Michael R Wiley1, Lawrence Fakoli2, Andrew G Letizia3, Stephen R Welch4, Jason T Ladner5, Karla Prieto1, Daniel Reyes1, Nicole Espy6, Joseph A Chitty6, Catherine B Pratt1, Nicholas Di Paola6, Fahn Taweh2, Desmond Williams7, Jon Saindon4, William G Davis4, Ketan Patel4, Mitchell Holland8, Daniel Negrón8, Ute Ströher4, Stuart T Nichol4, Shanmuga Sozhamannan9, Pierre E Rollin4, John Dogba2, Tolbert Nyenswah2, Fatorma Bolay2, César G Albariño4, Mosoka Fallah2, Gustavo Palacios10. 1. Department of Environmental, Agricultural and Occupational Health, College of Public Health, University of Nebraska Medical Center, Omaha, NE, USA; Center for Genome Sciences, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD, USA. 2. National Public Health Institute of Liberia, Monrovia, Liberia. 3. Naval Medical Research Unit Three Ghana Detachment, Accra, Ghana. 4. US Centers for Disease Control and Prevention, Atlanta, GA, USA. 5. Center for Genome Sciences, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD, USA; Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, USA. 6. Center for Genome Sciences, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD, USA. 7. US Centers for Disease Control and Prevention, Atlanta, GA, USA; US Centers for Disease Control and Prevention, Monrovia, Liberia. 8. Noblis, Falls Church, VA, USA. 9. Defense Biological Product Assurance Office, Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense (CBRND)-Joint Project Lead, CBRND Enabling Biotechnologies, Frederick, MD, USA; Logistics Management Institute, Tysons, VA, USA. 10. Center for Genome Sciences, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD, USA. Electronic address: gustavo.f.palacios.civ@mail.mil.
Abstract
BACKGROUND: An alarming rise in reported Lassa fever cases continues in west Africa. Liberia has the largest reported per capita incidence of Lassa fever cases in the region, but genomic information on the circulating strains is scarce. The aim of this study was to substantially increase the available pool of data to help foster the generation of targeted diagnostics and therapeutics. METHODS: Clinical serum samples collected from 17 positive Lassa fever cases originating from Liberia (16 cases) and Guinea (one case) within the past decade were processed at the Liberian Institute for Biomedical Research using a targeted-enrichment sequencing approach, producing 17 near-complete genomes. An additional 17 Lassa virus sequences (two from Guinea, seven from Liberia, four from Nigeria, and four from Sierra Leone) were generated from viral stocks at the US Centers for Disease Control and Prevention (Atlanta, GA) from samples originating from the Mano River Union (Guinea, Liberia, and Sierra Leone) region and Nigeria. Sequences were compared with existing Lassa virus genomes and published Lassa virus assays. FINDINGS: The 23 new Liberian Lassa virus genomes grouped within two clades (IV.A and IV.B) and were genetically divergent from those circulating elsewhere in west Africa. A time-calibrated phylogeographic analysis incorporating the new genomes suggests Liberia was the entry point of Lassa virus into the Mano River Union region and estimates the introduction to have occurred between 300-350 years ago. A high level of diversity exists between the Liberian Lassa virus genomes. Nucleotide percent difference between Liberian Lassa virus genomes ranged up to 27% in the L segment and 18% in the S segment. The commonly used Lassa Josiah-MGB assay was up to 25% divergent across the target sites when aligned to the Liberian Lassa virus genomes. INTERPRETATION: The large amount of novel genomic diversity of Lassa virus observed in the Liberian cases emphasises the need to match deployed diagnostic capabilities with locally circulating strains and underscores the importance of evaluating cross-lineage protection in the development of vaccines and therapeutics. FUNDING: Defense Biological Product Assurance Office of the US Department of Defense and the Armed Forces Health Surveillance Branch and its Global Emerging Infections Surveillance and Response Section.
