Vaccine Effectiveness against Medically Attended Laboratory-Confirmed Influenza in Japan, 2011–2012 Season

Abstract

The objective of this study was to estimate influenza vaccine effectiveness (VE) against medically attended, laboratory-confirmed influenza during the 2011–2012 season in Japan using a test-negative case-control study design. The effect of co-circulating non-influenza respiratory viruses (NIRVs) on VE estimates was also explored. Nasopharyngeal swab samples were collected from outpatients with influenza-like illnesses (ILIs) in a community hospital in Nagasaki, Japan. Thirteen respiratory viruses (RVs), including influenza A and B, were identified from the samples using a multiplex polymerase chain reaction. The difference in VE point estimates was assessed using three different controls: ILI patients that tested negative for influenza, those that tested negative for all RVs, and those that tested positive for NIRVs. The adjusted VE against medically attended, laboratory-confirmed influenza using all influenza-negative controls was 5.3% (95% confidence interval [CI], −60.5 to 44.1). The adjusted VEs using RV-negative and NIRV-positive controls were −1.5% (95% CI, −74.7 to 41) and 50% (95% CI, −43.2 to 82.5), respectively. Influenza VE was limited in Japan during the 2011–2012 season. Although the evidence is not conclusive, co-circulating NIRVs may affect influenza VE estimates in test-negative case-control studies.

Potential of the test-negative design for measuring influenza vaccine effectiveness: a systematic review

“…The majority of studies made VE estimates for patients of all ages (n=48; one excluded children <10y [85]), with the remainder targeted at adults (≥15y; n=12; 2 restricted to adults ≥50y [27, 87]), children (n=9 [19, 26, 29, 31, 47, 59, 62, 81, 94]), elderly (n=4 [51, 53, 72, 95]), children and adults aged 50+ (n=1 [84]), pregnant women (n=1 [89]), military (n=2 [28, 40]), healthcare workers (n=1 [42]) or people at high-risk or in a target group for vaccination (n=7 [14, 18, 20, 25, 43, 44, 52]).…”

“…Twelve studies attempted to control for misclassification associated with shedding by including the days since symptoms onset as a covariate, either as a linear term (n=2 [31, 96]) or stratified (n=4 [35, 58, 77, 78]) and the remainder did not clearly specify how the variable was included [18, 97, 66, 85, 86, 89]. This may represent over-adjustment as the duration of symptoms is not a confounder that is a common cause of exposure and outcome [110, 111].…”

“…(Where a study listed “PCR” as the method of detection it was assumed this was RT-PCR.) Three studies indicated the use of rapid test kits [25, 85, 86]. Fifty-eight studies specified that the RT-PCR was real-time, although it is probable that all studies used a real-time assay.…”

Effectiveness of inactivated influenza vaccine against laboratory-confirmed influenza pneumonia among adults aged ≥65 years in Japan

“…The detection limits of the multiplex PCR assays were 10 -100 copies per reaction as reported previously [14]. Influenza virus subtyping was performed for influenza A-positive samples via RT-PCR of the influenza HA genes using previously published methods [15,16].…”

The Characteristics of Influenza-Like Illness Management in Japan

“…Contrary to the recommendation of the Infectious Disease Society of America [18], Japanese physicians usually use RIDT, rather than a molecular assay such as reverse-transcription polymerase chain reaction (RT-PCR). This may be because the rapid test has extremely high sensitivity and specificity in the early phases of symptoms [16,[19][20][21] and most patients in Japan visit physicians in these early stages, making the rapid test more appropriate.…”