Severe falciparum malaria is difficult to diagnose accurately in children in
high transmission settings. Using data from 2,649 patients enrolled in four
studies of severe illness in three countries (Bangladesh, Kenya, and Uganda),
we fitted Bayesian latent class models using two diagnostic biomarkers: the
platelet count and the plasma PfHRP2 concentration. In severely ill patients
with clinical features consistent with severe malaria, a combined platelet count
≤ 150,000 per µL and a plasma PfHRP2 concentration ≥ 1,000 ng/mL had an
estimated sensitivity of 74% and specificity of 93% in identifying ‘true’ severe
falciparum malaria. Compared to misdiagnosed children, patients with true
severe malaria had higher parasite densities, lower hematocrits, lower rates
of invasive bacterial disease, and a lower prevalence of both HbAS and HbSS.
We estimate one third of African children enrolled in clinical studies of severe
malaria in high transmission settings had another cause of severe illness.