Therapeutic and Prophylactic Effects of the Surfactant Protein D Mimetic CGSPS18 Against Schistosoma mansoni in Biomphalaria alexandrina and Mice.

Abstract

BACHGROUND: Schistosomiasis remains difficult to control due to persistent transmission via freshwater snails and reliance on praziquantel (PZQ) as the primary treatment. Novel adjunctive strategies targeting multiple stages of the parasite life cycle are needed. This study investigated the surfactant protein D (SP-D) mimetic CGSPS18 as a potential complementary agent against Schistosoma mansoni. MATERIALS AND METHODS: The efficacy of CGSPS18 was evaluated using complementary murine, snail, and in vitro models. In mice, therapeutic PZQ monotherapy was compared with prophylactic and therapeutic combination regimens of CGSPS18 and PZQ, assessing worm burden, oogram patterns, and tissue egg counts. In vitro assays tested the larvicidal activity of CGSPS18 against miracidia and cercariae. In Biomphalaria alexandrina, prophylactic and therapeutic exposure to a sublethal concentration of CGSPS18 was evaluated by survival rate, infection rate, hemocyte parameters, phagocytic activity, and histopathological changes. RESULTS: CGSPS18 demonstrated rapid, concentration-dependent larvicidal activity, achieving 100% mortality of miracidia and cercariae at 50-100 ppm within 10 minutes. In snails, post-infection treatment improved 8-week survival (40.0% vs. 30.0% in infected controls) and significantly reduced infection rates (60.0% vs. 89.67%), alongside alterations in hemocyte profiles, enhanced phagocytic activity, and sporocyst morphological changes. In mice, both therapeutic PZQ monotherapy and therapeutic CGSPS18 + PZQ achieved complete adult worm clearance, with no significant difference between groups. The prophylactic regimen showed only partial efficacy. CONCLUSION: CGSPS18 exhibits promising laboratory larvicidal activity and beneficial effects in the snail host model. However, in the murine model, co-administration with PZQ did not enhance therapeutic outcomes compared to PZQ alone, although it did not compromise its efficacy. These findings support further mechanistic, safety, and dose-optimization studies rather than definitive claims of synergy or immediate field applicability.Schistosomiasis remains difficult to control because transmission through freshwater snails sustains reinfection, while treatment still relies heavily on praziquantel (PZQ). This study evaluated the surfactant protein D (SP-D) mimetic CGSPS18 in complementary murine, snail, and in vitro models of Schistosoma mansoni. In mice, therapeutic PZQ monotherapy was compared with prophylactic and therapeutic combination regimens containing CGSPS18 by assessing worm burden, oogram patterns, and tissue egg counts. In vitro, CGSPS18 was tested against miracidia and cercariae. In Biomphalaria alexandrina, prophylactic and therapeutic exposure to a sublethal concentration of CGSPS18 was evaluated by survival, infection rate, hemocyte parameters, phagocytic activity, and histopathology. CGSPS18 showed rapid concentration-dependent larvicidal activity, producing 100% mortality of miracidia and cercariae at 50-100 ppm within 10 min. In snails, post-infection treatment improved 8-week survival (40.0% vs. 30.0% in infected controls) and reduced the infection rate (60.0% vs. 89.67%), with associated changes in hemocyte profiles, phagocytic activity, and sporocyst morphology. In mice, therapeutic PZQ alone and therapeutic CGSPS18 + PZQ both achieved complete adult worm clearance, with no significant difference between them, whereas the prophylactic regimen was only partially effective. Overall, CGSPS18 showed promising laboratory larvicidal activity and favorable effects in the snail model. In the murine model, co-administration with PZQ did not outperform PZQ monotherapy but also did not compromise PZQ efficacy. These findings support further mechanistic, safety, and dose-optimization studies rather than definitive claims of synergy or field applicability.