Lessons in the Wake of a Lassa fever case in the Midwest U.S: epidemiology, management and preparedness gaps

BACKGROUND: Lassa fever (LF) is a zoonotic viral hemorrhagic disease endemic to West Africa that remains persistently neglected despite substantial morbidity, mortality, and outbreak potential. A fixed burden estimate is not available due to the absence of systematic surveillance across endemic regions; passive case detection, limited laboratory capacity, and significant underreporting make precise quantification impossible. Contemporary modeling now projects approximately 2.7 million Lassa virus infections each year across West Africa, with an estimated 3,900 deaths and 2.0 million disability-adjusted life years (DALYs) over a decade - figures that likely still underestimate the true burden (6,86). While most infections are mild or asymptomatic, severe disease is associated with high case-fatality rates, nosocomial transmission, and long-term sequelae. The most recent travel-associated case in the Midwest U.S highlights the ongoing risk of international spread and exposes critical gaps in recognizing and responding to rare but high-consequence pathogens, even in high-resource settings. METHODS: This narrative review synthesizes epidemiologic data, clinical studies, surveillance reports, and outbreak investigations to examine Lassa fever through the lens of outbreak detection, response, and preparedness. RESULTS: Early clinical recognition remains difficult due to non-specific presentations and, in non-endemic countries, ignoring travel and exposure history. Non-specific presentation and limited diagnostic tools access contributes to delayed diagnosis and extensive contact investigations. Molecular diagnostics, particularly RT-PCR, remain central to early diagnosis but are influenced by viral genetic diversity and sampling timing. Ribavirin continues to be widely used for treatment and post-exposure prophylaxis despite limited and heterogeneous evidence. Emerging antivirals, monoclonal antibodies, and vaccine candidates show promise but are not yet available for routine use. Outbreak control is further complicated by the complex ecology of Lassa virus, including rodent reservoirs, environmental drivers, and potential involvement of additional host species. CONCLUSIONS: Lassa fever remains a high-threat pathogen at the intersection of endemic disease and global outbreak preparedness. Travel-associated cases, like the most recent one in Iowa, consistently reveal gaps in infection prevention and control, exposure-risk assessment, and post-exposure management. Early suspicion, followed by immediate isolation, rapid engagement of public health authorities, and timely initiation of infection control and clinical measures is central to limiting downstream consequences. Addressing these gaps will require strengthened laboratory capacity, harmonized surveillance and response frameworks, accelerated development of medical countermeasures, and sustained investment in preparedness strategies applicable to both endemic and non-endemic settings. CLINICAL TRIAL NUMBER: Not applicable.