Schistosomal Granuloma Research Articles

The hepatic extramedullary hematopoiesis during experimental murine Schistosomiasis mansoni.

Many years ago, our research group has demonstrated extramedullary hematopoiesis in the peripheral zone of murine hepatic schistosomal granulomas. In the present study, we revisit this phenomenon using new technical and conceptual approaches. Therefore, newborn mice were percutaneously infected by Schistosoma mansoni cercariae and euthanized between 35- and 60-days post infection. Liver samples were submitted to histopathology and immunohistochemical analyses. Cells under mitosis and/or expressing Ki67 demonstrated the proliferation of hematopoietic cells both around the parasite’s eggs trapped in the liver and around hepatic vessels. After 50 days post infection, proliferating cells at different levels on differentiation were located preferentially in the peripheral zone of the granulomas, around the vessels and inside the sinusoids. The presence of acidic and sulfated glycoconjugates, reticular fibers and the absence of fibronectin characterized the microenvironment for attraction and maintenance of hematopoiesis. Some neutrophils secreted MMP9 from the earliest points of infection, indicating degradation of the extracellular matrix in regions of histolysis and a possible chemoattraction of hematopoietic stem cells to the liver. Fall-3+ cells and Sca-1+ cells indicated that early hematopoietic progenitors could be mobilized to the liver. Groups of vWF+ megakaryocytes suggest chemoattraction of these cells and/or migration, proliferation, and differentiation of very immature progenitors to this organ. The increase of blood vessels and extramedullary hematopoiesis in this environment, where markers of immature hematopoietic and endothelial cells have been identified, points to the possibility of the presence of progenitors for endothelial and hematopoietic cells in the liver during the infection. There is also the possibility of concomitant migration of more differentiated hematopoietic progenitors, that proliferate and differentiate in the liver, and the occurrence of angiogenesis caused by inflammation or release of ovular antigens that stimulate the activation and proliferation of endothelial cells. Altogether, these data increase knowledge about a murine model that is of interest for investigating the pathology of the schistosomiasis and also the dynamics of hematopoiesis.

Changing our view of the Schistosoma granuloma to an ecological standpoint.

Schistosomiasis, a neglected parasitic tropical disease that has plagued humans for centuries, remains a major public health burden. A primary challenge to understanding schistosomiasis is deciphering the most remarkable pathological feature of this disease, the granuloma - a highly dynamic and self-organized structure formed by both host and parasite components. Granulomas are considered a remarkable example of how parasites evolved with their hosts to establish complex and intimate associations. However, much remains unclear regarding life within the granuloma, and strategies to restrain its development are still lacking. Here we explore current information on the hepatic Schistosoma mansoni granuloma in the light of Ecology and propose that this intricate structure acts as a real ecosystem. The schistosomal granuloma is formed by cells (biotic component), protein scaffolds, fibres, and chemical compounds (abiotic components) with inputs/outputs of energy and matter, as complex as in classical ecosystems. We review the distinct cell populations ('species') within the granuloma and examine how they integrate with each other and interact with their microenvironment to form a multifaceted cell community in different space-time frames. The colonization of the hepatic tissue to form granulomas is explained from the point of view of an ecological succession whereby a community is able to modify its physical environment, creating conditions and resources for ecosystem construction. Remarkably, the granuloma represents a dynamic evolutionary system that undergoes progressive changes in the 'species' that compose its community over time. In line with ecological concepts, we examine the granuloma not only as a place where a community of cells is settled (spatial niche or habitat) but also as a site in which the functional activities of these combined populations occur in an orchestrated way in response to microenvironmental gradients such as cytokines and egg antigens. Finally, we assert how the levels of organization of cellular components in a granuloma as conventionally defined by Cell Biology can fit perfectly into a hierarchical structure of biological systems as defined by Ecology. By rethinking the granuloma as an integrating and evolving ecosystem, we draw attention to the inner workings of this structure that are central to the understanding of schistosomiasis and could guide its future treatment.

Hepatic myofibroblasts derived from Schistosoma mansoni-infected mice are a source of IL-5 and eotaxin: controls of eosinophil populations in vitro.

