Influenza

Influenza is an acute, highly contagious respiratory disease of dogs and cats caused by type A influenza viruses of the family Orthomyxoviridae. In dogs, the primary agents are canine influenza virus (CIV) H3N8 (equine-origin) and H3N2 (avian-origin). In cats, H3N2 and occasionally H5N1 (avian) have been reported. The disease is characterized by sudden onset of fever, coughing, nasal discharge, lethargy, and in severe cases, pneumonia. Influenza viruses are enveloped, negative-sense, segmented RNA viruses that undergo antigenic drift and shift, leading to new strains. The clinical syndrome ranges from subclinical infection to severe respiratory distress and secondary bacterial pneumonia. The disease is often self-limiting in immunocompetent animals, but morbidity can be high in crowded environments such as shelters and boarding facilities. The virus is transmitted via aerosolized respiratory secretions, fomites, and direct contact. The incubation period is typically 1-5 days, and viral shedding can occur before clinical signs appear, facilitating rapid spread. Diagnosis is confirmed by PCR, virus isolation, or serology (paired hemagglutination inhibition or ELISA). Treatment is primarily supportive, with emphasis on hydration, nutritional support, and management of secondary bacterial infections. Vaccines are available for canine influenza (H3N8 and H3N2) and are recommended for at-risk populations. The disease is not zoonotic, but dogs and cats can serve as intermediate hosts for reassortment events with human and avian strains, highlighting the importance of surveillance.

Influenza viruses belong to the family Orthomyxoviridae, genus Influenzavirus A. They are enveloped, negative-sense, single-stranded RNA viruses with a segmented genome (8 segments). The surface glycoproteins hemagglutinin (HA) and neuraminidase (NA) are the major antigenic determinants. In dogs, the most common subtypes are H3N8 and H3N2. H3N8 originated from equine influenza virus and was first identified in racing greyhounds in Florida in 2004. H3N2 is of avian origin and was first reported in South Korea in 2007, later spreading to China, Thailand, and the United States. In cats, H3N2 has been reported in Asia and the US, and H5N1 (highly pathogenic avian influenza) has caused sporadic infections in cats in Asia and Europe. The virus is inactivated by heat (56°C for 30 minutes), lipid solvents, detergents, and common disinfectants (e.g., quaternary ammonium compounds, bleach). Transmission occurs via inhalation of aerosolized droplets (coughing, sneezing), direct contact with respiratory secretions, and indirect contact via contaminated objects (fomites) such as food bowls, bedding, and clothing. The virus can survive on surfaces for up to 48 hours and on hands for up to 12 hours. The incubation period is 1-5 days, and viral shedding peaks during the first 3-4 days after infection, but can persist for up to 10-14 days in some animals. The virus infects ciliated epithelial cells of the respiratory tract, causing cell death and desquamation, which impairs mucociliary clearance and predisposes to secondary bacterial infections.

Influenza affects both dogs and cats, with no breed or sex predilection. All ages are susceptible, but puppies and kittens, as well as geriatric animals, are at higher risk for severe disease. The disease is highly contagious and spreads rapidly in dense populations such as shelters, boarding kennels, grooming facilities, and dog parks. In dogs, H3N8 has been reported in the United States, with outbreaks in multiple states, particularly in the Southeast and Northeast. H3N2 has been reported in Asia (China, South Korea, Thailand) and the United States, with outbreaks in the Midwest and East Coast. In cats, H3N2 has been reported in South Korea and the United States, and H5N1 has been reported in Asia and Europe. The incidence is seasonal, with peaks in fall and winter, similar to human influenza. The basic reproduction number (R0) in shelters has been estimated to be high, leading to rapid spread. Seroprevalence studies in dogs have shown that exposure is common in high-risk populations, with up to 20-30% seropositivity in some regions. The virus can also infect other species, including ferrets, guinea pigs, and occasionally humans, but sustained human-to-human transmission has not been documented. The disease is not reportable in most countries, but surveillance is important due to the potential for zoonotic transmission and reassortment with human strains.

