A Bayesian approach to estimate the age-specific prevalence of Schistosoma mansoni and implications for schistosomiasis control.
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ABSTRACT:
SUBMITTER: Raso G
PROVIDER: S-EPMC2756495 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background: The parasitic trematode Schistosoma mansoni is one of the major causative agents of human schistosomiasis, which afflicts 200 million people worldwide. Praziquantel is still the only drug used for schistosomiasis treatment and reduction in drug efficiency has prompting the search for new therapeutic compounds against this disease. Our group has demonstrated that heme crystallization into hemozoin (Hz) within S. mansoni gut is a major heme detoxification route involving lipid droplets in this process and acting as a potential chemotherapeutical target. In the present work, we investigated the effects of the antimalarial quinine (QN) in a murine schistosomiasis model by using a combination of biochemical, cell biology and molecular biology approaches. Methodology/Principal Findings: Treatment of S. mansoni-infected female Swiss mice with daily intraperitoneal injections of QN (75mg/kg/day) from 11th to 17th day after infection decreased not only total, males and females worm burden (46.2 %-51.0 %), eggs production, but also the granulomatous reaction to parasite eggs trapped in the liver. These effects correlated with a significant impairment of Hz production (40%) specifically in S. mansoni females, being parallel to remarkable ultrastructural changes in female worms, particularly in the gut epithelium. Microarray gene expression analysis indicated that QN treatment increased the expression of transcripts related to musculature, protein synthesis and repair mechanisms. Conclusions: The overall significant reduction in several disease burden parameters by QN treatment indicates that interference of Hz formation in S. mansoni is a valid chemotherapeutical target for development of new antischistosomal drugs.
2009-07-13 | GSE14751 | GEO
Project description:Schistosomiasis has been reported in 78 endemic countries and affects 240 million people worldwide. The digenetic parasite Schistosoma mansoni needs fresh water to compete its life cycle. There, it is susceptible to soluble compounds that can affect directly and/or indirectly the parasite's biology. The cercariae stage is one of the key points in which the parasite is vulnerable to different soluble compounds that can significantly alter the parasite's life cycle. Molluscicides are recommended by the World Health Organization for the control of schistosomiasis transmission and Euphorbia milii latex is effective against snails intermediate hosts.We used parasitological tools and electron microscopy to verify the effects of cercariae exposure to natural molluscicide (Euphorbia milii latex) on morphology, physiology and fitness of adult parasite worms. In order to generate insights into key metabolic pathways that lead to the observed phenotypes we used comparative transcriptomics and proteomics.We describe here that the effect of latex on the adult is not due to direct toxicity but it triggers an early change in developmental trajectory and perturbs cell memory, mobility, energy metabolism and other key pathways. We conclude that latex has not only an effect on the vector but applies also long lasting schistosomastatic action. We believe that these results are of interest not only to parasitologists since it shows that natural compounds, presumably without side effects, can have an impact that occurred unexpectedly on developmental processes. Such collateral damage is in this case positive, since it impacts the true target of the treatment campaign. This type of treatment could also provide a rational for the control of other pests. Our results will contribute to enforce the use of E. milii latex in Brazil and other endemic countries as cheap alternative or complement to mass drug treatment with Praziquantel, the only available drug to cure the patients (without preventing re-infection).
