Isothermal microcalorimetry to study drugs against Schistosoma mansoni

Background: Alternative antischistosomal drugs are required since praziquantel is virtually the only drug available for treatment and morbidity control of schistosomiasis. Manual microscopic reading is the current gold standard to assess the in vitro antischistosomal properties of test drugs, however it is labor intensive, subjective and difficult to standardize. Hence, there is a need to develop novel tools for antischistosomal drug discovery. Methods: The in vitro effect of praziquantel, oxamniquine, artesunate and mefloquine on metabolic activity and parasite motility of Schistosoma mansoni (newly transformed schistosomula (NTS) and 49 day-old adult worms) were studied using isothermal microcalorimetry (IMC). Results were compared to morphological readouts of viability. Results: Results obtained for the 4 drugs tested with phenotypic evaluation by microscopy and IMC showed a good correlation, but IMC also identified drug effects, which were not visible by microscopic evaluation, and IMC precisely determined the onset of action of the test drugs. Similar sensitivities on NTS and adult schistosomes were observed for praziquantel and mefloquine, while slight differences in the drug susceptibilities of the two development stages were noted with oxamniquine and artesunate. Conclusion: IMC is a useful tool for antischistosomal drug discovery, which should be further validated. In addition, our data support the use of NTS in in vitro schistosome drug assays