<p>Schistosomiasis remains as a parasitic disease with major morbidity, ongoing transmission, and economic burden, particularly in tropical regions. Praziquantel is the first-line treatment but has limited efficacy against juvenile stages of the parasite. In this context, this study assessed the repurposing potential of anthelmintics against <i>Schistosoma mansoni</i>, focusing on the schistosomicidal activity of nitazoxanide (NTZ), levamisole (LVZ), and thiabendazole (TBZ). In vitro, NTZ exhibited a significant schistosomicidal activity, emerging as a repurposing candidate. In contrast, LVZ and TBZ showed no significant schistosomicidal activity. NTZ was active from 40&#xa0;µg/mL, affecting schistosomula and adult worms in a dose-dependent manner. Ultrastructural analysis revealed wrinkling of the oral and ventral suckers and tegumental alterations in male worms, including shortening of ridges near the tubercles and the presence of multiple small protrusions. In vivo, NTZ showed partial efficacy, with 57.14% reduction in adult worm recovery, whereas PZQ achieved complete elimination. Infected animals presented a mean of 541.86 ± 273.13 viable eggs/cm<sup>2</sup>, while treatment with nitazoxanide (205&#xa0;mg/kg) or praziquantel (400&#xa0;mg/kg) reduced these values to 247.98 ± 109.68 and 144.92 ± 133.46 eggs/cm<sup>2</sup>, respectively. Combined administration of NTZ and PZQ resulted in the greatest reduction in viable egg counts, with a mean of 96.75 ± 49.55 eggs/cm<sup>2</sup>. Although praziquantel resistance has been reported, in this study it fully eliminated adult worms, while nitazoxanide showed lower but relevant activity against both schistosomula and adult stages. These findings confirm the efficacy of praziquantel against adult worms and highlight therapeutic potential of nitazoxanide, underscoring the need for further bioavailability studies.</p> Graphical Abstract <p></p>

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Nitazoxanide Exhibits Schistosomicidal Activity Against Schistosomula and Adult Schistosoma mansoni and Influences Praziquantel-Associated Outcomes

  • Cícero Jádson Da Costa,
  • Juliana Ellen de Melo Gama,
  • Alex José de Melo Silva,
  • Karina Lidianne Alcântara Saraiva,
  • Christina Alves Peixoto,
  • Roni Evêncio de Araújo,
  • Carlos André Laranjeira Miranda Filho,
  • Gustavo Henrique Aires Albuquerque,
  • Danielle Maria Nascimento Moura,
  • Sheilla Andrade De Oliveira

摘要

Schistosomiasis remains as a parasitic disease with major morbidity, ongoing transmission, and economic burden, particularly in tropical regions. Praziquantel is the first-line treatment but has limited efficacy against juvenile stages of the parasite. In this context, this study assessed the repurposing potential of anthelmintics against Schistosoma mansoni, focusing on the schistosomicidal activity of nitazoxanide (NTZ), levamisole (LVZ), and thiabendazole (TBZ). In vitro, NTZ exhibited a significant schistosomicidal activity, emerging as a repurposing candidate. In contrast, LVZ and TBZ showed no significant schistosomicidal activity. NTZ was active from 40 µg/mL, affecting schistosomula and adult worms in a dose-dependent manner. Ultrastructural analysis revealed wrinkling of the oral and ventral suckers and tegumental alterations in male worms, including shortening of ridges near the tubercles and the presence of multiple small protrusions. In vivo, NTZ showed partial efficacy, with 57.14% reduction in adult worm recovery, whereas PZQ achieved complete elimination. Infected animals presented a mean of 541.86 ± 273.13 viable eggs/cm2, while treatment with nitazoxanide (205 mg/kg) or praziquantel (400 mg/kg) reduced these values to 247.98 ± 109.68 and 144.92 ± 133.46 eggs/cm2, respectively. Combined administration of NTZ and PZQ resulted in the greatest reduction in viable egg counts, with a mean of 96.75 ± 49.55 eggs/cm2. Although praziquantel resistance has been reported, in this study it fully eliminated adult worms, while nitazoxanide showed lower but relevant activity against both schistosomula and adult stages. These findings confirm the efficacy of praziquantel against adult worms and highlight therapeutic potential of nitazoxanide, underscoring the need for further bioavailability studies.

Graphical Abstract