Dr. Ryo Ozuru
Fukuoka University

Leptospirosis remains one of the most significant infectious threats to human health in the Philippines, highlighting the urgent need for comprehensive countermeasures. In studying acute leptospirosis, particularly its severe form known as Weil’s disease, the use of appropriate animal models is essential for accurate evaluation of pathogenicity. At the same time, ethical considerations rooted in the 3Rs (Replacement, Reduction, and Refinement) principle call for careful deliberation not only on what is studied using animal models, but also on what should not be performed. This balance between scientific rigor and ethical responsibility forms the basis of advancing leptospirosis research through responsible animal experimentation. 

This study aims to promote effective and appropriately scoped animal experiments in leptospirosis research, ensuring scientific validity while minimizing unnecessary procedures. 

We previously employed an in vivo imaging system that enables real-time monitoring of Leptospira infection dynamics within live animals, eliminating the need for animal sacrifice at each time point. In parallel, we reanalyzed transcriptomic data derived from earlier animal experiments to generate and test hypotheses more efficiently, thereby maximizing the value of existing datasets and minimizing additional animal use. 

While Leptospira has long been believed to disseminate into the bloodstream immediately after percutaneous infection, our in vivo imaging results revealed a different early infection dynamic: the bacteria initially localize and persist in subcutaneous adipose tissue. Given that Leptospira utilizes long-chain fatty acids as a primary carbon source, this tissue likely serves as a rich nutritional reservoir before the pathogen disseminates to other organs. Furthermore, reanalysis of publicly available transcriptomic data from a dialysis membrane-encapsulation model in the rat peritoneal cavity identified specific metabolic pathways that are activated only within the host environment.

In alignment with the 3Rs principle, the use of in vivo imaging systems and the reanalysis of public omics data represent powerful strategies for reducing the number of animals used in experiments while enhancing the accuracy and relevance of findings. These approaches should be actively adopted in future studies to promote both ethical integrity and scientific advancement in leptospirosis research.