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A letter to the editor is presented in response to the article "Influenza vaccination: policy versus evidence," by T. Jefferson in the October 28, 2006 issue.

Replies to a comment by Hak and colleagues on the authors' study regarding the incremental benefits of pneumococcal vaccination over influenza vaccination alone among community-dwelling elderly persons. Evidence of the independent contributions of pneumococcal vaccinations in the high-risk cohort.

Abstract: With a retrospective nationwide cohort study in the Netherlands over 1992–2003, using mortality and viral surveillance data, the aim was to assess by means of rate difference methods the influenza-associated mortality in the elderly before and after the introduction of a nationwide influenza vaccination program in 1996 (vaccination coverage raised from below 50 to 80%). The average annual influenza-associated mortality declined in the years before and after the introduction from 131 to 105 per 100,000 persons (relative risk 0.80). The decline was largest in the age group 65–69 years (relative risk 0.54) and less in those aged 75 years and older. Validation by Serfling-type regression analysis revealed similar results. In conclusion, routine influenza vaccination among Dutch elderly was associated with a significant decrease in influenza-associated mortality, notably in those aged 65–69 years. [Copyright &y& Elsevier]

Abstract: Objectives: Although Internet-based surveys are becoming more common, little is known about agreement between administrative claims data and Internet-based survey self- and proxy-reported health care resource utilization (HCRU) data. This analysis evaluated the level of agreement between self- and proxy-reported HCRU data, as recorded through an Internet-based survey, and administrative claims–based HCRU data. Methods: The Child and Household Influenza-Illness and Employee Function study collected self- and proxy-reported HCRU data monthly between November 2007 and May 2008. Data included the occurrence and number of visits to hospitals, emergency departments, urgent care centers, and outpatient offices for a respondent''s and his or her household members'' care. Administrative claims data from the MarketScan® Databases were assessed during the same time and evaluated relative to survey-based metrics. Only data for individuals with employer-sponsored health care coverage linkable to claims were included. The Kappa (κ) statistic was used to evaluate visit concordance, and the intraclass correlation coefficient was used to describe frequency consistency. Results: Agreement for presence of a health care visit and the number of visits were similar for self- and proxy-reported HCRU data. There was moderate to substantial agreement related to health care visit occurrence between survey-based and claims-based HCRU data for inpatient, emergency department, and office visits (κ: 0.47–0.77). There was less agreement on health care visit frequencies, with intraclass correlation coefficient values ranging from 0.14 to 0.71. Conclusions: This study''s agreement values suggest that Internet-based surveys are an effective method to collect self- and proxy-reported HCRU data. These results should increase confidence in the use of the Internet for evaluating disease burden. [Copyright &y& Elsevier]

Abstract: Major national surveys do not collect the influenza vaccination status of all household members, thus limiting current understanding of household influenza vaccination patterns. In an early 2009 telephone survey of 800 households in the metropolitan Minneapolis-St Paul area, household respondents reported the age, gender, and 2008–2009 seasonal influenza vaccination status of all household members. After poststratification to adjust for nonresponse, the full household influenza vaccination rate for multiperson households is 35.2%, partial household influenza vaccination rate is 39.9% and the rate of complete household nonvaccination is 24.9%. Full household influenza vaccination is more common in households with an elderly resident, intermediate in households with a child under 5years of age, and less common in the remaining households. No household members are vaccinated in approximately 10% of multiperson households with either an elderly adult or young child; the corresponding rate in other households is 32.8%. An estimated 51.4% of households with children over 1 year of age have all children vaccinated against influenza; 43.5% of households with children had no children vaccinated against influenza. Households with younger children are more likely to have all children vaccinated and less likely to have no children vaccinated. We believe this is the first study to describe the prevalence of household influenza vaccination patterns. Continued efforts to monitor and increase household vaccination may be a valuable strategy to protect individuals and communities from influenza. [Copyright &y& Elsevier]

The article presents a study on the effect of various flexible sick leave policies (FSLPs) on workplace attendance of employees with self reported severe-influenza-like-illness (ILI) symptoms in the U.S. The study used a multivariate analyses to estimate the impact of FSLPs on employees' workplace attendance while they were experiencing severe ILI symptoms. The study finds that average duration of severe ILI symptoms are 3.0 days and that the employees who could telework has 29.7% lower rate.

