الفهرس 
IntroductionOnly 14 pages are availabe for public view
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Abstract
In 2015, it was estimated that about 66.5 million people (53.2 million teen-agers and 13.3 million adults) received PZQ. PZQ is most effective against adult worms and requires an intact immune response to be fully efficient. Nevertheless its efficacy. Unfortunately PZQ does not provide resistance against re-infection especially during childhood and adolescence.On the other hand, Ro (15-5458), the acridine derivative of class 9-acridanone-hydrazones (Ro) pervious study showed anti-schistosomal prophylactic effects against juvenile schistosomes through the inhibition of the expression of parasite genes. It is noteworthy that praziquantel is not effective at this stage of infection.Considering that antigens of juvenile schistosomes especially those of lung stage are potent inducers of protective immunity, the finding that receive great attention during radiation-attenuated larval vaccine which is the most successful experimental vaccine available till now. In addition, several evidences confirmed the existence of anti-schistosome immunity both in humans and experimental animals who managed to express a mixed rather than polarized TH1/TH2response. This has encouraged the research for the development of a vaccine that eliminates the parasite or ameliorates the resultant pathogenesis. Pathology is mainly the result of host’s immune response to parasite’s eggs. In most cases, the host-parasite relationship reaches a compromise or balanced immune response that permits the persistence both parties.Taking all together, the present study investigates the progression of schistosomiasis mansoni in C57BL/6 mice subjected to multiple rounds of light infection and Ro treatment targeting the lung stage parasite. Immune regulatory and histopathological consequences as well as adult worm tegumental topology were assessed as disease outcome criteria.In the present study, six weeks old female C57BL/6 mice were infected trice with sixty Schistosoma mansoni cercariae divided in three equal doses given at 6 week intervals and treated with 100 mg/kg Ro-15-5458 administered orally at day 6 of each infection (treated group; T). Control mice included: naive (N) received no infection or treatment, infected trice without treatment (re-infected; R) and infected once without treatment (prolonged infection; P). Result are summarized in the following: T group showed significant increase in serum IFN-γ, IL-4 and TGF-β1 levels at week 6 followed by a gradual significant decrease at weeks 12 and 18 post initial infections, all compared to N controls. However, both R and P groups showed gradual significant increase in all tested cytokines with time, compared to N controls.The immune regulation in T group was reflected on the worm burden that showed a complete elimination of the parasite at week 6 post-initial infection that followed by 50% and 20% reduction in the subsequent week 12 and 18 post-initial infection, respectively. Moreover the oviposition capability of adult worms that showed altered ova counts and oogram i.e. reduced numbers of ova and a shift to immature and dead eggs especially at weeks 12and 18. Moreover, histopathological investigation of liver sections from T group revealed a complete absence of egg-granulomatous inflammation at week 6 followed by minor sized ones at weeks 12 and 18, compared to R group. On the other hand, P group showed somehow similar pattern to R but to a lesser extent. On the other hand, the outcome of treatment regime was monitored at week 18 by assessing the tegumental topography of adult worms recovered from mice by scanning electron microscopy. T group showed the highest tegumental damage illustrated in the presence of multiple cracks, blebbing and loss of spines especially in female worms. In conclusion, Ro treatment has enhanced the immune regulation mechanisms on the cellular level to the favor of the host. This may recommend the need for repeated Ro chemotherapy with repeated infection and this study help the future development of an anti-pathology vaccine based on candidate antigens presented during this experimentally-induced immune response.