Year: 2017
Type: article
Abstract: (See the major article by Andrew et al, on pages 405–14.) Influenza causes annual epidemics of varying severity that affect persons of all ages. In the older adult population, influenza constitutes a particularly important public health burden. In population-based modeling studies in the United States, hospitalization rates are consistently highest among persons aged ≥65 years of age [1]. Similarly, deaths are much more frequent among older persons than younger persons. In a modeling analysis of population-based surveillance data covering the 2010–2011 through the 2012–2013 seasons in the United States, an estimated 71%–85% of influenza-associated deaths occurred among adults aged ≥65 years [2]. Among those 65 years and older, certain factors such as chronic medical conditions, frailty, and residence in an institution or nursing home further increase the risk of influenza-associated morbidity and mortality. Despite the decades-long recommendation for universal vaccination of persons aged ≥65 years, coverage rates for influenza vaccination remain stagnant and well below the Healthy People 2020 target of 90% [3]. The estimated coverage was only 63.4% for the 2015–2016 season for persons aged ≥65 years [4]. Vaccination coverage of this degree is unacceptable for our childhood immunization programs, yet has become the accepted norm for adults. In 2050, the population aged ≥65 years is projected to increase to 83.7 million, almost double the estimated population of 43.1 million in 2012 [5]. As the United States and other industrialized countries continue to experience this considerable growth in their older adult populations, preventive measures that maintain the health and productivity of individuals will be increasingly important. Lack of confidence in vaccine performance may adversely affect vaccine uptake. The effectiveness of influenza vaccines in older persons has been questioned. Given the known consequences of influenza illness in persons aged ≥65 years and the longstanding recommendations for its use, randomized placebo-controlled trials would be difficult to justify. Ideally, we would assess vaccine performance through comparative trials of 2 influenza vaccines, although these are expensive and not feasible on an annual basis. A more practical alternative is an observational study design, with the inherent challenges of adequately controlling for bias and confounding. In this issue of The Journal of Infectious Diseases, Andrew and colleagues use a test-negative case-control design to evaluate the effectiveness of influenza vaccination to prevent hospitalizations in persons aged ≥65 years [6]. The source of the cases was an active influenza surveillance system including approximately 16000 adult acute care beds in sentinel hospitals across Canada. Cases were those who met broad clinical criteria for sample collection and tested positive for influenza at any time during their hospitalization. Controls met the same sample collection criteria and tested negative for influenza. In addition to age, use of antiviral medications, and other health, behavioral, and sociodemographic characteristics, the authors assessed frailty using a validated frailty index [7]. In adjusted analyses, the authors reported a vaccine effectiveness against any strain of influenza in persons aged ≥65 years to be 58.0% (95% confidence interval, 34.2%–73.2%). Interestingly, age was not a significant factor in the final model. Frailty and number of children aged ≤5 years living in the household were the only covariates that contributed significantly to the model. Adjusted vaccine effectiveness ranged from 77.6% for nonfrail to no efficacy for the most frail patients [6]. This article adds important knowledge to our understanding of influenza vaccine performance. Importantly, as demonstrated here and elsewhere, influenza vaccine prevents hospitalization—a serious disease endpoint—in addition to ambulatory laboratory-confirmed influenza, the outcome measure for most clinical trials and case-control studies [1, 6, 8]. Furthermore, frailty was more important than age as a predictor of vaccine performance. This could have implications in regard to how we develop and deploy newer, more immunogenic influenza vaccines. The results emphasize the importance of influenza vaccine for everyone who has contact with frail older persons, to reduce the chances of transmitting influenza viruses to them. Several influenza vaccine formulations are now available for persons aged ≥65 years, including formulations designed specifically to enhance immunogenicity and vaccine performance. The formulations licensed and available for this age group include standard trivalent and quadrivalent vaccine, high-dose trivalent vaccine, MF-59 adjuvanted trivalent vaccine, and recombinant trivalent influenza vaccine. The Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices currently expresses no preference for any one of these vaccine formulations over another for this age group [1]. Head-to-head immunogenicity data support that both the high-dose influenza vaccine and the adjuvanted influenza vaccine are more immunogenic than standard-dose vaccine among persons aged ≥65 years [9, 10]. Furthermore, in a randomized controlled trial comparing high-dose vs standard-dose influenza vaccine conducted among >30000 community-dwelling persons aged ≥65 years, high-dose influenza vaccine was 24.2% more effective in preventing laboratory-confirmed influenza illness [11]. Subsequently, observational studies have supported an advantage for high-dose vaccine over standard vaccine in prevention of hospitalizations and deaths [12, 13]. Although immunogenicity and observational studies support the superiority of the adjuvanted product over the standard influenza vaccine, no randomized clinical trial comparisons are currently available [10, 14]. Likewise, no data directly comparing high-dose to adjuvanted influenza vaccines are available. As demonstrated by Andrew et al, persons aged ≥65 years are a heterogenous group in regard to frailty. All should receive influenza vaccine. For some older persons, the primary motivation for receiving influenza vaccine will be to avoid both serious complications of influenza as well as less serious illness that interferes with their ability to work, travel, and enjoy a physically active lifestyle. For others, the strongest motivation may be to decrease the risk of transmitting influenza to the more vulnerable persons with whom they have contact—friends or spouses who are more frail, for example, or grandchildren who are <6 months of age and unable to receive the vaccine. As healthcare providers, we need to continue to educate our patients and to strongly recommend the influenza vaccine. As researchers, our challenge is to assess vaccine effectiveness using the best possible methodologies, and to discern differences in the performance of different vaccine formulations in specific populations. These data, along with data from head-to-head vaccine comparisons, will best guide influenza vaccine policy going forward. Potential conflicts of interest. W. H. C. has served on the advisory boards of GlaxoSmithKline and Novavax. K. M. N. reports no potential conflicts of interest. Both authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
Authors: Kathleen M Neuzil, Wilbur H Chen
Institution: University of Maryland, Baltimore
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2736733159