Mechanically produced schistosomula as a higher-throughput tools for phenotypic pre-screening in drug sensitivity assays: current research and future trends.

Daniel Boamah,Stephanie Keyetat Tekwu,William Kofi Anyan,Veronique Penlap Beng,Alexander Kwadwo Nyarko,Kwabena Mante Bosompem,Emmanuel Mouafo Tekwu,Kofi Owusu Baffour-Awuah

doi:10.1186/s40364-016-0075-2

Abstract

It is crucial to develop new antischistosomal drugs since there is no vaccine and the whole world is relying on only a single drug for the treatment of schistosomiasis. One of the obstacles to the development of drugs is the absence of the high throughput objective screening methods to assess drug compounds efficacy. Thus for identification of new drug compounds candidates, fast and accurate in vitro assays are unavoidable and more research efforts in the field of drug discovery can target schistosomula. This review presents a substantial overview of the present state of in vitro drug sensitivity assays developed so far for the determination of anti-schistosomula activity of drug compounds, natural products and derivatives using newly transformed schistosomula (NTS). It highlights some of the challenges involved in in vitro compound screening using NTS and the way forward.

Highlights

Hundreds of millions of people are living at risk of schistosomiasis infection [1]
- This technique requires that the supernatant must be removed from the drug assay without aspirating the schistosomula and the drug assay should be diluted to an acceptable fluorescence range as needed
One of the great deal of new drug discovery against schistosomes is dependent on in vitro whole parasite screens

Summary

Background

Hundreds of millions of people are living at risk of schistosomiasis infection [1]. More than 207 million people are infected worldwide with 85% living in Africa. The parasite viability was assessed microscopically [15] This approach of in vitro drug screening based on the phenotype of the whole adult worm organism usually requires the intensive use of laboratory animals (hamster, rats, mice) since there is no existing in vitro life cycles for Schistosoma. Parasites obtained following this protocol is morphologically or biochemically closed enough to those recovered from natural infections [33, 48] This makes the mechanical transformation the best alternative method for large production of schistosomula for high-throughput studies such as gene expression, identification of drug targets and identification of effective drugs against schistosmes [37]. 25–50% of transformed schistosomula reach the ‘gut-closed’ stage by day 12 Significantly less cercariae heads separated from the tails by chemical method Low schistosomula yield and the possibility of contamination by host material Require use of live animals (rat, mice, hamster, ...) and skilled technician Less appropriate technique for high throughput. This assay, which uses the xCELLigence system was a new application or device to monitoring cells in a

Methods

Objective

Findings

Conclusion