key: cord-0746085-ydohiuyj authors: Truyen, Uwe; Addie, Diane; Belák, Sándor; Boucraut-Baralon, Corine; Egberink, Herman; Frymus, Tadeusz; Gruffydd-Jones, Tim; Hartmann, Katrin; Hosie, Margaret J.; Lloret, Albert; Lutz, Hans; Marsilio, Fulvio; Pennisi, Maria Grazia; Radford, Alan D.; Thiry, Etienne; Horzinek, Marian C. title: Feline panleukopenia. ABCD guidelines on prevention and management date: 2009-07-31 journal: Journal of Feline Medicine & Surgery DOI: 10.1016/j.jfms.2009.05.002 sha: f28d99f0bdfb16c5fa56764d922953ab797bfc8e doc_id: 746085 cord_uid: ydohiuyj Abstract Overview Feline panleukopenia virus (FPV) infects all felids as well as raccoons, mink and foxes. This pathogen may survive in the environment for several months and is highly resistant to some disinfectants. Infection Transmission occurs via the faecal–oral route. Indirect contact is the most common route of infection, and FPV may be carried by fomites (shoes, clothing), which means indoor cats are also at risk. Intrauterine virus transmission and infection of neonates can occur. Disease signs Cats of all ages may be affected by FPV, but kittens are most susceptible. Mortality rates are high – over 90% in kittens. Signs of disease include diarrhoea, lymphopenia and neutropenia, followed by thrombocytopenia and anaemia, immunosuppression (transient in adult cats), cerebellar ataxia (in kittens only) and abortion. Diagnosis Feline panleukopenia virus antigen is detected in faeces using commercially available test kits. Specialised laboratories carry out PCR testing on whole blood or faeces. Serological tests are not recommended, as they do not distinguish between infection and vaccination. Disease management Supportive therapy and good nursing significantly decrease mortality rates. In cases of enteritis, parenteral administration of a broad-spectrum antibiotic is recommended. Disinfectants containing sodium hypochlorite (bleach), peracetic acid, formaldehyde or sodium hydroxide are effective. Vaccination recommendations All cats – including indoor cats – should be vaccinated. Two injections, at 8–9 weeks of age and 3–4 weeks later, are recommended, and a first booster 1 year later. A third vaccination at 16–20 weeks of age is recommended for kittens from environments with a high infection pressure (cat shelters) or from queens with high vaccine-induced antibody levels (breeding catteries). Subsequent booster vaccinations should be administered at intervals of 3 years or more. Modified-live virus vaccines should not be used in pregnant queens or in kittens less than 4 weeks of age. Feline panleukopenia virus causes a systemic infection. The virus is transmitted via the faecal-oral route, initially replicates in tissues of the oropharynx and is then distributed via a cellfree viraemia to virtually all tissues. The genome of FPV is a single-stranded DNA molecule, which requires cells in the S-phase of division for its replication, and virus growth is therefore restricted to mitotically active tissues. All 'autonomous' parvoviruses require cellular DNA polymerases that synthesise the complementary DNA strand -this is the first step in viral DNA replication and a prerequisite for transcription. The virus infects lymphoid tissues, and through cellular depletion can cause a functional immunosuppression. Lymphopenia may arise directly as a result of lymphocytolysis, but also indirectly, following lymphocyte migration into tissues. The bone marrow is affected as well, and virus replication has been described in early progenitor cells, explaining the dramatic effect on virtually all myeloid cell populations. 15 This is also reflected by the defining panleukopenia that is observed in FPV-infected cats. 16 The hallmark of FPV infection is diarrhoea, caused by the shortening of the intestinal villi due to a loss -sometimes complete -of epithelial cells. 17 The virus replicates in the rapidly dividing cells of the crypts of Lieberkühn, impairs regeneration of the intestinal epithelium and the lesions described above are the result (Figs 1 and 2) . Their severity correlates with the turnover rate of these cells, and co-infection with enteric viruses such as feline coronavirus may aggravate the disease. Intrauterine or perinatal infection may affect the central nervous system of the fetus, leading to cerebellar ataxia and intention tremor in affected kittens. The FPV feline ataxia syndrome results from an impaired development of the cerebellum due to lytic virus replication in the Purkinje cells (Table 1) . 