Universal Influenza Vaccination Strategies: A Call for Action

Introduction Influenza: Burden of Disease—Efforts at Prevention Lisa Jackson, MD, MPH Influenza Prevention and Treatment: The Advisory Committee on Immunization Practices 2008 Guidelines Robert B. Belshe, MD School Influenza Vaccination Programs—The Maryland Model Marge Hoffmaster, RN Practical Issues of Influenza Vaccination—Challenges and Strategies Stanley L. Block, MD

Introduction

Influenza is an old disease, but its prevention and control comprise a dynamic and contemporary science. The latest data are compiled annually by the Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices (ACIP). Awareness of the ACIP recommendations in preparation for each influenza season is an obligation for all healthcare providers who treat children at risk for complications from influenza.

Vindico Medical Education organized a panel of influenza experts to review the latest ACIP recommendations and discuss the burden of disease, recent data, and current status of efforts to prevent influenza. The panel also addressed how these factors can control influenza in the community. Specifically, what provides the basis for expansion of the ACIP vaccination recommendations? Why aren’t vaccination rates reaching recommended levels? What feasible options are available to improve immunization coverage? What are comparative benefits and risks of the 2 types of vaccines?

I thank the panel for their contributions to the discussion and the development of this monograph, which summarizes the discussions to provide the reader with a succinct overview of the salient aspects of influenza—the disease and its prevention.

Pedro A. Piedra, MD
Course Director

Course Chair Pedro A. Piedra, MD, Department of Pediatrics Section of Infectious Diseases Baylor College of Medicine Houston, TX Faculty Robert B. Belshe, MD, Professor of Medicine, Pediatrics and Molecular Microbiology Saint Louis University School of Medicine, St Louis, MO Stan L. Block, MD, Professor of Clinical Pediatrics, University of Louisville Professor of Clinical Pediatrics, University of Kentucky President, Kentucky Pediatric Research, Bardstown, KY Lisa Jackson, MD, MPH, Senior Investigator, Group Health Care for Health Studies Seattle, WA Marge Hoffmaster, RN, Supervisor of Health Services, Carroll County Public Schools Westminster, MD

Influenza: Burden of Disease—Efforts at Prevention

Lisa Jackson, MD, MPH

Influenza continues to exert an often unacknowledged health burden in the United States, particularly in young children. Ongoing research to understand the details of this disease, including its incidence, epidemiology, complications, and costs, proceeds in parallel with efforts to improve its treatment and prevention.

Burden of Disease

The Underrecognized Burden of Influenza in Young Children

In recent years, major advances have been made in understanding the burden of influenza in children, made possible in part by the implementation of 2 surveillance systems by the Centers for Disease Prevention and Control (CDC): the New Vaccine Surveillance Network and the Emerging Infections Program. Both involve widespread testing in the hospital setting and, for new vaccine surveillance, in the outpatient setting as well. Previously, testing was not routinely performed; accordingly, most true influenza infections in children were undetected. Two studies resulting from the New Vaccine Surveillance Network provide valuable summary information on the burden of influenza in young children.

For the surveillance system, testing is done throughout the year, allowing acquisition of data supporting that the majority of influenza cases occur from November through April. However, the proportion of hospitalizations for acute respiratory tract infection or fever that are attributable to influenza varies by year and month within this interval.

As part of the New Vaccine Surveillance Network, Poehling et al recently published the results of a prospective, 4-year (2000-2004) study in 3 US counties.¹ Children <5 years old admitted to surveillance hospitals or presenting to selected outpatient clinics and emergency departments with a diagnosis of acute respiratory tract infection or fever were eligible, and nasal and throat swabs were obtained from enrolled children. The average annual rate of hospitalization with laboratory-confirmed influenza in the entire cohort was 0.9 per 1000 children, based on county census populations. The data revealed that children aged <6 months were at the highest risk of hospitalization for influenza, accounting for nearly one-half of all hospitalizations; and 80% were <2 years of age (Figure 1). Significantly, only 28% of all of the hospitalized children with laboratory-confirmed influenza had a diagnosis of influenza. Of 160 hospitalized children in the surveillance system with confirmed influenza infection, only 52 (33%) had been tested for influenza as part of their clinical care.

Figure 1. Rate of Hospitalizations Attributable to Influenza per 1000 Children by Age Group and Study Year

Culture results for outpatients were obtained in 2 of the study seasons (2002-2003 and 2003-2004), with 16% of 1742 enrolled children having confirmed influenza infections. Two differences between hospitalizations and outpatient visits are apparent. First, cases were more evenly distributed among the age groups, and older children were represented more than those <6 months old. Second, the rate of outpatient visits for influenza was at least 10-fold higher than that for hospitalization.

The investigators concluded that influenza causes a significant health burden, not only by the number of hospitalizations, upon which the recommendation to vaccinate children aged 6-23 months was based, but also by a tremendous number of outpatient visits. This increased understanding of the actual burden of influenza supports the need for improved infection control, antiviral therapy, and education about the importance of vaccination.

The Influenza Burden in Children with Asthma

Another publication based on the same patient cohort revealed that the risk of hospitalization because of influenza among children 6-59 months of age with asthma was much greater than the risk for same-aged healthy children.² Overall, the average annual influenza-attributable hospitalization rate was 1.0 per 1000 in children with asthma, compared with 0.4 per 1000 in healthy children. The subgroup of children aged 6-23 months with asthma had significantly more hospitalizations (2.8 cases per 1000) compared with healthy children (0.6 cases per 1000; P<0.05); whereas older children, aged 24-59 months, with asthma had a nonsignificantly greater hospitalization rate compared with healthy children (0.6 versus 0.2 per 1000 children, respectively, P>0.05).

Outpatient visits for influenza in 2002-2003 were approximately 60 cases per 1000 for children with or without asthma. In 2003-2004, however, significantly more visits were attributable to influenza in children with asthma compared with healthy children, in both the 6- to 23-month-old (316 versus 152 per 1000 children, respectively) and 24- to 59-month-old (188 versus 102 per 1000 children, respectively) age groups.

These data indicated that the influenza burden among children with asthma was substantially greater than it was among healthy children. The investigators emphasized that targeted strategies to increase vaccination rates in both children with asthma and healthy children in this age group are needed to reduce this burden.

