Novel Diagnostic Biomarker Discovery and Validation for Malaria

Using proteomic methods, we identified four novel biomarkers that are upregulated at the mRNA and/or protein level in A. gambiae mosquitoes infected with Plasmodium parasites. We showed that mice bitten by mosquitoes produce antibodies against salivary proteins that can be detected by standard serological methods. We further found that similar antibodies can be found in the blood of humans exposed to Anopheles mosquito bites. Serology of positive infectious mosquito bites represents a new paradigm in diagnostic testing for malaria, circumventing many of the limitations of current tests that cause false negative results, including the abilities to: (a) detect exposure to infectious mosquito bites in the absence of clinical symptoms (Asymptomatic reservoir); (b) detect exposure to P. falciparum isolates that have deleted gene targets; and, (c) detect exposure to non-falciparum malaria species. In this Phase I proposal, we will develop our prototype assay and determine its technical functional performance characteristics using well controlled laboratory samples. In a follow-on Phase II proposal, we will determine functional performance characteristics using hundreds of human specimens from endemic areas, driving towards statistically significant assay performance characteristics and enabling studies for regulatory approval.