18, 19 Although FPV affects cats of all ages, kittens are most susceptible. Mortality rates are high -over 90% in kittens (Fig 3) . The biological half-life of maternally derived antibodies (MDA) is about 10 days. 20, 22 Having waned below a haemagglutination inhibition titre of about 40, MDA do not protect reliably against infection, but may still interfere with active immunisation. In most cats, MDA remain at protective titres until 6-8 weeks of age. However, later vaccinations have proven to offer advantages, 23 Since the endo thelio chorial placen tation of the cat restricts materno fetal passage of solutes, immunoglobulins of the IgG isotype can reach the fetus only during the last third of gestation and contribute to less than 10% of the kitten's maternal immunity. Therefore, sufficient colostrum must be ingested to acquire protective levels of neutralising antibodies from the queen. Maximum absorption occurs around the eighth hour of life. Later, the kitten's intestinal cells are replaced by epithelium that can no longer absorb and transport antibodies. Kitten serum antibody titres generally approach 50% of those of the dam, but vary depending on individual colostrum intake -which explains the large variations between littermates. 24 Titres decrease in the first weeks of life by decay and dilution in the growing kitten. By analogy with CPV, an immunity gap around 8-12 weeks of age is postulated, when antibody levels are too low to protect against natural infection, but still high enough to interfere with vaccination ( Fig 4) . 22 A cat diagnosed with feline panleukopenia, based on clinical signs and confirmed by laboratory evidence, should be kept in isolation. Supportive therapy and good nursing significantly decrease mortality. Restoration of fluid, electrolytes and acid-base balance, preferably by intravenous drip, is most important in symptomatic treatment ( Fig 5) . As the gut barrier is often destroyed in FPVinfected cats, intestinal bacteria may invade the Active immune response Antibodies play an important role in the immune response to FPV, and MDA efficiently protect kittens from fatal infection. Passively acquired immunity is later replaced by an active response, either by vaccination or as a consequence of natural infection. Active immunity is solid and long lasting, and can be achieved by both inactivated and modified-live virus (MLV) vaccines. 26 Feline panleukopenia virus antiserum has been used to protect cats before a vaccine-induced, active response is obtained. 27 In kittens, this postpones the time at which active immunisation would be successful. The cellular immune response against one parvovirus capsid protein (VP2 ) is mediated by CD4+ and CD8+ T lymphocytes in the context of the major histocompatibility complex type II, as evidenced by the production of interleukin 2 by T lymphocytes stimulated with CPV-2. 28 Feline panleukopenia can be diagnosed by virus isolation from blood or faeces in cultures of CrFK or MYA-1 cells and by the demonstration of haemagglutination of porcine erythrocytes. 29, 30 However, these methods are now rarely used for routine diagnosis. In practice, FPV antigen is detected in faeces using commercially available latex agglutination or immunochromatographic tests. 13, 31 These tests have an acceptable sensitivity and specificity when compared with reference methods. 32 Tests marketed for the detection of both FPV antigen and CPV-2 antigen may be used to diagnose FPV in faeces [EBM grade I]. Diagnosis by electron microscopy has lost its importance due to more specific, rapid and automated alternatives. Specialised laboratories offer PCR-based testing of whole blood or faeces. Whole blood is recommended in cats without diarrhoea or when no faecal samples are available. 33, 34 The analytical sensitivity of the antigen tests can be compromised by the presence of antibodies, which may bind to viral epitopes and render them inaccessible to the monoclonal antibodies in the test kit. 35 This may lead to false negative results in samples from cats recently infected with FPV. Antibodies to FPV can be demonstrated by ELISA or indirect immunofluorescence, but these tests are of limited diagnostic value as they do not differentiate between infectionand vaccination-induced antibodies. 36, 37 The presence of antibodies is taken as proof of protection against panleukopenia under field conditions. 38 Courtesy of Albert Lloret blood stream. Bacteraemia in combination with the existing neutropenia may lead to sepsis in these immunocompromised patients. Prevention of sepsis is essential, and a broad-spectrum antibiotic with proven efficacy against Gram-negative and anaerobic bacteria is recommended. Examples are amoxicillin/clavulanic acid or piperacillin in combination with aminoglycosides, fluoroquinolones, cephalosporins or piperacillin/tazobactam. However, the potential side effects of these drugs should be taken into consideration. Antibiotics should be administered parenterally (preferably intravenously). Oral intake of water and food should be restricted only if vomiting persists; feeding should be continued for as long as possible, and restarted as soon as possible. Beneficial effects of early enteral nutrition have been reported in canine parvovirosis [EBM grade IV]. 