Dec 2, 2008 (CIDRAP News) – Researchers who surveyed thousands of Minnesota college students over four years found that those who got flu shots had a 30% lower rate of flu-like illness during flu seasons than those who skipped the shots, according to a report published this week.
Those who received flu shots also were significantly less likely to go to a doctor or bungle an assignment or test because of an influenza-like illness (ILI), according to the report by Kristin L. Nichol, MD, MPH, and colleagues, of the Minneapolis VA Medical Center and the University of Minnesota. Their report was published yesterday in the Archives of Pediatrics and Adolescent Medicine.
"Influenza vaccination was associated with substantial reductions in ILI and ILI-associated health care use and impairment of school performance," the report states. "College and university students can experience substantial benefits from influenza vaccination."
College-age people are not among those for whom flu shots are officially recommended, unless they happen to be close contacts of others who are at risk for serious flu complications. This year, however, the Centers for Disease Control and Prevention (CDC) extended flu immunization recommendations to include all children aged 5 through 18.
On the basis of previous research, Nichol and colleagues estimated that from 9% to 20% of college students come down with the flu each year. To assess the effects of flu shots in students, they conducted an Internet-based survey at the University of Minnesota during four successive flu seasons, from 2002-03 through 2005-06. In the last season they also included St. Olaf College in Northfield, Minn.
Internet surveys used
Each October, all full-time students were invited by e-mail to participate in the study, which included baseline and follow-up surveys conducted on a secure Web site. The primary outcome measure was the percentage of students experiencing an ILI—defined as a respiratory illness with fever and cough—during the flu season. The surveys covered November through March, but the flu season was defined retrospectively using data from the Minnesota Department of Health.
To limit bias, the researchers in their statistical analysis adjusted for differences between vaccinated and unvaccinated groups in a number of variables, including age, sex, high-risk status (due to diabetes, asthma, or heart disease), smoking status, general health level, and number of recent physician visits. Also, to limit the possibility that apparent benefits of vaccination would not represent actual reductions in flu cases, they assessed ILI rates in months that were covered by the surveys but were not part of the flu season.
Over the 4 years, the researchers recruited 12,975 students who completed a baseline and at least one follow-up survey and gave their vaccination status. Overall, 30.2% of the students reported being vaccinated. Vaccinated students were somewhat older than unvaccinated ones and were slightly more likely to be women. (About 71% of participants in the study overall were women.)
Close to a quarter of the students—24.1%—reported an ILI during the flu season. That included 20.9% of vaccinated students and 25.5% of the others. After adjustment for potential confounding variables, that translated into a 30% reduction in ILI (adjusted odds ratio [OR], 0.70; 95% confidence interval [CI], 0.56-0.89).
As measured by certain secondary outcomes related to ILI, the benefits of vaccination were even greater, according to the report. The immunized students were 47% less likely to see a healthcare provider for an ILI (adjusted OR, 0.53; 95% CI, 0.35 to 0.82), 46% less likely to use antibiotics (adjusted OR, 0.54; 95% CI, 0.32 to 0.90), 40% less likely to do poorly on an assignment (adjusted OR, 0.60; 95% CI, 0.40 to 0.90), and 47% less likely to do poorly on a test (adjusted OR, 0.53; 95% CI, 0.31 to 0.88).
The investigators found that immunized students lost significantly fewer days to illness than did the unvaccinated students. Overall, one day of ILI was prevented for every two people vaccinated, the report says.
Illness in non-flu months
The analysis showed that, in contrast to the findings for the flu season, vaccinated and unvaccinated students had nearly the same rates of ILI during non-flu periods (adjusted OR, 0.98; 95% CI, 0.73 to 1.3). "These findings suggest that our multivariable models performed well and do not suggest significant bias," the report says. In light of previous findings, the authors estimate that between 30% and 79% of the ILIs reported by the students were actual flu cases.
During the 4-year study period, the only season in which the flu vaccine matched up poorly with the predominant viruses in circulation was 2003-04. In analyzing that year's data separately, the authors found that the benefits of vaccination held up: immunized students had a 31% lower rate of ILI (adjusted OR, 0.69; 95% CI, 0.56 to 0.84).
The authors comment that previous studies of flu vaccine effectiveness in younger adults have mostly focused on working people. "Our study extends previous observations by clarifying the benefits of vaccination specifically among college and university students," they write. They also say that by following students for 4 years, they limited the risk of getting misleading results that comes with focusing on just one or two seasons.
At the same time, the researchers acknowledge certain limitations of their study. Because it is an observational study, there is a chance of "residual confounding" despite the adjustments for covariates, they say. Also, the reliance on self-reporting may have led to misclassification of some participants' vaccination status, and the Minnesota students may not have been fully representative of students nationwide.
The next flu-vaccine target group?
Lone Simonsen, PhD, MS, a George Washington University professor who has argued that some observational studies exaggerated the benefits of flu vaccination , especially in the elderly, welcomed the findings but raised questions about a couple of details. Simonsen is visiting professor and research director in George Washington's Department of Global Health.
"All in all, this is a study that highlights the benefits to an age-group that is probably the next on the target list going towards universal immunization: college kids," she told CIDRAP News via e-mail. "Previous studies have struggled to see the benefits in this age-group because the severe outcomes are so very low (hospitalizations for example)."
Calling the use of Internet reporting of ILI "interesting," Simonsen said she would be concerned about validity, but she found it reassuring that the vaccinated and unvaccinated students had about the same ILI rates in the non-epidemic periods. "It is good that Nichol et al now embrace this strategy for testing for confounding bias," she said, adding, "One thing that bothers me a tad is that the non-epidemic winter period findings are not shown in tables and figures—it is a very important aspect of the study."
"I am not surprised that influenza vaccine can prevent 30% of ILI episodes in periods when influenza circulate—this is consistent with a good vaccine response as the authors conclude, similar to the expected 70% to 90% VE [vaccine effectiveness] for a laboratory-confirmed [influenza]," Simonsen said.
The one "big surprise" to her was that benefits of vaccination persisted in the season when the vaccine was not a good match for circulating viruses. "The authors see this as a great thing—but it makes me wonder how this can be true, and if it is true, does that mean we shouldn't bother with all that effort to identify antigenically matched vaccine strains each season," she said.
Simonsen said Nichol and colleagues cite several studies that showed good vaccine effectiveness in "mismatched seasons," but she knows of several others that showed much poorer results. "So I'd say the jury is still out on this one," she commented.
Nichol KL, D'Heilly S, Ehlinger EP. Influenza vaccination among college and university students: impact on influenzalike illness, health care use, and impaired school performance. Arch Ped Adol Med 2008 Dec;162(12):1113-8 [Abstract]
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