Schistosoma mansoni Soluble Egg Antigens Induce Expression of the Negative Regulators SOCS1 and SHP1 in Human Dendritic Cells via Interaction with the Mannose Receptor.

PubMed

Klaver, Elsenoor J; Kuijk, Loes M; Lindhorst, Thisbe K; Cummings, Richard D; van Die, Irma

2015-01-01

Schistosomiasis is a common debilitating human parasitic disease in (sub)tropical areas, however, schistosome infections can also protect against a variety of inflammatory diseases. This has raised broad interest in the mechanisms by which Schistosoma modulate the immune system into an anti-inflammatory and regulatory state. Human dendritic cells (DCs) show many phenotypic changes upon contact with Schistosoma mansoni soluble egg antigens (SEA). We here show that oxidation of SEA glycans, but not heat-denaturation, abrogates the capacity of SEA to suppress both LPS-induced cytokine secretion and DC proliferation, indicating an important role of SEA glycans in these processes. Remarkably, interaction of SEA glycans with DCs results in a strongly increased expression of Suppressor Of Cytokine Signalling1 (SOCS1) and SH2-containing protein tyrosine Phosphatase-1 (SHP1), important negative regulators of TLR4 signalling. In addition, SEA induces the secretion of transforming growth factor β (TGF-β), and the surface expression of the costimulatory molecules Programmed Death Ligand-1 (PD-L1) and OX40 ligand (OX40L), which are known phenotypic markers for the capacity of DCs to polarize naïve T cells into Th2/Treg cell subsets. Inhibition of mannose receptor (MR)-mediated internalization of SEA into DCs by blocking with allyl α-D-mannoside or anti-MR antibodies, significantly reduced SOCS1 and SHP1 expression. In conclusion, we demonstrate that SEA glycans are essential for induction of enhanced SOCS1 and SHP1 levels in DCs via the MR. Our data provide novel mechanistic evidence for the potential of S. mansoni SEA glycans to modulate human DCs, which may contribute to the capacity of SEA to down-regulate inflammatory responses.

The allergens of Schistosoma mansoni

PubMed Central

Harris, W. G.

1973-01-01

Ten antigen fractions were prepared from adult Schistosoma mansoni by extraction into borate-buffered saline, precipitation at pH 4.6 and separation on Sephadex G-100. The allergic activity of these antigens was assayed by a modified Prausnitz—Kustner type reaction in rats; this test system was found to be sensitive and consistent, allowing differences in allergenicity between antigens to be accurately assessed. Skin-reactivity was detected in both acid-soluble and acid-insoluble fractions. Specific allergenicity was located in peak 3 of a G-100 separation of the acid-soluble fraction and in peaks 1 and 2 of a G-100 separation of the acid-insoluble fraction suggesting that the allergens of S. mansoni were of at least two types: (1) a protein of mol. wt above 150,000 precipitated at pH 4.6, and (2) a protein of mol. wt 20–30,000 remaining in solution at this pH. It is suggested that both these allergens are glycoproteins. Non-specific histamine-releasing agents were found in peak 1 of the G-100 separation of the acid-soluble material. ImagesFIG. 1 PMID:4122335

Schistosoma mansoni: cercarial responses to irradiance changes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Saladin, K.S.

1982-02-01

Cercariae of Schistosoma mansoni alternate between active swimming and passive drifting. They began swimming in response to either an increase or decrease in irradiance experienced during the passive phase. The number of cercariae reacting to a shadow was proportional to the magnitude of the stimulus. The shadow response may be mediated by the cercaria's ciliary receptors. About half as many cercariae reacted to an irradiance increase as to an equivalent decrease. This report is the first quantitative study of photosensory stimulus-response relationships in schistosome cercariae.

Prolyl Oligopeptidase from the Blood Fluke Schistosoma mansoni: From Functional Analysis to Anti-schistosomal Inhibitors

PubMed Central

Fajtová, Pavla; Štefanić, Saša; Hradilek, Martin; Dvořák, Jan; Vondrášek, Jiří; Jílková, Adéla; Ulrychová, Lenka; McKerrow, James H.; Caffrey, Conor R.; Mareš, Michael; Horn, Martin

2015-01-01

Background Blood flukes of the genus Schistosoma cause schistosomiasis, a parasitic disease that infects over 240 million people worldwide, and for which there is a need to identify new targets for chemotherapeutic interventions. Our research is focused on Schistosoma mansoni prolyl oligopeptidase (SmPOP) from the serine peptidase family S9, which has not been investigated in detail in trematodes. Methodology/Principal Findings We demonstrate that SmPOP is expressed in adult worms and schistosomula in an enzymatically active form. By immunofluorescence microscopy, SmPOP is localized in the tegument and parenchyma of both developmental stages. Recombinant SmPOP was produced in Escherichia coli and its active site specificity investigated using synthetic substrate and inhibitor libraries, and by homology modeling. SmPOP is a true oligopeptidase that hydrolyzes peptide (but not protein) substrates with a strict specificity for Pro at P1. The inhibition profile is analogous to those for mammalian POPs. Both the recombinant enzyme and live worms cleave host vasoregulatory, proline-containing hormones such as angiotensin I and bradykinin. Finally, we designed nanomolar inhibitors of SmPOP that induce deleterious phenotypes in cultured schistosomes. Conclusions/Significance We provide the first localization and functional analysis of SmPOP together with chemical tools for measuring its activity. We briefly discuss the notion that SmPOP, operating at the host-parasite interface to cleave host bioactive peptides, may contribute to the survival of the parasite. If substantiated, SmPOP could be a new target for the development of anti-schistosomal drugs. PMID:26039195

Transmission of Schistosoma mansoni in Rhino Camp, Uganda.

