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COMMENTARY |
Division of Infectious Diseases,
Children's Memorial Hospital,
Chicago, IL 60614
Influenza vaccine recommendations have been (for years) prioritizing persons who are most vulnerable to the severe complications of this disease. The priority groups for inactivated influenza vaccination have included, among others, adults aged 65 years and older and children aged 6 to 23 months. Although the vaccine has a moderate effect on mortality of the elderly, preventing 1 death for every 302 vaccines (annual mortality risk reduction of 15% [hazard ratio: 0.85; 95% confidence interval: 0.75–0.96]),1 51000 people, mostly elderly, die each year in the United States from influenza-related disease. Repeated disruptions in vaccine availability (in 4 of the last 5 seasons) may be an obstacle to the prevention of influenza and its severe complications. In response to the most recent vaccine shortage (in the 2004–2005 season), the Centers for Disease Control and Prevention has recommended vaccination only for the indicated populations and that people who were not at high risk should not receive vaccine.2 A more refined prioritization plan is developed for the 2005–2006 season, because there is uncertainty about the vaccine supply. Although this strategy is consistent with prior approaches and seems to be a reasonable public health intervention, new paradigms should be considered. Is there an alternative vaccination strategy that will reduce morbidity and mortality in years with vaccine shortages?
The first question: Does vaccination of "high-risk populations" really achieve the desired protection? Several lines of evidence suggest that annual vaccination of geriatric patients (ie, >65 years of age) has only a limited effect. Thompson et al3 documented a significant increase in influenza-associated hospitalizations among the elderly in the last 2 decades despite an impressive increase in vaccine coverage for this population (from 15–20% in 1980 to 65% in 1999). In a study conducted by Potter et al,4 vaccination of patients in a geriatric long-term care facility did not affect mortality. In addition, several recent studies showed that the increase in vaccine coverage for this population did not lead to reduction in influenza-associated excess deaths.5,6 A recent study that examined influenza-related deaths in the US elderly population by estimating seasonal excess all-cause deaths suggested that previous observational studies probably overestimated the "mortality benefits" of the vaccine.7 This study estimated that <10% of all winter deaths are caused by influenza and suggested the possibility that the "very ill elderly, whose fragile health would make them highly likely to die, are less likely to be vaccinated."7 Even if they had been vaccinated, the antibody response to vaccination declines rapidly after the age of 65,8 and evaluation of the inactivated vaccine efficacy in people older than 70 years showed "little difference in the incidence of influenza and influenza like illness between vaccinated and nonvaccinated participants."9 A suboptimal immune response also occurs in the newly added "priority population" of infants 6 to 23 months of age. Analysis of 5 controlled studies of inactive influenza vaccine in children younger than 9 years showed an efficacy of 63% (95% confidence interval: 45–70) and even lower efficacy for children younger than 5 years.10 Another recent assessment of the efficacy and effectiveness of the inactivated vaccine in children showed that it had a lower efficacy (65%) in children older than 2 years (compared with that of the live attenuated vaccine [79%]).11 Its effectiveness in this age group was only 28% (compared with 38% effectiveness of the live attenuated vaccine). In addition, in children younger than 2 years, the inactivated vaccine had "similar effects to placebo."11
The second question: Would annual vaccination of healthy children (ie, day care and school aged) be more beneficial to high-risk groups than immunizing them directly? Children have the highest infection rate of any age group during the influenza season, and they are major contributors to the spread of this infection to others.12,13 Several studies document the substantial benefit to the surrounding contacts of vaccinating child care–aged and/or school-aged children. Hurwitz et al14 observed that by immunizing children who are in child care, an 80% reduction in infection rate of their older unvaccinated siblings occurred (compared with siblings of unvaccinated toddlers). Rudenko et al15 found reduced illness rates of staff and unvaccinated children as vaccination rates of children in their school increased. Monto et al16 documented a significant reduction (17.5–48.1%) in influenza-associated illnesses in all age groups of a community (Tecumseh, MI) in which 85% of school-aged children were vaccinated compared with an unvaccinated community (Adrian, MI). In addition, Piedra et al17 documented that vaccination of 