Abstract: Acute respiratory illnesses (ARI), comprising influenza-like illness (ILI) and other wintertime respiratory illnesses (ORI), impose substantial health and economic burdens on the United States. Little is known about the impact of ILI among household members (HHM), particularly children, on employees’ productivity. To quantify the impact of employee and HHM-ILI and ARI on employee productivity, a prospective, observational cohort study was conducted among employees from three large US companies. Employees who had at least one child living at home (N =2013) completed a monthly survey during the 2007–2008 influenza season, reporting the number of days missed from work and hours of presenteeism due to: (1) personal ILI, (2) HHM-ILI, and (3) personal and HHM-ARI. Employee ILI ranged from 4.8% (April) to 13.5% (February). Employees reporting ILI reported more absences than employees not reporting ILI (72% vs 30%, respectively; P <0.001). Overall, 61.2% of employees surveyed had at least one child with an ILI; these employees missed more days of work due to HHM illness than employees without an ARI-ill child (0.9 days vs 0.3 days, respectively; P <0.001). Employees with ILI were less productive, on average, for 4.8h each day that they worked while sick, 2.5h of which was attributable to ILI. HHM illnesses accounted for 17.7% (1389/7868 days) of employee absenteeism, over half of which was due to HHM-ARI. ILI causes a significant amount of employee absence. Household members, particularly children, comprise a sizable proportion of general illness and injury-related employee absences. [Copyright &y& Elsevier]

Abstract: Older adults (≥65 years of age) are particularly vulnerable to influenza illness. This is due to a waning immune system that reduces their ability to respond to infection, which leads to more severe cases of disease. The majority (∼90%) of influenza-related deaths occur in older adults and, in addition, catastrophic disability resulting from influenza-related hospitalization represents a significant burden in this vulnerable population. Current influenza vaccines provide benefits for older adults against influenza; however, vaccine effectiveness is lower than in younger adults. In addition, antigenic drift is also a concern, as it can impact on vaccine effectiveness due to a mismatch between the vaccine virus strain and the circulating virus strain. As such, vaccines that offer higher and broader protection against both homologous and heterologous virus strains are desirable. Approaches currently available in some countries to meet this medical need in older adults may include the use of adjuvanted vaccines. Future strategies under evaluation include the use of high-dose vaccines; novel or enhanced adjuvantation of current vaccines; use of live attenuated vaccines in combination with current vaccines; DNA vaccines; recombinant vaccines; as well as the use of different modes of delivery and alternative antigens. However, to truly evaluate the benefits that these solutions offer, further efficacy and effectiveness studies, and better correlates of protection, including a precise measurement of the T cell responses that are markers for protection, are needed. While it is clear that vaccines with greater immunogenicity are required for older adults, and that adjuvanted vaccines may offer a short-term solution, further research is required to exploit the many other new technologies. [Copyright &y& Elsevier]

Background: The clinical features and incidence of human coronavirus (HCoV) infections in chronically ill older adults need better definition.Methods: HCoV infection was determined on the basis of a 4-fold increase in serum antibody and the detection of HCoV by reverse-transcription polymerase chain reaction. Laboratory-documented influenza (LDI) was detected by serologic assay and culture. HCoV illnesses were compared with other acute respiratory illnesses identified by active surveillance, during the 1998-99 winter respiratory-virus season, of 2215 patients with chronic obstructive pulmonary disease who were > or = 50 years old and who received influenza vaccines.Results: HCoV-229E and HCoV-OC43 were associated with 90 (14%) of 665 illnesses (HCoV-229E in 22, HCoV-OC43 in 67, and both in 1), LDI with 107 (16%) of 678 illnesses. In multivariate logistic regression analysis, myalgia was less likely with HCoV infection than with LDI (OR, 0.27 [95% confidence limit, 0.13-0.58]). A majority of these HCoV and LDI illnesses exhibited each of 11 symptoms and signs of acute respiratory illness. Spirometric results worsened most often with LDI, and many acute respiratory illnesses, regardless of etiology, were associated with hospitalization. A total of 8 illnesses were associated with HCoV-NL63, 1 with HCoV-HKU1.Conclusions: The frequencies of HCoV and LDI illnesses were similar. HCoV illness was less severe than LDI illness, was accompanied by multiple respiratory and systemic symptoms, and was associated with hospitalization. [ABSTRACT FROM AUTHOR]

