Enrollment at each study site began when the percentage of clinical laboratory specimens testing positive for influenza began to increase in the community or on the week of 17 January 2011, whichever came first, and ended after either 12 weeks of surveillance or 2 weeks without cases. Accordingly, the period of enrollment was 17 January 2011 to 14 April 2011 at the sites in Marshfield, Wisconsin; 1 December 2010 to 27 April 2011 at the sites in Ann Arbor and Detroit, Michigan; 24 December 2010 to 1 May 2011 at the sites in Rochester, New York; and 4 December 2010 to 26 March 2011 at the sites in Nashville, Tennessee. During this period, 5137 subjects were enrolled in the study of which 1113 (22%) were influenza positive. The epidemic curve of enrollment of virus-positive cases and virus-negative controls is shown in Figure .
Numbers of influenza-positive acute respiratory illness cases (red bars) and influenza reverse transcription polymerase chain reaction–negative acute respiratory illness controls (blue bars) by week of enrollment.
In total, 380 subjects were excluded from the final analysis of effectiveness, including 74 virus-positive and 306 virus-negative subjects (Figure ). The main reason for exclusion from the analysis was inability to verify vaccination history from medical records, which resulted in exclusion of 306 of 5122 (6%) potential subjects. Other reasons for exclusion included determination that the onset of symptoms was >7 days prior to enrollment (59 subjects), inconclusive rRT-PCR results (13 subjects), and inadvertent enrollment of infants too young to receive influenza vaccine (2 subjects). In addition, 45 subjects who received vaccine within 14 days of illness onset were also excluded from the analysis of VE.
Numbers of subjects enrolled and excluded from the final analysis of vaccine effectiveness. PCR, polymerase chain reaction.
The characteristics of the subjects analyzed in the study are shown in Table . Influenza cases were more likely than rRT-PCR–negative ARI controls to be enrolled in the emergency department or outpatient settings and less likely to be enrolled in the hospital setting. Cases were more likely than controls to be aged 9–49 years, non-white, and uninsured. Cases were less likely than controls to have recognized influenza high-risk conditions, and cases tended to have a shorter duration of symptoms prior to sampling than did the controls.
Descriptive Characteristics of Enrolled Patients With Medically Attended Acute Respiratory Infections by Case/Control Status
Regardless of whether they were cases or controls, unvaccinated subjects were more likely to be seen in the emergency department, to be aged 9–49 years, to be non-white, and to lack health insurance (Table ). In addition, presence of an influenza high-risk condition was associated with increased likelihood of vaccination. The great majority of vaccinated subjects in each age group studied received inactivated influenza vaccines, and overall only 8% of the subjects received live attenuated influenza vaccine (LAIV). The most commonly administered vaccine was Fluzone (Sanofi Pasteur; trivalent inactivated vaccine containing 15 μg hemagglutinin of each component), which accounted for 69% of all of the vaccines received by subjects in the analysis. Only 11 subjects received the high-dose Fluzone (Sanofi Pasteur; trivalent inactivated vaccine containing 60 μg HA of each component).
Descriptive Characteristics of Enrolled Patients With Medically Attended Acute Respiratory Infections by Vaccination Status
The overall age-adjusted VE for receipt of inactivated or live attenuated vaccine was 60% (95% CI, 53%–66%; Table ). Vaccine effectiveness was similar by age group but declined among those aged ≥65 years. In this age group, VE was 38% and was not statistically significant. However, because relatively few elderly subjects were evaluated, the estimate of VE in this age group was imprecise. There was substantial VE in children aged 6 months–2 years (58%; 95% CI, 31%–74%), although the estimate was slightly lower than that in children aged 3–8 years (69%; 95% CI, 56%–77%). The overall VE in children aged 6 months–8 years was 63% (95% CI, 52%–72%). Among vaccinated children aged 6 months–8 years, 704 of 1029 (68%) had been fully vaccinated, and 325 of 1029 (32%) had been partially vaccinated, according to ACIP recommendations [6
]. Adjusted VE for fully vaccinated children was 68% (95% CI, 56%–77%) and was 55% (95% CI, 36%–68%) for partially vaccinated children.
Percent Vaccinated by Case/Control Status and Crude and Adjusted Vaccine Effectivenessa by Age Group and Vaccine
Because LAIVs are currently licensed for use in individuals aged 2–49 years, we also made specific estimates of VE for LAIVs in this age range (Table ). The effectiveness of at least 1 dose of LAIV in children aged 2–8 years was similar to that of Trivalent Inactivated Vaccine in this age group (adjusted VE, 70%). Effectiveness of LAIVs in those aged 9–49 year olds was lower (adjusted VE, 41%), as was VE for inactivated vaccine (adjusted VE, 52%). However, because LAIVs were rarely used in this age group, the estimate was not precise. Our results suggested that VE for LAIVs was higher among enrolled subjects aged 2–8 years than among those aged 9–49 years.
Vaccine effectiveness did not vary by enrollment site. For subjects enrolled as outpatients, adjusted VE was 59% (95% CI, 52%–67%); for those enrolled in the emergency department, it was 61% (95% CI, 40%–75%); and for those enrolled as inpatients, VE was 61% (95% CI, 38%–76%). Adjusted VE was slightly higher in individuals without a known influenza high-risk condition (62%; 95% CI, 53%–69%) than in those with high-risk conditions (54%; 95% CI, 40%–64%).
During the study period, we detected 334 cases of influenza A H3N2, 373 cases of influenza A H1N1, and 333 cases of influenza B. All viral isolates assessed at the CDC for antigenic relatedness to the vaccine strains by hemagglutination inhibition tests using postinfection ferret antisera were antigenically similar to the vaccine strains. Adjusted VE estimates by influenza type and subtype are shown in Table . Vaccine effectiveness was similar for each of the 3 components of the vaccine among children, and although lower overall, VE was also similar between types and subtypes in adults aged ≥50 years. However, the estimates of VE for influenza A H3N2 and influenza B in adults aged 9–49 years were substantially lower than for influenza A H1N1 and were also lower than the estimates in other age groups.
Adjusted Vaccine Effectiveness for Influenza Type and Subtype