National Strategic Research Institute at the University of Nebraska

 

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, US 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, US Centers for Disease Control and Prevention
Jon Saindon, US Centers for Disease Control and Prevention
William G. Davis, US Centers for Disease Control and Prevention
Ketan Patel, US Centers for Disease Control and Prevention
Mitchell Holland, Northern Arizona University
Daniel Negrón, Northern Arizona University
Ute Ströher, US Centers for Disease Control and Prevention
Stuart T. Nichol, US Centers for Disease Control and Prevention
Shanmuga Sozhamannan, Defense Biological Product Assurance Office
Pierre E. Rollin, US 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, US 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, Vol 19 December 2019, pp 1371-1378

Comments

U.S. 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 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.

Share

COinS