AVIAN FLU

AVIAN FLU - Sheila M. Seed, BS, Pharm, MPH, RPH; Walter K. Goljan, MD
BASICS
DESCRIPTION
Avian influenza A subtype H5N1 is highly pathogenic and aggressive form of influenza. Presents with influenza-like symptoms, with lower respiratory tract symptoms (limited upper respiratory tract symptoms). Has a high mortality rate in elderly and very young.
GENERAL PREVENTION
• Consider with any patient with influenza-like symptoms who has had close contact with H5N1 or ill poultry.
• Chemoprophylaxis with antivirals should be considered if H5N1 circulating in community.
EPIDEMIOLOGY
Predominate age: All age groups
Prevalence
Rare
RISK FACTORS
• Direct contact with H5N1 virus.
• Contact with infected poultry
• Close contact with infected person
ETIOLOGY
• Infected poultry (domesticated ducks, turkeys, chickens)
• Low incidence of human-to-human transmission in household clusters and health care workers
ASSOCIATED CONDITIONS
Severe respiratory distress (common in severe cases)

DIAGNOSIS
PRE HOSPITAL
• Respiratory infection (incubation period 7 days).
• Standard precautions during transport.
SIGNS AND SYMPTOMS
• Primary phase (1-5)[A]
- Influenza-like 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
History
• Known close contact with suspected or confirmed case.
• Close contact with infected poultry
• Travel within 10 days in high-risk area
Physical Exam
• Lab abnormalities (1,3,5)[A]
- Leukopenia (mainly lymphopenia)
- Thrombocytopenia (mild to moderate)
- Elevated aminotransferases (slight-moderate)
- Disseminated intravascular coagulation
- Decreased leukocyte, platelet, and lymphocyte counts (associated with increase risk of death)
• Chest radiograph (1,3,5)[A]
• Consolidation-bilateral and multifocal
- After 7 days-patchy lobar and interstitial infiltrates.
- Pleural effusions with cavitation (less common)
• Respiratory (1,3,5)[A]
- Respiratory distress
- Tachypnea
- Inspiratory crackles
TESTS
Lab
• CBC with differential
• Liver profile
• Chemical profile
• Blood culture
Imaging
Chest radiograph
Diagnostic Procedures/Surgery
• Lab confirmation of H5N1 virus is done case-by-case and requires one of the following (1,4)[A]
- Positive influenza A/H5 (Asian lineage) virus-real time reverse transcription polymerase chain reaction (LRN labs)
- Positive immunofluorescence test for antigen with use of monoclonal antibody against H5.
- Positive viral culture
- 4-fold rise in H5-specific antibody titer in paired serum samples.
DIFFERENTIAL DIAGNOSIS
• Acute respiratory syndrome
• Influenza
• Pneumonia
• SARS
TREATMENT
PRE-HOSPITAL
Standard and droplet precautions
STABILIZATION
• Ventilatory support within 48 hours (1,3)[B]
• Broad-spectrum antibiotics, antivirals agents, with or without corticosteroids until lab confirmation of H5N1 virus (5)[A]
GENERAL MEASURES
Nursing
• Use standard and droplet precautions.
• N-95 masks
MEDICATION (DRUGS)
All patients should receive neuraminidase inhibitors as soon as possible pending results of diagnostic lab tests.
ALERT
The use of amantadine (Symmetrel) and rimantadine (Flumadine) are not considered beneficial unless access to newer agents are unavailable. No vaccine is commercially available.
First Line
• Treatment of mild-moderate cases (1,5)[C]: Oseltamivir (Tamiflu) 75 mg PO b.i.d. for 5 days
• Treatment of severe cases (1,5)[C]: Oseltamivir(Tamiflu) 150 mg b.i.d. for 7-10 days
• Postexposure prophylaxis (1,5)[C]: Oseltamivir (Tamiflu) 75 mg PO once a day for 7-10 days
• Adverse effects: Generally well tolerated; nausea, vomiting, diarrhea, abdominal pain, headache, insomnia, bronchitis, vertigo.
• Drug interactions: Not metabolized by CYP450; drug interactions with drugs metabolized by this system are unlikely. Does not affect metabolism of acetaminophen.