Influenza virus enters the respiratory tract via inhalation and attaches to sialic acid receptors on ciliated epithelial cells of the nasal mucosa, trachea, bronchi, and bronchioles. The HA protein binds to sialic acid-containing receptors, and the virus is internalized via receptor-mediated endocytosis. The low pH of the endosome triggers a conformational change in HA, leading to fusion of the viral envelope with the endosomal membrane and release of the viral ribonucleoprotein (RNP) into the cytoplasm. The RNP is transported to the nucleus, where transcription and replication of the viral RNA occur. New viral particles are assembled at the cell membrane and bud off, with NA cleaving sialic acid residues to release the virus. Viral replication leads to cell death and desquamation of the respiratory epithelium, exposing the basement membrane and impairing mucociliary clearance. This allows bacteria to colonize and invade, leading to secondary bacterial pneumonia. The host immune response includes innate immunity (interferons, natural killer cells, macrophages) and adaptive immunity (humoral and cell-mediated). However, the virus can suppress the immune response by inducing apoptosis of immune cells and downregulating cytokine production. The clinical signs are due to both direct viral cytopathology and the inflammatory response. In severe cases, the virus can spread to the lower respiratory tract, causing interstitial pneumonia, alveolar edema, and hemorrhage. Systemic signs such as fever and lethargy are mediated by pro-inflammatory cytokines (IL-1, IL-6, TNF-α). In cats, H5N1 infection can cause systemic disease with involvement of the liver, kidney, and brain, due to the virus's ability to replicate in multiple organs. The disease is typically self-limiting in immunocompetent animals, but secondary bacterial infections can lead to severe pneumonia and death.

Intrinsic factors: Age (puppies and kittens are more susceptible due to immature immune systems; geriatric animals may have decreased immune function), immunosuppression (due to concurrent diseases such as canine distemper, feline leukemia virus, or feline immunodeficiency virus, or due to corticosteroid therapy), and genetic factors (brachycephalic breeds may have compromised respiratory function, increasing the risk of severe disease). Extrinsic factors: High population density (shelters, boarding facilities, dog parks), poor ventilation, stress (transport, weaning, overcrowding), poor nutrition, and concurrent infections (e.g., Bordetella bronchiseptica, Mycoplasma spp., Streptococcus equi subsp. zooepidemicus). Lack of vaccination is a significant risk factor. Environmental factors such as cold weather and high humidity can increase viral survival and transmission. Fomites and human handlers can also transmit the virus between animals.

The clinical signs of influenza in dogs and cats are similar to those of other respiratory infections. The incubation period is 1-5 days. The disease can be subclinical, mild, or severe. In mild cases, animals may show a soft, moist cough that persists for 10-21 days, nasal discharge (serous to mucopurulent), ocular discharge, sneezing, lethargy, and reduced appetite. Fever (103-106°F) is common in the acute phase. In severe cases, animals may develop high fever, dyspnea, tachypnea, crackles and wheezes on thoracic auscultation, and cyanosis. Secondary bacterial pneumonia can lead to purulent nasal discharge, productive cough, and systemic signs such as depression and anorexia. In cats, H3N2 infection can cause similar signs, but also may include oral ulcers and conjunctivitis. H5N1 infection in cats can cause severe systemic disease with neurological signs (seizures, ataxia) and sudden death. The clinical course is typically 2-4 weeks, but coughing may persist for several weeks. In shelter environments, the disease can spread rapidly, with high morbidity but low mortality (usually <5% in dogs, but can be higher in kittens or immunocompromised animals).

The differential diagnoses for canine and feline influenza include other respiratory pathogens and non-infectious causes. Key differentials include: 1) Canine infectious respiratory disease complex (CIRDC) - caused by Bordetella bronchiseptica, canine adenovirus type 2, canine parainfluenza virus, canine herpesvirus, canine respiratory coronavirus, and Mycoplasma spp. These agents cause similar clinical signs, but influenza often has a more acute onset and higher fever. PCR panels can differentiate. 2) Feline herpesvirus type 1 (FHV-1) - causes upper respiratory signs, conjunctivitis, and corneal ulcers; PCR can differentiate. 3) Feline calicivirus (FCV) - causes oral ulcers, pneumonia, and lameness; PCR can differentiate. 4) Canine distemper virus - causes respiratory, gastrointestinal, and neurological signs; PCR or serology can differentiate. 5) Bacterial pneumonia (primary) - caused by Streptococcus, E. coli, etc.; may be secondary to viral infection; thoracic radiographs and cytology can help. 6) Allergic bronchitis or asthma - chronic cough, eosinophilic inflammation; no fever or nasal discharge. 7) Foreign body aspiration - acute onset cough, unilateral nasal discharge; imaging and endoscopy can identify. 8) Neoplasia (e.g., pulmonary adenocarcinoma) - chronic cough, weight loss; imaging and biopsy. 9) Cardiogenic pulmonary edema - cough, dyspnea, crackles; cardiac evaluation (echocardiography) can differentiate. 10) Parasitic infections (e.g., Aelurostrongylus abstrusus in cats) - chronic cough; fecal examination or Baermann test.

