What are the symptoms and treatment for a patient suspected of having H5N1 (Avian Influenza) influenza?

H5N1 Influenza: Clinical Presentation and Management

Clinical Symptoms

H5N1 influenza presents with fever (100% of cases), cough, and dyspnea, but is distinguished from seasonal influenza by frequent gastrointestinal symptoms and rapid progression to severe pneumonia with high mortality. 1

Initial Presentation

• Fever is universal (present in 100% of documented cases across all age groups) 1
• Respiratory symptoms include cough (57-100%), dyspnea (100% in hospitalized patients), and sore throat (20-86%) 1
• Upper respiratory symptoms such as rhinorrhea occur in 20-57% of cases 1

Distinguishing Gastrointestinal Features

• Diarrhea occurs in 14-100% of patients, which is notably more common than in seasonal influenza 1
• Vomiting and abdominal pain are reported in 14-40% of cases 1
• These gastrointestinal symptoms often appear early in the disease course and can precede respiratory symptoms 1

Laboratory Abnormalities

• Lymphopenia is present in 57-100% of cases and correlates with poor prognosis 1
• Deranged liver function tests occur in 29-100% of patients and are associated with worse outcomes 1
• Thrombocytopenia develops in 14-86% of cases 1
• Leukopenia is found in 29-100% of patients 1

Disease Progression and Severity

• Pneumonia develops within 14 days of symptom onset in 61-100% of hospitalized patients 1
• Rapidly progressive respiratory failure is the hallmark of severe disease, often requiring ventilatory support 1
• Multi-organ failure can occur, including acute respiratory distress syndrome (ARDS), Reye's syndrome, and involvement of liver and brain 1
• Death occurs an average of 10 days after illness onset, with most patients dying from progressive respiratory failure 1
• Overall mortality rate exceeds 40% among hospitalized patients, with rates as high as 55-86% in some cohorts 1

Age Distribution

• Children and young adults are predominantly affected, with half of patients aged ≤18 years in documented outbreaks 1
• The mean age ranges from 4-40 years across different outbreaks 1

Treatment Approach

Oseltamivir 75 mg twice daily for 5 days should be initiated immediately in adults with confirmed or suspected H5N1 infection, as early treatment (within 48 hours of symptom onset) significantly reduces mortality. 1

First-Line Antiviral Therapy

• Oseltamivir is the primary treatment with dosing at 75 mg orally twice daily for adults and weight-based dosing for children 1
• Pediatric dosing: 30 mg twice daily for weight ≤15 kg; 45 mg twice daily for 15-23 kg; 75 mg twice daily for ≥24 kg 1
• Dose reduction by 50% is required if creatinine clearance is <30 mL/minute 1
• Treatment should begin as soon as possible, ideally within 48 hours of symptom onset, though benefit may extend to 6-8 days after onset 1, 2, 3

Alternative Neuraminidase Inhibitors

• Zanamivir may be administered if oseltamivir is unavailable or if oseltamivir-resistant strains are suspected, though it has lower bioavailability outside the respiratory tract 1
• Zanamivir requires ability to use the diskhaler device 1

M2 Inhibitors (Amantadine/Rimantadine)

• Amantadine or rimantadine should NOT be used alone as first-line treatment when neuraminidase inhibitors are available due to high resistance rates and rapid development of resistance 1
• Consider amantadine only if neuraminidase inhibitors are unavailable and the virus is known to be susceptible, guided by local resistance patterns 1

Combination Therapy

• Combination of neuraminidase inhibitor plus M2 inhibitor may be considered in severely ill patients, but only in the context of prospective data collection with standardized clinical and virological monitoring 1

Treatment Efficacy and Timing

• Oseltamivir reduces mortality by approximately 49% when initiated early 2
• Early treatment (≤2 days after symptom onset) is particularly effective in patients without respiratory failure (odds ratio 0.17) 3
• Patients with advanced respiratory failure requiring ventilation at the time of oseltamivir initiation have significantly higher mortality despite treatment 3
• Treatment benefit may extend up to 6-8 days after symptom onset, particularly in severely ill and immunosuppressed patients 1, 2, 3

Critical Management Pitfalls

Common Errors to Avoid

• Do not delay treatment waiting for laboratory confirmation—initiate oseltamivir based on clinical suspicion in patients with appropriate exposure history and influenza-like illness 1
• Do not use standard seasonal influenza dosing assumptions—H5N1 may require higher doses or longer duration, though current guidelines recommend standard dosing pending further evidence 4, 5
• Do not rely on antibiotics alone—secondary bacterial infections are not the primary cause of pneumonia in H5N1 1
• Do not use corticosteroids routinely—adjunctive corticosteroid therapy has not been shown to improve survival and may be harmful 3

High-Risk Situations Requiring Special Consideration

• Immunocompromised patients and those on long-term corticosteroids may benefit from treatment initiated >48 hours after symptom onset 1
• Pregnant women should receive the same treatment as non-pregnant adults, as the high case fatality rate outweighs potential medication risks 1
• Patients unable to mount adequate febrile response (immunocompromised, very elderly) may still require treatment despite lack of documented fever 1

Chemoprophylaxis for Exposed Individuals

Oseltamivir chemoprophylaxis should be administered to high-risk exposure contacts for 7-10 days after last known exposure, using the same dose as for seasonal influenza. 1

Risk-Based Approach

• High-risk exposures (unprotected close contact with confirmed H5N1 patient or infected poultry) warrant oseltamivir prophylaxis 1
• Moderate-risk exposures may receive oseltamivir prophylaxis 1
• Low-risk exposures should probably not receive prophylaxis, with stronger recommendation against prophylaxis in pregnant women with low-risk exposure 1
• Chemoprophylaxis should begin as soon as possible after exposure status is known 1