Integration of genomic sequencing into the response to the Ebola virus outbreak in Nord Kivu, Democratic Republic of the Congo

Articles https://doi.org/10.1038/s41591-021-01302-z Integration of genomic sequencing into the response to the Ebola virus outbreak in Nord Kivu, Democratic Republic of the Congo Eddy Kinganda-Lusamaki1,2,10 ✉, Allison Black 3,4,10, Daniel B. Mukadi2,10, James Hadfield4,10, Placide Mbala-Kingebeni1,2,10, Catherine B. Pratt 5,10, Amuri Aziza1, Moussa M. Diagne6, Bailey White5, Nella Bisento1, Bibiche Nsunda1, Marceline Akonga1, Martin Faye6, Ousmane Faye6, Francois Edidi-Atani1,2, Meris Matondo-Kuamfumu1,2, Fabrice Mambu-Mbika1,2, Junior Bulabula1,2, Nicholas Di Paola7, Matthias G. Pauthner 8, Kristian G. Andersen8, Gustavo Palacios 7,11, Eric Delaporte9,11, Amadou Alpha Sall6,11, Martine Peeters9,11, Michael R. Wiley5,11, Steve Ahuka-Mundeke1,2,11, Trevor Bedford3,4,11 ✉ and Jean-Jacques Muyembe Tamfum1,2,11 On 1 August 2018, the Democratic Republic of the Congo (DRC) declared its tenth Ebola virus disease (EVD) outbreak. To aid the epidemiologic response, the Institut National de Recherche Biomédicale (INRB) implemented an end-to-end genomic surveillance system, including sequencing, bioinformatic analysis and dissemination of genomic epidemiologic results to frontline public health workers. We report 744 new genomes sampled between 27 July 2018 and 27 April 2020 generated by this surveillance effort. Together with previously available sequence data (n = 48 genomes), these data represent almost 24% of all laboratory-confirmed Ebola virus (EBOV) infections in DRC in the period analyzed. We inferred spatiotemporal transmission dynamics from the genomic data as new sequences were generated, and disseminated the results to support epidemiologic response efforts. Here we provide an overview of how this genomic surveillance system functioned, present a full phylodynamic analysis of 792 Ebola genomes from the Nord Kivu outbreak and discuss how the genomic surveillance data informed response efforts and public health decision making. S ince the first documented outbreak of EVD in Yambuku, DRC, in 1976, further outbreaks have occurred sporadically in that country. In June 2018, laboratory capacity for performance of whole-genome EBOV sequencing was established in the DRC at the INRB in Kinshasa. The establishment of sequencing capacity enabled genomic surveillance over the entire duration of the Nord Kivu EVD outbreak (1 August 2018 to 25 June 2020). At the time of writing, we had generated 792 full and partial genome sequences representing ~24% of laboratory-confirmed cases of EVD in the region. Comparative analysis of pathogen genomes can support traditional epidemiologic surveillance by improving the capacity to detect and define clusters of related infections, thereby facilitating detailed investigations of spatiotemporal disease dynamics. During the 2013–2016 West African EVD outbreak, analysis of viral genomic data was used to differentiate sexual EVD transmission from standard human-to-human transmission1, and to demonstrate that large, sustained case counts were attributable to many cocirculating transmission chains of varying size2. Genomic data were also used to detect the emergence of the A82V variant that rose to high frequency during the epidemic, perhaps due to the variant’s increased infectivity in humans3,4. Despite its utility, genomic surveillance presents challenges for many public health agencies. Assembly and analysis of pathogen genomic data can require both advanced computational infrastructure and analysts trained in disciplines that have not historically been a part of public health, including bioinformatics, computational biology and data science5. This means that the ability of public health agencies to analyze and interpret genomic data within an epidemiologic context often lags behind laboratory capacity to perform sequencing6. We sought to increase the utility of viral genomic data during the Nord Kivu EVD outbreak by regular generation and analysis of EBOV sequence data, releasing the results as genomic epidemiology situation reports. These reports, written in both English and French, allowed representation of interactive genomic data visualization alongside written scientific interpretations. Here we provide an overview of this end-to-end genomic surveillance system, Institut National de Recherche Biomédicale, Kinshasa, Democratic Republic of the Congo. 2Service de Microbiologie, Cliniques Universitaires de Kinshasa, Kinshasa, Democratic Republic of the Congo. 3Department of Epidemiology, University of Washington, Seattle, WA, USA. 4Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. 5Department of Environmental, Agricultural, and Occupational Health, University of Nebraska Medical Center, Omaha, NE, USA. 6Institut Pasteur de Dakar, Dakar, Senegal. 7Center for Genome Sciences, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD, USA. 8Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA, USA. 9TransVIHMI, Institut de Recherche pour le Développement, Institut National de la Santé et de la Recherche Médicale, Université de Montpellier, Montpellier, France. 10These authors contributed equally: Eddy Kinganda-Lusamaki, Allison Black, Daniel B. Mukadi, James Hadfield, Placide Mbala-Kingebeni, Catherine B. Pratt. 11These authors jointly supervised this work: Gustavo Palacios, Eric Delaporte, Amadou Alpha Sall, Martine Peeters, Michael R. Wiley, Steve Ahuka-Mundeke, Trevor Bedford, Jean-Jacques Muyembe Tamfum. ✉e-mail: ; 1 710 Nature Medicine | VOL 27 | April 2021 | 710–716 | www.nature.com/naturemedicine Nature Medicine describing sequencing intensity over the course of the Nord Kivu outbreak and patterns of data release. We then describe the broad epidemic dynamics inferred from phylogeographic analysis of all 792 publicly available EBOV genomes. Finally, we discuss how the genomic data supported public health decision making and issues that impacted the actionability of the data. Results Overview of the genomic surveillance system. Between 27 July 2018 and 25 June 2020, clinical diagnostic specimens were collected from individuals presenting with EVD-like symptoms. A convenience sample of EBOV-positive specimens was selected for sequencing, which occurred at either a mobile laboratory in Katwa or at INRB. In total, 792 EVD genomes were sequenced: 48 of these sequences were previously published7 and 744 were analyzed here for the first time. Samples were sequenced over the full temporal span of the outbreak (Fig. 1a). While the complex geographical and political situation in eastern DRC affected sequencing intensity over time (Fig. 1a), there is minimal geographic bias. The number of sequenced cases from each health zone (the operational jurisdiction for health services in the DRC) is proportional to the total number of confirmed cases reported from that health zone (Fig. 1b). To promote open data sharing and to facilitat (...truncated)