Abstract: Background: Laboratory diagnosis of influenza has previously relied on viral isolation in culture. Rapid antigen tests (RATs) are now available but few studies have examined their use in older adults under routine clinical conditions. Objectives: To determine the utility of the RAT in older adults presenting to a large medical center and how test results impacted clinical care. Study design: Retrospective chart review of patients tested for influenza during the 2003–2004 and 2004–2005 influenza seasons. Clinical data were correlated with the results of laboratory testing. Results: Eighty-four adults tested positive for influenza. Adding the results of the RAT to symptom complexes predictive of influenza significantly enhanced the ability to diagnose influenza in the acute setting. The positive predictive value of fever plus cough increased from 32% to 92% with a positive RAT. The RAT also directed appropriate antiviral therapy. 20/22 (91%) patients with a positive RAT and symptoms ≤48h received antiviral treatment compared to only 1/12 (8%) patients with a negative RAT and a positive culture. Conclusions: Under routine clinical conditions rapid influenza testing enhances the ability to quickly diagnose influenza and can be used to guide early treatment decisions in older adults. [Copyright &y& Elsevier]

Objective: Influenza vaccination rates remain far below national goals in the US. Expanding influenza vaccination in non-traditional settings such as worksites and pharmacies may be a way to enhance vaccination coverage for adults, but scant data exist on the cost effectiveness of this strategy. The aims of this study were to (i) describe the costs of vaccination in non-traditional settings such as pharmacies and mass vaccination clinics; and (ii) evaluate the projected health benefits, costs and cost effectiveness of delivering influenza vaccination to adults of varying ages and risk groups in non-traditional settings compared with scheduled doctor's office visits. All analyses are from the US societal perspective. Methods: We evaluated the costs of influenza vaccination in non-traditional settings via detailed telephone interviews with representatives of organizations that conduct mass vaccination clinics and pharmacies that use pharmacists to deliver vaccinations. Next, we constructed a decision tree to compare the projected health benefits and costs of influenza vaccination delivered via non-traditional settings or during scheduled doctor's office visits with no vaccination. The target population was stratified by age (18-49, 50-64 and ⩾65 years) and risk status (high or low risk for influenza-related complications). Probabilities and costs (direct and opportunity) for uncomplicated influenza illness, outpatient visits, hospitalizations, deaths, vaccination and vaccine adverse events were derived from primary data and from published and unpublished sources. Results: The mean cost (year 2004 values) of vaccination was lower in mass vaccination ($US17.04) and pharmacy ($US11.57) settings than in scheduled doctor's office visits ($US28.67). Vaccination in non-traditional settings was projected to be cost saving for healthy adults aged ⩾50 years, and for high-risk adults of all ages. For healthy adults aged 18-49 years, preventing an episode of influenza would cost $US90 if vaccination were delivered via the pharmacy setting, $US210 via the mass vaccination setting and $US870 via a scheduled doctor's office visit. Results were sensitive to assumptions on the incidence of influenza illness, the costs of vaccination (including recipient time costs) and vaccine effectiveness. Conclusion: Using non-traditional settings to deliver routine influenza vaccination to adults is likely to be cost saving for healthy adults aged 50-64 years and relatively cost effective for healthy adults aged 18-49 years when preferences for averted morbidity are included. [ABSTRACT FROM AUTHOR]

