Prevalence of antibodies against seasonal influenza A and B viruses in children in Netherlands

Abstract

To gain insight into the age at which children become infected with influenza viruses for the first time, we analyzed the seroprevalence of antibodies against influenza viruses in children 0 to 7 years of age in the Netherlands. Serum samples were collected during a cross-sectional population-based study in 2006 and 2007 and were tested for the presence of antibodies against influenza A/H1N1, A/H3N2, and B viruses representative of viruses present in previous influenza seasons using the hemagglutination inhibition assay. The seroprevalence of antibodies to influenza virus was higher in children 1 to 6 months of age than in children 7 to 12 months of age, which likely reflects the presence of maternally derived antibodies. The proportion of study subjects >1 year of age with detectable antibodies against influenza viruses gradually increased with age until they reached the age of 6 years, when they all had antibodies to at least one influenza A virus. These findings may have implications for the development of vaccination strategies aiming at the protection of young children against seasonal and/or pandemic influenza virus infection.

FIG. 1.

Seroprevalence of antibodies against individual influenza viruses. Serum samples from children 0 to 7 years of age were tested for the presence of antibodies against representative influenza A/H3N2 (A), A/H1N1 (B), and B (C) virus strains. For each age group, representative influenza viruses to which they may have been exposed were selected according to their age. Indicated are the strains that have been used to evaluate serum samples for the presence of antibodies and the percentage of serum samples in which antibodies against each influenza virus antigen were detected. Shaded areas, not tested.

FIG. 2.

Seroprevalence of antibodies against influenza viruses in children 1 to 12 months of age. (A) Seroprevalences of antibodies against influenza A/H3N2, A/H1N1, and B viruses of the 2000 to 2007 influenza seasons in children 1 to 6 months of age (gray bars) and 7 to 12 months of age (white bars). Serum samples were tested for the presence of antibodies against multiple antigens, as is indicated for influenza A/H3N2 (B), influenza A/H1N1 (C), and B (D) viruses. Bars indicate the percentage of the serum samples in which antibodies were detected, and error bars indicate the 95% confidence intervals.

FIG. 3.

Seroprevalence of antibodies against influenza A and B viruses depends on age. (A) The percentages of serum samples from children in which antibodies against at least one of the representative influenza viruses were detected were calculated for influenza A/H1N1 viruses (light gray bars), influenza A/H3N2 viruses (white bars), and all influenza A viruses (dark gray bars). (B) The same procedures were used to calculate the seroprevalence of antibodies against at least one of the influenza B viruses from the Victoria lineage (light gray bars) and the Yamagata-lineage (white bars) and all influenza B viruses (dark gray bars). Bars indicate the percentage of the serum samples in which antibodies were detected, and error bars indicate the 95% confidence intervals.

FIG. 4.

Correlation of titers of antibodies against individual influenza A virus strains in 4-year-old children. Correlations between the titers of antibodies against multiple representative influenza A/H3N2 viruses, influenza A/H1N1 viruses, and influenza B viruses are shown. Dots indicate individual serum samples, and the Pearson correlation coefficient was calculated for all data points for which antibodies against at least one influenza virus was detected. For influenza B viruses, the letter behind the name of each strain indicates the lineage to which the virus belongs (V, Victoria lineage; Y, Yamagata lineage). Neth and Ned, Netherlands.

FIG. 5.

Difference in proportion of seropositive individuals for each age group compared to proportion for the previous age group. Unadjusted (light gray) and adjusted (dark gray) proportions controlled for estimated differences in the severity of flu incidence throughout the lives of individuals in each group. For the adjustment, the mean total weighted influenza season time experienced by the individuals of each age group was first calculated using information about the date of birth and date of sample collection and relevant influenza-like illness data. Next, the differences in this mean for each age group compared to the mean for the previous age group were calculated, alongside an overall mean difference between age groups. Finally, the adjustments were made by scaling the value for each age group by the factor by which it differed from the overall mean for the data set, to account for age groups that had lived through a time of abnormally high or low flu incidence. For age 0, only individuals more than 220 days old were included to reduce the chance of detecting potential maternal immunity rather than genuine exposure, and values for age 0 were plotted assuming a previous seroprevalence of 0%. Error bars indicate the 95% confidence intervals.