Antischistosomal effects of Ficus carica leaves extract and/or PZQ on Schistosoma mansoni infected mice.

Currently, praziquantel (PZQ) is the only drug of choice used for treatment of human schistosomes because of its safety and broad-spectrum activity. It is reported that the repeated chemotherapy is complicated by the occurrence of drug resistance to schistosomiasis. So there is an urgent need to develop new drug combinations therapy. The current study aimed to evaluate antischistosomal activity of F. carica leaves extract alone or in combination with PZQ on Schistosoma mansoni infected mice. Mice were experimentally infected with Schistosoma mansoni and orally administrated 6 weeks' post-infection with Fig leaves extract and/or PZQ. Schistosoma mansoni (S. mansoni)-infected mice were separated into four groups: untreated (I), treated with PZQ in dose of 200 mg/kg bw (II), treated with Fig leaves extract dose of 400 mg/kg bw (III). Group IV was treated with dose of Fig leaves extract-PZQ as in groups II and III, respectively. The effect was detected parasitologically using ova count technique and oogram pattern in intestine and liver. The greatest antischistosomal effect was achieved using orally administered Fig leaves extract-PZQ as indicated by total worm burden, tissue egg count and oogram pattern. Fig leaves extract + PZQ induced the therapeutic efficacy over the PZQ dose alone in intestine and liver as shown by a complete absence of immature worms, a very high reduction in the total numbers of tissue egg load (59.81% vs. 61.43% & 67.96% vs. 73.46%), mature eggs (37.86 ± 1.4 vs. 34.14 ± 1.9) and increasing in the total number of dead eggs (62.14 ± 1.4vs.67.29 ± 1.76). The results suggested the curcumin in combination with PZQ as a strong schistosomicidal regimen against S. mansoni. In addition, F. carica leaves extract is a promising for PZQ potentiating its antischistosomal action in animal model infected with S. mansoni. Therefore, the present work conclude that combined treatment has a synergetic effect and could be more promising in the management of schistosomiasis.

Comparative ultrastructural observations of the Egyptian schistosomes: Schistosoma mansoni and Schistosoma haematobium.

An ultrastructural topography has been made to the tegumental architectures of two Egyptian schistosomes namely S. mansoni and S. haematobium hosted in a model animal namely Cricentus auratus. The distribution of sensory papillae on the oral sucker were arranged in one circle around the rim in addition to some papillae in upper part of inner zone in male, female S. mansoni and in male S. haematobium. The differences in the types of papillae, their distribution and shape of ridges on various parts of the body surface which are quite specific for each species was studied. Also, the ventral tegument of female's displays larger and more numerous sensory papillae. Both ciliated and non-ciliated papillae were observed in this work which makes a link with another species of schistosome S. japonicum. Another characteristic feature in this study is unique of male of S. haematobium, the extensive formation of ridges and transformation to microvilli in the posterior region in males. These finding may provoke further study of schistosomes hosted in animal model for more detailed investigation at the molecular level.

Cholinergic components of nervous system of Schistosoma mansoni and S. haematobium (Digenea: Schistosomatidae).

A comparison has been made for the first time between the cholinergic components of the nervous system of important human digeneans namely Schistosoma mansoni and Schistosoma haematobium from infected hamster (Cricentus auratus) in Egypt. In each parasite, the central nervous system consists of two cerebral ganglia and three pairs of nerve cords (ventral, lateral, and dorsal) linked together by some transverse connectives and numerous ring commissures. Peripheral cholinergic innervation was detected in oral and ventral suckers and in some parts of female reproductive system in both species, but there were some differences. The possible functions of some of these nervous components are discussed.

Transmission electron microscopic observations on ultrastructural alterations in Schistosoma mansoni adult worms recovered from C57BL/6 mice treated with radiation-attenuated vaccine and/or praziquantel in addition to passive immunization with normal and vaccinated rabbit sera against infection.