Objective: To assess whether change in HRQOL over a seven-year period was associated with subsequent mortality and hospitalization, after adjusting for important covariates, in a cohort of U.S. Veterans., Methods: We used data from a cohort of Veterans who completed a HRQOL survey in 1998 (Short-Form 36 for Veterans [SF-36V]) and a 2006 follow-up (SF-12V) HRQOL survey and SF12V scores were calculated at both time-points. We used logistic regression analyses to model the relationship between changes in the SF12-V physical component (PCS) and mental health component (MCS) scores and 1-year hospitalization and 1-year and 3.3-year mortality after the 2006 follow-up survey., Results: 13,900 participants provided data for both the initial and follow-up surveys. We found no significant associations between changes in PCS or MCS and one-year hospitalization after adjusting for follow-up HRQOL and other covariates. We found significant but relatively weak associations between changes in MCS and our mortality outcomes., Conclusion: Given the follow-up MCS and PCS, change in PCS over the previous 7 years added little information for predicting mortality and hospitalization Although the change in MCS added some information for predicting mortality. Therefore, knowledge of patient's current HRQOL generally provides meaningful information for predicting subsequent mortality and hospitalization., (Copyright © 2021. Published by Elsevier Inc.)

Background: High-dose, inactivated, trivalent influenza vaccine (HD) is associated with higher rates of side effects than standard dose (SD) vaccine, which may represent a barrier to use., Methods: We surveyed subjects ≥65 years who received either HD or SD vaccine at the Minneapolis Veteran Affairs Health Care System clinics on October 27, 28, or 29, 2015. Research assistants conducted a 17-item telephone survey of influenza vaccine recipients to inquire about self-reported health and symptoms experienced the week after vaccination., Results: A total of 547 HD recipients and 541 SD recipients responded to the survey. The 2 groups were similar at baseline with respect to age, gender, and presence of high-risk medical conditions. At least ≥95% of individuals in both HD and SD groups reported that their overall health was the same or better than usual during the week after vaccination. Thirty-seven percent of HD recipients and 22% of SD recipients reported a local or systemic side effect ( P < .001), most of which were mild to moderate. Only 7 of 547 (1.3%) HD recipients and 3 of 541 (0.6%) SD recipients reported a severe side effect ( P = .34). There was no significant difference in healthcare visits between the groups., Conclusions: Side effects were more common among subjects ≥65 years who received HD influenza vaccine compared with SD vaccine. These side effects were well tolerated and were not associated with impairment of general health status. These findings should reassure patients and their providers of the safety and tolerability of the HD influenza vaccine., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Children have high rates of healthcare utilization due to influenza. In addition, children also transmit influenza to others in their households and the community. The costs of influenza in children include the direct medical care costs from increased outpatient visits and hospitalizations, and also indirect costs due to productivity losses especially for their parents and due to transmission of the virus to others. A variety of studies using different methods and assumptions have assessed the cost-effectiveness of influenza vaccination of children, and many find that vaccination is either cost saving or cost effective., (Published by Elsevier Ltd.)

Objective: To examine the benefit-risk profile of live attenuated influenza vaccine (LAIV) across a range of clinical scenarios in which we varied assumptions regarding both the percentage of children who would receive LAIV in lieu of trivalent inactivated influenza virus (TIV) and the extent of off-label use., Study Design: Model of expected benefits and risks of immunization of young children against influenza., Methods: We estimated expected numbers of cases of influenza illness (FLU), medically significant wheezing (MSW), and hospitalization in a single influenza season under alternative assumptions regarding use of LAIV in lieu of TIV, based on projections from a large phase III trial., Results: Assuming no use of LAIV in nonindicated children (aged <24 months and those with history of recurrent wheezing or asthma), and 50% use in lieu of TIV among children in the indicated population, there would be 2099 fewer FLU cases per 100,000 children aged 12 to 59 months, and no change in MSW or hospitalization. If LAIV also were used in lieu of TIV among 20% of children aged 12 to 23 months and 20% of children aged 24 to 59 months with a history of recurrent wheezing or asthma, there would be a further reduction of 397 FLU cases and 12 hospitalizations per 100,000 children aged 12 to 59 months, but 51 additional MSW cases., Conclusions: Our study suggests that even if LAIV were sometimes used inadvertently in clinical practice in young children for whom it is not indicated, the overall balance of expected benefits and risks would remain favorable.

