Three-season effectiveness of inactivated influenza vaccine in preventing influenza illness and hospitalization in children in Japan, 2013–2016

doi:10.1016/j.vaccine.2018.01.024

Vaccine

Volume 36, Issue 8, 14 February 2018, Pages 1063-1071

https://doi.org/10.1016/j.vaccine.2018.01.024 Get rights and content

Highlights

•
Three-season vaccine effectiveness in preventing influenza illness was 45% (N = 12,888).
•
Three-season vaccine effectiveness in preventing hospitalization was 52%.
•
Vaccine effectiveness was highest in young group and declined with age thereafter.
•
Low or no significant VE was demonstrated in infants or in adolescents.

Abstract

Objectives

We assessed the vaccine effectiveness (VE) of inactivated influenza vaccine (IIV) in children 6 months to 15 years of age in 2015/16 season. In addition, based on the data obtained during the three seasons from 2013 to 2016, we estimated the three-season VE in preventing influenza illness and hospitalization.

Methods

Our study was conducted according to a test-negative case-control design (TNCC) and as a case-control study based on influenza rapid diagnostic test results.

Results

During 2015/16 season, the quadrivalent IIV was first used in Japan. The adjusted VE in preventing influenza illness was 49% (95% confidence interval [CI]: 42–55%) against any type of influenza, 57% (95% CI: 50–63%) against influenza A and 34% (95% CI: 23–44%) against influenza B. The 3-season adjusted VE was 45% (95% CI: 41–49%) against influenza virus infection overall (N = 12,888), 51% (95% CI: 47–55%) against influenza A (N = 10,410), and 32% (95% CI: 24–38%) against influenza B (N = 9232). An analysis by age groups showed low or no significant VE in infants or adolescents. By contrast, VE was highest in the young group (1–5 years old) and declined with age thereafter. The 3-season adjusted VE in preventing hospitalization as determined in a case-control study was 52% (95% CI: 42–60%) for influenza A and 28% (95% CI: 4–46%) for influenza B, and by TNCC design, it was 54% (95% CI: 41–65%) for influenza A and 34% (95% CI: 6–54%) for influenza B.

Conclusion

We demonstrated not only VE in preventing illness, but also VE in preventing hospitalization based on much larger numbers of children than previous studies.

Introduction

Annual estimates of the effectiveness of influenza vaccine assessed by a test-negative case-control (TNCC) design have been reported in recent years [1], [2], [3], [4], [5], [6], [7], and the TNCC design has become the standard design for assessing vaccine effectiveness (VE). However, because most of the subjects of these recent studies were adults and the elderly, none of these studies clearly confirmed the VE of inactivated influenza vaccine (IIV) in children, especially the VE by age groups of children.

Since almost all children with a fever during an influenza epidemic in Japan receive an influenza rapid diagnostic test (IRDT) [8], in our previous studies we used the results of IRDTs as a basis for estimating the VE in children by the TNCC design [9], [10]. As a result, we were able to enroll much larger numbers of children with influenza-like illness—4727 in the 2013/14 season [9] and 3752 in the 2014/15 season [10]—than many other published studies, thereby providing an opportunity to compare the age-specific VE and estimate the VE in preventing hospitalization. Previous results have consistently confirmed a moderate VE in the 1- to 12-year-old group but shown low or no significant VE in infants and adolescents.

Although a meta-analysis did not yield convincing evidence that the influenza vaccine reduces mortality, hospitalizations, or serious complications in children [11], the results of our previous studies demonstrated that influenza vaccination was highly effective in reducing hospitalization of children with influenza A infection in the 2013/14 season [9] and 2014/15 season [10].

In this study, we investigated the VE of quadrivalent IIV during the epidemic caused by influenza A(H1N1)pdm09 and influenza B viruses in 2015/16 season, and based on the data obtained in over 12,000 children during the 3 consecutive seasons of 2013/14 [9], 2014/15 [10], and 2015/16, we estimated the 3-season VE in preventing influenza illness, especially the VE by age groups of children, and the VE in preventing hospitalization.

Section snippets

Epidemiology in the 2015/16 season

Influenza A(H1N1)pdm09 viruses, influenza A(H3N2) viruses, and influenza B viruses circulated in Japan in the 2015/16 season, and the dominant circulating influenza A strain was A(H1N1)pdm09, which was antigenically matched to the vaccine strain in Japan, A/California/7/2009. According to FluNet [12], 87.1% of the influenza A viruses isolated in Japan during the study period were the A(H1N1)pdm09 strain. All A(H1N1)pdm09 viruses belonged to clade 6B, and most of them (80%) were classified into

Characteristics of the enrollees in the 2015/16 season (Fig. 1)

A total of 4496 children were enrolled in the 2015/16 season, but 87 of them were excluded from the analysis for the following reasons: 50 were <6 months old or >15 years old, or their age was unknown; 17 had an unclear influenza vaccination history, and the date of 1 patient’s clinic visit had not been recorded; 4 had been counted twice; 3 had a fever <38 °C; 2 were both influenza A- and B-positive; and 1 had been diagnosed at another hospital. The details of those included in analysis

Discussion

During the 2015/16 season, the quadrivalent IIV was moderately effective against influenza A (mainly A/H1N1pdm09) and was also effective against influenza B (both Yamagata and Victoria lineages) in children (Table 2a). A high adjusted VE against influenza A was demonstrated in the 1- to 5-year-old group, but the VE declined with age. A similar tendency for the VE to decline with age was observed in the influenza B patients.

