«ABCD GUIDELINES ON: 2. FELINE HERPESVIRUS-1 2.1 Biology of the virus 2.1.1 Virus properties 2.1.2 Epidemiology 2.2 Pathogenesis 2.3 Immunity 2.3.1 ...»
Because the very low amounts of viral nucleic acids detectable by PCR may not be associated with disease, PCR positive results should be interpreted with caution. The sensitivity of PCR depends on the test (Maggs and Clarke, 2005) and it is advisable to use a system that includes a control that detects feline DNA to give an indication of how much material was on the swab, and to check for substances that might inhibit PCR. Due to its high sensitivity, PCR may also detect viral DNA in scrapings of the cornea and/or tonsils suggesting nonproductive infection (Maggs et al., 1999b; Reubel et al., 1993; Stiles et al., 1997a).
Consequently its predictive value for clinical infection may be poor, depending on the test sensitivity, the samples analysed (corneal scrapings and biopsies more frequently yield positive results than conjunctival ones) and the population tested (e.g. shelter cats are more likely to test positive than owned pet cats).
Additionally, many if not all PCR tests are able to detect FHV-1 DNA in modified-live vaccines (Maggs and Clarke, 2005) and it is not presently known if vaccinal strains may be detected in recently vaccinated animals and if so, for how long after vaccination.
A positive PCR result may represent low level shedding or viral latency and does not mean that the virus is responsible for clinical signs, although it indicates the possibility of recurring signs in the future. However, when quantitative real-time PCR is used (Vögtlin et al., 2002), the viral load present in the material tested may provide additional information on the etiological importance of the agent. When high loads are present in the nasal secretion or tears, this suggests active replication and therefore involvement of the virus in the clinical signs. If low copy numbers are detected in corneal scrapings, this would indicate a latent infection.
Molecular diagnosis may be more convenient for clinicians, because the use of fluorescein does not interfere with specificity of the test and samples can be mailed over several days at ambient temperature (Maggs 2005). It also allows the simultaneous detection in the same samples of other feline pathogens frequently implicated in respiratory and ocular diseases, especially Chlamydophila felis and, less reliably, feline calicivirus (Helps et al., 2003;
Marsilio et al., 2004).
184.108.40.206 Virus isolation If PCR is not available, virus isolation (VI) is an alternative method of diagnosing FHV-1 infection. Virus isolation is less sensitive than PCR but does indicate that replicationcompetent virus, not just DNA is present. VI also allows the simultaneous detection of feline calicivirus.
In cats undergoing primary FHV-1 infection, the virus can be easily detected by isolation from conjunctival, nasal or pharyngeal swabs or scrapings, or from post-mortem lung samples But during chronic infections when the aetiological origin of disease has to be confirmed, VI may be more difficult.
Asymptomatic carriers may also be detected by VI and both positive and negative predictive values of VI appear to be low in some studies (Gaskell and Povey, 1977; Maggs et al., 1999b). Samples must be collected before application of fluorescein or Rose Bengal stain ABCD guidelines on Feline Herpes Virus-1 7/17 which can inhibit viral replication in cell culture (Brooks et al., 1994; Storey et al., 2002) and clinical specimens should be sent quickly to the laboratory and is ideally refrigerated during shipping. For logistic reasons and despite its good sensitivity in acute disease, VI is not routinely used for FHV-1 infection diagnosis.
220.127.116.11 Immunofluorescent assay (IFA) FHV-1-specific proteins can be detected by immunofluorescent assay (IFA) on conjunctival or corneal smears or biopsy. As for VI, fluorescein instillation should be avoided before sampling. For IFA, this may give false positive results and interfere with the interpretation of the test. IFA has been reported to be less sensitive than VI or PCR, especially in chronic infections (Nasisse et al., 1993; Burgesser et al., 1999). Although no correlation between VI and IFA testing has been observed, combination of VI and IFA may predict the presence of virus better than either test alone (Nasisse et al., 1993; Maggs et al., 1999b). Because of lack of sensitivity and the interference with fluorescein, often used in ophthalmology practice, IFA is not the most suitable diagnostic test in chronic ocular diseases (Nasisse et al., 1993).
