Evaluation of Moderate to Severe Influenza Outcomes in Children (M2SFlu)

Evaluation of Moderate to Severe Influenza Disease in Children 6 Months to 8 Years in Colorado

The purpose of this study was to determine whether moderate-severe endpoints (including high fever, lower respiratory tract disease, acute otitis media, or serious extra-pulmonary complications) were predictive of hospitalization, intensive care admission, antibiotic use and other complications in children under 8 years of age.

Study Overview

• Status: Completed
• Conditions: Fever; Influenza; Otitis Media; Lower Resp Tract Infection; Encephalitic Infection; Myositis Viral
• Intervention / Treatment: Procedure: Respiratory nasal swab

Detailed Description

This prospective observational study aimed to determine the risk difference of hospitalization due to moderate to severe influenza compared with mild influenza among children aged 6 months to 8 years who were evaluated at Children's Hospital Colorado emergency department and urgent care during the 2016-2017 influenza season. In addition, the study intended to evaluate the risk difference for other health outcomes such as ICU admission, antibiotic and antiviral use, caregiver and child absenteeism and recurrent (>1) healthcare visits, and to compare the healthcare costs associated with management of moderate to severe versus mild influenza in children. Children who presented to Children's Hospital Colorado Emergency Department (ED) and urgent care affiliated sites (North Campus urgent care) with an influenza-like illness from December 2016 to April 2017 and during the 2016-2017 influenza season, were eligible for the study. Once enrolled in the study, the investigators collected respiratory samples (nasal swab specimens) for influenza testing by PCR, sociodemographic and clinical data including variables of interest outlined above, and followed the clinical outcome of these children for 14 days after their initial presentation. Some of the variables of interest the investigators collected are shown below.

• Study Type: Observational
• Enrollment (Actual): 1478

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado
    • Broomfield, Colorado, United States, 80023
      • Children's Hospital North Campus Urgent Care

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 8 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Children 6 months to 8 years of age and younger seeking evaluation and management of influenza-like illness (ILI) at any of the study sites will be eligible for participation in the study. The study will commence during the influenza season as determined by the department of microbiology and epidemiology at CHCO (the influenza season commences when there are 3 positive influenza PCR tests within a week), approximately from December 1, 2016 to April 30, 2017.

Description

Inclusion Criteria:

• Age 6 months to < 8 years
• Presentation to one of the study sites with signs and symptoms of influenza-like illness (temperature of >37.8⁰C and at least one of the following: cough, sore throat, runny nose or nasal congestion)
• Parents or guardians agreeing and consenting to medical information release, respiratory specimen collection and testing, email/phone call follow up and collection of leftover blood samples obtained during routine clinical care
• Patients seen during the 2016-2017 influenza season

Exclusion Criteria:

• Respiratory symptom duration > 14 days
• Nurse only visit
• Enrollment in the study within prior 14 days

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Moderate-to-severe Influenza; Children 6 weeks to 8 years of age with influenza-like illness and one of the following: Fever >39; Lower respiratory tract infection; Acute otitis media; Serious extra-pulmonary manifestations (myositis, encephalitis)	Procedure: Respiratory nasal swab; Nasal swabs will be obtained for testing by the study nurses. If a respiratory sample has already been collected as part of routine clinical care, this will replace the study collection, and no additional testing will be required.; Other Names: Nasal swab
Mild Influenza; Children 6 weeks to 8 years of age with influenza-like illness (ILI) without the criteria for moderate-to-severe disease (above)	Procedure: Respiratory nasal swab; Nasal swabs will be obtained for testing by the study nurses. If a respiratory sample has already been collected as part of routine clinical care, this will replace the study collection, and no additional testing will be required.; Other Names: Nasal swab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hospitalization	Hospitalization within 14 days of influenza infection diagnosis	0-14 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ICU Admission	Admission to the intensive care unit after influenza diagnosis	0-14 days
Antiviral Use	Antiviral use in children presenting to the ED or urgent care with influenza	0-14 days
Antibiotic Use	Antibiotic use in children presenting to the ED or urgent care with influenza	0-14 days
Recurrent Visits	Recurrent visits to the ED or healthcare provider in children presenting to the ED or urgent care with influenza	0-14 days
School Absenteeism	Absenteeism from school or daycare in patients presenting to the ED or urgent care with influenza	0-14 days
Work Absenteeism	Absenteeism from work in caregivers of children presenting to the ED or urgent care with influenza	0-14 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Injectable Influenza Vaccine (IIV) Hospitalization	Hospitalization among children who received IIV presenting to the ED or urgent care with influenza.	0-14 days

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Collaborators: GlaxoSmithKline
• Investigators: Principal Investigator: Edwin J Asturias, MD, University of Colorado, Denver; Study Director: Suchitra Rao, MD, University of Colorado, Denver

