Avian Flu – Causes, Symptoms, Diagnosis, Treatment and Ongoing care

Basics

Description

  • Avian influenza A subtype H5N1 is a highly pathogenic and aggressive form of influenza.
  • Presents with influenzalike symptoms, with lower respiratory tract symptoms (limited upper respiratory tract symptoms)
  • High mortality rate in elderly and very young

Epidemiology

Incidence

  • More than 490 confirmed human cases (60% fatality rate); primarily in Asia
  • Predominate age: All age groups

Prevalence

Rare

Risk Factors

  • Direct contact with H5N1 virus
  • Contact with infected poultry
  • Close contact with infected person
  • Travel to affected country within 10 days of symptom onset

General Prevention

  • Consider with any patient with influenzalike symptoms who has had close contact with H5N1 or ill poultry
  • 2007: Food and Drug Administration approved a vaccine for adults 18–65. Currently only available from the government.
  • Chemoprophylaxis with antivirals should be considered if H5N1 is circulating in the community.
  • Ongoing environmental screening is more accessible now with availability of avian fecal testing (1)[B].

Etiology

  • Infected poultry (domesticated ducks, turkeys, chickens)
  • Low incidence of human-to-human transmission in household clusters and health care workers
  • Incubation period: 7 days (range 2–3 days)

Commonly Associated Conditions

Severe respiratory distress (common in severe cases)

Oseltamivir, Avian influenza, Tamiflu, Asia, Flu Symptoms, h5n1, avian flu incubation period,

Diagnosis

  • Primary phase (2,3)[A]:
    • Influenzalike symptoms with lower respiratory tract symptoms
    • Temp >100.4°F (38°C)
    • Cough
    • Sore throat
    • Shortness of breath
    • Diarrhea (watery without blood)
    • Pleuritic pain
    • Bleeding of nose and gums
    • Conjunctivitis (rare)
  • Secondary acute phase:
    • Severe respiratory distress
    • Pneumonia not responsive to antibiotics
    • Multiorgan dysfunction
  • Respiratory (2,3)[A]:
    • Respiratory distress
    • Tachypnea
    • Inspiratory crackles

History

  • Known close contact with suspected or confirmed case
  • Close contact with infected poultry
  • Travel within 10 days in high-risk area

Diagnostic Tests & Interpretation

Lab

Initial lab tests

  • Complete blood count (CBC) with differential
  • Liver profile
  • Chemical profile
  • Blood culture
  • Lab abnormalities (2,4)[A]:
    • Leukopenia (mainly lymphopenia)
    • Thrombocytopenia (mild-to-moderate)
    • Elevated aminotransferases (slight-to-moderate)
    • Decreased leukocyte, platelet, and lymphocyte counts are associated with increased risk of death.

Imaging

Initial approach

Chest x-ray (CXR): Consolidation bilateral and multifocal (2,3)[A]:

  • After 7 days: Patchy lobar and interstitial infiltrates
  • Pleural effusions with cavitation (less common)

Follow-Up & Special Considerations

  • Admit to negative-pressure room; if not available, cohort with other confirmed cases.
  • Supplemental oxygen is essential to keep SaO2 >90% (3)[A].

Diagnostic Procedures/Surgery

Lab confirmation of H5N1 virus is done case-by-case and requires 1 of the following (2,5)[A]:

  • Positive influenza A/H5 (Asian lineage) virus real-time reverse transcription polymerase chain reaction (PCR) (Laboratory Response Network labs)
  • Positive immunofluorescence test for antigen with use of monoclonal antibody against H5
  • Positive isolation of H5N1 virus
  • 4-fold rise in H5-specific antibody titer in paired serum samples

Differential Diagnosis

  • Acute respiratory syndrome
  • Influenza
  • Pneumonia
  • Severe acute respiratory syndrome

Treatment

All patients should receive neuraminidase inhibitors as soon as possible pending results of diagnostic lab tests (within 24–48 hours after exposure).

Medication

Alert

The use of amantadine (Symmetrel) and rimantadine (Flumadine) is not considered beneficial unless access to newer agents is unavailable. Vaccine is available only through US Strategic National Stockpile to be distributed by public health officials.

First Line

  • Treatment of mild-to-moderate cases (2,3)[C]: Oseltamivir (Tamiflu) 75 mg p.o. b.i.d. for 5 days
  • Treatment of severe cases (2,3)[C]: Oseltamivir (Tamiflu) 150 mg b.i.d. for 7–10 days
  • Postexposure prophylaxis (2,3)[C]: Oseltamivir (Tamiflu) 75 mg p.o. once a day for 7–10 days
  • Adverse effects: Neuropsychiatric events (hallucinations, delirium, and abnormal behavior) have been reported. Monitor for abnormal behavior. Nausea, vomiting, diarrhea, abdominal pain, insomnia, bronchitis, vertigo.
  • Drug interactions: Not metabolized by CYP 450; drug interactions with drugs metabolized by this system are unlikely. Does not affect metabolism of acetaminophen.
  • Higher doses may be considered case-by-case if present with pneumonic illness.
  • Monitor for resistance; some H5N1 viruses isolated show resistance to oseltamivir.

Pediatric Considerations

  • Pediatric treatment is weight-based. Safety and efficacy not established for children <1 year of age (2,3)[C]:
    • Oseltamivir 30 mg p.o. b.i.d. for 5 days ≤15 kg
    • Oseltamivir 45 mg p.o. b.i.d. for 5 days >15–23 kg
    • Oseltamivir 60 mg p.o. b.i.d. for 5 days >23–40 kg
    • Oseltamivir 75 mg p.o. b.i.d. for 5 days >40 kg
  • Postexposure prophylaxis (2,3)[C]:
    • Dosing is weight-based as above but administered once daily for 7–10 days.

Geriatric Considerations

  • Renal impairment (2,3)[C]:
    • Creatinine clearance 10–30 mL/min
      • Treatment: Oseltamivir 75 mg/d p.o.
      • Postexposure prophylaxis: Oseltamivir 75 mg p.o. every other day or 30 mg p.o. daily
  • Hepatic impairment (2,4)[C]:
    • No dosage adjustment needed

Pregnancy Considerations

  • Oseltamivir is Category C
  • Use with caution only if potential benefits outweigh possible risk
  • Unknown if distributed in breast milk

Second Line

  • Zanamivir (Relenza) is considered 2nd-line agent. Not recommended for patients with underlying respiratory disease (asthma, chronic obstructive pulmonary disease) (3)[C].
  • Treatment (ages 13 to ≥65 years):
    • Zanamivir 10 mg (2 inhalations) b.i.d. for 5 days
  • Postexposure prophylaxis (ages 13 to ≥65):
    • Zanamivir 10 mg (2 inhalations) once daily for 7–10 days.
  • Adverse effects:
    • Hypersensitivity reactions: Bronchospasms and allergiclike reactions have occurred.
    • Diarrhea, nausea, vomiting, headache, dizziness, sinusitis, cough, throat infections
    • Some adverse effects due to lactose in powder of inhaler
  • Drug interactions: Not metabolized by CYP 450; drug interactions with drugs metabolized by this system are unlikely.

Pediatric Considerations

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  • Zanamivir is not licensed for use in children <7 years of age for treatment and <5 years for prophylaxis (3)[C]
  • Treatment (7–13 years of age): Zanamivir 10 mg (2 inhalations) b.i.d. for 5 days
  • Prophylaxis (5–13 years of age): Zanamivir 10 mg (2 inhalations) once daily 7–10 days

Geriatric Considerations

No dosage adjustment for renal or hepatic impairment (3)[C]

Pregnancy Considerations

  • Zanamivir is Category C
  • Use with caution only if potential benefits outweigh possible risk
  • Unknown if distributed in breast milk
  • Other medications (2,4)[C]:
    • Broad-spectrum antibiotics: Follow hospital protocols for community-acquired pneumonia.
  • High-dose corticosteroids use associated with increased mortality.
  • Immunomodulating drugs: No clear evidence of benefits, not recommended

Additional Treatment

General Measures

Ventilatory support within 48 hours (2,6)[B]

In-Patient Considerations

Initial Stabilization

  • Broad-spectrum antibiotics, antiviral agents, with or without corticosteroids until lab confirmation of H5N1 virus (3)[A]
  • Ventilatory support within 48 hours (2,6)[B]

Admission Criteria

If known H5N1 activity in the community, or if patient has traveled to country with H5N1 activity, admit if patient presents with:

  • Severe acute respiratory illness
  • Serious unexplained illness (encephalopathy or diarrhea)

Nursing

  • Use standard and droplet precautions.
  • N-95 masks

Discharge Criteria

  • If discharged early, family requires education of proper hand hygiene and infection-control measures (surgical mask).
  • Postexposure prophylaxis given to family members

Ongoing Care

Follow-Up Recommendations

Patient Monitoring

Clinical deterioration is rapid.

Patient Education

Hand hygiene, cough etiquette

Prognosis

Mortality rate is high. Median time to death was 9 days (range 6–17 days) with or without treatment.

Complications

  • Multiorgan failure, acute (2,4,5,6)[C]
  • Renal dysfunction
  • Cardiac compromise
  • Cardiac dilatation, supraventricular
  • Tachyarrhythmias
  • Ventilator-associated pneumonia
  • Pulmonary hemorrhage
  • Pneumothorax
  • Pancytopenia
  • Reye syndrome
  • Sepsis syndrome without documented bacteremia

References

1. Pannwitz G, Wolf C, Harder T. Active surveillance for avian influenza virus infection in wild birds by analysis of avian fecal samples from the environment. J Wildl Dis. 2009;45:512–8.

2. Beigel JH, et al. Avian influenza A (H5N1) infections in humans. N Engl J Med. 2005;350:1374–1385.

3. World Health Organization. WHO Intermin Guidelines for Avian Influenza Case Management. 2007. Accessed 4/12/2010 at http://www.searo.who.int/LinkFiles/Publication_CD-167-Interim-guidelines-AI.pdf.

4. World Health Organization. Clinical management of human infection with avian influenza A (H5N1) virus. August 15, 2007. Accessed 4/11/2010 at http://who.int/csr/disease/avian_influenza/guidelines/Clinical Management07.pdf.

5. Tran TH, Nguyen TL, Nguyen TD et al. Avian influenza A (H5N1) in 10 patients in Vietnam. N Engl J Med. 2004;350:1179–88.

6. Chotpitayasunondh T, Ungchusak K, Hanshaoworakul W et al. Human disease from influenza A (H5N1), Thailand, 2004. Emerg Infect Dis. 2005;11:201–9.

Additional Reading

Centers for Disease Control and Prevention CDC: Key facts about Avian Influenza (Bird Flu) and Avian Influenza (H5N1) Virus. Accessed 4/11/2010 at http://www.cdc.gov/flu/avian/gen-info/facts.

Codes

ICD9

  • 488.01 Influenza due to identified avian influenza virus with pneumonia
  • 488.02 Influenza due to identified avian influenza virus with other respiratory manifestations
  • 488.09 Influenza due to identified avian influenza virus with other manifestations

Snomed

55604004 Avian influenza (disorder)

Clinical Pearls

  • Consider avian influenza in the differential diagnosis for patients presenting with acute febrile respiratory illness and recent travel to high-risk areas (especially Asia) or who have spent time on poultry farms.
  • Oseltamivir is considered 1st-line antiviral treatment: May need double usual dosage in patients with pneumonia.
  • Perform: CBC, CXR, rapid tests for Ag detection, nasopharyngeal swabs for PCR, blood cultures, AST/ALT/CD4.

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