A novel test could enable early diagnosis of and better treatments for leptospirosis

Three-dimensional structure organization of paralogous PF07598 gene family VM proteins. (A) L. interrogans encoding LA3490 shows the representation of the AlphaFold 3D-generated model of full-length VM proteins (~640 aa), comprising a multi-globular domain N-terminal to C-terminal (blue to red color) residues visualized in PyMOL 2.4.0 https://pymol.org/2/. VM proteins are predicted with high confidence to have two tandemly repeated, N-terminal ricin B-like (RBL) lectin domains. N-terminal (RBL1) β-trefoil folds identified as ricin B domains. (B) L. interrogans naturally encodes a variant VM protein, LA0591, which lacks the N-terminal domains (RBL1 and RBL2) and consists only of a C-terminal domain (313 amino acids). (C) Structural alignment between the full-length LA0591 protein and the C-terminal region of LA3490 suggests an RMSD of 0.523. Credit: Microbiology Spectrum (2025). DOI: 10.1128/spectrum.00018-25

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 appear 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.”