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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

2019; Elsevier BV; Volume: 19; Issue: 6 Linguagem: Inglês

10.1016/s1473-3099(19)30118-5

1474-4457

Placide Mbala‐Kingebeni, Amuri Aziza, Nicholas Di Paola, Michael R. Wiley, Sheila Makiala‐Mandanda, Katie Caviness, Catherine Pratt, Jason T. Ladner, Jeffrey R Kugelman, Karla Prieto, Joseph A Chitty, Peter A. Larson, Brett Beitzel, Ahidjo Ayouba, Nicole Vidal, Stomy Karhemere, Mamadou Diop, Moussa Moïse Diagne, Martin Faye, Ousmane Faye, Aaron Aruna, Justus Nsio, Felix Mulangu, Daniel Mukadi‐Bamuleka, Patrick Mukadi, John Kombe, Anastasie Mulumba, Christian Julián Villabona‐Arenas, Elisabeth Pukuta, Jeanette Gonzalez, Maggie L. Bartlett, Shanmuga Sozhamannan, Stephen M Gross, Gary P Schroth, Roger Tim, Junhua Zhao, Jens H. Kuhn, Boubacar Diallo, Michel Yao, Ibrahima Socé Fall, Bathe Ndjoloko, Mathias Mossoko, Audrey Lacroix, Éric Delaporte, Mariano Sánchez-Lockhart, Amadou A. Sall, Jean‐Jacques Muyembé‐Tamfum, Martine Peeters, Gustavo Palacios, Steve Ahuka‐Mundeke,

Viral Infections and Vectors

BackgroundThe 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.MethodsWe 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.FindingsThe 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.InterpretationThe 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.FundingDefense Biological Product Assurance Office.