TY - JOUR
T1 - Medical countermeasures during the 2018 Ebola virus disease outbreak in the North Kivu and Ituri Provinces of the Democratic Republic of the Congo
T2 - a rapid genomic assessment
AU - Mbala-Kingebeni, Placide
AU - Aziza, Amuri
AU - Di Paola, Nicholas
AU - Wiley, Michael R.
AU - Makiala-Mandanda, Sheila
AU - Caviness, Katie
AU - Pratt, Catherine B.
AU - Ladner, Jason T.
AU - Kugelman, Jeffrey R.
AU - Prieto, Karla
AU - Chitty, Joseph A.
AU - Larson, Peter A.
AU - Beitzel, Brett
AU - Ayouba, Ahidjo
AU - Vidal, Nicole
AU - Karhemere, Stomy
AU - Diop, Mamadou
AU - Diagne, Moussa M.
AU - Faye, Martin
AU - Faye, Ousmane
AU - Aruna, Aaron
AU - Nsio, Justus
AU - Mulangu, Felix
AU - Mukadi, Daniel
AU - Mukadi, Patrick
AU - Kombe, John
AU - Mulumba, Anastasie
AU - Villabona-Arenas, Christian Julian
AU - Pukuta, Elisabeth
AU - Gonzalez, Jeanette
AU - Bartlett, Maggie L.
AU - Sozhamannan, Shanmuga
AU - Gross, Stephen M.
AU - Schroth, Gary P.
AU - Tim, Roger
AU - Zhao, Junhua J.
AU - Kuhn, Jens H.
AU - Diallo, Boubacar
AU - Yao, Michel
AU - Fall, Ibrahima S.
AU - Ndjoloko, Bathe
AU - Mossoko, Mathias
AU - Lacroix, Audrey
AU - Delaporte, Eric
AU - Sanchez-Lockhart, Mariano
AU - Sall, Amadou A.
AU - Muyembe-Tamfum, Jean Jacques
AU - Peeters, Martine
AU - Palacios, Gustavo
AU - Ahuka-Mundeke, Steve
N1 - Funding Information:
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. The content of this Article does not necessarily represent the official policy or views of the US Department of the Army, the US Department of Defense, the US Department of Health and Human Services, the US Government, or the institutions or companies affiliated with the authors.
Publisher Copyright:
© 2019 Elsevier Ltd
PY - 2019/6
Y1 - 2019/6
N2 - 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 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.
AB - 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 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.
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U2 - 10.1016/S1473-3099(19)30118-5
DO - 10.1016/S1473-3099(19)30118-5
M3 - Article
C2 - 31000464
AN - SCOPUS:85065874808
SN - 1473-3099
VL - 19
SP - 648
EP - 657
JO - The Lancet Infectious Diseases
JF - The Lancet Infectious Diseases
IS - 6
ER -