Suchergebnisse

Bundibugyo virus (BDBV) is one of four ebolaviruses known to cause disease in humans. Bundibugyo virus disease (BVD) outbreaks occurred in 2007–2008 in Bundibugyo District, Uganda, and in 2012 in Isiro, Province Orientale, Democratic Republic of the Congo. The 2012 BVD outbreak resulted in 38 laboratory-confirmed cases of human infection, 13 of whom died. However, only 4 BDBV specimens from the 2012 outbreak have been sequenced. Here, we provide BDBV sequences from seven additional patients. Analysis of the molecular epidemiology and evolutionary dynamics of the 2012 outbreak with these additional isolates challenges the current hypothesis that the outbreak was the result of a single spillover event. In addition, one patient record indicates that BDBV's initial emergence in Isiro occurred 50 days earlier than previously accepted. Collectively, this work demonstrates how retrospective sequencing can be used to elucidate outbreak origins and provide epidemiological contexts to a medically relevant pathogen.

Biosafety, biosecurity, logistical, political, and technical considerations can delay or prevent the wide dissemination of source material containing viable virus from the geographic origin of an outbreak to laboratories involved in developing medical countermeasures (MCMs). However, once virus genome sequence information is available from clinical samples, reverse-genetics systems can be used to generate virus stocks de novo to initiate MCM development. In this study, we developed a reverse-genetics system for natural isolates of Ebola virus (EBOV) variants Makona, Tumba, and Ituri, which have been challenging to obtain. These systems were generated starting solely with in silico genome sequence information and have been used successfully to produce recombinant stocks of each of the viruses for use in MCM testing. The antiviral activity of MCMs targeting viral entry varied depending on the recombinant virus isolate used. Collectively, selecting and synthetically engineering emerging EBOV variants and demonstrating their efficacy against available MCMs will be crucial for answering pressing public health and biosecurity concerns during Ebola disease (EBOD) outbreaks.

On August 1, 2018, the Democratic Republic of the Congo declared its tenth Ebola virus disease outbreak. To aid the epidemiologic response, the Institut National de Recherche Biomédicale implemented an end-to-end genomic surveillance system, including sequencing, bioinformatic analysis, and dissemination of genomic epidemiologic results to frontline public health workers. We report 744 new genomes sampled between July 27, 2018 and April 27, 2020 generated by this surveillance effort. Together with previously available sequence data (n = 48 genomes), these data represent almost 24% of all laboratory-confirmed Ebola virus infections in DRC in the analyzed period. We inferred spatiotemporal transmission dynamics from the genomic data as new sequences were generated and disseminated the results to support epidemiologic response efforts. Here, we provide an overview of how this genomic surveillance system functioned, present a full phylodynamic analysis of 792 Ebola genomes from the Nord Kivu outbreak, and discuss how the genomic surveillance data informed response efforts and public health decision-making.