Proceedings of the Southern European Veterinary Conference and Congreso Nacional de AVEPA

www.ivis.org Proceedings of the Southern European Veterinary Conference and Congreso Nacional de AVEPA Oct. 18-21, 2012 - Barcelona, Spain Next Conference: Oct. 17-19, 2013 - Barcelona, Spain Reprinted in the IVIS website with the permission of the SEVC - AVEPA

AN UPDATE ON FELINE INFECTIOUS DISEASE CONTROL AND VACCINATION Dr Andrew Sparkes Veterinary Director International Society of Feline Medicine Feline respiratory viruses & acute upper respiratory tract disease AURTD is one of the most common reasons for presentation of cats to veterinary surgeons in practice. Greater knowledge of its cause and epidemiology, coupled with the introduction of vaccines has helped in devising strategies to control AURTD but this is still a problematic area and disease is common. The major agents that have been implicated in AURTD in cats are: Feline caclicivirus Feline herpesvirus Chlamydophila felis Bordetella bronchiseptica The most important of these are feline herpesvirus (FHV) and feline calicivirus (FCV). Other viruses have been isolated from cats with AURTD (e.g. Reovirus) but are now thought to play a minor role, if any, in this disease. Chlamydophila felis is now recognised as an important ocular pathogen in cats. It causes conjunctivitis but usually no or minimal other upper respiratory tract signs such as sneezing and nasal discharge (chlamydophilosis is considered later). Bordetella bronchiseptica can act as a p rimary respiratory tract pathogen but generally in young kittens. Other bacteria are important but mainly as secondary opportunist invaders. A wide variety of bacteria are isolated from cats with AURTD including Pasteurella multocida, Staphylococci spp., Streptococci spp. and frequently enteric bacteria such as E. coli, faecal streptococci, Klebsiella spp., which are sometimes the predominant organisms. This results from the cleaning behaviour of cats, frequently licking at their perianal area and then at the external nares - this has implications for the choice of antibiotics for treatment. FCV and FHV - Clinical disease There is a single serotype of FHV implicated in AURTD and the disease caused by this virus is sometimes referred to as feline viral rhinotracheitis. It is a typical DNA herpesvirus. FCV is an RNA virus that displays considerable antigenic variation and it is likely that no two isolates of FCV are identical. The classical clinical picture of AURTD is very familiar. FHV produces severe disease with pronounced ocular signs including conjunctivitis. O cular and nasal discharges are usually profuse and there may be coughing. The disease is usually more severe in young kittens, and older debilitated cats. The clinical picture in FCV infection is much more variable in severity

reflecting the multiple variants of the virus. The disease can be as severe as FHV infection but is generally milder, sometimes producing minimal, or no disease. Oral ulceration is a common feature of infection. In severe cases of AURTD the cat will be pyrexic, dejected, inappetant and dehydrated. Failure to groom, particularly in the presence of tongue ulcers, leads to an unkempt coat. Possible complications of AURTD Although conjunctivitis is more commonly associated with FHV infection, FCV has also been isolated frequently from cats with conjunctivitis. Affected cats have sometimes shown no other signs of AURTD. Keratitis and corneal ulceration are a complication of some cases of AURTD. This is most often seen associated with FHV particularly in cat shelters, with rampant endemic, untreated disease. Chronic gingivitis remains one of the major problems in feline medicine. T he association with immunosuppressive agents, including FeLV but particularly FIV, with some cases has been appreciated in recent years. However this represents only a small proportion (probably under 20%) of cases of chronic gingivitis and the pathogenesis of most cases remains unclear. There is, however, a v ery striking association between gingivitis and FCV isolation, with FCV being isolated from greater than 80% of cases of gingivitis. Skin ulceration is an uncommon feature, which can occur with either virus but particularly FHV. There may or may not be other, more typical signs of AURTD, but with FHV the skin ulceration (usually on the face but sometimes more widespread) is more typically a feature of chronic disease. A transient shifting lameness is now also well recognised as a syndrome associated with FCV described as the limping syndrome. This may result from natural infection with FCV but can also be seen shortly following vaccination. The syndrome is usually seen in kittens receiving their primary vaccination course and may occur after either the first or second vaccination. Signs are typically of depression, pyrexia and s hifting lameness involving one or more limbs and often rapidly changing form one leg to another this is a transient polyarthritis and resolves within a few days. Outbreaks of highly virulent and often lethal FCV infection have recently been described in the United States and in Europe. The causative virus strains are most commonly referred to as virulent systemic feline calicivirus (VS-FCV). In contrast to the common strains, VS-FCV causes systemic disease characterized by severe inflammatory responses, widespread infection, multiorgan failure, and commonly death. Mortality is up to 70%. Fortunately, outbreaks are rare. Characteristics of carrier status in FHV and FCV FHV Carriers common (80%-100% infected cats) Virus excreted intermittently - latent infection Excretion precipitated by stress FCV Carriers common (~50% infected cats) Virus excreted continuously Long term virus excretion - may be lifelong