Incidence, Epidemiology, Complications, Costs, and Risk Factors for Prolonged Stay in Children Hospitalized with Influenza

A single-center retrospective study of 745 patients ≤21 years old in Philadelphia was the largest US cohort study of children hospitalized with community-acquired laboratory confirmed influenza.³ Data from this study were used to estimate the age-specific incidence of influenza-related hospitalizations, describe the characteristics and clinical course of these children, and identify risk factors for prolonged hospitalization. During the 4-year study period (2000-2004), the hospitalization rate for confirmed influenza was 7 per 10,000 child-years of observation. One-fourth of the children were <6 months of age, and approximately three-fourths (77%) were <5 years old, with a median age of 1.8 years. Thus, 174 patients aged >5 years were hospitalized with influenza, supporting the extension of the Advisory Committee on Immunization Practices (ACIP) vaccination recommendations to include children aged 12-17 years. Approximately one-half (49%) of the 745 children had medical conditions recognized by the ACIP as increasing the risk for influenza-related complications, and 14% had at least 2 high-risk conditions. Approximately one-fourth (24%) of the children had asthma, 12% had neurologic or neuromuscular disease (NNMD), which was added to the ACIP list of high-risk conditions in 2005, 8% had immunosuppression related to HIV and/or malignancies, and 7% had cardiac disease. Children hospitalized with laboratory-confirmed influenza who had high-risk medical conditions were significantly older than children without these conditions (median age 3.1 versus 0.7 years, respectively; P<0.001), and the predicted probability of prolonged length of stay (>6 days) for children with cardiac disease, NNMD, or both, was 23%, 33%, and 68%, respectively, regardless of age. In addition, NNMD was shown to be independently associated with prolonged hospitalization among these children.

A similar single-center, retrospective cohort study was reported by Ampofo et al based on 325 children admitted with laboratory-confirmed influenza during 3 viral seasons (2001-2004) in the Salt Lake City area.⁴ The overall population-based rate of hospitalization was 2.7 per 10,000 children per year, and ranged from 25.3 for children <6 months of age to 0.6 for children 7-14 years old. Although children aged ≥2 years had lower hospitalization rates, they contributed a higher absolute number of hospitalizations and had significantly increased pneumonia rates, ICU admissions, and requirement for mechanical ventilation. Based on these data, the investigators predicted that the 2006 revision to the ACIP guidelines that expanded vaccination recommendations to include children aged 24-59 months targets 80% of children hospitalized for influenza. Extrapolating their overall hospitalization rate to the US population, they estimated that influenza results in 20,000 hospitalizations per year in children ≤17 years old, at a median total hospital cost of $55 million.

More than one-third (37%) of the children in the study had at least 1 high-risk condition, with asthma being present in 45%, and neurologic, cardiovascular, metabolic, and immunosuppressive disorders in 23%, 21%, 8%, and 7%, respectively. The authors agreed that their data also support the ACIP recommendation of vaccination for all children 6-59 months of age, especially because it may increase coverage in high-risk children.

Influenza Prevention

The FDA has licensed two types of influenza vaccines in the United States: the trivalent inactivated influenza vaccine (TIV), which is administered by intramuscular injection, and the live-attenuated influenza vaccine (LAIV), which is administered by nasal spray. Five brands of TIV and a single LAIV are available. The indication for LAIV includes children as young as 2 years and adults up to 49 years. Three pivotal trials support the use of LAIV in children ≥2 years old: 2 placebo-controlled studies each performed during 2 seasons and a 1-year head-to-head trial comparing LAIV to TIV. Trials of the vaccine in children <2 years of age are ongoing and are reviewed elsewhere in this monograph.

Randomized Controlled Trials of Trivalent Inactivated Influenza Vaccine versus Placebo

A randomized, double-blind, placebo-controlled trial of TIV for preventing acute otitis media enrolled 786 children aged 6-24 months before the 1999-2000 and 2000-2001 flu seasons in Pittsburgh.⁵ Two doses of the vaccine or placebo were administered intramuscularly 4 weeks apart, and follow-up was at least biweekly through March 31, which in the 1999-2000 season was followed by monthly visits until November 15.

In the first season, influenza was epidemic in the community, with documented influenza reaching 15.9% in the placebo group, compared with 5.5% in the TIV group. Accordingly, vaccine efficacy was 66% (95% confidence interval [CI], 34%-82%) for that season. In the second season, culture-confirmed influenza was identified in 3.6% of vaccinated children and in 3.3% of 123 children in the placebo group, for an efficacy rate of -7% (95% CI, -247% to 67%). Healthcare utilization was similar between groups in the first season, although use was actually higher in the vaccinated group in the second season. Differences did not reach statistical significance, and the vaccine was well-tolerated. The proportion of children having at least one episode of acute otitis media was not different between groups in either season. The investigators concluded that, despite this failure to demonstrate prevention of otitis media, the limited protection against influenza achieved with the vaccine supports immunizing healthy infants and young children.

In a 2-year randomized, double-blind, placebo-controlled study conducted by Belshe et al, when vaccine strains were well-matched for the circulating strains in the first year of the study, LAIV administration resulted in a 95% (95% CI, 89%-97%) reduction of laboratory-documented influenza disease in children 2-7 years of age (Figure 2).⁶ In the second year of the study, vaccine and circulating strains were mismatched, yet an efficacy of 87% (95% CI, 78% to 93%) was observed.

Figure 2. Absolute Efficacy of LAIV in Children Aged 24 to 71 Months LAIV – live attenuated influenza vaccine

Figure 3. Relative Efficacy of LAIV and TIV in Children Aged 2-5 Years LAIV – live attenuated influenza vaccine, TIV – trivalent inactivated vaccine

Multicenter Trial of Live-Attenuated Influenza Vaccine versus Trivalent Inactivated Influenza Vaccine versus Placebo

In a recent randomized, double-blind, head-to-head trial comparing the efficacy of LAIV with TIV in 16 countries, 8475 children aged 6-59 months were enrolled in October 2004.⁷ The rate of influenza in the LAIV group was more than 50% lower than that in the TIV group (Figure 3). More cases were attributed to mismatched strains in the TIV group compared with the LAIV group. The influenza rate for mismatched A/H3N2 was 4.5% with TIV and 0.9% with LAIV (P<0.001).

The safety endpoint of medically significant wheezing was observed more frequently in children aged 6-23 months who received LAIV (LAIV: 5.9%; TIV: 3.8%; P=0.002). For children aged 24-59 months, an age group that is currently included in the LAIV indication, wheezing was slightly, but nonsignificantly, higher in the TIV group (2.5%) compared with the LAIV group (2.1%).

In summary, LAIV demonstrated high levels of efficacy against influenza, with significantly higher efficacy compared to TIV, and cross-protection was observed against the mismatched A/H3N2 strain. Although there appears to be an increase in wheezing in children <24 months of age following LAIV, this was not observed in children >24 months old.

Cost-Effectiveness of the Influenza Vaccine in Children

Lewis et al calculated the number of vaccinations needed to prevent 1 hospitalization or 1 outpatient visit for influenza infection.⁸ Their calculations were based on estimates from 3 published studies of the burden of outpatient and inpatient influenza infection in children aged 6-23 months and 24-59 months. To accommodate the real world variation in influenza vaccine effectiveness from year to year, they varied estimates of influenza vaccine effectiveness from 25%-75%. The number of vaccinations needed decreased with both increasing vaccine effectiveness and increasing influenza season severity. In addition, because the burden of illness is greater in younger children, fewer children would need to be vaccinated to prevent a single hospitalization. For example, at 50% effectiveness, 1031-3050 children 6-23 months of age would need to be vaccinated; whereas 4255-6897 children aged 24-59 months would need to be vaccinated to prevent a single hospitalization. Moreover, there are significantly more outpatient visits for influenza. Thus, in this model, the number of vaccinations at 50% efficacy needed to prevent 1 outpatient visit was 12-42, with the range reflecting differences in season severity.

