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

Placide Mbala-Kingebeni, Amuri Aziza, Nicholas Di Paola, Michael R. Wiley, Sheila Makiala-Mandanda, Katie Caviness, Catherine B. 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 M. Diagne, Martin Faye, Ousmane FayeAaron Aruna, Justus Nsio, Felix Mulangu, Daniel Mukadi, Patrick Mukadi, John Kombe, Anastasie Mulumba, Christian Julian Villabona-Arenas, Elisabeth Pukuta, Jeanette Gonzalez, Maggie L. Bartlett, Shanmuga Sozhamannan, Stephen M. Gross, Gary P. Schroth, Roger Tim, Junhua J. Zhao, Jens H. Kuhn, Boubacar Diallo, Michel Yao, Ibrahima S. Fall, Bathe Ndjoloko, Mathias Mossoko, Audrey Lacroix, Eric Delaporte, Mariano Sanchez-Lockhart, Amadou A. Sall, Jean Jacques Muyembe-Tamfum, Martine Peeters, Gustavo Palacios, Steve Ahuka-Mundeke

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)648-657
Number of pages10
JournalThe Lancet Infectious Diseases
Volume19
Issue number6
DOIs
StatePublished - Jun 2019

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Ebola Hemorrhagic Fever
Ebolavirus
Democratic Republic of the Congo
Disease Outbreaks
Genome
Membrane Glycoproteins
Biological Products
Computer Simulation
Vaccines
Monoclonal Antibodies
Polymerase Chain Reaction
Mutation
Therapeutics

ASJC Scopus subject areas

  • Infectious Diseases

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

In: The Lancet Infectious Diseases, Vol. 19, No. 6, 06.2019, p. 648-657.

Research output: Contribution to journalArticle

Mbala-Kingebeni, P, Aziza, A, Di Paola, N, Wiley, MR, Makiala-Mandanda, S, Caviness, K, Pratt, CB, Ladner, JT, Kugelman, JR, Prieto, K, Chitty, JA, Larson, PA, Beitzel, B, Ayouba, A, Vidal, N, Karhemere, S, Diop, M, Diagne, MM, Faye, M, Faye, O, Aruna, A, Nsio, J, Mulangu, F, Mukadi, D, Mukadi, P, Kombe, J, Mulumba, A, Villabona-Arenas, CJ, Pukuta, E, Gonzalez, J, Bartlett, ML, Sozhamannan, S, Gross, SM, Schroth, GP, Tim, R, Zhao, JJ, Kuhn, JH, Diallo, B, Yao, M, Fall, IS, Ndjoloko, B, Mossoko, M, Lacroix, A, Delaporte, E, Sanchez-Lockhart, M, Sall, AA, Muyembe-Tamfum, JJ, Peeters, M, Palacios, G & Ahuka-Mundeke, S 2019, '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', The Lancet Infectious Diseases, vol. 19, no. 6, pp. 648-657. https://doi.org/10.1016/S1473-3099(19)30118-5
Mbala-Kingebeni, Placide ; Aziza, Amuri ; Di Paola, Nicholas ; Wiley, Michael R. ; Makiala-Mandanda, Sheila ; Caviness, Katie ; Pratt, Catherine B. ; Ladner, Jason T. ; Kugelman, Jeffrey R. ; Prieto, Karla ; Chitty, Joseph A. ; Larson, Peter A. ; Beitzel, Brett ; Ayouba, Ahidjo ; Vidal, Nicole ; Karhemere, Stomy ; Diop, Mamadou ; Diagne, Moussa M. ; Faye, Martin ; Faye, Ousmane ; Aruna, Aaron ; Nsio, Justus ; Mulangu, Felix ; Mukadi, Daniel ; Mukadi, Patrick ; Kombe, John ; Mulumba, Anastasie ; Villabona-Arenas, Christian Julian ; Pukuta, Elisabeth ; Gonzalez, Jeanette ; Bartlett, Maggie L. ; Sozhamannan, Shanmuga ; Gross, Stephen M. ; Schroth, Gary P. ; Tim, Roger ; Zhao, Junhua J. ; Kuhn, Jens H. ; Diallo, Boubacar ; Yao, Michel ; Fall, Ibrahima S. ; Ndjoloko, Bathe ; Mossoko, Mathias ; Lacroix, Audrey ; Delaporte, Eric ; Sanchez-Lockhart, Mariano ; Sall, Amadou A. ; Muyembe-Tamfum, Jean Jacques ; Peeters, Martine ; Palacios, Gustavo ; Ahuka-Mundeke, Steve. / 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. In: The Lancet Infectious Diseases. 2019 ; Vol. 19, No. 6. pp. 648-657.
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abstract = "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 {\'E}quateur 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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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

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.

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