1. Medical countermeasures during the 2018 Ebola virus disease outbreak in the North Kivu and Ituri Provinces of the Democratic Republic of the Congo: a rapid genomic assessment
- Author
-
Aaron Aruna, Ousmane Faye, Martine Peeters, Stomy Karhemere, Jean Jacques Muyembe-Tamfum, Amadou A. Sall, Ibrahima Socé Fall, Audrey Lacroix, Katie Caviness, Daniel Mukadi, Mariano Sanchez-Lockhart, Moussa Moïse Diagne, Bathe Ndjoloko, Christian Julian Villabona-Arenas, Elisabeth Pukuta, Jeffrey R. Kugelman, Felix Mulangu, Karla Prieto, Nicholas Di Paola, Joseph A. Chitty, Sheila Makiala-Mandanda, Anastasie Mulumba, Nicole Vidal, Steve Ahuka-Mundeke, Brett Beitzel, Gary P. Schroth, Patrick Mukadi, Eric Delaporte, Maggie L. Bartlett, Jason T. Ladner, Junhua J. Zhao, Boubacar Diallo, Mathias Mossoko, Catherine B. Pratt, Jens H. Kuhn, Amuri Aziza, Michael R. Wiley, Peter A. Larson, John Kombe, Martin Faye, Michel Yao, Jeanette Gonzalez, Roger Tim, Placide Mbala-Kingebeni, Ahidjo Ayouba, Gustavo Palacios, Shanmuga Sozhamannan, Justus Nsio, Mamadou Diop, Stephen M. Gross, Recherches Translationnelles sur le VIH et les maladies infectieuses (TransVIHMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche pour le Développement (IRD)-Université Montpellier 1 (UM1)-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Universtié Yaoundé 1 [Cameroun]-Université de Montpellier (UM), Institut de Recherche pour le Développement (IRD [France-Sud]), Université de Montpellier (UM), Institut National de Recherche Biomédicale [Kinshasa] (INRB), Institut National de la Santé et de la Recherche Médicale (INSERM), University of Nebraska Medical Center, University of Nebraska System, Institut Pasteur de Dakar, Réseau International des Instituts Pasteur (RIIP), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Army Medical Research Institute of Infectious Diseases [USA] (USAMRIID), This work was supported by the Defense Biological Product Assurance Office through a task order award to the National Strategic Research Institute (FA4600-12-D-9000). We thank Laura Bollinger (National Institute of Allergy and Infectious Diseases, Frederick, MD, USA) for critically editing this manuscript. This work was funded in part through Battelle Memorial Institute's prime contract with the US National Institute of Allergy and Infectious Diseases under contract number HHSN272200700016I., Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques er émergentes (TransVIHMI), and Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Université Montpellier 1 (UM1)
- Subjects
0301 basic medicine ,viruses ,[SDV]Life Sciences [q-bio] ,Genomics ,Biology ,ZMapp ,medicine.disease_cause ,Antiviral Agents ,Disease Outbreaks ,03 medical and health sciences ,0302 clinical medicine ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,medicine ,Humans ,030212 general & internal medicine ,Ebola Vaccines ,Pathogen ,Retrospective Studies ,Ebola virus ,GeneXpert MTB/RIF ,Transmission (medicine) ,Antibodies, Monoclonal ,Outbreak ,Hemorrhagic Fever, Ebola ,Biological product ,Ebolavirus ,Virology ,3. Good health ,030104 developmental biology ,Infectious Diseases ,Medical Countermeasures ,Democratic Republic of the Congo ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology ,medicine.drug - Abstract
Summary Background The real-time generation of information about pathogen genomes has become a vital goal for transmission analysis and characterisation in rapid outbreak responses. In response to the recently established genomic capacity in the Democratic Republic of the Congo, we explored the real-time generation of genomic information at the start of the 2018 Ebola virus disease (EVD) outbreak in North Kivu Province. Methods We used targeted-enrichment sequencing to produce two coding-complete Ebola virus genomes 5 days after declaration of the EVD outbreak in North Kivu. Subsequent sequencing efforts yielded an additional 46 genomes. Genomic information was used to assess early transmission, medical countermeasures, and evolution of Ebola virus. Findings The genomic information demonstrated that the EVD outbreak in the North Kivu and Ituri Provinces was distinct from the 2018 EVD outbreak in Equateur Province of the Democratic Republic of the Congo. Primer and probe mismatches to Ebola virus were identified in silico for all deployed diagnostic PCR assays, with the exception of the Cepheid GeneXpert GP assay. Interpretation The first two coding-complete genomes provided actionable information in real-time for the deployment of the rVSVΔG-ZEBOV-GP Ebola virus envelope glycoprotein vaccine, available therapeutics, and sequence-based diagnostic assays. Based on the mutations identified in the Ebola virus surface glycoprotein (GP12) observed in all 48 genomes, deployed monoclonal antibody therapeutics (mAb114 and ZMapp) should be efficacious against the circulating Ebola virus variant. Rapid Ebola virus genomic characterisation should be included in routine EVD outbreak response procedures to ascertain efficacy of medical countermeasures. Funding Defense Biological Product Assurance Office.
- Published
- 2019