Extrapolated to the national level, at 50% effectiveness, if 50% of children aged 6-59 months were vaccinated, approximately 2250 hospitalizations and 270,000 to 650,000 outpatient visits for influenza-attributable illnesses would be avoided. These estimates conservatively did not consider indirect effects of vaccination, such as herd immunity that would benefit the vaccinated child’s family members and other contact persons. The investigators concluded that influenza vaccination in children can significantly reduce influenza-attributable medical visits, even with modest vaccine efficacy.

Luce et al modeled the cost-effectiveness of LAIV and TIV using data for children aged 24-50 months from the head-to-head clinical trial and other trials.⁹ Costs were calculated from the probability of children experiencing specific clinical events and costs of resource use. Effectiveness was determined by the number of influenza cases avoided and the number of quality adjusted life years (QALY) lost due to time spent in a reduced health state or mortality. Several conservative assumptions were made, such as ignoring herd immunity and using a greater price difference between LAIV and TIV based on the less expensive thimerosal-containing TIV instead of the more costly preservative-free LAIV ($2.80/dose difference). In addition, the model did not accommodate for compliance when 2 doses of the vaccine were to be given.

They found that, although acquisition costs were $7.72 higher per child for LAIV compared to TIV, LAIV reduced the number of influenza cases, decreased healthcare use by the children, and lessened productivity losses by parents. Accordingly, LAIV resulted in direct and indirect cost savings of $15.80 and $37.72 per vaccinated child, respectively. Overall, the net savings per child vaccinated with LAIV compared with TIV was $45.80. The authors estimated that approximately 4346 cases of uncomplicated influenza, 1225 cases of complicated influenza, 138 hospitalizations, 250 emergency department visits, and 7058 outpatient visits can be avoided for every 100,000 children vaccinated with LAIV. They also estimated that this would result in a cost savings of up to $4.58 million.

References

1. Poehling KA, Edwards KM, Weinberg GA, et al, for the New Vaccine Surveillance Network. N Engl J Med. 2006;355:31-40.
2. Miller EK, Griffin M R, Edwards KM, et al, and the New Vaccine Surveillance Network. Pediatrics. 2008;121:1-8.
3. Coffin S E, Zaoutis TE, Rosenquist AB et al. Pediatrics. 2007;119:740-748.
4. Ampofo K, Gesteland PH, Bender J, et al. Pediatrics. 2006;118:2409-2417.
5. Hoberman A, Greenberg DP, Paradise JL, et al. JAMA. 2003;290:1608-1616.
6. Block SL, Reisinger KS, Hultquist M, Walker RE, for the CAIV-T Study Group. Antimicrob Agents Chemother. 2007;51:4001-4008.
7. Belshe RB, Ambrose CS, Tingting Y. Vaccine. 2008;Suppl 4:D10-D16.
8. Lewis EN, Griffin MR, Szilagyi PG, et al. Pediatrics. 2007;120:467-472.
9. Luce BR, Nichol KL, Belshe RB, et al. Vaccine. 2008;26:2841-2848.
10. Neuzil KM, Hohlbein C, Zhu Y. Arch Pediatr Adolesc Med. 2002;156:986-991.
11. Block SL, Yogev R, Hayden FG, Ambrose CS, Zeng W, Walker RE. Vaccine. 2008;26:4940-4946.

Influenza Prevention and Treatment: The Advisory Committee on Immunization Practices 2008 Guidelines

Robert B. Belshe, MD

Influenza prevention is multifaceted and includes adopting both proven and recommended strategies. Proven strategies include vaccination with the live-attenuated influenza vaccine (LAIV) or trivalent inactivated influenza vaccine (TIV), and the use of antiviral agents that include M2 and neuraminidase inhibitors. Recommended strategies are primarily behavioral and endeavor to reduce the transmission of the virus.

Reducing the transmission of influenza was reported during the 1918 influenza epidemic: people who were ill responded to admonitions to stay home and avoid contact, which resulted in a concomitant decrease in the transmission rate of the flu. Restricting group settings and day care can also reduce transmission. Although no extensive data support that it is effective, anecdotal evidence shows that, with normal school closings during the winter holidays, the flu burden decreases, only to resurge once schools are back in session.

Hygiene standards, such as covering the mouth and nose when coughing and sneezing, and frequent hand washing, may reduce transmission on fomites, or inanimate objects upon which the virus can be conveyed. Although these practices should be encouraged, their effectiveness has not been proven. Flu is most likely transmitted primarily as an aerosol and less often as a fomite.

Cohorting hospitalized patients with influenza should be fairly intuitive. A susceptible person should never be put in a room with a patient who has influenza. In addition, droplet precautions in hospitals are important; however, they are probably more effective at limiting transmission of other diseases. Nonetheless, they are a wise precaution that should be implemented.

Influenza Vaccines: 2008-2009 Season

Six influenza vaccines have been approved for use in the United States (Table 1).¹ Five vaccines are TIV and only one is LAIV, also called the cold-adaptive vaccine. Three of the TIV vaccines are approved for only adults, 1 is approved for children aged at least 4 years, and 1 is approved for children as young as 6 months old. The single LAIV is approved for children starting at age 2 through adults aged 49 years.

Table 1. FDA-Approved Influenza Vaccines, 2008-2009 Season

Table 2. Influenza Vaccine Production and Distribution, US, 1980-2007

Table 3. Live Attenuated Influenza Vaccine Effectiveness in Children (Aged 15-71 Months) by Various Outcomes

Availability of influenza vaccine in the United States has undergone a dramatic increase, almost doubling since 2000 (Table 2). The millions of doses produced but not distributed indicate that supply should not be an issue. Vaccine doses distributed, however, is considered to be an unreliable surrogate for actual use. Vaccine production for 2007 included approximately 12 million LAIV and 130 million TIV doses.

The 3 strains used in the vaccine for the 2008–2009 season are different than those in the previous vaccines. The same antigens are used for the TIV and LAIV vaccines, which are selected by a panel of experts that includes international collaborators from the World Health Organization, public health authorities, and other influenza experts. For influenza A, the 3 strains are Brisbane/59/2007 (H1N1)-like and, for influenza B, the 3 strains are Florida/4/2006-like antigens.¹

Strategy for Influenza Prevention: 2008-2009

Historically, influenza prevention comprised identifying and vaccinating people at highest risk of hospitalization and death. However, this approach had modest success, with failures from 2 major sources: (1) the high-risk population was not adequately identified and vaccinated; and (2) the vaccine has modest efficacy in high-risk populations, particularly the elderly. Accordingly, that strategy is being reevaluated and modified by including age-based recommendations and adding anyone who is likely to transmit the virus to high-risk individuals. This would include all household members of high-risk people.

