Richard B. Ford, DVM, MS, Diplomate ACVIM & ACVPM (Hon)
Dr. Ford highlights the several important variables that influence both the justification to vaccinate for feline infectious respiratory disease and the quality of immunity derived from vaccination.
Four vaccines are currently available to aid in the prevention of upper respiratory disease (URD) in cats associated with exposure to (Table 1):
- Feline herpesvirus-1 (cause of feline rhinotracheitis)
- Feline calicivirus
- Chlamydophila felis
- Bordetella bronchiseptica.
| Table 1. Feline Upper Respiratory Infections Controlled By Vaccination | ||
| Prevalence | Transmission | Zoonotic Risk |
| Feline Herpesvirus-1 (double-stranded DNA virus) | ||
| Highly prevalent as a latent virus | • Direct cat-to-cat contact • Virus survives up to 18 H in external environment • Carrier state develops following infection • Virus highly susceptible to common disinfectants |
Feline infections are not zoonotic |
| Feline Calicivirus (single-stranded RNA virus) | ||
| Highly prevalent | • Direct cat-to-cat contact • Virus survives for days to weeks in external environment • Carrier state can develop following infection • Virus most susceptible to household bleach:water (1:30) |
Feline infections are not zoonotic |
| Chlamydophila felis (gram-negative, obligate intracellular bacterium) | ||
| Low prevalence in household cats Slightly higher prevalence in high-density populations |
• Direct cat-to-cat contact • Bacterium can survive only a few days in external environment (room temp) • Carrier-states recognized in cats, with shedding from reproductive tract of adult cats following ocular infection |
Feline infections have been implicated, but not well documented, in connection with human conjunctivitis |
| Bordetella bronchiseptica (gram-negative coccobacillus) | ||
| Relatively prevalent | • Bacterium exists in a nonpathogenic state in respiratory tract of cats and dogs • Transmission occurs following direct cat-to-cat contact; aerosol transmission less likely |
Minor zoonotic risk* |
| *Opportunistic human infections have been reported following contact with infected dogs | ||
None of the feline respiratory vaccines completely prevent infection or development of a carrier state. They do, however, mitigate the severity of respiratory disease. Table 2 summarizes feline respiratory disease vaccine types and routes of administration.
However, several important variables influence not only the justification to recommend vaccination but the quality of immunity an individual cat derives following administration of a vaccine.
| Table 2. Feline Upper Respiratory Disease Vaccines | ||
| Vaccine | ||
| Herpesvirus-1 (FCV-1) + calicivirus (FCV) | Modified-live virus; nonadjuvanted | Subcutaneous |
| Herpesvirus-1 (FCV-1) + calicivirus (FCV) | Killed virus; adjuvanted | Subcutaneous |
| Herpesvirus-1 (FCV-1) + calicivirus (FCV) | Modified-live virus; nonadjuvanted | Intranasal (mucosal) |
| Bi-valent calicivirus (FCV) | Killed virus; adjuvanted | Subcutaneous |
| Bordetella bronchiseptica | Avirulent, live bacteria; nonadjuvanted | Intranasal ONLY |
| Chlamydophila felis | Avirulent, live bacteria; nonadjuvanted | Subcutaneous |
| Chlamydophila felis | Killed bacteria; adjuvanted | Subcutaneous |
VIRAL DISEASE AGENTS
Feline Herpesvirus-1
Feline herpesvirus-1 (FHV-1) is the respiratory pathogen that causes the most severe clinical signs in cats.
Clinical Signs. Sneezing, rhinitis (often times ulcerative), tracheitis, conjunctivitis, keratitis, and oral ulceration characterize acute infection (Figure 1). Occasionally, localized skin lesions occur.
Figure 1. A 5- to 6-week-old kitten infected with feline herpesvirus-1
Disease Course. Kittens are the most susceptible to exposure, especially as maternally-derived antibody (MDA) levels decline. Cats that survive initial infection develop a latent infection that typically persists for the life of the cat. Cats latently infected with FHV-1 can manifest episodic reactivation of the latent herpesvirus, with viral shedding often following pharmacologic (eg, corticosteroid administration) or physiologic stress.1
Feline Calicivirus
Feline calicivirus (FCV) infection is highly prevalent in the feline population. Over 40 strains of FCV have been identified, some of which mutate to become highly virulent, or virulent systemic (VS), FCV strains.
