Effectiveness of influenza vaccines in preventing severe influenza illness among adults: A systematic review and meta-analysis of test-negative design case-control studies

Abstract

Summary Objectives Summary evidence of influenza vaccine effectiveness (IVE) against hospitalized influenza is lacking. We conducted a meta-analysis of studies reporting IVE against laboratory-confirmed hospitalized influenza among adults. Methods We searched Pubmed (January 2009 to November 2016) for studies that used test-negative design (TND) to enrol patients hospitalized with influenza-associated conditions. Two independent authors selected relevant articles. We calculated pooled IVE against any and (sub)type specific influenza among all adults, and stratified by age group (18–64 and 65 years and above) using random-effects models. Results We identified 3411 publications and 30 met our inclusion criteria. Between 2010–11 and 2014–15, the pooled seasonal IVE was 41% (95%CI:34;48) for any influenza (51% (95%CI:44;58) among people aged 18–64y and 37% (95%CI:30;44) among ≥65 years). IVE was 48% (95%CI:37;59), 37% (95%CI:24;50) and 38% (95%CI:23;53) against influenza A(H1N1)pdm09, A(H3N2) and B, respectively. Among persons aged ≥65 year, IVE against A(H3N2) was 43% (95%CI:33;53) in seasons when circulating and vaccine strains were antigenically similar and 14% (95%CI: −3;30) when A(H3N2) variant viruses predominated. Conclusions Influenza vaccines provided moderate protection against influenza-associated hospitalizations among adults. They seemed to provide low protection among elderly in seasons where vaccine and circulating A(H3N2) strains were antigenically variant.

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

“…The TND is less susceptible to bias due to differences in health care-seeking behavior among cases and controls and provides reliable IVE estimates [18,19]. Recently, TND studies have been widely used to estimate IVE against medically attended influenza and influenza-associated hospitalization [8,9].…”

“…On the other hand, evidence is still limited for the beneficial effect of influenza vaccination against influenza-related severe outcomes such as pneumonia. Previous studies have estimated the IVE against all-cause pneumonia or influenza-related hospitalization in older adults [9,[26][27][28]; however, these studies used less specific outcomes and may have underestimated the true IVE [17]. The TND study by Grijalva et al demonstrated that the overall estimate of IVE against hospitalization with laboratory-confirmed influenza pneumonia was 56.7% (95% CI, 31.9-72.5%) [10].…”

“…Our IVE estimates against influenza pneumonia in older adults may be higher than generally expected values. IVE is commonly lower for severe outcomes than for medically attended influenza and is lower in older adults than in children [3,9]. In addition, IVE is usually lower for the H3N2 stain than for the H1N1pdm09 strain [4].…”

“…However, its clinical benefit has long been discussed because vaccine responses are reduced by an age-related decline in adaptive immunity [6,7]. Positive results have been reported from recent meta-analyses: influenza vaccines reduce medically attended influenza by 20-44% [8] and influenza-associated hospitalization by 37% in older adults [9]. However, evidence is lacking for the protective effect of influenza vaccination on influenza pneumonia, including primary influenza pneumonia and secondary bacterial pneumonia.…”

The impact of repeated vaccination using 10-year vaccination history on protection against influenza in older adults: a test-negative design study across the 2010/11 to 2015/16 influenza seasons in Ontario, Canada

“…Influenza vaccination is the primary strategy to prevent influenza-related morbidity and mortality, especially for older adults, who are at higher risk of severe outcomes [1]. In this age group, influenza vaccines are 24-63% effective in preventing laboratory-confirmed influenza [2][3][4]. Due to frequent changes in circulating virus strains, annual vaccination is recommended.…”