| S-EPMC5550001 | biostudies-other
Project description:Background: The parasitic trematode Schistosoma mansoni is one of the major causative agents of human schistosomiasis, which afflicts 200 million people worldwide. Praziquantel is still the only drug used for schistosomiasis treatment and reduction in drug efficiency has prompting the search for new therapeutic compounds against this disease. Our group has demonstrated that heme crystallization into hemozoin (Hz) within S. mansoni gut is a major heme detoxification route involving lipid droplets in this process and acting as a potential chemotherapeutical target. In the present work, we investigated the effects of the antimalarial quinine (QN) in a murine schistosomiasis model by using a combination of biochemical, cell biology and molecular biology approaches. Methodology/Principal Findings: Treatment of S. mansoni-infected female Swiss mice with daily intraperitoneal injections of QN (75mg/kg/day) from 11th to 17th day after infection decreased not only total, males and females worm burden (46.2 %-51.0 %), eggs production, but also the granulomatous reaction to parasite eggs trapped in the liver. These effects correlated with a significant impairment of Hz production (40%) specifically in S. mansoni females, being parallel to remarkable ultrastructural changes in female worms, particularly in the gut epithelium. Microarray gene expression analysis indicated that QN treatment increased the expression of transcripts related to musculature, protein synthesis and repair mechanisms. Conclusions: The overall significant reduction in several disease burden parameters by QN treatment indicates that interference of Hz formation in S. mansoni is a valid chemotherapeutical target for development of new antischistosomal drugs. The perfused adult female worms were incubated with cold RNAlater solution (Ambion) and kept at 4 0C until RNA extraction. Total RNA was extracted using Trizol reagent (Invitrogen) according to the manufacture's instructions. RNA was quantified using Nanodrop ND-1000 UV/Vis spectrophotometer and its quality was assured with Agilent 2100 Bioanalyzer, a micro fluidics-based electrophoresis platform. 1 μg total RNA from each sample was amplified using the T7-RNA polymerase based SuperScript Indirect RNA amplification system (Invitrogen) and subsequently 3 μg of aminoallyl-modified amplified RNA was labeled using Cy3 or Cy5 by indirect labeling (General Electric). Amplification and labeling were done according to manufacturer specifications. The Cy3 and Cy5 labeled samples were then combined, dried and re-suspended in hybridization buffer (50 % formamide, 25 % RNase free water and 25 % Microarray Hybridization buffer 4x) (General Electric). Pools of RNA from worms treated with QN were hybridized against RNA from control worms. In order to ensure the uniformity of data, all experiments were performed using slides from the same printing batch and dyes from the same lot. The same washing protocol was used and immediately after washing we scanned the slides using the same parameters. Technical and biological replicates were performed. Dye swap was employed in order to account for dye biases. A total of eight different replicated data values were obtained for each probe on the array. The samples were hybridized overnight to cDNA microarray slides containing 4,000 elements in duplicate (GEO accession: GPL3929) using ASP hybridization chambers (GE, USA) at 42 °C. Slides were washed once for 3 minutes in low stringency wash solution at 45 °C (1 x SSC + 0.2 % SDS), followed by one wash for 5 minutes in medium stringency wash solution (0.1 x SSC + 0.2%SDS) and one wash of 1 minute in high stringency wash solution (0.1 x SSC). Moreover, slides were air dried and scanned using a microarray dual channel laser scanner (GenePix 4000B, Molecular Devices, USA) at 5 μm resolution, 100 % laser power and PMT levels were adjusted in order to obtain similar average intensities of red and green signal. Data were extracted using Array Vision 8.0 program. To correct for systematic biases on the data originated from small differences in the labeling and/or detection efficiencies between the fluorescent dyes, expression ratios were logged (base 2) and normalized using a locally weighted linear regression (LOWESS) algorithm [60]. Normalized log2 (ratios) were further analyzed with the Significance Analysis of Microarrays tool (SAM) [61] using a 0.1 % false discovery rate (FDR) to find differentially expressed genes. The genes identified in the previous step were filtered using a 1.7 fold change cut-off in at least 4 out of the 8 data points. This step is critical in identifying more biological relevant changes. It is important to stress that the fold change filter was used after the identification of differentially expressed genes, and our results are not influenced by the potentially misleading effects caused by the use of arbitrary thresholds to trim data sets before significance testing .
2010-06-24 | E-GEOD-14751 | biostudies-arrayexpress
Project description:An essential mission of the Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) was to help inform global health practices related to the control and elimination of schistosomiasis. To provide more accurate, evidence-based projections of the most likely impact of different control interventions, whether implemented alone or in combination, SCORE supported mathematical modeling teams to provide simulations of community-level Schistosoma infection outcomes in the setting of real or hypothetical programs implementing multiyear mass drug administration (MDA) for parasite control. These models were calibrated using SCORE experience with Schistosoma mansoni and Schistosoma haematobium gaining and sustaining control studies, and with data from comparable programs that used community-based or school-based praziquantel MDA in other parts of sub-Saharan Africa. From 2010 to 2019, models were developed and refined, first to project the likely SCORE control outcomes, and later to more accurately reflect impact of MDA across different transmission settings, including the role of snail ecology and the impact of seasonal rainfall on snail abundance. Starting in 2014, SCORE modeling projections were also compared with the models of colleagues in the Neglected Tropical Diseases Modelling Consortium. To explore further possible improvement to program-based control, later simulations examined the cost-effectiveness of combining MDA with environmental snail control, and the utility of early impact assessment to more quickly identify persistent hot spots of transmission. This article provides a nontechnical summary of the 11 SCORE-related modeling projects and provides links to the original open-access articles describing model development and projections relevant to schistosomiasis control policy.
| S-EPMC7351296 | biostudies-literature
Project description:Malaria and schistosomiasis coinfections are common, and chronic schistosomiasis has been implicated in affecting the severity of acute malaria. However, whether it enhances or attenuates malaria has been controversial due the lack of appropriately controlled human studies and relevant animal models. To examine this interaction, we conducted a randomized controlled study using the baboon (Papio anubis) to analyze the effect of chronic schistosomiasis on severe malaria. Two groups of baboons (n = 8 each) and a schistosomiasis control group (n = 3) were infected with 500 Schistosoma mansoni cercariae. At 14 and 15 weeks postinfection, one group was given praziquantel to treat schistosomiasis infection. Four weeks later, the two groups plus a new malaria control group (n = 8) were intravenously inoculated with 10(5) Plasmodium knowlesi parasites and monitored daily for development of severe malaria. A total of 81% of baboons exposed to chronic S. mansoni infection with or without praziquantel treatment survived malaria, compared to only 25% of animals infected with P. knowlesi only (P = 0.01). Schistosome-infected animals also had significantly lower parasite burdens (P = 0.004) than the baboons in the P. knowlesi-only group and were protected from severe anemia. Coinfection was associated with increased spontaneous production of interleukin-6 (IL-6), suggesting an enhanced innate immune response, whereas animals infected with P. knowlesi alone failed to develop mitogen-driven tumor necrosis factor alpha and IL-10, indicating the inability to generate adequate protective and balancing immunoregulatory responses. These results indicate that chronic S. mansoni attenuates the severity of P. knowlesi coinfection in baboons by mechanisms that may enhance innate immunity to malaria.
| S-EPMC4862699 | biostudies-literature
Project description:The G×E concept, in which genotype × environment interactions bring about the phenotype, is widely used to describe biological phenomena. We propose to extend the initial notion of the concept, replacing G by 'inheritance system'. This system, comprised of both genome and epigenome components, collectively interacts with the environment to shape the development of a phenotype. In the case of the human blood fluke Schistosoma mansoni, responsible for intestinal bilharzia, the phenotypic trait that is most relevant to global health is infection success. Taking a systems biology view we show how genetic and epigenetic interactions result in ephemeral, but also heritable, phenotypic variations that are important for infection success.
| S-EPMC6125318 | biostudies-literature
Project description:The X-ray crystal structure of arginase from Schistosoma mansoni (SmARG) and the structures of its complexes with several amino acid inhibitors have been determined at atomic resolution. SmARG is a binuclear manganese metalloenzyme that catalyzes the hydrolysis of l-arginine to form l-ornithine and urea, and this enzyme is upregulated in all forms of the parasite that interact with the human host. Current hypotheses suggest that parasitic arginases could play a role in host immune evasion by depleting pools of substrate l-arginine that would otherwise be utilized for NO biosynthesis and NO-dependent processes in the immune response. Although the amino acid sequence of SmARG is only 42% identical with that of human arginase I, residues important for substrate binding and catalysis are strictly conserved. In general, classical amino acid inhibitors such as 2(S)-amino-6-boronohexanoic acid (ABH) tend to bind more weakly to SmARG than to human arginase I despite identical inhibitor binding modes in each enzyme active site. The identification of a patch on the enzyme surface capable of accommodating the additional Cα substitutent of an α,α-disubstituted amino acid inhibitor suggests that such inhibitors could exhibit higher affinity and biological activity. The structures of SmARG complexed with two different α,α-disubstituted derivatives of ABH are presented and provide a proof of concept for this approach in the enhancement of enzyme-inhibitor affinity.
