Infectious Diseases, Prevention and Control

Background: Schistosomiasis is a worldwide health problem and Praziquantel is the only drug currently used for the treatment. There is some evidence that extensive monotherapy of Praziquantel may be leading to drug resistance in the parasite. Method: A total of 146 compounds were examined in vitro for antischistosomal potential against adult and early mature Schistosoma mansoni worms using a well-cultured medium. Worms were treated with different concentrations of phosphodiesterase inhibitors and after 5 days, a worm was assayed in terms of viability, motility, a death of worms, female ovipositing capacity and worm coupling. Result: Findings of one or two repeat experiments revealed potential antischistosomal activities against adult mature schistosomes, expressed as worm killing/and or sluggish worm movement, worm pairing and female ovipositing capacity for 52 compounds. However, the effect was recorded at high concentrations, resulting in worm killing for 26% of the compounds (13) with the survivors showing sluggish worm movement. All compounds showed worm killing at high concentrations of 100 µM and 50 µM revealed, worm uncoupling with an absence of ova. At the concentrations of 25 µM and 10 µM, 4% and 8% out of a total of 13 compounds showed the same profile. Reduction in the number of eggs was recorded for most of the compounds (34%) with less concentrations in the presence of living intact couples. 33% of the compounds showed no worm killing, uncoupling with an absence of eggs was recorded. In four out of 52 compounds (7%), no worm killing with an absence of ova was recorded despite the presence of intact couples. In 46 out of 52 promising compounds, only male worms were affected where 100% of them were killed. Meanwhile, the insult to early mature worms was more pronounced. Expression and cloning analysis of PDEs in S. mansoni adult and early mature worms revealed higher expression of Sm4A, Sm4C and Sm11 in adult and early mature male worms than in female worms. Sm9C is highly expressed in a juvenile male. Conclusion: PDE inhibitors showed potential against schistosomiasis In vitro with insult mainly targeting worm ovipositing.