Hepatocellular carcinoma associated with chronic Schistosoma mansoni infection in a chimpanzee

Hepatocellular carcinoma associated with chronic Schistosoma mansoni infection in a chimpanzee, estimated to be a 12-year-old and born in West Africa, is reported. The hepatic tumor appeared as a solitary firm nodule, and histological examination revealed well-differentiated hepatocellular carcinoma with a trabecular pattern. Hepatitis B virus and hepatitis C virus infections were excluded by serological testing in that animal. This is the first report of hepatocellular carcinoma in the chimpanzee with schistosomiasis.     

Intermediate host specificity in Schistosoma mansoni

Miracidia of Schistosoma mansoni penetrate into many kinds of snails, but development of normal sporocysts takes place only in certain species of Biomphalaria. Different populations of this snail vary greatly in laboratory infection rates with S. mansoni originating from diverse geographic localities. Cross-exposure experiments show that compatibility factors exist in both snails and parasites. Susceptibility of stocks of Biomphalaria to particular strains of S. mansoni is genetically determined and may be modified by selection in the laboratory. In a compatible snail, the sporocyst develops without host tissue reaction; in incompatible snails the early larvae are rapidly surrounded by amebocytes and fibroblasts, and destroyed. This reaction resembles the generalized host cellular response elicited by any foreign body. An individual snail exposed to many miracidia may have both developing and encapsulated sporocysts side by side within its tissues. The weight of current evidence suggests that elicitation or absence of this cellular response resides in the recognition or nonrecognition of the sporocyst as a foreign body. The sporocyst tegument surface, which forms within a few hours after miracidial penetration, may have a molecular conformation identical with that of the snail, or may be able to bind specific host molecules, so that detection and subsequent encapsulation by host cells are averted. Presuming genetic determination of the sporocyst surface structure and of the host cell detection capability, differing infection rates would result from the particular frequencies of relevant genes in the populations concerned.     

Morbidity associated with Schistosoma mansoni infection in north-eastern Democratic Republic of the Congo

BackgroundReducing morbidity is the main target of schistosomiasis control efforts, yet only rarely do control programmes assess morbidity linked to Schistosoma sp. infection. In the Democratic Republic of Congo (DRC), and particularly in north-eastern Ituri Province, little is known about morbidity associated with Schistosoma mansoni infection. For this reason, we aimed to assess intestinal and hepatosplenic morbidity associated with S. mansoni infection in Ituri Province.Methods/Principal findingsIn 2017, we conducted a cross-sectional study in 13 villages in Ituri Province, DRC. S. mansoni infection was assessed with a Kato-Katz stool test (2 smears) and a point-of-care circulating cathodic antigen (POC-CCA) urine test. A questionnaire was used to obtain demographic data and information about experienced intestinal morbidity. Each participant underwent an abdominal ultrasonography examination to diagnose hepatosplenic morbidity. Of the 586 study participants, 76.6% tested positive for S. mansoni. Intestinal morbidity reported in the two preceding weeks was very frequent, and included abdominal pain (52.7%), diarrhoea (23.4%) and blood in the stool (21.5%). Hepatosplenic morbidity consisted of abnormal liver parenchyma patterns (42.8%), hepatomegaly (26.5%) and splenomegaly (25.3%). Liver pathology (adjusted odds ratio [aOR] 1.20, 95% confidence interval [CI] 1.06–1.37, p = 0.005) was positively and significantly associated with S. mansoni infection. Hepatomegaly (aOR 1.52, 95% CI 0.99–2.32, p = 0.053) and splenomegaly (aOR 1.12, 95% CI 0.73–1.72, p = 0.619) were positively but not significantly associated with S. mansoni infection at the individual level. At the village level, S. mansoni prevalence was positively associated with the prevalence of hepatomegaly and splenomegaly. High-intensity S. mansoni infections were associated with diarrhoea, blood in the stool, hepatomegaly, splenomegaly, and liver parenchyma (C, D, E and F pathology patterns). Four study participants were diagnosed with ascites and five reported hematemesis.Conclusions/SignificanceOur study documents a high burden of intestinal and hepatosplenic morbidity associated with S. mansoni infection status in Ituri Province. The findings call for targeted interventions to address both S. mansoni infection and related morbidity.     

Polymorphism associated with the Schistosoma mansoni tetraspanin-2 gene

A vaccine against schistosomiasis would contribute significantly to reducing the 3-70 million disability-adjusted life years lost annually to the disease. Towards this end, inoculation with the large extracellular loop (EC-2) of Schistosoma mansoni tetraspanin-2 protein (Sm-TSP-2) has proved effective in reducing worm and egg burdens in S. mansoni-infected mice. The EC-2 loop of Schistosoma japonicum TSP-2, however, has been found to be highly polymorphic, perhaps diminishing the likelihood that this antigen can be used for vaccination against this species. Here, we examine polymorphism of the EC-2 of Sm-TSP-2 in genetically unique worms derived from six individuals from Kisumu, Kenya.     

