Use of proteomics as a platform for evaluating new biomarkers for improving diagnosis of Plasmodium vivax for the purpose of malaria elimination

Currently available malaria lactate dehydrogenase (LDH) and aldolase-based rapid diagnostic tests (RDTs) are insufficiently sensitive to detect the asymptomatic, submicroscopic Plasmodium vivax (Pv) reservoir in order to achieve malaria elimination. Studies using ultra-sensitive diagnostic techniques have described large reservoirs of asymptomatic submicroscopic Pv infections, associated with gametocytemia, that were undetectable by RDTs but are likely to be contributing to ongoing transmission of parasite. Given the challenges associated with eliminating Pv, new diagnostic tools based on more sensitive biomarkers are urgently required in order to meet the target product profile for point of care tests for Pv in order to detect this asymptomatic reservoir. An unbiased strategy to investigate Pv derived proteins in infected subjects would prove valuable to identify candidate biomarkers for early diagnosis. Mass spectrometry-based proteomics is a valuable platform in this regard and can be used for identification of novel biomarkers for malaria. Proteomic studies performed on clinical plasma samples with high parasitemia identified several Pv proteins that may be good candidates for Pv diagnosis. At QIMR Berghofer, an induced blood stage malaria (IBSM) model has been established to facilitate rapid evaluation of antimalarial drugs in both Plasmodium falciparum (Pf) and Pv. This low parasitemia model, with samples able to be taken pre and post treatment, is also ideally suited for evaluating biomarker dynamics. We are currently undertaking mathematic modelling work to evaluate the dynamics of Plasmodium vivax LDH (PvLDH) during an IBSM infection to identify key parameters in order to better understand the performance of PvLDH-based RDTs. This platform may also be suitable for identifying new biomarkers for the purpose of improving detection of submicroscopic parasitemia.

Diagnostics
P. vivax

Nov 2019 — Oct 2023

$15,000

Australia
Malaysia

Australian Centre for Research Excellence in Malaria Elimination (ACREME)