Currently, influenza vaccination is recommended for individuals 6 months and older who have chronic underlying medical conditions placing them at risk for serious complications from influenza. This immunization is also recommended for all adults 50 years and older and health care workers, household members, or others at least 6 months old who are in contact with high-risk individuals (Table 1).1
The rate of influenza vaccination among those 65 years and older has been steadily increasing during the past decade, from 33% to 67% in 1998 (Centers for Disease Control and Prevention, Behavioral Risk Factor Surveillance System, unpublished data, 1998).1 This is in marked contrast to the low (30%) vaccination rate among high-risk populations younger than 65 years (Centers for Disease Control and Prevention, Behavioral Risk Factor Surveillance System, unpublished data, 1998), particularly high-risk children, whose vaccination rate has been estimated to be as low as 10%.2
This low influenza vaccine coverage rate among children for whom immunization is recommended is in stark contrast to coverage for routinely recommended pediatric vaccines, which generally exceed 90%. Low coverage for influenza vaccine may reflect a lack of knowledge by providers regarding the recommendations, inadequate systems to identify and recall children who need to be vaccinated, and low knowledge of and interest in vaccination by parents. Improving the protection of high-risk children through vaccination of the children themselves and their family members should be a priority of pediatric practice.
During the next year or so, pediatricians and immunization experts will hold formal discussions about expanding the recommendation for annual influenza vaccination in the United States to include healthy young children. The American Academy of Pediatrics (AAP) and the Advisory Committee on Immunization Practices (ACIP) will consider making this recommendation in response to evidence that otherwise healthy infants and toddlers have high rates of serious influenza-related medical complications.1 A routine recommendation would also increase coverage among high-risk children for whom influenza-related hospitalizations may be 4 to 20 times more frequent than for healthy children. (The lower end of this range is for children younger than 2 years, because both high-risk and healthy children in this age group have high influenza hospitalization rates. This narrows the differential between them.)3
Current Recommendations for Influenza Vaccination of Children
However, pediatricians have questioned the feasibility of adding another vaccination to the crowded pediatric schedule, especially because it would be given each year in the fall and winter months. There are approximately 51A million children who are 6 to 23 months old in the United States and another 3.8 million who are 24 to 35 months old.4 Thus, the AAP and the ACIP will carefully consider the safety, efficacy, cost-benefit ratio, and feasibility of using the current inactivated vaccine and the new spray vaccine before making an expanded recommendation for routine influenza vaccination of all young children.
WHY ARE HEALTHY YOUNG CHILDREN BEING CONSIDERED AT HIGH RISK FOR SERIOUS INFLUENZA-RELATED MEDICAL COMPLICATIONS?
Several studies have shown that otherwise healthy infants and toddlers in the United States have high rates of influenza-related hospitalizations that are comparable to those of older children and middle-aged adults who are at high risk (Table 2). Neuzil et al.5 analyzed 19 years of Tennessee Medicaid data for healthy enrolled children who were younger than 15 years from 1973 to 1993. They estimated the average annual rate of hospitalizations for cardiopulmonary conditions attributable to influenza by subtracting the baseline rate from the rate during influenza season. The study indicated elevated rates of hospitalization due to influenza that were highest for those younger than 6 months (104 hospitalizations per 10,000 children). These rates decreased with increasing age. The rates of influenza-related hospitalization for healthy children younger than 1 year and for those 1 to 3 years old were high, however. Not only were these two greater than the rate for older healthy children, but they were also similar to or greater than the rates for high-risk women 50 to 64 years old6 for whom vaccination is recommended.