PubMed

Loroni-Lakwo, T; Odongo-Aginya, E I; Schweigmann, U; Schickerling, S; Lindner, D; Doehring-Schwerdtfeger, E

1994-03-01

Non-participant observations totalling 204 hours relevant to the transmission of Schistosoma mansoni infection were carried out in Rhino Camp at the shores of Albert Nile in North Uganda. A cross-sectional study of 636 individuals from Rhino Camp revealed a prevalence of S. mansoni infection of 77.8%. Occupational and domestic purposes were the most important reasons for water contact, whereas recreational purposes ranked lower and mainly concerned children. Both sexes were equally active in water contacts. A distinct preference of Nile water was noted despite availability of borehole water in the area. It is concluded that control measures against schistosomiasis have to take into consideration that water contact for recreational purposes might be minimized, whereas it is expected to be extremely difficult to reduce occupational and domestic water contacts.

Schistosoma mansoni P-glycoprotein levels increase in response to praziquantel exposure and correlate with reduced praziquantel susceptibility.

PubMed

Messerli, Shanta M; Kasinathan, Ravi S; Morgan, William; Spranger, Stefani; Greenberg, Robert M

2009-09-01

One potential physiological target for new antischistosomals is the parasite's system for excretion of wastes and xenobiotics. P-glycoprotein (Pgp), a member of the ATP-binding-cassette superfamily of proteins, is an ATP-dependent efflux pump involved in transport of toxins and xenobiotics from cells. In vertebrates, increased expression of Pgp is associated with multidrug resistance in tumor cells. Pgp may also play a role in drug resistance in helminths. In this report, we examine the relationship between praziquantel (PZQ), the current drug of choice against schistosomiasis, and Pgp expression in Schistosoma mansoni. We show that levels of RNA for SMDR2, a Pgp homolog from S. mansoni, increase transiently in adult male worms following exposure to sub-lethal concentrations (100-500 nM) of PZQ. A corresponding, though delayed, increase in anti-Pgp immunoreactive protein expression occurs in adult males following exposure to PZQ. The level of anti-Pgp immunoreactivity in particular regions of adult worms also increases in response to PZQ. Adult worms from an Egyptian S. mansoni isolate with reduced sensitivity to PZQ express increased levels of SMDR2 RNA and anti-Pgp-immunoreactive protein, perhaps indicating a role for multidrug resistance proteins in development or maintenance of PZQ resistance.

Schistosoma mansoni P-glycoprotein levels increase in response to praziquantel exposure and correlate with reduced praziquantel susceptibility

PubMed Central

Messerli, Shanta M.; Kasinathan, Ravi S.; Morgan, William; Spranger, Stefani; Greenberg, Robert M.

2009-01-01

One potential physiological target for new antischistosomals is the parasite’s system for excretion of wastes and xenobiotics. P-glycoprotein (Pgp), a member of the ATP-binding cassette superfamily of proteins, is an ATP-dependent efflux pump involved in transport of toxins and xenobiotics from cells. In vertebrates, increased expression of Pgp is associated with multidrug resistance in tumor cells. Pgp may also play a role in drug resistance in helminths. In this report, we examine the relationship between praziquantel (PZQ), the current drug of choice against schistosomiasis, and Pgp expression in Schistosoma mansoni. We show that levels of RNA for SMDR2, a Pgp homolog from S. mansoni, increase transiently in adult male worms following exposure to sublethal concentrations (100 – 500 nM) of PZQ. A corresponding, though delayed, increase in anti-Pgp immunoreactive protein expression occurs in adult males following exposure to PZQ. The level of anti-Pgp immunoreactivity in particular regions of adult worms also increases in response to PZQ. Adult worms from an Egyptian S. mansoni isolate with reduced sensitivity to PZQ express increased levels of SMDR2 RNA and anti-Pgp-immunoreactive protein, perhaps indicating a role for multidrug resistance proteins in development or maintenance of PZQ resistance. PMID:19406169

Immunization with recombinantly expressed glycan antigens from Schistosoma mansoni induces glycan-specific antibodies against the parasite

PubMed Central

Prasanphanich, Nina Salinger; Luyai, Anthony E; Song, Xuezheng; Heimburg-Molinaro, Jamie; Mandalasi, Msano; Mickum, Megan; Smith, David F; Nyame, A Kwame; Cummings, Richard D

