Correspondence
Vaccination against Influenza in Healthy Adults
N Engl J Med 1996; 334:402-404February 8, 1996
- Article
To the Editor:
Nichol et al. (Oct. 5 issue)1 report that during one influenza season, immunization against influenza significantly reduced the frequency of respiratory illness in healthy, working adults. About three quarters of the subjects had not previously been immunized. Our concern is whether subsequent influenza shots given annually would be as effective as they are the first time they are administered. Hoskins et al.2 studied the effectiveness of annual vaccinations against influenza at a boys' boarding school and found that over a four-year period, the cumulative attack rate for three successive outbreaks (approximately 40 to 50 percent) was the same irrespective of whether the subjects had received zero, one, two, or three vaccinations. Perhaps more important, the protective effect of vaccination appeared to be limited to boys receiving the vaccine for the first time. Our own observations were that during the last winter of type A Asian (H2N2) influenza activity (1967–1968), influenza shots were only 27 percent effective,3 whereas a year later — during the first year of Hong Kong (H3N2) influenza activity — shots were over 90 percent effective.4
If the data of Nichol et al. are analyzed separately with respect to subjects with and those without prior immunization against influenza, is there a difference in effectiveness?
4 ReferencesParker A. Small, Jr., M.D.
University of Florida College of Medicine, Gainesville, FL 32610Bradley S. Bender, M.D.
Veterans Affairs Medical Center, Gainesville, FL 326081
Nichol KL ,Lind A ,Margolis KL , et al. The effectiveness of vaccination against influenza in healthy, working adults. N Engl J Med 1995;333:889-893
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Hoskins TW ,Davies JR ,Smith AJ ,Miller CL ,Allchin A . Assessment of inactivated influenza-A vaccine after three outbreaks of influenza A at Christ's Hospital. Lancet 1979;1:33-35
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Waldman RH ,Mann JJ ,Small PA Jr . Immunization against influenza: prevention of illness in man by aerosolized inactivated vaccine. JAMA 1969;207:520-524
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Waldman RH ,Bond JO ,Levitt LP , et al. An evaluation of influenza immunization: influence of route of administration and vaccine strain. Bull World Health Organ 1969;41:543-548
Web of Science | Medline
To the Editor:
Nichol et al. report on the clinical effectiveness of influenza vaccine in healthy, working adults and point out that the use of the vaccine would result in net savings of $46.85 per subject vaccinated. They concluded that the “results of this study should therefore be generalizable to other working adults.”
I agree with the editorial comments of Patriarca and Strikas (Oct. 5 issue)1 regarding the amazing pandemic-like attack rate of influenza-related respiratory illnesses (at least 35 percent) during an influenza season with a low-to-moderate incidence, and with their cautions about the applicability of these results to the entire working population. In France the rates of visits to physicians for influenza-like illnesses based on a national survey of a representative subgroup of 500 general practitioners since 19842 have ranged from 1.4 to 6.5 percent among the working population (during the 1994–1995 influenza season, the rate was 2.0 percent). Moreover, these rates are undoubtedly overestimated, because of the nonspecific features of influenza-like illnesses.
Nichol et al. miss an important point when they advocate vaccination of healthy, working adults on the basis of cost–benefit arguments. They give no information about influenza-related illnesses during previous influenza seasons. Previous influenza infection is likely to be protective against subsequent infection with the same subtype of influenza, despite antigenic drift.3 This phenomenon was well described when the H1N1 subtype reemerged in 1977 after a 20-year absence and attacked mostly persons born after 1950,4 and it is exemplified by the decrease in the attack rates with age for all influenza subtypes.5 The savings associated with vaccination against influenza thus needs to take into account the protective immunity in previously infected people (both vaccinated and unvaccinated) and must be averaged over successive influenza seasons. If each subtype reappears every three years, acquired protective immunity lasts six years after infection, the efficacy of the vaccine is 80 percent, and the mean attack rate is 10 percent among susceptible workers, sequential vaccination would probably cost more than it would save (average, $6 per subject vaccinated per year according to our estimates).
Recently, a national health insurance company asked INSERM (the French national institute for health and medical research) to identify which segment of the French population it should cover in terms of vaccination against influenza. The expert committee, which included clinicians, epidemiologists, virologists, and economists, reviewed more than 500 studies.6 One of the committee's conclusions was that economic arguments alone were not strong enough to promote vaccination against influenza among working adults.
6 ReferencesFabrice Carrat, M.D., Ph.D.
INSERM Unité 263, 75571 Paris, France1
Patriarca PA ,Strikas RA . Influenza vaccine for healthy adults? N Engl J Med 1995;333:933-934
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Computer networking as a tool for public health surveillance: the French experimentMMWR Morb Mortal Wkly Rep 1992;41:Suppl:101-110
Medline3
Gill PW ,Murphy AM . Naturally acquired immunity to influenza type A: lessons from two coexisting subtypes. Med J Aust 1985;142:94-98
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Glezen WP ,Keitel WA ,Taber LH ,Piedra PA ,Clover RD ,Couch RB . Age distribution of patients with medically-attended illnesses caused by sequential variants of influenza A/H1N1: comparison to age-specific infection rates, 1978-1989. Am J Epidemiol 1991;133:296-304
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Monto AS ,Ohmit SE ,Margulies JR ,Talsma A . Medical practice-based influenza surveillance: viral prevalence and assessment of morbidity. Am J Epidemiol 1995;141:502-506
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Expertises Collectives de l'INSERM. La grippe: stratégies de vaccination. Paris: INSERM, 1994.
