Influenza

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Seasonal Influenza

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Seasonal (or common) Influenza (H1N1, H2N2, H3N2)

• A acute viral upper and lower respiratory tract illness that is transmitted
person-to-person; most people have some immunity.

• U.S. flu season runs from November to April (peak between late December
and early March).

• 5-20% of the U.S. population gets the flu every year; > 200,000 hospitalized; 36,000 deaths

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Novel H1N1 influenza (Swine)

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• A new influenza virus first detected in the United States in April 2009; most children and young adults have no immunity; 4th generation descendent of 1918 H1N1 virus

• WHO declared a pandemic on June 1, 2009 (virus identified in >120 countries; as of July 2009 there were 98,000 cases; 700 deaths)

• Associated with severe disease and death usually in those < 60 years of age; aggressive clinical course (severe pneumonia -> ventilator-dependent respiratory failure -> ARDS)

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Avian Influenza (aka “bird flu”) (H5N1)

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• A naturally occurring highly pathogenic H5N1 influenza virus infection in wild birds that is deadly to domestic bowl; can be transmitted to people and people-to-people. No known human immunity; often deadly (mortality >60%)

• Current outbreak started 12/03

• Resistant to amantadine and rimantadine; some resistance to oseltamivir

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Interpret viral nomenclature

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• A/Brisbane/59/2007 (H1N1) [Subtype/Location 1st isolated/isolate/year isolated (surface proteins)]

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Viral Subtypes

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• Influenza A typically causes moderate to severe illness in all age groups; infects humans and animals; more rapid antigenic drift than influenza B; associated with more extensive and severe outbreaks

• Influenza B typically causes milder disease and primarily affects children;
humans only.

• Influenza C rarely causes disease in humans; no epidemics reported

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Viral Transmission

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• Inhale virus-laden droplets (aerosolized by coughing and sneezing).

• Hand-to-hand or other personal contact with virus-laden secretions and fomite transmission occurs but is less common.

• The virus initially infects the respiratory epithelium (ciliated columnar epithelial cells) then spreads to other respiratory cells in 4-6 hours; replicated in respiratory epithelium (destroys the cells)

• Incubation period typically 2 days (range 1-5 days).

• Virus sheds for 2-5 days; shedding starts 1 to 2 days before symptoms begin and ends 4-5 days after the onset of symptoms; found in all body secretions

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Prevention - General recommendations (all types of influenza )

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• Wash hands with soap and water or alcohol-based hand cleaner
• Avoid touching eyes, nose or mouth
• Avoid close contact (stay at least six feet away from sick person)
• If sick, cover mouth and nose with tissue when coughing or sneezing
• If sick, stay home and minimize contact with other people until 7 days after symptoms began or until symptom-free for 24 hours, whichever is longer

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Prevention - Face Masks and N95 Respirators

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• Face masks
- disposable (single use only)
- protects from splashes or sprays (virus-containing aerosols can penetrate)

• N95 (or higher) Respirators
- protects from virus-containing aerosols (seal tightly)
- not recommended for children or for those with facial hair

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Viral Diagnosis

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• Clinical and epidemiological characteristics

• Isolate the virus from clinical specimen (nasopharynx, throat, sputum)

• Increased influenza IgG by serologic assay

• Direct antigen testing for type A virus

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Influenza Symptoms

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-Diarrhea
-Malaise
-Myalgia
-Vomiting
-Chills
-Sore Throat
-Headache
-Coryza
-Anorexia
-Cough
-Fever

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Characterize Influenza

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• Abrupt onset of systemic symptoms.

• Body temperature rises rapidly to 38-41C within first 24 hours then declines over next
few days.

• Respiratory symptoms become more prominent as systemic symptoms resolve.

• Most symptoms resolve within 3-7 days.

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Complications of Influenza

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1. Post-viral asthenia – weeks of weakness and lassitude (especially in the elderly).
2. Secondary bacterial respiratory infections (S. pneumonia, S. aureus, H. influenza).
3. Asthma or COPD exacerbations.
4. Croup (young children) – laryngotracheobronchitis
5. ARDS – acute respiratory distress syndrome (diffuse pulmonary edema)
6. Reye’s Syndrome – encephalopathy of young children (severe vomiting, confusion, coma, brain swelling); increased risk with concomitant aspirin
7. Myositis – muscle inflammation
8. Rhabdomyolysis – skeletal muscle degradation w/ myoglobinuria and renal failure
9. Guillain-Barre Syndrome – post-viral paralytic syndrome


*The elderly are at high risk of cardiovascular, pulmonary, and renal deterioration.