Objectives: To quantify employees' preferences, as measured by willingness to pay, to prevent influenza in themselves and in their child and adult household members and to examine factors associated with willingness to pay., Study Design: Prospective observational cohort study of a convenience sample of employees from 3 large US employers. Participants had at least 1 child (< or = 17 years) living in their household for at least 4 days per week., Methods: Each month from November 2007 to April 2008, employees completed Web-based surveys regarding acute respiratory illness in their household. In the final survey, employees were presented with descriptions of influenza and questions regarding their willingness to pay to prevent influenza. Factors associated with willingness to pay were examined using multivariate ordinary least squares regression analysis of the log of willingness to pay., Results: Among 2006 employees, 31.3% were female, the mean age was 41.7 years, 85.3% were of white race/ethnicity, and the mean household size was 4.0. Employees' median (mean) willingness to pay to prevent influenza was $25 ($72) for themselves, $25 ($82) for their adult household members, and $50 ($142) (P <.01) for children. However, influenza vaccination rates were approximately equal for children (27.5%), employees (31.5%), and other adult household members (24.5%). This finding may be explained by barriers such as cost, dislike of vaccinations, and disagreement with national influenza vaccination recommendations, which were significantly associated with lower willingness to pay for prevention of influenza (P <.05)., Conclusion: Employees expressed a stronger preference to prevent influenza in their children than in themselves or other household members; however, modifiable barriers depress vaccination rates.

Randomized, controlled trials are the gold standard study design. However, ethical constraints and practical considerations may necessitate other types of studies for evaluating influenza vaccine effectiveness in the elderly--a high priority group for annual vaccination in many countries. Observational studies therefore comprise the bulk of the vaccine effectiveness evidence in older persons, but these types of studies can be susceptible to selection bias and residual confounding. All observational studies should utilize strategies to minimize the impact of bias and confounding. Recent studies questioning the plausibility of reported mortality benefits among vaccinated elderly persons may themselves be based on assumptions that are susceptible to important limitations and multiple biases. Future studies that incorporate prospectively collected information on functional status, life expectancy, and other types of data may provide additional insights into these concerns. At present, even after taking into account the potential for residual bias and confounding, most studies confirm the benefits of vaccination among the elderly for reducing hospitalization and death.

Background: Uncertainties regarding influenza disease impact and benefits of vaccination may contribute to low vaccination rates among adults aged 50-64 years., Methods: This prospective cohort study assessed the burden of influenza-like illness (ILI) among working adults aged 50-64 years and the effectiveness of influenza vaccination in reducing the rate of ILI and productivity losses. Employees of the University of Minnesota (Minneapolis) were invited via e-mail to participate in the study during October 2006. The study data were collected using internet-based surveys at baseline (October 2006) and during the follow-up period (from November 2006 through April 2007). Months included in the 2006-2007 influenza season were identified retrospectively from Minnesota Department of Health surveillance data. Vaccine effectiveness for reducing the rate of ILI, ILI-associated health care use, the number of days of illness, work loss, and reduced on-the-job productivity during the influenza season were assessed using multivariable regression models after controlling for important confounders., Results: Four hundred ninety-seven persons were included in the study, 85 (17.1%) of whom experienced an ILI. Among unvaccinated participants, ILI was responsible for 45% of all days of illness during the influenza season, 39% of all illness-related work days lost, and 49% of all days with illness-related reduced on-the-job productivity. In the multivariable regression analyses, vaccination was associated with a significant reduction in the rate of ILI (adjusted odds ratio, 0.48; 95% confidence interval, 0.27-0.86) and fewer days of illness, absenteeism, and impaired on-the-job performance., Conclusion: ILIs were common among our study participants, accounting for a large portion of illness, work loss, and impaired work performance during the influenza season. Vaccination was associated with substantial health and productivity benefits. Vaccine delivery should be improved for this high-priority group.

