The Open Syndrome Definition as a Machine-Readable Standard for Public Health: Design and Implementation Study.

Background: Case definitions are essential for effectively communicating public health threats. However, the absence of a standardized, machine-readable format poses significant challenges to interoperability, epidemiological research, data sharing, and the application of computational methods, including artificial intelligence. These barriers complicate collaboration across regions and organizations and hinder technological progress in public health. Objective: This study aims to propose and release the first open, machine-readable format for representing case and syndrome definitions, together with tools and resources that enable their standardized and scalable use. Methods: We developed the Open Syndrome Definition, a structured, machine-readable schema for representing case and syndrome definitions. We compiled official public health case definitions from multiple institutions and converted them into standardized, machine-readable representations using open-source tools. These tools, available through GitHub under the Massachusetts Institute of Technology license, automate the translation of narrative definitions into structured data. We also created a platform for browsing, analyzing, and contributing new definitions on our initiative website. Results: The Open Syndrome Definition format enabled consistent, automated representation of case definitions across different diseases and jurisdictions. The conversion tools achieved high semantic fidelity, as assessed by qualitative expert review, between narrative and structured representations, supporting human verification and automated analysis. The dataset and accompanying tools demonstrated structural and semantic interoperability by standardizing definitions from various health systems into a unified format and integrating existing medical ontologies through JSON for Linked Data. To further illustrate practical applicability and downstream usage, we introduced a data filtering prototype that allows users to upload their own datasets and verify the results against the standardized definitions. Conclusions: The Open Syndrome Definition establishes a foundation for consistent and machine-readable public health definitions, facilitating reproducible research and interoperability at scale. By enabling systematic data exchange and artificial intelligence-driven analysis, it strengthens public health preparedness and supports more rapid, coordinated responses to emerging health threats.