Treatment of AURTD Intravenous or subcutaneous fluid therapy is invaluable to maintain hydration and various options are available for tube feeding of cats to provide nutritional support. Effective, safe and practical antiviral agents are not yet widely available and antibiotic treatment is therefore essential for the control of secondary bacterial infection. Famciclovir is an antiviral agent that may be effective for FHV though.. Recombinant feline interferon omega is available as a commercial product in the veterinary market, and while there are no good published studies to document the efficacy of this product in acute FCV and FHV infections, these are situations where there is some logic to its use and 5-10 days of therapy (at injectable anti-viral doses) has some rationale, although studies documenting efficacy are lacking. Providing adequate analgesia is another important concern, and once rehydrated, the use of NSAIDs is now common-practice and strongly recommended. Feline Chlamydophilosis Chlamydophila felis is an ocular pathogen (causing conjunctivitis). Chlamydophila is an obligate intracellular bacterium with conjunctival epithelial cells being the major target of infection. Transmission of infection is mainly via direct contact between cats. Mild URTD signs may also occur (sneezing and mild nasal discharge). Diagnosis Culture or PCR tests on conjunctival swabs is usually used to diagnose infections. For optimal diagnosis a dry sterile swab should be firmly rolled over the conjunctiva to cause desquamation of epithelial cells. Treatment The drugs of choice for Chlamydophila therapy are topical and systemic tetracyclines (e.g. tetracycline ophthalmic ointment and doxycylcine per os). In young kittens there is some concern about discolouration of the teeth when using systemic tetracyclines, and in this situation amoxycilin/clavulanate may be a suitable alternative. G enerally therapy is continued for 4-6 weeks or for 1-2 weeks beyond resolution of clinical signs. L onger therapy (8-12 weeks) is required with amoxycillin/clavulanate as compared to doxycycline. I n a colony situation it is important to treat all the cats, irrespective of whether they are showing clinical signs. Feline bordetellosis Recent studies have helped to define the role of Bordetella bronchiseptica as a primary pathogen in cats. Bordetalla are gram negative rods. Although severe disease has rarely been reported with Bordetella, there is no doubt that this can be both a primary and secondary pathogen in cats. A variety of clinical signs can be seen ranging from signs typical of AURTD (with sneezing and nasal discharge being the predominant signs); signs similar to 'kennel cough' in dogs (i.e. predominantly tracheitis and coughing), to signs of severe pneumonia. However, it would appear that most infected cats either develop no significant clinical disease or develop AURTD and/or coughing. Epidemiologically it is clear that Bordetella can be transmitted between dogs and c ats, and although not a common cause of disease, Bordetella should be considered in cats showing signs of AURTD. Diagnosis and treatment Bordetella can be i solated from orpharyngeal or nasal swabs and, particularly in a multicat household with AURTD this part of the investigation should not be overlooked. Culture or PCR techniques are available. When identified as a pathogen, Bordetella will usually respond readily to appropriate therapy and in cats the antibiotics of choice are doxycycline and fluoroquinolones.