Background: The US Advisory Committee on Immunization Practices (ACIP) recently expanded the influenza vaccine recommendation to include children 24-59 months of age. In a large head-to-head randomized controlled trial, live attenuated influenza vaccine, trivalent (LAIV) demonstrated a 54% relative reduction in culture-confirmed influenza illness compared with trivalent inactivated influenza vaccine (TIV) among children aged 24-59 months., Objective: To evaluate the relative cost and benefit between two influenza vaccines (LAIV and TIV) for healthy children 24-59 months of age., Methods: Using patient-level data from the clinical trial supplemented with cost data from published literature, we modeled the cost-effectiveness of these two vaccines. Effectiveness was measured in quality-adjusted life years (QALY) and cases of influenza avoided. The analysis used the societal perspective., Results: Due to its higher acquisition cost, LAIV increased vaccination costs by USD7.72 per child compared with TIV. However, compared with TIV, LAIV reduced the number of influenza illness cases and lowered the subsequent healthcare use of children and productivity losses of parents. The estimated offsets in direct and indirect costs saved USD15.80 and USD37.72 per vaccinated child, respectively. LAIV had a net total cost savings of USD45.80 per child relative to TIV. One-way and probabilistic sensitivity analyses indicated that the model was robust across a wide range of relative vaccine efficacy and cost estimates., Conclusions: Due to its increased relative vaccine efficacy over TIV, LAIV reduced the burden of influenza and lowered both direct health care and societal costs among children 24-59 months of age.

Background: Laboratory diagnosis of influenza has previously relied on viral isolation in culture. Rapid antigen tests (RATs) are now available but few studies have examined their use in older adults under routine clinical conditions., Objectives: To determine the utility of the RAT in older adults presenting to a large medical center and how test results impacted clinical care., Study Design: Retrospective chart review of patients tested for influenza during the 2003--2004 and 2004--2005 influenza seasons. Clinical data were correlated with the results of laboratory testing., Results: Eighty-four adults tested positive for influenza. Adding the results of the RAT to symptom complexes predictive of influenza significantly enhanced the ability to diagnose influenza in the acute setting. The positive predictive value of fever plus cough increased from 32% to 92% with a positive RAT. The RAT also directed appropriate antiviral therapy. 20/22 (91%) patients with a positive RAT and symptoms < or =48 h received antiviral treatment compared to only 1/12 (8%) patients with a negative RAT and a positive culture., Conclusions: Under routine clinical conditions rapid influenza testing enhances the ability to quickly diagnose influenza and can be used to guide early treatment decisions in older adults.

Background: Reliable estimates of the effectiveness of influenza vaccine among persons 65 years of age and older are important for informed vaccination policies and programs. Short-term studies may provide misleading pictures of long-term benefits, and residual confounding may have biased past results. This study examined the effectiveness of influenza vaccine in seniors over the long term while addressing potential bias and residual confounding in the results., Methods: Data were pooled from 18 cohorts of community-dwelling elderly members of one U.S. health maintenance organization (HMO) for 1990-1991 through 1999-2000 and of two other HMOs for 1996-1997 through 1999-2000. Logistic regression was used to estimate the effectiveness of the vaccine for the prevention of hospitalization for pneumonia or influenza and death after adjustment for important covariates. Additional analyses explored for evidence of bias and the potential effect of residual confounding., Results: There were 713,872 person-seasons of observation. Most high-risk medical conditions that were measured were more prevalent among vaccinated than among unvaccinated persons. Vaccination was associated with a 27% reduction in the risk of hospitalization for pneumonia or influenza (adjusted odds ratio, 0.73; 95% confidence interval [CI], 0.68 to 0.77) and a 48% reduction in the risk of death (adjusted odds ratio, 0.52; 95% CI, 0.50 to 0.55). Estimates were generally stable across age and risk subgroups. In the sensitivity analyses, we modeled the effect of a hypothetical unmeasured confounder that would have caused overestimation of vaccine effectiveness in the main analysis; vaccination was still associated with statistically significant--though lower--reductions in the risks of both hospitalization and death., Conclusions: During 10 seasons, influenza vaccination was associated with significant reductions in the risk of hospitalization for pneumonia or influenza and in the risk of death among community-dwelling elderly persons. Vaccine delivery to this high-priority group should be improved., (Copyright 2007 Massachusetts Medical Society.)

