A single human cerebral malaria histopathologic study can be worth a thousand experiments

Severe malaria is a density-dependent disease that comprises infected-erythrocyte sequestration, with or without monocytic infiltration, as seen in renal, placental, and lung tissues from severe malaria patients. HIV induces a chronic proinflammatory state with higher numbers of inflammasome-activated monocytes and platelets circulating. The epidemiological and pathological study of S. E. Hochman et al. that was published in a recent issue of mBio (Hochman SE, Madaline TF, Wassmer SC, Mbale E, Choi N, et al., mBio 6:e01390-15, 2015, doi:10.1128/mBio.01390-15) analyzes a large cohort of Malawian children and shows that cerebral malaria in younger HIV-negative children presents as an acute disease predominated by sequestered infected erythrocytes. In contrast, they show that case presentation in older HIV-positive children is as a more lethal acute on chronic disease marked by double the monocytic infiltrates and 5 times as many platelets. This study suggests that cerebral involvement in severe malaria is a pathology similar to that of other organ involvement of severe malaria, with a bias in HIV-positive individuals toward more monocytic infiltrates. The study also addresses the important association of severe malaria and HIV prevalence.