The diagnostic approach to suspected influenza should follow a stepwise algorithm. Step 1: Clinical suspicion - based on acute onset of respiratory signs in a dog or cat with a history of exposure to other animals (shelter, boarding, dog park). Step 2: Initial diagnostic tests - complete blood count (CBC), serum biochemistry, and thoracic radiographs. CBC may show lymphopenia, neutropenia, or neutrophilia with a left shift. Radiographs may reveal interstitial or bronchial patterns, and in severe cases, alveolar patterns consistent with pneumonia. Step 3: Specific viral testing - collect nasal, pharyngeal, or oropharyngeal swabs (using synthetic swabs with viral transport media) within 3-4 days of clinical signs for RT-PCR (reverse transcription polymerase chain reaction) to detect viral RNA. PCR is highly sensitive and specific and can differentiate subtypes (H3N8, H3N2). Step 4: Virus isolation - can be performed on swabs or lung tissue, but requires specialized laboratories and takes 3-7 days. Step 5: Serology - acute and convalescent (2-3 weeks later) serum samples for hemagglutination inhibition (HI) or ELISA to detect a four-fold rise in antibody titers. This is useful for retrospective diagnosis or epidemiological studies. Step 6: If secondary bacterial pneumonia is suspected, perform a transtracheal wash or bronchoalveolar lavage (BAL) for cytology and bacterial culture and sensitivity. Step 7: In fatal cases, necropsy with histopathology and PCR on lung tissue can confirm the diagnosis. Step 8: Rule out other respiratory pathogens using a respiratory PCR panel (e.g., canine respiratory disease panel or feline upper respiratory panel) to differentiate from other viral and bacterial agents.

Hematology: In the acute phase, lymphopenia is common due to viral-induced lymphocyte apoptosis. Neutropenia may occur early, followed by neutrophilia with a left shift if secondary bacterial infection develops. Monocytosis may be seen in recovery. Serum biochemistry: Changes are usually non-specific. Mild elevations in liver enzymes (ALT, AST) may occur due to fever or systemic inflammation. Creatinine and BUN may be elevated if dehydration is present. Electrolyte imbalances (hyponatremia, hypokalemia) can occur due to reduced intake and fluid losses. Urinalysis: Usually unremarkable; specific gravity may be elevated due to dehydration. Blood gas analysis: In severe pneumonia, hypoxemia (decreased PaO2) and hypercapnia (increased PaCO2) may be present. Specific biomarkers: C-reactive protein (CRP) may be elevated in inflammatory conditions, but is not specific. Procalcitonin has been studied in dogs but is not widely used. Serology/PCR: RT-PCR on respiratory swabs is the preferred diagnostic test. Serology (HI or ELISA) can be used for retrospective diagnosis. Virus isolation is possible but not routinely performed. Endocrine assays: Not indicated unless concurrent endocrine disease is suspected.

Thoracic radiographs are the primary imaging modality. In mild cases, radiographs may be normal or show a mild bronchial pattern. In more severe cases, an interstitial pattern may be present. With secondary bacterial pneumonia, alveolar patterns (patchy or lobar) are common, often affecting the cranioventral lung lobes. In severe viral pneumonia, a diffuse miliary interstitial pattern may be seen. Radiographs can also help rule out other causes of cough, such as cardiomegaly or foreign bodies. Ultrasonography of the thorax may be used to evaluate lung consolidation and pleural effusion, but is less commonly performed. Computed tomography (CT) is more sensitive than radiography for detecting early lung changes and can be useful in severe or chronic cases, but is not routinely indicated. Endoscopy (tracheoscopy or bronchoscopy) can be used to visualize the airways and collect samples (BAL) for cytology and culture. Fluoroscopy is not typically used for diagnosis but may be helpful in evaluating dynamic airway collapse.

Cytology: Tracheal wash or BAL fluid in influenza cases typically shows neutrophilic inflammation with or without bacteria. In early viral infection, there may be a mixed inflammatory infiltrate with lymphocytes and macrophages. Intranuclear or intracytoplasmic inclusion bodies are not typically seen in influenza. Histopathology: On necropsy, the lungs show necrotizing bronchitis and bronchiolitis with desquamation of epithelial cells, edema, and hemorrhage. In severe cases, there is interstitial pneumonia with alveolar edema and hyaline membrane formation. Secondary bacterial pneumonia is characterized by suppurative inflammation with intralesional bacteria. Immunohistochemistry (IHC) can be used to detect viral antigens in formalin-fixed tissues. Special stains (e.g., Gram stain) can help identify bacteria.