| S-EPMC4138072 | biostudies-literature
Project description:BackgroundSchistosoma haematobium and Schistosoma mansoni are blood flukes that cause urogenital and intestinal schistosomiasis, respectively. In Côte d'Ivoire, both species are endemic and control efforts are being scaled up. Accurate knowledge of the geographical distribution, including delineation of high-risk areas, is a central feature for spatial targeting of interventions. Thus far, model-based predictive risk mapping of schistosomiasis has relied on historical data of separate parasite species.MethodologyWe analyzed data pertaining to Schistosoma infection among school-aged children obtained from a national, cross-sectional survey conducted between November 2011 and February 2012. More than 5,000 children in 92 schools across Côte d'Ivoire participated. Bayesian geostatistical multinomial models were developed to assess infection risk, including S. haematobium-S. mansoni co-infection. The predicted risk of schistosomiasis was utilized to estimate the number of children that need preventive chemotherapy with praziquantel according to World Health Organization guidelines.Principal findingsWe estimated that 8.9% of school-aged children in Côte d'Ivoire are affected by schistosomiasis; 5.3% with S. haematobium and 3.8% with S. mansoni. Approximately 2 million annualized praziquantel treatments would be required for preventive chemotherapy at health districts level. The distinct spatial patterns of S. haematobium and S. mansoni imply that co-infection is of little importance across the country.Conclusions/significanceWe provide a comprehensive analysis of the spatial distribution of schistosomiasis risk among school-aged children in Côte d'Ivoire and a strong empirical basis for a rational targeting of control interventions.
| S-EPMC4270510 | biostudies-literature
Project description:This text presents complementary data corresponding to schistosomiasis mansoni׳s vector control and toxicity on Schistosoma mansoni cercariae using potassium usnate. This information support our research article "Potassium Usnate Toxicity Against Embryonic Stages of the Snail Biomphalaria glabrata and Schistosoma mansoni Cercariae" [1], and focuses on the analysis of the detailed data regarding the different concentrations of potassium usnate and their efficiency to B. glabrata mortality and non-viability and S. mansoni cercariae mortality etiologic agent of the disease.
| S-EPMC6231030 | biostudies-literature
Project description:Schistosomiasis is a debilitating infection provoked by parasitic flatworms called schistosomes. The species Schistosoma mansoni is endemic in Africa, where it causes intestinal schistosomiasis. Recently, an ?-carbonic anhydrase (CA, EC 4.2.1.1) was cloned and characterized from this organism and designated as SmCA. The protein is expressed in the tegument (skin) of S. mansoni at the host-parasite interface. Recombinant SmCA possesses high catalytic activity in the CO2 hydration reaction, similar to that of human CA isoform II with a kcat of 1.2 × 106 s-1 and a kcat/KM of 1.3 × 108 M-1·s-1. It has been found that schistosomes whose SmCA gene is suppressed using RNA interference are unable to establish a robust infection in mice, suggesting that the chemicals that inhibit SmCA function should have the same debilitating effect on the parasites. In this study, a collection of aromatic/heterocyclic sulfonamides were investigated as possible SmCA inhibitors. Several sulfonamides inhibited SmCA with medium to weak potency (KI values of 737.2 nM-9.25 ?M), whereas some heterocyclic compounds inhibited the enzyme with KI values in the range of 124-325 nM. The ?-CA from S. mansoni, SmCA, is proposed as a new anti-schistosomiasis drug target.
| S-EPMC7084386 | biostudies-literature