Immunohistochemical investigations of treatment with Ro 13-3978, praziquantel, oxamniquine and mefloquine in Schistosoma mansoni-infected mice [PublishAheadOfPrint]

To date there is only one drug in use, praziquantel, to treat more than 250 million people afflicted with schistosomiasis, a debilitating parasitic disease. The aryl hydantoin Ro 13-3978 is a promising drug candidate with superior in vivo activity to praziquantel against both adult and juvenile Schistosoma mansoni. Given the drugs' contrasting low activity in vitro, and the timing of its onset of action in vivo, it was postulated that immune-assisted parasite clearance could contribute to the drug's in vivo activity. We undertook histopathological studies to investigate this hypothesis. Infected mice were treated with an effective dose of Ro 13-3978 (100 mg/kg) and were dissected before and after the drugs in vivo onset of action. The veins and livers were excised, paraffin-embedded, sectioned and macrophages (IBA-1), neutrophils (Neutro), B-cells (CD45R) and T-cells (CD3) were stained by immunohistochemistry. For comparison, samples from infected-untreated mice and mice treated with effective doses of praziquantel (400 mg/kg), oxamniquine (200 mg/kg) and mefloquine (100 mg/kg) were examined. At 24 h after treatment with Ro 13-3978, significant macrophage recruitment to the veins was observed, along with a modest increase in circulating B cells and at 48 h, neutrophils and T cells are also present. Treatment with praziquantel and oxamniquine showed a similar pattern of recruitment but with comparatively higher cellular levels, whereas mefloquine treatment resulted in minimal cell recruitment until 3 d post-treatment. Our study sheds light on the immediate immune responses to antischistosomal treatment in mice and provides further insight into immune effector mechanisms of schistosome clearance.

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