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 Équateur 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 rVSV[DELTA]G-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 (GP.sub.12) 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. Author Affiliation: (a) Institut National de Recherche Biomédicale, Kinshasa, Democratic Republic of the Congo (b) TransVIHMI, Institut de Recherche pour le Développement, Institut National de la Santé et de la Recherche Médicale, Université de Montpellier, Montpellier, France (c) Service de Microbiologie, Cliniques Universitaires de Kinshasa, Kinshasa, Democratic Republic of the Congo (d) Center for Genome Sciences, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD, USA (e) College of Public Health, Northern Arizona University, Flagstaff, AZ, USA (f) Department of Pathology and Microbiology, Northern Arizona University, Flagstaff, AZ, USA (g) University of Nebraska Medical Center, Omaha, NE, USA (h) The Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, USA (i) Command and General Staff College, Fort Leavenworth, KS, USA (j) Institut Pasteur de Dakar, Dakar, Senegal (k) Direction Générale de Lutte contre la Maladie, Kinshasa, Democratic Republic of the Congo (l) l'Organisation Mondiale de la Santé, Kinshasa, Democratic Republic of the Congo (m) Centre for the Mathematical Modelling of Infectious Diseases, London School of Hygiene & Tropical Medicine, London, UK (n) Defense Biological Product Assurance Office, Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense-Joint Project Management Office for Guardian, Frederick, MA, USA (o) The Tauri Group, Alexandria, VA, USA (p) Illumina, San Diego, CA, USA (q) Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD, USA (r) World Health Organization, Geneva, Switzerland * Correspondence to: Dr Gustavo Palacios, Center for Genome Sciences, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA (footnote)* Contributed equally (footnote)[Dagger] Joint senior authors Byline: Placide Mbala-Kingebeni, MD (a,b,c,*), Amuri Aziza, MSc (a,*), Nicholas Di Paola, ScD (d,*), Michael R Wiley, PhD (d,e,*), Sheila Makiala-Mandanda, PhD (a,c), Katie Caviness, PhD (d), Catherine B Pratt, MSc (d,e), Jason T Ladner, PhD (g,h), Jeffrey R Kugelman, PhD (i), Karla Prieto, MSc (d,e), Joseph A Chitty, BSc (d), Peter A Larson, PhD (d), Brett Beitzel, PhD (d), Ahidjo Ayouba, PhD (b), Nicole Vidal, PhD (b), Stomy Karhemere, DVM (a), Mamadou Diop, MSc (j), Moussa M Diagne, PhD (j), Martin Faye, PhD (j), Ousmane Faye, PhD (j), Aaron Aruna, MPH (k), Justus Nsio, MPH (k), Felix Mulangu, MPH (k), Daniel Mukadi, MD (c), Patrick Mukadi, MD (a), John Kombe, MPH (k), Anastasie Mulumba, MD (l), Christian-Julian Villabona-Arenas, ScD (m), Elisabeth Pukuta, MSc (a), Jeanette Gonzalez, MSc (d), Maggie L Bartlett, BSc (d,f), Shanmuga Sozhamannan, PhD (n,o), Stephen M Gross, PhD (p), Gary P Schroth, PhD (p), Roger Tim, PhD (p), Junhua J Zhao, PhD (p), Jens H Kuhn, MD (q), Boubacar Diallo, MD (r), Michel Yao, MSc (r), Ibrahima S Fall, MD (r), Bathe Ndjoloko, MD (k), Mathias Mossoko, MPH (k), Audrey Lacroix, PhD (b), Eric Delaporte, PhD (b), Mariano Sanchez-Lockhart, PhD (d,f), Amadou A Sall, PhD (j), Jean-Jacques Muyembe-Tamfum, PhD (a,c), Martine Peeters, PhD (b,[Dagger]), Gustavo Palacios, PhD [gustavo.f.palacios.civ@mail.mil] (d,*,[Dagger]), Steve Ahuka-Mundeke, PhD (a,c,[Dagger])