Izurieta et al.3 conducted a study of healthy children younger than 18 years from 1992 to 1997 using clinical databases from two managed care organizations on the West Coast. They estimated the rate of hospitalizations for acute respiratory disease attributable to influenza, based on subtracting a baseline hospitalization rate from the rate during influenza season. They also removed periods when influenza did not predominate. Most of their data were from two seasons that had considerable separation between the peak respiratory syncytial virus (RSV) and the influenza seasons. Healthy children younger than 2 years had an elevated rate of hospitalization due to influenza. This reached approximately 9 to 11 hospitalizations per 10,000 person-months for healthy children younger than 2 years who were enrolled in the managed care organizations, and was as high as that for 5- to 17-year-old children with high-risk conditions.
Annual Rate of Hospitalizations Due to Influenza, per 10,000 Persons
Studies of children in Houston8 and in a prepaid health plan in Oregon11 found similar trends and comparable elevated rates of hospitalizations for young children during influenza epidemics. The study in Houston found the highest rates among those younger than 1 year and both studies found that rates remained elevated in those younger than 4 years.
One caveat in interpreting incidence data is the difficulty in identifying influenza infections and distinguishing between the influenza season and the RSV season, especially because these seasons vary from year to year.101516 The studies cited here could not completely remove hospitalizations caused by RSV and other winter viruses,17 but two of the studies probably minimized the problem. The Tennessee Medicaid study repeated the analysis after removing data from when RSV was circulating, and obtained similar results. One editorial18 expressed concern that the Tennessee Medicaid study and the study of two managed care organizations may have been conservative in adjusting for hospitalizations due to non-influenza causes, so actual rates may be higher than estimated.
An ongoing study is ascertaining all laboratory-confirmed influenza hospitalizations in young children in counties around Nashville, Tennessee, and Rochester, New York. The study will provide population-based estimates that explicitly distinguish influenza-specific hospitalizations from those associated with other respiratory infections.
Healthy children rarely die of influenza. More than 90% of deaths due to influenza are among individuals 65 years and older.1 The studies cited here either did not discuss deaths or found them to be rare. The Tennessee Medicaid study reported 8 deaths per million, with most occurring among those younger than 1 year.
AVAILABLE AND CANDIDATE INFLUENZA VACCINES
Inactivated injectable vaccines are the only influenza vaccines currently licensed in the United States. These vaccines have a long history of use and are considered safe and efficacious.19 Although mild, local reactions can be seen at the injection site and mild fever, malaise, myalgia, and other systemic symptoms can occur, more severe reactions are uncommon. The vaccine can be given to children as young as 6 months and neither minor illness nor the administration of other vaccines is a contraindication.1 Studies have found that influenza vaccination is not associated with increased exacerbations of asthma in children with this disorder.2 Actually, immunization can prevent exacerbations of asthma caused by influenza infection.
The application for licensure of an intranasal spray vaccine was submitted to the Food and Drug Administration in October 2000.20 The vaccine is a live, attenuated, trivalent vaccine. Although there have been no studies that directly compare it with inactivated vaccines, one large clinical trial showed 93% efficacy during one influenza season in healthy children 15 to 71 months old.21 The application was submitted for use in healthy children and adults 12 months to 64 years old. The timing and the number of doses would probably be the same as those for the inactivated vaccines.
FEASIBILITY AND COST-EFFECTIVENESS OF ROUTINE VACCINATION OF YOUNG CHILDREN
The feasibility and cost-effectiveness of such an expanded recommendation are currently unclear. Studies are under way to evaluate these issues. Regardless of whether the recommendation is expanded, barriers to vaccination need to be overcome, including changing the perception that influenza is a brief illness without serious health effects. We must improve our ability to keep track of high-risk children and remind and encourage parents to bring them and their household contacts in for vaccinations. Flexible hours and locations for immunizations that are more convenient for parents would also help. From 1998 to 1999, almost 40% of those 65 years and older received their influenza vaccination outside of a medical office (Centers for Disease Control and Prevention, Behavioral Risk Factor Surveillance System, unpublished data, 1998). Although pediatric vaccination outside the medical home may not be optimal or widely accepted, the licensure of a new intranasal spray vaccine for influenza may make administration feasible in alternative sites.
