What are the recent updates for managing and preventing influenza?

Recent Updates in Influenza Management and Prevention

Vaccination Updates

All influenza vaccines for the 2021-2022 season and beyond are quadrivalent formulations, as trivalent vaccines are no longer available in the United States. 1

• The vaccine composition is updated annually based on circulating strains, with the 2021-2022 season featuring new influenza A(H1N1)pdm09 and A(H3N2) components while influenza B components remained unchanged from the previous season 1
• For children aged 6-35 months, Afluria Quadrivalent is the only vaccine available in a 0.25-mL prefilled syringe, while Fluzone Quadrivalent is now only available in 0.5-mL presentation for this age group (though 0.25-mL dosing can be drawn from multidose vials) 1
• Annual influenza vaccination remains the cornerstone of prevention and should be offered before and throughout the influenza season when not contraindicated 1

Antiviral Treatment: Critical Updates

Antiviral treatment should be initiated as early as possible for all hospitalized children with suspected influenza, those with severe or progressive illness, and children at high risk of complications, regardless of vaccination status or time since symptom onset. 2

High-Risk Groups Requiring Treatment

Children requiring immediate antiviral treatment include: 1, 2

• All children younger than 5 years (especially those under 2 years)
• Children with chronic pulmonary disease (including asthma and cystic fibrosis)
• Children with hemodynamically significant cardiovascular disease
• Children with renal, hepatic, hematologic (including sickle cell disease), or metabolic disorders (including diabetes)
• Children with immunosuppression from any cause
• Children with neurologic and neurodevelopmental conditions
• Any hospitalized child with suspected influenza

First-Line Antiviral: Oseltamivir

Oral oseltamivir remains the antiviral drug of choice for managing influenza infections in children, available in capsule and oral suspension formulations (6 mg/mL concentration). 1, 2

Updated Dosing Guidelines

Treatment dosing for 5 days: 1, 2

• Adults and adolescents ≥13 years: 75 mg twice daily
• Children ≥12 months:
  • ≤15 kg: 30 mg twice daily

  • 15-23 kg: 45 mg twice daily

  • 23-40 kg: 60 mg twice daily

  • 40 kg: 75 mg twice daily

• Infants 9-11 months: 3.5 mg/kg per dose twice daily
• Term infants 0-8 months: 3 mg/kg per dose twice daily

Chemoprophylaxis dosing for 10 days (or up to 6 weeks during community outbreaks): 1

• Use once-daily dosing at the same weight-based doses listed above
• For infants 0-2 months: Not recommended unless situation is critical due to limited safety data 1

Alternative Antiviral Agents

Inhaled zanamivir is an equally acceptable alternative for patients without chronic respiratory disease, though it is more difficult to administer. 1, 3

• Zanamivir dosing: 10 mg (two 5-mg inhalations) twice daily for treatment, once daily for prophylaxis in children ≥7 years for treatment and ≥5 years for prophylaxis 1
• Contraindication: Should not be used in patients with underlying respiratory conditions such as asthma or COPD due to bronchospasm risk 3

Intravenous peramivir is approved for acute uncomplicated influenza in non-hospitalized children ≥2 years who have been symptomatic for no more than 2 days. 1, 3

Baloxavir marboxil, a cap-dependent endonuclease inhibitor, is approved for treatment of uncomplicated influenza in patients ≥12 years who have been symptomatic for no more than 48 hours. 3

• Baloxavir demonstrated 86% efficacy in preventing influenza in household contacts when administered within 48 hours of exposure 1

Critical Timing Considerations

Treatment should not be delayed while waiting for confirmatory influenza test results, and the greatest effect on outcomes occurs when treatment is initiated within 48 hours of symptom onset. 2, 4

• Early initiation within 12 hours is even more efficacious 5
• However, treatment is still recommended for high-risk patients even if more than 48 hours have passed since symptom onset 2
• Negative rapid antigen tests should not be used to rule out influenza or make treatment decisions due to low sensitivity 2

Antiviral Resistance Surveillance

The majority of currently circulating influenza viruses remain susceptible to oseltamivir, zanamivir, peramivir, and baloxavir. 1

• High levels of resistance to amantadine and rimantadine persist, so these drugs should not be used unless resistance patterns change significantly 1, 3
• Continuous monitoring by the CDC tracks resistance patterns, which can change over time 1
• Resistance characteristics can change during treatment, especially in severely immunocompromised patients 1