20% to 25% of children 1.5 to 18 years of age with trivalent cold-adapted influenza vaccine resulted in herd immunity in adults. They observed an 8% to 18% reduction in medically attended acute respiratory illness in adults older than 35 years. Even more impressive is the result of a Japanese program in which mandatory immunization of children 5 to 15 years of age prevented 37000 to 47000 deaths annually from all causes and 10000 to 12000 deaths annually from pneumonia and/or influenza, almost all in the elderly.18 Several modeling studies have suggested that the annual influenza burden could be reduced significantly from the current level of population vaccination if >50% of children were vaccinated.19,20
Vaccination of only 20% of children 6 months to 18 years of age (15 million children) would have a striking impact on the total number of cases in both children (49% reduction) and adults (43% reduction).19 The effect on hospitalization and death of those older than 65 years also would be dramatic. The model predicts that hospitalizations would decline from 42800 to 24600 (43% reduction), and mortality would also decline by 43% (from 34400 to 19800). In addition, the economic cost saving (direct and indirect) would be significant (an estimated reduction of 44.5% from $11.0 billion to $6.1 billion).19
Thus, the data suggest that, when there is limited availability of influenza vaccine, the solution should not be limitation of the vaccine to high-risk populations but rather a more daring, evidence-based, and far-reaching approach that urges immunization of child care/school-aged children. Additional benefits of such a strategy may be substantial reduction in outpatient visits, utilization of antibiotics, absenteeism from school, and parents' work loss caused by influenza-related morbidity. Studies comparing these potential benefits after direct vaccination of high-risk groups versus vaccination of children only are needed. To reach such a goal, the policy-making organizations (eg, the Advisory Committee on Immunization Practices and Committee on Infectious Diseases of the American Academy of Pediatrics) should immediately consider recommending routine vaccination of healthy children. This should be facilitated by educating caregivers about the community-wide benefits of routine vaccination of healthy children and establishing guidelines for national immunization days in child care facilities and schools, especially if a shortage of influenza vaccine occurs again. The intranasal live attenuated vaccine, which was approved by the US Food and Drug Administration only for healthy individuals 5 to 49 years of age, could be used to vaccinate healthy school children, and the inactivated influenza vaccine can be given to individuals with a high risk of complications from influenza for whom the live attenuated vaccine is not currently recommended. The data support a reevaluation of the current recommendations even in years without a shortage. A broader vaccination strategy including immunization of both high-risk groups and child care/school-aged children would not only augment the reduction in influenza-related disease burden among the elderly but also reduce the observed disease burden among children and the community at large. To achieve this goal, at least 100 to 120 million doses per year will be needed. Policies to increase the domestic production of influenza vaccine should be developed to guarantee the availability and distribution of such a demand.
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FOOTNOTES |
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Address correspondence to Ram Yogev, MD, Division of Infectious Diseases, Children's Memorial Hospital, 2300 Children's Plaza, Box 155, Chicago, IL 60614. E-mail: ryogev{at}childrensmemorial.org
No conflict of interest declared.
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REFERENCES |
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 TOP REFERENCES |
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This article has been cited by other articles:
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  Committee on Infectious Diseases Prevention of Influenza: Recommendations for Influenza Immunization of Children, 2007-2008 Pediatrics, April 1, 2008; 121(4): e1016 - e1031. [Abstract] [Full Text] [PDF]
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P. A. Piedra, M. J. Gaglani, C. A. Kozinetz, G. B. Herschler, C. Fewlass, D. Harvey, N. Zimmerman, and W. P. Glezen Trivalent Live Attenuated Intranasal Influenza Vaccine Administered During the 2003 2004 Influenza Type A (H3N2) Outbreak Provided Immediate, Direct, and Indirect Protection in Children Pediatrics, September 1, 2007; 120(3): e553 - e564. [Abstract] [Full Text] [PDF]
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G. R. Greene, A. Lowe, and D. D'Agostino Influenza Vaccine for School-Aged Children Pediatrics, August 1, 2006; 118(2): 840 - 841. [Full Text] [PDF]
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R. Yogev Influenza Vaccine for School-Aged Children: In Reply Pediatrics, August 1, 2006; 118(2): 841 - 842. [Full Text] [PDF]
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