Treatment of influenza is primarily supportive, as the virus is self-limiting. Hospitalization is indicated for animals with severe respiratory distress, dehydration, or suspected secondary bacterial pneumonia. Fluid therapy: Administer balanced crystalloids (e.g., Lactated Ringer's solution) at maintenance rates (60-100 ml/kg/day for dogs, 40-60 ml/kg/day for cats) or higher if dehydrated. Correct electrolyte imbalances. Nutritional support: Offer highly palatable food; if anorexic, consider appetite stimulants (e.g., mirtazapine in cats) or feeding tubes (nasoesophageal or esophagostomy) for prolonged anorexia. Oxygen therapy: Provide supplemental oxygen (40-60% FiO2) via oxygen cage, nasal cannula, or mask for hypoxemic animals. Nebulization with saline (0.9% NaCl) for 15-20 minutes 2-3 times daily can help loosen secretions. Coupage (gentle chest percussion) can aid in expectoration. Antimicrobial therapy: Antibiotics are indicated if secondary bacterial pneumonia is suspected or confirmed. First-line choices include amoxicillin-clavulanate (12.5-25 mg/kg PO q8-12h) or doxycycline (5-10 mg/kg PO q12h). For severe cases, consider broader-spectrum coverage with a fluoroquinolone (e.g., enrofloxacin 5-10 mg/kg PO/IV q24h) combined with a beta-lactam. Antiviral therapy: Oseltamivir (Tamiflu) has been used experimentally in dogs and cats at doses of 2-4 mg/kg PO q12h for 5 days, but its efficacy is unproven and it is not routinely recommended. It may be considered in severe outbreaks or in immunocompromised animals, but must be started early (within 48 hours of clinical signs). Cough suppressants: Generally avoided, as coughing helps clear secretions. However, in cases of severe, non-productive coughing, antitussives such as butorphanol (0.05-0.1 mg/kg PO q6-12h) or hydrocodone (0.22 mg/kg PO q6-12h) may be used cautiously. Bronchodilators: May be beneficial in animals with bronchospasm; aminophylline (10 mg/kg PO q8h) or terbutaline (0.01 mg/kg SC or 0.625-1.25 mg/cat PO q12h) can be used. Anti-inflammatory drugs: Non-steroidal anti-inflammatory drugs (NSAIDs) are not routinely recommended due to potential renal and gastrointestinal side effects, but may be used for fever if needed (e.g., carprofen 2.2 mg/kg PO q12h in dogs). Glucocorticoids are contraindicated due to immunosuppression. Nursing care: Keep the animal in a warm, well-ventilated area. Isolate infected animals to prevent spread. Use appropriate disinfection protocols (e.g., accelerated hydrogen peroxide, bleach) for contaminated surfaces.

The prognosis for influenza is generally good, with most animals recovering within 2-4 weeks. Mortality is low (<5% in dogs, but can be higher in kittens or immunocompromised animals). Factors associated with a worse prognosis include: severe pneumonia requiring oxygen therapy, secondary bacterial pneumonia, extreme age (very young or old), concurrent immunosuppressive diseases, and lack of vaccination. Animals that develop acute respiratory distress syndrome (ARDS) have a guarded prognosis. With appropriate supportive care, most animals recover fully, but coughing may persist for several weeks. In shelter outbreaks, the disease can cause significant morbidity, but with proper management, the outbreak can be controlled.

Recheck animals 7-14 days after initial diagnosis to assess clinical resolution. For animals with pneumonia, repeat thoracic radiographs in 2-4 weeks to document resolution. Monitor for complications such as chronic bronchitis or bronchiectasis. If secondary bacterial pneumonia was treated, ensure the full course of antibiotics is completed. For animals that were hospitalized, schedule a recheck 3-5 days after discharge. In outbreak situations, quarantine new arrivals for 2 weeks and monitor for clinical signs. Vaccination: For dogs, administer the bivalent H3N8/H3N2 vaccine (e.g., Nobivac Canine Flu H3N8/H3N2) as a two-dose series 2-4 weeks apart, then annually. For cats, there is no commercially available influenza vaccine in the US; however, in Asia, a vaccine for H3N2 is available. Advise owners to avoid high-risk environments (e.g., dog parks, boarding facilities) during outbreaks. Provide client education on biosecurity measures, including hand washing and disinfection of fomites.

