Host biomarkers for early identification of severe imported Plasmodium falciparum malaria

Abstract

Background: Severe imported P. falciparum malaria is a source of morbi-mortality in non-endemic regions. WHO criteria don't accurately classify patients at risk of complications. There is a need to evaluate new tools such as biomarkers to better identify patients with severe imported malaria. Methods: A case-control study was conducted in Barcelona, from January 2011–January 2021. Adult patients with microbiologically confirmed P. falciparum malaria were classified according to WHO criteria. Patients with imported non-malarial fevers were included as controls. In each group, angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), soluble triggering receptor expressed on myeloid cells (sTREM-1), C-reactive protein (CRP) and platelets were measured and their concentrations were compared between groups. New groups were made with a modified WHO severity classification and biomarkers’ performance was evaluated using multiple imputation models. Results: 131 participants were included: 52 severe malaria, 30 uncomplicated malaria and 49 non-malarial fever cases. All biomarkers except sTREM-1 showed significant differences between groups. Using the modified WHO severity classification, Ang-2 and CRP presented the best AUROC; 0.79 (95%CI 0.64–0.94) and 0.80(95%CI 0.67–0.93). A model combining CRP and Ang-2 showed the best AUROC, of 0.84(95%CI 0.68–0.99), with the highest sensitivity and specificity: 84.6%(95%CI 58.9–98.1) and 77.4% (95%CI 65.9–87.7), respectively. Conclusions: The combination of Ang-2 and CRP may be a reliable tool for the early identification of severe imported malaria. The use of a rapid prognostic test including the mentioned biomarkers could optimize imported malaria management, with the potential to decrease the rate of complications and hospitalizations in patients with imported malaria.

Keywords

• Imported malaria
• Severe malaria
• Biomarkers
• Diagnosis