Lassa Virus Circulating in Liberia: A Retrospective Genomic Characterisation

Authors

• Michael R. Wiley, University of Nebraska Medical CenterFollow
• Lawrence S. Fakoli, Liberian Institute for Biomedical ResearchFollow
• Andrew G. Letizia, Naval Medical Research Unit Three Ghana Detachment, Accra
• Stephen R. Welch, United States Centers for Disease Control and Prevention
• Jason T. Ladner, United States Army Medical Research Institute of Infectious Diseases
• Karla Prieto, University of Nebraska Medical Center
• Daniel Reyes, University of Nebraska Medical Center
• Nicole Espy, United States Army Medical Research Institute of Infectious Diseases
• Joseph A. Chitty, United States Army Medical Research Institute of Infectious Diseases
• Catherine B. Pratt, University of Nebraska Medical Center
• Nicholas Di Paola, United States Army Medical Research Institute of Infectious Diseases
• Fahn Taweh, National Public Health Institute of Liberia
• Desmond Williams, United States Centers for Disease Control and Prevention
• Jon Saindon, United States Centers for Disease Control and Prevention
• William G. Davis, United States Centers for Disease Control and Prevention
• Ketan Patel, United States Centers for Disease Control and Prevention
• Mitchell Holland, Northern Arizona University
• Daniel Negrón, Northern Arizona University
• Ute Ströher, United States Centers for Disease Control and Prevention
• Stuart T. Nichol, United States Centers for Disease Control and Prevention
• Shanmuga Sozhamannan, Defense Biological Product Assurance Office
• Pierre E. Rollin, United States Centers for Disease Control and Prevention
• John Dogba, National Public Health Institute of Liberia
• Tolbert Nyenswah, National Public Health Institute of Liberia
• Fatorma Bolay, National Public Health Institute of Liberia
• César G. Albariño, United States Centers for Disease Control and Prevention
• Mosoka Fallah, National Public Health Institute of Liberia
• Gustavo Palacios, United States Army Medical Research Institute of Infectious DiseasesFollow

Date of this Version

12-2019

Document Type

Article

Citation

The Lancet: Infectious Diseases (December 2019) 19: 1,371-1,378

Comments

United States government work

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 United States Centers for Disease Control and Prevention (Atlanta, Georgia) 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.