39 A highly digestible diet is preferred, but if the cat does not accept it, any diet is better than no food intake at all. If vomiting persists, anti-emetics should be considered. Vitamin supplements, particularly B vitamin complex, can be given to prevent thiamine deficiency (which occurs only infrequently). Hypoproteinaemic cats may require plasma or whole blood transfusions to restore oncotic pressure. Plasma transfusion in combination with heparin may control disseminated intravascular coagulation, as it supplements anti-thrombin III and other important plasma proteins. In anorexic, seriously vomiting and/or diarrhoeic cats, or in patients with persistent hypoproteinaemia, parenteral nutrition is required, preferably via a central venous catheter in the jugular vein. 40 Immune serum containing FPV antibodies can be used to prevent infection of susceptible animals. The prophylactic efficacy of this measure has been demonstrated in dogs and may be expected to operate also in cats [EBM grade IV]. 41, 42 Feline recombinant interferon-omega is effective in the treatment of parvoviral enteritis in dogs and also inhibits replication of FPV in cell culture. 29, [43] [44] [45] So far, no data are available on the efficacy of this cytokine in FPV-infected cats, but it is expected to perform well -if not better -in the homologous host [EBM grade IV]. Susceptible kittens and unvaccinated older animals should not be in contact with other cats until they are properly immunised. In a disease outbreak, passive immunisation can be used to protect young kittens with an incomplete vaccination history, colostrumdeprived kittens or unvaccinated adult cats. Anti-FPV serum can be given subcutaneously or intraperitoneally and may protect for 2-4 weeks. 47 If a product of equine origin is used, repeated administration is not recommended as this may lead to anaphylactic reactions. 40 These animals should not be vaccinated within 3 weeks of passive immunisation. Because of the serious consequences of an infection and the ubiquity of the virus, vaccination is recommended for every cat; FPV vaccines belong to the 'core' category (see box on page 543). Even cats kept strictly indoors cannot avoid encountering the virus, since it is so stable in the environment that it can be transmitted on fomites. 50, 51 Random source populations with unknown vaccination histories, continuous resident turnover and high risk for infectious disease are characteristics of most shelters. Budget constraints become a crucial management aspect, and only vaccines that demonstrate a clear benefit against common and serious shelter diseases will be employed. Feline panleukopenia virus has re-emerged as a major cause of mortality in cats in shelters and rescue homes. With rare exceptions, all kittens and cats over 4-6 weeks of age should therefore be vaccinated, regardless of physical condition, pregnancy or housing status. Kittens should be vaccinated beginning at 4 weeks of age in the face of an outbreak, and at 6 weeks of age otherwise, using MLV vaccines. 47, 54 Cats of unknown status should not be housed together. Vaccination should be repeated every 3-4 weeks in kittens until 16 weeks of age. In the face of an outbreak, the more rapid onset of immunity induced by MLV preparations makes them preferable to killed preparations. Passive immunisation can be used in shelters; it is useful at admission if the disease is present, as it provides immediate protection. The efficacy of immunoglobulins in preventing panleukopenia was proven experimentally and in the field some 50 years ago. It depends on Hygiene Due to the extreme physicochemical stability of FPV, contaminated cages, litter trays, food dishes, water bowls, shoes and clothing can play an important role in transmission, and attention to hygiene is of utmost importance. The virus is resistant to many common disinfectants, but is inactivated by products containing peracetic acid, formaldehyde, sodium hypochlorite or sodium hydroxide. 