Circulating Cell-Free Nucleic Acid Detection for Wuchereria bancrofti Infections

Area of Science:

• Parasitology
• Molecular Diagnostics
• Tropical Medicine

Background:

• Human lymphatic filariasis (LF) is a debilitating parasitic disease caused by Wuchereria bancrofti (Wb) and Brugia malayi (Bm).
• Current diagnostic methods for LF can be invasive or lack sensitivity.
• Circulating cell-free nucleic acids (ccfDNA/ccfRNA) in plasma offer a minimally invasive approach for detecting parasitic infections.

Purpose of the Study:

• To identify and validate parasite-specific RNA and DNA biomarkers in plasma for LF detection.
• To evaluate the diagnostic sensitivity and utility of these biomarkers for assessing infection and treatment response.

Main Methods:

• Plasma-RNA sequencing was performed on individuals with active Wb infection and uninfected controls.
• Developed and tested assays for detecting Wb and/or Bm ccfDNA and ccfRNA.
• Assessed the sensitivity of WbTR1 ccfDNA as a biomarker in Wb-infected individuals across multiple geographic locations.

Main Results:

• Six RNA targets specific to Wb and/or Bm were identified.
• Both ccfDNA and ccfRNA assays were successfully used in Wb-infected individuals.
• The WbTR1 DNA assay demonstrated high sensitivity, detecting Wb ccfDNA in 71% of microfilaria-positive individuals.
• WbTR1 ccfDNA levels became undetectable within one year post-treatment.

Conclusions:

• Plasma-derived ccfDNA and ccfRNA are promising tools for diagnosing LF.
• The WbTR1 ccfDNA biomarker shows significant potential for sensitive detection of Wuchereria bancrofti infection.
• ccfDNA/RNA detection facilitates assessment of infection status and treatment efficacy in LF.