Vaccination Safe and efficacious vaccines are available for both Chlamydophila and Bordetella. While routine all cats would be very hard to justify given the relatively low prevalence of clinical disease associated with these agents, there may be some situations in which vaccination is both warranted and valuable to afford protection. Feline panleukopenia Feline panleukopenia virus (FPV) is a parvovirus closely related to other parvoviruses infecting dogs, mink, raccoons, raccoon dogs, foxes and other canids. FPV is a non-enveloped, singlestranded DNA virus, which is highly resistant to physical (environmental) factors that may degrade other viruses, and to chemical substances. In contaminated environments, it may remain infectious for weeks or even months. Diseased animals shed virus at high titres in their faeces, and virus quickly accumulates in affected shelters and catteries. As it is highly contagious and relatively resistant, susceptible animals may still become infected, even after a seemingly thorough disinfection of the premises. It is therefore recommended that only successfully vaccinated kittens and cats should enter such an environment. Although few data on FPV prevalence are available, individual cases and outbreaks in colonies are regularly reported by diagnostic laboratories and breeding catteries and rescue shelters are particularly at risk due to the number of cats kept in close confinement. Clinical disease FPV causes a systemic infection. The virus is transmitted via the faecal-oral route, it initially replicates in tissues of the oropharynx and is then distributed via a cell-free viraemia to virtually all tissues. Replication of the parvovirus with its single-stranded DNA genome requires cells in the S-phase of division and is therefore restricted to mitotically active tissues. The reason for this is that parvoviruses require cellular DNA polymerases that synthesize the complementary DNA strand, which is the first step in viral DNA replication and a prerequisite for transcription. The virus readily infects lymphoid tissues and can cause cellular depletion and a f unctional immunosuppression. Lymphopenia may arise as a result of lymphocytolysis but may also result from indirect effects, such as lymphocyte migration into tissues. The bone marrow is also affected, and virus replication has been described in early progenitor cells, which may explain the dramatic effect on virtually all myeloid cell populations. This is also reflected by the defining panleukopenia observed in blood samples from FPV infected cats. The hallmark of FPV replication is the shortening of the intestinal villi due t o a s ometimes complete loss of epithelial cells in the gut. The virus replicates in the rapidly dividing cells of the epithelium, the crypts of Lieberkuhn. This impairs the regeneration of the epithelium and results in the lesions described above. The severity of these lesions appears to correlate with the turnover rate of these cells, and co-infection with enteric viruses like feline coronavirus may enhance the severity of disease. Intrauterine transmission or perinatal infection may affect the central nervous system. A welldescribed feline cerebellar ataxia syndrome is recognised that results from an impaired development of the cerebellum due to lytic virus replication in the Purkinje cells in the infected kitten.. Diagnosis of FPV Feline panleukopenia can be diagnosed directly by isolation of the virus from blood or faeces in cell cultures and their presence can also be detected indirectly (e.g. in faeces) or by the use of rapid viral antigen tests. The gold standard diagnostic test for FPV remains histopathology combined with virus isolation/pcr as his will demonstrate the typical histopathological lesions caused by FPV.

