Immune Biomarkers Predictive of Severe Malaria Progression Across Pediatric and Adult Cohorts

Taliikwa Nicholas Ceaser

Department of Pharmacognosy Kampala International University Uganda

Email:ceaser.taliikwa@studwc.kiu.ac.ug

ABSTRACT

Severe malaria, predominantly caused by Plasmodium falciparum, progresses unpredictably from uncomplicated infection to life-threatening complications, including cerebral malaria, severe anemia, and metabolic acidosis. Immune responses varied substantially between pediatric and adult populations, influencing disease trajectory and clinical outcomes. Identification of reliable immune biomarkers capable of predicting progression to severe disease remains a critical unmet need for early intervention strategies. This review synthesized current evidence on immune biomarkers that predict severe malaria progression, evaluating their performance across pediatric and adult cohorts while examining age-dependent immunological differences that modulate predictive capacity. A comprehensive analysis of literature examining soluble immune mediators, cellular markers, and functional immune parameters associated with severe malaria progression in diverse age groups was conducted. Elevated cytokines, including tumor necrosis factor alpha, interleukin 6, and interleukin 10, demonstrated prognostic value but showed variable performance across age groups. Thrombocytopenia and parasite biomass markers, including plasma histidine-rich protein 2 provided complementary prognostic information. Pediatric cohorts exhibited distinct immunological profiles characterized by innate immune predominance and limited regulatory responses, while adults demonstrated enhanced adaptive immunity but increased immunopathology. Functional assays measuring phagocytic capacity and antibody-dependent cellular responses showed promise but required standardization. Most studies demonstrated methodological limitations, including small sample sizes, single time point assessments, and inadequate validation across diverse transmission settings. Immune biomarker panels incorporating endothelial dysfunction markers, inflammatory cytokines, and parasite burden indicators offered potential for risk stratification, though age-specific thresholds and validation in prospective clinical trials remain essential for clinical implementation.

Keywords: Severe malaria, Immune biomarkers, Cytokines, Endothelial activation, Age-dependent immunity

CITE AS: Taliikwa Nicholas Ceaser (2026). Immune Biomarkers Predictive of Severe Malaria Progression Across Pediatric and Adult Cohorts. RESEARCH INVENTION JOURNAL OF BIOLOGICAL AND APPLIED SCIENCES 6(1):31-37. https://doi.org/10.59298/RIJBAS/2026/613137