A Dual, Systematic Approach to Malaria Diagnostic Biomarker Discovery

Clin Infect Dis. 2022 Jan 7;74(1):40-51. doi: 10.1093/cid/ciab251.


Background: The emergence and spread of Plasmodium falciparum parasites that lack HRP2/3 proteins and the resulting decreased utility of HRP2-based malaria rapid diagnostic tests (RDTs) prompted the World Health Organization 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 the 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 2 novel malaria diagnostic biomarkers compatible for use in an RDT format: glyceraldehyde 3-phosphate dehydrogenase and dihydrofolate reductase-thymidylate synthase.

Conclusions: Overall, our results pave the way for the development of next-generation malaria RDTs based on new antigens by identifying 2 lead candidates with favorable diagnostic features and partially de-risked product development prospects.

Keywords: DHFR-TS; GAPDH; biomarker; diagnostics; malaria.

Publication types

  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Antigens, Protozoan
  • Biomarkers / analysis
  • Diagnostic Tests, Routine / methods
  • Humans
  • Malaria* / diagnosis
  • Malaria, Falciparum* / diagnosis
  • Plasmodium falciparum / genetics
  • Protozoan Proteins
  • Sensitivity and Specificity


  • Antigens, Protozoan
  • Biomarkers
  • Protozoan Proteins