Differences in novel Schistosoma mansoni Sm25 and Sm29 rapid diagnostic test performance based on sample matrix.

Abstract

Introduction: Schistosomiasis is a neglected tropical disease caused by parasitic worms of the genus Schistosoma. As schistosomiasis control programs approach elimination as a public health problem, there is an urgent need for sensitive diagnostic assays that can easily be deployed in the field at low cost. For schistosomiasis transmission interruption and surveillance use cases, the diagnostic Target Product Profile (TPP) proposed a two-step testing strategy involving an initial point-of-care screening test capable of detecting either current or former infections with sensitivity > 0.95, specificity > 0.80, and result stability ≥ 0.5 hours. To meet this need, Drugs and Diagnostics for Tropical Diseases designed two novel rapid diagnostic test (RDT) prototypes that detect antibodies against recombinant Schistosoma mansoni antigens: Sm25 and Sm29.

Methods: We evaluated the performance of these RDT prototypes using serum, whole blood, and dried blood spots (DBS). RDT results were determined by two visual readers and a Lumos automated reader, which also provided a quantitative readout of test line intensity. Lumos results were used to quantify test line stability over time. Further, we compared RDT results to other serologic assays (ELISA and the multiplex bead assay) that detect antibodies against Sm25, Sm29 and two additional S. mansoni antigens.

Results: While both Sm25 and Sm29 RDTs exhibited high specificity and stability that surpassed TPP criteria, their sensitivity fell short of TPP goals. Sensitivity was highest with serum, followed by DBS, then whole blood, which would be the most useful for point-of-care settings. In addition, we identified a gap in the ability of currently used recombinant antigens to detect all people infected with S. mansoni, regardless of test platform.

Discussion: Our findings underscore that while these prototypes represent a promising start, there is still a case for novel antigen discovery and generation of RDTs with increased sensitivity to meet TPP criteria.