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Now published in The Lancet

Characterization of Ebola Virus from an Ongoing Outbreak in Ituri and North Kivu, DR Congo to Guide to Response Activities

30 Pages Posted: 18 Apr 2019

See all articles by Laura McMullan

Laura McMullan

Government of the United States of America - Viral Special Pathogens Branch

Mike Flint

Government of the United States of America - Viral Special Pathogens Branch

Ayan Chakrabarti

Government of the United States of America - Viral Special Pathogens Branch

Lisa Guerrero

Government of the United States of America - Viral Special Pathogens Branch

Michael K. Lo

Government of the United States of America - Viral Special Pathogens Branch

Danielle Porter

Gilead Sciences, Inc.

Stuart T. Nichol

Government of the United States of America - Viral Special Pathogens Branch

Christina F. Spiropoulou

Government of the United States of America - Viral Special Pathogens Branch

Cesar Albarino

Government of the United States of America - Viral Special Pathogens Branch

More...

Abstract

Background: The ongoing Ebola virus (EBOV) outbreak in the Ituri and North Kivu provinces of the Democratic Republic of Congo (DRC) is the second largest ever recorded. Despite civil unrest, outbreak control measures, and the administration of experimental therapies and a vaccine, have been initiated. Lacking a virus isolate from this outbreak, we rescued recombinant, infectious EBOV-Ituri virus from plasmid DNA.

Methods: We report a phylogenetic analysis of EBOV-Ituri. In addition, we evaluated experimental therapeutics currently undergoing clinical trials in DRC: remdesivir (GS-5734) and ZMapp monoclonal antibodies (mAbs) to inhibit EBOVI-Ituri. We also tested diagnostic assays used in DRC for detection of the EBOV-Ituri sequence despite having mismatches in the primer binding sites. EBOV-Ituri results were compared with the 2013-2016 outbreak EBOV-Makona.

Findings: Our analysis suggests there are at least 2 EBOV strains in DRC, which have independently crossed into the human population. The EBOV-Ituri strain initially grew significantly slower than EBOV-Makona from the 2013-2016 outbreak, yet reached similar titers by 72H p.i. EBOV-Ituri was similar to EBOV-Makona in its susceptibility to inhibition by remdesivir, neutralizing ZMapp, and other EBOV mAbs. The Xpert Ebola and CDC RT-qPCR diagnostic assays detected EBOV-Ituri with high sensitivity despite primer site binding mismatches.

Interpretation: Our findings provide a rationale for the continued testing of investigational therapies, confirm the effectiveness of the diagnostic assay used in the region, and establish a paradigm for the use of reverse genetics-launched strains to inform response activities in an ongoing outbreak.

Funding: US Centers for Disease Control and Prevention.

Declaration of Interest: Danielle Porter is an employee of Gilead.

Ethical Approval: Not needed.

Keywords: Virus, outbreak, epidemiology, Ebola, public health

Suggested Citation

McMullan, Laura and Flint, Mike and Chakrabarti, Ayan and Guerrero, Lisa and Lo, Michael K. and Porter, Danielle and Nichol, Stuart T. and Spiropoulou, Christina F. and Albarino, Cesar, Characterization of Ebola Virus from an Ongoing Outbreak in Ituri and North Kivu, DR Congo to Guide to Response Activities (April 17, 2019). Available at SSRN: https://ssrn.com/abstract=3373854 or http://dx.doi.org/10.2139/ssrn.3373854

Laura McMullan (Contact Author)

Government of the United States of America - Viral Special Pathogens Branch ( email )

Atlanta, GA 30329
United States

Mike Flint

Government of the United States of America - Viral Special Pathogens Branch

1600 Clifton Road
MS G-14
Atlanta, GA 30329
United States

Ayan Chakrabarti

Government of the United States of America - Viral Special Pathogens Branch

1600 Clifton Road
MS G-14
Atlanta, GA 30329
United States

Lisa Guerrero

Government of the United States of America - Viral Special Pathogens Branch

1600 Clifton Road
MS G-14
Atlanta, GA 30329
United States

Michael K. Lo

Government of the United States of America - Viral Special Pathogens Branch

1600 Clifton Road
MS G-14
Atlanta, GA 30329
United States

Danielle Porter

Gilead Sciences, Inc.

333 Lakeside Dr
Foster City, CA 94404
United States

Stuart T. Nichol

Government of the United States of America - Viral Special Pathogens Branch

1600 Clifton Road
MS G-14
Atlanta, GA 30329
United States

Christina F. Spiropoulou

Government of the United States of America - Viral Special Pathogens Branch

1600 Clifton Road
MS G-14
Atlanta, GA 30329
United States

Cesar Albarino

Government of the United States of America - Viral Special Pathogens Branch ( email )

Atlanta, GA 30329
United States

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