration and enlargement of the mesenteric lymph nodes and the spleen. The surface of the intestine, particularly the duodenum, ileum and jejunum, presents erosions of the mucosa and atrophy of the villi; haemorrhagic processes are clearly evident (Fig. 1). Microscopically, the intestinal crypts are dilated and filled with mucous material, with severe inflammation of the lamina propria.

In sub-acute infections, the following signs can be observed: mild pyrexia, depression, and enteritis, at times profuse and haemorrhagic; the clinical signs persist for more than three days and, with good hydration, a full recovery of the patient is usually possible. Subclinical infections are  typical of adult cats, where no typical clinical signs are present but laboratory tests usually evidence a mild to severe leucopenia.

In the first trimester of pregnancy, the infection causes foetal death and resorption, while in later stages the infection is responsible for the birth of subjects with cerebellar hypoplasia (Fig. 2) (feline ataxia syndrome). Affected kittens have a plantigrade gait with tremors, motor incoordination and ataxia (Video 1). Clinical signs are not usually present until 2-3 weeks of age. More severe cases may include the occurrence of seizures, behavioural impairment and retinal damage, independently from the cerebellar hypoplasia.

DIAGNOSIS

In unvaccinated cats, the disease may be suspected on the basis of the clinical signs, which are often characteristic, and the simultaneous detection  in the haematological examination of a severe leucopenia, which is strongly suggestive of FPL. In the more acute phases, the leucocyte count can range from 50 to 3000 cells/ml; patients with less severe clinical forms have a count which varies between 3000 to 7000 celll/ml. A drastic reduction of leucocytes often accompanies the severity of the disease, which becomes all the more fatal as the leucocyte count drops. Commercial diagnostic assays (ELISA) are useful for detecting the presence of Parvovirus in faecal samples; of limited diagnostic value are the isolation of the virus, in view of the limited or absent cytopathic effects produced in culture, and serological tests, due to the difficulty in detecting a significant increase in the antibody titre. The CPV ELISA detection assay on faeces is therefore a practical and simple examination, which gives a good indication about FPV infection.

Confirmation of the infection may result from an histopathologic assessment of the small intestine, the mesenteric lymph nodes and the spleen. At necropsy, a rapid diagnosis can be made by means of fluorescent antibodies on the affected spleen and small intestine. In the epithelial cells of the small intestine some type B intracellular inclusions may be present. The presence of cerebellar hypoplasia in the foetus and the newborn is also suggestive of FPL.

TREATMENT

There is no specific treatment for FPL; mortality can be reduced with an appropriate supportive therapy, in particular with an intravenous fluid replacement therapy with electrolyte integration. In the initial periods of the disease, the administration of food and per os products should be avoided, in order to prevent vomiting. The use of anti-emetics (metoclopramide 0.2-0.4 mg/kg s.c. every 6-8 hours) and gastrointestinal protective drugs (kaolin-pectin or bismuth subsalicylate) may be appropriate, together with a transfusion in those cats which develop severe anaemia, hypotension or hypoproteinemia (plasma proteins <  5.0 g/dl). The presence of severe neutropenia may lead to septic episodes. The prevention of sepsis is therefore essential and the administration of broad spectrum antibiotics with proven effects against anaerobic and gram-negative bacteria is indicated. An example may be ampicillins or cephalosporins, or amoxicillin/clavulanate or piperacillin, in combination with aminoglycosides, fluoroquinolones or metronidazole, which are useful for controlling secondary bacterial infections and preventing complications that are often the main cause of death in these animals. Also in this case the parenteral administration of drugs is preferable. Vitamin supplements, in particular with B-complex vitamins, may be useful for supporting the marrow and preventing a possible, although rare, thiamine deficiency.

Antiviral Therapy
In at-risk cats, the use of hyperimmune sera containing anti-FPV antibodies may be considered for the prevention of the infection, while their effectiveness in already sick animals remains questionable.

