Abstract
BackgroundHelminth parasites cause untold morbidity and mortality to billions of people and livestock. Anthelmintic drugs are available but resistance is a problem in livestock parasites, and is a looming threat for human helminths. Testing the efficacy of available anthelmintic drugs and development of new drugs is hindered by the lack of objective high-throughput screening methods. Currently, drug effect is assessed by observing motility or development of parasites using laborious, subjective, low-throughput methods.Methodology/Principal FindingsHere we describe a novel application for a real-time cell monitoring device (xCELLigence) that can simply and objectively assess anthelmintic effects by measuring parasite motility in real time in a fully automated high-throughput fashion. We quantitatively assessed motility and determined real time IC50 values of different anthelmintic drugs against several developmental stages of major helminth pathogens of humans and livestock, including larval Haemonchus contortus and Strongyloides ratti, and adult hookworms and blood flukes. The assay enabled quantification of the onset of egg hatching in real time, and the impact of drugs on hatch rate, as well as discriminating between the effects of drugs on motility of drug-susceptible and –resistant isolates of H. contortus.Conclusions/SignificanceOur findings indicate that this technique will be suitable for discovery and development of new anthelmintic drugs as well as for detection of phenotypic resistance to existing drugs for the majority of helminths and other pathogens where motility is a measure of pathogen viability. The method is also amenable to use for other purposes where motility is assessed, such as gene silencing or antibody-mediated killing.
Highlights
Billions of people are infected with helminths in developing countries, resulting in many thousands of deaths annually [1,2]
Drugs are available but resistance is problematic in livestock parasites and is a looming threat for human helminths
New drug discovery and resistance monitoring is hindered as drug efficacy is assessed by observing motility or development of parasites using laborious, subjective, low-throughput methods evaluated by eye using microscopy
Summary
Billions of people are infected with helminths in developing countries, resulting in many thousands of deaths annually [1,2]. While chemotherapy is available for most parasitic helminths, widespread use of anthelmintics in livestock has resulted in the emergence of drug-resistant parasites [4,5]. Despite the impact of helminths on the health of humans and livestock, the anthelmintic pharmacopoeia is small. This is due in part to the high cost and limited financial return from drug development, for human helminth infections. Anthelmintic drugs are available but resistance is a problem in livestock parasites, and is a looming threat for human helminths. Drug effect is assessed by observing motility or development of parasites using laborious, subjective, low-throughput methods
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