BACKGROUND: An alarming rise in reported Lassa fever cases continues in west Africa. Liberia has the largest reported per capita incidence of Lassa fever cases in the region, but genomic information on the circulating strains is scarce. The aim of this study was to substantially increase the available pool of data to help foster the generation of targeted diagnostics and therapeutics. METHODS: Clinical serum samples collected from 17 positive Lassa fever cases originating from Liberia (16 cases) and Guinea (one case) within the past decade were processed at the Liberian Institute for Biomedical Research using a targeted-enrichment sequencing approach, producing 17 near-complete genomes. An additional 17 Lassa virus sequences (two from Guinea, seven from Liberia, four from Nigeria, and four from Sierra Leone) were generated from viral stocks at the US Centers for Disease Control and Prevention (Atlanta, GA) from samples originating from the Mano River Union (Guinea, Liberia, and Sierra Leone) region and Nigeria. Sequences were compared with existing Lassa virus genomes and published Lassa virus assays. FINDINGS: The 23 new Liberian Lassa virus genomes grouped within two clades (IV.A and IV.B) and were genetically divergent from those circulating elsewhere in west Africa. A time-calibrated phylogeographic analysis incorporating the new genomes suggests Liberia was the entry point of Lassa virus into the Mano River Union region and estimates the introduction to have occurred between 300-350 years ago. A high level of diversity exists between the Liberian Lassa virus genomes. Nucleotide percent difference between Liberian Lassa virus genomes ranged up to 27% in the L segment and 18% in the S segment. The commonly used Lassa Josiah-MGB assay was up to 25% divergent across the target sites when aligned to the Liberian Lassa virus genomes. INTERPRETATION: The large amount of novel genomic diversity of Lassa virus observed in the Liberian cases emphasises the need to match deployed diagnostic capabilities with locally circulating strains and underscores the importance of evaluating cross-lineage protection in the development of vaccines and therapeutics. FUNDING: Defense Biological Product Assurance Office of the US Department of Defense and the Armed Forces Health Surveillance Branch and its Global Emerging Infections Surveillance and Response Section.
Authors: Matthew L Boisen; Eghosa Uyigue; John Aiyepada; Katherine J Siddle; Lisa Oestereich; Diana K S Nelson; Duane J Bush; Megan M Rowland; Megan L Heinrich; Philomena Eromon; Adeyemi T Kayode; Ikponmwosa Odia; Donatus I Adomeh; Ekene B Muoebonam; Patience Akhilomen; Grace Okonofua; Blessing Osiemi; Omigie Omoregie; Michael Airende; Jacqueline Agbukor; Solomon Ehikhametalor; Chris Okafi Aire; Sophie Duraffour; Meike Pahlmann; Wiebke Böhm; Kayla G Barnes; Samar Mehta; Mambu Momoh; John Demby Sandi; Augustine Goba; Onikepe A Folarin; Ephraim Ogbaini-Emovan; Danny A Asogun; Ekaete A Tobin; George O Akpede; Sylvanus A Okogbenin; Peter O Okokhere; Donald S Grant; John S Schieffelin; Pardis C Sabeti; Stephan Günther; Christian T Happi; Luis M Branco; Robert F Garry Journal: Sci Rep Date: 2020-05-26 Impact factor: 4.379
Authors: Megan L Heinrich; Matthew L Boisen; Diana K S Nelson; Duane J Bush; Robert W Cross; Anatoliy P Koval; Andrew R Hoffmann; Brandon J Beddingfield; Kathryn M Hastie; Megan M Rowland; Irina Aimukanova; Sophia Koval; Raju Lathigra; Viktoriya Borisevich; Mambu Momoh; John Demby Sandi; Augustine Goba; Lkponmwosa Odia; Francis Baimba; John O Aiyepada; Benevolence Ebo; Philomena Eromon; Chinedu Ugwu; Onikepe Folarin; Testimony Olumade; MacDonald N Onyechi; Johnson Etafo; Rashidat Adeyemi; Elijah E Ella; Maryam Aminu; Simji S Gomerep; Matthew Afam Eke; Olusola Ogunsanya; George O Akpede; Danny O Asogun; Sylvanus A Okogbenin; Peter O Okokhere; Johan Holst; Jeffrey G Shaffer; John S Schieffelin; Thomas W Geisbert; Erica Ollmann Saphire; Christian T Happi; Donald S Grant; Robert F Garry; Luis M Branco Journal: Sci Rep Date: 2020-09-29 Impact factor: 4.379