Lassa Virus—A Persistent and Evolving Threat

Lassa virus (LASV), the most important human pathogen within the Arenaviridae family, causes Lassa fever (LF), an acute hemorrhagic fever disease endemic in West Africa with high case fatality rates, particularly in pregnant women. Currently, there are no licensed vaccines or antivirals approved for clinical use against LASV infection. Despite its significant impact on public health, important knowledge gaps remain regarding LASV disease burden, transmission dynamics, pathogenesis, and virus−host interactions, impeding effective disease control and development of therapeutic interventions. The emergence of new lineages and the remarkable genetic diversity of LASV poses substantial challenges to accurate and prompt diagnosis, epidemiological surveillance, and the development of broad-spectrum medical countermeasures. Here, we synthesize current knowledge on the disease burden of LF, recent outbreaks, the geographic distribution and genetic diversity of LASV, infection and transmission in natural reservoirs and other susceptible hosts, emerging evidence suggesting possible sexual transmission, viral pathogenesis, host immune responses, diagnostic advances and challenges, and ongoing preclinical and clinical efforts to develop effective vaccines and antivirals.