Although the current treatment of schistosomiasis relies largely on praziquantel (PZQ), it has not been successful in significantly reducing the overall rate of disease cases, one of the suggested reasons being the inevitable resistance to PZQ. Previous studies showed that radiation-attenuated vaccine provides protection against Schistosoma mansoni in a host of various species. In the present study, we evaluated the effect of various vaccination strategies in C57BL/6 mice, including single or multiple vaccination strategy, subcurative dose (20 mg/kg) of PZQ, and a combination of single vaccination with subcurative dose of PZQ. Treatment either with subcurative dose of PZQ or with a single vaccination of attenuated cercariae (500 per mouse), caused significant reduction in total worm burden, hepatic, and intestinal ova counts of 43.03, 73.2, and 59.5 and 37.97, 52.02, and 26.3%, respectively. Furthermore, tegumental changes were observed. In multiple vaccinated group, there was an extensive lysis in tegumental layers. High deformations in gastrodermis, testis cells, vitelline cells, and oocytes were recorded. Also, this study is to explore the role of humoral immunity using highly resistant rabbits that had been exposed to three immunizations with ultraviolet (UV)-irradiated cercariae (8000 per rabbit in each immunization), and their sera were tested for their ability to transfer protection. The reduction in challenge worm burden had reached 32.76-43.64% when compared with recipients of normal serum or no serum. The reduction in hepatic and intestinal ova counts reached to 74.4 and 71.08% in group immunized with vaccinated rabbit sera. Swelling and extensive lysis of tegumental layers, gastrodermis lumen, spermatocytes, and deformation of oocytes were recorded with more severity than that recorded in normal rabbit sera group. Our findings recorded that multiple vaccination strategy is the most effective strategy then passive transfer of vaccinated rabbit. This gives guiding in the design the appropriate therapeutic strategy.

Ultrastructural changes of adult Schistosoma mansoni worms recovered from C57BL/6 mice passively immunized with normal and vaccinated rabbit sera in vivo.

The purpose of the study is to explore the role of humoral immunity against Schistosoma mansoni infection in C57BL/6 mice using highly resistant rabbits that had been exposed to three separate immunizations with ultraviolet (UV)-irradiated cercariae (8,000 attenuated cercariae/rabbit in each immunization), and their sera were tested for their ability to transfer protection against S. mansoni challenge. The present study showed the reduction in challenge worm burden had reached 32.76-43.64% when compared with recipients of normal serum or no serum. The surface topography of the worms collected from immunized mice with either normal rabbit sera (NRS) or vaccinated rabbit sera (VRS) revealed severe tegumental alterations, especially in the VRS group. Worms collected from groups that were immunized by NRS or VRS postinfection (200 normal cercariae/mouse) by day 42. Worms from group immunized with NRS showed damage in the tegument, characterized by severe swelling or erosion of tegumental folds, accompanied by changes in tubercles, swelling, shortening, and loss of spines in male worms. The alteration in female tegument was characterized by swelling of tegumental folds, atrophy of ventral sucker, damage of sensory papillae along all the body, severe peeling in some regions, and appearance of few small blebs. VRS induced more severe tegumental damage than NRS in both male and female worms. Severe shrunken vesicles were protruded from the surface between the two suckers. The tegument of the male showed a collapse of tubercles followed by the appearance of vesicles on their surfaces, fusion, erosion, and superficial focal peeling of tegumental folds. In the female worms, severe damage to the oral sucker, the surface between the two suckers, extensive peeling, severe swelling of the tegument, and damage of sensory papillae. In conclusion, the present study support the hypothesis that high levels of antibodies were developed in rabbit sera after multiple exposures to attenuated cercariae of S. mansoni. Furthermore, immunization might have transferred protection against the infection, indicated by severe morphological alterations, a sign of elimination of the worms. Further investigation is being carried out to reveal the molecular mechanisms underlying the transfer of protection.

Structural changes of Schistosoma mansoni adult worms recovered from C57BL/6 mice treated with radiation-attenuated vaccine and/or praziquantel against infection.

Although the current treatment of schistosomiasis relies largely on praziquantel (PZQ), it has not significantly reduced the overall number of disease cases, perhaps due to inevitable resistance to PZQ. Previous studies showed that radiation-attenuated vaccine gives protection levels for Schistosoma mansoni in host various species. In the present study, we evaluated the effect of various vaccination strategies in C57BL/6 mice, including single or multiple vaccination strategy, subcurative dose (20 mg/kg) of PZQ, and a combination of single vaccination with subcurative dose of PZQ. Groups of five mice were sacrificed postinfection in 42 days and schistosomes were collected by perfusion and examined by scanning electron microscopy. Treatment either with subcurative dose of PZQ or with a single vaccination of attenuated cercariae (500 per mouse), caused significant reduction in total worm burden, hepatic and intestinal ova counts 43.03%, 73.2%, 59.5% and 37.97%, 52.02%, 26.3%, respectively. Furthermore, tegumental changes were observed, including severe swelling, fusion of tegumental folds, vesicle formation, and loss or shortening of the spines on the tubercles. However, multiple vaccination strategy resulted in much higher reduction in total worm burden, hepatic and intestinal ova count. However, multiple vaccination strategy resulted in high reduction of worm burden, hepatic and intestinal ova counts 72.5%, 90.7%, 65.79%, respectively, and further causing swollen, disruption of tubercles teguments and erosion, extensive peeling, fusion of tegumental folds. Our findings suggest that multiple vaccination strategy is the most effective strategy to clear schistosomal infection, indicating its potential in guiding the design of appropriate therapeutic strategy against schistosomes.