What’s new with the flu?

Influenza season is approaching, and it is timely to review the latest recommendations for the use of immunization for prevention, and pharmacotherapy for treatment and prophylaxis.

Annual recommendations from the CDC include new prevention strategies. Clinicians should be aware of differences in vaccine products for infants and children for the 2010-11 influenza season.

Influenza infection and illness can have a significant effect on pediatric morbidity. Rates of infection with influenza viruses are highest among children, and rates of serious illness are high in the elderly (65 years and older) and young children (<2 years of age). Children with certain medical conditions are at increased risk (Table 1).

Influenza illness serious enough to require hospitalization is highest among older adults (65 years) and is similar in younger children (<2 years). Fortunately, death due to influenza is much less common in children as compared with older adults — 0.4 deaths/100,000 vs. 98.3 deaths/100,000, respectively. In past years, pediatric deaths have occurred more commonly in children who did not have an identifiable underlying medical condition considered to be higher risk for disease complications. However, pediatric deaths during the 2009-2010 A (H1N1) pandemic occurred more commonly in children with underlying high-risk medical conditions. These data suggest that all children 6 months of age should be targeted for influenza immunization.

2010-11 influenza season recommendations from the CDC

Recommendations from the Advisory Committee on Immunization Practices from the CDC for the 2010-11 influenza season include several changes over past years. Most notable for this year’s recommendations are an expansion for routine immunization, regardless of concomitant medical conditions, to include adults 19 to 49 years of age. Recommendations for all children 6 months of age to receive influenza vaccine continue for the 2010-11 season. This season’s vaccine products contain viral antigens or whole viruses from three strains — two influenza A strains and one influenza B strain. One of the influenza A strains in vaccine products is derived from a 2009 pandemic influenza A (H1N1) virus.

New to this year’s recommendations is advice for pediatric clinicians to consider, including vaccine dosing for younger children and differences in vaccine product pediatric labeling for use in infants and children. As this season’s vaccine products contain an influenza A (H1N1) strain similar to last season’s pandemic influenza A (H1N1) virus, a younger child’s (6 months – 8 years) past history of immunization for influenza A (H1N1) is important to assess. Most notable for this season’s recommendations are for children younger than 9 years of age whom did not receive immunization directed against influenza A (H1N1) last season, regardless of immunization history for seasonal influenza virus (Table 2).

Vaccine products

Five vaccine products are available for use in the pediatric population this season (Table 3).

They differ by FDA-approved age labeling. Most products contain no thimerosal (mercury preservative). The CDC has recommended not to routinely use one pediatric product, Afluria, this season for children 6 months to 8 years of age. This is due to increased reports of post-vaccination fever and febrile seizure occurrence in children 6 months to 8 years who received an antigenically equivalent product during the influenza season in Australia and New Zealand. Rates of fever and febrile seizures occurred in these children at a rate ninefold greater than expected after receipt of an antigenically similar vaccine used in these countries. The reason for this increase in adverse effects is not known. Afluria can be given routinely to children 9 years of age and older. If other vaccine products are not available, Afluria can be given to children 5 to 8 years of age with concomitant medical conditions that increase risk for influenza complications.

One of the influenza vaccine products listed in Table 3 is FluMist, an attenuated live virus vaccine administered intranasally. Some children may prefer FluMist to other vaccine products, as it is not a “shot.”

However, FluMist is labeled for use in specific populations – those aged 2 years and older; children without concomitant risk factors that increase risk of influenza complications; and nonpregnant females. Children with asthma or children who have had a wheezing episode within the previous 12 months should not receive FluMist.

The CDC recommends screening parents with the following question: “In the past 12 months, has a health care provider ever told you that your child had wheezing or asthma?” Children whose caregivers answer “yes” to this question should not receive FluMist. Some data are available from clinical trials comparing FluMist with inactivated injectable vaccine. In the largest study of almost 8,000 children, intranasal attenuated live virus vaccine was compared with inactivated injectable vaccine in a randomized, doubleblind manner during the 2004-05 influenza season (Belshe, 2007).

There were 54.9% fewer cases of culture-confirmed influenza in children that received intranasal vaccine as compared with children that received inactivated vaccine. Although this large, controlled trial provides useful data and information, the CDC guidelines do not recommend a preference for either type of vaccine, as more data are needed to identify which patient-specific characteristics or populations are most likely to benefit from one vaccine over another.

Whatever vaccine product is used, health care professionals should strive to increase immunization coverage, as immunization coverage levels of children in recent years have been less than optimal. Data from several national surveys indicate that coverage rates for children in recent years vary from approximately 20% to 40%.

Pharmacotherapy of influenza disease

Although four antiviral agents are commercially available, only two of these have clinical use for treatment of influenza disease in infants and children — oseltamivir (Tamiflu) and zanamivir (Relenza).

Amantadine and rimantadine have no role for treatment, as viral resistance to these agents of the adamantine class is high. As of the date of this writing, recommendations for the pharmacotherapy of influenza disease and prophylaxis from the CDC have not been released for the 2010-11 season. Data from the 2009-10 influenza season reported by the CDC, with more than 99% of viral isolates identified as influenza A (H1N1), reveal that 98.7%, 100%, and 0.2% of viral isolates were sensitive to oseltamivir, zanamivir, and the adamantine class, respectively. During the 2009-10 season, rare reports of influenza A (H1N1) resistance to oseltamivir occurred. Since April 2009, 67 cases of influenza A (H1N1) resistant to oseltamivir have been reported.

Clinicians can view the CDC’s website for national and regional viral resistance patterns.

Oseltamivir is labeled for the treatment and prophylaxis of influenza for ages 1 year. This medication is available as an oral capsule (30 mg, 45 mg, 75 mg) and as an oral suspension (12 mg/mL, tutti-fruti flavored). It is important for clinicians to note that the dosing device available with the Tamiflu product contains graduated markings of 30 mg, 45 mg, and 60 mg – these graduated markings indicate mg-amounts, and not volume-amounts (ie, not as milliliter), as do most pediatric volume dosing devices. Reports of dosing errors have occurred because of this confusion. Prescribers should write Tamiflu orders as “mg per dose,” and not volume per dose. For example, for a 30-lb, 2-year old child, dosing for Tamiflu oral suspension 12 mg/mL should be written as: 30 mg twice daily for 5 days (and not 2.5 mL twice daily for 5 days). Zanamivir is available as an oral inhalation disk, and is labeled for use in ages 7 years for treatment and for ages 5 years for prophylaxis. Zanamivir should not be used for children with underlying airway disease, including asthma, due to increased risk of serious bronchospasm.

It is important for clinicians to consider that not all children may significantly benefit from the use of oseltamivir and zanamivir. As both of these agents act by inhibiting viral replication, their use early in infection – within 48 hours of disease onset - is most likely to be effective. Children most likely to benefit from antiviral pharmacotherapy include children younger than 2 years of age and children with underlying medical conditions that can increase the risk of disease complications (pulmonary, cardiovascular, renal, hepatic, neurologic, hematologic, metabolic, and immunosuppressive disorders, and long-term aspirin therapy). Children ill enough to require hospitalization may also benefit from pharmacotherapy. Children 2 to 4 years of age without high-risk medical conditions and children with mild disease do not necessarily require pharmacotherapy, as benefits from treatment may not be clinically significant.

For more information:

• Belshe RB. NEJM. 2007;356:685-96
• CDC. MMWR. 2010;59(RR-8):1-62.
• CDC. MMWR. 2010;59(31):989-992