2.5.2 Detection of infection by serology FHV antibodies can be detected by serum neutralization or ELISA in serum, aqueous humour and cerebrospinal fluid (Dawson et al., 1998; Maggs et al., 1999b). The seroprevalence is very high in cats due to natural infection and vaccination. Consequently, the presence of specific antibodies does not correlate with disease and active infection (Maggs et al., 1999b).
Moreover, antibody detection does not allow differentiation between infected and vaccinated animals, neutralizing antibodies are undetectable until 20 to 30 days after a primary infection and antibody titres may be low in animals with either acute or chronic disease. Consequently serology has a very limited value in the diagnosis of feline herpesvirus infection (Nasisse and Weigler, 1997; Maggs et al., 1999b; Maggs, 2005).
2.6 Feline herpesvirus disease management
2.6.1 Supportive Treatment The restoration of fluids, electrolytes and the acid-base balance (e.g. replacement of losses of potassium and bicarbonate due to salivation and reduced food intake), preferably by intravenous administration, is required in cats with severe clinical signs. Food intake is extremely important. Many cats with FHV infection do not eat because of their loss of smell due to nasal congestion or because of ulcers in the oral cavity. Food may be blended to cause less pain when eating, should be highly palatable, and may be warmed up to increase the smell. Appetite stimulants (e.g. cyproheptadine) may be used. If the cat is not eating for more than three days, placement of a nasal or an oesophageal feeding tube is indicated.
Antibiotics should be given to treat all acute cases of feline upper respiratory tract disease to prevent secondary bacterial infections. Broad-spectrum antibiotics with good penetration in the respiratory tract should be given.
Cats severely affected by FHV-1 need intensive nursing care and appropriate supportive therapy is very important. If there is nasal discharge, this should be cleaned away several times a day with physiologic saline solution, and be treated afterwards with local ointment.
Drugs with mucolytic effects (e.g. bromhexine) may be helpful. Eye drops or ointment can be
n.d. = not determined; eod = every other day; sid = once daily; bid = twice daily; tid = three times daily.
It should be noted that the above drugs may not be readily available or licensed for cats.
Other drugs have been proposed for the treatment of FHV-1 ocular infections, including bromovinyldeoyuridine, cidofovir, HPMA, pencyclovir, ribavirin, valacyclovir, vidarabine, foscarnet and lactoferrin. However, the efficacy of these drugs is not supported by appropriate data.
2.7 General recommendations on vaccine type and vaccination protocol
FHV-1 infection is common and may induce severe disease. ABCD therefore recommends that all cats should be vaccinated against FHV-1. FHV-1-vaccines provide protection by inducing both humoral immunity, associated with a serological response, and cellular immunity. Vaccination provides good protection against clinical disease, but in common with many localised respiratory tract infections, it does not provide 100% protection (approx.
90+% reduction in clinical scores has been achieved following experimental challenge soon after vaccination)(Gaskell et al., 2007). Less effective protection can be expected in some vaccinated individuals in particular circumstances following exposure to virus, e.g. extreme challenge, immunosuppression. There is no evidence that any variation in isolates of FHV-1 creates problems in protection provided by vaccination.
Vaccination protects from the development of clinical signs, but not necessarily from infection. However, there is some evidence that it can reduce subsequent excretion of virus.
(Gaskell et al., 2007).
Currently, FHV-1 vaccines are usually combined with FCV, either in divalent vaccines (only in some countries) or, more commonly with other antigens. Both modified live and inactivated parenteral vaccines are available. Subunit FHV-vaccines and modified intranasal vaccines have been available previously or are available outside Europe, however they are not currently available in Europe.
Both inactivated and modified live FHV-1 vaccines have relative advantages and disadvantages. There is generally little reason to prefer any specific FHV vaccine for routine vaccination, particularly since these are all based on a single serotype. Modified live vaccines retain some pathogenic potential and may rarely induce disease if administered incorrectly, i.e. accidentally aerosolised or intake of vaccine virus spilt on the skin.
The value of serological tests in predicting protection is controversial. Methodological issues can complicate comparison of titres and some suggest that titres are not good predictors of protection. In other studies, cats without any evidence of seroconversion appear to show protection (Lappin et al., 2002; Mouzin 2004). Cats that have been vaccinated usually develop an anamnaestic response following exposure.
