The mechanistic, diagnostic and prognostic utility of biomarkers in severe malaria.

Malaria remains an important global cause of severe illness and mortality. This literature review summarizes available data on how biomarkers might be applied to diagnose, prognosticate and provide mechanistic insights in patients with severe malaria. Of the large number of candidate biomarkers, only PfHRP2 has consistently demonstrated clinical utility and, when incorporated into rapid antigen detection tests, has shown diagnostic sensitivity above 95%, which is at least as good as light microscopy. As a quantitative test, PfHRP2 also shows some promise in differentiating severe malarial from non-malarial disease in areas where asymptomatic carriage of malaria parasites is common, and possibly as a tool to estimate sequestered parasite burden and subsequent mortality. Biomarkers such as pLDH and panmalarial antigen have lower sensitivity for non-falciparum malaria in rapid antigen detection tests. There is an urgent need to discover and validate better biomarkers for incorporation into rapid antigen detection tests in countries where Plasmodium vivax is a common cause of severe disease. A large number of host-derived acute-phase reactants, markers of endothelial dysfunction and immune mediators have been proposed as biomarkers. Although they have provided mechanistic insights into the immunopathology of severe malaria, their roles as clinical tools remain uncertain.