Why Are Children More Prone to Fatal Influenza?

Allison Bitonti-Brito, PharmD Candidate
Published Online: Thursday, November 5th, 2015
Influenza A virus is a prominent cause of morbidity and mortality in children, even more so than in adults.
Last year’s flu season saw 146 pediatric deaths.1 Overall, influenza has an annual prevalence rate estimated at 5% to 10% in adults and 20% to 30% in children, which is a stark difference.2
Although the exact reason behind this phenomenon is unknown, a few theories were recently summed up in a review article published in JAMA Pediatrics.3
It has been speculated that the increased influenza severity and incidence in children may be due to increased viral replication, decreased ability to clear the virus, greater inflammatory response, more susceptibility to secondary bacterial infections, or a combination of all of these factors.
In a study on rhesus monkeys, increased viral replication and decreased secretion of interferon alpha (IFN-α), which is involved in the destruction of foreign pathogens, was found in infant monkeys, but not in their adult counterparts. In addition, studies in both mice and human infants suggest that there is also a decrease in the secretion of interferon gamma (IFN-γ), which is primarily secreted from natural killer (NK) cells.
IFN-γ has direct antiviral activity and aids in clearing pathogens. Non-functional NK cells may be the cause of the decrease in IFN-γ.
An emerging theory for the increased prevalence of influenza A virus in children is that they have an enhanced inflammatory response leading to increased morbidity and mortality. Several studies have found that increased pro-inflammatory cytokine interleukin-6 (IL-6) in the pediatric population has a direct effect on flu severity.
A recent prospective study also found that infants and young children had higher levels of inflammatory nasal cytokines and type I IFNs than adults—which coincides with the theory that inflammation, not innate immune deficiency, is to blame for the difference in morbidity and mortality.
Possibly due to a counter response of excessive inflammation, interleukin-10 (IL-10) seems to be elevated in children. Because IL-10 has anti-inflammatory properties, it is potentially detrimental to the host because it increases the risk for secondary bacterial infection.
Co-infection has been reported in 43% to 75% of fatal cases of influenza A virus in children.
These review findings provide a roadmap for future research to determine why the pediatric population is more prone to serious flu infection.

1. US Centers for Disease Control and Prevention. FluView: Influenza-Associated Pediatric Mortality. http://gis.cdc.gov/GRASP/Fluview/PedFluDeath.html. Accessed October 20, 2015.
2. World Health Organization. Influenza (seasonal). http://www.who.int/mediacentre/factsheets/fs211/en/. Published March 2014. Accessed October 20, 2015.
3. Coates BM, Staricha KL, Wiese KM, Ridge KM. Influenza A Virus Infection, Innate Immunity, and Childhood. JAMA Pediatr. 2015;169(10):956-963.

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