Using clinical data from thousands of adults and children with malaria, a University of Oxford-led team has uncovered two new markers of severe disease that have the potential to improve diagnosis. Diagnosing severe malaria caused by Plasmodium falciparum infection in children in high-transmission settings remains difficult due to the high coincidence of malaria with other febrile illnesses. Aiming to overcome this issue, the researchers analyzed data from 2,649 severely ill children and adults in low-transmission and high-transmission settings in Africa. As reported in Science Translational Medicine this week, by fitting Bayesian latent class models using a combination of platelet counts and plasma concentrations of the malarial parasite protein histidine-rich protein 2 (PfHRP2), they found that diminished platelet counts and elevated plasma concentrations of PfHRP2 served as robust diagnostic markers of severe malaria. The study authors also discover that a proportion of children enrolled in several malaria clinical studies in high-transmission settings have severe febrile illness caused by other types of pathogens. "Our results suggest that the high rates of misdiagnosis could be reduced substantially by incorporating measurement of platelet counts and plasma PfHRP2 concentrations in the diagnostic criteria," they write.