In an exploratory analysis of an inactivated quadrivalent influenza vaccine (IIV4) trial in children 6–35 months without risk factors for influenza, we evaluated clinical presentation of influenza illness and vaccine impact on health outcomes.
This phase III trial was conducted in 13 geographically diverse countries across 5 influenza seasons (2011–2014). Children were randomized 1:1 to IIV4 or control. Active surveillance was performed for influenza-like episodes (ILE); influenza was confirmed by reverse transcription polymerase chain reaction (RT-PCR). The total vaccinated cohort was evaluated (N = 12,018).
5702 children experienced ≥1 ILE; 356 (IIV4 group) and 693 (control group) children had RT-PCR-confirmed influenza. Prevalence of ILE was similar in RT-PCR-positive and RT-PCR-negative cases regardless of vaccination. Breakthrough influenza illness was attenuated in children vaccinated with IIV4; moderate-to-severe illness was 41% less likely to be reported in the IIV4 group than the control group [crude odds ratio: 0.59 (95% confidence intervals: 0.44−0.77)]. Furthermore, fever >39°C was 46% less frequent following vaccination with IIV4 than with control [crude odds ratio: 0.54 (95% confidence intervals: 0.39−0.75)] in children with breakthrough illness. Health outcome analysis showed that, each year, IIV4 would prevent 54 influenza cases per 1000 children and 19 children would need to be vaccinated to prevent 1 new influenza case.
In addition to preventing influenza in 50% of participants, IIV4 attenuated illness severity and disease burden in children who had a breakthrough influenza episode despite vaccination.
From the *GSK, Rockville, Maryland
†National Autonomous University of Santo Domingo, Santo Domingo, Dominican Republic
‡GSK, Wavre, Belgium
§American University of Beirut, Beirut, Lebanon
¶GSK, King of Prussia, Pennsylvania
‖Khon Kaen University, Khon Kaen, Thailand
**icddr, b, Dhaka, Bangladesh
††Dr Castroviejo Primary Health Care Center, Madrid, Spain
‡‡Centro Médico Dominicano, Santo Domingo, Dominican Republic
§§Complutense University of Madrid, Madrid, Spain
¶¶KEM Hospital Research Centre, Pune, India
‖‖Instituto Hispalense de Pediatría, Sevilla, Spain
***Tecnologia en Investigacion, San Pedro Sula, Honduras
†††National Autonomous University of Honduras, Tegucigalpa, Honduras
‡‡‡FISABIO-Public Health, Valencia, Spain
§§§Eskisehir Osmangazi University, Eskisehir, Turkey
¶¶¶NIHR Southampton Clinical Research Facility and NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom
‖‖‖Hospital Infantil Universitario La Paz, Madrid, Spain
****Mary Chiles General Hospital, Manila, Philippines
††††University of the Philippines – Philippine General Hospital, Manila, Philippines
‡‡‡‡Uludag University, Bursa, Turkey
§§§§NIHR Manchester Clinical Research Facility, Royal Manchester Children’s Hospital, Manchester, United Kingdom
¶¶¶¶Center of Postgraduate Medical Education, Warsaw, Poland
‖‖‖‖Centre for Community Medicine, All India institute of Medical Sciences, New Delhi, India
*****Research Institute for Tropical Medicine, Manila, Philippines
†††††Paediatric Institute Mares-Riera, Blanes, Spain
‡‡‡‡‡Hospital Clínico Universitario de Santiago, Santiago, Spain
§§§§§University of Hradec Kralove, Hradec Kralove, Czech Republic
¶¶¶¶¶Center for Excellence in Pediatric Infectious Diseases and Vaccines, Chulalongkorn University, Bangkok, Thailand
‖‖‖‖‖Medicentrum 6 s.r.o., Prague, Czech Republic
******Nicolaus Copernicus University in Torun, Collegium Medicum, Bydgoszcz, Poland; University Hospital No 2, Bydgoszcz, Poland
††††††GSK, Bangalore, India
‡‡‡‡‡‡St. Hedwig of Silesia Hospital, Trzebnica, Poland
§§§§§§EBA Centelles, Barcelona, Spain
¶¶¶¶¶¶GSK, King of Prussia, Pennsylvania
‖‖‖‖‖‖The Flu4VEC Study Group members are listed in the Supplemental Digital Content 1, http://links.lww.com/INF/D555.
Accepted for publication April 4, 2019.
J.D. and L.R. are co-lead authors.
A.S. and B.I. are co-last authors.
Varsha K. Jain, MD is currently at the Bill & Melinda Gates Foundation, Seattle, Washington.
Bruce L. Innis, MD is currently at the current affiliation: PATH, Washington, DC.
The trial registration number was Clinicaltrials.gov Identifier: NCT01439360.
Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (www.pidj.com).
Address for correspondence: Jasur Danier, MD, 14200 Shady Grove Rd, Rockville, MD 20850. E-mail: email@example.com.