Basics
Description
An acute febrile illness characterized by fever, malaise, and respiratory symptoms
Epidemiology
- Although influenza affects people of all ages, the highest morbidity and mortality occur in young children <2 years old, the geriatric population, and those with high-risk conditions.
- Influenza epidemics occur almost exclusively during winter months, peak ~2 weeks after the index case, and last 4-8 weeks.
- Attack rates are highest among school-aged children (range 10-40%).
- An estimated 10-20% outpatient visits among children <5 years old attributable to influenza
- Transmission of influenza virus occurs via large respiratory droplets or contact with contaminated surfaces.
- After an incubation period of 1-4 days, viral shedding starts 24 hours before symptom onset and usually continues for 7 days.
- Prolonged shedding in young children and immunocompromised individuals
Risk Factors
High-risk conditions for severe disease include the following:
- Chronic pulmonary disease (i.e., asthma)
- Hemodynamically significant cardiac disease
- HIV and other immunodeficiencies
- Chronic immunosuppressive therapy
- Hemoglobinopathies (i.e., sickle cell disease)
- Long-term salicylate use
- Chronic renal dysfunction
- Chronic metabolic disease, morbid obesity
- Neuromuscular disorders
General Prevention
- Vaccination
- Routine influenza vaccination for ALL individuals ≥6 months old
- Prioritize vaccination for those at highest risk for influenza complications and their close contacts, including young children ages 6-59 months, older adults ≥50 years, adults and children with certain chronic diseases and high-risk conditions, long-term care facility residents, American Indians/Alaska Natives, pregnant women, health care professionals, out-of-home caregivers and household contacts of all children <5 years old OR children 5-18 years old with high-risk conditions (see "Risk Factors"ť).
- Vaccine types
- Trivalent inactivated influenza vaccine (TIV) approved for ages ≥6 months; administered as an intradermal injection
- Quadrivalent influenza vaccines newly available for 2013-2014 season and beyond; include second influenza B strain
- Inactivated: Fluarix (GlaxoSmithKline) for ages ≥3 years and Fluzone (Sanofi Pasteur) for ages ≥6 months
- Live-attenuated influenza vaccine (LAIV); for healthy nonpregnant 2-49-year-olds; administered as an intranasal spray
- Trivalent cell culture-based inactivated vaccine (Flucelvax, Novartis) for ages ≥18 years
- Recombinant hemagglutinin vaccine (FluBlok, Protein Sciences) for ages 18-49 years; egg-free
- Special vaccination considerations:
- There is no preferential recommendation for one vaccine product over another for children who can receive more than one of the available vaccines.
- Children ≤8 years old receiving seasonal influenza vaccination for the first time should receive 2 doses of vaccine at least 4 weeks apart.
- LAIV not recommended for individuals with high-risk conditions, young children (ages 2-4 years) with history of wheezing in past year, contacts of severely immunocompromised persons (such as contacts of BMT patients in a protected environment), or children receiving chronic aspirin therapy
- LAIV can be given simultaneously with other live or inactivated vaccines. However, after administration of any live vaccines, a minimum of 4 weeks should pass before administering another live vaccine.
- Contraindications to vaccination: history of severe allergic reaction to any vaccine component or after previous influenza vaccine dose
- Precautions: Those with history of Guillain-Barr © syndrome within 6 weeks of previous influenza vaccination should consult a physician before receiving the vaccine.
- Influenza vaccines can be safely administered to children with history of egg allergy (see http://www.cdc.gov/flu/professionals/acip/ for specific recommendations).
- Postexposure chemoprophylaxis
- Indicated for high-risk children who are unvaccinated or were vaccinated within 2 weeks of exposure, immunocompromised patients who have a poor vaccine response, or to control outbreaks in institutions housing high-risk people
- Chemoprophylaxis should begin within 48 hours of exposure to be most effective.
Etiology
- Orthomyxoviruses influenza types A, B, and C. Influenza C virus has not been reported as a cause of influenza epidemics.
- Influenza A subtypes defined by 2 surface antigens: hemagglutinin and neuraminidase.
- Currently circulating subtypes include pH1N1 (pmd09) and H3N2.
- Mild variation, or antigenic drift, for both A and B viruses results in seasonal epidemics; antigenic shift occurs only with A viruses and results in pandemics.
Diagnosis
Clinical case definition of influenza-like illness is fever (≥100 °F) AND cough and/or sore throat but may look similar to other respiratory illnesses.
- Positive predictive value of these symptoms for influenza lower (~65%) among children <5 years old
- Clinical presentation varies with age:
- Infants and young children are less likely to present with typical symptoms but may have higher fever and more severe respiratory symptoms.
History
- Abrupt onset of illness, beginning with chills, headache, malaise, and dry cough
- Subsequent increase in respiratory tract symptoms that can range from mild cough to severe respiratory distress (infants)
- Other symptoms: fever, anorexia, myalgias, sore throat, irritability
- Younger children may have GI complaints including vomiting, diarrhea, and severe abdominal pain.
- Children may also present with otitis media.
Physical Exam
- Cough is the predominant respiratory sign. Infants and small children may exhibit a "barky"ť cough (croup).
- Nasal congestion with conjunctival and pharyngeal injection
- Cervical adenopathy, especially in children
- Neonates may appear septic with apnea, circulatory collapse, or petechiae.
- A generalized macular or maculopapular rash is sometimes observed.
Diagnostic Tests & Interpretation
Laboratory testing can confirm diagnosis, provide surveillance data, and help guide treatment and infection control decisions because clinical symptoms alone may not accurately identify all influenza cases. However, during periods of high influenza activity when the likelihood of infection is high and a child has symptoms consistent with influenza, testing may not be indicated.
- Gold standard: RT-PCR or viral culture
- RT-PCR preferred: most accurate and sensitive; results within 3-8 hours
- Only viral culture can be used to measure subtype and antiviral resistance of circulating strains but requires 3-10 days.
- Direct immunofluorescent antibody (DFA) and indirect immunofluorescence antibody (IFA) tests have moderate sensitivity (60-70%) and excellent specificity (>95%) and are completed within 2-4 hours.
- Predictive value greatly affected by prevalence of circulating influenza.
- Rapid antigen testing (RIDT) available for diagnosing influenza A and influenza B. Results available in ~15 minutes but with wide range of sensitivities (22-77% in community settings) which may limit their usefulness.
- A negative test result should not guide management, especially when community prevalence is high.
- Serology: Look for 4-fold rise in serum antibody titers between acute and convalescent samples (at least 10-14 days apart); not helpful for clinical decision making
- Special considerations for laboratory testing:
- The false-positive rate for DFA, IFA, and rapid antigen testing may be as high as 20% (influenza A) and 40% (influenza B).
- Nasopharyngeal aspirates rather than swabs may reduce false-positive rate by 5-10%.
- Tests most sensitive <4 days of symptom onset
Imaging
Chest x-ray
- May be normal despite significant respiratory involvement
- X-rays of patients with lower airway disease are indistinguishable from those in patients with other viral lower respiratory infections.
Ancillary Laboratory Data
- Leukocyte count may be high, low, or normal with a variable differential.
- Arterial blood gas analysis or pulse oximetry to evaluate oxygenation in severe cases of influenza infection. Infants without radiologic evidence of lower respiratory tract infection can experience apnea or rapid decrements in pulmonary function.
- May see elevated creatine phosphokinase (CPK) with benign acute viral myositis. If with myoglobinuria, consider acute viral rhabdomyolysis, which can damage the kidneys. May require hospitalization and hydration.
Differential Diagnosis
- Viral infections including but not limited to respiratory syncytial virus, parainfluenza, adenovirus
- Streptococcus pyogenes, Mycoplasma pneumoniae, or Legionella spp infection
- Bacterial sepsis in young infants
Treatment
Medication
- Antiviral treatment is recommended for any patient who is
- Hospitalized
- Has severe or progressive illness
- At high risk for complications
- Treatment most effective when initiated <2 days after symptom onset but may still reduce morbidity and mortality for hospitalized patients or patients with severe disease if started up to 5 days after symptom onset.
- Treatment of healthy children with suspected or confirmed influenza in the outpatient setting is at the clinician's discretion but should be initiated <2 days after symptom onset.
- Neuraminidase inhibitors: the recommended antiviral medications for both treatment of and chemoprophylaxis against influenza A and B
- Dosage recommendations:
- Zanamivir is approved for treatment in children ≥7 years and prophylaxis in children ≥5 years of age.
- Treatment: two 10-mg inhalations b.i.d. — 5 days
- Prophylaxis: two 10-mg inhalations once per day — 10 days
- Can cause bronchospasm so should not be used in patients with history of chronic pulmonary diseases such as asthma
- Oseltamivir is approved for treatment in children ≥2 weeks of age and prophylaxis in children ≥1 year of age.
- Dose depends on age and weight (<1 year: 3 mg/kg/dose; >1 year and <15 kg: 30 mg; 15-23 kg: 45 mg; >23-40 kg: 60 mg; >40 kg: 75 mg), twice per day — 5 days for treatment and once daily — 10 days for prophylaxis
- May cause nausea and vomiting
- Amantadine hydrochloride and rimantadine: approved for treatment of influenza A in children >1 year of age but NOT recommended for either treatment or prophylaxis due to increasing resistance. Neither effective against influenza B.
- Resistance to neuraminidase inhibitors <1% among currently circulating influenza strains
- Investigational parenteral medications: peramivir and zanamivir
- For severely ill high-risk patients with suspected or confirmed oseltamivir-resistant infection
- Available through emergency investigational new drug protocol only
- Consider longer course of therapy if patient remains severely ill after 5 days.
- Preexposure prophylaxis can be considered for very high-risk patients who cannot be protected through other means when there is high risk of exposure to influenza cases.
- Duration depends on expected duration of exposure, but 4-6 weeks has been well tolerated.
- Chemoprophylaxis should not be given within 14 days after LAIV receipt as the vaccine strains are susceptible to the antiviral medications.
Additional Treatment
General Measures
- Most patients with influenza infection require supportive oral hydration, antipyresis, and routine decongestant therapy.
- With the exception of young infants, previously healthy children with influenza infection rarely require emergency treatment.
- Humidified air, with oxygen as needed, is helpful to most patients with respiratory symptoms.
- Airway maneuvers, including endotracheal intubation, may be required for severe laryngotracheitis or patients with hypoxia that is unresponsive to high-flow oxygen administration.
Ongoing Care
Follow-up Recommendations
When to expect improvement:
- Fever associated with influenza infection usually lasts up to 5 days. Recrudescence of fever does not necessarily signify the onset of a secondary bacterial infection.
- Cough may last up to 2 weeks.
- Lethargy or malaise may persist for up to 2 weeks.
- Influenza A infection usually lasts longer than influenza B or influenza C infection.
Complications
- Secondary bacterial infections including pneumonia (pneumococcal or staphylococcal)
- Otitis media (24%)
- Sinusitis
- Primary progressive viral pneumonia
- Pulmonary hemorrhage
- Acute myositis during convalescence
- More common with influenza B
- Marked by extreme muscle tenderness, especially in the calf muscles
- Rhabdomyolysis/myoglobinuria
- Elevated transaminase levels
- Reye syndrome: fatty degeneration of the liver and diffuse encephalopathy; associated with aspirin use during acute illness
- More commonly associated with influenza B but may also occur with influenza A
- Febrile convulsions
- Drug toxicity: Influenza infection may result in increased serum levels of certain medications that are metabolized by the liver.
