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Viral respiratory pathogens (Proceedings)
Feline herpesvirus is a common pathogen of domestic cats.
Feline herpesvirus (FHV) is a common pathogen of domestic cats. The virus is a ds DNA virus with a lipid envelope. The virus primarily targets epithelia of the upper respiratory tract and conjunctiva, and only rarely spreads beyond these regions to cause disease. As with all herpesviruses, after acute infection it enters a latent state in innervating sensory nerves. In cats, this most commonly occurs in the trigeminal ganglion. From this latent state, the virus can be reactivated leading to replication in the epithelia, virus shedding, and in a minority of cats, disease. Termed recrudescence, it can be stimulated by any stressor, including trauma, concurrent disease, parturition, boarding, or changes in social hierarchy.
The typical presentation of FHV infection is that of upper respiratory tract disease: sneezing, nasal and/or ocular discharge, depression, and decreased appetite. Conjunctivitis is not uncommon, and can progress to severe hyperemia and chemosis, with mucopurulent ocular discharge. Infection may lead to corneal ulceration. Less common manifestations of FHV are ulcerative dermatitis and stomatitis.
Diagnostics for FHV infection primarily involves virus detection, as most cats are seropositive from either natural exposure or vaccination. Antigen detection using immunofluorescence is fast and inexpensive; however, sensitivity is relatively low, especially in chronic infections. Virus isolation remains the gold standard. However, in chronic infections, notably chronic conjunctivitis or other ocular disease, the virus may be neutralized by locally-produced antibody leading to false negative results. Genetic detection using polymerase chain reaction (PCR) has high sensitivity, such that subclinical, and even latent infections may be detected. Thus, positive results must be interpreted in light of other clinical information.
Advancements have been made in the treatment of FHV infection in cats. Nucleoside analogs developed for human herpesvirus infections have shown some efficacy against feline herpesvirus, at least in vitro. Toxic side effects have been reported with some, such as acyclovir, but others, such as ganciclovir may prove to be useful clinically. Topical administration of antiviral medications has been used with some success, and include trifluridine and idoxuridine. Interferon (IFN) has been used with some success, and has been shown to be efficacious in vitro (human alpha IFN – US; and feline omega IFN – Europe). L-lysine given orally inhibits viral protein synthesis and restricts virus replication. It is optimal when used early in infection, or as a means to prevent recrudescence during stress. Experimentally, lactoferrin has been shown to inhibit virus attachment and entry, and may be eventually be available as an antiviral treatment for FHV.
Protection following recovery is not long-lived, and reinfections may occur. Antigenic variation is not a significant problem with feline herpesvirus, thus, the antigenic coverage of vaccines is adequate. Non-adjuvanted modified live vaccines are recommended. Vaccines do not prevent infection, nor production of the carrier state. They do offer protection from disease, however.
Feline calicivirus (FCV) continues to be an important respiratory pathogen of cats. It is a nonenveloped virus making it very hardy in the environment, and easily spread by fomites. It is a ss RNA virus with a significant mutation rate. This may lead to changes in antigenicity (many strains that vary antigenically exist) as well as virulence.
Clinical presentations with FCV infection can vary from mild upper respiratory tract disease to viral pneumonia to lethal systemic disease. The typical presentation is similar to FHV infection, though the ocular discharge generally remains serous, corneal ulcers do not occur, and oral ulcers are common. The majority of infections are mild and self-limiting. However, following recovery, infection with shedding in oropharyngeal secretions may persist for periods of week to months, even in the face of vaccination. Lameness, ulcerative dermatitis, and gingivitis have also been associated with FCV, though the pathogenesis is unclear.
