WormAssay: A Novel Computer Application for Whole-Plate Motion-based Screening of Macroscopic Parasites

Abstract

Lymphatic filariasis is caused by filarial nematode parasites, including Brugia malayi. Adult worms live in the lymphatic system and cause a strong immune reaction that leads to the obstruction of lymph vessels and swelling of the extremities. Chronic disease leads to the painful and disfiguring condition known as elephantiasis. Current drug therapy is effective against the microfilariae (larval stage) of the parasite, but no drugs are effective against the adult worms. One of the major stumbling blocks toward developing effective macrofilaricides to kill the adult worms is the lack of a high throughput screening method for candidate drugs. Current methods utilize systems that measure one well at a time and are time consuming and often expensive. We have developed a low-cost and simple visual imaging system to automate and quantify screening entire plates based on parasite movement. This system can be applied to the study of many macroparasites as well as other macroscopic organisms.

Plant-Based Solutions to Global Livestock Anthelmintic Resistance

“…Identification of nematode survival can be established by counting under a microscope. This process can be automated using the WormAssay protocol, where a high definition camera is attached to an inverted microscope to detect parasite motility and the captured images are analyzed using specially-designed algorithms (Marcellino et al 2012;Storey et al 2014). When feasible, using the latter method will provide more accurate, reproducible results.…”

A murine macrofilaricide pre-clinical screening model for onchocerciasis and lymphatic filariasis

“…It is debatable whether macrofilaricides with a total reliance on adaptive immunity would be suitable for indications in chronic filariasis patients who typically display hyporesponsive T cell profiles to filarial antigens [37,45,46]. Furthermore, identification of 'hits' within in vitro culture screening assays [29,47] would fail to identify drugs with a reliance on host adaptive immune responses and as such, these candidates would be suitable for in vivo evaluation in SCID mice. However, should drugs emerge with putative T or B cell adaptive immune-pharmacological mechanisms, the availability of comparative Bm and Onchocerca macrofilaricide screens in WT mice, SCID mice and gerbils would serve as useful pre-clinical assessment tools to dissect the mode of action and spectrum of anti-filarial effects.…”

An automated high-throughput system for phenotypic screening of chemical libraries onC. elegansand parasitic nematodes

“…The 71 "WormAssay" system quantifies the motility of macroscopic parasites such as Brugia malayi adult 72 worms (Marcellino et al, 2012). This system has been further developed into "The Worminator", 73 which quantifies smaller, microscopic nematode stages and has been validated by quantifying the 74 activity of several anthelmintics (Storey et al, 2014).…”