Contrary to expectations, we found that the 3-season VE was highest in

Acknowledgment

Additional members of the Keio Pediatric Influenza Research Group include Motoko Fujino, MD (Saiseikai Central Hospital, Tokyo), Mio Kono, MD (National Hospital Organization, Saitama National Hospital, Wako), Makoto Yoshida, MD (Sano Kousei General Hospital, Sano), Anna Goto, MD (Fuji Heavy Industries Health Insurance Society Ota Memorial Hospital, Ota), Mayumi Ishikawa, MD (Saitama City Hospital, Saitama), Naoko Yoshida, MD (Kyosai Tachikawa Hospital, Tachikawa), Michiko Myokai, MD (Shizuoka

Financial support

None.

Potential conflicts of interests

N.S. has received speakers' honoraria from Astellas, Daiichi Sankyo, Denka Seiken and Takeda, none of which was in connection with the work presented here.

M.S. has received speakers’ honoraria from Astellas, Daiichi Sankyo, Japan Vaccine and MSD; and grant support from Japan Vaccine, none of which was in connection with the work presented here.

K.M. has received speakers’ honoraria from Japan Vaccine and MSD, none of which was in connection with the work presented here.

For other authors, none

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Citation Excerpt :
Although children aged 6–11 months are included in the recommended group, the vaccine effectiveness (VE) for this specific age group has not been proved recently. Our series of VE studies since the 2013/14 season [7,9–13] demonstrated that vaccines in younger (6–11 months) and older (6–15 years old) children tended to be less effective. We showed significant VE against influenza A in the 2018/19 season for children aged 6–11 months (63% [95% confidence interval (CI), 15–84]) [7], but the VE for this age was not statistically significant against either influenza A and B in other seasons (95 %CI of the odds ratio included 1.0).
We have reported the vaccine effectiveness of inactivated influenza vaccine in children aged 6 months to 15 years between the 2013/14 and 2018/19 seasons. Younger (6–11 months) and older (6–15 years old) children tended to have lower vaccine effectiveness. The purpose of this study is to investigate whether the recent vaccine can be recommended to all age groups.
The overall adjusted vaccine effectiveness was assessed from the 2013/14 until the 2020/21 season using a test-negative case-control design based on rapid influenza diagnostic test results. Vaccine effectiveness was calculated by influenza type and by age group (6–11 months, 1–2, 3–5, 6–12, and 13–15 years old) with adjustments including influenza seasons.
A total of 29,400 children (9347, 4435, and 15,618 for influenza A and B, and test-negatives, respectively) were enrolled. The overall vaccine effectiveness against influenza A, A(H1N1)pdm09, and B was significant (44% [95% confidence interval (CI), 41–47], 63% [95 %CI, 51–72], and 37% [95 %CI, 32–42], respectively). The vaccine was significantly effective against influenza A and B, except among children 6 to 11 months against influenza B. The age group with the highest vaccine effectiveness was 1 to 2 years old with both influenza A and B (60% [95 %CI, 55–65] and 52% [95 %CI, 41–61], respectively). Analysis for the 2020/21 season was not performed because no cases were reported.
This is the first report showing influenza vaccine effectiveness by age group in children for several seasons, including immediately before the coronavirus disease (COVID-19) era. The fact that significant vaccine effectiveness was observed in nearly every age group and every season shows that the recent vaccine can still be recommended to children for the upcoming influenza seasons, during and after the COVID-19 era.
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View all citing articles on Scopus

¹: See complete list of the Keio Pediatric Influenza Research Group co-authors in the online version.

View full text

Three-season effectiveness of inactivated influenza vaccine in preventing influenza illness and hospitalization in children in Japan, 2013–2016

Highlights

Abstract

Objectives

Methods

Results

Conclusion

Introduction

Section snippets

Epidemiology in the 2015/16 season

Characteristics of the enrollees in the 2015/16 season (Fig. 1)

Discussion

Acknowledgment

Financial support

Potential conflicts of interests

Lancet Respir Med

J Infect Chemother

Vaccine

Vaccine

Effectiveness of seasonal influenza vaccine for adults and children in preventing laboratory-confirmed influenza in primary care in the United Kingdom: 2015/16 end-of-season results

Euro Surveill

Vaccine effectiveness in preventing laboratory-confirmed influenza in primary care patients in a season of co-circulation of influenza A(H1N1)pdm09, B and drifted A(H3N2), I-MOVE Multicentre Case-Control Study, Europe 2014/15

Euro Surveill

2014–2015 influenza vaccine effectiveness in the United States by vaccine type

Clinl Infect Dis

Influenza vaccine effectiveness in the Netherlands from 2003/2004 through 2013/2014: the importance of circulating influenza virus types and subtypes

PloS One

Intraseason waning of influenza vaccine protection: evidence from the US influenza vaccine effectiveness network, 2011–2012 through 2014–2015

Clin Infect Dis

Early 2016/17 vaccine effectiveness estimates against influenza A(H3N2): I-MOVE multicentre case control studies at primary care and hospital levels in Europe

Euro Surveill

Effectiveness of trivalent inactivated influenza vaccine in children estimated by a test-negative case-control design study based on influenza rapid diagnostic test results

PLoS One

Trivalent inactivated influenza vaccine effective against influenza A(H3N2) variant viruses in children during the 2014/15 season, Japan

Euro Surveill

Vaccines for preventing influenza in healthy children

Cochrane Database Syst Rev