Pediatric Considerations
• Pediatric treatment is weight-based. Safety and efficacy not established for children 1 year of age (1,5)[C]
- Oseltamivir 30 mg PO b.i.d. for 5 days 15 kg.
- Oseltamivir 45 mg PO b.i.d. for 5 days >15-23 kg
- Oseltamivir 60 mg PO b.i.d. for 5 days >23-40 kg
- Oseltamivir 75 mg PO b.i.d. for 5 days >40 kg
• Postexposure prophylaxis (1,5) [C]
- Dosing is weight-based as above but administered once daily for 7-10 days.
Geriatric Considerations
• Renal impairment (1,5)[C]
- Creatinine clearance 10-30 mL/min
 Treatment: Oseltamivir 75 mg PO daily.
 Postexposure prophylaxis: Oseltamivir 75 mg PO every other day or 30 mg PO daily
• Hepatic impairment (1,5)[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 second-line agent. Not recommended for patients with underlying respiratory disease (asthma, COPD) (5)[C]
• Treatment (ages 13-65 years)
- Zanamivir 10 mg (2 inhalations) b.i.d. for 5 days.
• Postexposure prophylaxis (ages 13-65)
- Zanamivir 10 mg (2 inhalations) once daily for 7-10 days.
• Adverse effects
- Hypersensitivity reactions: Bronchospasms and allergic-like 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 CYP450; drug interactions with drugs metabolized by this system are unlikely.
Pediatric Considerations
• Zanamivir is not licensed for use in children 7 years of age for treatment and 5 years for prophylaxis (5)[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 (5)[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 (1,5)[C]
- Broad-spectrum antibiotics: Follow hospital protocols for community-acquired pneumonia.
- Corticosteroids: No clear evidence of benefits
- Interferon-: No basis for use
FOLLOW-UP
DISPOSITION
Admission Criteria
If known H5N1 activity in community, or if patient has traveled to country with H5N1 activity, admission should be considered if patient presents with
• Severe acute respiratory illness
• Serious unexplained illness (encephalopathy or diarrhea)
Discharge Criteria
If discharged early, family requires education of proper personal hygiene and infection-control measures. Postexposure prophylaxis given to family members.
PROGNOSIS
Mortality rate is high (some reports >50%). Median time to death was 9 days (range 6-17 days) with or without treatment.
COMPLICATIONS
• Multiorgan failure, acute (1-4)[C]
• Renal dysfunction
• Cardiac compromise
• Cardiac dilatation, supraventricular tachyarrhythmias
• Ventilator-associated pneumonia
• Pulmonary hemorrhage
• Pneumothorax
• Pancytopenia
• Reye syndrome
• Sepsis syndrome without documented bacteremia.
PATIENT MONITORING
Clinical deterioration is rapid.
REFERENCES
1. Beigel JH, Farrar J, et al. Avian influenza A (H5N1) infections in humans. N Engl J Med. 2005;350:1374-1385.
2. World Health Organization. WHO international guidelines on clinical management of humans infected by influenza A (H5N1). February 20, 2004. Accessed Sep 19, 2006 at http://who.int/csr/disease/avian_influenza/guidelines/Guidelines_Clinical%20Management_H5N1_rev.pdf.
3. Chotpitayasunondh T, Ungchusak K, Hanshaoworakul W, et al. Human disease from influenza A (H5N1), Thailand, 2004. Emerg Infect Dis. 2005;11:201-209.
4. Hien TT, Liem NT, Dung NT, et al. Avian influenza A (H5N1) in 10 patients in Vietnam. N Engl J Med. 2004;350:1179-1188.
5. World Health Organization. WHO Rapid advice guidelines on pharmacological management of humans infected with avian influenza A (H5N1) virus. May 2006. Accessed Sep 19, 2006 at http://who.int/csr/disease/avian_influenza/guidelines/pharmamanagement/en.
ADDITIONAL READING
Centers for Disease Control and Prevention CDC: Question  Answers about Avian Influenza http://www.cdc.gov/flu/avian/gen-info/qa.htm.
MISCELLANEOUS
Report any cases to public health officials surveillance is necessary to monitor for possible pandemic.