Tissue Egg Counts Research Articles

The interaction of Schistosoma mansoni infection with diabetes mellitus and obesity in mice

Human schistosomiasis is one of the most prevalent parasitic diseases worldwide. Various host factors can affect the host–parasite interactions. Therefore, the aim of the present work was to determine the parasitological, histopathological, biochemical, and immunological status of Schistosoma mansoni-infected hosts with metabolic disorders to identify the underlying possible mechanisms of these comorbidities. The study animals were divided into four groups. Group I represented the control groups, namely, the normal control group, the S. mansoni-infected control group, and the noninfected type 1 diabetes (T1DM), type 2 diabetes (T2DM), and obesity groups. The mice of the other three groups underwent induction of T1DM (Group II), T2DM (Group III) and obesity (Group IV) before being infected with S. mansoni. All mice were subjected to body weight measurement, blood glucose and insulin assessment, parasitological evaluation of adult worm count, tissue egg count and intestinal oogram. Histopathological and immunohistochemical study using anti-glial fibrillary acidic protein (GFAP) in hepatic stellate cells (HSCs) and image analysis of Masson’s trichrome-stained liver sections using ImageJ (Fiji) software were carried out. Additionally, immunological analysis of tumour necrosis factor (TNF) beta, interleukin-5 (IL-5), IL-10, Forkhead box P3 (FOXP3) and pentraxin 3 (PTX3) levels besides biochemical study of total lipid profile were evaluated. The present study revealed a significant increase in the adult worm count and tissue egg output in the obesity group compared to the infected control group. The oogram of counted eggs showed prevalence of immature eggs in T1DM group, while T2DM and obese groups showed prevalence of mature eggs. The fibrosis area percentage showed significant increase in T2DM and obese groups while it was decreased in T1DM group in comparison to infected control group. Our data also showed significant increase in the levels of TNF-β, IL-5, PTX3 in T1DM, T2DM and obesity groups in comparison to infected control group, whilst the levels of FOXP3 and IL-10 were increased in the infected groups in comparison to their noninfected controls. Moreover, infected T1DM, T2DM and obesity groups showed higher blood glucose and lipid profile in comparison to the infected control group. However, these parameters were improved in comparison to their noninfected controls. In sum, induction of T2DM and obesity increased tissue egg counts, mature egg percentage, and fibrosis density, while schistosome infection induced changes in the lipid profile and blood glucose levels in infected diabetic and obese groups and impacted favorably insulin levels in obese mice. By better understanding the complexities of host–parasite interactions, efforts to reduce the burden of these debilitating diseases can be improved.

Praziquantel-encapsulated niosomes against Schistosoma mansoni with reduced sensitivity to praziquantel.

Introduction: Praziquantel (PZQ) is the only commercially available drug for schistosomiasis. The current shortage of alternative effective drugs and the lack of successful preventive measures enhance its value. The increase in the prevalence of PZQ resistance under sustained drug pressure is, therefore, an upcoming issue.Objective: To overcome the tolerance to PZQ using nanotechnology after laboratory induction of a Schistosoma mansoni isolate with reduced sensitivity to the drug during the intramolluscan phase.Materials and methods: Shedding snails were treated with PZQ doses of 200 mg/kg twice/ week followed by an interval of one week and then repeated twice in the same manner. The success of inducing reduced sensitivity was confirmed in vitro via the reduction of cercarial response to PZQ regarding their swimming activity and death percentage at different examination times.Results: Oral treatment with a single PZQ dose of 500 mg/kg in mice infected with cercariae with reduced sensitivity to PZQ revealed a non-significant reduction (35.1%) of total worm burden compared to non-treated control mice. Orally inoculated PZQ- encapsulated niosomes against S. mansoni with reduced sensitivity to PZQ successfully regained the pathogen’s sensitivity to PZQ as evidenced by measuring different parameters in comparison to the non-treated infected animals with parasites with reduced sensitivity to PZQ. The mean total worm load was 1.33 ± 0.52 with a statistically significant reduction of 94.09% and complete eradication of male worms. We obtained a remarkable increase in the percentage reduction of tissue egg counts in the liver and intestine (97.68% and 98.56%, respectively) associated with a massive increase in dead eggs and the complete absence of immature stages.Conclusion: PZQ-encapsulated niosomes restored the drug sensitivity against laboratory- induced S. mansoni adult worms with reduced sensitivity to PZQ.

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 newdrug 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 6weeks' 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 200mg/kg bw (II), treated with Fig leaves extract dose of 400mg/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 againstS. 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.

Effect of celecoxib against different developmental stages of experimental Schistosoma mansoni infection

Due to the high prevalence of schistosomiasis and the wide use of praziquantel solely for mass drug administration to control the disease, there is a great concern about the potential emergence of reduced susceptibility strains. This, together with the concern that praziquantel is ineffective against juvenile worms highlight the importance of developing an alternative anti-schistosomal drug. Using nonsteroidal anti-inflammatory drugs against schistosome infection is considerable. The present study evaluated the effect of oral administration of five days celecoxib regimen (20 mg/kg/day) against different developmental stages of Schistosoma mansoni infection. This regimen induced significant reduction in worm burden, tissue egg count, individual female fecundity and the mean percentage of immature and mature eggs with increased mean percentage of dead eggs. More importantly, celecoxib was more potent than praziquantel in all these parasitological parameters (except in the worm burden when given against the adult stage where the difference was statistically non-significant). Scanning and transmission electron microscopy of the adult worms revealed severe tegumental damage, laceration of the muscular layers and oedema of the syncytial layer. There was disruption of the testicular, ovarian and vitelline glandular tissues with signs of apoptosis and abnormalities of the spermatozoa and the oocytes. Additionally, celecoxib induced reduction in the number and the size of the hepatic granulomata and also amelioration of the hepatic tissue pathology.

An Insight into the Potential Parasitological Effect ofSchistosoma mansoniAntigens in Infected Mice: Prophylactic Role of Cercarial Antigen

Schistosomiasis is a multifactorial disease that includes environmental, behavioral, parasitic, vector, and host factors. This study aimed to assess the protective effect of single and polyvalent antigens from cercarial antigen preparations (CAPs), soluble worm antigen preparations (SWAPs), and soluble egg antigens (SEAs) which were used as candidate vaccines in an experimental model of Schistosoma mansoni-infected mice. The efficiency of the antigens was tested by determining their effects on fecal egg count, egg viability analysis, and tissue egg counts. Histological and morphometric analyses of granulomas in liver and intestine tissues were performed. In the present study, all immunized groups showed a significant reduction in the average fecal egg count and tissue egg load compared with infected mice. The most substantial reduction in fecal egg count was observed in the combined vaccinated group (23.23 ± 3.2). The group vaccinated with CAP before infection showed the highest reduction in tissue egg load (liver and intestine: 85.22 and 91.70%, respectively). Immunized animals showed a highly significant reduction in the numbers of hepatic granulomas compared with the infected non-immunized group. In conclusion, combining these different antigens (CAP, SWAP, and SEA) augments the protective immunity compared with other immunized groups.

Bevacizumab as a potential anti-angiogenic therapy in schistosomiasis: A double-edged, but adjustable weapon.

Investigating the anti-angiogenic effect of bevacizumab on chronic schistosomiasis mansoniin atrial to hinder the Schistosome-induced angiogenesis and porto-systemic shunting complications. The immunohistochemical expression of CD34, VEGF-R1, PCNA and α-SMA (angiogenesis markers) was analysed in the lung, liver and gastrointestinal junctions of chronic Smansoniinfected mice after intraperitoneal injection of bevacizumab. The effect of prolongedadministration of bevacizumab with praziquantel was also assessed through parasitic load, protective index, granuloma and fibrous tissue evaluation. A regression in thevascular activity and microvascular density wasobserved in the infected mice after receivingbevacizumab. They had a significantly less VEGF-R1, PCNA, CD-34 and α-SMA expression in comparison to the infected untreatedmice. The least tissue egg count was reported in mice received bevacizumab for 6weeks (Mean=27120). However, they had persistent liver granulomas, and massively amalgamated fibrosis. Interestingly, the least faecal egg and tissue worms counts (Mean=112, 13.4), and thehighest protection index (39.26) were reported in mice received bevacizumab for 3weeks, with marked granuloma, and fibrous tissue resolution. Bevacizumabhas a promising protective effect against the Schistosoma-induced angiogenesis. As an adjuvant to praziquantel, it is important to adjust the appropriateduration of administration that achieves the best schistosomicidal effect without impeding granuloma and fibrous tissue resolution.

Biological and proteomic studies of Schistosoma mansoni with decreased sensitivity to praziquantel

The impact of the laboratory induced Schistosoma mansoni with decreased PZQ sensitivity on the biological performance of its different developmental stages and the concomitant structural changes of adult worms’ total proteins were investigated. PZQ exposed snails showed stoppage of cercarial shedding for eight weeks followed by progressive significant reduction of cercarial production along four successive weeks. In the vertebrate host, in comparison to Schistosoma mansoni susceptible isolate, inoculated cercariae with decreased PZQ sensitivity led to an evident decrease in male to female ratio associated with significant reduction in tissue egg counts and significant increase in dead egg percentage. Significant reduction in the fecundity was also determined. Interestingly, eggs from adult worms with decreased PZQ sensitivity showed two unique features as they found to be smaller and more spherical in addition to the observation of hourglass shaped miracidium in about 10% of the detected mature eggs. Proteomic analysis of adult worms with decreased sensitivity to PZQ using mass spectrometry revealed up-regulation of Ca2+ ATPase 2 and Hsp70. This study can point to the increase incidence of the neuroschistosomiasis due to the small size eggs of Schistosoma mansoni with reduced PZQ sensitivity. These worms can also impact the epidemiology in the field. The study can also provide help to elucidate underlying potential molecular mechanisms of resistance that could lead to possible strategies to reverse drug resistance.

Qualitative and quantitative methods for estimating Spirorchiidiasis burden in sea turtles

Infection by blood flukes Hapalotrema mistroides and Neospirorchis sp. (Digenea: Spirorchiidae) has been recently reported in Caretta caretta (Linnaeus, 1758) in the Mediterranean Sea. Observations of post mortem lesions are generally used to assess disease severity, and few attempts have been made to standardize the evaluation of the parasitic burden from tissue egg counts. Faeces and spleen homogenates of 105 loggerheads from the northwestern Adriatic Sea were submitted to a sedimentation-flotation technique for the research of spirorchiid eggs; molecular techniques were used for unequivocal identification. Egg quantification for positive faeces and spleen samples was achieved using a modified McMaster method. Spleen samples were also submitted to quantification through the only method cited in the literature for similar purposes, which involves preventive chemical digestion. Correlations between splenic counts obtained from the two different methods and between faecal and splenic egg burdens were calculated using Spearman's rho test. Concordance between studies on eggs in faeces and spleen tissue was also calculated. Eggs of H. mistroides and Neogen-11 were found in spleen and faecal samples. Strong correlations were found between splenic egg burdens calculated from the two methods for H. mistroides, demonstrating that the modified McMaster method can be used for quantification. A multiplying factor must be used before drawing comparisons, as egg burdens are higher in value when measured after chemical digestion. High concordance was obtained from a qualitative examination of faeces and spleen tissue of H. mistroides, showing that copromicroscopic examination can be used for in vivo diagnosis. As weak correlations were found between faecal and splenic egg counts, faecal burden cannot be regarded as indicative of disease severity. For Neogen-11, low concordance was found between faeces and spleen tissue, likely reflecting lower levels of egg embolization in organs.

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

Background and study aim: The target for a schistosoma vaccine or treatment is the reduction in morbidity. The hope for vaccine or treatment is to decrease worm burden and egg pathology to the least percentage, this work aimed to compare between schistosomulae lung stage antigen (SLAP) with and without adjuvant (IL12) and artesunate (ART) treatment regarding their effect especially on liver cell apoptosis. Materials and Methods: Schistosomulae were extracted from the lungs 18 days post infection with Schistosoma mansoni. Eight groups of Swiss albino mice (8 mice each group) were classified as follows: Group A was served as healthy control group, group B was infected with ±100 cercariae and served as infected control group, group C infected then treated by artesunate monotherapy (400mg/kg) single oral dose 6 weeks post infection. ,group D was immunized with 50ug of SLAP then infected,, group E infected then treated by artesunate monotherapy (400 mg/kg) single oral dose 3 weeks post infection, group F was immunized with 50ug of SLAP and 100ug of IL12,group G was immunized with 50ug of SLAP and 100ug of IL12 then infected then treated by artesunate monotherapy (400 mg/kg) single oral dose 6 weeks post infection, group H was immunized with 50ug of SLAP and 100ug of IL12 infected then treated by artesunate monotherapy (400 mg/kg) single oral dose 3 weeks post infection. All groups vaccinated with SLAP vaccine were given booster doses after2 weeks of the first doses. Seven weeks post infection mice were sacrificed for parasitological parameters measurements (worm burden, tissue egg load and oogram pattern), histopathological and immunohistochemical studies using P53 and Bcl-2 markers for determination of liver cells apoptosis. Results and Conclusion: Apoptosis detected by immunohistochemical studies is a good evaluation method. IL12 potentiated the protective effect of SLAP vaccine, ART 3 weeks post infection is better than 6 week post infection in reduction of liver pathology and apoptosis. The combination of both (SLAP+IL12+ART 3 weeks post infection) is the best regarding the reduction of tissue egg count, worm burden, hepatic immunopathology and apoptosis.

Schistosoma mansoni: In vivo evaluation of Phyllanthus amarus hexanic and ethanolic extracts

Human schistosomiasis is an important neglected tropical disease caused by blood flukes of the genus Schistosoma and is responsible for more than 280,000 deaths annually. Treatment for this disease relies currently on a single drug, praziquantel (PZQ). Concerns regarding PZQ resistance and insensitivity of juvenile schistosomes have increased the interest in resorting to medicinal plants for alternative drug therapies. This study aimed to perform an in vivo schistosomicidal activity evaluation of crude hexanic (HE) and ethanolic (EE) extracts obtained from Phyllanthus amarus in mice infected with Schistosoma mansoni (BH strain). Mice were treated orally with a single dose of 100 or 250 mg/kg, on two different infection periods, 30 and 45 days post-infection (dpi). Parameters such as worm recovery, faecal egg count, intestinal tissue egg count and liver histopathology were evaluated. Treatment against young adult (30 dpi) and adult (45 dpi) worms were more effective compared to the control group treated with PZQ. At a concentration of 250 mg/kg (30 dpi) EE showed a 54.4% female reduction and a 61.2% total worm reduction whilst at a concentration of 100 mg/kg (45 dpi) HE showed a 40.6% female worm reduction and a 45.3% total worm reduction. Histopathological examination showed a granuloma decrease in both number and size for groups treated with 250 mg/kg of HE (45 dpi) or EE (30 or 45 dpi). From these results, it can be concluded that both hexanic and ethanolic extracts have antischistosomal activities, however, act differently according to the parasites age. The schistosomicidal activity results in groups treated 30 days post infection is extremely important since praziquantel does not show activity against the juvenile forms of Schistosoma.

Insulin growth factor inhibitor as a potential new anti-schistosoma drug: An in vivo experimental study

Background and objectiveTyrphostin “AG1024” is an insulin growth factor-1 receptor (IGF-1R) inhibitor that displayed an effect on the viability of larval and mature schistosomes in vitro. We sought to investigate the possible in vivo role of AG1024 as a potential new anti-Schistosoma drug against immature and adult stages of Schistosoma mansoni and its effect on the degree of hepatic fibrosis and insulin pathway. MethodsThe study included a control non-infected group and 5 groups of S. manosoni-infected CD-1 albino mice (20 mice each) assigned to treatment as follows: vehicle-treated, early AG1024, 30μg/100μl DMSO, IP for 10days started 30days post-infection (dpi), early praziquantel (PZQ), 500mg/kg orally for 2days (30dpi), late AG1024 (60dpi), and late PZQ (60dpi). All mice were sacrificed 12 weeks post-infection. Parasitological, chemical and histopathological parameters were studied. Immunohistochemistry of TGF-β and GLUT4 in liver sections was done to further evaluate the effect of AG1024 on the degree of hepatic fibrosis and insulin signaling pathway, respectively. ResultsEarly administration of AG1024 (30dpi) resulted in significant reduction of hepatic and intestinal tissue egg count with a reduction of 79.99% and 89.1% respectively. Late administration of AG1024 (60dpi) led to 77.78% reduction of intestinal eggs count; however, hepatic egg count wasn’t reduced significantly. No reduction in worm burden was recorded for both administration regimens. Both regimens lead to significant decrease of both ALT and AST, mean hepatic granuloma diameter but an increase in fibrosis percentage (65.2% and 55% respectively). Both early and late treatment with AG1024 showed a significant increment of TGF-β expression by 71.4% and 39.3%, respectively (p<0.0001) compared to PZQ-treated and infected non-treated groups. Hepatic GLUT4 expression was significantly decreased compared to infected non-treated group (p<0.001) and the corresponding PZQ-treated group. ConclusionEarly AG1024 administration induced more significant results compared to early PZQ with a promising activity against egg production and subsequent reduction of tissue egg load rather than direct schistosomicidal effect; however, it induced granuloma fibrosis, TGF-β expression, and disrupted the insulin signaling pathway.

Effect of phenyl vinyl sulphone cysteine protease inhibitor on Schistosoma mansoni: in vitro and in vivo experimental studies.

The present work aimed to study the effect of phenyl vinyl sulphone (PVS), a CPI, on different stages of Schistosoma (S.) mansoni in an in vitro culture study and in experimentally infected mice, compared to PZQ. As regards the in vitro study, different concentrations of PVS (1, 2, 4, 6, 8 and 10µg/ml) and PZQ (1µg/ml) were assessed by % worm mortality for schistosomula and adults, and hemoglobin degradation by schistosomula. In vivo study included 8 groups of mice. Intraperitoneal PVS, subgroup (a), and oral PZQ, subgroup (b), were assessed at different durations post infection (pi); at 1, 3, 5 and 7weeks pi (groups I, II, III and IV, respectively). Infection, PVS, PZQ, and normal control groups (groups V-VIII) were included. The anti-schistosomal effects of PVS were assessed by parasitological, histopathological and haematological parameters. In in vitro study, PVS had a schistosomicidal effect in a concentration and time dependent manner, PVS showed 100% schistosomula mortality at day 2 and 92% adult worm mortality at day 5. Furthermore, PVS decreased hemoglobin degradation by schistosomula. In in vivo study, PVS showed a decrease in total worm burden and tissue egg load in intestine and liver with an increase in number of dead ova in intestine of mice. Furthermore, PVS resulted in a decrease in number, size and cellularity of hepatic granulomas and an increase in hemoglobin concentration.PVS was better than PZQ in reducing each of tissue egg count in intestine at 5 and 7weeks pi, and hepatic granuloma size at 3, 5 and 7weeks pi. These results suggest that PVS can be a promising chemotherapeutic agent in Schistosoma mansoni infection.

Schistosoma mansoni cercarial elastase (SmCE): differences in immunogenic properties of native and recombinant forms.

The Schistosoma mansoni cercarial elastase (SmCE) has previously been shown to be poorly immunogenic in mice. However, a minority of mice were able to produce antibodies against SmCE after multiple immunizations with crude preparations containing the enzyme. These mice were partially protected against challenge infections of S. mansoni. In the present study, we show that in contrast to the poor immunogenicity of the enzymatically active native form of SmCE derived from a crude preparation (cercarial transformation fluid), immunization of CBA/Ca mice with two enzymatically inactive forms, namely purified native SmCE or a recombinant SmCE fused to recombinant Schistosoma japonicum glutathione S-transferase (rSmCE-SjGST), after adsorption onto aluminum hydroxide adjuvant, induced specific anti-SmCE immunoglobulin G (IgG) in all mice within 2 weeks of the second immunization. The IgG antibody response to rSmCE-SjGST was mainly of the IgG1 subclass. These results suggest that inactive forms of the antigen could be used to obtain the optimum immunogenic effects as a vaccine candidate against schistosomiasis. Mice immunized with the rSmCE-SjGST on alum had smaller mean worm burdens and lower tissue egg counts when compared with adjuvant alone- and recombinant SjGST-injected controls. The native SmCE was antigenically cross-reactive with homologous enzymes of Schistosoma haematobium and Schistosoma margrebowiei.

Repositioning of chlorambucil as a potential anti-schistosomal agent

As parasites and cancer cells share many lifestyle and behavioral resemblances, repositioning of anti-cancerous agents as anti-parasitic is quite trendy, especially those sharing the same therapeutic targets. Therefore, the current study investigated the in vitro efficacy of ascending concentrations of chlorambucil (0.5–20μg/ml) against adult Schistosoma mansoni worms, over 72h. Additionally, its in vivo effects against the different developmental stages of the worm were assessed, after an oral dose of 2.5mg/kg/day for five successive days, through evaluating the worm load reduction and worms' morphological alterations and oogram changes. In addition to tissue egg count, a histopathological study of the liver was conducted. In vitro, chlorambucil demonstrated noticeable anti-schistosomal effects in the form of progressive reductions of the worms' viability in a dose dependent manner. Complete worm death was achieved at 72h incubation with 5μg/ml drug concentration. In vivo, chlorambucil induced a significant reduction in the total worm load against all developmental stages. Its highest impact was evident against the juvenile stage, where it induced 75.8% total worm load reduction, and 89.2% and 86.7% intestinal and hepatic egg counts reduction, respectively, along with ogram alterations. Besides, it induced significant shortening of both male and female worms and promoted an amelioration of hepatic histopathology. Results show that chlorambucil possesses favorable in vitro and in vivo anti-schistosomal activity. The highest in vivo efficacy was against the juvenile stage of S. mansoni, significantly superior to praziquantel, with extended potency to the adult stage. Further studies are recommended for chlorambucil target verification and to enhance its therapeutic efficacy.

Protective capacity of cercarial transformation fluid alone or in combination with crude cercarial antigen against challenge infections of Schistosoma mansoni in mice.

Schistosomiasis is the second major parasitic disease in the world after malaria. It affects 201.5 million cases in Africa alone. The aim of this research was to explore alternative vaccination strategies against experimental schistosomiasis mansoni. We assessed the effect of cercarial transformation fluid (CTF) singly and in combination with crude cercarial antigen (CCA) using alum as an adjuvant. The combined antigens gave the best results, as evidenced by a significant reduction in the worm load (62.07%), tissue egg count (78.16%, 86.46%) in liver and intestine respectively, and hepatic granuloma size (29.96%). Scanning electron microscopy revealed changes in the tegument, in the form of roughness and appearance of vesicles and furrows between the tegumental tubercles. Also, resorption of the ventral sucker and dimples replacing its spines were observed. The female tegument was irregular and its posterior end showed loss of spines and sensory bulbs. Moreover, there was a significant decrease in liver enzymes (alanine transaminase (ALT) and aspartate transaminase (AST)) compared to infected control mice. A significant elevation in CD4+T-lymphocytes, denoting amelioration of the immune status, in mice that received combined antigens was also observed. It can be concluded that combined antigens demonstrate potential as a vaccine against Schistosoma mansoni.

Antischistosomal activity of Mirazid in experimental schistosomiasis mansoni: exploring the controversy

Background Mirazid (MZD) was licensed in Egypt for treatment of schistosomiasis in the year 2002; the drug gained much attention experimentally and clinically, with conflicting views on its efficacy. Objective The study aimed to evaluate MZD anti-schistosomal activity in an animal model at a selected dose. Materials and methods Swiss albino mice (n=36) were infected with Schistosoma mansoni and divided into two equal groups of 18 mice each: group 1 was the nontreated infected control group given only the vehicle; gourp 2 was infected and treated with MZD at a dose of 500 mg/kg for 5 days per os 7 weeks postinfection. Efficacy of the drug was assessed parasitologically with fecal egg counts evaluated every other day until the animal was euthanized at 1, 2, and 4 weeks post-treatment (WPT); worm burden, tissue egg count and oogram pattern were studied at 1, 2, and 4 WPT. Results MZD reduced fecal egg counts in infected mice (69.6%) and reduced total worm load (71.9%) and tissue egg counts in the intestine and the liver (66 and 77.4%, respectively) at 4 WPT. The drug changed oogram pattern with progress of treatment. Conclusion MZD has moderate antischistosomal activity in animal models.

Evaluation of the in vivo effect of ivermectin on Schistosoma mansoni in experimentally-infected mice

Objective: To evaluate the effect of ivermectin on mice experimentally infected with Schistosoma mansoni. Methods: Ivermectin was given to mice 42 days p.o. in two treatment regimens: a single dose of 25 mg/kg or the same dose for two consecutive days. Results: In both regimens, there were significant reductions in female worms, hepatic tissue egg count and early immature ova, in addition to significant reductions in the count and size of hepatic granuloma. The same dose for two consecutive days resulted in significant reductions in male, total worms, and intestinal tissue egg load. In both regimens, scanning electron microscopy revealed tegumental alternations as bleb formation, erosion and necrosis more evident with the double dose. In addition, high dose showed extensive erosions of male worms with destruction of the gynaecophoric canal. In females, marked destruction of the tegumental surface was extending to both ventral and oral suckers. Conclusions: Ivermectin has promising anti-schistosomal effects. However, further research is needed to test the effect of ivermectin on schistosomiasis especially in combination with other antischistosomal agents, to avoid any possible resistance from monotherapy.

Impairment of intestinal barrier and secretory function as well as egg excretion during intestinal schistosomiasis occur independently of mouse mast cell protease-1

Deposition of Schistosoma mansoni eggs in the intestinal mucosa is associated with recruitment of mucosal mast cells (MMC) expressing mouse mast cell protease-1 (mMCP-1). We investigated the involvement of mMCP-1 in intestinal barrier disruption and egg excretion by examining BALB/c mice lacking mMCP-1 (Mcpt-1(-/-)). Tissue and faecal egg counts from 6 weeks until 12 weeks post-infection (w p.i.) revealed no differences between wild type (WT) and Mcpt-1(-/-)mice. Using chamber experiments on ileal tissue revealed that at 8 w p.i., the epithelial barrier and secretory capacity were severely impaired, whereas no difference was found between WT and Mcpt-1(-/-)mice in this respect. However, a fragmented distribution of the tight junction (TJ) protein occludin, but not of claudin-3 or ZO-1, was observed in WT mice at 8 w p.i., while no changes in TJ integrity were seen in Mcpt-1(-/-)mice. Therefore, we conclude that in contrast to the situation in Trichinella spiralis-infected mice, in schistosomiasis, mMCP-1 is not a key mediator in egg excretion or impairment of the intestinal barrier. The marked decrease in ileal secretory capacity during S. mansoni egg excretion suggests that the mechanisms facilitating the passage of schistosoma eggs through the gut wall are directed more particularly at the epithelial cells.

Synthesis of Substituted Pyrimidinedione Derivatives as Potential Schistosomicidal Agents

A novel series of substituted tetrahydropyrimidinediones has been synthesized and evaluated for their schistosomicidal activity both in vitro and in vivo using praziquantel as a therapeutic control. All the tested compounds except compounds (4), (6) and (7a) showed in vitro schistosomicidal activity, however only compound (9) showed in vivo activity in Swiss strain albino mice as evidenced by significant reduction in worm load , tissue egg count , liver granuloma number and size, and histopathological study of the liver. Moreover, electron microscopy scanning of adult S. mansoni recovered from treated animals with compound 9 revealed tegumental changes. These data point to 2-(2,6-dioxo-1,2,3,6- tetahydropyrimidin-4-yl)isoindoline-1,3-dione (9) as a promising new antischistosomal agent. Keywords: Tetrahydropyrimidinediones, Schistosomicidal activity, Praziquantel

Decreased basal non-insulin-stimulated glucose uptake by diaphragm in streptozotocin-induced diabetic mice infected with Schistosoma mansoni

It had been suggested that chronic exposure to Schistosoma mansoni prevents the onset of Th1-mediated diseases such as diabetes mellitus. The present study was carried out on four groups of mice: (1) control group, (2) group infected with S. mansoni, (3) group injected with streptozotocin to induce diabetes, and (4) group infected and then 3 months postinfection injected with streptozotocin. No differences were detected between the infected non-diabetic and infected diabetic groups regarding worm burden, tissue egg count, and oogram. At the same time, results showed a reducing effect of S. mansoni infection on the rate of glucose uptake by the diaphragm with reduction in glycogen content of soleus muscle. This an important issue since skeletal muscle is the primary site for insulin-stimulated glucose disposal. In conclusion, because of the detected depressed peripheral glucose uptake by the diaphragm, the protecting effect of helminths infection in diabetes should be reconsidered, to be able to devise therapeutic strategies for the treatment of autoimmune diseases.