Influenza is the most common cause of admission of children to the emergency department (ED) in many countries during winter months. Among children admitted to the ED at Milan University's Institute of Pediatrics during the 2003–2004 winter season with influenza-like illness (ILI) due to either influenza, respiratory syncytial virus (RSV), human metapneumovirus, coronavirus, rhinovirus, or adenovirus, 30% of illnesses were due to influenza virus (Fig. 1). 1 Rates of ED admissions for children with a laboratory diagnosis of influenza in the first 5 years of life are high. A study among approximately 2700 Italian children aged 0–3 and 4–5 years found the rate of ED admission for influenza in the 2001–2002 season to be 17.4 and 12.9%, respectively.2 During the 2002–2003 season, the rate of admission for ages 0–3 and 4–5 years was 5.5 and 4.4%, respectively.
Cardiopulmonary disorder-related admissions during the influenza season are high during the first 5 years of life, according to data from a U.S. Medicaid program.3 The study showed that the average excess annual hospitalizations for cardiopulmonary conditions per 10,000 children during an influenza season were 104 for children aged <6 months, 50 for those 6 to <12 months, 19 for those 1 to <3 years, 9 for those 3 to <5 years, and 4 for those 5 to <15 years. Investigators also found that, in absence of high-risk conditions, the rate of hospital admission for influenza in the first 2 years of life was even higher than that observed in adolescents and adults with chronic disorders. These findings show that, in the first 2 years of life, even healthy children are at higher risk of hospitalization than children with illnesses for whom vaccination is specifically recommended. Still, the rate of hospitalization for influenza in children 2–4 years of age is also relatively high.4,5
Interplay of Influenza-Like Illnesses
A study of 3310 children revealed that there is a different distribution of influenza infection by age and influenza virus strain (Fig. 2). There is not a significant difference in infection rates of type A influenza virus across age groups. However, type B influenza tends to infect school-age children (>5 years of age) more often than children younger than 5 years of age.6
An overlap exists in the clinical presentation among different viral infections caused by influenza A and influenza B as well as infections due to RSV, adenovirus, and other viruses (Table 1). 6,7 Determining the underlying cause of an ILI in a child in the ED is complicated by this overlap. Predictably, the number of outpatient visits and courses of antibiotics are also high among children who are positive for ILI infections.
Influenza-Related Deaths and Serious Complications
A U.S. study of the 153 influenza-related deaths occurring during the 2003 and 2004 influenza season in children <18 years of age and reported by state health departments revealed that half of deaths were in previously healthy children.8 Only 33% of deceased children had an underlying disorder thought to increase the risk of influenza-related complications. A number of the healthy children (63%) were <5 years of age. This study underscores the need to make influenza vaccine coverage a priority.
Complications of Childhood Influenza
Complications of childhood influenza include nosocomial transmission to hospitalized children with risk factors that make them vulnerable and neurologic events. A study by Newland et al showed that influenza in children between 6 and 23 months of age was a risk factor for neurologic complications, mainly seizures.9 Among the study's 842 children who were hospitalized with influenza, 72 had at least one neurologic complication (mostly seizures) related to influenza. The study also showed that independent risk factors for influenza-related neurologic complications were an age of 6–23 months and underlying neurologic or neuromuscular disorders.
Cost of Influenza
The high cost of influenza is associated largely with therapeutics, particularly antibiotics and antipyretics, and to a lesser degree with diagnostics, room costs, and supplies.7,10 Costs related to prevention include those to patients as well as those absorbed by the healthcare system. These costs are likely to be greater for management of influenza in children <6 months of age but are certainly a consideration in older children, regardless of the presence of high-risk conditions.
