A clinical endpoint of moderate-to-severe (M/S) influenza has been proposed in children, defined as fever >39 ⁰C, otitis media, lower respiratory tract infection, or serious extrapulmonary manifestations. This definition has not been evaluated against clinically-relevant outcomes like hospitalization, emergency room care, antimicrobial use and child/parental absenteeism.
Methods: We conducted a prospective observational study of children aged 6 months-8 years with influenza at the Children’s Hospital Colorado Emergency Department (ED) and its affiliates during two influenza seasons (2016-17 & 2017-18). Children with influenza-like-illness (ILI) were enrolled and tested for influenza by polymerase chain reaction (PCR). Parents of influenza cases and matched influenza-negative controls were contacted two weeks later for follow up. The primary outcome was hospitalization for M/S influenza versus mild influenza. Secondary outcomes included recurrent ED visits, antimicrobial use, child/parental absenteeism. Interim analyses were conducted using SAS v9.4.
Results: Among the 1480 enrolled children with ILI, 410(28%) tested positive for influenza by PCR. The median age of influenza cases was 4.0 years (IQR 2.2-6.1), and 20% were considered high-risk for influenza complications. Of influenza cases, 284 (69%) met the definition for M/S influenza. Among M/S influenza subjects, 8.4% were hospitalized, compared with 1.6% with mild influenza (Risk difference (RD) 6.9%; 95% CI: 3.0-10.8, p <0.01). Subjects with M/S influenza were more likely to receive antibiotics (RD 12.0%, 95% CI: 3.4-20.6, p <0.01) with a trend to higher antiviral use (RD 6.9%, 95% CI: -0.7-14.5, p = 0.09). There was no significant difference for recurrent ED visits nor child/parental absenteeism. After adjusting for comorbidities, age, and influenza strain, the relative risk (RR) of hospitalization or recurrent ED visits was higher among those with M/S influenza versus mild influenza (RR 2.18, 95% CI: 1.02-4.64, p = 0.04).
Conclusion: Children with M/S influenza have a higher risk of hospitalization compared with mild disease. This proposed definition is a useful clinical endpoint to study the public health and clinical impact of influenza interventions in children.
A. Moss, None
E. Yanni, GSK: Employee , Salary .
R. Bekkat-Berkani, GSK: Employee , Salary .
A. Schuind, GSK: Employee , Salary .
B. Innis, GSK: Employee , Salary .
J. Cotter, None
R. Mistry, GSK: Investigator , Research support .
E. J. Asturias, GSK: Investigator , Research grant and Research support .