Current issues of ACP Journal Club are published in Annals of Internal Medicine


Vaccination against influenza had both health and economic benefits for healthy, working adults

ACP J Club. 1996 Mar-April;124:52. doi:10.7326/ACPJC-1996-124-2-052

Source Citation

Nichol KL, Lind A, Margolis KL, et al. The effectiveness of vaccination against influenza in healthy, working adults. N Engl J Med. 1995 Oct 5;333:889-93. [PubMed ID: 7666874]



To determine the effectiveness of vaccination against influenza in healthy, working adults.


Analysis of health-related data and costs from a randomized, double-blind, placebo-controlled trial with follow-up for 1 influenza season.


Community-based study in the Minneapolis-St. Paul area of the United States.


849 volunteers between 18 and 64 years of age (mean age 40 y, 63% women) who were employed full time and had no medical conditions that would place them at high risk for complications of influenza. Exclusion criteria were pregnancy, a history of immediate hypersensitivity reactions to eggs or thimerosal, or previous vaccination against influenza. 99% completed the study.


424 participants were allocated to injection of trivalent subvirion influenza vaccine (containing 15 mg of antigen from the component strains A/Texas/36/91, A/Shangdong/9/93, and B/Panama/45/90; Fluzone, Connaught Laboratories, Swiftwater, PA), and 425 were allocated to placebo (vaccine diluent).

Main Cost and Outcome Measures

Upper respiratory illnesses (defined as a sore throat associated with either fever or cough for > 24 h), absenteeism from work, and visits to physicians because of upper respiratory illnesses. The economic benefits of vaccination were based on the primary study outcomes of sick leave and visits to physicians related to respiratory illness. Costs were calculated from the social perspective as combined direct and indirect costs.

Main Results

61% of the vaccine recipients compared with 69% of the placebo recipients had ≥ 1 upper respiratory illness (P = 0.018). Vaccination resulted in fewer days of sick leave caused by upper respiratory illness (P = 0.001) and fewer visits to physicians (P = 0.004). Combined cost savings were estimated to be U.S. $46.85 per person vaccinated, consisting of U.S. $5.99 direct savings in medical costs and U.S. $40.86 in indirect costs.


Vaccination against influenza in healthy, working adults was associated with health benefits and cost savings of U.S. $46.85 per person vaccinated.

Sources of funding: In part, Blue Cross Blue Shield of Minnesota Foundation and Connaught Laboratories.

For article reprint: Dr. K.L. Nichol, Acting Chief of Medicine (111), Veterans Affairs Medical Center, One Veterans Drive, Minneapolis, MN 55417, USA. FAX 612-727-5659.


Justified by overwhelming evidence showing that immunization can reduce morbidity and mortality, primary care and public health influenza immunization programs have historically targeted persons at high risk for death or complications of influenza. For healthy persons, the evidence that supports routine influenza immunization to reduce these outcomes is not compelling. Nichol and colleagues, in their cost-effectiveness analysis, examined different outcomes: direct costs associated with medical care and indirect costs associated with loss of productive labor. The study participants were young, highly educated, and prosperous and had good or excellent self-reported health status; most were nonsmokers. Arm soreness was the only clinically significant side effect of immunization. From the perspectives of employer and society, indirect cost savings from immunization greatly exceeded direct cost savings.

In fairness, the economic magnitude of immunization and, thus, of the conclusions supported by Nichol and colleagues are sensitive to the epidemiologic characteristics of influenza and the economic assumptions made, as is also pointed out by Patriarca and Strikas (1). For example, the cost-effectiveness of immunization would be reduced if the prevailing influenza strain was less closely matched to the vaccine components or had a lower attack rate (2). The cost-effectiveness also would be reduced if more persons were included who had previously been immunized for influenza. On the other hand, a more specific case definition for influenza infection than that used by the authors might substantially increase the observed cost-effectiveness. The savings will be greater during years of epidemic influenza. Finally, cost-effectiveness will be greater in industries that have highly skilled, highly paid employees.

When studies that have varying prevalence of influenza confirm these results, employers, primary care providers, and managed care organizations should consider expanded influenza immunization efforts such as worksite immunization programs. These efforts probably will save money more by maintaining worker productivity than by reducing health care costs.

William P. Moran, MD, MS
Bowman Gray School of Medicine of Wake Forest UniversityWinston-Salem, North Carolina, USA


1. Patriarca PA, Strikas RA. Influenza vaccine for healthy adults? [Editorial]. N Engl J Med. 1995;333:933-4.

2. Bridges CB, Thompson WW, Meltzer MI, et al. Effectiveness and cost-benefit of influenza vaccination of healthy working adults. JAMA. 2000;284:1655-63.