Harnessing Extracellular Vesicles for Precision Diagnostics and Infectious Disease Management: Integrating Host‐ and Pathogen‐Derived Cues

ABSTRACT Conventional infectious disease diagnostics often rely on detecting pathogen‐derived factors or an immune response directed against them to diagnose disease. However, these approaches can lack the specificity to distinguish active and latent infections or pathogenic infections from non‐pathogenic colonization events. Extracellular vesicles (EVs)—nanoscale vesicles that are abundantly secreted by most cells, particularly in response to disease and cell injury—can carry pathogen‐specific factors that indicate the presence and virulence state of a pathogen, as well as immune and inflammatory responses. EVs carrying both types of factors can thus provide valuable information about the presence, identity, and pathogenic phenotype of a microbe in an individual with a suspected infection. Evaluating EVs present in saliva, urine, blood, and other accessible biofluids that contain both host and pathogen information (hpEVs) can thus aid in disease detection, stratification, and monitoring. This review discusses the relevance of EVs to infection and highlights methods that can be used to analyze hpEVs for future clinical applications, including new signal amplification strategies, single vesicle–resolution analysis methods, microfluidic platforms, and AI‐based data analysis approaches. It also discusses key challenges that must be addressed to enable development and adoption of hpEV applications for disease diagnosis and management.