Epidemic Dynamics Revealed in Dengue Evolution

被引:87
作者
Bennett, S. N. [1 ]
Drummond, A. J. [2 ]
Kapan, D. D. [3 ]
Suchard, M. A. [4 ]
Munoz-Jordan, J. L. [5 ]
Pybus, O. G. [6 ]
Holmes, E. C. [7 ]
Gubler, D. J. [1 ,8 ]
机构
[1] Univ Hawaii Manoa, Dept Trop Med Med Microbiol & Pharmacol, Asia Pacific Inst Trop Med & Infect Dis, JA Burns Sch Med, Honolulu, HI 96822 USA
[2] Univ Auckland, Dept Comp Sci, Auckland 1, New Zealand
[3] Univ Hawaii Manoa, Ctr Conservat & Res Training, Honolulu, HI 96822 USA
[4] Univ Calif Los Angeles, Dept Biomath Biostat & Human Genet, David Geffen Sch Med, Los Angeles, CA 90024 USA
[5] Ctr Dis Control & Prevent, Dengue Branch, Div Vector Borne Infect Dis, San Juan, PR USA
[6] Univ Oxford, Dept Zool, Oxford OX1 3PS, England
[7] Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA
[8] Duke NUS Grad Med Sch, Singapore, Singapore
关键词
adaptive evolution; phylodynamics; dengue; virus; epidemics; population bottlenecks; PUERTO-RICO; MODEL; THAILAND; PATTERN;
D O I
10.1093/molbev/msp285
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:811 / 818
页数:8
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