BackgroundHepatic myofibroblasts are relevant for pathogenesis of S. mansoni infection. In normal liver, these perisinusoidal cells are quiescent, express the lipocyte phenotype, and are located in the Disse’s space, being the major site of vitamin A storage. When activated, they convert to myofibroblasts and contribute to granulomatous and diffuse liver fibrosis. In the present work, we observed that myofibroblasts obtained from granulomatous periovular inflammatory reactions in schistosome-infected mice (GR-MF) produce in vitro immunomodulatory cytokines for eosinophil activation: IL-5 and eotaxin.Methods and resultsThe secretory activity of GR-MF was detected after TGF-β and IL-13 stimulation using 2D and 3D cell culture systems. In a mixed co-culture system using GR-MF with hematopoietic bone marrow cells from infected mice, we observed eosinophil survival that was dependent upon IL-5 and eotaxin, since antibodies against this cytokines decreased eosinophil population, as measured by eosinophil peroxidase activity.ConclusionThese results indicate that GR-MF may contribute to maintenance of local eosinophilia in schistosomal hepatic granulomas, and can function as immunoregulatory cells, besides their role in production of fibrosis.Electronic supplementary materialThe online version of this article (doi:10.1186/s13071-015-1197-3) contains supplementary material, which is available to authorized users.

Schistosome infection-derived Hepatic Stellate Cells are cellular source of prostaglandin D2: Role in TGF-β-stimulated VEGF production

Hepatic Stellate Cells (HSCs) play a crucial role in pathogenesis of liver inflammation and fibrosis. During chronic liver injury, HSCs lose vitamin A and transform into myofibroblastic cells. In schistosomal granulomas, these activated HSCs are called GR-HSCs. Schistosomal-triggered hepatic fibrogenesis has TGF-β as the most potent fibrogenic stimulus, that also controls gene expression of the angiogenic molecule VEGF in HSCs. COX-dependent production of prostaglandins (PGs) also play role in angiogenic processes. Besides angiogenic roles, prostanoids control immunomodulation of Schistosoma mansoni infection. Specifically, schistosoma-derived PGD2 has emerged as a key parasite regulator of immune defense evasion, while no role is still established to host PGD2. Therefore, the aim of this work is to investigate the ability of GR-HSCs to synthesize COX-derived PGD2 and a potential role of this prostanoid in VEGF production by GR-HSCs in vitro. Here, we confirmed that GR-HSCs express COX-2, which displayed perinuclear localization. While unstimulated GR-HSCs produce basal levels of PGD2, TGF-β stimulation besides increasing COX2- mRNA levels, enhanced synthesis/secretion of PGD2 in GR-HSCs supernatant. Moreover, GR-HSCs-derived PGD2 mediate VEGF production by TGF-β-stimulated GR-HSCs, since the pre-treatment with HQL-79, an inhibitor of hematopoietic PGD synthase inhibited both PGD2 synthesis and VEGF secretion by TGF-β-stimulated GR-HSCs. All together, our findings show an autocrine/paracrine activity of GR-HSCs-derived PGD2 on TGF-β-induced VEGF production by GR-HSCs, unveiling a role for PGD2 as important regulator of HSCs activation in hepatic granulomas from schistosome infected mice.

Schistosoma prevalence in appendicitis.

Schistosomiasis is a waterborne trematode with numerous subtypes affecting different areas of the body. Rob Ferreira Hospital is located in an endemic area for schistosomiasis in the Lowveld region of South Africa. We set out to determine the prevalence of Sch istosoma in appendicitis. From 2009 to 2013, all appendix samples removed in theatre were reviewed. A total of 304 cases were retrieved. Viable ova, calcified ova, or schistosomal granulomas was considered proof of exposure. Thirty-one out of the 304 cases revealed evidence of schistosomal exposure, equating to 10.2 %. A prevalence of more than 10 % is truly significant seeing as how a delayed diagnosis can lead to serious complications, or how a misdiagnosis can result in unnecessary and often protracted treatment with harmful drugs.

