Canine Influenza: An Emerging Disease

S Hutsell, DVM candidate 2010; MS Camus, DVM, Clinical Pathology Resident

Historical Background

Canine influenza was first identified during a respiratory disease outbreak in racing greyhounds in Florida in January 2004. Twenty-two animals were ill and 8 died acutely with massive pulmonary hemorrhages noted on postmortem examination. A virus that had not been previously identified in dogs was isolated from one case. The virus was a novel type A orthomyxovirus similar to a known H3N8 equine influenza virus. Over the next year, several more outbreaks of canine influenza virus (CIV) were identified at other racetracks in Texas and Iowa. Archived samples taken from greyhound respiratory disease outbreaks prior to 2004 were also examined for CIV, and one serum sample from 2000 tested positive for CIV antibodies.¹

In June 2006, another influenza outbreak occurred in thousands of greyhounds at five different tracks in Florida. Eighteen of these dogs died from fulminant hemorrhagic bronchopneumonia syndrome, for which the complete underlying pathology is still unknown. In many of the dogs that recovered, CIV was detected by real-time RT-PCR and/or serology. CIV was also isolated from the lungs of 6 affected dogs that died.²

As a result of the initial deaths, the non-racing canine population was examined for the presence of CIV. In 2005, seventy dogs with respiratory disease in a Florida shelter, four Florida veterinary clinics, and one veterinary clinic in New York were tested for serologic presence of CIV antibodies. Ninety-seven percent of the shelter and pet dogs were positive for these antibodies.³ Since then, CIV has continued to spread and has now been detected in dogs in 30 states and the District of Columbia, and is very prevalent in many communities in Colorado, Florida, New York, and Pennsylvania.⁴ The peracute hemorrhagic bronchopneumonia seen in the Florida greyhounds in 2004 has not yet been observed in the pet population. Fatal cases of pneumonia have occurred in the pet population, but the fatality rate is less than 10%.²

Serologic evidence indicates sustained horizontal transmission of canine influenza H3N8 virus between dogs in the United States. Similarly, equine influenza virus (H3N8) was also found to cause an outbreak of severe respiratory disease in 92 English Foxhounds in the United Kingdom in 2002.⁵

Clinical Presentation

CIV causes similar respiratory disease symptoms to other “kennel cough” pathogens, including Bordetella bronchiseptica, adenovirus, and parainfluenza virus. Nearly all confirmed CIV cases in the pet population investigated at the Animal Health Diagnostic Center (AHDC) at Cornell University originated at animal shelters, boarding kennels, or animal day care facilities. However, all naïve dogs are susceptible to CIV, and high morbidity rates (60-80%) are expected. The onset of clinical signs is typically less than 5 days after infection. Peak viral shedding occurs 2-4 days after infection, meaning that dogs may be at their most infectious prior to showing signs of disease.

Affected dogs are often lethargic, anorectic, have a low grade fever, and have nasal discharge that progresses from clear to mucopurulent. The most common sign is a persistent dry cough that lasts for several weeks, despite treatment. After the first week of coughing, 10-20% of dogs progress to more severe signs, including a high fever (104-106ºF) with increased respiratory rate and effort, which are typically associated with secondary pneumonia.

Diagnostic imaging: Thoracic radiographs in affected patients have shown a range of pathology, from mild bronchointerstitial infiltrates to consolidation of all lung lobes.²

Nasal swab cultures: Cultures have revealed a variety of Gram positive and Gram negative bacteria, including Staphylococcal spp., hemolytic and nonhemolytic Streptococcal spp., Pasteurella multocida, Klebsiella pneumoniae, Escherichia coli, and Mycoplasma spp.² The canine influenza virus replicates in the epithelial tissue lining the nasal passages, trachea, bronchi, and bronchioles. Viral replication results in epithelial cell necrosis and exposure of the basement membrane, which predisposes to secondary bacterial infection, which commonly progresses to pneumonia.⁴ The nasal discharge and pneumonia are generally antibiotic responsive, indicating that the bacteria also function as true secondary pathogens.

Clinicopathological findings: A complete blood count may show mild leukopenia, which is typical of many viral infections, or leukocytosis characterized by a neutrophilia with a left shift. The inflammatory leukogram is most commonly seen if the affected dog develops a secondary bacterial infection. Mild increases in kidney and liver enzymes may be present on serum chemistry profiles in dogs with pneumonia and compromised tissue oxygenation resulting from hypoxia.⁶ In cytologic specimens of fluid obtained by transtracheal wash or bronchoalveolar lavage, neutrophils are the predominant cell type, with fewer macrophages and, in some instances of secondary pneumonia, intracellular bacteria.