The use of intravenous recombinant Feline Interferon (rFeIFN-omega) seems capable of reducing mortality by 4 to 6 times; the efficacy of the treatment is greater the sooner it is started (2.5 MU/kg i.v. every 24 hours for 3-4 days). Response to therapy can be monitored by conducting a leucocyte count for 48-72 hours; the increase in white blood cells usually occurs within 24-48 hours. Feline IFN omega has demonstrated optimal effects in the treatment of canine Parvovirus; in the cat, however, its effectiveness is more doubtful. While the results are exceptional in vitro, numerous clinical studies have shown some limitations in the use of this cytokine in terms of resolving the pathology; this is probably linked to the fact that the product is all the more effective, as stated, the more acute is the viraemia. If the use of the drug is delayed, its effectiveness is reduced.  

PREVENTION

Prevention is the main strategy against the spread of this disease. Kittens and adult cats should always be vaccinated. Booster vaccinations should be performed every 2 years for cats living indoors, and every year for cats that go outdoors.

PASSIVE IMMUNISATION
Immunity against this virus is primarily humoural and may be induced by natural infection or by vaccination, or it may be the consequence of a passive transfer of maternal antibodies: in any case, the resulting protection is, in general, complete and prevents both disease and infection.

In at-risk environments, the mechanism of passive immunisation may be used to protect kittens that have not received colostrum or have a history of incomplete or unknown vaccinations, but also to protect unvaccinated adult cats that must be put into colonies. Sera with Anti-FPV antibodies may be administered subcutaneously or intraperitoneally and are able to provide protection for 2-4 weeks. These animals should therefore be vaccinated within three weeks of immunisation.

VACCINATION
Due to the severe consequences of infection and the risk of spreading the virus, vaccination is recommended in all cats. The FPV vaccine therefore falls within the category of “core” vaccines, i.e., “essential” vaccines, as prescribed by the guidelines for the vaccination of cats.

Both live, attenuated vaccines and inactivated vaccines are effective in preventing this pathology. The former have the power to stimulate an early immune response as well as the formation of persistent high-titre antibodies and may be immunogenic also in the presence of low-titre  colostral antibodies; the latter prove to be totally innocuous in terms of possible excretion into the environment.

Kittens protected by passive immunity received through colostrum generally do not usually develop an active immune response before 12 weeks of age; after this period, the antibody titre of maternal origin is instead too low to be considered protective.

In general, vaccination against panleucopenia is therefore performed between the 6^th and 12^th week: as in canine parvovirusinfection,however, this period corresponds with the window of vulnerability, in which immunity of maternal origin no longer guarantees protection of the kitten from the disease, but is still able to interfere with the antigenic stimulation of the vaccine. Precisely because of this possible reduction in the effectiveness of the vaccination in this age bracket, it is advisable to perform regular boosters every 3-4 weeks, until the kitten reaches 12 weeks of age. If the first vaccination is instead performed at 12 weeks or more,  a booster vaccine after a 3-4 week interval is advisable.

The minimum duration of immunity (DOI) following vaccination is 7 years: as a result, after the first vaccine series and an initial annual booster, a booster interval of maximum three years is considered protective.

Side-effects related to anti-panleucopenia vaccination are rare, while problems in pregnant queens vaccinated with a live, attenuated vaccine have been reported, with consequent possible development of neurological disorders in the developing foetuses; similar problems, with the same type of vaccine, have also been described in kittens vaccinated before 4 weeks of age.

Vaccination of the immunocompromised cat
Vaccines cannot provide optimal protection in the presence of conditions that compromise the immune system. Immunosuppression may result from various conditions: malnutrition, genetics, acquired immunodeficiency (FIV- FeLV, systemic diseases, use of immunosuppressive or cytostatic drugs, environmental stress. Immunosuppressed patients should be protected with particular care against infectious diseases by the use of vaccines. Vaccines with live, modified panleucopenia virus should in any case be administered with great care.

Cats treated with corticosteroids. In subjects under treatment with corticosteroids, vaccination should be considered with caution. In patients undergoing treatment with cortisones, clearly depending on the dosage used and the duration of treatment, vaccines should be avoided.

Cats with chronic diseases. In cats affected by chronic debilitating diseases, vaccination is often necessary. In general, it is advisable to use vaccinations regardless of the underlying disease (IRC, stabilised diabetes, hyperthyroidism), in the same manner as in healthy animals. On the contrary, cats with acute-onset diseases (diabetic ketoacidosis), that are febrile or weak, should NOT be vaccinated.