Virulent systemic disease (VSD) has been recognized relatively recently. In affected cats, signs may include high fever, depression, anorexia, edema, particularly of the head and limbs, and ulcerative dermatitis of the face, pinnae, and feet. Systemic involvement with multiorgan dysfunction has also been noted, and affected tissues included lungs, pancreas, and liver. In the majority of these occurrences, the index case has originated from a shelter or rescue facility. Both vaccinated and unvaccinated cats have been affected, with significant mortality rates reported. The specific viral factor(s) responsible for this virulent phenotype have not been identified, and no molecular markers have been found. The mutation or mutations responsible appear to evolve independently in each outbreak, and the isolates from VSD episodes characterized thus far are distinct from one another.
Currently, no specific antiviral medication for FCV exists. A recent study showed efficacy of virus-specific compounds in blocking FCV replication in vivo. It was safe, reduced disease development, virus shedding, and mortality.
Persistent infections following recovery from acute disease are not uncommon. Infected cats may continue to shed the virus throughout their lifetime, but most shed for periods of weeks to a few months. Vaccination is the main means of control, and as with FHV, prevents disease, but not infection nor the carrier state. Most vaccines contain a single strain. Manufacturers are investigating the utility of and including additional strains in vaccines to increase the spectrum of protection. Newer vaccinal strains appear to induce neutralizing antibodies against a higher proportion of caliciviral field strains. However, because of the strain variability, it will be difficult to achieve a vaccine that provides protection to all strains in circulation. In addition, it is important to bear in mind that inclusion of two or more strains isolated from different disease manifestations does not necessarily insure broad protection against the varied pathogenic phenotypes.
Environmental decontamination is also important for control in multi-cat situations. During outbreaks of VSD due to FCV, strict quarantine measures and barrier nursing is required to prevent the spread.
In January 2004, an outbreak of respiratory disease occurred in racing greyhounds in Florida. While some animals exhibited mild disease, others developed severe pneumonia, with a case fatality rate of 36%. Virus isolations on post mortem samples resulted in identification of an influenza virus. Further characterization of the virus showed the greatest similarity to equine influenza virus A (H3N8). Archived sera was subsequently tested for antibodies, and revealed evidence of infection in dogs as far back as 2000. Since then, evidence of infection has been found in many geographic locales in the US, and among shelter and pet dogs in addition to racing greyhounds. The transmission of equine influenza to dogs was an uncommon occurrence of interspecies spread of a whole virus without reassortment. From viral analyses of subsequent occurrences, it appears this was a single interspecies transfer of virus due to point mutations rather than reassortment of gene segments.
After an incubation of 2-5 days, most dogs exhibit symptoms similar to kennel cough, with moist cough, fever, and nasal discharge. Because most dogs are immunologically naïve to influenza, adults as well as puppies may be susceptible to infection. Diagnostics include serology and virus detection. Serology is helpful because the virus is not included in current vaccines. Virus detection can be done on tracheal swabs or washes, using virus isolation or PCR. Treatment is generally supportive.
Before a new vaccine for canine influenza can be recommended, it will be necessary to investigate the epidemiology of this virus, including the prevalence of infections. It is likely that vaccination of dogs at high risk, such as in shelter situations or boarding kennels, will be recommended. The vaccine choice will depend upon independent efficacy studies.
Canine Respiratory Coronavirus
In 2003, a group 2 coronavirus was found in tracheal samples from a large kenneled dog population with a prevalence of respiratory disease. Genetic analysis revealed that it was most closely related to bovine coronavirus, and not to the enteric canine coronavirus, a group 1 coronavirus. Coronaviruses are associated with respiratory disease in many other species of mammals and birds, so it is not surprising that a coronavirus associated with respiratory disease would be found in dogs. The virus was found in both upper and lower respiratory tract tissues. Serologic studies of the kenneled dogs found a 99% infection rate, indicating the highly contagious nature of the virus. Subsequent investigations have shown a significant infection rate in North America and Europe.
Disease associated with respiratory canine coronavirus appears to be mild, but it may predispose to more severe disease due to infection with other agents. For respiratory disease in well-vaccinated dogs, this agent should be considered. Diagnosis may be done with serology (be sure to request canine RESPIRATORY coronavirus as it is distinct from the enteric canine coronavirus) and virus detection with virus isolation or PCR. Treatment is supportive, and usually directed to secondary bacterial infection. No vaccine is currently available.