Publications and helpful links

General Publications

• Wilkes JJ, Leckerman KH, Coffin SE, Keren R, Metjian TA, Hodinka RL, Zaoutis TE. Use of antibiotics in children hospitalized with community-acquired, laboratory-confirmed influenza. J Pediatr. 2009 Mar;154(3):447-9. doi: 10.1016/j.jpeds.2008.09.026.
• Coffin SE, Zaoutis TE, Rosenquist AB, Heydon K, Herrera G, Bridges CB, Watson B, Localio R, Hodinka RL, Keren R. Incidence, complications, and risk factors for prolonged stay in children hospitalized with community-acquired influenza. Pediatrics. 2007 Apr;119(4):740-8. doi: 10.1542/peds.2006-2679.
• Izurieta HS, Thompson WW, Kramarz P, Shay DK, Davis RL, DeStefano F, Black S, Shinefield H, Fukuda K. Influenza and the rates of hospitalization for respiratory disease among infants and young children. N Engl J Med. 2000 Jan 27;342(4):232-9. doi: 10.1056/NEJM200001273420402.
• Neuzil KM, Mellen BG, Wright PF, Mitchel EF Jr, Griffin MR. The effect of influenza on hospitalizations, outpatient visits, and courses of antibiotics in children. N Engl J Med. 2000 Jan 27;342(4):225-31. doi: 10.1056/NEJM200001273420401.
• Salo H, Kilpi T, Sintonen H, Linna M, Peltola V, Heikkinen T. Cost-effectiveness of influenza vaccination of healthy children. Vaccine. 2006 Jun 5;24(23):4934-41. doi: 10.1016/j.vaccine.2006.03.057. Epub 2006 Apr 7.
• Ferdinands JM, Olsho LE, Agan AA, Bhat N, Sullivan RM, Hall M, Mourani PM, Thompson M, Randolph AG; Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network. Effectiveness of influenza vaccine against life-threatening RT-PCR-confirmed influenza illness in US children, 2010-2012. J Infect Dis. 2014 Sep 1;210(5):674-83. doi: 10.1093/infdis/jiu185. Epub 2014 Mar 26.
• Heikkinen T, Silvennoinen H, Heinonen S, Vuorinen T. Clinical and socioeconomic impact of moderate-to-severe versus mild influenza in children. Eur J Clin Microbiol Infect Dis. 2016 Jul;35(7):1107-13. doi: 10.1007/s10096-016-2641-9. Epub 2016 Apr 16.
• Jain VK, Rivera L, Zaman K, Espos RA Jr, Sirivichayakul C, Quiambao BP, Rivera-Medina DM, Kerdpanich P, Ceyhan M, Dinleyici EC, Cravioto A, Yunus M, Chanthavanich P, Limkittikul K, Kurugol Z, Alhan E, Caplanusi A, Durviaux S, Boutet P, Ofori-Anyinam O, Chandrasekaran V, Dbaibo G, Innis BL. Vaccine for prevention of mild and moderate-to-severe influenza in children. N Engl J Med. 2013 Dec 26;369(26):2481-91. doi: 10.1056/NEJMoa1215817. Epub 2013 Dec 11.
• Rao S, Moss A, Lamb M, Innis BL, Asturias EJ. Vital sign predictors of severe influenza among children in an emergent care setting. PLoS One. 2022 Aug 12;17(8):e0272029. doi: 10.1371/journal.pone.0272029. eCollection 2022.
• Rao S, Moss A, Lamb MM, Asturias EJ. Evaluation of Influenza Vaccine Effectiveness Among Young Children Receiving Consecutive Versus Nonconsecutive Vaccination During Influenza A(H3N2)-Predominant Seasons. J Pediatric Infect Dis Soc. 2021 Apr 3;10(3):359-362. doi: 10.1093/jpids/piaa080.
• Rao S, Yanni E, Moss A, Lamb MM, Schuind A, Bekkat-Berkani R, Innis BL, Cotter J, Mistry RD, Asturias EJ. Evaluation of a New Clinical Endpoint for Moderate to Severe Influenza Disease in Children: A Prospective Cohort Study. J Pediatric Infect Dis Soc. 2020 Sep 17;9(4):460-467. doi: 10.1093/jpids/piz075.

Study record dates

Study Major Dates

• Study Start (Actual): January 30, 2017
• Primary Completion (Actual): May 4, 2018
• Study Completion (Actual): May 5, 2018

Study Registration Dates

• First Submitted: November 29, 2016
• First Submitted That Met QC Criteria: November 29, 2016
• First Posted (Estimate): December 1, 2016

Study Record Updates

• Last Update Posted (Actual): February 4, 2021
• Last Update Submitted That Met QC Criteria: January 15, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: intensive care unit; hospitalization; school absenteeism; work absenteeism
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; RNA Virus Infections; Virus Diseases; Respiratory Tract Infections; Respiratory Tract Diseases; Disease Attributes; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Otorhinolaryngologic Diseases; Ear Diseases; Orthomyxoviridae Infections; Otitis; Infections; Communicable Diseases; Influenza, Human; Myositis; Otitis Media
• Other Study ID Numbers: 16-1785

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided