الفهرس 
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Abstract
Over the past 25 years, therapy and control of schistosomiasis has come to rely heavily on one drug, praziquantel. Recent reports on the possible development of resistance to praziquantel generated great need to find effective alternatives. Several studies reported the promising antischistosomal properties of a number of antimalarial drugs, and one of which was MFQ. Mefloquine is an already established drug for human use. Thus, the present study was carried to test the in vivo efficacy of MFQ against the Egyptian Schistosoma mansoni strain.
This study was carried on one hundred Swiss strain albino mice. The infected animals were divided into two groups: juvenile (group I) and adult (group II) models. Each mouse was experimentally infected with eighty Schistosoma mansoni cercariae. Group I (Juvenile Infection Model) included 60 mice. Thirty mice served as control (infected, untreated), ten were sacrificed with each corresponding infected treated subgroup. Another thirty mice were treated orally with 400mg/kg MFQ in vehicle 21 days post infection, and were subdivided into three subgroups (a, b, and c) according to the time of sacrifice, which was on the third, seventh and fourteenth days post-treatment respectively. Group II (Adult Infection Model) included 40 mice. Ten mice served as control (infected, untreated), and were sacrificed 49 days post-infection. Thirty mice were treated orally with 400mg/kg MFQ in vehicle, 49 days post infection, and were subdivided into three subgroups (a, b, and c) according to the time of sacrifice which was on the third, seventh and fourteenth days post-treatment. Efficacy of MFQ on experimental schistosomiasis mansoni was assessed in the present work by parasitological and histopathological studies.
The parasitological study included assessment of the worm load, tissue–egg load and changes in the worm morphology under the ordinary light and the electron microscopes. Hepatocardiac perfusion was done for all animals. Recovered schistosomes from the hepatic and mesenteric vessels were counted and sexed. Some juvenile and adult worms were stained with carmine stain for further light microscopic examination to assess the size and morphology of the worms. The remaining worms were fixed for the electron microscopic study. Tissue-egg counting in the liver and intestine was performed. The histopathological study included assessment of the number, size and cellular components of the bilharzial granulomata in both the liver and intestinal tissues. Results were tabulated and statistical analysis was performed.
Assessment of the effect of MFQ showed that the juvenile worm load was significantly reduced by 51.64%, 66.98% and 73.41% by the third, seventh and fourteenth days post-treatment respectively, compared to the untreated mice. As regards the adult model, treated animals showed total worm load reduction by 51.44% on the third day post-treatment, 67.48% on the seventh day post-treatment and 73.30% on the fourteenth day post-treatment. Adult female worm load reduction was 61.67%, 78.63% and 85.73% in the three subgroups. Finally reduction in the coupled worms reached 58.11%, 82.07% and 84.00% respectively. Worm load reduction was statistically significant in all treated subgroups versus the control. Hepatic shift of schistosomes was clearly detected in treated mice since the third day post-treatment in the juvenile and adult models. Hepatic worm load reached a maximum of 95.6% in the treated subgroups. However, it did not exceed 40% of the total worm load in untreated mice.
Hepatic-egg load reduction reached 78.33% and 89% on the seventh and the fourteenth days post-treatment respectively compared to untreated control mice. Intestinal-egg load reduction reached 90.48% by the seventh day post-treatment. Moreover, examination of 100 randomly chosen eggs in the intestinal tissue showed progressive reduction of immature eggs from the third day up to the fourteenth day post-treatment.
The effect of MFQ varied on the perimeter of the juvenile and adult schistosomes. The shape of the worms was clearly affected after treatment. Juvenile and adult Schistosoma mansoni worms showed tegumental irregularities, gut dilatation and non-uniform pigment filling of the gut. Besides, treated adult female schistosomes showed vague ovarian boundaries and abnormal uterine components.
Electron microscopic scanning of the treated juvenile and adult worms showed severe tegumental alterations in the form of several contraction rings, focal swellings, small sized blebbings and adherent host leucocytes. Adult male worms showed loss of spines on their tegumental surface. Transmission electron microscopic examination of adult worms showed tegumental disruption and lysis. Disruption of the nuclear membrane and several areas of lysis were seen in the area of subtegumental and gut epithelial cells.
Histopathological examination of hepatic and intestinal sections from treated mice of adult model showed significant reduction in the number and size of granulomata in the treated subgroups. Several granulomata appeared without eggs in the center, together with invasion of lymphocytes and fibroblasts. Sections of corresponding untreated group showed typical bilharzial granulomata with eggs in the center.
The results of the present study made it obvious that MFQ led reduction in the juvenile and adult worm load, diminished egg production, and altered worm shape and egg compostion. Besides, drug treatment led to smaller number and size of the bilharzial granulomata. Thus, it can be concluded that, MFQ could be valuable for providing an alternative safe antischistosomal agent.