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Background  Schistosomiasis is one of the most significant diseases in tropical countries and affects almost 200 million people worldwide. The application of molluscicides to eliminate the parasite's intermediate host,  Biomphalaria glabrata , from infected water supplies is one strategy currently being used to control the disease. Previous studies have shown a potent molluscicidal activity of crude extracts from  Piper  species, with extracts from  Piper tuberculatum  being among the most active.    Methods and Findings  The molluscicidal activity of  P. tuberculatum  was monitored on methanolic extracts from different organs (roots, leaves, fruit and stems). The compounds responsible for the molluscicidal activity were identified using  1 H NMR and ESIMS data and multivariate analyses, including principal component analysis and partial least squares. These results indicated that the high molluscicidal activity displayed by root extracts (LC 50  20.28 µg/ml) was due to the presence of piplartine, a well-known biologically-active amide. Piplartine was isolated from  P. tuberculatum  root extracts, and the molluscicidal activity of this compound on adults and embryos of  B. glabrata  was determined. The compound displayed potent activity against all developmental stages of  B. glabrata . Next, the environmental toxicity of piplartine was evaluated using the microcrustacean  Daphnia similis  (LC 50  7.32 µg/ml) and the fish  Danio rerio  (1.69 µg/ml). The toxicity to these organisms was less compared with the toxicity of niclosamide, a commercial molluscicide.    Conclusions  The development of a new, natural molluscicide is highly desirable, particularly because the commercially available molluscicide niclosamide is highly toxic to some organisms in the environment (LC 50  0.25 µg/ml to  D. similis  and 0.12 µg/ml to  D. rerio ). Thus, piplartine is a potential candidate for a natural molluscicide that has been extracted from a tropical plant species and showed less toxic to environment.

Schistosomiasis Control Using Piplartine against Biomphalaria glabrata at Different Developmental Stages