Canine Distemper continues to be an important pathogen of dogs worldwide. Novel CDV strains have been identified in recent years throughout the world. Outbreaks have been associated with strains that appear to be derived from distant geographic locales. For example, the Arctic lineage has been found in Italy and isolates from dogs in Hungary have been found to resemble those from North America. Distinct isolates have also been detected in North America. In 2004, phylogenetic analysis of virus from four clinical cases in the US identified three strains genetically distant from strains that were previously identified in North America. The dogs in three of these four cases had recently been vaccinated. Genetic characterization of the viruses from these cases found they were novel for the continental US. Outbreaks among raccoons in the Chicago area in 1998 and 2001 were also due to genetically distant lineages; in addition, the 2001 variant appeared to be more lethal. Circulation in wildlife populations may lead to virus variants in antigenicity as well as virulence. An investigation of North American isolates in 2007 identified genotypes distinct from vaccinal strains. Genetic diversity has been associated with vaccine failures.
Previously, ante mortem confirmation of infection depended upon antigen detection or evidence of a rising titer, as the virus is difficult to propagate in the laboratory. Diagnostics for canine distemper have improved with the advent of PCR detection of the virus. Testing may be done on respiratory swabs, fluids (washes), and tissue, blood, and urine. Control relies primarily on vaccination. Recently, recombinant vaccines for CDV have become available. These vaccines incorporate the genes for the envelope glycoproteins in a canarypox vector. In this way, immunity to CDV is induced without the risk of intact live CDV. Studies have shown that the antibody response and protection afforded by this vaccine is similar to that of MLV.
D. Addie, H. Poulet, M. C. Golder, M. McDonald, S. Brunet, J-C. Thibault, M. J. Hosie. 2008. Ability of antibodies to two new caliciviral vaccine strains to neutralise feline calicivirus isolates from the UK. Veterinary Record. 163, 355-357.
Crawford,P. C., E. J. Dubovi, W. L. Castleman, I. Stephenson, E. P. J. Gibbs, L. Chen, C. Smith, R. C. Hill, P. Ferro, J. Pompey, R. A. Bright, M.J. Medina, Influenza Genomics Group, C. M. Johnson, C. W. Olsen, N. J. Cox, A. I. Klimov, J. M. Katz, and R. O. Donis. 2005. Transmission of Equine Influenza Virus to Dogs. Science, 310, 21 OCTOBER, 482-5.
Decaro, N., Costantina Desario, Gabriella Elia, Viviana Mari, Maria Stella Lucente, Paolo Cordioli, Maria Loredana Colaianni, Vito Martella, Canio Buonavoglia. 2007. Serological and molecular evidence that canine respiratory coronavirus is circulating in Italy. Veterinary Microbiology 121 (2007) 225–230.
Demeter, Z., B. Lakatos, E. A. Palade, T. Kozmac, P. Forgach, and M. Rusvai. 2007. Genetic diversity of Hungarian canine distemper virus strains. Veterinary Microbiology, 122(3-4): p. 258-269.
Erles, K., Crista Toomey, Harriet W. Brooks, and Joe Brownlie. 2003. Detection of a group 2 coronavirus in dogs with canine infectious respiratory disease. Virology 310:216–223
Gaskell, Rosalind, Susan Dawson, Alan Radford, Etienne Thiry. Feline herpesvirus. Vet. Res. 38 (2007) 337–354.
Hargis, A. M., P. E. Ginn, J. Mansell, and R. L. Garger. 1999. Ulcerative facial and nasal dermatitis in cats associated with Feline Herpesvirus-1. Vet Derm, 10:267-74.
Junge, R.E., K. Bauman, M. King, and M. E. Gompperet. 2007. A serologic assessment of exposure to viral pathogens and Leptospira in an urban raccoon (Procyon lotor) population inhabiting a large zoological park. Journal of Zoo and Wildlife Medicine, 38(1):18-26.
