A systematic review of the evidence on the effectiveness and risks of inactivated influenza vaccines in different target groups

Abstract

Purpose

To systematically review the evidence regarding the efficacy, effectiveness and risks of the use of inactivated influenza vaccines in children, healthy adults, elderly individuals and individuals with co-morbidities such as diabetes, chronic lung disease, cardiovascular disease, kidney or liver disease and immune suppression.

Methods

The Cochrane database of systematic reviews was searched for relevant reviews and supplemented with searches of the Cochrane Central Register of Controlled Trials database and Medline. Two reviewers independently assessed review and trial quality and extracted data.

Results and conclusions

The inactivated influenza vaccine has been proven effective in preventing laboratory-confirmed influenza among healthy adults (16–65 years) and children (≥6 years) (GRADE A evidence). However, there is strikingly limited good-quality evidence (all GRADE B, C or not existing) of the effectiveness of influenza vaccination on complications such as pneumonia, hospitalisation and influenza-specific and overall mortality. Inconsistent results are found in studies among children younger than 6 years, individuals with COPD, institutionalised elderly (65 years or older), elderly with co-morbidities and healthcare workers in elderly homes, which can only be explained by bias of unknown origin. The vaccination of pregnant women might be beneficial for their newborns, and vaccination of children might be protective in non-recipients of the vaccine of all ages living in the same community (one RCT, Grade B evidence).

Introduction

The vaccines currently used against seasonal influenza contain antigens against three influenza strains (A/H1N1, A/H3N2 and B), which are altered yearly to target the strains that are predicted to circulate in the upcoming season (WHO) [1].

In Europe, only inactivated vaccines, i.e., “killed” whole virion, split virion (fragmented envelopes) or subunit (purified envelope antigens) vaccines are used [2]. More recently, and especially for the A/H1N1 pandemic influenza strain, new (adjuvanted) vaccines were introduced worldwide. Live attenuated vaccines have been available in the United States of America since 2003 but were only recently approved for use in the European Union [3]. The immune response to inactivated influenza vaccines, which is measured by counting haemagglutinin antibodies in the serum, begins one week after vaccination and peaks between 2 and 4 weeks [4]. After vaccination with an inactivated vaccine, the protective immune response lasts for 6–12 months in healthy adults [5]. In general, children and elderly individuals have lower immune responses [4].

The yearly influenza vaccination of at-risk individuals became common practice worldwide after the Second World War [6]. Elderly individuals (65 or older), who account for approximately 90% of all influenza-related deaths [7], chronically ill individuals regardless of age and children with chronic acetylsalicylic acid (ASA) intake are the most important target groups [8]. Until now, the European guidelines have not found enough evidence to target other groups, but caregivers, health care workers and pregnant women are strongly advised to receive vaccinations [8]. In general, the European Guidelines [8] are more conservative than those in the United States of America [9]. An extensive literature search was performed to evaluate vaccination against seasonal influenza in primary care. We looked for evidence of efficacy (against laboratory-proven influenza only, unless stated otherwise), effectiveness (against clinically defined influenza-like illness, unless stated otherwise) and potential risks of the use of inactivated vaccines in several target groups: adults (16–65 years), healthy children (younger than 16 years), elderly (65 years or older), pregnant women, healthcare workers and individuals of all ages with chronic medical conditions.