FeLV positive cats (Feline leukaemia virus). Retrovirus-infected cats should be isolated within the domestic environment in order to limit environmental spread, but also to limit their possible exposure to other infectious agents. In these conditions,  FeLV positive cats should be regularly vaccinated against FPV; in these subjects the possibility of more frequent vaccinations should be considered, as it has been shown that FeLV positive cats may develop a lower immune response to vaccinations.  Although there is no scientific evidence that these cats are at greater risk of vaccine-induced diseases, inactivated or recombinant preparations should be used.

FIV positive cats (Feline immunodeficiency virus). FIV infected healthy cats are able to develop a normal immune response following the administration of an antigen, however the primary immune response may be reduced or delayed. Some cases of  vaccine-induced panleucopenia following  the use of MLV-FPV vaccines have therefore been reported. In addition, a stimulation of lymphocytes with alteration or reduction in the CD4+/CD8+ ratio has also been proven.  This could be indicative of a potential risk of progression of the infection as a result of immune stimulation and consequent replication of the FIV virus. Based upon these observations, only FIV-seropositive cats at high risk of exposure should be vaccinated, and only using inactivated or recombinant vaccines.

Prevention in breeding establishments and catteries
In breeding establishments, where births can be programmed, vaccinations may be organised so as to provide the newly born kittens with the maximum possible amount of protective maternal antibodies. Kittens born from vaccinated queens can therefore be regularly vaccinated at the age of 12 weeks. The vaccination of pregnant or lactating queens should be avoided.

The problem of prevention is particularly significant in catteries; in these establishments, the panleucopenia viraemia is in fact a re-emerging problem and can be the cause of a high mortality rate. Unfortunately, notwithstanding the resulting costs, all kittens from the age of 4-6 weeks are to be vaccinated, obviously after prior assessment of their physical conditions. Kittens should then be vaccinated again after 4 weeks.

Particularly in catteries and breeding establishments, special attention should be paid to the fact that if cases of panleucopenia have occurred, cured patients may still shed the virus through their faeces for approximately 25 days;  these cats should therefore not be entrusted to people who have other unvaccinated kittens or adult cats.

In the presence of cases of panleucopenia, litter trays, bowls and cages should be cleaned carefully. Disinfection is with sodium hypochlorite (bleach) at 7%, using a spray and leaving to dry. Sodium hypochlorite is found or can be ordered in the pharmacy at a 15% concentration: dilution 1:2; gloves and mask should always be used when cleaning. Other disinfectants are not effective against this virus, which can survive in the environment for over 6 months. In the case of a death at home due to panleucopenia, it is additionally suggested not to host other unvaccinated kittens or cats for at least 6 months.

HYGIENIC RULES
General principles for controlling infectious diseases. The transmission of a disease from a sick cat or from a healthy carrier to a susceptible animal can occur in different ways, however, the most common is through direct contact, followed by the use of contaminating materials such as food, water and litter trays; a third way is through the airways, by which the virus or other agents can be shed through the aerosol, i.e., microscopic droplets that an animal emits through sneezing or coughing.

Cats that are persistently or latently infected with some agents such as herpes virus, calicivirus or FeLV are often an endless source of infection for kittens or other young animals.

It is therefore essential that the breeder or the cattery managers are aware of the basic principles of the transmission of infectious diseases.  Proper cleaning and disinfection are the basic elements for maintaining an ideal, healthy environment:  organic residues and all materials of daily use (scoops, litter trays, brushes, etc.) should, if possible, be removed from the premises and washed and disinfected with suitable disinfectants on a daily basis. This is all the more important the more dangerous the infectious disease present.

 The general rules to be applied for an effective control of the majority of infectious agents are:

1. no overcrowding
2. good air-renewal systems
3. requent change of litter trays
4. cage disinfection at least once a week
5. routine vaccination programmes
6. separation of suspected infected animals from healthy animals

An attempt should also be made to reduce the number of clearly or latently infected animals; the presence of an Herpes virus rhinotracheitis in 2-3 month-old kittens, which have no contact with extraneous cats, is a clear sign of the presence of one or more healthy carriers inside the breeding establishment/cattery. In general, if possible, never mix or bring into contact different litters; never share litter trays, bowls or food between different litters, unless previously washed and disinfected. In the presence of cases of panleucopenia, carefully clean litter trays, bowls and cages. Disinfect with sodium hypochlorite (bleach) at 7-10% using a spray and leave to dry.

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