- Rare sequelae in severe cases of influenza infection:
- Focal and diffuse myocarditis
- Diffuse cerebral edema
- Mediastinal lymph node necrosis
- Sudden death
- Guillain-Barr © syndrome
- Encephalitis
Patient Monitoring
Signs to watch for:
- Clinical signs of secondary bacterial infection
- Deteriorating mental or respiratory status after initial improvement
- Myoglobinuria in the face of muscle pain
Additional Reading
- Chung EY, Huang L, Schneider L. Safety of influenza vaccine administration in egg-allergic patients. Pediatrics. 2010;125(5):e1024-e1030. [View Abstract]
- Dawood FS, Chaves SS, P ©rez A, et al. Complications and associated bacterial co-infections among children hospitalized with seasonal or pandemic influenza, United States, 2003-2010. J Infect Dis. 2014;209(5):686-694. [View Abstract]
- Dawood FS, Fiore AE, Kamimoto L, et al. Burden of seasonal influenza hospitalization in children, United States, 2003 to 2008. J Pediatr. 2010;157(5):808-814. [View Abstract]
- Grohskopf LA, Shay DK, Shimabukuro TT, et al. Recommendations of the Advisory Committee on Immunization Practices-United States, 2013-2104. MMWR 2013;62(RR07):1-43.
- Fiore AE, Fry A, Shay D, et al. Antiviral agents for the treatment and chemoprophylaxis of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR. 2011;60(1):1-24. [View Abstract]
- Stebbins S, Stark JH, Prasad R, et al. Sensitivity and specificity of rapid influenza testing of children in a community setting. Influenza Other Respir Viruses. 2011;5(2):104-109. [View Abstract]
Codes
ICD09
- 487.1 Influenza with other respiratory manifestations
- 488.12 Influenza due to identified 2009 H1N1 influenza virus with other respiratory manifestations
- 487.0 Influenza with pneumonia
- 488.19 Influenza due to identified 2009 H1N1 influenza virus with other manifestations
- 487.8 Influenza with other manifestations
- 488.11 Influenza due to identified 2009 H1N1 influenza virus with pneumonia
- 488.81 Influenza due to identified novel influenza A virus with pneumonia
- 488.89 Influenza due to identified novel influenza A virus with other manifestations
- 488.82 Influenza due to identified novel influenza A virus with other respiratory manifestations
ICD10
- J11.1 Influenza due to unidentified influenza virus with other respiratory manifestations
- J10.1 Flu due to oth ident influenza virus w oth resp manifest
- J11.00 Flu due to unidentified flu virus w unsp type of pneumonia
- J11.89 Influenza due to unidentified influenza virus w oth manifest
- J09.X2 Flu due to ident novel influenza A virus w oth resp manifest
SNOMED
- 6142004 Influenza (disorder)
- 231000124101 Influenza A virus subtype H1 2009 pandemic strain present (finding)
- 195878008 Pneumonia and influenza (disorder)
- 441345003 Influenza B virus present (finding)
- 63039003 Influenza with respiratory manifestation other than pneumonia (disorder)
FAQ
- Q: When is it safe for a child with influenza to return to day care or school?
- A: Older children with influenza may shed the virus in nasal secretions for up to 7 days from onset of symptoms and younger children even longer. Therefore, older children with influenza may return to school 1 week after onset of symptoms, and infants and toddlers should remain home for 10-14 days.
- Q: Can a child on chronic steroid therapy be immunized against influenza?
- A: In general, children who require maintenance steroid therapy for their underlying illness should still receive influenza immunization. If possible, immunize while the child is on the lowest possible dose of steroids.
- Q: Is chemoprophylaxis an acceptable alternative for protecting children against influenza?
- A: In general, chemoprophylaxis should not be used as a substitute for vaccination. Specific recommendations and indications for chemoprophylaxis can be found at www.cdc.gov/flu/professionals/antivirals/summary-clinicians.htm.