Epidemic Dynamics Revealed in Dengue Evolution
Epidemic Dynamics Revealed in Dengue Evolution
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DOI：
10.1093/molbev/msp285
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发表时间：
2010-04-01
影响因子：
10.7
通讯作者：
Gubler, D. J.
中科院分区：
文献类型：
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作者：
Bennett, S. N.;Drummond, A. J.;Gubler, D. J.
登革热是一种新出现的热带疾病，每年感染数千万人。登革热是一种具有潜在严重出血表现的发热性疾病，由蚊媒病毒(DENV-1至-4)引起，这种病毒在热带大城市中心的地方性传播中保持不变，流行周期为3至5年。波多黎各(PR)是加勒比地区的一个主要人口中心，自20世纪70年代末开始引入多种登革热血清型以来，该国经历了越来越严重的流行病。我们记录了1981至1998年间DENV-4病毒的系统动力学，这是一个戏剧性的生态扩张时期，在此期间也发生了进化变化。病毒进化的时间尺度足够短，以至于可以从遗传多样性数据中阐明病毒传播的动态。具体地说，通过将这20年来PR中的病毒序列数据与确诊病例计数相结合，我们表明周期性流行病的模式与使用贝叶斯马尔科夫链蒙特卡罗方法从采样病毒序列估计的有效种群规模的合并估计强烈相关。因此，我们表明，观察到的流行病学动态与多样性的类似波动相关，包括流行病间遗传多样性的严重减少与可能极大影响DENV进化动态的种群瓶颈相适应。基于遗传数据的平均有效种群数量似乎在隔离计数之前增加，这表明后者存在潜在的偏见，并有理由对DENV活动进行更积极的监测。我们的分析明确地将流行病学和序列数据整合在一个联合模型中，可用于进一步探索传染病的传播模式。
Dengue is an emerging tropical disease infecting tens of millions of people annually. A febrile illness with potentially severe hemorrhagic manifestations, dengue is caused by mosquito-borne viruses (DENV-1 to -4) that are maintained in endemic transmission in large urban centers of the tropics with periodic epidemic cycles at 3- to 5-year intervals. Puerto Rico ( PR), a major population center in the Caribbean, has experienced increasingly severe epidemics since multiple dengue serotypes were introduced beginning in the late 1970s. We document the phylodynamics of DENV-4 between 1981 and 1998, a period of dramatic ecological expansion during which evolutionary change also occurs. The timescale of viral evolution is sufficiently short that viral transmission dynamics can be elucidated from genetic diversity data. Specifically, by combining virus sequence data with confirmed case counts in PR over these two decades, we show that the pattern of cyclic epidemics is strongly correlated with coalescent estimates of effective population size that have been estimated from sampled virus sequences using Bayesian Markov Chain Monte Carlo methods. Thus, we show that the observed epidemiologic dynamics are correlated with similar fluctuations in diversity, including severe interepidemic reductions in genetic diversity compatible with population bottlenecks that may greatly impact DENV evolutionary dynamics. Mean effective population sizes based on genetic data appear to increase prior to isolation counts, suggesting a potential bias in the latter and justifying more active surveillance of DENV activity. Our analysis explicitly integrates epidemiologic and sequence data in a joint model that could be used to further explore transmission models of infectious disease.