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1. Genetic diversity and molecular epidemiology of Middle East Respiratory Syndrome Coronavirus in dromedaries in Ethiopia, 2017–2020

Author

Ziqi Zhou, Abraham Ali, Elias Walelign, Getnet F. Demissie, Ihab El Masry, Takele Abayneh, Belayneh Getachew, Pavithra Krishnan, Daisy Y.M. Ng, Emma Gardner, Yilma Makonnen, Eve Miguel, Véronique Chevalier, Daniel K. Chu, Ray T. Y. So, Sophie Von Dobschuetz, Gezahegne Mamo, Leo L. M. Poon, Malik Peiris, City University of Hong Kong [Hong Kong] (CUHK), Ethiopian Public Health Institute (EPHI), Addis Ababa University (AAU), Food and Agriculture Organization of the United Nations [Rome, Italie] (FAO), Haramaya University (HU), National Veterinary Institute [Debre Zeit, Ethiopia] (NVI), The University of Hong Kong (HKU), Animal, Santé, Territoires, Risques et Ecosystèmes (UMR ASTRE), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM), Département Systèmes Biologiques (Cirad-BIOS), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), Institut Pasteur de Madagascar, Réseau International des Instituts Pasteur (RIIP), and UK Health Security Agency [London] (UKHSA)

Subjects
Epidemiology, [SDV]Life Sciences [q-bio], Immunology, genetic instability, General Medicine, molecular epidemiology, Microbiology, MERS-CoV, Infectious Diseases, Virology, evolution, Drug Discovery, Parasitology, Ethiopia
Abstract

International audience; Middle East respiratory syndrome coronavirus (MERS-CoV) is enzootic in dromedary camels and causes zoonotic infection and disease in humans. Although over 80% of the global population of infected dromedary camels are found in Africa, zoonotic disease had only been reported in the Arabia Peninsula and travel-associated disease has been reported elsewhere. In this study, genetic diversity and molecular epidemiology of MERS-CoV in dromedary camels in Ethiopia were investigated during 2017–2020. Of 1766 nasal swab samples collected, 61 (3.5%) were detected positive for MERS-CoV RNA. Of 484 turbinate swab samples collected, 10 (2.1%) were detected positive for MERS-CoV RNA. Twenty-five whole genome sequences were obtained from these MERS-CoV positive samples. Phylogenetically, these Ethiopian camel-originated MERS-CoV belonged to clade C2, clustering with other East African camel strains. Virus sequences from camel herds clustered geographically while in an abattoir, two distinct phylogenetic clusters of MERS-CoVs were observed in two sequential sampling collections, which indicates the greater genetic diversity of MERS-CoV in abattoirs. In contrast to clade A and B viruses from the Arabian Peninsula, clade C camel-originated MERS-CoV from Ethiopia had various nucleotide insertions and deletions in non-structural gene nsp3, accessory genes ORF3 and ORF5 and structural gene N. This study demonstrates the genetic instability of MERS-CoV in dromedaries in East Africa, which indicates that the virus is still actively adapting to its camel host. The impact of the observed nucleotide insertions and deletions on virus evolution, viral fitness, and zoonotic potential deserves further study.

Published
2023
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2. A data compendium associating the genomes of 12,289 Mycobacterium tuberculosis isolates with quantitative resistance phenotypes to 13 antibiotics

