Evaluating seasonality of influenza in the tropics: Case study in Vietnam

项目摘要 流感是一种全球性的持续性病毒性疾病，高病例数导致死亡和损失， 年生产力。在世界上的温带地区，如美国，流感每年出现一次。 冬季周期，随着季节变化的影响，尽管 不同的亚型和病毒株在每个季节占主导地位。在热带地区， 流感没有明确的季节性模式，这表明年度或气候因素可能 并不影响这些地区的传播。热带地区包括世界上许多资源有限的地区， 呼吸道疾病研究资金不足，流感疫苗接种没有得到优先考虑。传输图样 可以通过使用数学模型来描述流感的流行，该模型结合了已知的生物学特性。 机制，如感染性，恢复和感染后免疫的持续时间，以描述 病毒的动力学或群体水平的行为。模型可以包含流感的周期模式 动态，它可以包括与日历年对齐的季节周期以及非年度周期性 周期;模型还可以包含不规则的流行病，尽管这对建模更具挑战性， 常见于当前的文献中。不规则的流行病可以被视为“政权转换”， 发病率持续较低的地方病时期和发病率持续较短的流行病时期之间的过渡 发病率上升的时期。本研究的目的是调查潜在的循环或非循环动力学的流感 在热带地区，以越南为例进行研究。第一个目标是定义描述循环或非循环的模式 动力学，然后使用数学模型来显示在什么条件下非循环动力学可以存在。 可能允许非循环动力学的流感特征可能包括以下免疫持续时间： 感染、交叉免疫和种群结构。第二个目标是寻求使用发达国家的模式以及 作为来自越南的流感数据，以确定流感动态是否遵循周期或非周期模式。 将这些结果与使用温带地区流感数据的相同分析进行比较， 比较热带和温带地区年周期的强度。第三个目标是确定 流感病毒的特征，人口模式或外部因素，可能能够解释周期性 或越南流感动态中观察到的非周期性模式。这将显示流感的特征 或外部因素为越南未来流感发病率提供了最有力的预测。研究报告的用途 结果包括越南流感疫苗接种策略更加明智和适时。的 本研究的新奇之处在于对热带地区的循环或非循环模式进行了明确的测试， 不太常见的调查，以及一种机械建模方法，以确定非 热带地区流感传播的年度行为。

PROJECT SUMMARY Influenza is a persistent viral disease worldwide, with high case counts leading to deaths and losses in productivity yearly. In temperate regions of the world, such as the United States, influenza appears in annual wintertime cycles, with the influences of changing seasons creating predictable patterns of incidence, despite the fact that different subtypes and strains of the virus predominate during each season. In tropical regions, distinct seasonal patterns are not well established for influenza, suggesting that annual or climatic forces may not dictate transmission in these areas. The tropics include many resource-limited areas of the world where respiratory disease research is underfunded and influenza vaccination is not prioritized. Transmission patterns of influenza can be described through the use of mathematical models, which incorporate known biological mechanisms, such as infectivity, recovery, and duration of immunity following infection, in order to describe the dynamics, or population-level behaviors, of the virus. Models can incorporate cyclic patterns of influenza dynamics, which can include both seasonal cycles aligning with a calendar year as well as nonannual periodic cycles; models can also incorporate irregular epidemics, though this is more challenging to model and less commonly seen in current literature. Irregular epidemics can be viewed as “regime switches,” which describes transitions between endemic time periods with consistently low incidence and epidemic time periods with short periods of elevated incidence. This study aims to investigate potentially cyclic or acyclic dynamics of influenza in the tropics, using Vietnam as a case study. The first aim seeks to define patterns describing cyclic or acyclic dynamics and then use a mathematical model to show under what conditions acyclic dynamics can exist. Influenza characteristics that could allow acyclic dynamics potentially include duration of immunity following infection, cross-immunity, and population structure. The second aim seeks to use the developed model as well as influenza data from Vietnam to determine whether influenza dynamics follow cyclic or acyclic patterns. Comparing these results to identical analyses using data from temperate regions influenza data will allow us to compare the strength of annual cycles between tropical and temperate regions. The third aim seeks to identify characteristics of influenza virus, population patterns, or external factors that may be able to explain the cyclic or acyclic patterns observed in influenza dynamics in Vietnam. This will show what characteristics of influenza or external factors provide the strongest predictions of future influenza incidence in Vietnam. Uses of the study results include better informed and appropriately-timed vaccination strategies for influenza in Vietnam. The main points of novelty in this study lie in the explicit testing for cyclic or acyclic patterns in the tropics, which is less commonly investigated, and a mechanistic modeling approach to identify the potential causes of non- annual behavior of influenza transmission in the tropics.