Predictive Models for Biomedicine & Environment, Bruno Kessler Foundation, Trento, Italy.
PLoS One. 2013 Oct 7;8(10):e74785. doi: 10.1371/journal.pone.0074785. eCollection 2013.
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.
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.
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.
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.
从全球多个国家开展的针对 2009 年甲型 H1N1 流感(A/H1N1pdm)影响的评估研究中,出现了一种普遍模式,即与儿童和青年相比,老年人的发病率较低。负责观察到的感染风险的生物学或社会机制仍有待深入研究。
使用为诊断目的或从临床实验室获得的常规确定而保留的剩余血清,来确定大流行前后血清中针对 A/H1N1pdm 的免疫水平。使用血凝抑制(HI)测定法测量抗体滴度。为了研究某些年龄组是否具有更高的感染风险,在考虑的年龄组中,通过对大流行前后血清学数据进行精确二项式 95%CI 计算,得出了具有保护抗体(≥1∶40)的存在。为了估计感染的年龄特异性易感性,我们使用了年龄结构的 SEIR 模型。
通过比较意大利大流行前后的血清学数据,我们发现与其他国家观察到的年龄特异性发病率相似。在意大利第一个 A/H1N1pdm 季节结束时,累积发病率估计为 16.3%(95%CI 9.4%-23.1%)。建模结果排除了以下假设,即仅接触网络的年龄特异性特征和大流行前的免疫水平是导致观察到的感染风险的年龄特异性的原因。这意味着感染的年龄特异性易感性,怀疑在大流行中起重要作用,不仅由 HI 测量的大流行前 H1N1pdm 抗体水平决定。
我们的结果呼吁开展新的研究,以更好地确定可能决定观察到的年龄相关易感性模式的生物学机制。此外,我们的结果强调需要在任何未来的大流行中尽早估计年龄相关的差异易感性,以获得更可靠的实时关键流行病学参数估计。