Clinical Signs. Most strains cause acute upper respiratory signs characterized by sneezing and oral/nasal ulceration. Secondary bacterial infections are common and may culminate in pneumonia and death, particularly in kittens. Although uncommon, VS calicivirus can cause edematous and ulcerative skin infections, hemorrhagic syndromes, pancreatitis, jaundice, and high mortality.2
Transmission of Feline Upper Respiratory Disease
Transmission of feline URD, whether viral or bacterial in origin, most often occurs following direct cat-to-cat contact with infected nasal, ocular, or oral secretions.1,3 Indirect contact with contaminated sources (feeding dishes, clothing, hands) also transmits these diseases. Transmission through aerosolized microdroplets from infected cats can occur over short distances (less than 3–4 feet), but is not regarded as a primary route.4
Disease Course. Following recovery from the more common acute FCV infection, cats may develop a chronic carrier state, with persistent viral shedding, lasting from weeks to years. Chronic carrier cats may manifest paroxysmal sneezing, nasal discharge, or chronic gingivitis/stomatitis (Figure 2). Some affected cats have no clinical signs but shed virulent virus continuously from the oropharynx, posing a significant risk to susceptible cats/kittens.
Figure 2. An adult male Rex presented for chronic nasal/ocular discharge and paroxysmal sneezing episodes; calicivirus carrier state was confirmed
BACTERIAL DISEASE AGENTS
Chlamydophila felis, a gram negative intracellular bacterium, is a minor pathogen in the spectrum of agents that cause feline infectious URD.
Chlamydophila felisClinical Signs. Although sneezing and nasal discharge can occur during infection, conjunctivitis with chemosis and mucoid ocular discharge are the most common clinical manifestations (Figure 3).
Figure 3. Conjunctivitis and chemosis in an adult female cat confirmed to have Chlamydophila felis
Disease Course. Clinical signs typically develop 5 to 10 days following exposure. Chronic carrier cats have been identified.
Bordetella bronchiseptica
Bordetella bronchiseptica, a gram negative bacterium, has adapted to the respiratory tract of several species, including humans, and exists as part of the normal respiratory flora of many cats and dogs.
Clinical Signs. Clinical signs of feline bordetellosis are characterized by cough and, occasionally, bronchopneumonia. Ocular and nasal discharge have also been observed.
Disease Course. For yet undetermined reasons, B bronchiseptica is able to up-regulate a virulence gene complex, resulting in the release of potent toxins capable of causing severe upper and lower respiratory disease in dogs and cats.5 Kittens, especially those co-infected with feline viral URD (FVURD), may develop fatal complications associated with pneumonia. In contrast, primary bordetellosis in adult cats appears to be uncommon.1
CORE VACCINES
Vaccine Types
Three types of combination FHV-1 plus FCV vaccine are available; an inactivated, bi-valent FCV vaccine is also available. Most vaccines sold in the U.S. and Canada are combined with other vaccines (eg, feline parvovirus or feline leukemia).
- Modified-live virus (nonadjuvanted) vaccine is recommended over killed virus products for routine use.
- Use of killed (adjuvanted) virus vaccine is reserved for use in pregnant queens, retrovirus positive cats, or in high-density populations, where there is minimal evidence of respiratory disease.6
- An inactivated (adjuvanted) bi-valent vaccine, which contains 1 conventional respiratory virus strain plus 1 strain of VS calicivirus, is available in the U.S. and Canada. A study published by the manufacturer has shown that vaccinated cats developed reduced clinical signs following challenge with a homologous FCV strain.3 Additional studies are needed before this vaccine can be recommended for routine use.
- Onset of immunity following intranasal (IN) vaccination may be faster (by a few days) than that of parenteral (MLV) vaccination.
- IN vaccines immunize at an earlier age because there is less MDA interference in the upper respiratory tract.
Recommended Protocol: Kittens
- A combination feline parvovirus (FPV), FHV-1, and FCV vaccine is recommended for all cats, beginning as early as 6 to 8 weeks of age, regardless of vaccine type.
- Kittens should receive an additional dose every 3 to 4 weeks until 16 to 20 weeks of age.
- The extended vaccination age (16–20 weeks) for kittens is intended to avoid interference from MDA associated with FPV.
Recommended Protocol: Adult Cats
- All cats should be revaccinated 1 year following completion of the initial series.
- Revaccination no more often than every 3 years is recommended for household pet cats living in low-density environments.
- Annual revaccination is indicated for cats housed in high-density environments, where risk for exposure to respiratory disease is high.
Limitations
FVURD continues to represent a significant health threat to the feline population. Mortality is typically low among infected cats, especially if supportive medical therapy is available. Morbidity, on the other hand, is particularly high…despite routine vaccination.
Cats housed in high-density environments are at significant risk for infection. Individuals responsible for the management of these populations face significant financial risk associated with treating large numbers of affected cats or the need to depopulate.
NONCORE VACCINES
Vaccine Types
Both inactivated (killed, adjuvanted) and attenuated (avirulent live, nonadjuvanted) vaccines are available as an aid in preventing clinical signs associated with Chlamydophila felis (formerly, Chlamydia psittaci) infection.
