Authors

J QUINTANA¹; S A Babayan²; P Dickinson¹; A Ivens¹; A H Buck¹;  ¹ The University of Edinburgh, UK;  ² University of Glasgow , UK

Discussion

The secretion of extracellular RNAs (exRNAs) by parasitic nematodes has opened new avenues for the development of novel biomarkers for helminthiasis, including filariasis. These are catalogued as some of the major neglected tropical diseases, which together account for more than 120 million infections in tropical and subtropical regions. One outstanding question is whether the secretion of small RNAs is developmentally regulated in parasitic nematodes. Here, we present in vivo and in vitro data that show the presence of ubiquitous, as well as sex- and potentially stage-specific miRNA markers in Excretion/Secretion (ES) products from larval and adult stages from the rodent filarial nematode Litomosoides sigmodontis. Moreover, a subset of these miRNAs, including female-specific miRNA markers, are found in biofluids from infected vertebrate hosts, including gerbils, mice, cattle and humans. Using infected BALB/c mice as a model for filarial infection, we tested the performance of a subset of parasite-derived miRNAs as biomarkers, and significantly discriminated between infected animals and naive controls with high sensitivity (~80%) and specificity (100%). Taken together, our data constitute the first report of a comprehensive and detailed characterisation of the miRNA secretion throughout filarial development in vitro and in vivo, and provide strong evidence to support the development of biomarkers to detect ongoing infections, including the presence of reproductively active female worms.