Figure

Figure. . . . Study selection for a review of the vaccination of health care workers to protect patients at risk for acute respiratory disease.

The full study protocol is registered with the UK National Institute for Health Research International Prospective Register of Systematic Reviews (www.crd.york.ac.uk/PROSPERO [registration no. CRD420111092]). We searched several electronic health care databases, sources of evidence-based reviews, guidelines, and gray literature in accordance with the specifications of each database (Figure). In addition, we contacted domain experts and vaccine manufacturers to identify unpublished data and undertook citation and reference tracking for all included papers. Thesaurus-indexed and free text terms were defined for the population, intervention, and outcome parameters; peer reviewed; and adapted as necessary for each search engine.

Eligibility criteria were defined a priori as follows:

• Types of study: any experiment, observational study, or systematic review reporting on the effectiveness of vaccination (including influenza or pneumococcal vaccines) of HCWs for protecting patients at higher risk for severe or complicated respiratory infection.

• Types of participants: persons at higher risk for severe or complicated illness as a result of acute respiratory infection (as defined in World Health Organization [1] and Advisory Committee on Immunization Practices guidance [17]), who have received or are receiving care from an HCW.

• Types of intervention: influenza or pneumococcal vaccination of any worker providing medical, nursing, social, or personal health care (because no uniformly accepted definition of an HCW exists, it was defined by the peer-reviewed terms specified in the search strategy).

• Types of outcome measure: cases or consultations, death or hospitalization for acute respiratory disease, influenza, ILI, or pneumococcal disease.

Published and unpublished reports from any year that were written in Chinese, English, French, Japanese, Portuguese, Russian, or Spanish were considered. A 3-stage process was used to assess eligibility for inclusion screening first by title, then abstract, and then full text. Two reviewers undertook this in parallel for stages 1 and 2 and independently for stage 3. Consensus was reached by discussion; when reviewers disagreed, a third reviewer was consulted for a final decision. Where multiple reports were identified for the same piece of original research, the most recent peer-reviewed source was selected.

Two reviewers independently extracted data from each included, by using a predefined, piloted template. The risk for bias was assessed by using the Cochrane Collaboration tool (20) for experimental and prospective cohort studies, the Downs and Black tool (21) for other observational studies, and the US Agency for Healthcare Research and Quality (22) domain and element-based evaluation instrument for systematic reviews. Again, consensus was reached by discussion, with engagement of a third reviewer as necessary. No additional information was sought from corresponding authors. Data were synthesized qualitatively by using a narrative approach in accordance with the framework described by the Economic and Social Research Council and recommended by the University of York Centre for Reviews and Dissemination (23).

Evidence is limited for the effectiveness of vaccination of HCWs for protecting patients at higher risk for severe or complicated respiratory illness. Despite the broad question posed, extensive searching, and large number of resultant hits, our search resulted in a low yield of studies, all of which focused on influenza with no consideration for pneumococcal infection. This finding is perhaps not surprising because pneumococcal vaccination is not routinely recommended for HCWs and little, if any, evidence exists of nosocomial spread. A consistent direction of effect was observed across multiple outcome measures, with virtually all studies noting a trend toward a protective effect of vaccinating HCWs. This consistency adds to the degree of confidence in interpreting our overall findings. Given that most studies were carried out in long-term care facilities, we conclude that vaccination of HCWs against influenza is likely to offer protection for this patient group. However, future reviews that specifically examine the effect of vaccinating other outpatient providers, such as home HCWs and hospital staff in acute care, short-stay settings, would clearly be of value. These findings are more difficult to extrapolate to other at-risk groups, although some, albeit limited, evidence was identified from other settings to suggest a similar effect.

