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

Placide Mbala-Kingebeni¹, Catherine B Pratt², Michael R Wiley², Moussa M Diagne³, Sheila Makiala-Mandanda⁴, Amuri Aziza⁵, Nicholas Di Paola⁶, Joseph A Chitty⁶, Mamadou Diop³, Ahidjo Ayouba⁷, Nicole Vidal⁷, Ousmane Faye³, Oumar Faye³, Stormy Karhemere⁵, Aaron Aruna⁸, Justus Nsio⁸, Felix Mulangu⁸, Daniel Mukadi⁹, Patrick Mukadi⁵, John Kombe⁸, Anastasie Mulumba¹⁰, Sophie Duraffour¹¹, Jacques Likofata¹², Elisabeth Pukuta⁵, Katie Caviness⁶, Maggie L Bartlett¹³, Jeanette Gonzalez⁶, Timothy Minogue¹⁴, Shanmuga Sozhamannan¹⁵, Stephen M Gross¹⁶, Gary P Schroth¹⁶, Jens H Kuhn¹⁷, Eric F Donaldson¹⁸, Eric Delaporte⁷, Mariano Sanchez-Lockhart¹³, Martine Peeters⁷, Jean-Jacques Muyembe-Tamfum⁴, Amadou Alpha Sall³, Gustavo Palacios¹⁹, Steve Ahuka-Mundeke²⁰

Affiliations

¹ 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.
² 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.
³ Institut Pasteur de Dakar, Dakar, Senegal.
⁴ Institut National de Recherche Biomédicale, Kinshasa, Democratic Republic of the Congo; Service de Microbiologie, Cliniques Universitaires de Kinshasa, Kinshasa, Democratic Republic of the Congo.
⁵ Institut National de Recherche Biomédicale, Kinshasa, Democratic Republic of the Congo.
⁶ Center for Genome Sciences, US Army Medical Research Institute of Infectious Diseases, Frederick, MD, USA.
⁷ TransVIHMI, Institut de Recherche pour le Développement, Institut National de la Santé et de la Recherche Médicale, Université de Montpellier, Montpellier, France.
⁸ Direction Générale de Lutte contre la Maladie, Kinshasa, Democratic Republic of the Congo.
⁹ Service de Microbiologie, Cliniques Universitaires de Kinshasa, Kinshasa, Democratic Republic of the Congo.
¹⁰ Monsieur le Représentant de l'Organisation Mondiale de la Santé, Democratic Republic of the Congo.
¹¹ Monsieur le Représentant de l'Organisation Mondiale de la Santé, Democratic Republic of the Congo; Bernhard-Nocht-Institut für Tropenmedizin, Hamburg, Germany.
¹² Laboratoire Provinciale, Mbandaka, Democratic Republic of the Congo.
¹³ 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.
¹⁴ Diagnostics Services Division, US Army Medical Research Institute of Infectious Diseases, Frederick, MD, USA.
¹⁵ 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.
¹⁶ Illumina, San Diego, CA, USA.
¹⁷ Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD, USA.
¹⁸ Division of Antiviral Products, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA.
¹⁹ Center for Genome Sciences, US Army Medical Research Institute of Infectious Diseases, Frederick, MD, USA. Electronic address: gustavo.f.palacios.civ@mail.mil.
²⁰ Service de Microbiologie, Cliniques Universitaires de Kinshasa, Kinshasa, Democratic Republic of the Congo; Institut National de Recherche Biomédicale, Kinshasa, Democratic Republic of the Congo.

PMID: 31000465
DOI: 10.1016/S1473-3099(19)30124-0

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

Placide Mbala-Kingebeni et al. Lancet Infect Dis. 2019 Jun.

. 2019 Jun;19(6):641-647.

doi: 10.1016/S1473-3099(19)30124-0. Epub 2019 Apr 15.

Authors

Affiliations

¹ 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.
² 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.
³ Institut Pasteur de Dakar, Dakar, Senegal.
⁴ Institut National de Recherche Biomédicale, Kinshasa, Democratic Republic of the Congo; Service de Microbiologie, Cliniques Universitaires de Kinshasa, Kinshasa, Democratic Republic of the Congo.
⁵ Institut National de Recherche Biomédicale, Kinshasa, Democratic Republic of the Congo.
⁶ Center for Genome Sciences, US Army Medical Research Institute of Infectious Diseases, Frederick, MD, USA.
⁷ TransVIHMI, Institut de Recherche pour le Développement, Institut National de la Santé et de la Recherche Médicale, Université de Montpellier, Montpellier, France.
⁸ Direction Générale de Lutte contre la Maladie, Kinshasa, Democratic Republic of the Congo.
⁹ Service de Microbiologie, Cliniques Universitaires de Kinshasa, Kinshasa, Democratic Republic of the Congo.
¹⁰ Monsieur le Représentant de l'Organisation Mondiale de la Santé, Democratic Republic of the Congo.
¹¹ Monsieur le Représentant de l'Organisation Mondiale de la Santé, Democratic Republic of the Congo; Bernhard-Nocht-Institut für Tropenmedizin, Hamburg, Germany.
¹² Laboratoire Provinciale, Mbandaka, Democratic Republic of the Congo.
¹³ 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.
¹⁴ Diagnostics Services Division, US Army Medical Research Institute of Infectious Diseases, Frederick, MD, USA.
¹⁵ 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.
¹⁶ Illumina, San Diego, CA, USA.
¹⁷ Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD, USA.
¹⁸ Division of Antiviral Products, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA.
¹⁹ Center for Genome Sciences, US Army Medical Research Institute of Infectious Diseases, Frederick, MD, USA. Electronic address: gustavo.f.palacios.civ@mail.mil.
²⁰ Service de Microbiologie, Cliniques Universitaires de Kinshasa, Kinshasa, Democratic Republic of the Congo; Institut National de Recherche Biomédicale, Kinshasa, Democratic Republic of the Congo.

PMID: 31000465
DOI: 10.1016/S1473-3099(19)30124-0

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^-3 substitutions per site per year with "Tumba" vs 1·06 × 10^-3 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.

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Comment in

Retrospective versus real-time Ebola virus sequencing.
Carroll MW. Carroll MW. Lancet Infect Dis. 2019 Jun;19(6):567-568. doi: 10.1016/S1473-3099(19)30207-5. Epub 2019 Apr 15. Lancet Infect Dis. 2019. PMID: 31000466 No abstract available.

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

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

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