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

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.

Multi-center screening of the Pathogen Box collection for schistosomiasis drug discovery

“…Among the inherent variables were parasite strain, culture medium, whether or not the parasites were pre-incubated prior to addition of compounds and the detection system employed. In this context, field isolates of S. mansoni with differential susceptibilities PZQ are known [46] and the choice of culture medium can influence the viability of schistosomula [7, 8, 17]. Evaluating the possible influences of these variables on the data, however, was not a goal of the current study.…”

In Vitro Assessment of Anthelmintic Activities ofRauwolfia vomitoria(Apocynaceae) Stem Bark and Roots against Parasitic Stages ofSchistosoma mansoniand Cytotoxic Study

“…Infections with schistosomes occur when cercariae penetrate and enter into the body through intact skin. Therefore, preventing such penetration of cercariae into the skin is also a potential form of transmission control [ 6 ]. Over the years, many topical agents have been evaluated for their ability to block penetration of cercariae into the skin and some of these compounds are highly effective but have not been used clinically due to their potential toxicity and difficulty in formulation and/or applying under field conditions [ 39 ].…”

“…Despite the public health importance of schistosomiasis and the risk that the disease might further spread and intensify, schistosomiasis control programs in endemic countries are based mainly on chemotherapy [ 4 ]. As it is today for some neglected tropical diseases such as trypanosomiasis and leishmaniasis, the treatment of schistosomiasis was almost as difficult and toxic until the 1970s when praziquantel (PZQ) was discovered [ 5 , 6 ]. In 1988, PZQ was brought to the market [ 5 ] and it is so far the only drug available and recommended by World Health Organization (WHO) for the treatment and control of schistosomiasis [ 6 ].…”

“…As it is today for some neglected tropical diseases such as trypanosomiasis and leishmaniasis, the treatment of schistosomiasis was almost as difficult and toxic until the 1970s when praziquantel (PZQ) was discovered [ 5 , 6 ]. In 1988, PZQ was brought to the market [ 5 ] and it is so far the only drug available and recommended by World Health Organization (WHO) for the treatment and control of schistosomiasis [ 6 ]. This drug is safe and effective against all Schistosoma species [ 7 ] and has been used for the last 30 years.…”

Use of kinase inhibitors against schistosomes to improve and broaden praziquantel efficacy

“…Therefore, we investigated 2-day-old schistosomula in order to focus on a developmental stage with a limited sensitivity period and 7-day-old schistosomula, which are insensitive to PZQ, to test the effects of 15 different CaMKII (selective and non-selective) inhibitors on parasite survival. Given the considerable numbers of parasites required to achieve statistical power and, consequently, the extremely large number of animals needed to provide such worm numbers, with potential animal ethics concerns, mechanically produced schistosomula have generally been used as a high throughput tool for phenotypic pre-screening in drug efficacy studies (de Moraes et al, 2012;Tekwu et al, 2016), a trait followed here. Mechanically transformed schistosomula are commonly used for drug screening assays.…”