Evidence supports that school-aged children are responsible for much of the influenza transmission. The potential herd effect that can be achieved by vaccinating children could provide a tremendous secondary benefit and reduce the influenza burden on the community. In fact, many experts believe universal vaccination of school-aged children will reduce transmission in the community, prevent disease in high-risk elderly, reduce the costs associated with influenza, and interrupt influenza outbreaks.

Accordingly, this year, vaccination targets recommended by the ACIP include¹:

• All children aged 6 months to 18 years
• Children and adolescents at high risk for influenza complications (6 months to 18 years of age), including those receiving long-term aspirin therapy and who might be at risk for Reye syndrome after influenza virus infection
• All household members of high-risk people
• Household contacts and caregivers of children aged <5 years and adults aged ≥50 years, with particular emphasis on vaccinating contacts of children aged <6 months
• Everyone aged ≥50 years (approximately one-third of the population ≥50 years of age has a high-risk condition)
• Women who will be pregnant during the influenza season
• Adults and children who have the following should be vaccinated:

• Chronic conditions that increase risk: chronic pulmonary (including asthma), cardiovascular (except hypertension), renal, hepatic, hematologic, or metabolic disorders (including diabetes mellitus)
• Immunosuppression
• Any condition (eg, neuromuscular dysfunction) that can compromise respiratory function

• Residents of nursing homes/chronic care facilities (currently receiving the best coverage, with >80% being vaccinated)
• Healthcare personnel
• Household contacts and caregivers of people with medical conditions that put them at high risk for severe complications from influenza

Children aged 6 months to 8 years who have not been previously vaccinated should receive 2 vaccine doses. The second dose should be administered ≥4 weeks after the first dose. All other children aged 6 months to 8 years who have previously received ≥1 vaccine dose at any time should receive 1 dose of the 2008–2009 influenza vaccine.

Live-Attenuated Influenza Vaccine versus Trivalent Inactivated Influenza Vaccine versus Placebo

In adults, TIV and LAIV appear to be similarly effective. In children, a 2-year blinded study of LAIV versus placebo was performed, with children aged 15-71 months vaccinated at time 0 and 3 months later in the fall when wild-type influenza began to occur.² Approximately 18% of the placebo group had culture-confirmed influenza, compared with only 1% of children in the vaccine group. In the second year of the study, children were revaccinated with either vaccine or placebo and, at the end of the second year, 30% of the placebo recipients had one or more episodes of culture-confirmed influenza, compared with less than 3% of vaccinated children, for an overall 2-year efficacy of 92%. This result was higher than what was historically experienced with inactivated influenza vaccines. In addition, the year 2 efficacy against antigenically drifted variants was 86%.

Effectiveness measures in that study indicated that all febrile illness underwent a significant reduction of 21% and 19% in the first and second years, respectively. Not only does that represent very high effectiveness of the vaccine, but it also indicates that about 20% of fevers in this population were due to influenza. Statistically significant reductions in febrile otitis media, antibiotic use for febrile illness, and visits to the doctor in the vaccinated children were also demonstrated (Table 3).

More recently, a head-to-head trial demonstrated that LAIV is more protective against influenza than TIV.³ Children were vaccinated in October and 80% received a second dose of vaccine in November. Children who were previously vaccinated received only 1 dose of vaccine, and all children were cultured for influenza whenever they had an illness suggestive of the flu. Almost 10% of children aged 24-59 months had culture-positive influenza despite receiving 2 doses of TIV, compared with approximately 4.5% of children given LAIV, and influenza rates between groups diverged quickly, beginning in January at the onset of the flu season. Compared with TIV, LAIV was associated with a significant reduction in culture-confirmed influenza and with a significant reduction in lower respiratory disease. In addition, LAIV-vaccinated children had fewer cases of otitis media associated with the flu, and there was greater efficacy against antigenically drifted viruses, as well as against those that were well-matched, in the LAIV group.

Duration of Immunity with Live-Attenuated Influenza Vaccine

Several studies provide information on the duration of immunity following vaccination with LAIV. Four studies that were performed in children aged 6 months to 18 years were reviewed by Ambrose et al.⁴ There was no significant difference in vaccine efficacy in year 1 whether children were vaccinated 1-5 months, 5-9 months, or 9-12 months previously. In each case, efficacy was in the 70%-80% range.

In the second year of one of the studies, some children who had previously been vaccinated received placebo. Those children retained 56% efficacy in the second influenza season, which is a substantial protection. The influenza virus is constantly changing; accordingly, not only waning immunity, but also a different circulating virus would be expected to reduce protection. These data indicate that protection after LAIV is very durable.

Comparative Adverse Events of Live-Attenuated Influenza Vaccine and Trivalent Inactivated Influenza Vaccine versus Placebo

Both TIV and LAIV are generally well-tolerated. With the inactivated vaccine, most reactions, particularly pain, tend to be at the injection site. There may be hypersensitivity events with TIV and LAIV associated with the egg proteins, as both are made in eggs. The preservative thimerosal is in some of the TIV preparations and has been associated with unproven toxicity concerns related to its mercury component. Joint statements in 1999 from the FDA, National Institutes of Health, Centers for Disease Control and Prevention, American Academy of Pediatrics, and the Health Resources Services Administration urged vaccine manufacturers to reduce or eliminate thimerosal in vaccines⁵; LAIV does not contain thimerosal. Adverse events associated with LAIV typically include mild runny nose and nasal congestion. Initially, a concern about potential transmission of virus from the live vaccine existed. However, as >10 million live vaccine doses have now been given, transmission of influenza vaccine virus is likely a nonissue.

Wheezing Following Live-Attenuated Influenza Vaccine

In studies with children <2 years of age, wheezing events were associated with the live vaccine, which was not a finding for children ≥24 months of age. In fact, in the original trials of LAIV versus placebo, children aged ≥4 years receiving LAIV had 60% less wheezing 6 months post-vaccination compared to those receiving placebo. In a later study comparing TIV with LAIV during the 2004-2005 flu season, approximately 1700 children in each group were <24 months of age.⁵ Within 42 days after the first dose, there were 55 cases of wheezing in the LAIV group and 34 cases in the TIV group (adjusted rate difference 1.18; 95% CI, 0.13-2.29), which achieved statistical significance and contributed to recommending LAIV for children aged ≥24 months. Children aged ≥24 months with preexisting wheezing were more likely to have another wheezing event regardless of the vaccine, which approached approximately 10%. This was not considered to be related to the vaccine.

