#18,885
Although the 2024-2025 flu season hasn't quite ended, last winter's influenza-related hospitalizations are reportedly the highest in nearly 15 years (see MMWR: Influenza-Associated Hospitalizations During a High Severity Season (United States, 2024–25),
A particularly painful subset of these severe cases were pediatric - and while likely an undercount - the CDC reports 280 pediatric flu related deaths over the past 12 months; the highest total since the 2009-2010 pandemic.
In the past (see Neuroinfluenza: A Review Of Recently Published Studies), severe neurological presentation from influenza infection was thought to be `rare', but in recent years we've seen indications that its incidence may be rising.
The CDC's MMWR describes IAE and ANE as:
Influenza-associated encephalopathy (IAE), a recognized complication of influenza, refers to neurologic syndromes triggered by influenza virus infection of the respiratory tract, resulting in a dysregulated host inflammatory response and leading to varying degrees of brain dysfunction (1,2).
One of the most severe forms of IAE is acute necrotizing encephalopathy (ANE), a condition that disproportionately affects children and is characterized by rapid neurologic decline and neuroimaging with evidence of necrosis or hemorrhage involving the thalami; ANE has a poor prognosis and can result in lasting neurologic sequelae or death (2,3).
While you'll want to follow the links to read both reports in their entirety, a brief overview of yesterday's two MMWR reports follow. I'll have a postscript after the break.
Influenza-Associated Pediatric Deaths — United States, 2024–25 Influenza Season
Weekly / September 25, 2025 / 74(36);565–569
Katie Reinhart, PhD1; Stacy Huang, MPH1; Krista Kniss, MPH1; Carrie Reed, DSc1; Alicia Budd, MPH1 (VIEW AUTHOR AFFILIATIONS)View suggested citation
Summary
What is already known about this topic?
Influenza can cause severe illness and death among all persons, including children.
What is added by this report?
The 2024–25 influenza season had the highest number of pediatric deaths reported (280) since child deaths became nationally notifiable in 2004, except for the 2009–10 influenza A(H1N1)pdm09 pandemic. Approximately one half of children who died from influenza had an underlying medical condition, and 89% were not fully vaccinated.
What are the implications for public health practice?
All persons aged ≥6 months who do not have contraindications should receive an annual influenza vaccination to prevent influenza and its complications, including influenza-associated death.
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Abstract
Influenza-associated deaths among children aged <18 years have been nationally notifiable since 2004. The highest number of pediatric deaths reported during a single season since reporting of influenza-associated pediatric deaths began (excluding the 2009–10 influenza A[H1N1]pmd09 pandemic) occurred during the 2024–25 season.Through September 13, 2025, a total of 280 influenza-associated pediatric deaths were reported, representing a national rate of 3.8 deaths per 1 million children. The median age at death was 7 years, and 56% of children who died had at least one underlying medical condition. Influenza A viruses were associated with 240 (86%) of the deaths. Forty percent of children who died were treated with influenza antiviral medications. Among the 208 pediatric decedents with available data who were eligible for influenza vaccine, 89% were not fully vaccinated.
CDC recommends that all persons aged ≥6 months who do not have contraindications receive the influenza vaccine each year, ideally by the end of October.
Pediatric Influenza-Associated Encephalopathy and Acute Necrotizing Encephalopathy — United States, 2024–25 Influenza Season
Weekly / September 25, 2025 / 74(36);556–564
Amara Fazal, MD1; Elizabeth J. Harker, MPH1; Varsha Neelam, MPH1; Samantha M. Olson, MPH1; Melissa A. Rolfes, PhD1; Katie Reinhart, PhD1; Krista Kniss, MPH1; Aaron Frutos, PhD1,2; Jerome Leonard, MD1,2; Carrie Reed, DSc1; Vivien G. Dugan, PhD1; Haytham Safi, MD3; Theresa M. Dulski, MD3,4; Adrianna Stanley-Downs, MD5; Aaliya Bhatti, MPH5; Isaac Armistead, MD6; Suchitra Rao, MBBS7; Carola Torres-Diaz, MPH8; Ashlin Thomas, MPH8; Andy Weigel, MSW9; Michael Patten, DO9; Mallory Sinner, MPH10; Dawn Nims, MPH10; Crystal Mattingly, MPH10; Valerie Gosack, MLS11; Amy Voris12; Jaime Redkey, MS13; Felicia A. Scaggs Huang, MD14,15; Danielle DeCesaris, MPH14; Carrie Tuggle, MPH16; Kristina A. Betters, MD17; Julie Hand, MSPH18; Anna Krueger, MS19; Dina Z. Potter, MD19; Curi Kim, MSPH20; Rachel Park, MSc20; Sue Hong, MD21; Hannah E. Edelman, MD21; Sue Kim, MPH22; Justin Henderson, MPH22; Melissa McMahon, PhD23; Jeffrey Sanders, MPH23; David A. Hunstad, MD24; Emma L. Doran, MD25; Khalil Harbi, MSPH25; Derek Julian, MPH26; Hannah Ball, MPH26; John Dreisig, MPH27; Deepam Thomas, MPH28; Justin Faybusovich, MPH28; Yomei P. Shaw, PhD29; Nancy Eisenberg, MPH30; Richa Chaturvedi, MPH31; Ashleigh Faulstich, MPH31; Rachel E. Wester, MPH32; Donna L. Gowie32; Nicholas Fisher33; Melissa Sutton, MD34; Sameh W. Boktor, MD35; Jonah M. Long, MPH35; Patricia Marshall, MS36; Abby L. Berns, MPH36; Lindsey McAda, MPH37; Sarah Winders, MPH38; Pamela Gomez Pinedo, MPH39; Jade Murray, MPH39; Ta’Kindra Westbrook, MPH40; Anna Unutzer, MPH41; Scott Lindquist, MD41; Thomas E. Haupt, MS42; Kaylyn Baum, MPH43; Molly Wilson-Murphy, MD44,45; Carol Glaser, MD5,45; Kathleen Harriman, PhD5,45; James W. Antoon, MD, PhD17,45; Keith P. Van Haren, MD45,46; Adrienne G. Randolph, MD45,47; Andrew Silverman, MD45,46; Annabelle de St. Maurice, MD45,48; Sascha Ellington, PhD1; Timothy M. Uyeki, MD1,*; Shikha Garg, MD1,*; CDC Influenza-Associated Encephalopathy Collaborators (VIEW AUTHOR AFFILIATIONS)View suggested citation
Summary
What is already known about this topic?
