Zinder Daniel, Bedford Trevor, Baskerville Edward B, Woods Robert J, Roy Manojit, Pascual Mercedes
BMC Evol Biol. 2014 Dec 24;14:272. doi: 10.1186/s12862-014-0272-2.
Influenza A/H3N2 has been circulating in humans since 1968, causing considerable morbidity and mortality. Although H3N2 incidence is highly seasonal, how such seasonality contributes to global phylogeographic migration dynamics has not yet been established. In this study, we incorporate time-varying migration rates in a Bayesian MCMC framework. We focus on migration within China, and to and from North-America as case studies, then expand the analysis to global communities.
Incorporating seasonally varying migration rates improves the modeling of migration in our regional case studies, and also in a global context. In our global model, windows of increased immigration map to the seasonal timing of epidemic spread, while windows of increased emigration map to epidemic decline. Seasonal patterns also correlate with the probability that local lineages go extinct and fail to contribute to long term viral evolution, as measured through the trunk of the phylogeny. However, the fraction of the trunk in each community was found to be better determined by its overall human population size.
Seasonal migration and rapid turnover within regions is sustained by the invasion of 'fertile epidemic grounds' at the end of older epidemics. Thus, the current emphasis on connectivity, including air-travel, should be complemented with a better understanding of the conditions and timing required for successful establishment. Models which account for migration seasonality will improve our understanding of the seasonal drivers of influenza, enhance epidemiological predictions, and ameliorate vaccine updating by identifying strains that not only escape immunity but also have the seasonal opportunity to establish and spread. Further work is also needed on additional conditions that contribute to the persistence and long term evolution of influenza within the human population, such as spatial heterogeneity with respect to climate and seasonality.
甲型H3N2流感自1968年以来一直在人类中传播，导致了相当高的发病率和死亡率。尽管H3N2的发病率具有高度季节性，但这种季节性如何影响全球系统发育地理迁移动态尚未明确。在本研究中，我们在贝叶斯MCMC框架中纳入了随时间变化的迁移率。我们以中国境内以及往返北美的迁移情况作为案例研究，然后将分析扩展到全球范围。
纳入季节性变化的迁移率改进了我们在区域案例研究以及全球背景下对迁移的建模。在我们的全球模型中，移民增加的窗口与疫情传播的季节性时间相对应，而移民减少的窗口与疫情衰退相对应。季节性模式还与当地谱系灭绝并未能对长期病毒进化做出贡献的概率相关，这通过系统发育树的主干来衡量。然而，发现每个群体中主干的比例更好地由其总人口规模决定。
区域内的季节性迁移和快速更替是由旧疫情末期“肥沃的疫区”的入侵所维持的。因此，当前对包括航空旅行在内的连通性的重视，应辅之以对成功建立所需条件和时机的更好理解。考虑迁移季节性的模型将改善我们对流感季节性驱动因素的理解，增强流行病学预测，并通过识别不仅能逃避免疫而且有季节性机会建立和传播的毒株来改进疫苗更新。还需要进一步研究有助于流感在人群中持续存在和长期进化的其他条件，例如气候和季节性方面的空间异质性。