The live vaccine is not recommended for children <5 years old who have reactive airway disease if they have recurrent wheezing; these children should receive TIV. In a head-to-head trial in Europe comparing a single dose of TIV and LAIV in children aged 6-17 years with a clinical diagnosis of asthma, both LAIV and TIV were similarly well-tolerated.⁶ There were wheezing events, but they were not significantly different between the 2 groups, although children receiving LAIV had a greater incidence of runny nose/nasal congestion (66.2%) than TIV (52.5%) recipients, consistent with experiences in children without asthma. Approximately 70% of TIV recipients reported injection site reactions. Significantly, protection against flu in these asthmatic children was 35% greater following LAIV compared to the inactivated vaccine.

In a safety study, Gaglani et al reported that, among healthy children aged 1.5-18 years with a history of intermittent wheezing, there was no increased risk of new-onset asthma through 4 consecutive years of single annual LAIV doses. ⁸ In addition, children without a history of wheezing were also not at increased risk for new-onset asthma.

Treatment of Influenza

Two surface proteins on the influenza virus are targets for pharmacologic intervention: neuraminidase and M2 blockers.

Neuraminidase is an enzyme that is responsible for releasing new viral particles from infected cells. If the enzyme is blocked with a neuraminidase inhibitor, the virus aggregates as a clump and does not release from infected cells. Therefore, it theoretically does not transmit to other cells. There are inconsistent data, however, on whether viral shedding is reduced.

Two neuraminidase inhibitors are approved for use in the United States: zanamivir, an inhaled powder approved for treatment of children >7 years of age and for prophylaxis of children aged >5 years; and oseltamivir, approved for the treatment and prevention of influenza in children aged >1 year. Zanamivir is not absorbed when given orally. Therefore, it must be inhaled into the lungs with a puffer that requires some patient assistance. Oseltamivir is well-absorbed when given orally.

Although they are not virus-free, patients given neuraminidase inhibitors within the first 48 hours after the onset of illness report feeling better within 24 hours. There is little viral resistance to neuraminidase inhibitors, although some has been reported for H1N1. Most H3 and most influenza B are susceptible to neuraminidase inhibitors.

M2 is an ion channel that is a small, minor component of the virus surface but is an important regulatory protein that allows the interior of the virus to be acidified during its absorption and penetration phase. Amantadine and rimantadine are two ion channel blockers that inhibit acidification of the interior of the virus and prevent viral infection at the cell surface. However, many isolates of influenza—particularly influenza H3N2—are completely resistant to M2 inhibitors; accordingly, these compounds are not currently recommended.

The CDC provides recommendations for whom antiviral treatment is appropriate¹:

• People hospitalized with laboratory-confirmed influenza
• People with laboratory-confirmed influenza and pneumonia, with bacterial coinfection, or who are at high risk for influenza complications
• People presenting to medical care with laboratory-confirmed influenza within 48 hours of influenza illness onset who want to decrease the duration or severity of their symptoms and transmission of influenza to others at higher risk for complications

Summary

Influenza is a common and serious disease in children and adults. Children are important vectors for the transmission of influenza; accordingly, they present an important target for influenza vaccination. Both TIV and LAIV have efficacy against influenza, although LAIV is significantly more effective than inactivated vaccines in healthy children aged >2 years. In addition, it provides sustained protection against influenza of similar strains for several months and provides some protection against strains that have undergone antigenic drift. The treatment of influenza with antiviral agents can shorten the disease by 1 to 2 days and prevent complications, and is recommended for anyone who is likely to transmit the virus to high-risk individuals.

References

1. Fiore AE, Shay DK, Broder K, et al, and the Centers for Disease Control and Prevention (CDC), Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2008 Aug 8; 57(RR-7):1-60.
2. Belshe RB, Gruber WC. Pediatr Infect Dis J. 2000;19:S66-71.
3. Belshe RB, Ambrose CS, Tingting Y. Vaccine. 2008;26(Suppl 4):D10-D16.
4. Ambrose CS, Yi T, Walker RE, Connor EM. Pediatr Infect Dis J. 2008;27:744-748.
5. Centers for Disease Control and Prevention. MMWR. 1999;48:996-998.
6. Belshe RB, Edwards KM, Vesikari T, et al, and the CAIV-T Comparative Efficacy Study Group. N Engl J Med. 2007;356:685-696.
7. Fleming DM, Crovari P, Wahn U, et al, and the CAIV-T Asthma Study Group. Pediatr Infect Dis J. 2006;25:860-869.
8. Gaglani MJ, Piedra PA, Riggs M, et al. Pediatr Infect Dis J. 2008;27:444-452.
9. Kaiser L, Wat C, Mills T, et al. Arch Intern Med. 2003;163:1667-1672.
10. Jefferson T, Rivetti A, Harnden A, Di Pietrantonj C, Demicheli V. Cochrane Database Syst Rev. 2008;(2):CD004879.

School Influenza Vaccination Programs—The Maryland Model

Marge Hoffmaster, RN

It has been known for many years that school children are the primary transmitters of the influenza virus (Figure 1).¹ A longitudinal community study in Tecumseh, Michigan, in the 1960s demonstrated that the highest frequency of influenza infection was in the school-aged population.² Significantly, when school children received the inactivated vaccine, the entire community witnessed a threefold reduction in influenza. In Japan, vaccination of school children was mandatory for several years starting in 1977.³ When the law was in place, vaccination rates for school children ranged between 50% and 85%. During that period, deaths attributed to pneumonia and influenza decreased by 10,000 to 12,000 per year, and deaths from all causes by 37,000 to 49,000 per year, supporting that herd immunity was providing protection to others in the community, including the high-risk elderly. After the law was repealed in 1994, vaccination rates decreased with a concomitant increase in mortality rates.

Figure 1. Children Introduce and Spread Influenza

Recent studies also demonstrated a significant effect on community health when children received influenza vaccination. For example, a community-based study in Texas from 1999-2001 provided cold-adapted live-attenuated influenza vaccine (LAIV) to 20%-25% of children aged 1.5-18 years. During that interval, adults >35 years of age in intervention communities experienced an indirect significant reduction in medically attended acute respiratory illness.⁴ In addition, the effect of a school-based vaccination program on absenteeism, which is of critical concern to school systems, was the focus of a recent intervention launched in Carroll County, Maryland, in 2005.⁵ In that study, 12,090 students in the 21 county elementary schools were offered free vaccination with LAIV. A vaccination rate of 44% was achieved, which represented 85% of students who remained eligible after screening for chronic diseases. In 2005, absenteeism decreased significantly compared with control schools, not only in Carroll County elementary schools, but also in high schools, as well. Middle schools showed a similar, but nonsignificant, difference in absenteeism.

With this clear evidence pointing to the benefits of vaccinating school children, why are influenza vaccination rates for children in the United States so low, with coverage in children 2-17 years of age for the 2004-2005 flu season at 12.3%?⁶ The vaccination rate in children with high-risk conditions was higher but still at an unacceptable 34.8%. Can school-based vaccination programs provide the solution? The answers to these questions are considered throughout this monograph and are reiterated here, focusing on those especially related to in-school programs. In addition, the necessary—and often challenging—components of a school-based influenza immunization program are reviewed, based on the Carroll County experience.