Treatment Efficacy and Benefits

Timely oseltamivir treatment reduces the median duration of illness by 36 hours (26%) and decreases the risk of otitis media by 34% in children. 2

• Treatment reduces the duration of symptoms and fever as well as the risk of hospitalization and death 2
• Neuraminidase inhibitors diminish the need for antibacterials to treat secondary complications 5
• In influenza-infected children aged 1-12 years, oseltamivir reduced total composite time to freedom from illness by 1.5 days compared to placebo 4

Safety Profile

Vomiting is the most frequent side effect of oseltamivir, occurring in approximately 5% of treated patients, and is less likely when taken with food. 2, 4

• Diarrhea may occur in children under 1 year of age 2
• Despite reports of neuropsychiatric adverse effects, reviews of controlled trial data have failed to establish a link between oseltamivir and neurologic or psychiatric events 2
• Serious skin/hypersensitivity reactions such as Stevens-Johnson Syndrome are rare but require immediate discontinuation 4

Chemoprophylaxis Updates

Post-exposure chemoprophylaxis should be initiated within 48 hours of exposure in high-risk individuals, using once-daily dosing rather than treatment doses. 1

• Chemoprophylaxis is not a substitute for vaccination and should be targeted at high-risk groups on a case-by-case basis 1
• Oseltamivir 75 mg once daily for 7 days significantly reduces the risk of illness in household contacts when administered within 48 hours of symptom onset in the infected person 6
• For seasonal prophylaxis during community outbreaks, oseltamivir 75 mg once daily for up to 6 weeks reduced laboratory-confirmed influenza from 5% to 1% in healthy unvaccinated adults 4

Live Attenuated Influenza Vaccine (LAIV) Considerations

Children taking influenza antiviral medications should not receive LAIV until 48 hours after stopping therapy, and LAIV effectiveness will be decreased in children receiving oseltamivir or other antivirals. 1

• If antiviral agents are necessary for treatment within 5-7 days of LAIV immunization, reimmunization may be indicated 1
• LAIV should not be administered within 2 weeks before oseltamivir use unless medically indicated 4

Special Populations

Infants Under 1 Year

For infants 0-8 months with influenza, oseltamivir 3 mg/kg twice daily for 5 days is recommended, with treatment initiated as soon as possible even if more than 48 hours have passed since symptom onset. 2

• Oseltamivir is the only approved antiviral agent for infants under 1 year, with no approved alternatives 3
• Pharmacokinetic data support the 3 mg/kg twice daily dose in this age group 1

Pregnant Women

Pregnant women can receive influenza vaccine safely during any trimester, and oseltamivir remains the preferred antiviral agent during pregnancy. 1, 3

• Breastfeeding is recommended to protect against influenza by activating innate antiviral mechanisms 1

Renal Impairment

Dosage adjustments are required for patients with renal impairment: 4

• Creatinine clearance >30-60 mL/min: Reduce to 30 mg twice daily for treatment, once daily for prophylaxis
• Creatinine clearance >10-30 mL/min: Reduce to 30 mg once daily for treatment, once every other day for prophylaxis
• ESRD on hemodialysis: 30 mg immediately, then 30 mg after every hemodialysis cycle for treatment

COVID-19 Pandemic Context

Influenza vaccination is particularly important during the SARS-CoV-2 pandemic to reduce the burden of respiratory illnesses and preserve healthcare infrastructure capacity. 1

• The heavily suppressed global influenza activity during the COVID-19 pandemic is expected to return upon relaxation of travel restrictions and nonpharmaceutical interventions 7
• Understanding the effect of SARS-CoV-2 and influenza virus co-circulation on treatment outcomes is a priority for the 2021-2022 season and beyond 1

Warning Signs Requiring Immediate Medical Attention

Parents should seek immediate care for: 2

• Difficulty breathing, fast breathing, or chest retractions
• Fever persisting beyond 3-4 days or returning after improvement
• Seizures, altered mental status, or extreme irritability

Infection Control Measures

Limit exposure to other household members, especially high-risk individuals, and practice good hand hygiene for all household members. 2

• Consider prophylactic oseltamivir for high-risk household contacts if exposed within the last 48 hours 2