Rapid Fire Presentation 8th International Conference on Plasmodium vivax Research 2022

Incremental performance of new lactate dehydrogenase-based Plasmodium vivax rapid diagnostic tests (#325)

Allison Golden 1 , Rebecca Barney 1 , Greg Bizilj 1 , Ihn Kyung Jang 1 , Thanh Phan 1 , Jordi Landier 2 , Francois H Nosten 2 , Gonzalo J Domingo 1 , Hannah C Slater 1
  1. PATH, Seattle, WA, United States
  2. Shoklo Malaria Research Unit, Mae Sot, Thailand

Diagnostic tests to detect Plasmodium (P.) vivax have challenges because of both its unique life cycle compared to P. falciparum and limited biomarkers with acceptable sensitivity. Low parasite densities, lower numbers of circulating parasites, and correspondingly lower antigen levels are common with P. vivax infections. The result is rapid diagnostic tests (RDTs) that are inadequate for clinical care. Next generation RDTs have improved limits of detection (LOD) for P. vivax-specific lactate dehydrogenase (PvLDH). We present analysis of the analytical detection limit of the RapiGEN BIOCREDIT Malaria Ag Pf/Pv (pLDH/pLDH) as compared to a WHO-prequalified standard RDT using characterized panels containing recombinant antigen, in vitro cultured parasite antigen, and clinical samples alongside international standards and specificity controls. The quantification of antigen in the panels was performed using a high-sensitivity multiplex quantitative antigen assay. This platform was also used to quantify antigen in samples from clinical settings and understand antigen distribution in both symptomatic and asymptomatic cases. The analytical detection limits were applied to PvLDH antigen distributions to model the impact of improved LOD on clinical sensitivity. PvLDH antigen distribution in 349 PCR-positive samples from asymptomatic individuals from a low-transmission area of Eastern Myanmar and 114 microscopy-positive samples from febrile individuals from multiple countries were compared. This modeling showed that febrile cases would be detected in majority by both standard and RapiGEN RDTs, though with increases in the RapiGEN RDTs that may be important for clinical cases currently missed by microscopy. RapiGEN RDTs were predicted to increase the detection of asymptomatic cases. This work demonstrates the need for RDTs with improved sensitivity for LDH, understanding the dependence of clinical performance on antigen distribution, and a method for rapidly assessing the ability of new rapid tests to meet clinical needs using high sensitivity antigen distribution data.