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Seasonal Influenza Vaccine

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• Annual trivalent inactivated vaccine (TIV) (adults) (October – November) 2009-2010 TIV (same influenza A strains as 2008-2009 vaccine):
A/Brisbane/59/2007 (H1N1)-like
A/Brisbane/10/2007 (H3N2)-like
B/Brisbane/60/2008-like

- Indicated for age 6 months and older

• Live attenuated influenza vaccine (LAIV)

- Approved for use in healthy children, adolescents and adults 2-49 yrs.

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Novel H1N1 Influenza Vaccine

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Vaccine Investigational

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State the CDC priority groups for the 2009 novel H1N1 vaccine.

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- K-12 students and staff (all ages)
- Children ( 6 months) and staff (all ages) at child care centers
- Pregnant women
- Children 6 months – 4 years
- New parents and household contacts children < 6 months
- Non-elderly adults < 65 yrs with medical conditions that increase the risk for complications
-Health care and emergency services workers (all ages)

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State the CDC priority groups for the 2009 seasonal flu vaccine.

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- children 6-23 months
- children 6 months to 18 years taking long-term aspirin therapy
- women who will be pregnant during the flu season
- adults and children with pulmonary or cardiac disease
- adults and children who required regular medical follow-up or hospitalization during preceding year for chronic metabolic diseases (DM), renal dysfunction, hemoglobinopathies, immunosupression (disease, drugs)
- adults and children with any condition than can compromise respiratory function or ability to handle respiratory secretions (cognitive dysfunction, spinal cord injuries, seizure disorders, neuromuscular disease)
- residents of NH or other chronic care facilities that house persons of any age who have chronic medical conditions
- persons > 65 years of age

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Initial Therapy - Influenza A (seasonal) H1N1

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CHEMOPROPHYLAXIS: Zanamivir or Rimantadine

TREATMENT: Zanamivir or Rimantadine

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Initial Therapy - Influenza A H3N2

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CHEMOPROPHYLAXIS: Oseltamivir or Zanamivir

TREATMENT: Oseltamivir or Zanamivir

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Initial Therapy - Influenza B

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CHEMOPROPHYLAXIS: Oseltamivir or Zanamivir

TREATMENT: Oseltamivir or Zanamivir

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Initial Therapy - Unknown subtype

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CHEMOPROPHYLAXIS: Zanamivir or
Oseltamivir + Rimantadine


TREATMENT: Zanamivir or
Oseltamivir + Rimantadine

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Chemoprophylaxis - Influenza

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• Adjunct if late vaccination and local outbreak
• Supplement to vaccination if impaired immune function and local outbreak
• Primary prevention if not vaccinated and local outbreak
• Duration of therapy
- Community: Continue for 5-7 days after last known exposure
- LTC/hospital: Minimum of 2 weeks; continue for up to one week after last known case identified
- Pre-exposure: Continue for 10 days after last known exposure

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Treatment - Influenza

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• Hydration

• Rest

• Antipyretic/analgesic (no salicylates for children < 18 years of age)

• Antivirals
- Recommended for all hospitalized patients with confirmed, probable or
suspected novel H1N1 influenza
- Recommended for all other patients at high risk for influenza-related complications
- Start within 48 hours of onset and continue for five days (safety and efficacy if started >48 hours not known but may benefit)
- Reduce signs and symptoms 50%
- Decrease viral shedding
- Slight reduction in duration of symptoms (by about one day)
- Significantly decreases pneumonia and bronchitis complications

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Oseltamivir Emergency Use Authorization (EUA) for Novel Influenza (H1N1) in Children Younger than 1 Year of Age (CDC 2009) - Age: < 3 months

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Treatment (5 days): 12 mg twice daily

Prophylaxis (10 days): Not recommended unless situation judged critical (limited data in this age group)

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Oseltamivir Emergency Use Authorization (EUA) for Novel Influenza (H1N1) in Children Younger than 1 Year of Age (CDC 2009) - Age: 3-5 months

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Treatment (5 days): 20 mg twice daily•

Prophylaxis (10 days): 20 mg once daily

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Oseltamivir Emergency Use Authorization (EUA) for Novel Influenza (H1N1) in Children Younger than 1 Year of Age (CDC 2009) - Age: 6-11 months

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Treatment (5 days): 25 mg twice daily

Prophylaxis (10 days): 25 mg once daily

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Oseltamivir (Tamiflu) - Adults

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TREATMENT (5 days):
75 mg twice per day

PROPHYLAXIS:
75 mg once per day

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Oseltamivir (Tamiflu) - Children > or equal to 12 months