Influenza remains an important cause of illness and death in this country. Even though we have safe and effective vaccines, vaccination rates among the elderly and other high-risk groups remain static and well below national goals. Health care providers can boost these vaccination rates by educating themselves, by recommending that their patients be vaccinated, and by implementing evidence-based strategies such as programs to remind themselves and patients to be vaccinated, to utilize standing orders for nurses or other qualified professionals to offer and administer vaccines, and to provide feedback on performance. We should also consider alternative paradigms for vaccine delivery, and be sure to be vaccinated ourselves.

Seasonal influenza continues to have a huge annual impact in the United States, accounting for tens of millions of illnesses, hundreds of thousands of excess hospitalizations, and tens of thousands of excess deaths. Vaccination remains the mainstay for the prevention of influenza. In the United States, 2 types of influenza vaccine are currently licensed: trivalent inactivated influenza vaccine and live attenuated influenza vaccine. Both are safe and effective in the populations for which they are approved for use. Children, adults <65 years of age, and the elderly all receive substantial health benefits from vaccination. In addition, vaccination appears to be cost-effective, if not cost saving, across the age spectrum. Despite long-standing recommendations for the routine vaccination of persons in high-priority groups, US vaccination rates remain too low across all age groups. Important issues to be addressed include improving vaccine delivery to current and expanded target groups, ensuring timely availability of adequate vaccine supply, and development of even more effective vaccines. Development of a vaccine against potentially pandemic strains is an essential part of the strategy to control and prevent a pandemic outbreak. The use of existing technologies for influenza vaccine production would be the most straightforward approach, because these technologies are commercially available and licensing would be relatively simple. Approaches currently being tested include subvirion inactivated vaccines and cold-adapted, live attenuated vaccines. Preliminary results have suggested that, for some pandemic antigens, particularly H5, subvirion inactivated vaccines are poorly immunogenic, for reasons that are not clear. Data from evaluation of live pandemic vaccines are pending. Second-generation approaches designed to provide improved immune responses at lower doses have focused on adjuvants such as alum and MF59, which are currently licensed for influenza or other vaccines. Additional experimental approaches are required to achieve the ultimate goal for seasonal and pandemic influenza prevention--namely, the ability to generate broadly cross-reactive and durable protection in humans.

Nontraditional settings (NTS) are increasingly utilized for adult vaccination but concerns exist about their safety. We conducted this analysis of 542,445 persons vaccinated at an NTS in Minnesota to assess the safety of influenza vaccination in NTS. A total of 112 adverse events (AEs) were reported, 95 immediate and 17 late. Most AEs were mild and resolved within several minutes. 63 persons (.01%) had a vasovagal reaction to vaccination and 22 (.004%) reported an injection site problem. Immediate hypersensitivity reactions were very rare with only 10 (.002%) vaccine recipients having an immediate reaction for which epinephrine was required. Fifteen (.003%) individuals required evaluation in an emergency room or physician's office because of an AE. No deaths were reported. We conclude that influenza vaccine administration in mass vaccination clinics is safe and adverse events after influenza vaccination in NTS are extremely low.

