Reconstructing the Historical and Genomic Epidemiology of Lassa Fever in Nigeria: A Phylodynamic Study Across All Six Geopolitical Zones

Lassa fever is an endemic viral haemorrhagic fever in Nigeria with recurrent annual epidemic waves, and the evolutionary dynamics, spatial spread, and host-virus interface governing its epidemiology across the six geopolitical zones have not been reconstructed using full genome sequence data from a nationally representative study. This study reconstructs the historical and genomic epidemiology of Lassa fever in Nigeria through a phylodynamic analysis integrating 450 complete Lassa virus genome sequences obtained from confirmed Lassa fever cases across all six zones between 2019 and 2024. Serum specimens from cases registered in the NCDC national Lassa fever database are processed at biosafety level 3 facilities, with genome amplification using a modified primer scheme and sequencing by Oxford Nanopore Technology. Maximum likelihood and Bayesian phylogenetic inference are conducted using IQ-TREE2 and BEAST2, with time-resolved phylogenies reconstructed using strict and relaxed molecular clocks. Spatial diffusion of lineages is modelled using continuous phylogeographic methods in BEAST. Rodent host sample co-analysis examines cross-species transmission bottlenecks. The Viral Phylodynamics Framework and One Health Epidemiology Theory provide the theoretical basis. Original contributions include the most genomically comprehensive national Lassa fever phylodynamic study ever conducted, redefining our understanding of lineage diversity and geographic spread in Nigeria. Findings will directly inform the NCDC National Lassa Fever Multi-Year Preparedness Plan. Keywords: Lassa fever, phylodynamics, genomic epidemiology, Nigeria, viral haemorrhagic fever.