New Haven, Conn. — In a new study, Yale School of Medicine (YSM) researchers unveiled a novel diagnostic method for detecting leptospiral virulence-modifying (VM) proteins in the blood and urine of hamsters, an advance that could pave the way for early diagnosis of the tropical disease leptospirosis in humans and improved treatment options. The findings were published in the journal Microbiology Spectrum .
Found around the world, leptospirosis affects approximately 1 million people annually, with nearly 60,000 fatalities. The disease is caused by the bacterium Leptospira and is spread through the urine of infected animals. Despite the potential of the disease to cause severe illness when left untreated, early diagnosis has been a significant challenge due to the lack of sensitive and specific diagnostic methods.
The research, led by Yale's Dr. Joseph M. Vinetz and his team, in collaboration with Luna Bioscience, a company founded by Vinetz to develop vaccines for emerging global infectious diseases, has led to the development of a monoclonal antibody (mAb)-based capture immunoassay. This assay detects VM proteins, a recently identified family of leptospiral proteins crucial for disease pathogenesis.
"We have long known that leptospirosis severely impacts multiple organ systems, leading to conditions like jaundice, acute kidney injury, and pulmonary hemorrhage," said Vinetz, a professor of medicine (infectious diseases) at YSM. "Our discovery of these VM proteins as circulating exotoxins gives us a specific target for both diagnostics and potential therapeutic interventions."
Leptospirosis is the first systemic bacterial disease mediated by a toxin — such as tetanus, botulism, or diphtheria — that has the potential for rapid antigen detection by a novel test, he added.
The research lays the groundwork for developing rapid, inexpensive diagnostics that can be used in resource-limited settings, where leptospirosis is most prevalent, according to Vinetz, who is also a professor of epidemiology (microbial diseases) at the Yale School of Public Health. The novel diagnostic method holds promise for transforming leptospirosis management globally, he said.
"By enabling early detection, health care providers can initiate timely treatments, potentially saving lives and mitigating disease severity," Vinetz said. "Furthermore, understanding the role of VM proteins in disease pathogenesis could lead to new therapeutic targets and vaccine development opportunities."
This study was supported by the National Institutes of Health (grants R01AI108276, U19AI115658, 1R41AI174377, and 1R41AI181135). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Additional support was provided by the America's Foundation and Luna Bioscience, Inc.
