Pandemic influenza A/H1N1pdm in Italy: age, risk and population susceptibility

Abstract

Background: A common pattern emerging from several studies evaluating the impact of the 2009 A/H1N1 pandemic influenza (A/H1N1pdm) conducted in countries worldwide is the low attack rate observed in elderly compared to that observed in children and young adults. The biological or social mechanisms responsible for the observed age-specific risk of infection are still to be deeply investigated.

Methods: The level of immunity against the A/H1N1pdm in pre and post pandemic sera was determined using left over sera taken for diagnostic purposes or routine ascertainment obtained from clinical laboratories. The antibody titres were measured by the haemagglutination inhibition (HI) assay. To investigate whether certain age groups had higher risk of infection the presence of protective antibody (≥1∶40), was calculated using exact binomial 95% CI on both pre- and post- pandemic serological data in the age groups considered. To estimate age-specific susceptibility to infection we used an age-structured SEIR model.

Results: By comparing pre- and post-pandemic serological data in Italy we found age- specific attack rates similar to those observed in other countries. Cumulative attack rate at the end of the first A/H1N1pdm season in Italy was estimated to be 16.3% (95% CI 9.4%-23.1%). Modeling results allow ruling out the hypothesis that only age-specific characteristics of the contact network and levels of pre-pandemic immunity are responsible for the observed age-specific risk of infection. This means that age-specific susceptibility to infection, suspected to play an important role in the pandemic, was not only determined by pre-pandemic levels of H1N1pdm antibody measured by HI.

Conclusions: Our results claim for new studies to better identify the biological mechanisms, which might have determined the observed pattern of susceptibility with age. Moreover, our results highlight the need to obtain early estimates of differential susceptibility with age in any future pandemics to obtain more reliable real time estimates of critical epidemiological parameters.

Figure 1. Serolgy and risk of infection by age.

(A) Pre-pandemic seroprevalence (green), post-pandemic seroprevalence (red) and difference between post- and pre- seroprevalence (blue). Vertical bars represent 95% CI. An individual is considered to be seropositive when HI titre is ≥40 (B) Average (blue points) and 95% CI (vertical blue bars) of the probability distribution of the final fraction of infected individuals by age in moving windows of 25 study participants. The inset refers to pre- and post- pandemic data (colors as in panel A). An individual is considered to be seropositive when HI titre is ≥40 (C) As A, but considering seropositive individuals having HI titre ≥10. (D) as B, but considering seropositive individuals having HI titre ≥10.

Figure 2. Relative susceptibility to infection.

(A) Average value of the age-specific susceptibility to infection in age groups 5–14 years, 15–64 years and 65+ years, relative to that of the class 0–4 years. Vertical lines represent 95% CI. Colors refer to the contact matrix assumed, namely red for CM1 , blue for CM2 and green for CM3 . In this panel we assume that individuals are seropositive when HI titre is ≥40; in addition we assume that at the beginning of the simulations there are no fully immune individuals. (B) as A, but we assume that individuals are seropositive when HI titre is ≥10. (C) as A, but assuming pre-existing full immunity in the different age groups as obtained by the analysis of pre-pandemic sera. (D) as B, but assuming pre-existing full immunity in the different age groups as obtained by the analysis of pre-pandemic sera.