Simply demonstrating the virus in a faecal sample may not be enough to confirm a diagnosis as it appears that antigen or PCR tests will be p ositive in some healthy cats (probably reflecting transient passage of virus acquired from the environment, and/or shedding of vaccine virus). Clinical signs, combined with the demonstration of panleucopenia together with demonstration of virus in faeces (PCR or antigen test) does however provide strong evidence of disease. FPV disease management A cat showing clinical signs of feline panleukopenia should be kept in isolation. Supportive therapy and good nursing care significantly decreases mortality caused by infection. Restoration of fluid and el ectrolyte and of the acid-base balance preferably by intravenous drip is most important in symptomatic treatment. As the gut barrier often is destroyed in FPV-infected cats, intestinal bacteria may readily cause bacteriaemia, facilitated by the existing neutropenia, leading to sepsis in these immunocompromised patients. Prevention of sepsis is essential, and a broad-spectrum antibiotic with a proven efficacy against gram-negative and anaerobic bacteria is recommended. Examples are amoxicillin/clavulanic acid or piperacillin in combination with aminoglycosides, fluoroquinolones, or cephalosporins. The potential side effects of these drugs should be taken into consideration. Antibiotics should be administered parenterally (preferentially intravenously). Oral intake of water and food should only be restricted if vomiting persists and feeding should be continued as long as possible, and restart as soon as possible. Beneficial effects of early enteral nutrition have been reported in canine parvovirosis. 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, antiemetics should be used. Due to the extreme stability of FPV, contaminated cages, litter trays, food dishes, water bowls, shoes and clothing can play an i mportant role in transmission, and attention to hygiene is of utmost importance. The virus is resistant to many common disinfectants, but can be inactivated by products that contain peracetic acid, formaldehyde, sodium hypochlorite, or sodium hydroxide. Sodium hypochlorite (household bleach, 1:30 dilution) can be used on smooth hard surfaces like litter trays that tolerate this disinfectant, while formaldehyde gas can be used for room disinfection. Susceptible kittens and unvaccinated older animals should not be in contact with other cats until they are properly immunized. Once a di sease outbreak occurs, passive immunization can be u sed to protect susceptible cats (young kittens with an i ncomplete vaccination history, colostrum-deprived kittens or unvaccinated cats). Modified live and inactivated vaccines are both highly effective against FPV. In most situations the choice of which to use is not important, however, pregnant cats and very young kittens should not receive MLV vaccines (due to the potential to cause cerebellar hypoplasia) but in the face of an outbreak of disease, MLV vaccines will provide a more rapid onset of immunity. Feline vaccination is a consensus emerging? Prevention of disease is the ultimate goal of veterinarians, and there is no doubt that the widespread use of vaccines has contributed enormously to achieving that ambition. The current prevalence of vaccination in cat populations is not high enough to achieve a good level of herd immunity and elimination of infectious agents and so containment and control is a more realistic goal, along with protection of the individual animal. N evertheless, as has been stated by the World Small Animal Association (WSAVA) Vaccine Guidelines Group (VGG), our aim should be to vaccinate every animal and each individual animal less frequently. In recent years, two particular lines of evidence have caused a re-evaluation of traditional vaccine recommendations. The first is the recognition that vaccination is not innocuous and that serious side effects sometimes occur. Various side effects are associated with vaccination with studies suggesting a prevalence of between 3% and 25% depending on the vaccine and how the data is collected. Most of these adverse reactions are mild and transient, but occasionally severe and life-threatening events can occur such as severe hypersensitivity reactions or the more recently

recognised injection-site sarcoma phenomenon in cats. The recognition of such devastating side effects, albeit seen rarely, challenges the notion that vaccination is a s afe procedure and that vaccine intervals are not an important consideration. The second strand of evidence has come from studies of duration of immunity (DOI) for vaccines. In the past, there has been a tendency for minimum DOI studies to be done for licensing purposes and/or for arbitrary annual vaccination boosters to be r ecommended. S ome vaccine manufacturers are now undertaking the (more expensive) studies to determine more than just minimal DOI for vaccines, and other studies have emerged that have provided good evidence on prolonged DOI for a number of vaccines. Thus the combined knowledge of occasional serious adverse reactions to vaccination, and for some vaccines growing evidence of a DOI well in excess of a year, has led to a serious re-evaluation of vaccination recommendations. There are now three international panels that have been e stablished to provide guidelines on feline vaccination protocols the American Association of Feline Practitioners Feline Vaccine Advisory Panel which first reported in 1998 and was updated in 2000 and most recently in 2006, the WSAVA VGG which reported in 2007, and the European Advisory Board on Cat Diseases (ABCD) which reported in 2009. The major recommendations from these three bodies are summarised in Tables 1-9. W hile there are differences between the recommendations of the three groups (as can be seen), there is a clear consensus among them too on many aspects. All the groups recommend that vaccines should not be given needlessly; that an annual health check is advisable irrespective of whether vaccines are given; that owners should be i nvolved with discussions, and the risks and benefits of vaccination explored so that informed consent is given; that adverse reactions to should be properly reported to vaccine manufacturers and regulatory authorities; and that vaccines should be regarded as core (where all cats is justifiable) and non-core (where vaccination can only be justified in certain circumstances). All three groups have also recommended booster vaccination schedules that include extended intervals (beyond the traditional 12 months), especially for the core vaccines (where more data is available), but that choices should be made on an individual basis and protocols cannot be formulated that are suitable for all cats in all circumstances. These are important principles and show the way to a more enlightened use of vaccines in the future. Perhaps of note is the fact that in the USA, since 1998 when the AAFP first introduced recommendations suggesting booster vaccination for core vaccines may given less frequently (e.g. every three years), despite apparent widespread uptake of this recommendation there have been no reports or suggestions of outbreaks of disease that would otherwise have been prevented. More information is still needed to reconcile some of the discrepancies between the recommendations of these three groups and to provide a g reater evidence base for ongoing refinement and changes to these recommendations, but there is now emerging an international consensus whereby veterinarians can clearly identify with the WSAVA stated aim of vaccinating every animal but each individual less frequently.