Methionine uptake of larval and adult Schistosoma mansoni;

The uptake of methyl-¹⁴C-methionine by schistosomula, 21 day-old and adult Schistosoma mansoni in vitro has been investigated. Ligation of the adult pharynx and comparison between the kinetics of uptake of schistosomula and adults suggests that methionine is absorbed, in the system described, primarily via the tegument. All stages of the parasite examined absorb methionine by, at least, two kinetically distinguishable systems, one which is saturable and a second which appears to be simple diffusion. The saturable system has relatively low specificity for amino acids but shows no affinity for other classes of compounds. The effects of pH, temperature, metabolic inhibitors, and sodium ion concentration have been examined. The results are discussed with reference to schistosome gut function and also to the differential response to chemotherapy according to age of infection.     

Experimental models of Schistosoma mansoni infection

Experimental models of Schistosoma mansoni infections in mammals have contributed greatly to our understanding of the pathology and pathogenesis of infection. We consider here hepatic and extrahepatic disease in models of acute and chronic infection. Experimental schistosome infections have also contributed more broadly to our understanding of granulomatous inflammation and our understanding of Th1 versus Th2 related inflammation and particularly to Th2-mediated fibrosis of the liver.     

Schistosoma mansoni infection alters co-stimulatory molecule expression and cell activation in asthma

Chronic schistosomiasis induces Th2/T regulatory responses which are able to down-modulate allergic inflammation and asthma. Because co-stimulatory molecules and IL-10 are essential for inducing tolerance, the aim of this study was to determine by flow cytometry, the expression of CD28, CTLA4, CD40L, CD80, CD86, HLA-DR, IL-10 and IL-10 receptor, by mononuclear cells from asthmatic individuals infected with Schistosoma mansoni and compare with non-infected individuals. Peripheral blood mononuclear cells were stained with fluorochrome conjugated antibodies for the expression of co-stimulatory molecules, and for intracellular CTLA4 and IL-10 expression. There was no significant difference in the frequency of T cells expressing CD28 between the two groups. However, the frequency of TCD4⁺ cells expressing CTLA4 and CD40L was higher in infected asthmatics. The frequency of monocytes expressing CD80 and CD86 did not differ between groups, while the expression of HLA-DR and IL-10 receptor was higher on monocytes of infected individuals. Furthermore, monocytes and CD4⁺CD25⁺ cells of infected individuals expressed higher levels of IL-10. We conclude that, besides alternatively-activated monocytes that are, together with CD4⁺CD25⁺ cells, important sources of IL-10, CTLA4 and CD40L expression may also participate in the down-modulation of inflammatory allergic response in S. mansoni-infected asthmatics.     

Neuroinflammatory implication of Schistosoma mansoni infection in the mouse

Schistosomiasis is a parasitic disease due to Schistosoma mansoni. Schistosome infection is known to induce granulomas not only in the spleen, bladder, liver and intestine but also in the brain and spinal cord resulting in severe neuropathological and psychiatric disorders though the interaction between Schistosoma mansoni infection and the nervous system has received on the whole little attention. In the present review it has been discussed recent findings from experimental Schistosoma mansoni infection in mouse nervous system. We show that brain granulomas are associated with a significant alteration in the constitutive levels of nerve growth factor (NGF), a trophic factor playing an essential role in nerve growth and differentiation and in preventing neuronal damages. Animals infected with schistosomes suffered also of increased pain sensitivity which was inhibited by TNF-alpha antibody injections and not by anti-NGF. These findings suggest that the neuropathological dysfunctions in neuroschistosomiasis may be linked to changes in the basal levels and/or activity of neurotrophic factors caused by local formation of granulomas.     

Human resistance to Schistosoma mansoni is associated with IgG reactivity to a 37-kDa larval surface antigen

The aim of this work was to determine whether human resistance to Schistosoma mansoni was associated with increased antibody reactivity to certain larval surface Ag. To this end, young residents of a hyperendemic area were selected for their low or high susceptibility to reinfection after parasitologic cure, and the reactivity of their sera to individual larval surface Ag was determined at different times before and after treatment. The data showed that six Ag: 202, 165, 90 to 92, 85, 72, and 37 kDa are the principal targets on the larva of IgG in the sera of resistant subjects. The comparative study, by immunoblotting and ELISA on purified Ag, of the sera from high and low susceptibility subjects indicates that IgG reactivity toward the 37-kDa Ag may be associated with resistance. This work and ongoing vaccination trials carried out in mice suggest that the 37-kDa Ag may have vaccinating potentials.     

