In early 2018 Nigeria experienced an unprecedented increase in Lassa fever cases with widespread geographic distribution. We report 77 Lassa virus genomes generated from patient samples, 14 from 2018, to investigate whether recent changes in the virus genome contributed to this surge. Our data argue that the surge is not attributable to a single Lassa virus variant, nor has it been sustained by human-to-human transmission. We observe extensive viral diversity structured by geography, with major rivers appearing to act as barriers to migration of the rodent reservoir. Together our results support that the 2018 Lassa fever surge was driven by crossspecies transmission from local rodent populations of multiple viral variants from different lineages.

Lassa virus (LASV) is the causative agent of Lassa fever (Lf), an often-fatal hemorrhagic disease. Lf is endemic in nigeria, Sierra Leone and other West African countries. Diagnosis of LASV infection is challenged by the genetic diversity of the virus, which is greatest in Nigeria. The ReLASV Pan-Lassa Antigen Rapid test (pan-Lassa RDt) is a point-of-care, in vitro diagnostic test that utilizes a mixture of polyclonal antibodies raised against recombinant nucleoproteins of representative strains from the three most prevalent LASV lineages (ii, iii and iV). We compared the performance of the pan-LASV RDT to available quantitative PCR (qPCR) assays during the 2018 LF outbreak in Nigeria. For patients with acute LF (RDT positive, IgG/IgM negative) during initial screening, RDT performance was 83.3% sensitivity and 92.8% specificity when compared to composite results of two qPCR assays. 100% of samples that gave Ct values below 22 on both qPCR assays were positive on the Pan-Lassa RDT. There were significantly elevated case fatality rates and elevated liver transaminase levels in subjects whose samples were RDt positive compared to RDt negative.