Author

Brankin, Alice, Malone, Kerri, Barilar, Ivan, Battaglia, Simone, Borroni, Emanuele, Pires Brandao, Angela, Cabibbe, Andrea Maurizio, Carter, Joshua, Chetty, Darren, Cirillo, Daniela María, Claxton, Pauline, Clifton, David, Cohen, Ted, Coronel, Jorge, Crook, Derrick, Dreyer, Viola, Earle, Sarah, Escuyer, Vincent, Ferrazoli, Lucilaine, Gāo, George Fú, Gardy, Jennifer, Gharbia, Saheer, Teixeira Ghisi, Kelen, Ghodousi, Arash, Gibertoni Cruz, Ana Lúıza, Grandjean, Louis, Grazian, Clara, Groenheit, Ramona, Guthrie, Jennifer, He, Wencong, Hoffmann, Harald, J., Sarah, Hunt, Martin, Ismail, Nazir Ahmed, Jarrett, Lisa, Joseph, Lavania, Jou, Ruwen, Kambli, Priti, Khot, Rukhsar, Knaggs, Jeff, Koch, Anastasia, Kohlerschmidt, Donna, Kouchaki, Samaneh, Lachapelle, Alexander, Lalvani, Ajit, Grandjean Lapierre, Simon, Laurenson, Ian, Letcher, Brice, Lin, Wan-Hsuan, Liu, Chunfa, Liu, Dongxin, Mandal, Ayan, Mansjö, Mikael, Matias, Daniela, Meintjes, Graeme, de Freitas Mendes, Flávia, Merker, Matthias, Mihalic, Marina, Millard, James, Miotto, Paolo, Mistry, Nerges, Moore, David, Musser, Kimberlee A., Ngcamu, Dumisani, Ngoc Nhung, Hoang, Niemann, Stefan, Soli Nilgiriwala, Kayzad, Nimmo, Camus, O'Donnell, Max, Okozi, Nana, Siqueira Oliveira, Rosangela, Omar, Shaheed Vally, Paton, Nicholas, Peto, Timothy Ea, Watanabe Pinhata, Juliana Maira, Plesnik, Sara, Puyen, Zully, Rabodoarivelo, Marie, Rakotosamimanana, Niaina, Rancoita, Paola, Rathod, Priti, Robinson, Esther, Rodger, Gillian, Rodrigues, Camilla, Rodwell, Timothy, Roohi, Aysha, Santos-Lazaro, David, Shah, Sanchi, Kohl, Thomas Andreas, Smith, Grace, Solano, Walter, Spitaleri, Andrea, Supply, Philip, Steyn, Adrie, Surve, Utkarsha, Tahseen, Sabira, Thuong, Nguyen, Thwaites, Guy, Todt, Katharina, Trovato, Alberto, Utpatel, Christian, van Rie, Annelies, Vijay, Srinivasan, Walker, Timothy, Walker, A. Sarah, Warren, Robin M., Werngren, Jim, Wijkander, Maria, Wilkinson, Robert, Wilson, Daniel, Wintringer, Penelope, Xiao, Yu-Xin, Yang, Yang, Zhao, Yanlin, Yao, Shen-Yuan, Zhu, Baoli, Fowler, Philip, Iqbal, Zamin, Consortium, The CRyPTIC, University of Oxford, European Bioinformatics Institute [Hinxton] (EMBL-EBI), EMBL Heidelberg, Forschungszentrum Borstel - Research Center Borstel, IRCCS San Raffaele Scientific Institute [Milan, Italie], Casa de Oswaldo Cruz [Rio de Janeiro] (COC), Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Instituto Adolfo Lutz [São Paulo, Brazil], Stanford School of Medicine [Stanford], Stanford Medicine, Stanford University-Stanford University, Africa Health Research Institute [Durban/Mtubatuba] (AHRI), University of Edinburgh, Yale School of Public Health (YSPH), Universidad Peruana de Ciencias Aplicadas (Lima) (UPC), Wadsworth Center, New York State Department of Health [Albany], Chinese Center for Disease Control and Prevention, Bill & Melinda Gates Foundation [Seattle], UK Health Security Agency [London] (UKHSA), Universita Vita Salute San Raffaele = Vita-Salute San Raffaele University [Milan, Italie] (UniSR), University College of London [London] (UCL), University of New South Wales [Sydney] (UNSW), Public Health Agency of Sweden, University of British Columbia [Vancouver], Public Health Ontario - Santé publique Ontario, Synlab Academy, Synlab Holding Deutschland GmbH, Mannheim, National Institute for Communicable Diseases [Johannesburg] (NICD), Taipei Medical University, PD Hinduja Hospital & Research Institute, Mumbai, University of Cape Town, University of Surrey (UNIS), Imperial College London, Université de Montréal (UdeM), PRA Health sciences [Mumbai], London School of Hygiene and Tropical Medicine (LSHTM), Oxford University Clinical Research Unit [Ho Chi Minh City] (OUCRU), German Centre for Infection Research - partner site Hamburg-Lübeck-Borstel-Riems (DZIF), Columbia University Irving Medical Center (CUIMC), National University of Singapore (NUS), Socios En Salud [Lima, Peru], Institut Pasteur de Madagascar, Réseau International des Instituts Pasteur (RIIP), Foundation for Innovative New Diagnostics (FIND), University of California [San Diego] (UC San Diego), University of California (UC), Universidad Peruana Cayetano Heredia (UPCH), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), National TB control Program [Islamabad, Pakistan], University of Antwerp (UA), Stellenbosch University, Wellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa), Institute of Infectious Disease and Molecular Medicine, Department of Medicine, University of Cape Town, The Francis Crick Institute [London], Shanghai Jiao Tong University School of Medicine, Chinese Academy of Sciences [Beijing] (CAS), and Wellcome Trust (200205/Z/15/Z)Bill and Melinda Gates Foundation (OPP1133541)National Institute for Health Research Oxford Biomedical Research CentreNational Institute for Health Research (NIHR) Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial ResistanceWellcome Trust (203919/Z/16/Z)National Mega Project on Major Infectious Disease Prevention (2018ZX10103001)H2020 Marie Skłodowska-Curie Actions (EIPOD3)Unitaid (2019-32-FIND MDR)FAPESP (17/16082-7)FAPESP (2012/51756-5)National Natural Science Foundation of China (81991534)Beijing Municipal Science and Technology Commission (Z201100005520041)Wellcome Trust International Intermediate Fellowship (206724/Z/17/Z)Wellcome TrustSouth African Medical Research Councilthe Rhodes Trust and Stanford Medical Scientist Training Program (T32 GM007365)National Institute for Health Research (NIHR) Health Protection Research Unit in Respiratory Infections at Imperial College LondonFonds de Recherche en Santé du QuébecWellcome Trust (203583/Z/16/Z)Research Foundation Flanders (G0F8316N)Wellcome Trust (98316)Wellcome Trust (214321/Z/18/Z)Wellcome Trust (203135/Z/16/Z)National Research Foundation South Africa (64787)Wellcome Trust (201470/Z/16/Z)National Institute of Allergy and Infectious Diseases (1R01AI146338)GOSH (1R01AI146338)GOSH/ICH Biomedical Research CentreOxford Medical Research Council Doctoral Training Partnership (NDM Prize Studentship)Nuffield Department of Clinical MedicineSir Henry Dale Fellowship (101237/Z/13/B)The Robertson FoundationNIHRWellcome Trust (214560/Z/18/Z)Rhodes TrustWellcome Trust (FC0010218)UK Research and Innovation (FC0010218)Cancer Research UK (FC0010218)National Institutes of HealthCenters for Disease Control and PreventionUSAIDBill and Melinda Gates FoundationWellcome Trust (203141/Z/16/Z)NIHR Oxford Biomedical Research Centre (BRC BRC-1215-20008)Deutsches Zentrum für InfektionsforschungPublic Health ScotlandCenters for Disease Control and Prevention (U60OE000103)Division of Intramural Research, National Institute of Allergy and Infectious Diseases (AI-117312)

