Analytical sensitivity analysis and clinical impact modeling of Rapigen rapid diagnostics tests for malaria

Analytical performance analysis through laboratory benchmarking can more objectively compare the performance of malaria rapid diagnostic tests (RDTs). We present the analytical detection limits of the Rapigen BIOCREDIT Malaria Ag Pf/Pv (pLDH/pLDH), the Rapigen BIOCREDIT Malaria Ag Pf (pLDH/HRPII), and two best-in-class World Health Organization (WHO)-prequalified comparator RDTs, generated using standardized panels containing recombinant antigen, in vitro cultured parasites, international standards, and clinical samples. Detection limits of HRP2, PfLDH, and PvLDH were determined for the Rapigen and comparator RDTs as antigen concentration and in international units (IU)/mL. The Rapigen Ag Pf (pLDH/HRPII) detected 3.9 and 3.9 IU/mL for PfLDH and HRP2, respectively, while the Ag Pf/Pv (pLDH/pLDH) detected 3.9 and 5.0 IU/mL for PfLDH and PvLDH, respectively. The comparator HRP2/PfLDH and HRP2/PvLDH detected 15.6 and 31.3 IU/mL for HRP2 and PfLDH and 15.6 and 50.0 IU/mL for HRP2 and PvLDH, respectively. The RDT clinical sensitivity was predicted through application of analytical detection limits to antigen concentration distributions from clinical symptomatic and asymptomatic cases. 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 and improve the detection of hrp2 deletions through PfLDH detection. Through the benchmarking and simulation of clinical sensitivity, a method for rapidly assessing the ability of new RTDs to meet clinical needs using high-sensitivity antigen distribution data is presented.