2018 Ebola virus disease outbreak in Équateur Province, Democratic Republic of the Congo: a retrospective genomic characterisation.

Gary P Schroth, Sophie Duraffour, Jacques Likofata, Elisabeth Pukuta, Katie Caviness, Maggie L Bartlett, Jeanette Gonzalez, Timothy Minogue, Shanmuga Sozhamannan, Stephen M Gross, Anastasie Mulumba, Jens H Kuhn, Eric F Donaldson, Eric Delaporte, Mariano Sanchez-Lockhart, Martine Peeters, Jean-Jacques Muyembe-Tamfum, Amadou Alpha Sall, Gustavo Palacios, Steve Ahuka-Mundeke, Nicole Vidal, Catherine B Pratt, Michael R Wiley, Moussa M Diagne, Sheila Makiala-Mandanda, Amuri Aziza, Nicholas Di Paola, Joseph A Chitty, Mamadou Diop, Ahidjo Ayouba, Placide Mbala-Kingebeni, Ousmane Faye, Oumar Faye, Stormy Karhemere, Aaron Aruna, Justus Nsio, Felix Mulangu, Daniel Mukadi, Patrick Mukadi, John Kombe

Journal: The Lancet. Infectious diseases 2020;19(6):641-647

PMID: 31000465

Full Text on Elsevier Science View on PubMed

Abstract

BACKGROUND

The 2018 Ebola virus disease (EVD) outbreak in Équateur Province, Democratic Republic of the Congo, began on May 8, and was declared over on July 24; it resulted in 54 documented cases and 33 deaths. We did a retrospective genomic characterisation of the outbreak and assessed potential therapeutic agents and vaccine (medical countermeasures).

METHODS

We used target-enrichment sequencing to produce Ebola virus genomes from samples obtained in the 2018 Équateur Province outbreak. Combining these genomes with genomes associated with known outbreaks from GenBank, we constructed a maximum-likelihood phylogenetic tree. In-silico analyses were used to assess potential mismatches between the outbreak strain and the probes and primers of diagnostic assays and the antigenic sites of the experimental rVSVΔG-ZEBOV-GP vaccine and therapeutics. An in-vitro flow cytometry assay was used to assess the binding capability of the individual components of the monoclonal antibody cocktail ZMapp.

FINDINGS

A targeted sequencing approach produced 16 near-complete genomes. Phylogenetic analysis of these genomes and 1011 genomes from GenBank revealed a distinct cluster, confirming a new Ebola virus variant, for which we propose the name "Tumba". This new variant appears to have evolved at a slower rate than other Ebola virus variants (0·69 × 10 substitutions per site per year with "Tumba" vs 1·06 × 10 substitutions per site per year without "Tumba"). We found few sequence mismatches in the assessed assay target regions and antigenic sites. We identified nine amino acid changes in the Ebola virus surface glycoprotein, of which one resulted in reduced binding of the 13C6 antibody within the ZMapp cocktail.

INTERPRETATION

Retrospectively, we show the feasibility of using genomics to rapidly characterise a new Ebola virus variant within the timeframe of an outbreak. Phylogenetic analysis provides further indications that these variants are evolving at differing rates. Rapid in-silico analyses can direct in-vitro experiments to quickly assess medical countermeasures.

FUNDING

Defense Biological Product Assurance Office.

Address: Institut National de Recherche Biomédicale, Kinshasa, Democratic Republic of the Congo; TransVIHMI, Institut de Recherche pour le Développement, Institut National de la Santé et de la Recherche Médicale, Université de Montpellier, Montpellier, France; Service de Microbiologie, Cliniques Universitaires de Kinshasa, Kinshasa, Democratic Republic of the Congo.; Center for Genome Sciences, US Army Medical Research Institute of Infectious Diseases, Frederick, MD, USA; College of Public Health, University of Nebraska Medical Center, Omaha, NE, USA.; Institut Pasteur de Dakar, Dakar, Senegal.; Institut National de Recherche Biomédicale, Kinshasa, Democratic Republic of the Congo; Service de Microbiologie, Cliniques Universitaires de Kinshasa, Kinshasa, Democratic Republic of the Congo.; Institut National de Recherche Biomédicale, Kinshasa, Democratic Republic of the Congo.; Center for Genome Sciences, US Army Medical Research Institute of Infectious Diseases, Frederick, MD, USA.; TransVIHMI, Institut de Recherche pour le Développement, Institut National de la Santé et de la Recherche Médicale, Université de Montpellier, Montpellier, France.; Direction Générale de Lutte contre la Maladie, Kinshasa, Democratic Republic of the Congo.; Service de Microbiologie, Cliniques Universitaires de Kinshasa, Kinshasa, Democratic Republic of the Congo.; Monsieur le Représentant de l'Organisation Mondiale de la Santé, Democratic Republic of the Congo.; Monsieur le Représentant de l'Organisation Mondiale de la Santé, Democratic Republic of the Congo; Bernhard-Nocht-Institut für Tropenmedizin, Hamburg, Germany.; Laboratoire Provinciale, Mbandaka, Democratic Republic of the Congo.; Center for Genome Sciences, US Army Medical Research Institute of Infectious Diseases, Frederick, MD, USA; Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, USA.; Diagnostics Services Division, US Army Medical Research Institute of Infectious Diseases, Frederick, MD, USA.; Defense Biological Product Assurance Office, Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense-Joint Project Management Office for Guardian, Frederick, MD, USA; Logistics Management Institute, Tysons, VA, USA.; Illumina, San Diego, CA, USA.; Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD, USA.; Division of Antiviral Products, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA.; Center for Genome Sciences, US Army Medical Research Institute of Infectious Diseases, Frederick, MD, USA. Electronic address: [email protected].; Service de Microbiologie, Cliniques Universitaires de Kinshasa, Kinshasa, Democratic Republic of the Congo; Institut National de Recherche Biomédicale, Kinshasa, Democratic Republic of the Congo.

DOI: 10.1016/S1473-3099(19)30124-0

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MeSH Terms: Antiviral Agents, Democratic Republic of the Congo, Disease Outbreaks, Ebola Vaccines, Ebolavirus, Genomics, Hemorrhagic Fever, Ebola, Humans, Retrospective Studies