Parasite extracellular vesicles: From molecular cargo to biomarkers and therapeutic targets

Extracellular vesicles (EVs) are increasingly recognized as active mediators of host–parasite communication rather than passive by-products of infection. Across protozoan and helminth parasites, EVs transport selectively packaged molecular cargo – including proteins, lipids, and nucleic acids – that modulate host immune responses, coordinate parasite populations, and contribute to disease pathogenesis. Emerging clinical and experimental studies highlight their translational relevance. In visceral leishmaniasis, proteomic analysis of plasma-derived EVs has identified host proteins that distinguish active disease from post-treatment states, while in malaria, EV-associated RNA cargo released from infected erythrocytes reflects parasite developmental dynamics and disease severity. Helminth-derived vesicles similarly carry conserved microRNAs and immunomodulatory molecules capable of altering host inflammatory pathways. These findings position parasite EVs as potential biomarkers for infection staging, treatment monitoring, and relapse surveillance. Experimental investigations further suggest that vesicle biology may be harnessed for therapeutic purposes. EV-associated antigens have shown partial protective efficacy in vaccination models, and engineered or hybrid vesicle systems are being explored as delivery vehicles for therapeutic cargo. At the same time, pharmacological disruption of vesicle biogenesis or uptake has emerged as a potential strategy to interfere with parasite communication pathways. Despite these advances, translation into clinical practice remains limited. Most studies rely on small discovery-stage cohorts and heterogeneous analytical methods, highlighting the need for standardized isolation protocols, validated biomarkers, and multicenter clinical evaluation. Integration of emerging technologies – including single-vesicle profiling, advanced imaging, and multi-omic approaches – may further clarify the biological functions and diagnostic value of parasite-derived EVs. Together, current evidence indicates that EVs represent a promising interface between parasite biology and translational innovation. Continued progress in methodological standardization, biomarker validation, and scalable therapeutic strategies will be essential to realize the potential of EV-based diagnostics and interventions for parasitic diseases.