Influenza, Avian

Essentials of Diagnosis

• Most human cases occur after exposure to infected poultry

• Clinically indistinguishable from seasonal influenza

• Epidemiologic factors assist in diagnosis

• Rapid antigen assays confirm diagnosis but do not distinguish avian from seasonal influenza

General Considerations

• Birds are the natural hosts

• Avian influenza A

  • Outbreaks occur in poultry occasionally

  • Virus has become endemic in poultry in some countries, mostly in Southeast Asia and Egypt

• Occasionally, avian influenza viruses may infect humans or other mammals, including domestic cats and dogs

• Illness in humans ranges from mild disease to rapid progressive severe disease and death depending on the subtype

• Risk factors for human infection

  • Direct or indirect exposure to infected live or dead poultry or contaminated environments, such as live bird markets

  • Slaughtering and handling carcasses of infected poultry

• The emergence of H5, H7, and H9 avian influenza virus subtypes in humans raises concern that the virus may undergo genetic re-assortment or mutations in some of the genes and develop greater human-to-human transmissibility with the potential to produce a global pandemic

Demographics

• Human infections with H5N1 viruses have been reported to the World Health Organization from 16 countries; the first report in the Americas was in Canada in 2014, and approximately 60% of the cases have died

• Average case fatality rate of 40%

• Infections with other H7 avian influenza viruses (H7N2, H7N3, and H7N7) have occurred sporadically around the world

• Rare human cases of influenza H9N2 are also reported

Symptoms and Signs

• Fever

• Lower respiratory symptoms (cough and dyspnea); upper respiratory tract symptoms are less common

• Gastrointestinal symptoms are reported more frequently in H5N1 infections

• Conjunctivitis is reported in influenza H7 infections

• Other systems can also be involved leading to neurologic manifestations (encephalopathy, seizure) and liver impairment

• Prolonged febrile states and generalized malaise are common

• Bacterial superinfection is reported

Differential Diagnosis

• Typical influenza (clinically indistinguishable)

• Common cold

• Primary bacterial pneumonia

• Infectious mononucleosis

• Mycoplasma infection

• Early Legionnaires disease

• Chlamydophila pneumoniae infection (TWAR)

• Acute HIV infection

• Meningitis

• In returning tropical traveler: malaria, dengue, typhoid

Laboratory Tests

• Commercial rapid antigen tests are not optimally sensitive or specific for detection of H5N1 influenza and should not be the definitive test for influenza

• Diagnostic yield can be improved by early collection of samples, preferably within 7 days of illness onset

• More sensitive RT-PCR assays are available through many hospitals and state health departments

• An initial negative result in the right clinical setting warrants retesting

• Throat swabs or lower respiratory specimens (such as tracheal aspirate or bronchoalveolar lavage fluid) may provide higher yield of detection than nasal swabs When highly pathogenic strains (eg, H5N1) are suspected, extreme care in the handling of these samples must be observed during preliminary testing

• Positive samples must then be forwarded to the appropriate public health authorities for further investigations (eg, culture) in laboratories with the adequate level of biosafety (level 3)

Medications

• Oseltamivir

  • 75 mg orally twice daily for 5 days administered within 48 hours from onset of illness

  • Higher dose (150 mg twice daily) and possible combination therapy with amantadine or rimantadine (in countries where A (H5N1) viruses are likely to be susceptible to adamantanes) may be considered in those patients with pneumonia or progressive disease

  • Twice daily oseltamivir is also recommended for H7N9 influenza infections

  • Longer courses of therapy (eg, 10 days) should be considered in hospitalized patients with severe illness and persistent viral shedding

  • Resistance to oseltamivir is reported

• Peramivir

  • Dosage: 600 mg daily intravenously

  • Reduced to 200 mg for kidney dysfunction

  • Duration: minimum of 5 days and a maximum of 10 or more days (depending on severity of illness)

• Zanamivir (10 mg inhaled daily for 10 days) may be considered

• Successful treatment with administration of convalescent plasma is reported

Therapeutic Procedures

• Supportive measures with adequate hydration, analgesics, and rest

Complications

• Mortality rate of > 50%

• Respiratory failure, usually without bacterial infection is usually the cause of death

• Other complications include

  • Bacterial pneumonia

  • Pulmonary hemorrhage

  • Pancytopenia

  • Reye syndrome (a severe form of hepatic failure that occurs rarely, particularly in young children given salicylates during influenza B or varicella infections)

Prevention

• Postexposure prophylaxis

  • 75 mg of oseltamivir orally or 10 mg of inhaled zanamivir twice daily for 5–10 days from last known exposure, depending on length of exposure

  • Personnel exposed to those patients should be monitored for symptoms

  • Careful surveillance of new human cases and prudent stockpiling of medications with establishment of an infrastructure for dissemination are essential modalities of control

• Nonpharmacologic means of control

  • Masks

  • Social distancing

  • Quarantine

  • Travel limitations

  • Infrastructure development, particularly for emergency departments

• Current vaccines do not provide cross-protection against strains of the H5, H7, and H9 influenza viruses

• The United government has pre-pandemic stockpiles of adjuvanted H5N1 vaccines and H7N9 vaccines that are not available for public. The highly diverse genetic nature and the rapid evolution of the avian influenza viruses has resulted in the emergence of viruses that are distinct from stockpiled vaccines. New vaccine development is ongoing to generate vaccines against H7N9 and H5N1 with broadened protection against unmatched strains. Some of these vaccines are understudy in preclinical and clinical trials, however no vaccines are currently commercially available for humans.

• Two H5N1 vaccines, including one adjuvanted, are licensed (but not marketed) in the United States

  • Vaccine is administered as two 1-mL doses 28 days apart and is indicated for adults aged 18-64 years

  • The adjuvanted vaccine is indicated for persons over age 6 months and requires two doses 21 days apart

• One human vaccine against H5N1 influenza is licensed but not yet marketed in the United States

• While no commercial H7N9 vaccines are available, two large trials are under way with vaccine and treatment evaluation units

Prognosis

• Poorer outcomes in the young

• Respiratory failure, multi-organ dysfunction, and septic shock are the usual causes of death

When to Refer

• All cases should be reported to local health authorities

When to Admit

• Suspected avian influenza cases require quarantine and some require admission

• All confirmed cases should be admitted because of the high mortality rate