To the Editor:
Patriarca and Strikas's lukewarm endorsement of widespread vaccination of healthy, working adults against influenza fails to consider the economic benefits such a policy would have in preventing illness in the elderly and chronically ill. A case–control study from Canada found that vaccination against influenza lowered by 27 to 30 percent not only the rates of hospitalization and death due to influenza and pneumonia, but also the death rate from all conditions.1 Despite our efforts, however, the majority of those at high risk for complications of influenza are not vaccinated yearly.2 Those at high risk are also less likely to have protective antibody levels after vaccination.2 By immunizing younger, healthier adults, who might otherwise serve as vectors of disease, we could lower the overall incidence of influenza in the community and decrease the likelihood that people at high risk for complications would encounter the virus. The economic and health benefits of this indirect effect could be enormous.
2 ReferencesTimothy B. McCall, M.D.
176 Pearl St., Cambridge, MA 021391
Fedson DS ,Wajda A ,Nicol JP ,Hammond GW ,Kaiser DL ,Roos LL . Clinical effectiveness of influenza vaccination in Manitoba. JAMA 1993;270:1956-1961
CrossRef | Web of Science | Medline2
ACP Task Force on Adult Immunization, Infectious Diseases Society of America. Guide for adult immunization. 3rd ed. Philadelphia: American College of Physicians, 1994.
Author/Editor Response
The authors reply:
To the Editor: The study by Hoskins et al. referred to by Drs. Small and Bender is frequently cited as evidence that annual vaccination against influenza may result in decreasing vaccine effectiveness, but the results of the study should be interpreted cautiously. Assessments of vaccine effectiveness focused on the 1976 influenza season, when the match between vaccine and circulating strains of virus was poor. Furthermore, the outcomes of febrile illness in students at a boarding school may have limited applicability to other populations.1 On the other hand, a recent trial in healthy adults has confirmed the efficacy of annual vaccination against influenza.2 In our trial, prior immunization was associated with a somewhat higher, though statistically nonsignificant, degree of effectiveness (unpublished data).
We agree with Dr. Carrat that the benefits of vaccination when averaged over a period of several years will depend on a number of factors, including the costs of influenza-associated morbidity, the type and severity of influenza, attack rates, and vaccine efficacy during each season. How preexisting immunity would additionally contribute to economic-benefits models is not clear. Over the past eight years in the United States, for example, we have not observed a cyclic reappearance of circulating influenza-virus strains that might have been adequately covered by previous years' vaccines. Given this year-to-year antigenic variation it is likely that vaccination would be beneficial for healthy, working adults over multiple seasons, as has previously been demonstrated for the elderly.3,4
Dr. Carrat also raises an important question about the magnitude of the benefit observed in our trial. One possible explanation for our findings is a pandemic-like attack rate among the study subjects. We have no reason to believe that such was the case during our study. A more likely and biologically plausible explanation is that vaccination against influenza prevented not only influenza but also associated, secondary illnesses. In addition to reducing the incidence of influenza, vaccination in the elderly reduces the rates of influenza-associated complications such as secondary pneumonia, exacerbations of underlying medical conditions, and death.4 In children, vaccination decreases episodes of acute otitis media, which are usually of bacterial origin.5 Our findings suggest that illness due to influenza may represent only the tip of the iceberg with respect to influenza-associated morbidity in healthy, working adults as well. Vaccination may therefore result in reductions in morbidity that go beyond reductions in cases of influenza. It should not be surprising that vaccination of healthy, working adults against influenza has substantial health-related and economic benefits.
5 ReferencesKristin L. Nichol, M.D., M.P.H.
Minneapolis Veterans Affairs Medical Center, Minneapolis, MN 55417Karen L. Margolis, M.D., M.P.H.
Hennepin County Medical Center, Minneapolis, MN 554151
Nicholson KG. Annual vaccination: conclusions and recommendations. In: Hannoun HC, Kendal AP, Klenk HD, Ruben FL, eds. Options for the control of influenza II. Amsterdam: Elsevier Science, 1993:451-5.
2
Keitel WA ,Cate TR ,Couch RB . Efficacy of sequential annual vaccination with inactivated influenza virus vaccine. Am J Epidemiol 1988;127:353-364
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Mullooly JP ,Bennett MD ,Hornbrook MC , et al. Influenza vaccination programs for elderly persons: cost-effectiveness in a health maintenance organization. Ann Intern Med 1994;121:947-952
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Nichol KL ,Margolis KL ,Wuorenma J ,Von Sternberg T . The efficacy and cost effectiveness of vaccination against influenza among elderly persons living in the community. N Engl J Med 1994;331:778-784
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Clements DA ,Langdon L ,Bland C ,Walter E . Influenza A vaccine decreases the incidence of otitis media in 6- to 30-month-old children in day care. Arch Pediatr Adolesc Med 1995;149:1113-1117
Web of Science | Medline