One vaccine is currently available as an aid in the prevention of Bordetella bronchiseptica infection in cats. The product is an avirulent live bacterin (monovalent, non-adjuvanted) approved for IN administration only (no parenteral administration). Cats should not receive the canine B bronchiseptica vaccine because its constituency is different than that of the feline B bronchiseptica vaccine.
Recommended Protocol: Chlamydophila felis
- C felis vaccines are typically combined with various other vaccines.
- Indications for administering vaccine are generally limited to cats residing in multiple-cat households, where the risk for exposure to C felis has been confirmed.
- If indicated, 2 initial doses should be administered 3 to 4 weeks apart; annual vaccination is recommended for cats in which the risk for exposure is sustained.
Recommended Protocol: Bordetella bronchiseptica
- Indications for vaccinating cats against B bronchiseptica are generally limited to high-density housing environments, where the risk for exposure to infected cats or dogs is known.
- Kittens appear to be at greatest risk, especially if coinfected with FHV-1 or FCV.
- A single dose (0.2 mL), administered into 1 nostril, can be administered as early as 8 weeks of age; annual revaccination is recommended for cats at risk for exposure.
Limitations
Cats are not expected to develop protective (sterile) immunity following vaccination against either C felis or B bronchiseptica.7 Vaccination is only expected to mitigate, not prevent, clinical signs.
Furthermore, the prevalence of clinical disease associated with C felis appears to be relatively low in the U.S. and Canada, especially among household cats. Determining risk for infection among individual cats, however, is complicated by the paucity of epidemiologic studies. Estimates of infection range from 10% to 30% of cats with upper respiratory signs; C felis has been recovered from a small percentage of cats without clinical signs.8
B bronchiseptica can be recovered as part of the normal bacterial flora from the respiratory tract of healthy cats. The role of B bronchiseptica as a single-agent infection in cats with respiratory disease has not been determined; therefore, it is particularly difficult to assess disease risk and indications for vaccination.
The limitations cited justify categorizing these vaccines as noncore. Additionally, both C felis and B bronchiseptica are susceptible to doxycycline (10 mg/kg Q 24 H, or 5 mg/kg Q 12 H, PO for 7–10 days), which can be administered to treat an active infection.
VACCINE PRIMER
Adjuvant: A chemical, microbial, constituent, or mammalian protein commonly added to killed (inactivated) vaccine to enhance the immune response to a selected antigen.
Attenuated (avirulent live and -live): Vaccine that contains the live virus or bacteria as the immunizing antigen. The virulence of the organism (antigen) is reduced, but is still capable of infecting cells and replicating following inoculation.
Killed, or inactivated: Vaccine that contains killed virus or bacteria as the immunizing antigen; following inoculation, the antigen is incapable of infecting cells or replicating.
PREVENTION & MANAGEMENT
Vaccination
Despite the limitations outlined, all cats should receive the initial series of vaccines against FHV-1 and FCV. The revaccination interval varies depending on the exposure risk of the individual cat:
- Cats living inside and in households with low population density can be protected if revaccinated every 3 years.
- Cats residing in high-density populations are likely to have a high exposure risk and should be revaccinated annually.
The recommendation to vaccinate against C felis or B bronchiseptica should, on the other hand, be limited to:
- Households, where infection, and associated clinical signs, has been confirmed
- Cats, especially kittens, residing in high-density populations (shelter-housed cats, breeding colonies).
Vaccination of individual household cats living in low-density environments is unlikely to be necessary, and veterinarians should use discretion when recommending vaccination against chlamydiosis and bordetellosis.
High-Density Populations
Physical separation of vaccinated cats from nonvaccinated cats and, when feasible, separating cats with a known history of respiratory disease is important in reducing the risk of exposing healthy cats to chronic carrier cats. Also, separating susceptible kittens from the adult (chronic virus carrier) population is fundamental in reducing the incidence of acute infections, particularly with FHV-1 and FCV.
Feeding
Within high-density populations, feeding should be ordered in such a way that healthy cats are fed first and cats with signs of upper respiratory disease are fed last. Ideally, disposable gloves should be used between cats or between cages of cohoused cats. Disposable feeding bowls should also be used; however, if using washable food bowls, soak bowls in fresh solution of 1 part household bleach to 30 parts water (1:30). Allow bowls to thoroughly dry before using.
Ventilation
Adequate ventilation, defined as 16 air exchanges per hour, is important to:
- Reduce the concentration of virus within the environment
- Maintain a healthy population.
Why does FVURD continue to pose such a significant threat to the feline population if vaccination against these virus infections is routine and widespread?