Assessment of mefloquine in-vivo efficacy on juvenile and adult stages of Schistosoma haematobium (Egyptian strain)

Background The large-scale use of praziquantel might result in selection of drug-resistant parasites. Hence, there is an important need to develop new antischistosomal compounds. Objective This study aimed for assessment of antischistosomal properties of an antimalarial drug, mefloquine (MFQ), on juvenile and adult Schistosoma haematobium worms. Materials and methods Infected hamsters were divided into two main groups, I and II, each subdivided into (a) and (b) subgroups. Groups Ia and IIa received 200 mg/kg MFQ as single oral dose, 49 and 82 days postinfection, respectively. Groups Ib and IIb served as untreated controls, respectively. Ten days later, animals were killed. Parasitological assessment (worm burden, tissue egg load, and oogram pattern), histopathological examination, and scanning electron microscopy were performed to evaluate MFQ efficacy. Results MFQ treatment of the juvenile group Ia resulted in considerable worm burden reductions of 75.9, 69.6, and 88.6% for male, female, and coupled worms, respectively. In the treated adult group IIa, the corresponding results were 24.8 and 95% for male and coupled worms, respectively. Separate female worms were detected only in the treated groups. In group IIa treated animals, MFQ also had an observed but statistically insignificant effect on tissue egg load and oogram pattern. Schistosomal granuloma area, diameters, and numbers were insignificantly decreased. Tegumental changes of treated worms in the form of shrunken deformed tegument, loss or flattening of tubercles, furrows, and blebbing were observed. Conclusion Results concluded by this study elucidate promising MFQ antischistosomal efficacy on both juvenile and adult stages of S. haematobium with more evident effect on juvenile forms, which enforces the potential use of MFQ as an effective antischistosomal drug.

Expression of IFN‐γ, IL‐4, and IL‐17 in cutaneous schistosomal granuloma

Cutaneous schistosomal granuloma (CSG) is a rare dermatological disease, the clinical and histopathological features of which are well defined. Although a panoramic picture of its immunopathogenesis in humans is not yet available, it is believed to be induced by T helper1 (Th1), Th2, or Th17 cytokines in animals. This study evaluated the expression of different types of Th cytokines, including Th1 cytokine interferon-γ (IFN-γ), Th2 cytokine interleukin-4 (IL-4), and Th17 cytokine IL-17, in human CSG. This study included nine patients with CSG. Dermatological examinations were conducted in all subjects. Skin biopsy specimens were stained with hematoxylin and eosin (H&E). Immunohistochemical examination was performed using three monoclonal anti-human antibodies against IFN-γ, IL-4, and IL-17 to evaluate Th1, Th2, and Th17 cytokines, respectively. The most common site of CSG manifestation was the paraumbilical area, which was affected in 66.7% of patients. All lesional skin biopsy specimens revealed multiple dermal granulomas surrounding schistosomal eggs. Positive immunoreactivity for IFN-γ, IL-4, and IL-17 was present in dermal inflammatory infiltrate in 88.9, 11.1, and 88.9% of subjects, respectively. There were statistically significant negative correlations between the duration of disease and both IFN-γ and IL-17 (P≤0.05), and a statistically significant positive correlation between IFN-γ and IL-17 (P≤0.05). This study suggests that CSG is formed by the action of both Th1 (IFN-γ) and Th17 (IL-17) cytokines, which have been shown to be directed against the schistosomal egg to induce a cell-mediated immune response.

Schistosoma mansoni granuloma in late evolutive phase, in a case of tumoral form in man

Authors describe human schistosomal granuloma in late chronic phase, from the morphological and evolutionary viewpoints. The study was based on a histological analysis of two fragments obtained from a surgical biopsy of peritoneum and large intestine of a 42-year-old patient, with a pseudotumoral form mimicking a peritoneal carcinomatosis associated to the schistosomiasis hepatointestinal form. Two hundred and three granulomas were identified in the pseudotumor and 27 in the intestinal biopsy, with similar morphological features, most in the late chronic phase, in fibrotic healing. A new structural classification was suggested for granulomas: zone 1 (internal), 2 (intermediate) and 3 (external). Regarding granuloma as a whole, we may conclude that fibrosis is likely to be controlled by different and independent mechanisms in the three zones of the granuloma. Lamellar fibrosis in zone 3 seems to be controlled by matrix mesenchymal cells (fibroblasts and myoepithelial cells) and by inflammatory exudate cells (lymphocytes, plasmocytes, neutrophils, eosinophils). Annular fibrosis in zone 2, comprising a dense fibrous connective tissue, with few cells in the advanced phase, would be controlled by epithelioid cells involving zone 1 in recent granulomas. In zone 1, replacing periovular necrosis, an initialy loose and tracery connective neoformation, housing stellate cells or with fusiform nuclei, a dense paucicellular nodular connective tissue emerges, probably induced by fibroblasts. In several granulomas, one of the zones is missing and granuloma is represented by two of them: Z3 and Z2, Z3 and Z1 or Z2 and Z1 and, ultimately, by a scar.