Constraints to Influenza Vaccination Programs

The perceived lack of importance of influenza vaccination plays a major role in the low vaccination rates. In the middle of an epidemic, everyone wants to be vaccinated. However, preventing an epidemic requires convincing people of the importance of participating in vaccination programs. As emphasized repeatedly, myths regarding vaccination must be dispelled, and benefits must be understood, including that they outweigh the risks. The health effects of influenza are too often discounted, and the fact that healthcare providers themselves often do not promote or emphasize the need for the preventative benefits of immunization can contribute to poor program acceptance. Accordingly, education is a primary need that must be fulfilled before target immunization rates can be achieved.

Lack of access can also provide a barrier to immunization. This can include availability of the vaccine itself, financial access by the individual, and access to the physician’s office related to time or distance factors. A school-based program could address the first 2 issues and resolve the latter concern. In addition, skepticism about government programs that may be viewed as “taking over” our children is widespread. This barrier can be addressed by trusted, informed physicians who promote vaccination to their patients.

Components of a Successful School-Based Influenza Vaccination Program

A school-based vaccination program is, of necessity, a multidisciplinary process, requiring effective and efficient collaboration and cooperation among the participating entities if the program is to succeed. Nine key and inter-related components comprise such a program, and they must be coordinated and running smoothly to avoid obstacles that may prevent successful implementation and to help establish program sustainability (Figure 2).

Figure 2. Multiple Requirements for a School-Based Immunization Program

Global Requirements

The vaccine must be available to all eligible individuals. Vaccine administration must be efficient and coordinated, targeting at least 30 children vaccinated per hour per healthcare provider. To be acceptable to the administration, there must be minimal disruption of the school schedule.

Adequate space must be available to handle the workflow, with sufficient work stations. Containers for medical waste must be available; these may possibly be obtainable through volunteers. Schools cannot be expected to provide them or to dispose of the medical waste.

Schools keep records of mandatory immunizations, and most states have immunization information systems (IIS), or registries. Registry use should be encouraged. Because it is considered a public health activity, reporting immunizations to an IIS is exempt from the Health Insurance Portability and Accountability Act of 1996 (HIPAA) Privacy Rule.⁶

Multidisciplinary Partnerships

Key players that can make or break establishing a school-based vaccination program include:

• Vaccine suppliers. Without vaccine, there can be no vaccination program.
• Educational institutions. In addition to respecting school schedules, educating institutional partners about the benefits of immunization can greatly assist with team building:

• “If you vaccinate, they will be in school.”
• With its access to data and the adult population, the school system can provide valuable communication and data assets to move the program forward.

• Health. Local health departments are either tangentially or intricately involved with the school system.

• County health department. Will be an advocate for the program, but a relationship must be established before program launch.
• Local hospital. Can be an excellent resource for staff and possibly materials.
• Private practitioners. Must be included in the planning from the beginning. Assure they are aware of the benefits of vaccination, and encourage them to promote the benefits to their patients, serving as an educational resource.

• Community partners. Although community partners may not be involved in program planning from the beginning, they can be valuable resources.

• Public and private resources. Can assist with promoting the project.
• Media. Involving the media early in the project can preempt negative speculative responses.
• Parents. The Parent Teachers Association (PTA) should be contacted as soon as there is an agreement to proceed, to promote the project.

Funding

One of the first questions the school system will have is, “Who is going to pay for it?”

• Grants. Without grant funding, access for all eligible individuals cannot be assured. The greatest participation can be achieved with across the board grant funding.
• Vaccines for Children (VFC). Schools have information on who qualifies for the VFC program. Feasible, good participation can be achieved with a combination of grant and VFC support, although it adds additional effort to administer the program through 2 funding sources.
• Private insurance. Billing private insurance can be challenging. It requires considerable staff time, information provided may be incorrect, and denials related to delayed response to vaccine recommendation expansions can obviate the efforts.
• Self-pay. If parental payment is required, participation of children who are most in need of the vaccination can be significantly restricted.

If VFC, private insurance, and self-pay combine to sponsor the project, and vaccines are administered outside of school, participation will be adversely affected.

Education

Decision makers should be educated first, although all participants in the program at all levels must be adequately informed. The clerical staff who will be preparing and processing the paperwork must understand the importance of their contribution. Stress the need to adhere to deadlines, and assure information is available to give to the community. This labor-intensive activity has a large payoff in the success of the program. Allow adequate time for dissemination and follow-up questions. A professional information resource could be a live person; however, an interactive Web site, if properly maintained by nurses, medical or pharmacy students, or other healthcare professionals, may be adequate. Assure appropriate technical information is conveyed, including side effects of the vaccine and that it is an FDA-approved product. As with required vaccines, there will be controversy about recommended vaccines. Anticipate questions and have answers ready. Use multiple venues that the school system has available and tap into their established methods of communicating with students and parents.

Vaccine Logistics

Vaccine ordering, delivery, storage, administration, medical waste disposal, and documentation must be carefully planned. Local health departments or hospitals may assist with ordering the vaccine. Depending on partnership relationships, a county health officer or hospital physician may order the vaccine for you.

Estimate the number of doses required as accurately as possible. If the program includes an entire school system, break it down into the number of immunizations per site. This removes the clinic day burden of having to separate bulk vaccine, and the logistics of transferring vaccines from a central storage area to the site while assuring temperature requirements are maintained. If a schedule change requires clinic deferral, assure a place is available where the vaccines can be stored; for example, the local health department or hospital. Don’t expect the schools to have storage capabilities.

Permissions

The vaccines will most likely be given without parental presence, so permission forms must be thorough, easy to understand (a fourth-grade level is recommended), and available in multiple languages as relevant. Children of immigrants are particularly important to reach out to, because they are often underserved, either due to misunderstanding of the US healthcare system or lack of insurance. Children with illiterate parents also access healthcare infrequently, so efforts must be made to assure these children are included. Be aware of and take advantage of school system services that provide interpreters and regular liaison persons for illiterate parents.

Although parents self-report children’s health concerns, double check with school system records and rely on your relationship with private physicians to facilitate identification of students with chronic health concerns who may be candidates for the trivalent inactive influenza vaccine rather than the LAIV. Assure that any physician contacts are made and necessary sign-off forms are completed in advance. If programs are limited to elementary schools, accommodations for students who may be pregnant should be unnecessary.

Staffing

This is a labor-intensive program, so overplan. Assure adequate management of paperwork, from preparing forms, collating returned information, and processing disbursements. Staff training must be undertaken well in advance of the clinics. It is preferable to have site-based support staff who are familiar with the system, have a vested interest in proper performance, and can be given oversight of their work. In addition, site staff should have adequate liability coverage.