1. Centers for Disease Control and Prevention. Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACLP). MMWR. 2001;50(RR04):l-46.
2. Kramarz P, DeStefano F, Gargiullo R Chen RT, Vaccine Safety Datalink Team. Accounting for disease severity in assessing the association of influenza vaccine with asthma exacerbation. Pharmacoepidemiology and Drug Safety. 1998; 7:113.
3. Izurieta HS, Thompson WW, Kramarz P, et al. Influenza and the rates of hospitalization for respiratory disease among infants and young children. N Engl J Med. 2000342:232-239.
4. U.S. Census Bureau. Quarterly Projections of the Resident Population by Age, Sex, Race, and Hispanic Origin: Middle Series. Washington, DC: U.S. Census Bureau; November 2, 2000.
5. Neuzil KM, Mellen BG, Wright PF, Mitchel EF Jr, Griffin MR. The effect of influenza on hospitalizations, outpatient visits, and courses of antibiotics in children. N Engl J Med. 2000;342:225-231.
6. Neuzil KM, Reed GW, Mitchel EF Jr, Griffin MR. Influenzaassociated morbidity and mortality in young and middleaged women. JAMA. 1999;281:901-907.
7. Neuzil KM, Wright PF, Mitchel EF Jr, Griffin MR. The burden of influenza illness in children with asthma and other chronic medical conditions. Pediatrics. 2000;137:856-864.
8. Perrotta DM, Decker M, Glezen WR Acute respiratory disease hospitalizations as a measure of impact of epidemic influenza. Am J Epidemiol. 1985;122:468-476.
9. Glezen WP, Decker M, Perrotta DM. Survey of underlying conditions of persons hospitalized with acute respiratory disease during influenza epidemics in Houstoa 1978-1981. American Review of Respiratory Disease. 1987;136:550-555.
10. Glezen WR Morbidity associated with the major respiratory viruses. Pediatr Ann. 1990;19:535-536, 538, 540.
11. Mullooly TP, Barker WH. Impact of type A influenza on children: a retrospective study. Am J Public Health. 1982;72:10081016.
12. Barker WH. Excess pneumonia and influenza associated hospitalization during influenza epidemics in the United States, 1970-78. Am J Public Health. 1986;76:761-765.
13. Barker WH, Mullooly JR Impact of epidemic type A influenza in a defined adult population. Am J Epidemiol. 1980;112: 798-811.
14. Glezen WR Influenza surveillance in an urban area. Canadian Journal of Infectious Diseases. 1993;4:272-274.
15. Glezen WR Taber LH, Frank AL, Gruber WC, Piedra PA. Influenza virus infections in infants. Pediatr Infect Dis J. 1997;16:1065-1068.
16. Shay DK, Holman RC, Newman RD, Liu LL, Stout JW, Anderson LJ. Bronchiolitis-associated hospitalizations among US children, 1980-1996. JAMA. 1999;282:1440-1446.
17. Mcintosh K, Lieu T Is it time to give influenza vaccine to healthy infants? N Engl J Med. 2000342:275-276.
18. Glezen WR Influenza and hospitalizations in children. N Engl J Med. 2000;342:1752-1753.
19. Edwards KM, Dupont WD, Westrich MK, Plummer WD Jr, Palmer PS, Wright PF. A randomized controlled trial of coldadapted and inactivated vaccines for the prevention of influenza A disease. J Infect Dis. 1994;169:68-76.
20. Aviron. Aviron submits biologies license application for FluMist [press release]. Mountain View, CA: Aviron; October 31, 2000.
21. Belshe RB, Mendelman PM, Treanor J, et al. The efficacy of live attenuated, cold-adapted, bivalent, intranasal influenzavirus vaccine in children. N Engl J Med. 1998338:1405-1412.
Current Recommendations for Influenza Vaccination of Children
Annual Rate of Hospitalizations Due to Influenza, per 10,000 Persons