Vector-borne diseases are a growing public health issue in the U.S. with more than 70,000 cases of tick-borne disease reported in 2022 alone. While the majority of these cases are due to bacteria that cause Lyme disease, tick-borne viruses represent an emerging but poorly understood threat.
The Bourbon virus (BRBV) is a relatively newly discovered tick-borne virus capable of causing severe illness. It was first isolated from a patient residing in Bourbon County, Kansas, in 2014. To date, human cases have only been reported in the U.S., with 5 cases occurring in three states: Kansas, Oklahoma, and Missouri. However, serosurveillance of St. Louis, Missouri, residents identified BRBV-specific serum-neutralizing antibodies in 3 of 440 individuals, suggesting BRBV infections are likely under-recognized.
The lone star tick is the primary vector, widely distributed throughout the central, eastern, southeastern, and south-central states. Although no cases of human disease have been identified in North Carolina, BRBV has been isolated from ticks while neutralizing antibodies have been detected in white-tailed deer across the state.
Diana L. Zychowski, MD, an infectious disease fellow with the Institute for Global Health and Infectious Diseases, and Gayan Bamunuarachchi, a post-doctoral research associate in infectious diseases at the Washington University School of Medicine in St. Louis, hypothesized that BRBV is circulating in North Carolina, being transmitted to humans, and possibly causing disease, but remains undiagnosed or misattributed to other tick-borne diseases.
To test of this hypothesis, researchers leveraged existing biorepositories of human sera to screen for the presence of BRBV-neutralizing antibodies. The results found four individuals residing in North Carolina to have BRBV-specific neutralizing antibodies.
“Diagnosing a case of Bourbon virus disease can be difficult because so little is known about it and the symptoms are similar to those of many other illnesses,” said Dr. Zychowski. “Overall, our findings suggest BRBV infections are likely more common than previously recognized, highlighting the need for improved diagnostics and surveillance.”
The Study
Human sera of 518 individuals from NC were collected between 2021-2023, with variable levels of known tick exposure, and screened for the presence of BRBV neutralizing antibodies. One hundred and sixty-two subjects belonged to a cohort of patients with confirmed Alpha-gal syndrome (AGS), a delayed-onset reaction following ingestion of mammalian meat products, also associated with the bite of a lone star tick. One hundred and fifty-six were from a repository of recent heart valve recipients undergoing surveillance for the development of immunoglobulin E to galactose-alpha-1,3-galactose (alpha-gal), and 200 were prenatal women. These cohorts were selected based on availability, with the AGS cohort representing the highest risk of tick exposure.
Results
Of the 518 samples, four [1 of 162 (AGS) and 3 of 156 (heart valve cohort)] were positive and all were from residents of N.C. While three individuals sought care for non-specific viral respiratory symptoms within the prior 10 years, there was no suspicion for a febrile tick-borne illness. Only one individual, with known AGS, had a documented history of tick bites.
“There are likely asymptomatic cases or more subtle manifestations of BRBV infection, particularly in immunocompetent hosts, similar to what we might see with other arboviral infections,” said Dr. Zychowski. “Clinicians must remain vigilant to identify individuals who may need viral testing.”
Given the presentation of non-specific viral symptoms and the lack of commercially available tests, the true number of cases and clinical symptoms remain yet to be fully described. New diagnostic approaches are needed to improve accessibility and time to diagnosis, which can not only prevent further invasive testing and unnecessary antibiotic exposure, but can also provide anticipatory guidance.
Authors include Scott P. Commins, MD, PhD, the William J. Yount Distinguished Professor of Medicine and Associate Chief for Allergy & Immunology; Ross M. Boyce, MD, MSc, Assistant Professor, Infectious Diseases and Epidemiology; and Adrianus C. M. Boon, PhD, Professor of Medicine, Molecular Microbiology and Pathology and Immunology.