ABCD guidelines on Feline Herpes Virus-1 10/17 2.7.1 Primary vaccination course ABCD recommends that all kittens should be vaccinated against FHV-1. Maternally derived immunity can interfere with the response to vaccination and the primary course of vaccination is usually started at around nine weeks of age, although some vaccines are licensed for use at an earlier age. Kittens should receive a second vaccination two to four weeks later, with the second given around twelve weeks of age. This protocol has been developed to ensure optimal protection. For longer intervals, no information is available and a new primary vaccination course should be considered.
In contrast to vaccines against certain other infectious agents, where single vaccination is acceptable for cats of unknown or uncertain vaccination status, in the case of FHV-1, they should also receive two vaccinations at an interval of two to four weeks, irrespective of the vaccination type.
2.7.2 Booster vaccinations Vaccination against FHV-1 prevents disease, reduces virus shedding and recrudescence.
Although the issue of recommended intervals between boosters is controversial, in view of currently available scientific evidence, ABCD recommends that boosters should be given at annual intervals to protect individual cats against FHV-1 field infections, with the exception of cats in low-risk situations (e.g. indoor-only cats without contact to other cats). In these cases, three-yearly intervals would be recommended. An informed decision should be made on the basis of a risk-benefit analysis, but annual boosters are particularly important to cats that may be exposed to high risk situations e.g. entry to boarding catteries, breeding cats.
Experimental studies and serological studies in field situations clearly indicate that immunity against FHV lasts longer than one year in most vaccinated cats (Lappin et al., 2002, Mouzin et al., 2004). However, there is a significant proportion of cats for which this is not true. Field studies have shown that almost 100% of cats either have serological titres against FCV and FPV, or show an anamnestic response following administration of a booster vaccine, but around 30% of the cat population appear to have no detectable titres against FHV and around 20% fail to show an anamnestic response following booster vaccinations (Lappin et al., 2002, Mouzin et al., 2004). Assessment of the duration of protection is complicated by failure of vaccination to provide 100% clinical protection shortly after vaccination has been administered, but in experimental vaccine efficacy studies, the efficacy of protection afforded by vaccination clearly decreases with time.
If booster vaccinations have lapsed, a single injection is considered adequate if the interval since the last vaccination is less than three years, but if it is more than three years, two vaccinations should be considered to ensure that optimal protection is provided.
Boosters using FHV vaccines produced by another manufacturer are acceptable.
Cats that have recovered from disease associated with FHV may not have lifelong protection against further episodes of disease. Furthermore, in most cases, definitive identification of the infectious agent involved in diagnostic testing will not usually have been undertaken and the cat may be susceptible to infection with other respiratory tract pathogens. Therefore, vaccination of recovered cats is generally recommended.
ABCD guidelines on Feline Herpes Virus-1 11/17
2.8 Feline herpesvirus disease control in specific situations 2.8.1 Shelters FHV-1 can represent a particular problem in cat shelters. Management to prevent and limit the potential for transfer of infection is as important as vaccination in control. In shelters where the incoming cats are mixed, very high infection rates for FHV-1 are frequently encountered. New cats should be quarantined for the first two weeks and cats should be kept individually – unless known to originate from the same household. The design of the shelter and management used should be aimed at avoiding cross infection of cats. New cats should be vaccinated as soon as possible once they have been assessed as healthy and no contraindications to vaccination have been identified. If there is a particular high risk, i.e. past or recent infection with FHV-1 in the shelter, a modified live vaccine may be preferable as it may provide earlier protection. If acute respiratory infection occurs in a shelter, definitive diagnosis of the agent involved with differentiation of FHV-1 and FCV can be useful in deciding on the appropriate preventative measures that should be adopted.
2.8.2 Breeding catteries FHV-1 can be a major problem in breeding catteries. Infection most often appears as an infection in young kittens prior to weaning. It typically occurs at around 4-8 weeks as maternally derived immunity (MDI) wanes. The source of infection is frequently the mother who is a carrier and has shown reactivation of latent infection following the stress of kittening and lactation.