Subjects
General Immunology and Microbiology, General Neuroscience, Extensively Drug-Resistant Tuberculosis, Antitubercular Agents, Microbial Sensitivity Tests, Mycobacterium tuberculosis, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, General Biochemistry, Genetics and Molecular Biology, Phenotype, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Drug Resistance, Multiple, Bacterial, Mutation, Tuberculosis, Multidrug-Resistant, Humans, Rifampin, General Agricultural and Biological Sciences
Abstract

The Comprehensive Resistance Prediction for Tuberculosis: an International Consortium (CRyPTIC) presents here a data compendium of 12,289 Mycobacterium tuberculosis global clinical isolates, all of which have undergone whole-genome sequencing and have had their minimum inhibitory concentrations to 13 antitubercular drugs measured in a single assay. It is the largest matched phenotypic and genotypic dataset for M. tuberculosis to date. Here, we provide a summary detailing the breadth of data collected, along with a description of how the isolates were selected, collected, and uniformly processed in CRyPTIC partner laboratories across 23 countries. The compendium contains 6,814 isolates resistant to at least 1 drug, including 2,129 samples that fully satisfy the clinical definitions of rifampicin resistant (RR), multidrug resistant (MDR), pre-extensively drug resistant (pre-XDR), or extensively drug resistant (XDR). The data are enriched for rare resistance-associated variants, and the current limits of genotypic prediction of resistance status (sensitive/resistant) are presented by using a genetic mutation catalogue, along with the presence of suspected resistance-conferring mutations for isolates resistant to the newly introduced drugs bedaquiline, clofazimine, delamanid, and linezolid. Finally, a case study of rifampicin monoresistance demonstrates how this compendium could be used to advance our genetic understanding of rare resistance phenotypes. The data compendium is fully open source and it is hoped that it will facilitate and inspire future research for years to come.

Published
2022
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