The results of all 4 RCTs (24–27) and 1 of the observational studies identified (28) previously had been pooled in a quantitative meta-analysis (19). The authors of this analysis concluded that evidence is lacking that vaccinating HCWs prevents influenza infection in elderly patients because the apparent benefits were confined to nonspecific outcome measures. We considered additional observational data that demonstrate consistency in the direction of the observed effects across specific and nonspecific outcome measures. Although the strength of evidence for more-specific measures is generally much weaker, these findings add greater weight to the hypothesis of a potential protective effect.

The recent position statement by the Society for Healthcare Epidemiology of America (38) suggests that further studies are not needed because the biological rationale for vaccination does not vary by practice setting. However, effect size might vary considerably because of patient characteristics and care patterns (staff deployment and duration of inpatient stay), and further evidence is needed among the most at-risk groups where benefits are probably greatest, to enable prioritization of resources, particularly where vaccine shortages or resource limitations might exist.

Previous authors have suggested that vaccination of HCWs might enable development of herd immunity. Realistically, herd immunity is difficult to achieve in health care settings, especially acute care short-stay settings, because of patient admissions and discharges, visitors, and staff turnover. That said, herd immunity might not be necessary to benefit patients; modeling studies (39) suggest a direct association between coverage and attack rates. Such studies (39) also suggest variation in the potential for transmission of infection by different staff groups, which should be explored in further detail.

This field of research has some inherent problems. These difficulties result in part from the difficulty of isolating the effect of HCW vaccination, disentangling it from other factors that might influence patient outcomes, such as patient vaccination (as demonstrated by Potter et al. [25]) and background influenza activity (as demonstrated by Hayward et al. [27]). Staff vaccination itself might be linked to additional confounding variables, such as organizational culture and professional beliefs. In fact, such confounding might explain the difference in findings between the work of Monto (36) and the other authors. Prospective collection of information relating to relevant transmission factors and infection control measures that were largely overlooked by the studies in this review should be used to enable appropriate adjustment in future studies. Furthermore, the most appropriate outcome measures are difficult to define because not all persons with laboratory-confirmed infection have symptoms of illness and vice versa. Future studies thus need to demonstrate consistent effects for a range of clearly defined outcomes by using valid measures across several different influenza seasons, with sufficient power to detect true underlying effects.

The findings of our review are subject to several limitations. Because 11 of the 14 primary research articles considered outcomes in long-term care facilities, generalizability to other at-risk groups is limited. In addition, we did not attempt to contact authors of original studies, and the conclusions drawn are limited by the reported detail. Although the number of reviewers was limited as far as possible, some inconsistency might have occurred in the selection, extraction, and assessment of data introducing potential bias, particularly where the opportunity for subjective judgment existed. We attempted to minimize inconsistency by using several standard assessment tools, but their use was limited by lack of information where components were not conducted because of the nature of the study design. Meta-analysis of the 4 RCTs identified had already been conducted, and although we identified additional observational data, the observed heterogeneity limited any further quantitative analysis.

Some wider possible effects of HCW vaccination, such as reduction in absenteeism because of illness, are beyond the scope of this review. Ethically, autonomy needs to be balanced with nonmaleficence, and this need must be addressed when policy decisions about vaccination are considered. Anikeeva et al. (40) reported that in a review of 15 studies focusing on the reasons staff accept influenza vaccine, self-protection was the most important. However, patient protection also was perceived as important, particularly among HCWs in settings with higher risk patients (40). Nevertheless, HCWs would be justified in claiming that the current evidence base is not especially strong and heavily weighted toward the benefits to patients receiving care in long-term care facilities, although limited evidence would not necessarily legitimize nonacceptance.

The existing evidence base is sufficient to sustain current recommendations for vaccinating HCWs on the grounds that some protection of high-risk patients against influenza seems likely. However, vaccination should be considered 1 element of a broad package of infection prevention and control measures, such as good hand and respiratory hygiene, environmental cleaning, protection against respiratory droplets, and cohorted care during outbreaks. Well-designed studies that strengthen the evidence base might increase compliance with guidelines, resulting in improved coverage.