Influenza-associated encephalopathy (IAE) is a rare, severe neurologic complication of influenza.
What is added by this report?
During the high-severity 2024–25 influenza season, 109 U.S. pediatric IAE cases were identified; 55% of affected children were previously healthy. Thirty-seven IAE cases were subcategorized as acute necrotizing encephalopathy (ANE), a severe form of IAE characterized by rapid neurologic decline and a poor prognosis. Overall, 74% of IAE patients were admitted to an intensive care unit, and 19% died; 41% of ANE patients died. Only 16% of vaccine-eligible IAE patients had received the 2024–25 influenza vaccine.
What are the implications for public health practice?
All children are at risk for severe neurologic complications of influenza. Annual influenza vaccination is recommended for all children aged ≥6 months to prevent influenza and associated complications, potentially including IAE.
Full Issue PDF
Abstract
In January 2025, CDC received several reports of deaths among children aged <18 years with a severe form of influenza-associated encephalopathy (IAE) termed acute necrotizing encephalopathy (ANE). Because no national surveillance for IAE currently exists, CDC requested notification of U.S. pediatric IAE cases from clinicians and health departments during the 2024–25 influenza season, a high-severity season with a record number of pediatric influenza-associated deaths.Among 192 reports of suspected IAE submitted to CDC, 109 (57%) were categorized as IAE, 37 (34%) of which were subcategorized as ANE, and 72 (66%) as other IAE; 82 reports did not meet IAE criteria and were categorized as other influenza-associated neurologic disease.The median age of children with IAE was 5 years and 55% were previously healthy, 74% were admitted to an intensive care unit, and 19% died; 41% of children with ANE died. Only 16% of children with IAE who were vaccination-eligible had received the 2024–25 influenza vaccine. Health care providers should consider IAE in children with encephalopathy or altered level of consciousness and a recent or current febrile illness when influenza viruses are circulating.
Annual influenza vaccination is recommended for all children aged ≥6 months to prevent influenza and associated complications, potentially including severe neurologic disease such as IAE and ANE.
While the current flu vaccine admittedly isn't a perfect solution, it can substantially reduce the burden of influenza.
In a related MMWR report on the effectiveness of the Southern Hemisphere's flu vaccine against hospitalization, the authors report: `During the 2025 Southern Hemisphere influenza season, seasonal influenza vaccination reduced influenza-associated outpatient visits by 50.4% and hospitalization by 49.7%.'
Along with pervasive anti-vaccine rhetoric on social media - we've also seen frequent demonization of antivirals - which have long been debunked (see Study Finds No Relationship Between Suicide & Oseltamivir In Pediatric Patients).
To be most effective, antivirals need to be taken early (first 24-48 hrs), yet many parents (and some doctors) remain slow to opt for antiviral treatment.A recent study (see JAMA Neuro: Influenza With and Without Oseltamivir Treatment and Neuropsychiatric Events Among Children and Adolescents) shows clear benefit for early administration of oseltamivir, with the authors writing:
In this cohort study, oseltamivir treatment during influenza episodes was associated with a reduced risk of serious neuropsychiatric events. These findings support oseltamivir use for prevention of these influenza-related complications.
While a sharp increase in pediatric IAE/ANE cases has been reported in the U.S. over the past year, it isn't clear whether this represents a genuine increase or is due to improved detection and reporting following the CDC's call for increased surveillance and reporting last February.
To sort this out, we'll need vastly improved surveillance and reporting over multiple flu seasons, as explained in yesterday's MMWR.
No consensus standardized diagnostic or surveillance case definitions for IAE currently exist. Additional measures are needed to develop and implement surveillance to improve understanding of the incidence, potential risk factors, severity, and public health impact of IAE in the United States.
CDC is integrating surveillance for IAE and ANE into existing CDC-sponsored surveillance systems for the 2025–26 influenza season to better understand these serious and potentially preventable complications of influenza.
But until we know more, the seasonal flu shot and early access to antiviral medications, are our best options to lower the impact of flu on pediatric (and adult) populations.
