Retrospective study of the use of an influenza disease two-tiered classification system to characterize clinical severity in US children

ABSTRACT

In children <5 years, influenza is associated with higher risk of serious disease and hospitalization when compared with other age groups. Influenza vaccination reduces the risk of influenza and vaccination may attenuate the severity of disease. Recent studies in Europe suggest that classifying influenza disease as mild versus moderate-to-severe (M-S) using a novel definition may be clinically significant. We retrospectively evaluated whether this M-S definition also characterized influenza severity in a cohort of US children. We included children <18 years at Kaiser Permanente Northern California with PCR-confirmed influenza during the 2013–2014 influenza season. We classified children as M-S if they had ≥1 symptom: fever >39°C, acute otitis media, lower respiratory tract infection (LRTI), or extra-pulmonary complications; otherwise, they were classified as mild. We used multivariable log-binomial models to assess whether M-S influenza disease was associated with increased healthcare utilization. Nearly half of the 1,105 influenza positive children were classified as M-S. Children 6–35 months had the highest proportion of M-S disease (35.1%), mostly due to LRTI (63.2%) and fever (44.6%). Children ≥6 months who had M-S disease were associated with a 1.6 to 2.8 times increased likelihood of having had an emergency department or any follow-up outpatient visits. Those who had M-S disease were associated with an increased likelihood of receiving antibiotics, with the highest likelihood in children 6–35 months (RR 9.0, 95% CI 4.1, 19.8). While more studies are needed, an influenza classification system may distinguish children with more clinically significant disease.

PLAIN LANGUAGE SUMMARY

What is the context?

• In children less than 5 years of age, influenza is associated with higher risk of serious disease and hospitalization. The authors evaluated whether classifying influenza as moderate-to-severe would be clinically relevant in US children.

What is new?

• Nearly half of influenza cases were classified as moderate-to-severe in this study, including the highest proportion of children between 6 months and 3 years of age. Children who had any emergency department or follow-up outpatient visits, or who received antibiotics were more likely to have moderate-to-severe influenza disease.

What is the impact?

• An influenza severity scale may distinguish children with more clinically significant disease.

KEYWORDS:

• Influenza
• health outcomes
• pediatric
• disease severity

Acknowledgments

Authors would like to acknowledge Business & Decision Life Sciences platform for editorial assistance and manuscript coordination on behalf of GSK. Amandine Radziejwoski coordinated manuscript development and editorial support.

Disclosure of Potential Conflicts of Interest

P. Buck, E. Yanni, R. Bekkat-Berkani, and A. Schuind are employees of the GSK group of companies. P. Buck, A. Schuind, E. Yanni, and R. Bekkat-Berkani hold shares in the GSK group of companies. N.P. Klein has received research grant support from the GSK group of companies, Sanofi Pasteur, Novartis, Merck, MedImmune, Pfizer, and Protein Sciences. A. Hsiao, A. Yee, J. Hansen, E.M. Lewis, and L. Aukes have no conflicts of interest.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

GlaxoSmithKline Biologicals SA funded this study [GSK study identifier: HO-16-17304], and all costs related to the development of this publication.