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Host biomarkers and parasite biomass are associated with severe malaria in Mozambican children: a case-control study
Rosauro Varo1,2, Antonio Sitoe2, Lola Madrid3
1Barcelona Institue for Global Health. Hospital Clínic-Universitat de Barcelona, Carrer Rosselló, 132, 5th 2nd., 08036, Barcelona, Spain.
Insights
Biomarkers indicating immune and endothelial activation, along with parasite biomass (HRP-2), were elevated in children with severe pediatric malaria (SM). These markers correlate with disease severity and may aid in risk stratification and treatment.
Area of Science:
- Tropical Medicine
- Pediatric Infectious Diseases
- Immunology
Background:
- Severe pediatric malaria (SM) is a critical global health challenge.
- Current clinical scores may not fully capture disease severity in children.
- Identifying laboratory biomarkers can improve risk stratification and disease management.
Purpose of the Study:
- To identify host biomarkers of immune and endothelial activation in children with SM.
- To assess parasite biomass markers in SM versus uncomplicated malaria (UM).
- To explore correlations between biomarkers and malaria severity.
Main Methods:
- A case-control study was conducted in southern Mozambique (2014-2016).
- Pediatric patients (<10 years) with Plasmodium falciparum SM (cases) and UM (controls) were recruited.
- Plasma levels of parasite biomass (HRP-2) and host response markers were compared.
Main Results:
- Biomarkers of immune and endothelial activation were significantly higher in children with SM.
- Hepatocyte growth factor (HGF) levels were significantly higher in SM cases.
- HRP-2 levels correlated strongly with several activation markers in both SM and UM groups.
Conclusions:
- Host biomarkers of immune and endothelial activation are associated with severe pediatric malaria.
- HRP-2 levels, alongside activation markers, show potential for risk-stratification.
- These biomarkers may offer targets for novel adjuvant therapies in malaria management.
Abstract:
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.