46 Sodium hypochlorite (household bleach, 1:30 dilution) can be used on smooth hard surfaces like litter trays, whereas formaldehyde gas can be used for room disinfection. the specific antibody titre, the volume administered, the relative importance of serum antibodies in controlling the particular infection, and the timing of administration. Products containing highly concentrated immunoglobulins are available in some European countries for cats (horse antibodies directed against FPV, feline herpesvirus and feline calicivirus). They are marketed for prophylactic and therapeutic use, with protection lasting for about 3 weeks. During this period, the cats cannot be vaccinated with a MLV product, because the immunoglobulins will neutralise the attenuated virus. Although large amounts of foreign (equine) protein are administered, allergic reactions and side effects are rare. Repeated treatment (at an interval of more than 1 week) should be avoided, as cats may display anaphylactic reactions. 40 Immune serum (see box on page 544) may also be prepared in the veterinary practice by bleeding healthy donor cats (preferably groups of recovered animals). Hyperimmune serum would be obtained from animals that had been repeatedly vaccinated. If such sera are used, their antibody content and consequently the duration of protection are obviously unknown. Feline panleukopenia virus has re-emerged as a major cause of mortality in cats in shelters and rescue homes. 49, 50 In the field, inactivated vaccines are not popular and have all but disappeared from the market (eg, in Germany, they are only used in exotic felids). There are no data to suggest that particular vaccine brands are more efficacious than others. The following considerations may influence the decision about the vaccine type: Kittens from immune queens are protected by MDA in the first weeks of life. However, the time at which a kitten will become susceptible to infection and/or can respond to vaccination is unknown; also, there is considerable variation between individuals. In general, MDA will have waned by 8-12 weeks of age to a level that allows an immunological response, and an initial vaccination at 8-9 weeks of age followed by a second injection 3-4 weeks later is commonly recommended. Many vaccines carry data sheet recommendations to this effect. However, kittens with poor MDA may be vulnerable (and capable of responding to vaccination) at an earlier age, while others may possess MDA at such high titres that they are incapable of responding to vaccination until some time after 12 weeks of age. No single primary vaccination policy will therefore cover all potential situations. The ABCD recommends that: The ABCD considers vaccines that protect against FPV infections as being core. Vaccination schedules used for privately owned cats are appropriate in most breeding catteries. Queens may receive boosters before breeding to maximise delivery of MDA to kittens. 56 The kittens from such queens may need an extra primary vaccination at 16-20 weeks [EBM grade I]. Pregnant cats should not routinely be vaccinated. Lactation is not known to interfere with the immune response in cats. However, any vaccination may stress the queen and result in a temporary decline in mothering ability and milk production. Vaccination of lactating queens should therefore be avoided. Usually serum is given subcutaneously; the recommended dose is 2-4 ml serum per kilogram body weight; intraperitoneal injection is more feasible in kittens. If intravenous administration is required for an instant effect, plasma (instead of serum) should be used. 54 Dr Karin de Lange for her judicious assistance in organising this special issue, her efforts at coordination, and her friendly deadlinekeeping. The tireless editorial assistance of Christina Espert-Sanchez is gratefully acknowledged. The groundwork for this series of guidelines would not have been possible without financial support from Merial. The ABCD particularly appreciates the support of Dr Jean-Christophe Thibault, who respected the team's insistence on scientific independence. ✜ Although protection starts rapidly after injection of modified-live virus vaccines, they should not be used in pregnant queens and in kittens less than 4 weeks of age. Emergence, natural history and variation of canine, mink and feline parvoviruses The evolution of parvovirus taxonomy Parvovirus infections in wild carnivores Canine and feline host ranges of canine parvovirus and feline panleukopenia virus. Distinct host cell tropisms of each virus in vitro and in vivo An annotated historical account of canine parvovirus Emergence and recent evolution of canine parvovirus Parvovirus host range, cell tropism and evolution Evolution of the feline subgroup parvoviruses and the control of canine host range Evolution of canine parvovirus involved loss and gain of the feline host range Isolation of canine parvovirus from a cat manifesting clinical signs of feline panleukopenia Canine parvoviren in Deutschland: ein update Mink enteritis parvovirus. Stability