Data from the United States and Europe reveal that the socioeconomic burden of influenza on both children and their families is significant (Table 2). Data from the households of children with influenza reveal that outpatient and ED visits; antipyretic, antibiotic, and other medication use; and lost parental or sibling work days is high, even higher than that observed for RSV.7,11
Reconsidering Strategies for Prevention
Given the healthcare burden of influenza in children, we have to reconsider our strategies for its prevention. In keeping with this, the World Health Organization (WHO) has recommended a vaccine for the 2008–2009 influenza season in the Northern Hemisphere that differs from the one recommended for the Southern Hemisphere by 1 viral type.12,13
Specifically, the WHO recommends that influenza vaccine for the 2008–2009 influenza season in the Northern Hemisphere contain the following constituents:
- an A/Brisbane/59/2007 (H1N1)-like virus
- an A/Brisbane/10/2007 (H3N2)-like virus
- a B/Florida/4/2006-like virus
The WHO recommends that vaccines used in the Southern Hemisphere for the 2008–2009 season contain the following constituents:
- an A/Solomon Islands/3/2006 (H1N1)-like virus
- an A/Brisbane/10/2007 (H3N2)-like virus
- a B/Florida/4/2006-like virus
The recommendation by the WHO for annual vaccination is an attempt to provide an adequate overlap between the vaccine and the circulating viruses. Annual changes in influenza vaccine composition are necessary because circulating influenza viruses in humans usually develop permanent antigenic changes that require annual modification of the influenza vaccine formulation. Updates in influenza vaccine composition should ensure the closest possible match between the influenza vaccine strains and the circulating influenza strains.
Authorities worldwide recommend vaccination for all children >6 months of age who have chronic pulmonary, cardiovascular, renal, hepatic, metabolic, diabetic, or immunologic disorders or conditions that can compromise respiratory function or increase the risk of aspiration.14 Moreover, vaccination is recommended for pediatric patients aged ≥6 months who are receiving long-term aspirin therapy and are at risk for developing Reye syndrome.14
Data on actual coverage in different countries show that compliance to these recommendations is low. Our study of the rate of influenza vaccination in Italian children at high risk for influenza complications due to chronic illness during 3 recent influenza seasons revealed that the rate of vaccination was sorely inadequate (Fig. 3). 15 Of the 5286 study participants aged <14 years who were seen in an ED on either of 2 days between 1 January and 30 April 2003, 274 (5.2%) were judged high-risk. Use of influenza vaccine had increased significantly by the final season (2000–2001, 5.1%; 2001–2002, 12.9%; 2002–2003, 26.3%; P < 0.001). Lowest vaccination rates occurred in children with asthma or cardiac disease. Our findings are consistent with data from other countries showing that the vaccination rate of high-risk children is 15–35%.
Parents of unvaccinated high-risk children (n = 202) gave the following reasons for lack of vaccination: lack of awareness, 173 (85.6%); inconvenience, 11 (5.5%); and concern about side effects, 18 (8.9%).15 Parents of vaccinated high-risk children (n = 72) gave the following reasons for having their children vaccinated: pediatrician's recommendation, 63 (87.5%); protection of parents, 6 (8.3%); protection of family elders, 2 (2.8%); and previous serious influenza-like illness, 1 (1.4%).15 Our finding that most compliance to the recommendation for vaccination of high-risk children was associated with a pediatrician's recommendation suggests that we should make certain that physicians who care for children with chronic disorders are informed about the epidemiology and prevention of influenza. Then, to raise awareness among families, we should distribute information that clearly explains influenza-related risks for their child as well as the measures to avoid influenza-related complications and hospitalizations associated with their child's high-risk condition.
In our own clinic this year, we attempted to improve the rate of vaccination among children with chronic asthma. This campaign was based on an active intervention program that compared the efficacy of 3 strategies for contacting children's families to arrange vaccination: families were called by a doctor other than their usual one for vaccination by an external operators, families were called by their usual doctor for vaccination given by an external operator, families were called and children vaccinated by doctors working in the outpatient asthma clinic. We found that this third system increased vaccination coverage among children with chronic asthma. Thus, this strategy should be considered as a means to increase vaccination of children with so-called high-risk conditions.
Differing Vaccination Policies for Healthy Children
In the United States, influenza vaccination is recommended for children aged 6 months to 18 years.14 However, the Centers for Disease Control (CDC) Web site recommends influenza vaccination for children aged 6 months to 18 years. Both recommendations differ from the norm in Europe. In Finland, for example, influenza vaccination is recommended for children aged 6 months to 3 years, even in the absence of high-risk conditions. It might be worth exploring why these countries promote different strategies for prevention of influenza in children, starting with the results of epidemiological studies.