Background: Upper respiratory tract illnesses (URIs) are a major cause of morbidity among adults, with substantial direct and indirect costs to society, but their impact among university students has not been well described. We sought to assess the impact of URIs (colds and influenza-like illnesses [ILIs]) on the health, academic and work performance, and health care use of university students., Methods: This was a cohort study of college students at the University of Minnesota, Twin Cities campus (Minneapolis-St. Paul), who were recruited during October 2002 and followed up from November 2002 through April 2003. All 42,000 registered students were invited via e-mail to participate. Baseline information was obtained in October 2002. Monthly follow-up information about colds or ILIs was obtained for the period of November 2002 through April 2003. Data were collected by use of Internet-based questionnaires., Results: Of 4919 volunteers, 3249 completed all follow-up surveys. The mean age was 22.7 years; 68% of the volunteers were female. Ninety-one percent had > or = 1 URI (83% had > or = 1 cold, and 36.7% had > or = 1 ILI). These URIs caused 6023 bed-days, 4263 missed school days, 3175 missed work days, and 45,219 days of illness. Of the cohort, 22.2% had > or = 1 health care visit, and 15.8% used antibiotics to treat a URI; 27.8% did poorly on a test and 46.3% did poorly on a class assignment. ILIs versus colds had a much greater impact on all parameters (e.g., general health level was 55%-60% lower with ILI vs. no URI and 33%-39% lower for colds vs. no URI; P < .001 for each)., Conclusion: Colds and ILIs were common and associated with substantial morbidity in university students. Enhanced efforts to prevent and control URIs, especially influenza vaccination, could improve the health and well-being of the 17 million college and university students in this country.

Influenza causes substantial morbidity across the age spectrum. However, the elderly are especially vulnerable to the serious complications of influenza that might result in hospitalisation or death, and high rates of influenza-associated excess hospitalisation or death that exceed by several-fold the rates seen among most other age groups have consistently been observed in many countries and across many seasons. Thus, the elderly are included among the high priority groups for routine influenza vaccination by many national health authorities. Inactivated influenza virus vaccines are widely available across the globe and are safe and effective. Vaccination of elderly persons has been associated with significant reductions in hospitalisations for pneumonia and influenza as well as hospitalisations for other cardiopulmonary disorders and even cerebrovascular disease. Vaccination has also been associated with reductions in influenza-associated and all-cause mortality during influenza seasons. The benefits of vaccination extend not only to community-dwelling elderly but also to elderly who reside in nursing homes. Likewise, vaccination provides benefits to the very old and to elderly persons with underlying co-morbidities as well as to the healthy elderly. Despite the substantially increased risk for serious complications and impressive benefits from vaccination among the elderly, influenza vaccine utilisation remains below target rates for this group in nearly all countries. The need for improved prevention and control of influenza is recognised as a priority for the global community--both to reduce the morbidity and mortality associated with epidemic influenza and to prepare for the next pandemic. Enhancing vaccine delivery to elderly persons would represent important progress toward that goal.

Background: Concerns about the safety and acceptability of vaccine administration in nontraditional settings might leave patients and their providers reluctant to take advantage of nontraditional settings for immunizations., Methods: Elderly persons who received pneumococcal vaccinations in these settings were surveyed with a structured questionnaire. They were asked about local and systemic symptoms during the postvaccination week versus a comparison time period., Results: Of the 1136 people included in the convenience sample, 636 responded (56%). Systemic symptoms were generally at similar or lower rates for the postvaccination week versus the comparison week, although fever was more common during the postvaccination week (3% vs 0.3%; P <.01). After vaccination 23.1% had any local symptom (soreness, redness, or swelling). Subjects who had been previously vaccinated were more likely to report local redness or swelling than were first-time vaccine recipients or people who were unsure of their vaccination status (13.1% vs 4.4% vs 1.4%, respectively; P =.001). In multivariate analyses, local symptoms were strongly associated with fever after vaccination (adjusted odds ratio, 13.15; P <.001), and revaccination was strongly associated with local symptoms (adjusted odds ratio, 3.77; P <.001). One hundred percent of respondents were very or somewhat satisfied with their experience, and >99% would recommend a nontraditional setting to a friend or family member., Conclusion: Nontraditional settings offer a safe and highly satisfactory option for the administration of pneumococcal vaccinations to the elderly.