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

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. Author Summary: The World Health Organization estimates that there are approximately 37 million people who are afflicted by Onchocerca volvulus (the parasitic worm that causes river blindness) and over 120 million people afflicted by the filarial worms Wuchereria and Brugia spp. (causative agents of lymphatic filariasis or elephantiasis). Current mass drug administration includes albendazole and either diethylcarbamazine or ivermectin. These drugs, however, are effective at killing the early larval stage (microfilariae) released from adult female worms but they do not kill the adult worms. Adult worms can live up to 10 or more years, releasing thousands of microfilariae per day. It is essential therefore to treat infected individuals with macrofilaricides in order to prevent the adult parasites from producing microfiliariae for the duration of the infection and to treat the disease. In order to screen candidate drugs for use as macrofilaricides, we have developed an inexpensive system and simple method for quantifying the effectiveness of drugs on parasite movement. The apparatus uses a commodity video camera, a computer and a newly developed free and open source software application to provide automated and quantitative measurements of parasite motility on each plate of worms. This system is not only useful for high throughput screening of macroparasites but can also be applied to the study of other macroscopic organisms as well.