Insights into the Early Epidemic Spread of Ebola in Sierra Leone Provided by Viral Sequence Data

Background and Methodology: The current Ebola virus epidemic in West Africa has been spreading at least since December 2013. The first confirmed case of Ebola virus in Sierra Leone was identified on May 25. Based on viral genetic sequencing data from 72 individuals in Sierra Leone collected between the end of May and mid June, we utilize a range of phylodynamic methods to estimate the basic reproductive number (R0). We additionally estimate the expected lengths of the incubation and infectious periods of the virus. Finally, we use phylogenetic trees to examine the role played by population structure in the epidemic. Results: The median estimates of R0 based on sequencing data alone range between 1.65-2.18, with the most plausible model yielding a median R0 of 2.18 (95% HPD 1.24-3.55). Importantly, our results indicate that, at least until mid June, relief efforts in Sierra Leone were ineffective at lowering the effective reproductive number of the virus. We estimate the expected length of the infectious period to be 2.58 days (median; 95% HPD 1.24-6.98). The dataset appears to be too small in order to estimate the incubation period with high certainty (median expected incubation period 4.92 days; 95% HPD 2.11-23.20). While our estimates of the duration of infection tend to be smaller than previously reported, phylodynamic analyses support a previous estimate that 70% of cases were observed and included in the present dataset. The dataset is too small to show a particular population structure with high significance, however our preliminary analyses suggest that half the population is spreading the virus with an R0 well above 2, while the other half of the population is spreading with an R0 below 1. Conclusions: Overall we show that sequencing data can robustly infer key epidemiological parameters. Such estimates inform public health officials and help to coordinate effective public health efforts. Thus having more sequencing data available for the ongoing Ebola virus epidemic and at the start of new outbreaks will foster a quick understanding of the dynamics of the pathogen.

[1]  G. Chowell,et al.  Early transmission dynamics of Ebola virus disease (EVD), West Africa, March to August 2014. , 2014, Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin.

[2]  Tanja Stadler,et al.  Bayesian Inference of Sampled Ancestor Trees for Epidemiology and Fossil Calibration , 2014, PLoS Comput. Biol..

[3]  Tanja Stadler,et al.  Mammalian phylogeny reveals recent diversification rate shifts , 2011, Proceedings of the National Academy of Sciences.

[4]  Carlos Castillo-Chavez,et al.  Temporal Variations in the Effective Reproduction Number of the 2014 West Africa Ebola Outbreak , 2014, PLoS currents.

[5]  Dong Xie,et al.  BEAST 2: A Software Platform for Bayesian Evolutionary Analysis , 2014, PLoS Comput. Biol..

[6]  P. Rollin,et al.  Ebola hemorrhagic fever in Kikwit, Democratic Republic of the Congo: clinical observations in 103 patients. , 1999, The Journal of infectious diseases.

[7]  J Bertolli,et al.  Clinical, virologic, and immunologic follow-up of convalescent Ebola hemorrhagic fever patients and their household contacts, Kikwit, Democratic Republic of the Congo. Commission de Lutte contre les Epidémies à Kikwit. , 1999, The Journal of infectious diseases.

[8]  S. Bonhoeffer,et al.  Birth–death skyline plot reveals temporal changes of epidemic spread in HIV and hepatitis C virus (HCV) , 2012, Proceedings of the National Academy of Sciences.

[9]  Tanja Stadler,et al.  Simulating trees with a fixed number of extant species. , 2011, Systematic biology.

[10]  A. Sanchez,et al.  Persistence and genetic stability of Ebola virus during the outbreak in Kikwit, Democratic Republic of the Congo, 1995. , 1999, The Journal of infectious diseases.

[11]  T. Stadler On incomplete sampling under birth-death models and connections to the sampling-based coalescent. , 2009, Journal of theoretical biology.

[12]  S. Dowell,et al.  Transmission of Ebola hemorrhagic fever: a study of risk factors in family members, Kikwit, Democratic Republic of the Congo, 1995. Commission de Lutte contre les Epidémies à Kikwit. , 1999, The Journal of infectious diseases.

[13]  W. Team Ebola Virus Disease in West Africa — The First 9 Months of the Epidemic and Forward Projections , 2014 .

[14]  Margaret Chan,et al.  Ebola virus disease in West Africa--no early end to the outbreak. , 2014, The New England journal of medicine.

[15]  J. Hyman,et al.  The basic reproductive number of Ebola and the effects of public health measures: the cases of Congo and Uganda. , 2004, Journal of theoretical biology.

[16]  C. Althaus Estimating the Reproduction Number of Ebola Virus (EBOV) During the 2014 Outbreak in West Africa , 2014, PLoS currents.

[17]  R. Colebunders,et al.  Epidemiologic and clinical aspects of the Ebola virus epidemic in Mosango, Democratic Republic of the Congo, 1995. , 1999, The Journal of infectious diseases.

[18]  A. Sanchez,et al.  The reemergence of Ebola hemorrhagic fever, Democratic Republic of the Congo, 1995. Commission de Lutte contre les Epidémies à Kikwit. , 1999, The Journal of infectious diseases.

[19]  Alessandro Vespignani,et al.  Assessing the International Spreading Risk Associated with the 2014 West African Ebola Outbreak , 2014, PLoS currents.

[20]  B. Finkenstädt,et al.  Statistical Inference in a Stochastic Epidemic SEIR Model with Control Intervention: Ebola as a Case Study , 2006, Biometrics.

[21]  D. Bausch,et al.  Outbreak of Ebola Virus Disease in Guinea: Where Ecology Meets Economy , 2014, PLoS neglected tropical diseases.

[22]  Christopher Dye,et al.  The international Ebola emergency. , 2014, The New England journal of medicine.

[23]  A Flahault,et al.  Understanding the dynamics of Ebola epidemics , 2006, Epidemiology and Infection.

[24]  D. Fisman,et al.  Early Epidemic Dynamics of the West African 2014 Ebola Outbreak: Estimates Derived with a Simple Two-Parameter Model , 2014, PLoS currents.

[25]  Erik M. Volz,et al.  Complex Population Dynamics and the Coalescent Under Neutrality , 2012, Genetics.

[26]  Tanja Stadler,et al.  Simultaneous reconstruction of evolutionary history and epidemiological dynamics from viral sequences with the birth–death SIR model , 2013, Journal of The Royal Society Interface.

[27]  Beda Joos,et al.  Estimating the basic reproductive number from viral sequence data. , 2012, Molecular biology and evolution.

[28]  Rachel S. G. Sealfon,et al.  Genomic surveillance elucidates Ebola virus origin and transmission during the 2014 outbreak , 2014, Science.

[29]  Tanja Stadler,et al.  Uncovering epidemiological dynamics in heterogeneous host populations using phylogenetic methods , 2013, Philosophical Transactions of the Royal Society B: Biological Sciences.