Schistosoma haematobium, une cause rare de compression médullaire

Human schistosomiasis is the second endemic disease after malaria. About 200 millions people are concerned, particularly in Africa, South America and Asia. Schistosomal spinal cord compression is under reported in Africa and not well known. Authors present the case of a 10-year-old boy with no suggestive past-medical story, admitted for spinal cord compression. MRI shows tumor like intra dural lesion. Schistosomal granuloma was found after lesion removal by posterior approach. Treatment was completed by praziquantel. Controversies of the treatment are presented.

Role of Leukotrienes on Protozoan and Helminth Infections

Leukotrienes (LTs), formed by the 5-lipoxygenase-(5-LO-) catalyzed oxidation of arachidonic acid, are lipid mediators that have potent proinflammatory activities. Pharmacologic or genetic inhibition of 5-LO biosynthesis in animals is associated with increased mortality and impaired clearance of bacteria, fungi, and parasites. LTs play a role in the control of helminth and protozoan infections by modulating the immune system and/or through direct cytotoxicity to parasites; however, LTs may also be associated with pathogenesis, such as in cerebral malaria and schistosomal granuloma. Interestingly, some proteins from the saliva of insect vectors that transmit protozoans and secreted protein from helminth could bind LTs and may consequently modulate the course of infection or pathogenesis. In addition, the decreased production of LTs in immunocompromised individuals might modulate the pathophysiology of helminth and protozoan infections. Herein, in this paper, we showed the immunomodulatory and pathogenic roles of LTs during the helminth and protozoan infections.

Diffuse pseudotumoral cerebral Schistosomiasis mansoni: a new form of presentation

AbstractWe describe two cases of cerebral schistosomiasis mansoni with multiple pseudotumoral lesions diagnosed by stereotactic brain biopsy. Both patients presented with seizures and one with left visual impairment. Imaging techniques revealed multiple brain lesions involving cerebral parenchyma, pons, cerebellum and thalamus. Brain histopathologic specimens of the patients showed multiple schistosomal granulomas in distinct evolutive phases. All patients presented good clinical response to treatment and reversion of the brain lesions. This new form of neuroschistosomiasis must be considered by those who work in the endemic area for Schistosoma mansoni.

Gastrointestinal basidiobolomycosis: an emerging fungal infection causing bowel perforation in a child

Basidiobolomycosis is an unusual fungal skin infection that rarely involves the gastrointestinal (GI) tract. We report a 10-year-old boy diagnosed as suffering GI basidiobolomycosis after being misdiagnosed first as suffering intestinal malignancy then schistosomiasis. The patient presented with fever, abdominal pain, vomiting, abdominal tenderness and rigidity with marked blood eosinophilia. Abdominal ultrasonographic and computed tomographic scans revealed a large caecal mass. Biopsy of the mass showed transmural granulomatous inflammation interpreted as schistosomal granuloma, ruling out lymphoma. The patient's condition deteriorated despite anti-schistosomal therapy. Emergency surgery was then performed, and caecal perforation was found. The mass was excised; cultures were negative and histopathological examination was suggestive of schistosomal granuloma. The mass recurred 3 weeks post-operatively. Second-opinion histopathological examination diagnosed Basidiobolus ranarum infection. Treatment with itraconazole produced marked improvement, with diminution of the mass. B. ranarum was unequivocally identified in the archival formalin-fixed and paraffin-embedded (FFPE) tissue by PCR. This case emphasizes the need to consider GI basidiobolomycosis in children presenting with fever, abdominal mass and eosinophilia, especially those complicated by bowel perforation.

Giant schistosomal granuloma mimicking rectum neoplasia: case report

We report the case of a young man from an area where schistosomiasis is endemic, in the state of Pernambuco, who presented with hemorrhage. Initially diagnosed as rectum neoplasia, subsequent investigation demonstrated rectal giant schistosomal granuloma. The diagnoses and clinical aspects of the case are discussed in this study.

