An automated, high-resolution phenotypic assay for adult Brugia malayi and microfilaria

TL;DR

This paper introduces an automated, high-resolution phenotypic assay for tracking and analyzing the motility of adult Brugia malayi worms and microfilaria in vitro, aiding drug testing for lymphatic filariasis.

Contribution

It presents a novel multi-parameter assay that accurately tracks complex worm behaviors and postures, improving drug screening capabilities for adult and microfilaria stages.

Findings

High-fidelity tracking of worm postures achieved

Quantitative analysis of drug effects on motility

Visual representation of behavior in space and time

Abstract

Brugia malayi are thread-like parasitic worms and one of the etiological agents of Lymphatic filariasis (LF). Existing anthelmintic drugs to treat LF are effective in reducing the larval microfilaria (mf) counts in human bloodstream but are less effective on adult parasites. To test potential drug candidates, we report a multi-parameter phenotypic assay based on tracking the motility of adult B. malayi and mf in vitro. For adult B. malayi, motility is characterized by the centroid velocity, path curvature, angular velocity, eccentricity, extent, and Euler Number. These parameters are evaluated in experiments with three anthelmintic drugs. For B. malayi mf, motility is extracted from the evolving body skeleton to yield positional data and bending angles at 74 key point. We achieved high-fidelity tracking of complex worm postures (self-occlusions, omega turns, body bending, and reversals) while providing a visual representation of pose estimates and behavioral attributes in both space and time scales.