A Dual, Systematic Approach to Malaria Diagnostic Biomarker Discovery.

Background The emergence and spread of P. falciparum parasites lacking HRP2/3 proteins and the resulting decreased utility of HRP2-based malaria rapid diagnostic tests (RDTs) prompted the World Health Organization (WHO) and other global health stakeholders to prioritize the discovery of novel diagnostic biomarkers for malaria. Methods To address this pressing need, we adopted a dual, systematic approach by conducting a systematic review of literature for publications on diagnostic biomarkers for uncomplicated malaria and a systematic in silico analysis of P. falciparum proteomics data for Plasmodium proteins with favorable diagnostic features. Results Our complementary analyses led us to two novel malaria diagnostic biomarkers compatible for use in an RDT format: glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and dihydrofolate reductase-thymidylate synthase (DHFR-TS). Conclusion Overall, our results pave the way for the development of next generation malaria RDTs based on new antigens by identifying two lead candidates with favorable diagnostic features and partially de-risked product development prospects.