Host biomarkers and parasite biomass are associated with severe malaria in Mozambican children: a case–control study

Severe pediatric malaria remains a pressing global health issue. Laboratory parameters may provide early risk and severity stratification for better disease management, beyond current clinical severity scores. This study aimed to identify host biomarkers of immune and endothelial activation and parasite biomass in children with severe malaria (SM) compared to uncomplicated malaria (UM). We conducted a case-control study in a rural hospital in southern Mozambique from 2014 to 2016, recruiting patients under 10 years old with Plasmodium falciparum SM as cases, and patients with UM matched by age, sex, and parasitemia as controls. We compared plasma levels of biomarkers associated with total parasite mass (HRP-2), biomarkers of host response to infection (Angpt-1, Angpt-2, sTie-2, BDNF, CysC, sFlt-1, IL-6, IL-8, IP-10, sTNFR-1 and sTREM-1). All biomarker levels except Angpt-1, BDNF and CysC were significantly higher in children with SM. HRP-2 levels significantly differed between cases and controls, strongly correlating with Angpt-2, sTie-2, sFlt-1, TNRF, and sTREM-1, both in SM and UM. In conclusion, host biomarkers indicative of immune and endothelial activation were associated with malaria severity and HRP-2, even after controlling for matching variables, potentially offering targets for risk-stratification and adjuvant therapy.