Pearls: 1) Influenza should be suspected in any dog or cat with acute onset of coughing and fever, especially with a history of exposure to other animals. 2) PCR is the most sensitive diagnostic test; collect swabs early (within 3-4 days of clinical signs). 3) Secondary bacterial pneumonia is the most common complication; monitor for worsening clinical signs and consider thoracic radiographs. 4) Vaccination is effective in reducing the severity of disease and viral shedding. 5) In shelters, isolate affected animals and implement strict biosecurity to prevent spread. Pitfalls: 1) Do not use glucocorticoids, as they can worsen the disease. 2) Do not use cough suppressants routinely, as coughing helps clear secretions. 3) Do not rely on serology for acute diagnosis, as it requires paired samples. 4) Do not forget to rule out other respiratory pathogens, as co-infections are common. 5) Do not underestimate the contagiousness; the virus can spread rapidly in a clinic or shelter. 6) Avoid using oseltamivir unless started early and under expert guidance, as resistance can develop.

Antimicrobials: Amoxicillin-clavulanate (Clavamox) - 12.5-25 mg/kg PO q8-12h for 7-14 days. Doxycycline - 5-10 mg/kg PO q12h for 7-14 days. Enrofloxacin (Baytril) - 5-10 mg/kg PO/IV q24h for 7-14 days (use with caution in cats due to retinal toxicity; do not exceed 5 mg/kg/day in cats). Azithromycin - 5-10 mg/kg PO q24h for 3-5 days, then every other day. Antivirals: Oseltamivir (Tamiflu) - 2-4 mg/kg PO q12h for 5 days (experimental; not FDA-approved for animals). Bronchodilators: Aminophylline - 10 mg/kg PO q8h (dogs), 6.6 mg/kg PO q12h (cats). Terbutaline - 0.01 mg/kg SC (dogs), 0.625-1.25 mg/cat PO q12h. Antitussives: Butorphanol - 0.05-0.1 mg/kg PO q6-12h (dogs), 0.05-0.1 mg/kg PO q6-12h (cats). Hydrocodone - 0.22 mg/kg PO q6-12h (dogs). NSAIDs: Carprofen - 2.2 mg/kg PO q12h (dogs) for fever/pain. Meloxicam - 0.1 mg/kg PO q24h (dogs) or 0.05 mg/kg PO q24h (cats) for short-term use. Fluid therapy: Lactated Ringer's solution or Normosol-R at maintenance rates (60-100 ml/kg/day for dogs, 40-60 ml/kg/day for cats) plus deficits. Oxygen: Administer at 40-60% FiO2 via oxygen cage or nasal cannula. Nebulization: 0.9% saline for 15-20 minutes q8h. Note: Adjust dosages for renal or hepatic impairment. Avoid NSAIDs in dehydrated or hypotensive animals. Monitor for drug interactions (e.g., enrofloxacin with theophylline can increase theophylline levels).

Key studies: 1) Crawford et al. (2005) first identified H3N8 canine influenza in racing greyhounds in Florida, demonstrating high morbidity and low mortality. 2) Song et al. (2008) reported H3N2 avian-origin influenza in dogs in South Korea, showing transmission from dogs to cats. 3) Deshpande et al. (2009) evaluated the efficacy of a H3N8 vaccine in dogs, showing reduced clinical signs and viral shedding. 4) Lee et al. (2011) demonstrated that H3N2 canine influenza virus can infect cats, causing respiratory disease. 5) Voorhees et al. (2017) described the spread of H3N2 in the United States, with multiple introductions from Asia. 6) A study by Jirjis et al. (2010) showed that the H3N8 vaccine provides partial cross-protection against H3N2. 7) A consensus statement from the ACVIM (2016) on canine respiratory disease recommends PCR for diagnosis and supportive care for treatment. 8) A study by Pulit-Penaloza et al. (2019) assessed the zoonotic potential of canine H3N2, showing that it can bind to human receptors but does not transmit efficiently. 9) A meta-analysis by Anderson et al. (2013) on the efficacy of oseltamivir in dogs found limited evidence of benefit. 10) The World Small Animal Veterinary Association (WSAVA) guidelines on vaccination recommend influenza vaccination for dogs at risk. Overall, the evidence supports the use of vaccination and supportive care as the mainstays of management.