Characterizing the Relationship of Histidine-Rich Protein-2 to the Neurologic Sequelae of Severe Malaria

Abstract

Despite improvements in malaria control and diagnostics, severe malaria continues to claim 800,000 lives every year. Plasmodium falciparum, the parasite that most often causes the severe forms of malaria, detoxifies its internal environment in the red blood cell stage of infection through a process mediated by the parasite-secreted histidine-rich protein 2 (pHRP2). pHRP-2 is widely used in diagnostics, yet its role in severe malaria is not well defined. Therefore, this project aimed to characterize the relationship of pHRP2 to the neurologic sequelae of severe malaria. My hypothesis was that pHRP2 levels would be significantly higher in children with severe disease, as compared to healthy controls and that higher levels would be associated with neurologic sequelae. pHRP2 levels were measured and compared between plasma samples from children diagnosed with cerebral malaria (CM), severe malarial anemia (SMA) and community controls (CC). CM samples were found to have the highest levels of pHRP2, followed by SMA and then CC. pHRP2 levels were also significantly increased in patients that had neurologic sequestration, as determined by retinopathy, and in patients who died from infection. The strong association between pHRP2 and severe disease, mortality and neurologic sequestration suggests that pHRP2 plays a role in the pathogenesis of severe malaria.