Table 1: Guideline recommendations for FPV vaccination Nature of vaccine Core Core Core kittens Begin from as early as 6 weeks, then every 3-4 weeks until 16 weeks of age Begin at 8-9 weeks with a second 3-4 weeks later and a final vaccine at 16 weeks of age Begin at 8-9 weeks with a second 3-4 weeks (minimum 12 weeks). Consider a final dose at 16-20 weeks of age Consider starting earlier than 8 weeks and repeating vaccination in cats 16w Vaccination of adult cats of unknown status A single dose of MLV in adults of unknown status followed by a booster after 1 year A single dose of MLV in adults of unknown status followed by a booster after 1 year primary course, then no more frequently than every 3 years primary course, then no more frequently than every 3 years primary course, then no more frequently than every 3 years unless special conditions apply Table 2: Guideline recommendations for FHV-1 and FCV vaccination Nature of vaccine Core Core Core kittens Begin as early as 6 weeks, then every 3-4 weeks until 16 weeks of age Begin at 8-9 weeks with a second 3-4 weeks later and a final vaccine at 16 weeks of age Begin at around 9 weeks with a second 2-4 weeks later (not earlier than 12w for FCV). Consider a third FCV dose at 16w in high-risk situations vaccination in cats 16w Two doses 2-4 weeks primary course, then every 3 years primary course, then every 3 years Annual for FHV-1, especially in high-risk situations, but for low-risk (e.g. indoor-only cats) 3- yearly intervals recommended. with lapsed If the interval since the last vaccination is 3 years a single dose is considered sufficient, if >3 years consider two doses If the interval since the last vaccination is 3 years a single dose is considered sufficient, if >3 years consider two doses

Table 3: Guideline recommendations for FeLV vaccination Nature of vaccine Non-core Non-core Non-core kittens Begin as early as 8 weeks then second 3-4 weeks later Begin as early as 8 weeks then second 3-4 weeks later Begin at 8-9 weeks with a second dose at 12 weeks vaccination in cats 16w Annually in cats at risk of exposure Annually in cats at risk of exposure Annually in cats at risk of exposure until 3-4 years of age, then every 2-3 years Table 4: Guideline recommendations for rabies vaccination Nature of vaccine Core where rabies endemic Non-core except where required by statute or disease is endemic Core where rabies endemic kittens A single dose as early as 8-12 weeks of age according to vaccine license A single dose as early as 8-12 weeks of age according to vaccine license A single dose as early as 8-12 weeks of age according to vaccine license. primary vaccine, then every 1-3 years according to state or government legislation and vaccine license primary vaccine, then every 1-3 years according to state or government legislation and vaccine license primary vaccine, then every 1-3 years according to state or government legislation and vaccine license Table 5: Guideline recommendations for Chlamydophila felis vaccination Nature of vaccine Non-core Non-core Non-core kittens from 9 weeks of age from 9 weeks of age starting at 8-10 weeks vaccination in cats 16w Annual where sustained risk of infection primary course, then no more frequently than every 3 years Annual

Table 6: Guideline recommendations for Bordetella bronchiseptica vaccination Nature of vaccine Non-core Non-core Non-core kittens Single IN dose from 8 weeks of age Single IN dose from 8 weeks of age Single IN dose from 8 weeks of age vaccination in cats 16w Single IN dose Single IN dose Single IN dose Annual where sustained risk of infection Annual where sustained risk of infection Annual where sustained risk of infection