Kapil, Sanjay, Robin W. Allison, Larry Johnston III, Brandy L. Murray, Steven Holland, Jim Meinkoth, and Bill Johnson. 2008. Canine Distemper Virus Strains Circulating among North American Dogs_Clin and Vacc Immunol, 15(4):707-12.
Kuehn, B.M., Multidisciplinary task force tackles Chicago distemper outbreak.Journal of the American Veterinary Medical Association, 2004. November 1: p. 1315-1317.
Lednicky, J.A., J. Dubach, M. J. Kinsel, T. P. Meehan, M. Bocchetta, L. L. Hungerford, N. A. Sarich, K. E. Witecki, M. D. Braid, C. Pedrak, and C. M. Houde., Genetically distant American Canine distemper virus lineages have recently caused epizootics with somewhat different characteristics in raccoons living around a large suburban zoo in the USA. Virology Journal, 2004. 1(2): p. 1-14.
Maggs, David J. Update on Pathogenesis, Diagnosis, and Treatment of Feline Herpesvirus Type 1Clinical Techniques in Small Animal Medicine. 20:94-101.
Martella, V., F. Cirone, G. Elia, E. Lorusso, N. Decaro, M. Campolo, C. Desario, M. S. Lucente, A. L. Bellacicco, M. Blixenkrone-Moller, L. E. Carmichael, and C. Buonavoglia. 2006. Heterogeneity within the hemagglutinin genes of canine distemper virus (CDV) strains detected in Italy. Veterinary Microbiology, 2006. 116(4): p. 301-309.
McVey, David Scott, and Melissa Kennedy. 2008. Vaccines for Emerging and Re-Emerging Viral Diseases of Companion Animals. VCNA, in press.
Van der Meulen, B. Garre, S. Croubels, and H. Nauwynck. 2006. In vitro comparison of antiviral drugs against feline herpesvirus 1. BioMed Central Vet Res, 2(13):1-7.
Pardo, I.D.R., G.C. Johnson, and S.B. Kleiboeker, Phylogenetic characterization of canine distemper viruses detected in naturally infected dogs in North America.Journal of Clinical Microbiology, 2005. 43(10): p. 5009-5017.
Pedersen, N. C., J.B. Elliott, A. Glasgow, A. Poland, K. Keel. 2000. An isolated epizootic of hemorrhagic-like fever in cats caused by a novel and highly virulent strain of feline calicivirus. Veterinary Microbiology 73 (2000) 281-300.
Poulet, H., S. Brunet, V. Leroy, and G. Chappuis, 2005. Immunisation with a combination of two complementary feline calicivirus strains induces a broad cross-protection against heterologous challenges. Veterinary Microbiology, 2005. 106(1-2): p. 17-31.
Priestnall, Simon L., Joe Brownlie, Edward J. Dubovi, Kerstin Erles. Serological prevalence of canine respiratory coronavirus. 2006. Veterinary Microbiology 115 (2006) 43–53.
Radford, A. D., K. P. Coyne, S. Dawson, C. J. Porter, and R. M. Gaskell. 2007. Feline calicivirus. Vet. Res. 38 (2007) 319–335.
Siebeck, Nicola, David J. Hurley, Maricarmen Garcia, Craig E. Greene, Roberto G. Köstlin, Phillip A. Moore, Ursula M. Dietrich. Effects of human recombinant alpha-2b interferon and feline recombinant omega interferon on in vitro replication of feline herpesvirus-1. AJVR, Vol 67, No. 8, August 2006 1406-1411.
Smith, A. W., P. L. Iversen, P. O'Hanley, D. E. Skilling, J. R. Christensen, S. S. Weaver, K. Longley, M. A. Stone, S. E. Poet, and D. O. Matson. 2008. Virus-specific antiviral treatment for controlling severe and fatal outbreaks of feline calicivirus infection. AJVR, 69(1): 23-32.