If site-based support staff are unavailable, community volunteers can be valuable assistants. They also have a vested interest and know the community. If they are already involved with the schools, they would already be screened and allowed in the schools. Their limited information access may be offset by the local school nurses. Professional volunteers can also be helpful, particularly if they know the students and are familiar with pediatric patients. State volunteer response teams may be contacted early in the planning stages about providing volunteer professionals who can administer the vaccines in the schools. It is essential to assure proper identification and assure that adequate liability coverage is in place for all volunteers.

Staff Preparation

It is important to have a central location for staff training and to have an established training schedule. Do not assume volunteers are familiar with the type of vaccine that will be administered; be sure the training is adequate. Roles and responsibilities must be clearly defined and understood by the volunteers. If volunteers are not community-based, maps to the site and to the various administrative site areas should be available. Volunteers should have a contact person to report to.

Prepare for the logistics of moving the vaccines to the site, including loading and unloading. Volunteers who are in close communication with the central site administrator should be available not only at the central location, but also at the hospital or health center vaccine storage area.

Arrange for basic supplies to be available at the site, including emergency medications. There should be at least 2 epinephrine pens at each site. If there will be an all-day clinic, assure there will be food for the volunteers.

Scheduling

Be sure to defer to the school sites for scheduling the clinics. Cooperation will be enhanced when school schedules are respected. There may be unavoidable scheduling conflicts, such as mandatory tests; secondary school schedules are less flexible than those of elementary schools.

When a schedule has been made, stick to it. Anticipate glitches such as weather-related school closings and be sure to have a backup plan to accommodate unplanned interruptions or cancellations. Remember that some students will be receiving a second vaccination, and adjustments for that date must be in the backup plan. Absenteeism is another consideration that must be accommodated, both for first and, when applicable, second vaccinations.

Summary

Education and communication are integral components of a successful school-based vaccination program. Involve physicians as much as possible. Media support is also important, and strong local support should not only provide the mainstay of the program, but it is necessary to allow timely response to problems that may arise. Make realistic timelines and adhere to them.

Advocate for registries. By combining immunization information from different sources into a single record for each individual, a registry can provide official and comprehensive immunization records regardless of vaccination location.⁶ They can remind families and providers when immunizations are due and help identify people at high risk.

School-based vaccine programs can be important tools in the effort to achieve recommended vaccination goals. If they are run efficiently and smoothly, they can provide substantial benefits to the community as well as to the school system.

References

1. Elveback LR, Fox JP, Ackerman E, et al. Am J Epidemiol. 1976;103:152-165.
2. Monto AS, Maassab HF. Dev Biol Stand. 1977;39:329-335.
3. Reichert TA, Sugaya N, Fedson DS, et al. N Engl J Med. 2001;344(12):889-896.
4. Piedra PA, Gaglani MJ, Kozinetz CA, et al. Vaccine. 2005;23:1540-1548.
5. Davis MM, King JC, Moag L, et al. Pediatrics. 2008;122:e260-e265.
6. Centers for Disease Control and Prevention. Immunization Information Systems. Questions Providers Ask About Immunization Information Systems. Available at: http://www.cdc.gov/vaccines/programs/iis/downloads/IIS-flyer-06-04-08.pdf. Accessed September 26, 2008.

Practical Issues of Influenza Vaccination—Challenges and Strategies

Stanley L. Block, MD

A tremendous gap exists between Advisory Committee on Immunization Practices (ACIP) vaccination recommendations and vaccination rates. About 80% of the US population is in one of the recommended groups, which would require more than 200,000,000 doses annually. However, only 120,000,000 doses are distributed; and actual vaccination is considerably less. Accordingly, barriers to utilization of these vaccines must be overcome if influenza illness is to be prevented.

Overcoming Barriers to Influenza Vaccination

Flu season is variable with an unpredictable onset., and durability of the vaccine can be an issue. Unpredictable supplies, including late-arriving orders, have also plagued vaccination implementation efforts. The American Medical Association has initiated a continuously updated Web-based Influenza Vaccine Availability Tracking System (IVATS) that lists vaccine brands, distributors, date updated, and status as “in stock” or “on order.”¹ Predicting usage is difficult, so pre-ordering large amounts of the injectable trivalent inactivated influenza vaccine (TIV) 9 months in advance can be problematic. The live-attenuated vaccine (LAIV) has a benefit in that practitioners can “order as they go”; that is, small orders can be made and shipments usually arrive within 2 to 3 days.

The primary constraint to influenza vaccination is education. Physician recommendation has been shown to play a significant positive role in increasing vaccination rates (Table 1).² With physician recommendation, 80% of adult patients will accept vaccination.

Table 1. Factors Associated with Adult Influenza Immunization

With proper education about increased susceptibility and decreased vaccine risks, rates of vaccination in children can increase dramatically. However, first, physicians must be convinced that influenza is a common and significant illness and that it poses risks to both children and adolescents. Physician complacency is evidenced by data indicating that <50% of healthcare workers are vaccinated.³ They must understand that the vaccine is effective, safe, and acceptable to both themselves and the patient. With proper education, practitioners can advocate for influenza vaccination, explaining its benefits, risks, and side effects, and dispelling misconceptions.

Because flu vaccination is not mandatory, many people assume they do not need it. A common misconception, even among physicians and healthcare providers, is that influenza is not a life-threatening disease, and that the vaccine is not meant for healthy children. Indeed, many myths about influenza and the vaccines exist (Table 2). Many people believe that the injectable vaccine is not suitable for young children. In fact, it has few contraindications, and they are limited to egg protein or vaccine component hypersensitivity and having had a life-threatening reaction after a previous influenza vaccination. Additional concerns that the vaccine is not effective create issues regarding credibility when strains responsible for the flu are not those used in the vaccine or when antigenic drift affects vaccine effectiveness. Another common misconception is that the influenza vaccine causes the flu. Some people believe that the thimerosal in the TIV vaccine causes autism spectrum disorders. Acceptance of TIV can also be adversely affected by children’s natural aversion to injections. Even adults complain about soreness and myalgia related to the injection.

Table 2. Misconceptions About Influenza Immunization for Children

Although doubts about childhood vaccine effectiveness are a deterrent to accepting vaccination, parental attitudes can change dramatically during an outbreak, especially when deaths in children occur. Daley et al performed a pre- and post-season survey of parents in the Denver area in 2003-2004, where 4 children died during the flu season.⁵ Comparing attitudes that changed from pre- to post-season, they found that 48% more parents believed that their child was susceptible to influenza, 58% changed their view to consider influenza infections as severe, and 66% associated fewer risks with the influenza vaccine than they did before the flu season. Media influences were associated with increased perceptions of influenza severity, and 82% of surveyed parents had their child immunized. Physician recommendation was a positive factor influencing immunization.

