Last year’s flu season was the deadliest for children in the past decade, according to two new reports from the CDC. 

The 280 deaths in children from influenza during the 2024-25 flu season represent the highest number since the 2009-2010 season, which was the year of the H1N1 pandemic, according to the Katie Reinhart, MD, of the CDC’s National Center for Immunization and Respiratory Diseases, and colleagues.

The pediatric flu-related deaths from 2024-2025 are the highest reported for a nonpandemic season since 2004, the first year in which child flu deaths were nationally notifiable, the researchers wrote. The data were published in the CDC’s Morbidity and Mortality Weekly Report (MMWR).

A majority (61%) of the 280 pediatric deaths last season occurred in children younger than 9 years, with a median age of 7 years. Overall, the highest influenza-associated mortality rate occurred in the youngest children, those younger than 6 months (11.1 per million children), and mortality was higher among girls (4.5 per million) than among boys (3.1 per million).

Vaccination status data were available for 208 of the children, and 89% of those eligible for vaccination had not been vaccinated.

For cases of pediatric deaths in which the influenza subtype was known, (H1N1pdm09) was the most common (56%); 43% were H3N2 viruses.

The findings were limited by several factors including underreporting, misclassification of underlying medical conditions, and missing data on medical conditions and complications, the researchers noted.

However, the results highlight the severity of influenza in children and support annual vaccination against the flu, they said. “All persons aged 6 months and older without a contraindication should receive an annual influenza vaccine; vaccinating children annually against influenza can help prevent severe illness and death,” the researchers wrote.

Rise of Flu’s Deadly Complications

In a separate report, Amara Fazal, MD, of the CDC’s National Center for Immunization and Respiratory Diseases, and colleagues identified 109 cases of influenza-associated encephalopathy (IAE); of these, 37 were subclassified as a severe form of IAE known as acute necrotizing encephalopathy (ANE).

Medscape Medical News previously reported a rise in IAE from none in the 2020-2021 flu season to a preliminary 14% in the 2024-2025 season.

According to the current report, the median patient age was 5 years, 46% were female patients, and 52% were non-Hispanic White individuals. Approximately half (55%) of the patients had no underlying medical conditions, but neurologic symptoms (mainly altered mental status) appeared a median of 2 days after the onset of illness.

Overall, 74% of the children were admitted to an ICU; 19% died, including 41% of those with ANE.

“Only 16% of children with IAE who were vaccination-eligible had received the 2024-2025 influenza vaccine,” the researchers wrote.

The findings were limited to the use of a convenience sample of cases, the possible underdiagnosis of IAE given the lack of standardized diagnostic criteria, and the use of electronic health records that did not include complete clinical and neuroimaging data, they said. However, “healthcare 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,” they concluded.

Don’t Underestimate Flu Risks and Vaccine Benefits

Tragically, children die of influenza in the US each year, but many remain unvaccinated, possibly because healthcare providers, patients, and families don’t recognize the severity of the infection, said Lori Handy, MD, MSCE, associate director of the Vaccine Education Center at the Children’s Hospital of Philadelphia and assistant professor of clinical pediatrics at the Perelman School of Medicine, both in Philadelphia, in an interview.

“The new data confirm how serious this infection can be in children and are a stark reminder for all of us of the need for vaccination,” said Handy, who was among the clinicians who contributed case information to the IAE report but was not involved in the analyses.

The finding to highlight is that the majority of children who died were not fully vaccinated, Handy emphasized. “The takeaway is that the vaccine truly protects from tragic endpoints of this disease, and anyone eligible for vaccine should be vaccinated,” she said. “Additionally, many children who died were otherwise healthy; influenza is a virus that can cause death in anyone, not just those with high-risk conditions,” Handy added.

Influenza-associated encephalopathy remains rare, but the data from the second MMWR report suggest that it happens more frequently than was previously appreciated, Handy told Medscape Medical News. The new IAE report is a case series, so more will be learned about this complication and its causes over time, she said.

The fact that only 16% of children with IAE who were eligible for vaccination received the influenza vaccine in 2024-2025 highlights the main benefit of the flu vaccine, which is the prevention of severe outcomes such as hospitalization and death, and these data can help clinicians strongly recommend vaccination to parents of all children, Handy noted.

Looking ahead to this year’s flu season, decreasing vaccination rates put more children at risk for severe disease and potentially death from influenza, said Handy. “All clinicians can strongly recommend vaccination for children to reduce these risks,” she said.

The MMWR research was supported by the CDC. Handy had no financial conflicts to disclose.