Also, an understanding of the relevance of household contacts, including contacts with children aged <59 months, adults aged >50 years, or persons with high-risk medical conditions that have to be vaccinated, may provide insight into strong recommendations by the United States and Finland for vaccination of children.
Recurrent Otitis Media and Influenza
Some categories of children, such as those with recurrent acute otitis media, require special consideration with respect to influenza vaccination. Influenza and other viral infections are associated with many, if not most, episodes of acute otitis media. Our group demonstrated the usefulness of inactivated, virosomal subunit influenza vaccine in children aged 1–5 years with recurrent acute otitis media. In those who were vaccinated, the recurrence rate was 35.8% compared with 63.6% in controls.16 This represented an overall prevention efficiency of 43.7% (95% CI: 18.6–61.1; P = 0.002). These data suggest not only that influenza vaccine is a valid option in reducing disease in otitis-prone children but also that it can reduce the socioeconomic burden in this comorbidity.
Recurrent Respiratory Infections and Influenza
Another group of children that warrants special consideration are those in daycare who experience recurrent respiratory infections consisting of cycles of pharyngitis, otitis, bronchitis, and pneumonia. We studied such a group during the 2001–2002 influenza season in Italy. The children had had at least 8 episodes of respiratory tract infection in the preceding year if they were aged <3 years or at least 6 episodes if they were aged >3 years. Children who were vaccinated with inactivated, virosomal-adjuvanted split-virus vaccine experienced fewer upper and lower respiratory tract infections and school absences due to respiratory illnesses and required fewer antimicrobial and antipyretic prescriptions.17 Family members of healthy children who received influenza vaccine had fewer respiratory tract infections and work absences and required fewer medical appointments and home assistance for ill children compared with household contacts of unvaccinated children (Table 3). 17 Thus, vaccination appears to offer significant benefits to children who are not typically at higher risk but who develop infections that occur in same-age playmates.
When we evaluated the efficacy of influenza vaccination in healthy children aged 2–5 years, we found that vaccination resulted in a significant reduction in both upper and lower respiratory tract infections and febrile respiratory illness as well as a reduction in the number of antibiotic and antipyretic prescriptions and missed school days.17 Collectively, these data suggest that, in otherwise healthy children, the most effective and cost-effective prevention strategy is universal vaccination of children aged 6 to 60 months. And this approach offers more benefits than a strategy of vaccination of children aged 6–24 months.
Reevaluating Current Strategies
Outcomes such as these have prompted reevaluation of recommendations for universal vaccination in pediatrics.18 The requirement of annual influenza vaccination by injection is problematic. However, the policy of universal vaccination for healthy people aged 6 months-18 years that is promoted in the United States is a simple strategy that could provide better coverage in children. Certainly the European Centre for Disease Prevention and Control called for more studies on influenza epidemiology and vaccination and a new system for monitoring trends in influenza. Perhaps the European Society for Pediatric Infectious Diseases (ESPID) should create a network for monitoring influenza in European countries. That would aid us in following our neighbors' strategies to reduce influenza, such as Finland's effort to vaccinate children aged 6–36 months. In this way, we should also compare results of different healthcare system efforts to reduce costs associated with childhood influenza.
Recent epidemiologic data suggest that we must reconsider existing strategies for influenza prevention. The first priority should be to improve influenza vaccination coverage in children who have severe chronic underlying diseases and in those with common recurrent respiratory disorders (including children with either recurrent acute otitis media or recurrent respiratory tract infections). Meanwhile, we need adequate evidence of the role of influenza and its complications as well as of the efficacy of vaccination in each of these categories. Still, we should remember that the majority of our patients are otherwise healthy children. In these healthy subjects, we must consider recent epidemiologic and socioeconomic data as well as results on influenza vaccines' efficacy in support of universal influenza vaccination of the pediatric population.
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