Effect of praziquantel prolonged administration on granuloma formation around Schistosoma japonicum eggs in lung of sensitized mice

Schistosomiasis remains a major public health problem and it is an immune disease. The schistosome egg is the primary parasite factor responsible for the overt disease. The eggs release the soluble antigen, which induces intensive tissue reaction, a granulomatous reaction to the eggs. If granuloma formation could be suppressed, overt disease might not develop. Praziquantel is an effective antischistosomal drug especially for adult worms. However, whether praziquantel has a suppressing effect on granuloma formation around schistosome eggs directly remains unclear. The purpose of the present study was to investigate the effect of praziquantel, especially administered persistently, on granuloma formation around Schistosoma japonicum eggs in the lung of sensitized mice. Thirty-six mice were divided into three groups averagely. Group A was a control group. First, the mice were injected with schistosomal eggs hypodermically in abdomen, and 10 days later injected with schistosomal eggs intravenously via a tail vein. Group B was a praziquantel short administration group. In addition to the injections of schistosomal eggs as the same of Group A, the mice were administered with praziquantel in a daily dose of 300 mg/kg for 3 days, from 1 day before the intravenous injection of the eggs. Group C was a praziquantel prolonged administration group. In addition to the injections of schistosomal eggs as the same of Group A, the mice were administered with praziquantel in a daily dose of 150 mg/kg for 5 days weekly until the mice were sacrificed. Three mice of each group were sacrificed on days 7, 14, 28, and 56, respectively after the intravenous injection of the eggs, and the lung tissues were fixed with formalin and the slices were HE stained. The granulomas containing eggs in their centers were selected, and 25-30 granulomas from the animals of each group were measured at each time period. The mean areas of egg granulomas of each group were calculated, and the neutrophilic granulocytes, eosinocytes, lymphocytes, fibroblasts, and macrophages within the egg granulomas were counted. The mean numbers of them of each group were calculated. All the data of each group were analyzed and compared statistically. On day 56 after the intravenous injection of the eggs, the mean area of schistosomal egg granulomas in group B was (227.4 ± 728.0) × 10(3) μm(2), less than that of [(297.9 ± 153.3) × 10(3) μm(2)] in group A, and the suppression rate was 23.7% (P < 0.05). On days 7, 14, 28, and 56, the mean areas of schistosomal egg granulomas in group C were (575.8 ± 155.6) × 10(3) μm(2), (310.5 ± 854.0) × 10(3) μm(2), (267.7 ± 513.3) × 10(3) μm(2), and (214.9 ± 446.4) × 10(3) μm(2), respectively, significantly less than those of [(692.7 ± 232.6) × 10(3) μm(2), (439.4 ± 165.0) × 10(3) μm(2), (385.7 ± 129.3) × 10(3) μm(2), and (297.9 ± 153.3) × 10(3) μm(2)] in group A. The suppression rates were 16.9%, 29.3%, 30.6%, and 27.9%, respectively (P values <0.05). On day 56, the mean numbers of neutrophilic granulocytes were 11.4 ± 5.0 in group A and 5.2 ± 3.1 in group C, respectively, with the suppression rate of 54.4% in group C (P < 0.05). On day 56, the mean numbers of eosinocytes within the egg granulomas were 2.3 ± 2.0, 0.1 ± 0.3, and 0.3 ± 0.6 in groups A, B, and C, respectively, with the suppression rate of 95.7% in group B and 87.0% in group C (P values <0.05). On day 56, the mean numbers of macrophages within egg granulomas were 14.3 ± 6.9 in group C, compared with 18.6 ± 8.2 in group A, the suppression rate was 23.1% (P < 0.05). On day 56, the mean numbers of fibroblasts within the egg granulomas were 6.6 ± 4.4 and 5.8 ± 2.6 in groups B and C, respectively, and compared with 14.3 ± 7.8 in group A, the increasing extents decreased by 53.8% and 59.4%, respectively (P values <0.05). Therefore, the administration of praziquantel, especially the prolonged administration, can suppress the formation of schistosomal egg granulomas, including reduction in the areas of granulomas and suppression of the inflammatory cells and the hyperplasia of fibroblasts within granulomas.

