Decoding Leukocyte Dynamics: Functional Biomarkers and Precision Diagnostics in Parasitic Infections.

BACKGROUND: Parasitic infections affect over 1.5 billion people globally, with leukocytes serving as critical mediators of both protective immunity and immunopathology. Traditional diagnostic approaches relying on static cell counts lack specificity and fail to capture the functional complexity of host-parasite interactions. OBJECTIVE: This review synthesizes cutting-edge evidence on how leukocyte functional dynamics, encompassing transcriptional, metabolic, and spatial profiles, revolutionize diagnostic precision, prognostic stratification, and therapeutic development in parasitic diseases. METHODS: We systematically evaluated recent advances in single-cell multi-omics, spatial transcriptomics, AI-driven flow cytometry, and CRISPR-based functional genomics applied to parasitic infections including malaria, leishmaniasis, schistosomiasis, and Chagas disease. KEY FINDINGS: Granulocyte NETosis exacerbates endothelial damage in malaria; monocyte transcriptional signatures predict leishmaniasis relapse; eosinophil activation markers distinguish active helminthiasis from allergic inflammation. Single-cell technologies reveal infection-specific immune subsets (TREM2highmacrophages promoting Leishmania persistence), while AI-enabled platforms identify prognostic signatures (CD19+/CD21lowB cells predicting severe malaria). Leukocyte ratios (NLR >7.5) stratify mortality risk, guiding immunomodulatory therapies including JAK inhibitors for schistosomiasis fibrosis and CAR-engineered macrophages for Trypanosoma cruzi clearance. CONCLUSIONS: The integration of functional leukocyte profiling with pathogen detection enables a "precision parasitology" framework, moving beyond pathogen-centric approaches to tailor interventions based on individual immune trajectories, overcoming drug resistance, and advancing elimination goals for neglected tropical diseases.