Most Children With Influenza-Associated Encephalopathy in 2025 Were Unvaccinated

Only 16% of children with influenza-associated encephalopathy (IAE) had received the 2024 to 2025 influenza vaccine, according to results of a report in Morbidity and Mortality Weekly.

The 2024 to 2025 influenza season had the highest pediatric influenza-associated mortality rate in the United States since surveillance began in 2004. A potential complication of influenza is IAE, a neurologic condition characterized by a dysregulated inflammatory response that leads to brain dysfunction. One of the most severe forms of IAE is acute necrotizing encephalopathy (ANE), which disproportionately affects children and can cause lasting sequelae or death.

In February of 2025, the US Centers for Disease Control and Prevention (CDC) called for reporting of pediatric IAEs. This study assessed trends in suspected or confirmed pediatric IAE in the 2024 to 2025 influenza season. A total of 192 case reports were received by the CDC, of which 109 were categorized as IAE, and 37 were subcategorized as ANE.

Health care providers should consider IAE in children with recent or current febrile illness with encephalopathy, monitor these children for clinical deterioration, and initiate appropriate supportive care.

The ANE and other IAE (n=72) cases occurred among children with a median age of 4 (IQR, 1-7) and 6 (IQR, 4-10) years, respectively. Among ANE cases, 49% were girls, 51% were White, and 51% had no underlying medical conditions. Among other IAE cases, 44% were girls, 52% were White, and 56% had no underlying medical conditions.

At admission, 91% of ANE patients and 86% of other IAE patients had altered mental status, and 92% and 82%, respectively, had fever. Influenza A was identified in 92% of ANE cases and 87% of other IAE cases, and 13% and 17% had received the seasonal influenza vaccine at least 14 days before illness onset. The median time from illness onset to neurologic symptoms was 2 days (IQR, 1–3) for all patients.

Compared with other IAE cases, children with ANE demonstrated more severe clinical outcomes. Abnormal neuroimaging outcomes were observed among more ANE cases than other IAE cases (97% vs 49%). Patients who survived with ANE also had longer hospital stays than those with other IAE (median, 30 vs 6 days), were more frequently admitted to the intensive care unit (100% vs 61%), and more often required invasive mechanical ventilation (89% vs 36%). In addition, a greater proportion of ANE patients had not returned to neurologic baseline at discharge (92% vs 37%) and experienced higher mortality (41% vs 8%).

Limitations include a lack of consensus on standardized diagnostic criteria for IAE. In addition, reporting of IAE cases to the CDC was voluntary, and likely is not representative of the actual IAE rates in the US.

The study authors concluded, “IAE is a serious neurologic complication of influenza that can affect healthy children as well as those with underlying medical conditions…Health care providers should consider IAE in children with recent or current febrile illness with encephalopathy, monitor these children for clinical deterioration, and initiate appropriate supportive care.”

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.