Interplay of cysteinyl leukotrienes and TGF-β in the activation of hepatic stellate cells from Schistosoma mansoni granulomas

Hepatic stellate cells (HSCs) have a critical role in liver physiology, and in the pathogenesis of liver inflammation and fibrosis. Here, we investigated the interplay between leukotrienes (LT) and TGF-β in the activation mechanisms of HSCs from schistosomal granulomas (GR-HSCs). First, we demonstrated that GR-HSCs express 5-lipoxygenase (5-LO), as detected by immunolocalization in whole cells and confirmed in cell lysates through western blotting and by mRNA expression through RT-PCR. Moreover, mRNA expression of 5-LO activating protein (FLAP) and LTC 4-synthase was also documented, indicating that GR-HSCs have the molecular machinery required for LT synthesis. Morphological analysis of osmium and Oil-Red O-stained HSC revealed large numbers of small lipid droplets (also known as lipid bodies). We observed co-localization of lipid droplet protein marker (ADRP) and 5-LO by immunofluorescence microscopy. We demonstrated that GR-HSCs were able to spontaneously release cysteinyl-LTs (CysLTs), but not LTB 4, into culture supernatants. CysLT production was highly enhanced after TGF-β-stimulation. Moreover, the 5-LO inhibitor zileuton and 5-LO gene deletion were able to inhibit the TGF-β-stimulated proliferation of GR-HSCs, suggesting a role for LTs in HSC activation. Here, we extend the immunoregulatory function of HSC by demonstrating that HSC from liver granulomas of schistosome-infected mouse are able to release Cys-LTs in a TGF-β-regulated manner, potentially impacting pathogenesis and liver fibrosis in schistosomiasis.

Effect of anluohuaxian tablet combined with γ-IFN on schistosomal liver fibrosis

The therapeutic effects of anluohuaxian tablet combined with gamma-IFN on schistosomal liver fibrosis and its mechanism were studied in a murine model and clinical cases of schistosomal liver fibrosis. Fifty Kunming mice were randomly divided into 5 groups: normal control group, infection control group, anluohuaxian tablet-treated group, gamma-IFN-treated group and combined treatment (anluohuaian tablet+gamma-IFN) group. Pathologic changes in liver, including hepatic pigmentation and the size of schistosomal egg granuloma, were observed by HE staining after treatment for 8 weeks. The expression of the type I and collagen III, and TIMP-1 was detected by immunohistochemistry. TGF-beta1 mRNA expression was examined by real-time fluorescent quantitative PCR. Sixty patients with schistosomal liver fibrosis were divided into treatment group and control group. The patients in treatment group were treated with anluohuaxian tablet in combination with gamma-IFN for 6 months. Before and after treatment, the changes of symptoms and signs, liver function, serum liver fibrosis indexes and imaging indexes were observed. The results showed that as compared with infection control group, all forms of treatments relieved the hepatic pathological injury with apparently diminished size of schistosomal egg nodules and decreased percentage of pigmentation (P<0.05). Furthermore, the expression of collagen I and III, TIMP-1, and TGF-beta1 mRNA in combined treatment group was significantly decreased as compared with anluohuaxian tablet-treated and gamma-IFN-treated groups (P<0.05). In the clinical observation, the serum liver fibrosis indexes, the portal vein width as well as the spleen thickness was significantly reduced in treatment group as compared with control group (P<0.05). It was concluded that the combined use of anluohuaxian tablet with gamma-IFN in schistosomal liver fibrosis could protect liver function, alleviate liver fibrosis, and could be used as a choice in treating patients with schiatosomal liver fibrosis.

Cerebellar Schistosomiasis: A Case Report with Clinical Analysis

The authors report here a rare case of cerebellar schistosomiasis identified by pathological diagnosis, lacking extracranial involvement. The clinical symptoms included headache, dizziness, and nausea. Studies in blood were normal and no parasite eggs were detected in stool. Computed tomography of brains showed hypodense signal, and magnetic resonance imaging showed isointense signal on T1-weighted images, hyperintense signal on T2-weighted images, and intensely enhancing nodules in the right cerebellum after intravenous administration of gadolinium. A high-grade glioma was suspected, and an operation was performed. The pathologic examination of the biopsy specimen revealed schistosomal granulomas scattered within the parenchyma of the cerebellum. The definitive diagnosis was cerebellar schistosomiasis japonica. A standard use of praziquantel and corticosteroid drugs was applied, and the prognosis was good. When the pattern of imaging examinations is present as mentioned above, a diagnosis of brain schistosomiasis should be considered.

