Post-pandemic seroprevalence of pandemic influenza A (H1N1) 2009 infection (swine flu) among children <18 years in Germany

Abstract

Background: We determined antibodies to the pandemic influenza A (H1N1) 2009 virus in children to assess: the incidence of (H1N1) 2009 infections in the 2009/2010 season in Germany, the proportion of subclinical infections and to compare titers in vaccinated and infected children.

Methodology/principal findings: Eight pediatric hospitals distributed over Germany prospectively provided sera from in- or outpatients aged 1 to 17 years from April 1(st) to July 31(st) 2010. Vaccination history, recall of infections and sociodemographic factors were ascertained. Antibody titers were measured with a sensitive and specific in-house hemagglutination inhibition test (HIT) and compared to age-matched sera collected during 6 months before the onset of the pandemic in Germany. We analyzed 1420 post-pandemic and 300 pre-pandemic sera. Among unvaccinated children aged 1-4 and 5-17 years the prevalence of HI titers (≥1∶10) was 27.1% (95% CI: 23.5-31.3) and 53.5% (95% CI: 50.9-56.2) compared to 1.7% and 5.5%, respectively, for pre-pandemic sera, accounting for a serologically determined incidence of influenza A (H1N1) 2009 during the season 2009/2010 of 25,4% (95% CI : 19.3-30.5) in children aged 1-4 years and 48.0% (95% CI: 42.6-52.0) in 5-17 year old children. Of children with HI titers ≥1∶10, 25.5% (95% CI: 22.5-28.8) reported no history of any infectious disease since June 2009. Among vaccinated children, 92% (95%-CI: 87.0-96.6) of the 5-17 year old but only 47.8% (95%-CI: 33.5-66.5) of the 1-4 year old children exhibited HI titers against influenza A virus (H1N1) 2009.

Conclusion: Serologically determined incidence of influenza A (H1N1) 2009 infections in children indicates high infection rates with older children (5-17 years) infected twice as often as younger children. In about a quarter of the children with HI titers after the season 2009/2010 subclinical infections must be assumed. Low HI titers in young children after vaccination with the AS03(B)-adjuvanted split virion vaccine need further scrutiny.

Figure 1. Reverse cumulative distribution curves of hemagglutination inhibition titers for antibodies against influenza A (H1N1) 2009 virus for different strata.

Post-pandemic children not vaccinated against influenza A (H1N1) 2009 aged 1–17, thereof 347 aged 1–4 and 960 aged 5–17 were tested and in addition 300 pre-pandemic controls and 101 children vaccinated against influenza A (H1N1) 2009. Children aged 1–4 exhibit lower titers compared to children aged 5–17 and all post-pandemic cases. Titers of pre-pandemic children aged 1–17 are distinctly lower. Children vaccinated against A (H1N1) 2009 exhibit higher titers compared to post-pandemic children having been infected with A (H1N1).

Figure 2. Reverse cumulative distribution curves of children vaccinated against the A (H1N1) 2009 virus <5 years (n = 23), > = 5 years (n = 78) and in children with laboratory-confirmed A (H1N1) 2009 infection <5 years (n = 6), > = 5 years (n = 19).

Vaccinated children and children with laboratory-confirmed A (H1N1) infection were mutually exclusive. Children vaccinated against the A (H1N1) 2009 virus exhibit lower titers compared to children with laboratory-confirmed A (H1N1) 2009 infection. This can be observed in both age groups with greater difference in younger children.