Achieving recommended vaccination goals would place a significant burden on primary care practices. The volume of patients under the current recommendations would overwhelm primary care physicians. Practice-level strategies that may minimize this burden include (1) using well child care visits and sick visits as opportunities for vaccination, (2) expanding the vaccination window so that influenza vaccination is provided over the maximum possible period, and (3) establishing vaccination-only clinics to efficiently manage additional visits.⁴ Many vaccination opportunities are missed when children visit the primary care physician for minor illnesses, and using LAIV can be time-sparing because most children are more compliant with the nasal spray than with injections.

Durability of the vaccine can affect plans of when to vaccinate. Typically, the injectable is given from late September/early October through early December. A new concept from the Centers for Disease Control (CDC) is to extend the vaccine season past December. The flu receives media attention during that time and interest is piqued. However, if the injectable vaccination is given too early and a late flu epidemic occurs, breakthrough cases of influenza become more likely.

With LAIV, a larger immunization window is feasible. Data show that LAIV has long durability, achieving 70% to 80% effectiveness for up to 12 months.⁶ Therefore, LAIV can be used to vaccinate children in the summer months and during sports physicals at the start of the school year, thereby increasing access to older children. The intranasal LAIV is particularly acceptable at a time when the children may already be getting up to 4 shots as part of their required immunizations for preschool and middle school.

In a recent study by Nolan et al, the safety, tolerability, and immunogenicity of LAIV administered concurrently with the measles-mumps-rubella (MMR) and varicella vaccines to healthy children 12-15 months of age was evaluated.⁷ The results showed that the combined administration of these vaccines was well-tolerated and provided equivalent immunogenicity compared with separate administration, which provides indirect reassurance for co-administration of MMR, varicella, and LAIV.

Older children may present opportunities for vaccination only when they are seen for mild illnesses or trauma. For these children, as mentioned earlier, misconceptions about the influenza vaccine may cause parents to decline vaccination at a time when their child is sick.

Scheduling appropriate return visits for children who require 2 doses—that is, vaccine-naïve children <9 years of age—must also be considered. Many studies have shown that 2 doses of TIV are required to achieve adequate immunity, compared with 89% efficacy achieved with a single dose of the LAIV.⁸ In addition, a recent open-label study comparing efficacy of 1 dose of TIV or LAIV in children 5-18 years old showed a significant reduction in influenza-positive illness, pneumonia, and influenza events in LAIV- but not TIV-vaccinated children.⁹

Immunization Rates

In data published by the CDC,^10,11 the immunization rate in children 6-23 months old who received 1 or more doses was 48% in the 2003-2004 season (Figure 1). Data for high-risk children 2-17 years old were available for 2 seasons and showed a decrease in the vaccination rate from 42% in 2003 to 35% in 2004. Similarly, rates decreased from 20% to 12% for healthy children 2-17 years old. More recent data from the ACIP acquired by 8 states in the Sentinel Site Project for the 2007-2008 season showed a similar vaccination rate for children 6-23 months old, where 41% received at least 1 vaccine dose. However, only one-half of the patients who received 1 dose, or 20% overall, were given the second dose.¹² For children 24-59 months old, a new group in this year’s ACIP influenza vaccination recommendations, full vaccination was achieved in only 15%.

Figure 1. Influenza Immunization Rates 2004–200510,11

Important Vaccine Attributes

Durability of immunity, protection against mismatched strains, and efficacy of a single dose are important attributes of influenza vaccine. With few children receiving the annual vaccine or returning for second doses, durability of the vaccine and cross-strain protection become important. In a recent study of LAIV durability, Halloran et al showed that LAIV provided cross-protection to a drift variant of the A/Panama/2007/99 (H3N2) vaccine strain.¹³ In addition, if a child who should get 2 doses comes in late in the season, the single-dose protection with LAIV makes it a preferred option.

Promoting Influenza Vaccination

Because LAIV is available as early as July in some offices, vaccination or counseling should be offered at every well visit and acute-care visit starting in late summer or early September and continuing into December. Walk-in clinic days on Saturdays, Sundays, and evenings are critical to increasing vaccination rates. Standing orders should be available at local health department clinics, pharmacies, grocery stores, and high school and middle school nurses’ offices.¹⁴

Flu vaccine posters, which are readily available on the CDC Web site, should be displayed prominently in every examination room.¹⁵ Screening and reminders can also help with vaccination success. Electronic medical records with pop-up reminders and flagged charts can be valuable. Documentation and tracking are essential to a successful program. Reminders can be put on bills, at the check-in counter, and in waiting rooms near the posters.

Attention to age issues, however, can be a challenge. For example, if a child 22 or 23 months old is in the office in November, should he or she be vaccinated with TIV or LAIV (which is off-label for children <2 years), or should the physician attempt to schedule a return visit to give LAIV when the child reaches 24 months?

Summary

Despite increasing vaccine availability and expanding patient groups recommended by the ACIP to receive the annual influenza vaccine, vaccination rates are considerably below target. A primary barrier is lack of education about the importance of the disease and the vaccines. Practitioners have an opportunity to positively affect immunization acceptance. In addition, they must understand the benefits of each type of vaccine and assure that their patients are given access to the best vaccine option. Finally, logistic constraints including vaccine supply and office and record management must be optimized. With attention to these needs, progress can be made to reduce the burden of influenza.

References

1. IVATS (Influenza Vaccine Availability Tracking System). American Medical Association. Available at: http://www.ama-assn.org/ama/pub/category/16919.html. Accessed September 26, 2008.
2. Armstrong K, Berlin M, Schwartz JS, Propert K, Ubel PA. Am J Prev Med. 2001;20:21-25.
3. Pearson ML, Bridges CB, Harper SA. MMWR 2006;55:1-16
4. Szilagyi PG, Iwane MK, Schaffer S, et al. Pediatrics. 2003;112:821-828.
5. Daley MF, Crane LA, Chandramouli V, et al. Pediatrics. 2006;117:e268-e277.
6. Ambrose CS, Yi T, Walker RE, Connor EM. Pediatr Infect Dis J. 2008;27:744-748.
7. Nolan T, Bernstein DI, Block SL, et al, and the LAIV Study Group. Pediatrics. 2008;121:508-516.
8. Belshe RB, Mendelman PM, Treanor J, et al. N Engl J Med. 1998;338:1405-1412.
9. Piedra PA, Gaglani MJ, Kozinetz CA, et al. Pediatrics. 2007;120:e553-e564.
10. Link MW, Mokdad AH, Balluz LS, et al. MMWR. 2004;53:1147-1153.
11. GL Euler GL, Bridges DB, Brown CJ, et al. MMWR. 2005;54:304-307.
12. Centers for Disease Control and Prevention (CDC). MMWR. 2008;57:1043-1046.
13. Halloran ME, Piedra PA, Longini IM, et al.Vaccine. 2007;25:4038-4045.
14. Kempe, A, Daley MF, Barrow J, et al. Pediatrics. 2005;115:146-154
15. Centers for Disease Control and Prevention. The Flu Gallery. Free Flu Materials. Available at: http://www.cdc.gov/flu/professionals/flugallery/. Accessed October 01, 2008.