Nov 24, 2010 (CIDRAP News) – Doubts about flu vaccine effectiveness in children younger than 2 years have kept some countries from recommending immunization for them, but Finnish researchers presented promising data yesterday that they say might prompt some to reconsider.
Finland and the United States are among the few countries that recommend routine flu vaccination for children ages 6 through 35 months, a measure designed to decrease the disease burden in the youngest children and prevent the spread of flu to others, especially those with high-risk conditions. However, there has been little evidence on the efficacy of seasonal flu vaccines in this age-group, especially in kids younger than 2.
In a prospective, nonrandomized cohort trial, the Finnish researchers found that the vaccine was 66% effective in children younger than 3 years and wasn't accompanied by adverse events. Their findings appeared yesterday in an early online report from Lancet Infectious Diseases. The investigation was part of a larger trial on antiviral treatment in children.
The scientists conducted the investigation during the 2007-08 flu season in Turku, Finland. The time frame marked the first year after the country launched a universal flu vaccination recommendation for children ages 6 to 35 months. The effectiveness of the vaccine against lab-confirmed infections was measured. The dose was 0.5 mL, double the dose for young children in the United States.
Parents and their children were recruited by mailed announcements and local advertisements. The study didn't include any exclusion criteria. Parents were asked to bring children to the study clinic, which was open throughout the flu season, each time the child had fever or respiratory symptoms. At each visit children were examined by a physician and respiratory swab samples were taken.
Children received the flu vaccine free at their local healthcare centers. Previously unvaccinated children received a second 0.5 mL dose 4 weeks after the first.
During the study period the circulating influenza A/H1N1 and H3N2 viruses were a good match to the seasonal vaccine, but the influenza B subtype was a mismatch.
Researchers calculated the effectiveness of the vaccine by comparing proportions of flu infections between fully vaccinated and unvaccinated children. They used a case-control analysis to assess if some children who were infected with flu weren't brought to the study clinic when they were sick. Children who had received only one dose were considered unvaccinated in the case-control analysis.
Of 631 children enrolled in the larger study, 154 were fully vaccinated, 21 were partially vaccinated, and 456 were unvaccinated. The researchers analyzed two subgroups, age 9 months to 2 years and 2 years to 3 years.
Influenza (type A or B) was confirmed in 7 (5%) of 154 fully vaccinated children and 61 (13%) unvaccinated children in the study, indicating that overall vaccine effectiveness was 66% (95% confidence interval [CI], 29% to 84%; P=.003), the report says.
In children under age 2, 4 (4%) of the 96 fully vaccinated participants and 21 (12%) of 172 unvaccinated participants contracted flu of either type, also indicating overall vaccine effectiveness of 66% (95% CI, 9% to 88%; P=.03).
When the researchers examined the results separately for influenza A and B, they found that the vaccine was effective against type A but not type B in both age subgroups. The effectiveness against the mismatched type B was 45% (95% CI, -34% to 78%; P=.20), whereas effectiveness against type A was 84% (95% CI, 40% to 96%; P=.003).
"These findings are clinically important, because the burden of influenza is particularly high among the youngest children, and hence both the need for and the benefit from an effective vaccine would be greatest in this age group," the authors wrote. "Our findings are in stark contrast with the widespread belief in many countries that influenza vaccines have poor effectiveness in children younger than 2 years."
They noted that the only other vaccine effectiveness study in children under age 3 was a two-season one that found an overall effectiveness of 66% in a normal flu season and no effectiveness during the next season, when flu activity was very low.
The findings also suggest that the clinical effectiveness of flu vaccine depends more on the antigen match than the age of the recipient, the group said. About half (33 of 71) of the flu cases in the study were caused by the mismatched B virus, but the overall effectiveness against all flu was 66%. They also noted that vaccine-induced antibody responses to influenza B viruses are lower than those against influenza A viruses, which also might partly explain the lack of effectiveness against influenza B infections.
The investigators cautioned that the higher vaccine dose might have contributed to the study's effectiveness findings. Though the dose is double that used elsewhere in young children, the group noted that safety data from Finnish government health officials have shown that the dose is well tolerated.
The authors acknowledged that the voluntary enrollment of the parents could introduce a selection bias, but they said the proportion of vaccinated children in the study, at 24%, was similar to 27% seen in all children of the same age in the city. The group also noted that prevalence of asthma and wheezing in the group was similar to that for that region of Finland.
Given the urban setting and little socioeconomic difference among Finnish families, they concluded that their results are generalizable, with unknown bias unlikely.
In an accompanying editorial, Dr Mark Steinhoff, director of the Global Health Center at Cincinnati Children's Hospital Medical Center, wrote that flu vaccination strategies have evolved over time from protecting just high-risk children to including healthy children who could spread the virus to others.
He said that study biases seem unlikely, given the strain-specific effectiveness findings against the backdrop of that season's flu circulating viruses.
Immunizing young children is a way to decrease work disruptions for parents and disrupt community viral transmission, and the Finnish study helps build a stronger case for including the youngest children in universal vaccination recommendations, Steinhoff wrote.
Assessing flu vaccine effectiveness with a similar study among young infants would provide another useful gauge that might help guide a broader flu immunization strategy, he added.
Heinonen S, Silvennoinen H, Lehtinen P, et al. Effectiveness of inactivated influenza vaccine in children aged 9 months to 3 years: an observational cohort study. Lancet Infect Dis 2010 Nov 23, early online publication [Abstract]
Steinhoff MC. Influenza in young children: burden, immunization, and policy. Lancet Infect Dis 2010 Nov 23, early online publication [Preview]