A new study led by researchers at the Institute for Global Health and Infectious Diseases at the University of North Carolina School of Medicine highlights a critical and persistent gap in the detection and treatment of Lassa fever, which is considered a high-consequence infectious disease, designated by the World Health Organization as one of the world’s top pandemic threats. The findings were published in The Lancet Infectious Diseases and draw on 6 years of data from Liberia, one of the countries most affected by the disease.1
Lassa fever, an Ebola-like illness primarily spread by rodents, causes thousands of deaths each year, particularly in Nigeria, Liberia, and Sierra Leone. The virus can also spread from person to person through direct contact with blood or bodily fluids. While largely concentrated in West Africa, the disease has clear global relevance: more than 32 imported cases have been reported worldwide, including in the United States, with roughly one-third proving fatal.
“Lassa fever remains a major public health threat in West Africa, with high rates of infection and death—often exceeding 20% in some settings,” said William A. Fischer II, MD, director of emerging pathogens for the Institute and lead author of the PREPARE study, which he co-led with David Wohl, MD. “Many of these deaths can be prevented with early and increased access to diagnostics, supportive care and potentially initiation of effective therapeutics.”1
Last year, Contagion interviewed Fischer and Wohl who detailed their work in a 2-part interview around caring for patients with high-consequence infectious disease, and their work around biopreparedness.
The PREPARE (Prevalence, Pathogenesis, and Persistence) study was conducted between July 2018 and August 2024 at Phebe and CB Dunbar Hospitals in central Liberia. Researchers enrolled 435 patients aged five years and older who were admitted with fever or with suspected Lassa fever. All participants underwent plasma LASV RNA RT-PCR testing, and confirmed cases were followed during hospitalization and for up to a year after discharge.1
The results reveal how frequently Lassa fever is missed in routine care. Among patients admitted with fever, 11% were infected with Lassa virus despite not being clinically suspected. Mortality was strongly linked to higher viral loads and weaker immune responses, and children were disproportionately affected: 43% of confirmed cases occurred in patients aged 5 to 17 years.1
What You Need to Know
More than one in ten febrile hospital admissions in central Liberia had undiagnosed Lassa fever, highlighting major diagnostic blind spots.
Higher viral loads and weaker immune responses were linked to mortality, emphasizing the importance of early detection and treatment.
Expanded access to PCR testing, point-of-care diagnostics, and new therapeutics is critical to reducing deaths and preventing wider outbreaks.
“These findings reveal how easily cases slip through routine clinical screening,” said Wohl. “Our data make it clear that without widening our diagnostic aperture to look beyond routine diagnostic assumptions, a substantial number of Lassa virus infections will be missed.”1
The researchers stress that limited access to PCR testing is only part of the problem. Clinical suspicion is often low because the symptoms of Lassa fever overlap with those of other common infections. Missed diagnoses not only worsen outcomes for patients but also increase the risk of transmission to healthcare workers and within hospitals. Because severe complications typically arise in the second week of illness, the window for effective intervention is narrow.1
“By detecting Lassa fever early, we can help those infected and also keep this dangerous pathogen from becoming a threat for those near and far,” Fischer said.1
An accompanying editorial in The Lancet Infectious Diseases underscores the urgent need for expanded point-of-care diagnostics, as well as vaccines and therapeutics, to reduce mortality and prevent outbreaks. The PREPARE study was funded by the US National Institute of Allergy and Infectious Diseases and the National Institutes of Health.2