On Feb. 27, 2025, the U.S. Centers for Disease Control and Prevention (CDC) announced that it is investigating reports of critically ill children with Influenza-associated encephalopathy or encephalitis (IAE), including acute necrotizing encephalopathy (ANE), a rare and potentially fatal complication of influenza.

IAE is not notifiable in the United States; however, in Japan, where encephalopathy and encephalitis due to an infection is notifiable, the number of cases among persons of all ages during 2010–2015 ranged from 64 to 105 per season. IAE was identified in 13% (nine of 68) of deaths in the U.S. during the 2024–25 influenza season (through February 8, 2025), including four with ANE.

Children of all ages, and especially those aged <5 years with certain underlying medical conditions, can experience severe or fatal complications associated with influenza virus infection, including pneumonia, myocarditis, pericarditis, and neurologic complications.

The Influenza-Associated Pediatric Mortality Surveillance System is a national surveillance system that collects data on all identified influenza-associated pediatric deaths, which have been nationally notifiable in the United States since 2004.

Health care providers should consider IAE in children with febrile illness and clinically compatible neurologic signs or symptoms, including but not limited to seizures, altered mental status, delirium, decreased level of consciousness, lethargy, hallucinations, or personality changes lasting >24 hours.