Day Troy, André Jean-Baptiste, Park Andrew
Department of Mathematics and Statistics, Queen's University, Kingston, Ontario, Canada.
Proc Biol Sci. 2006 Dec 7;273(1604):2945-53. doi: 10.1098/rspb.2006.3638.
Pandemic influenza remains a serious public health threat and the processes involved in the evolutionary emergence of pandemic influenza strains remain incompletely understood. Here, we develop a stochastic model for the evolutionary emergence of pandemic influenza, and use it to address three main questions. (i) What is the minimum annual number of avian influenza virus infections required in humans to explain the historical rate of pandemic emergence? (ii) Are such avian influenza infections in humans more likely to give rise to pandemic strains if they are driven by repeated cross-species introductions, or by low-level transmission of avian influenza viruses between humans? (iii) What are the most effective interventions for reducing the probability that an influenza strain with pandemic potential will evolve? Our results suggest that if evolutionary emergence of past pandemics has occurred primarily through viral reassortment in humans, then thousands of avian influenza virus infections in humans must have occurred each year for the past 250 years. Analyses also show that if there is epidemiologically significant variation among avian influenza virus genotypes, then avian virus outbreaks stemming from repeated cross-species transmission events result in a greater likelihood of a pandemic strain evolving than those caused by low-level transmission between humans. Finally, public health interventions aimed at reducing the duration of avian virus infections in humans give the greatest reduction in the probability that a pandemic strain will evolve.
大流行性流感仍然是一个严重的公共卫生威胁，而大流行性流感毒株进化出现所涉及的过程仍未完全被理解。在此，我们开发了一个用于大流行性流感进化出现的随机模型，并使用它来解决三个主要问题。（i）为了解释历史上大流行出现的速率，人类每年所需的禽流感病毒感染的最小数量是多少？（ii）如果人类中的此类禽流感感染是由反复的跨物种引入驱动，还是由禽流感病毒在人类之间的低水平传播驱动，那么它们更有可能产生大流行毒株吗？（iii）对于降低具有大流行潜力的流感毒株进化的概率，最有效的干预措施是什么？我们的结果表明，如果过去大流行的进化出现主要是通过人类中的病毒重配发生的，那么在过去250年中，人类每年必定发生了数千次禽流感病毒感染。分析还表明，如果禽流感病毒基因型之间存在具有流行病学意义的变异，那么由反复的跨物种传播事件引发的禽流感病毒暴发导致大流行毒株进化的可能性比由人类之间的低水平传播引起的暴发更大。最后，旨在减少人类中禽流感病毒感染持续时间的公共卫生干预措施能最大程度降低大流行毒株进化的概率。
