HOUSTON—This year, the Advisory Committee on Immunization Practices (ACIP) is once again recommending that all high-risk children older than 6 months receive the influenza vaccine.[1] Vaccination of all children ages 6 to 23 months is now also suggested because they are at increased risk for influenza-related hospitalization.

Despite these recommendations, the inactivated influenza vaccine (IIV) has not been widely used in children. “In general, the IIV is grossly underutilized in high-risk children, even though its use is recommended by the ACIP, … American Academy of Pediatrics, and American Academy of Family Physicians,” said Pedro A. Piedra, MD, Associate Professor in the Departments of Molecular Virology and Microbiology and Pediatrics at Baylor College of Medicine in Houston.

For this reason, he and his colleagues have been studying a better way to administer the flu vaccine to children—through their noses. Two studies show that intranasal administration is both safe and effective for children in this age-group.[2,3]

PAST AND PRESENT

In a 1998 phase III prelicensure efficacy trial, the intranasal trivalent, cold-adapted influenza vaccine (CAIV-T) had a 93% efficacy rate (95% confidence interval, 88% to 96%) against culture-confirmed influenza in young children.[2] More recently, Dr. Piedra and colleagues reported results of a four-year, phase III trial demonstrating that CAIV-T was safe and well tolerated in young children.[3] “The IIV is the only influenza vaccine that is currently licensed,” observed Dr. Piedra. “The … CAIV-T is administered by a nasal spray. In my opinion, this vaccine is more ‘child-friendly’ compared to the IIV because a needle is not involved in its administration.”

The new trial—sponsored by the National Institutes of Health and Aviron—enrolled 1,602 healthy children ages 15 to 71 months. In the first year of the study, children were randomized to receive placebo or one or two doses of CAIV-T. (The two-dose cohort received the second dose of CAIV-T about 60 days after the first dose.) In the second year, the placebo recipients were again given a placebo; all CAIV-T recipients were given only one dose of the intranasal vaccine. In years 3 and 4, both the placebo and vaccine groups were given CAIV-T, providing an opportunity to observe the safety of sequential annual administration of the vaccine.

After vaccine or placebo administration, parents were asked to record their children’s temperatures daily for 10 days, as well as the occurrence of cough, runny nose or nasal congestion, sore throat, irritability, chills, vomiting, muscle aches, decreased activity, and any other symptoms. The use of over-the-counter medications and prescription drugs was also recorded.

Parents were contacted by telephone every one to three weeks to inquire about acute respiratory symptoms occurring within 42 days of vaccination.

SYMPTOMS AFTER FIRST DOSE

Administration of the first dose of CAIV-T was associated with an increased incidence of mild side effects, such as runny nose, nasal congestion, vomiting, muscle aches, and fever. However, only a minority of vaccinated children were affected. Furthermore, subsequent doses produced fewer reactions. For example, after the second dose given in year 1, only runny nose and nasal congestion were more common among the children given CAIV-T. In year 2, the reactogenicity of CAIV-T did not differ significantly from that of placebo.

After the initial dose in year 1, symptoms were most likely to arise either within two days of vaccination or about a week later. In year 2, an increased incidence in mild runny nose or nasal congestion was seen only on the second day after administration. A significant rise in the use of analgesics/antipyretics was observed only after the first dose in year 1.

According to the authors, age, month of vaccination, and child care attendance may all have affected the incidence of respiratory symptoms associated with CAIV-T. Compared with older children, younger children were more likely to experience symptoms after vaccination—probably because of their lack of previous exposure to at least one of the influenza types used in the vaccine. The number of symptoms observed after CAIV-T also increased with the presence of a concurrent viral respiratory infection.

The decrease in the number of symptoms between the study’s first and second years was accompanied by a decrease in severity—the runny noses and nasal congestion reported in year 2 were even milder than those reported in year 1. The authors speculated that the strain used in year 1 induced sufficient immunity to reduce reactogenicity associated with the same strain used in year 2.

Dr. Piedra noted that people are often misinformed regarding the influenza vaccine. “As health care providers, we need to do a better job in educating our patients and the public of the significant … cost to society that is associated with influenza.” Providing accurate information on influenza to patients also makes a strong argument for the need for vaccine coverage. “IIV has been administered to millions of individuals with an excellent safety record,” he argued.

Dr. Piedra believes that when CAIV-T is licensed, “it will [be] another important tool to be used in … controlling epidemic influenza and for pandemic preparedness.”

The Making of a Vaccine

Bethesda, MD—Each February, the World Health Organization (WHO) recommends influenza virus strains for inclusion in the following season’s Northern Hemisphere influenza vaccine. Influenza surveillance is conducted by about 700 sentinel providers and 120 United States WHO and National Respiratory and Enteric Virus Surveillance System (NREVSS) collaborating laboratories.[1] Influenza virus isolates detected worldwide are collected and analyzed. This year, of the 23 influenza A (H1) viruses collected between June and September, all were similar to A/New Caledonia/20/99, the H1N1 component of the 2002-2003 influenza vaccine. Influenza B viruses are from two distinct lineages represented by B/Yamagata/16/88 and B/Victoria/2/87. Since March 2001, B/Victoria lineage viruses have been identified in many countries, including the United States. Thus, the B component of the 2002-2003 influenza vaccine belongs to the B/Victoria lineage. For the 2002-2003 influenza season, WHO has recommended A/New Caledonia/20/99-like (H1N1), A/Moscow/10/99-like (H3N2), and B/Hong Kong/330/01-like viruses for inclusion in the Northern Hemisphere influenza vaccine. In the United States, influenza vaccines will include A/New Caledonia/20/99 for the H1N1 component and antigenically equivalent strains of A/Panama/2007/99 for the H3N2 component and B/Hong Kong/1434/02 for the B/Hong Kong/330/01-like strain. Influenza surveillance reports for the United States are published weekly from October through May and are available through the CDC via telephone (888) 232-3228, fax (888) 232-3299 (request document number 361100), or on the CDC Web site. —Gale Jurasek

Reference 1. Centers for Disease Control and Prevention. Update: Influenza activity: United States and worldwide, June-September, 2002. MMWR Morb Mortal Wkly Rep. 2002;51:880-882.

—Gale Jurasek