Histopathology: In addition to sloughing of the damaged epithelium, histopathologic examination of affected respiratory tissue typically reveals a significant infiltration of neutrophils and macrophages within the submucosa.² On postmortem examination of the dogs from the 2004 outbreak who died from pneumonia secondary to CIV had pulmonary edema and congestion, epithelial necrosis and erosion in all airways, and suppurative rhinitis, tracheitis, bronchitis, bronchiolitis, and bronchopneumonia.²

Diagnosis

Because canine influenza is a relatively new disease, limited published information is available on optimum diagnostic testing. Influenza viruses are easily detectable with PCR. Nasal swabs have been shown to be more productive than pharyngeal swabs for detecting the presence of CIV, and virus is not generally detectable later than 8-9 days post infection.1 At Cornell’s ADHC, the preferred sample is a nasal swab with a collection time of not more than 3-4 days after onset of clinical signs. For dogs that have a more protracted clinical course prior to presentation to a veterinarian, the only methodology for identifying CIV is antibody detection.¹ In these cases, acute and convalescent (2-3 weeks later) serum samples should be submitted. A 4-fold rise in titers is consistent with infection. A single serum sample on dogs that have recovered from a respiratory infection can also be submitted, but positive test results will only indicate previous exposure to canine influenza, not recent infection. Tissues from dogs that have died acutely with respiratory signs should be submitted for virus isolation.⁷

Management

CIV is shed primarily in respiratory discharge and transmission can be via direct contact, fomites (contaminated objects such as hands, surfaces, clothing, etc.), and aerosol spread. The virus persists for less than one week in the environment. It can be inactivated by many commonly used disinfectants including alcohol, bleach, quaternary ammonium compounds, and potassium peroxymonosulfate (Trifectant ®).⁸ Infected dogs should be isolated from other populations, and exposed dogs should be identified and monitored closely for development of clinical signs. The signs of CIV are clinically indistinguishable from those of other upper respiratory infections. This can make the initial identification of exposed animals difficult. However, an outbreak of canine influenza typically involves a much larger percentage of susceptible dogs than other common etiologic agents, and clinical signs are seen in dogs with known vaccine histories against other respiratory pathogens.⁹

Because canine influenza is a newly emerging disease caused by a virus that is novel to the canine population, almost all dogs, regardless of breed, age, sex, or vaccination status, are susceptible to infection due to lack of previous exposure and subsequent development of an immune response. Canine influenza is a self limiting disease requiring no medical therapy in the majority of affected dogs.⁹ As with most viruses, there is no specific treatment other than supportive care and antibiotics for control of secondary bacterial infections. Cough suppressants are usually not helpful and should be avoided in dogs with a productive cough. Oseltamivir (Tamiflu®) is a drug developed for treatment of influenza in humans. This drug should not be used for treatment of canine influenza, as it serves as a primary line of defense against a human influenza pandemic. Also, no studies have been done to establish an appropriate dosing regimen in dogs. Additionally, CIV is not generally recognized in the first 48 hours post exposure, which is the recommended time to initiate drug therapy in humans.⁸ Depending on severity of clinical signs, dogs with pneumonia may also benefit from intravenous fluid therapy, nutritional support, oxygen therapy, nebulization and coupage.⁹

Prevention

On May 27, 2009, Intervet/Schering-Plough Animal Health was granted a conditional product license by the US Department of Agriculture for a canine influenza vaccine made from inactivated virus. The vaccine has been shown to reduce the incidence and severity of lung lesions, as well as the duration of coughing and viral shedding, and is administered by subcutaneous injection in two doses, two to four weeks apart. It is provisionally licensed for use in dogs older than 6 weeks of age.¹⁰ With a targeted vaccination program aimed at shelters, kennels, and racetracks, eradication of this virus could be possible before it evolves into a more virulent pathogen.¹

References

1. Dubovi EJ, Njaa BL. Canine Influenza. In Kapil S, Lamm CG (eds): Veterinary Clinics of North America Small Animal Practice: Emerging and Reemerging Viruses of Dogs and Cats. Vol 38. No 4. July 2008. pp 827-835.

2. Crawford, et al. Canine Influenza: Diagnosis, Clinical Disease, and Epidemiology. NAVC Proceedings 2007.

3. Crawford PC, Dubovi EJ, Castleman WL, et al. Transmission of equine influenza virus to dogs. Science 2005; 310(5747):482-485.

4. Available at: http://www.ufsheltermedicine.com/documents/CanineinfluenzaFAQ.Veterinarians.pdf Accessed Aug 2009.

5. Daly JM, et al. Transmission of equine influenza virus to English foxhounds. CDC Emerging Infectious Diseases. Vol. 14, No. 3, March 2008. pp 461-464.

6. Communication with Dr. Cynda Crawford, University of Florida. Aug 2009.

7. Available at: http://diagcenter.vet.cornell.edu/issues/civ.asp Accessed Aug 2009.

8. Available at: http://www.sheltermedicine.com/portal/is_canine_influenza_update.shtml Accessed Aug 2009.

9. Landolt and Lunn. Canine Influenza. In Kirk’s Current Veterinary Therapy XIV. 2009. pp 1291-1294.

10. Available at: http://www.aphis.usda.gov/newsroom/content/2009/06/caninevacc.shtml Accessed Aug 2009.

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