Rapid outbreak sequencing of Ebola virus in Sierra Leone identifies transmission chains linked to sporadic cases

Abstract

To end the largest known outbreak of Ebola virus disease (EVD) in West Africa and to prevent new transmissions, rapid epidemiological tracing of cases and contacts was required. The ability to quickly identify unknown sources and chains of transmission is key to ending the EVD epidemic and of even greater importance in the context of recent reports of Ebola virus (EBOV) persistence in survivors. Phylogenetic analysis of complete EBOV genomes can provide important information on the source of any new infection. A local deep sequencing facility was established at the Mateneh Ebola Treatment Centre in central Sierra Leone. The facility included all wetlab and computational resources to rapidly process EBOV diagnostic samples into full genome sequences. We produced 554 EBOV genomes from EVD cases across Sierra Leone. These genomes provided a detailed description of EBOV evolution and facilitated phylogenetic tracking of new EVD cases. Importantly, we show that linked genomic and epidemiological data can not only support contact tracing but also identify unconventional transmission chains involving body fluids, including semen. Rapid EBOV genome sequencing, when linked to epidemiological information and a comprehensive database of virus sequences across the outbreak, provided a powerful tool for public health epidemic control efforts.

Ebola Virus Shedding and Transmission: Review of Current Evidence

“…Whether virus can be cultured that long after remission remains to be determined. Sexual transmission during the ongoing EVD outbreak is now quite well documented [15,16] and has likely been the cause of sporadic EVD resurgence in West Africa in late 2015 and early 2016 [39].…”

“…Transmission through breastfeeding, even if highly suspected, has never been formally confirmed [39,72]. By use of nextgeneration sequencing, a case of transmission through breastfeeding from an asymptomatic mother, whose plasma tested negative and breast milk tested positive, to her 13-month-old baby has been described [39].…”

“…By use of nextgeneration sequencing, a case of transmission through breastfeeding from an asymptomatic mother, whose plasma tested negative and breast milk tested positive, to her 13-month-old baby has been described [39]. However, other modes of contamination could not be excluded.…”

“…One report relates a case of transmission of SUDV from an asymptomatic person 2 days before development of symptoms [46]. The case describe above of breastfeeding transmission from an asymptomatic mother raises new concerns about possibility of transmission from exposure to select body fluids of EVD survivors from which virus clearance is delayed [39].…”

Use of the Filovirus Animal Non-Clinical Group (FANG) Ebola virus immuno-assay requires fewer study participants to power a study than the Alpha Diagnostic International assay

“…Persistent genomic virus RNA signals have been detected in EVD survivors over a year after resolution of both clinical disease and viremia(Crozier, 2016; Deen et al, 2017; Uyeki et al, 2016). As a result, sexual and vertical transmission of the virus may occur, as evidenced by at least 3 EVD clusters in Liberia, Sierra Leone, and Guinea (Arias et al, 2016; Blackley et al, 2016;Fischer et al, 2016; Fischer and Wohl, 2016; Mate et al, 2015; Sow et al, 2016; Yang et al, 2015). Though the outbreak has ended, countermeasures should be developed to combat any potential reintroductions of EVD into the population by these or other traditional transmission routes.…”