Characterizing antibody responses to PfEMP1 as biomarkers of severe and uncomplicated malaria in Papua New Guinea
To characterize the immune response of children in Papua New Guinea who experienced an episode of severe or uncomplicated malaria by using immune markers to determine characteristics of the parasite causing severe disease, and to identify immune markers that best distinguish between severe and uncomplicated malaria.
Papua New Guinea has high transmission of malaria and surveillance tools are necessary to identify populations with the highest burden and risk of clinical disease. Serology has been explored for use in malaria exposure and transmission monitoring, but there are currently no reliable biomarkers that distinguish between severe and uncomplicated clinical malaria. The target antigens that are most important for severe disease and the features of the immune response that best correlate with disease presentation need to be defined.
We will assess serology responses to 20 recombinant proteins of PfEMP1 fragments that were either upregulated in parasites causing severe malaria in Papuan adults or are pathogenic binding fragments associated with severe malaria in Africa. The proteins are a subset of an original array that were selected as best correlates of clinical presentation in our recent Malawi study (unpublished). Antibody responses will be assessed for children in Madang province, PNG, at presentation to hospital with severe or uncomplicated malaria (157 and 82 children, respectively) and at 8 weeks follow up (121 and 52 children, respectively). A high throughput multiplex array system will be used: recombinant proteins are coupled to fluorescently labeled beads and exposed to a plasma sample simultaneously, then antibody titers and features are quantified with fluorescent detectors.