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TREATMENT (5 days):
equal or less than
15 kg 30 mg twice per day
16-23 kg 45 mg twice per day
24-40 kg 60 mg twice per day
>40 kg 75 mg twice per day

PROPHYLAXIS:
30 mg once per day
45 mg once per day
60 mg once per day
75 mg once per day

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Zanamivir (Relenza) - Adults

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TREATMENT (5 days):
Two 5-mg inhalations (10 mg total) twice per day

PROPHYLAXIS:
Two 5 mg inhalations (10 mg total) once per day

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Zanamivir (Relenza) - Children

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TREATMENT (5 days):
Two 5-mg inhalations (10 mg total) twice per day (age 7 years or older)

PROPHYLAXIS:
Two 5-mg inhalations (10 mg total) once per day (age, 5 years or older)

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Amantadine (Symmetrel) - Adults

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TREATMENT (5 days):
100 mg twice per day

PROPHYLAXIS:
1200 mg twice per day

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Amantadine (Symmetrel) - Children

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TREATMENT (5 days):
1-9 years: 5 mg/kg up to 150 mg in 2 divided doses; 10 and older use adult dose

PROPHYLAXIS:
1-9 years: 5 mg/kg up to 150 mg in 2 divided doses; 10 and older use adult dose

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Rimantadine (Flumadine) - Adults

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TREATMENT (5 days):
100 mg twice per day

PROPHYLAXIS:
100 mg twice per day

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Rimantadine (Flumadine) - Children

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TREATMENT (5 days):
1-9 years: 5 mg/kg up to 150 mg in 2 divided doses; 10 and older use adult dose

PROPHYLAXIS:
1-9 years: 5 mg/kg up to 150 mg in 2 divided doses; 10 and older use adult dose

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Oseltamivir (Tamiflu)

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• FDA-approved for the prophylaxis and treatment of influenza A and B
• MOA: inhibits neuraminidase (sialidase), an enzyme important for viral survival
• Marketed as 75 mg capsules and suspension (60 mg/5 ml)
• Decrease the dose by 50% if Clcr 10-30 ml/min; do not use if Clcr < 10 ml/min
• Gastrointestinal side effects (nausea, vomiting) common (around 10%; less if take with food)
• Transient neuropsychiatric events (self-injury or delirium); monitor closely for abnormal behavior
• Important drug interactions with drugs that manipulate renal tubular secretion (e.g., probenecid reduced
Clcr by 50%, doubling the plasma concentration)

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Zanamivir (Relenza)

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• FDA-approved for the prophylaxis and treatment of influenza A and B
• MOA: inhibits neuraminidase (sialidase), an enzyme important for viral survival
• Marketed as a powder for inhalation (5 mg per blister)
• Do not use if underlying airway disease

• Counseling regarding drug delivery very important (the Diskhaler is a very complicated system)

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Counsel the Use of Diskhaler Step A.

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Load the medicine into the Diskhaler

1. Pull the blue cover off.
2. Inspect the mouthpiece.
3. Pull the white mouthpiece tray all the way out.
4. Press the ridges on the side of the tray and pull the tray out of the device.
5. Place one silver medicine disk onto the brown wheel (flat side up).
6. Insert the white tray back into the device.

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Counsel the Use of Diskhaler Step B.

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Puncture the blister

1. Keep the Diskhaler level at all times to avoid spilling the medicine.
2. Lift the flap straight up so that the plastic needle punctures the top and bottom of the silver medicine disk.
3. Put the flap back into place.

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Counsel the Use of Diskhaler Step C.

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Inhale

1. Turn head away from device and exhale all the way out.
2. Seal lips around the white mouthpiece; do not cover the small holes on either side of the mouthpiece.
3. Breathe is through mouth steadily and deeply to end of inhalation.
4. Hold breath for a few seconds.
5. To take another inhalation, advance to the next blister (see Step D).

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Counsel the Use of Diskhaler Step D.

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Advance the medicine disk to the next blister

1. Pull the mouthpiece to extend the white tray without removing it.
2. Push the white tray in until it clicks.

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Adamantanes

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• FDA-approved for prophylaxis and treatment of influenza A but high levels of resistance.
• MOA: interfere with M2 protein (a membrane channel protein needed for viral unloading).
• Amantadine is associated with significant CNS side effects (nausea, dizziness, lightheadedness,
insomnia, anxiety, depression, ataxia, irritability, delirium, agitation, hallucinations, confusion, jitteriness,
difficulty concentrating, seizures). Also has anticholinergic effects (contraindicated in untreated angle
closure glaucoma); watch additive side effects with other drugs with anticholinergic properties
• Rimantadine has the same side effect profile but the side effects occur less frequently.