Praziquantel efficacy in mice infected with PZQ non‐susceptible S. mansoni isolate treated with artemether: parasitological, biochemical and immunohistochemical assessment

Abstract

Based on the fact that artemether (ART) affects immature schistosomes and that the effect of praziquantel (PZQ) mainly targets mature schistosomes, this work investigates the possible enhanced efficacy of PZQ in combination with ART in mice harboring a PZQ non-susceptible Schistosoma mansoni isolate. Associated schistosomal, inflammatory, hepatic histopathological changes have been investigated by examining the tissue markers expressing apoptosis using FAS (CD95), anti-apoptosis (Bcl2) and angiogenesis [vascular endothelial growth factor (VEGF)]. A batch of Swiss albino mice infected with a PZQ non-susceptible (EE10) S. mansoni isolate was divided into 12 groups. Animals of the first group were left without treatment as infected controls, while groups 2-6 received PZQ in increasing doses. The animals of group 7 received ART in double doses. Those comprising groups 8-12 received combined therapy of PZQ and ART in the same doses and at the same timings postinfection (PI) as those belonging to groups 2-6. Parasitological parameters, liver function, and histopathological and immunohistochemical studies of FAS, Bcl2 and VEGF antibodies were assessed. Combined administration of ART and PZQ reduced the ED(50) (the dose at which the worm burden was decreased by 50%) of PZQ. Typical granulomas were not seen in animals treated with ART alone and combined with PZQ, with least expression of FAS and VEGF and increased expression of Bcl2. The minimal histopathological changes recorded in mice treated with both ART and PZQ could be related to a synergistic/additive effect of ART, markedly reducing the intensity of infection. Improved liver function tests support the less severe histopathological changes under the influence of this treatment protocol. This study encourages human trials especially in areas where malaria is not endemic, and differing combination doses should be investigated in view of the antagonistic effect noticed with some dose regimens.

Changes in Liver Cell Apoptosis after Vaccination by Schistosomulae Antigen and/or Artesunat Treatment in Murine Schistosoma Mansoni

“…But in group H immunized by SLAP+IL12 then treated by ART 3 w post infection showed -ve reaction to Bcl-2 (similar to the reaction achieved by the control normal group), this can be explained by the prophylactic effect of SLAP +IL12 in addition to ART when taken early in schistosomiasis infection [62[. This in agreement with Botros et al [3] who recorded that any reduction in apoptosis was accompanied by an increase in Bcl-2 expression in all treated groups. This was explained by the fact that Bcl-2 expression (antiapoptosis) is known to possess protective properties against oxidative damage.…”

“…Its low cost, safety and efficacy against adult worms of all schistosome species led to its widespread use [2]. Appearance of PZQ-resistant strains may put the drug out of use [3]. Moreover, PZQ fails to prevent re-infection and has minor activity against immature worms [4], which can result in low cure rates in areas where schistosomiasis is hyper endemic [5].…”

Modelling approaches to predict and evaluate schistosomiasis immunization utilizing SEA loaded on chitosan nanoparticles via liver tissue differentiation and angiogenesis

“…18). These findings are supported by the results of Botros et al [63] who reported that the VEGF immunoexpression in liver of S. mansoni-infected mice showed high expression of proliferating endothelial blood vessels. Apparently FCA alone had no specific role in our vaccination experiment, as emphasized by our results (Fig.…”

Elimination of Schistosoma mansoni in infected mice by slow release of artemisone

“…Therefore, improved results are expected to derive from a combination therapy using PZQ and an artemisinin. Experiments in mice reveal an additive effect of artemisinin and PZQ in S. mansoni infection (Botros et al., 2010) and in hamsters infected with S. japonicum (Utzinger et al., 2001). However, treatment of infected human patients with the combinations in endemic areas did not improve the performance of PZQ probably because certain worm stages were not exposed simultaneously to the two drugs (Praticò et al., 2014, Saeed et al., 2016).…”