Desmin expression in fibroblasts of murine periovular granuloma during liver Schistosoma mansoni infection

We have studied the expression of the desmin gene, a muscle-specific intermediate filament protein in the granuloma cells of mouse liver infected with Schistosoma mansoni. In situ hybridization using a desmin DNA probe showed that fibroblastic cells in the granuloma strongly expressed desmin mRNAs, while in normal liver these cells did not express this mRNA to a detectable degree. The quantitative analysis of total RNAs demonstrated that the proportion of specific desmin mRNA increased from 14 to 18 weeks after infection and decreased at 20 weeks. The analysis of collagen gene expression indicated that the amount of type III collagen mRNAs was still increasing after 18 weeks from infection; in contrast, the amount of type I collagen mRNAs remained unchanged at that stage. A good correlation was observed between the detection of the specific mRNAs and the detection of both desmin and collagen molecules. Therefore, these data point to a coordinate induction of desmin and collagen gene expression during Schistosomal granuloma formation. They also suggest that the expression of the myofibroblast phenotype involves the induction of both genes.     

Metabonomic investigation of human Schistosoma mansoni infection

Schistosomiasis is a parasitic infection that is endemic in many developing countries in the tropics and subtropics afflicting more than 207 million people primarily in rural areas. After malaria, it is the second most important parasitic infection in terms of socio-economic and public health. Investigation of the host-parasite interaction at the molecular level and identification of biomarkers of infection and infection-related morbidity would be of value for improved strategies for treatment and morbidity control. To this end, we conducted a nuclear magnetic resonance (NMR) based metabonomics study involving a well-characterized cohort of 447 individuals from a rural area in Uganda near Lake Victoria with a high prevalence of Schistosoma mansoni, a species predominantly occurring in Africa including Madagascar and parts of South America. Cohort samples were collected from individuals at five time-points, before and after (one or two times) chemotherapy with praziquantel (PZQ). Using supervised multivariate statistical analysis of the recorded one-dimensional (1D) NMR spectra, we were able to discriminate infected from uninfected individuals in two age groups (children and adults) based on differences in their urinary profiles. The potential molecular markers of S. mansoni infection were found to be primarily linked to changes in gut microflora, energy metabolism and liver function. These findings are in agreement with data from earlier studies on S. mansoni infection in experimental animals and thus provide corroborating evidence for the existence of metabolic response specific for this infection.     

Natural versus drug-induced resistance in Schistosoma mansoni infection

Rodrigo Corrêa-Oliveira, Iramaya Rodrigues Caldas and Giovanni Gazzinelli here focus on the immune response of individuals with natural resistance to schistosomiasis, which differs significantly from that of post-treatment resistant and infected individuals. They suggest that the activation of T helper type 1 (Th1) and Th2 cells is needed for the induction of natural resistance against Schistosoma mansoni infection.     

Toxoplasma infection in male mice alters dopamine-sensitive behaviors and host gene expression patterns associated with neuropsychiatric disease

During chronic infection, the single celled parasite, Toxoplasma gondii, can migrate to the brain where it has been associated with altered dopamine function and the capacity to modulate host behavior, increasing risk of neurocognitive disorders. Here we explore alterations in dopamine-related behavior in a new mouse model based on stimulant (cocaine)-induced hyperactivity. In combination with cocaine, infection resulted in heightened sensorimotor deficits and impairment in prepulse inhibition response, which are commonly disrupted in neuropsychiatric conditions. To identify molecular pathways in the brain affected by chronic T. gondii infection, we investigated patterns of gene expression. As expected, infection was associated with an enrichment of genes associated with general immune response pathways, that otherwise limits statistical power to identify more informative pathways. To overcome this limitation and focus on pathways of neurological relevance, we developed a novel context enrichment approach that relies on a customized ontology. Applying this approach, we identified genes that exhibited unexpected patterns of expression arising from the combination of cocaine exposure and infection. These include sets of genes which exhibited dampened response to cocaine in infected mice, suggesting a possible mechanism for some observed behaviors and a neuroprotective effect that may be advantageous to parasite persistence. This model offers a powerful new approach to dissect the molecular pathways by which T. gondii infection contributes to neurocognitive disorders.     

An ultrastructural study of the effect of parasitism by larval Schistosoma mansoni on the calcium reserves of the host,Biomphalaria glabrata

Summary The tissues of Biomphalaria glabrata contain three types of calcium cells which can be differentiated by their location and the size and number of their contained corpuscles. X-ray analysis has confirmed the presence of calcium and magnesium in the corpuscles. Molluscs containing the larval stages of Schistosoma mansoni at 40 days post infection show disintegration of the calcareous corpuscles in Type-A calcium cells and erosion of the inner surface of the shell.Deceased