Ebola virus epidemiology, transmission, and evolution during seven months in Sierra Leone

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This article was published in Cell on June 18, 2015.

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Abstract

Summary

The 2013-2015 Ebola virus disease (EVD) epidemic is caused by the Makona variant of Ebola virus (EBOV). Early in the epidemic, genome sequencing provided insights into virus evolution and transmission, and offered important information for outbreak response. Here we analyze sequences from 232 patients sampled over 7 months in Sierra Leone, along with 86 previously released genomes from earlier in the epidemic. We confirm sustained human-to-human transmission within Sierra Leone and find no evidence for import or export of EBOV across national borders after its initial introduction. Using high-depth replicate sequencing, we observe both host-to-host transmission and recurrent emergence of intrahost genetic variants. We trace the increasing impact of purifying selection in suppressing the accumulation of nonsynonymous mutations over time. Finally, we note changes in the mucin-like domain of EBOV glycoprotein that merit further investigation. These findings clarify the movement of EBOV within the region and describe viral evolution during prolonged human-to-human transmission.

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Introduction

The 2013-2015 Western African Ebola virus disease (EVD) epidemic, caused by the Ebola virus (EBOV) Makona variant (Kuhn et al., 2014), is the largest EVD outbreak to date, with 26,648 cases and 11,017 deaths documented as of May 8, 2015 (WHO, 2015). The outbreak, first declared in March 2014 in Guinea and traced back to the end of 2013 (Baize et al., 2014), has also devastated the neighboring countries of Sierra Leone and Liberia, with additional cases scattered across the globe. Never before has an EBOV variant been transmitted among humans for such an sustained period of time.

Published EBOV Makona genomes from clinical samples obtained early in the outbreak in Guinea (three patients) and Sierra Leone (78 patients) (Baize et al., 2014; Gire et al., 2014), demonstrated that near-real-time sequencing could provide valuable information to researchers involved in the global outbreak response. Analysis of these genomes revealed that the outbreak likely originated from a single introduction into the human population in Guinea at the end of 2013 and was then sustained exclusively by human-to-human transmissions. Genomic sequencing further allowed the identification of numerous mutations emerging in the EBOV Makona genome over time. As a consequence, the evolutionary rate of the Makona variant over the timespan of the early phase of the outbreak could be estimated, and predictions made on the potential of this new EBOV variant to escape current candidate vaccines, therapeutics, and diagnostics (Kugelman et al., 2015).

While the insights gleaned from sequencing early in the outbreak informed public health efforts (Alizon et al., 2014; Stadler et al., 2014; Volz et al., 2014), the continued human-to-human spread of the virus raises questions about ongoing evolution and transmission of EBOV. Our laboratory teams in Sierra Leone, at Kenema (Kenema Government Hospital, KGH) and at Bo (US Centers for Disease Control and Prevention, CDC) continued to perform active diagnosis and surveillance in Sierra Leone following our initial study (Gire et al., 2014). After a 6-month delay of sample shipment due to regulatory uncertainty about inactivation protocols, we again began to determine EBOV genome sequences. We have sequenced samples at high depth and with technical replicates to characterize genetic diversity of EBOV both within (intrahost) and between (interhost) individuals. To support global outbreak termination efforts, we publicly released these genomes prior to publication as they were generated, starting with a first set of 45 sequences in December 2014 and continuing with regular releases of hundreds of sequences through May 2015.

Here we provide an analysis of