First, both FHV-1 and FCV are readily transmitted when infected cats are housed with susceptible cats. Second, FHV-1 and FCV vaccines currently sold in the U.S. and Canada do not provide “sterile” immunity.
What is sterile immunity?
The immunity a cat derives from vaccination does reduce the severity of clinical signs subsequent to exposure and infection; it does not, however, prevent infection nor does it prevent development of a carrier state and viral shedding.1 The immune response to both FHV-1 and FCV vaccination is, therefore, deemed “non-sterile” (regardless of the product used and route of administration). In contrast, the immune response subsequent to feline parvovirus (panleukopenia virus) vaccination is considered “sterile”; vaccinates receive protection from both infection and clinical disease if exposed.
How do you reduce the risk for infection?
As long as the number of cohoused cats remains low, exposure risk is low, and vaccination offers satisfactory protection. However, as the number of cats within a household increases, the risk that chronic virus carrier (viral shedding) cats will be introduced also increases. Vaccinated cats, if exposed, become infected and are likely to become chronic virus carriers. Susceptible, nonvaccinated cats, on the other hand, will become infected and develop the full spectrum of clinical signs of acute-onset upper respiratory infection.
To what degree is FVURD prevalent in the feline population?
Chronic virus carrier cats are highly prevalent in the population and disease is endemic in high-density populations. In addition, shelter-housed cats and those residing in rescue facilities have high infection rates despite routine vaccination. As the proportion of young, susceptible kittens within the population increases, the risk for serious clinical disease can be expected to increase as well.
Management of infectious respiratory disease in high density populations is complicated by the following:
- Adequately designed and maintained quarantine facilities are uncommon; the expense of constructing proper facilities with adequate ventilation, combined with high numbers of entrant cats received at certain times of year, make isolation impractical or ineffective.
- Segregating healthy, virus-free cats from healthy, virus-carrier cats requires virus isolation and time; neither option is practical in high-density, high-turnover environments.
- Strict vaccination at the time of intake, either by parenteral or IN routes, is unlikely to prevent infection or development of a virus-carrier state following exposure.
FCV = feline calicivirus; FHV-1 = feline herpesvirus-1; FPV = feline parvovirus; FVURD = feline viral upper respiratory disease; IN = intranasal; MLV = modified-live virus; MDA = maternally-derived antibody; URD = upper respiratory disease; VS = virulent systemic
References
- Gaskell RM, Dawson S, Radford A. Feline respiratory disease. In Greene CE (ed): Infectious Diseases of the Dog and Cat, 4th ed. Philadelphia: Elsevier-Saunders, 2012, pp 151-162.
- Coyne KP, Jones BR, Kipar A, et al. Lethal outbreak of disease associated with feline calicivirus infection in cats. Vet Rec 2006; 158:544-550.
- Sykes J, Anderson G, Studdert V, Browning G. Prevalence of feline Chlamydia psittaci and feline herpesvirus-1 in cats with upper respiratory tract disease. J Vet Intern Med 1999; 13:153.
- Disease information fact sheet: Feline calicivirus. J Fel Med Surg 2013; 15:Supplementary file. Available online at catvets.com.
- Huang C, Hess J, Gill M, Hustead D. A dual-strain feline calicivirus vaccine stimulates broader cross-neutralization antibodies than a single-strain vaccine and lessens clinical signs in vaccinated cats when challenged with a homologous feline calicivirus strain associated with virulent systemic disease. J Fel Med Surg 2010; 12:129-137.
- Scherk MA, Ford RB, Gaskell RM, et al. 2013 AAFP feline vaccination advisory panel report. J Fel Med Surg 2013; 15:785-808. Available online at catvets.com (search Practice Guidelines; 2013 AAFP Feline Vaccination Advisory Panel Report).
- Masubuchi K, Wakatsuki A, Iwamoto K, et al. Efficacy of a new inactivated Chlamydophila felis vaccine in experimentally-infected cats. J Feline Med Surg 2010; 12(8):609-613.
- Disease information fact sheet: Chlamydophila felis. J Fel Med Surg 2013; 15:Supplementary file. Available online at catvets.com.
Richard B. Ford, DVM, MS, Diplomate ACVIM & ACVPM (Hon), is Emeritus Professor of Medicine at North Carolina State University’s College of Veterinary Medicine. He is a retired Brigadier General from the USAF Reserve, where he was assigned to the Office of the Surgeon General at the Pentagon. Dr. Ford is also a past president of the NAVC Conference and continues his role as a member of the scientific program committee. His clinical interests are in the field of companion animal infectious disease; he is a prolific author and serves on both the AAHA Canine Vaccination Task Force and AAFP Feline Vaccination Advisory Panel. Dr. Ford received his DVM from Ohio State University and completed an internal medicine residency at Michigan State University. He held a previous faculty position at Purdue University.