Influenza vaccination of healthcare workers in acute-care hospitals: a case-control study of its effect on hospital-acquired influenza among patients

Data were extracted from a hospital-based, prospective surveillance study of ILI detailed elsewhere [9]. Briefly, this prospective surveillance study enrolled all ILI patients hospitalised between October 15 and April 15 in 2004-05, 2005-06 and 2006-07, in Edouard Herriot Hospital (Lyon, France), a tertiary, acute-care university hospital with 1,000 beds. Totally, 36 (84%) of the hospital's 43 adult short-stay units participated on a voluntary basis: 12 with 224 beds in 2004-05, 29 with 493 beds in 2005-06, and 30 with 537 beds in 2006-07. No specific infection transmission control measures were implemented during the study period. Standard procedures were followed throughout the hospital, with droplet precautions in case of ILI. Once a day, research nurses contacted participating units to search for new patients with ILI, defined as rectal or axillary temperature ≥ 37.8 C, in the absence of antipyretics, with cough or sore throat [10]. All incident cases of ILI during hospital stay were included. At ILI diagnosis, the following variables were analysed: date of admission and discharge, underlying diseases, start and end dates of clinical ILI features, potential sources of exposure to influenza within 5 days before ILI or influenza occurrence, outcome, influenza vaccination status and vaccination date. On the day of ILI suspicion, nasal swab testing served to confirm influenza in cases and controls. When incident ILI was detected (in patients or HCW), a research nurse visited the unit twice daily to document case follow-up and to find secondary cases, which were included in the surveillance according to clinical criteria similar to those for other ILIs. Each secondary ILI case was followed as an incident case, and the whole unit was monitored for 10 days after incident case onset to detect secondary cases. A potential influenza source was defined as the presence of at least 1 person with ILI (patient or HCW) in the units considered as being contagious, within 5 days before onset-from 1 day preceding ILI to 4 days thereafter.

A nested case-control investigation was conducted in this prospective surveillance study of hospital-acquired ILI [9]. Cases were patients with virologically-confirmed influenza occurring ≥ 72 h after admission in acute-stay units [1]. Controls were patients with ILI during hospitalisation with negative influenza results after nasal swab testing. Four controls per case, matched per influenza season (2004-05, 2005-06 and 2006-07), were randomly selected among all eligible controls. The exposure of interest was the proportion of HCW vaccinated against influenza in these units, collected prospectively by the occupational health department of the hospital. HCW vaccination was confirmed by occupational health department data. All HCW categories were included: physicians, nursing staff, ancillary and allied health staff. The proportion of vaccinated HCW was dichotomised according to the median of its distribution. Potential confounders were gender, likely sources of influenza in the same ward (other patients or HCW) within 5 days before influenza or another ILI occurrence during hospital stay, individual patient vaccination against influenza, type of ward, and underlying disease. Clinical suspicion of influenza was based on the above definition.

Categorical variables were compared by Fisher's exact test, and continuous variables, by the Mann-Whitney U-test. Conditional logistic regression was undertaken to assess factors associated independently with HAI among patients. Covariates with P < 0.15 after univariate analysis as well as gender and age were entered into the initial multivariate model, backward step-wise regression analysis was conducted, and the likelihood ratio test compared models until P < 0.15. Potential interactions between variables of the final model were tested 2 by 2. All tests were 2-tailed, and P < 0.05 was considered significant. The data were analysed by Stata software 8.0 (StataCorp LP 2003, College Station, TX). The protocol design was approved by the hospital's institutional review board. All patients received study information and gave signed, informed consent.

Among 55 patients analysed overall, 11 (20%) had laboratory-confirmed HAI. Median age was 77.3 years, and 41 (75%) were female. Totally, 13 (23%) were hospitalised in a medical unit, 8 (15%) in a surgical unit, 8 (15%) in an obstetrics-gynaecology unit, 26 (47%) in a short-term elderly patient unit, and none in an intensive care unit. Seven (13%) had chronic pulmonary disease, 26 (47%) had chronic cardiac disease, and 2 (4%) were immuno-compromised. One patient died during hospitalisation (unrelated to influenza). Twenty (36%) patients had at least 1 potential patient or HCW source of influenza infection in the same ward within 5 days before ILI or influenza occurrence. The median HCW vaccination rate in the units was 36% (0% to 67%) with a mean of 34%.

Figure 1 shows the repartition of cases and controls according to HCW vaccination rates in the units. The median proportion of vaccinated HCW in these units was 11.5% for cases vs. 36.1% for the controls (P = 0.11). After univariate analysis (Table 1), the presence of at least 1 influenza source in the ward increased the risk of HAI. After multivariate analysis (Table 2), a proportion of vaccinated HCW of more than 35% in the units, compared to a lower proportion, was protective against laboratory-confirmed HAI among patients (odds ratio = 0.07; 95% confidence interval 0.005-0.98), after adjusting for age and the presence of potential influenza sources in the units.