IL‐4 and reactive oxygen species are elevated in Egyptian patients affected with schistosomal liver disease

Schistosomiasis is a chronic liver disease that is endemic in rural areas of Egypt. Some patients may acquire infection and develop minimal complications while others may develop severe complications and progress to portal hypertension and cirrhosis especially if co-infected with hepatitis C virus (HCV). The reasons for this are poorly understood. Previous studies suggested an independent role for Th2-biased cytokine responses to schistosomal antigens in persistent hepatic fibrosis and development of complications. Studies in murine schistosomiasis demonstrated that the development of fibrosis requires the production of the profibrotic cytokines such as IL-4. On the other hand, previous studies have suggested that reactive oxygen species may play an important role in schistosomal granuloma formation and disease progression To investigate the status of the profibrotic IL-4 cytokine, oxidative stress (as indicated by thiobarbituric acid reactive substances), the antioxidants enzymes catalase and red blood cells glutathione content in a cohort of Egyptian patients affected with schistosomal hepatic disease and or hepatitis C infection. The current study included four groups: patients with isolated HCV infection (HCV), comprised of 22 patients aged (mean +/- SD) 51.3 +/- 4.7 years; patients with HCV and schistosomal hepatic fibrosis (SHF) (Co-infected patients), comprised of 22 patients aged 49.6 +/- 4.0 years, patients with pure chronic schistosomiasis comprised of 22 patients with chronic schistosomiasis aged 53.7 +/- 5.6 years and a control group, comprised of 22 control subjects aged 48.5 +/- 5.4 years. Thiobarbituric acid reactive substances (TBARS), Catalase activity and red blood cells glutathione contents were determined using chemical methods while plasma IL-4 was determined using a commercially available ELISA kit. A significant reduction in erythrocyte catalase activity in patients with isolated HCV infection, isolated SHF and those co-infected with SHF and HCV compared with the control group was found (P < 0.05). A similar pattern was found regarding erythrocyte glutathione content. Conversely TBARS level were significantly increased in patients with HCV, SHF and mixed groups compared with the control group (P < 0.05). Plasma IL-4-values were significantly increased in the three groups compared to the control subjects group. Furthermore, plasma IL-4 was significantly higher in patients with isolated SHF and those with SHF + HCV compared to the HCV alone patient group. Plasma IL-4 also correlated positively with portal vein diameter in SHF and SHF . HCV groups. (r = 0.54 and P < 0.05). Furthermore when all patients were analysed collectively, there was a positive correlation between plasma IL-4 and right lobe of the liver and plasma TBARS concentration. Schistosomal infection triggers a Th2 type immune response as indicated by the high plasma IL-4. It also triggers an increase in reactive oxygen species levels. These effects especially IL-4 lead to more reduction in the level of antioxidants enzymes (that may be already compromised in malnourished schistosomal patients) with the resultant disease progression and development of complications.

Clinical and pathological diagnosis of cerebral schistosomal granuloma

目的 对脑型血吸虫病肉芽肿的临床和病理诊断进行分析.方法 将患者手术中切除的脑部病变组织,采用快速或常规石蜡包埋切片,HE染色,显微镜下观察脑血吸虫病肉芽肿的病理形态.结果 组织切片中见血吸虫病肉芽肿,急性期,中央为新鲜虫卵肉芽肿,周围大量嗜酸性粒细胞浸润,形成嗜酸性肉芽肿.慢性期为退变虫卵,其外为增生的胶质细胞,上皮样细胞和异物巨细胞,形成假结核样结节,以及纤维组织增生、胶元化.结论 血吸虫病肉芽肿是脑型血吸虫病临床表现的病理基础,以血吸虫卵为中心形成的肉芽肿病变,是脑型血吸虫病的主要病理学形态特点。

Morbidity due to Schistosoma mansoni - Entamoeba histolytica coinfection in hamsters (Mesocricetus auratus)

Data on Schistosoma mansoni-Entamoeba histolytica coinfection are scarce in the literature. In the present study, hamsters that had been infected for 70 days with Schistosoma mansoni (LE strain) were inoculated via the portal vein with two strains of trophozoites of Entamoeba histolytica: ICB-EGG (highly virulent) and ICB-RPS (non-virulent). The most evident result of coinfection was increased morbidity and mortality, in comparison with either of the infections alone. Histologically, there were no evident signs of interaction between these two infections. The morphological findings of schistosomal granuloma and amoebic abscesses in the liver were similar to those seen in the respective single-infection controls. However, there was severe wasting of the animals with both infections and greater numbers of amoebic lesions in their livers. The results obtained indicated that schistosomiasis aggravates the course of amoebiasis in hamsters.