Circulating Cell-Free Nucleic Acid Detection for Wuchereria bancrofti Infections.

Abstract

Human lymphatic filariasis (LF) is primarily caused by the helminth parasites Wuchereria bancrofti (Wb) and Brugia malayi (Bm). Detecting parasitic circulating cell-free nucleic acids (ccfDNA/ccfRNA) in plasma is a promising approach for detection of active infections. Plasma RNA sequencing analyses from individuals with active Wb infection and uninfected controls identified 6 RNA targets that were specific to Wb and/or Bm. Assays developed to detect either ccfDNA and ccfRNA were successfully used in Wb-infected individuals, but DNA-based assays targeting WbTR1 were found to be the most sensitive biomarker of Wb circulating cell-free nucleic acids. Plasma-derived ccfDNA was identified in 71% (of all microfilaria-positive individuals) of Wb infections from India, the Cook Islands, Mali, Haiti, and Guyana. Following definitive treatment, time course analyses indicated that WbTR1 ccfDNA levels were undetectable within a year. Overall, ccfDNA/ccfRNA detection in lymphatic filariasis holds promise for assessment of infection and treatment response in Wb and Bm infections.