of virus kept under outdoor conditions Detection of feline parvovirus in dying pedigree kittens Kitten mortality in the United Kingdom: a retrospective analysis of 274 histopathological examinations Pathogenesis of feline panleukopenia virus and canine parvovirus Epidemiology and pathology of autonomous parvoviruses Pathogenesis of feline panleukopenia virus and canine parvovirus Pathogenesis of feline panleukopenia virus in susceptible newborn kittens II. Pathology and immunofluorescence Cerebellar ataxia and its congenital transmission in cats by feline panleukopenia virus Virus infections of carnivores Apoptosis in feline panleukopenia virus-infected lymphocytes Maternally derived immunity to feline panleukopenia A field trial to assess the effect of vaccination against feline herpesvirus, feline calicivirus and feline panleucopenia virus in 6-week-old kittens Gestion de la parvovirose en élevage canin Canine parvovirus infection Feline panleukopenia -feline infectious enteritis The Cornell book of cats Establishment and characterization of canine parvovirus-specific murine CD4+ T cell clones and their use for the delineation of T cell epitopes Isolation of feline parvovirus from peripheral blood mononuclear cells of cats in northern Vietnam Feline panleukopenia in Japan. II. Hemagglutinability of the isolated virus Latex agglutination test for detecting feline panleukopenia virus, canine parvovirus and parvoviruses of fur animals Comparison of different in-house test systems to detect parvovirus in faeces of cats A simple touch-down polymerase chain reaction for the detection of canine parvovirus and feline panleukopenia virus in feces Epizootiologic investigations of selected infectious disease agents in free-ranging Eurasian lynx from Sweden Panleukopenia-like syndrome of FeLV caused by co-infection with FeLV and feline panleukopenia virus Rapid enzyme-linked immunosorbent assay for detecting antibodies to canine parvovirus Prevalence of antibodies to feline parvovirus, calicivirus, herpesvirus, coronavirus and immunodeficiency virus and of feline leukemia virus antigen and the interrelationship of these viral infections in free-ranging lions in east Africa Use of serologic tests to predict resistance to feline herpesvirus 1, feline calicivirus and feline parvovirus infection in cats Effect of early enteral nutrition on intestinal permeability, intestinal protein loss and outcome in dogs with severe parvoviral enteritis Feline panleukopenie. Praxisrelevante fragen anhand eines fallbeispiels Pathogenesis of canine parvovirus enteritis: sequential virus distribution and passive immunization studies Treatment of dogs naturally infected with canine parvovirus with lyophilized canine IgG Treatment of canine parvoviral enteritis with interferon-omega in a placebo-controlled challenge trial Available online at www.sciencedirect.com Treatment of canine parvoviral enteritis with interferon-omega in a placebo-controlled field trial Inhibitory effects of recombinant feline interferon on the replication of feline enteropathogenic viruses in vitro Untersuchungen zur änderung der DVG-desinfektionsmittelrichtlinien (viruzidie) Infectious diseases of the dog and cat Impact of vaccination on parvovirus testing in kittens Serological responses of feral cats to vaccination in trap-neuter-return programs Feline panleukopenia and other enteric viral diseases Long-term immunity in cats vaccinated with an inactivated trivalent vaccine Efficacy of feline panleucopenia vaccine to prevent infection with an isolate of CPV2b obtained from a cat Characterisation of cross-reactivity of virus neutralising antibodies induced by feline panleukopenia virus and canine parvoviruses Infectious diseases of the dog and cat Failure of passive transfer in neonatal kittens: correction by administration of adult cat serum Strategies for controlling viral infections in feline populations Effects of prednisolone on the development of immune response to canine distemper virus in beagle pups Effect of primary-stage feline immunnodeficiency virus infection on subsequent feline calicivirus vaccination and challenge in cats Effects of incidental infections and immune activation on disease progression in experimentally feline immunodeficiency virus-infected cats Evidence for modulated immune response to Anaplasma phagocytophila sensu lato in cats with FIV-induced immunosuppression Use of a feline panleukopenia modified-live virus vaccine in cats in the primary stage of feline immunodeficiency virus-infection Immunization-induced decrease of the CDA+:CD8+ ratio in cats experimentally infected with feline immunodeficiency virus The European Advisory Board on Cat Diseases (ABCD) is indebted to