Phylodynamics of Infectious Disease Epidemics

We present a formalism for unifying the inference of population size from genetic sequences and mathematical models of infectious disease in populations. Virus phylogenies have been used in many recent studies to infer properties of epidemics. These approaches rely on coalescent models that may not be appropriate for infectious diseases. We account for phylogenetic patterns of viruses in susceptible–infected (SI), susceptible–infected–susceptible (SIS), and susceptible–infected–recovered (SIR) models of infectious disease, and our approach may be a viable alternative to demographic models used to reconstruct epidemic dynamics. The method allows epidemiological parameters, such as the reproductive number, to be estimated directly from viral sequence data. We also describe patterns of phylogenetic clustering that are often construed as arising from a short chain of transmissions. Our model reproduces the moments of the distribution of phylogenetic cluster sizes and may therefore serve as a null hypothesis for cluster sizes under simple epidemiological models. We examine a small cross-sectional sample of human immunodeficiency (HIV)-1 sequences collected in the United States and compare our results to standard estimates of effective population size. Estimated prevalence is consistent with estimates of effective population size and the known history of the HIV epidemic. While our model accurately estimates prevalence during exponential growth, we find that periods of decline are harder to identify.

[1]  W. O. Kermack,et al.  A contribution to the mathematical theory of epidemics , 1927 .

[2]  J. Doob Stochastic processes , 1953 .

[3]  Alexander Grey,et al.  The Mathematical Theory of Infectious Diseases and Its Applications , 1977 .

[4]  N. Ling The Mathematical Theory of Infectious Diseases and its applications , 1978 .

[5]  C. J-F,et al.  THE COALESCENT , 1980 .

[6]  J. Kingman On the genealogy of large populations , 1982, Journal of Applied Probability.

[7]  S. Tavaré Some probabilistic and statistical problems in the analysis of DNA sequences , 1986 .

[8]  P. Kaye Infectious diseases of humans: Dynamics and control , 1993 .

[9]  S. Tavaré,et al.  Sampling theory for neutral alleles in a varying environment. , 1994, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[10]  E. Holmes,et al.  Inferring population history from molecular phylogenies. , 1995, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[11]  C. Moritz,et al.  Genetic Patterns Suggest Exponential Population Growth in a Declining Species , 1996 .

[12]  M. Niu,et al.  Nevirapine, Zidovudine, and Didanosine Compared with Zidovudine and Didanosine in Patients with HIV-1 Infection , 1996, Annals of Internal Medicine.

[13]  D. Richman,et al.  Sequence clusters in human immunodeficiency virus type 1 reverse transcriptase are associated with subsequent virological response to antiretroviral therapy. , 1999, The Journal of infectious diseases.

[14]  O. Pybus,et al.  An integrated framework for the inference of viral population history from reconstructed genealogies. , 2000, Genetics.

[15]  J P Bru,et al.  Acute HIV infection: impact on the spread of HIV and transmission of drug resistance , 2001, AIDS.

[16]  J Theiler,et al.  Using human immunodeficiency virus type 1 sequences to infer historical features of the acquired immune deficiency syndrome epidemic and human immunodeficiency virus evolution. , 2001, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[17]  O. Pybus,et al.  The Epidemic Behavior of the Hepatitis C Virus , 2001, Science.

[18]  Noah A. Rosenberg,et al.  Genealogical trees, coalescent theory and the analysis of genetic polymorphisms , 2002, Nature Reviews Genetics.

[19]  S. Sampling theory for neutral alleles in a varying environment , 2003 .

[20]  Anne-Mieke Vandamme,et al.  U.S. Human Immunodeficiency Virus Type 1 Epidemic: Date of Origin, Population History, and Characterization of Early Strains , 2003, Journal of Virology.

[21]  Stephen M. Krone,et al.  The coalescent process in a population with stochastically varying size , 2003, Journal of Applied Probability.

[22]  O. Pybus,et al.  Unifying the Epidemiological and Evolutionary Dynamics of Pathogens , 2004, Science.

[23]  K. Strimmer,et al.  Inference of demographic history from genealogical trees using reversible jump Markov chain Monte Carlo , 2005, BMC Evolutionary Biology.

[24]  Daniel Falush,et al.  Germs, genomes and genealogies. , 2005, Trends in ecology & evolution.

[25]  O. Pybus,et al.  Bayesian coalescent inference of past population dynamics from molecular sequences. , 2005, Molecular biology and evolution.

[26]  Stéphane Hué,et al.  Genetic analysis reveals the complex structure of HIV-1 transmission within defined risk groups. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[27]  Martin Fisher,et al.  Transmission of HIV-1 during primary infection: relationship to sexual risk and sexually transmitted infections , 2005, AIDS.

[28]  Yun-Xin Fu Exact coalescent for the Wright-Fisher model. , 2006, Theoretical population biology.

[29]  Steven M Goodreau Assessing the Effects of Human Mixing Patterns on Human Immunodeficiency Virus-1 Interhost Phylogenetics Through Social Network Simulation , 2006, Genetics.

[30]  Michel Roger,et al.  High rates of forward transmission events after acute/early HIV-1 infection. , 2007, The Journal of infectious diseases.

[31]  Lisa M. Lee,et al.  Estimation of HIV incidence in the United States. , 2008, JAMA.

[32]  S. Frost,et al.  Sexual networks and the transmission of drug-resistant HIV , 2008, Current opinion in infectious diseases.

[33]  A. Rambaut,et al.  Episodic Sexual Transmission of HIV Revealed by Molecular Phylodynamics , 2008, PLoS medicine.