2014-01-01

Schistosomiasis caused by infection with parasitic helminths of Schistosoma spp. is a major global health problem due to inadequate treatment and lack of a vaccine. The immune response to schistosomes includes glycan antigens, which could be valuable diagnostic markers and vaccine targets. However, no precedent exists for how to design vaccines targeting eukaryotic glycoconjugates. The di- and tri-saccharide motifs LacdiNAc (GalNAcβ1,4GlcNAc; LDN) and fucosylated LacdiNAc (GalNAcβ1,4(Fucα1-3)GlcNAc; LDNF) are the basis for several important schistosome glycan antigens. They occur in monomeric form or as repeating units (poly-LDNF) and as part of a variety of different glycoconjugates. Because chemical synthesis and conjugation of such antigens is exceedingly difficult, we sought to develop a recombinant expression system for parasite glycans. We hypothesized that presentation of parasite glycans on the cell surface would induce glycan-specific antibodies. We generated Chinese hamster ovary (CHO) Lec8 cell lines expressing poly-LDN (L8-GT) and poly-LDNF (L8-GTFT) abundantly on their membrane glycoproteins. Sera from Schistosoma mansoni-infected mice were highly cross-reactive with the cells and with cell-surface N-glycans. Immunizing mice with L8-GT and L8-GTFT cells induced glycan-specific antibodies. The L8-GTFT cells induced a sustained booster response, with antibodies that bound to S. mansoni lysates and recapitulated the exquisite specificity of the anti-parasite response for particular presentations of LDNF antigen. In summary, this recombinant expression system promotes successful generation of antibodies to the glycans of S. mansoni, and it can be adapted to study the role of glycan antigens and anti-glycan immune responses in many other infections and pathologies. PMID:24727440

Longitudinal analysis of antigen specific response in individuals with Schistosoma mansoni infection in an endemic area of Minas Gerais, Brazil

PubMed Central

Matoso, Leonardo Ferreira; Oliveira-Prado, Roberta; Abreu, Mery Natali Silva; Fujiwara, Ricardo Toshio; LoVerde, Philip T.; Kloos, Helmut; Gazzinelli, Andréa; Correa-Oliveira, Rodrigo

2013-01-01

Background Immunoepidemiologic studies have shown a relationship between IgE and IgG4 antibodies with age and with resistance and susceptibility to infection. It is believed that the IgE and IgG4 responses to soluble egg antigen (SEA) can be used for serological analysis of infection and post-treatment status. This study aimed to evaluate the association between Schistosoma mansoni infection and anti-SEA IgG4 and IgE reactivities, and determine whether these reactivities could be used as biomarkers of infection. Methods Between 2001 and 2009, a longitudinal study was performed in which parasitologic and blood specimens and socioeconomic and water-contact information were collected from 127 individuals. All patients positive for S. mansoni infection were treated. Results Schistosomiasis prevalence and the geometric mean of the egg count in 2001 were 59% and 61.05, respectively, decreasing to 26.8% and 8.78 in 2009. IgG4 anti-SEA reactivity in infected individuals was significantly higher than that in uninfected individuals at all time points. Analysis of receiver-operating characteristic (ROC) area showed that the IgG4 anti-SEA antibodies were able to predict infection by S. mansoni at each time point. Conclusion IgG4 anti-SEA reactivity can be used as a biomarker for immune monitoring of the presence of infection with S. mansoni in endemic areas. PMID:24189480

Bioimmunological responses to Schistosoma mansoni and Fasciola gigantica worm homogenates either with or without saponin.

PubMed

Maghraby, Amany Sayed; Hamed, Manal Abdel-Aziz; Ali, Sanaa Ahmed

2010-06-03

In this study, we evaluated the biochemical, immunological, histopathological and antischistosomal activities of Schistosoma mansoni or Fasciola gigantica worm homogenates mixed either with or without saponin that was extracted from Atriplex nummularia. The immunization schedule was based on subcutaneous administration of two doses (50 microg /100 microl PBS) of each homogenate with time intervals of 15 days. After 15 days of the last homogenate inoculation, all mice were challenged with 100 Schistosoma mansoni cercariae and sacrificed after two months. Free radical scavengers and liver function enzymes were determined in mice liver. Worm counting and the histopathological picture of the liver were also done. Immunization with Schistosoma or Fasciola worm homogenates, mixed either with or without saponin, recorded an amelioration of the free radical scavenger levels, liver function enzymes and reduction in worm burden, as well as improvement of the histological feature of the liver, the number and size of granuloma, evidence of increased immune reaction manifested by a lymphocytic cuff surrounding the granuloma, diminution of its fibrotic and collagen content, and destruction of Schistosoma ova. Fasciola or Schistosoma worm antigens mixed with or without saponin succeeded to eliminate the product of oxidative stress and assistance in immune-mediated destruction of eggs that ameliorate the histopathological picture of the liver cells and preserve its function.

Telmisartan, an AT1 receptor blocker and a PPAR gamma activator, alleviates liver fibrosis induced experimentally by Schistosoma mansoni infection.

PubMed

Attia, Yasmeen M; Elalkamy, Essam F; Hammam, Olfat A; Mahmoud, Soheir S; El-Khatib, Aiman S

2013-07-05

Hepatic schistosomiasis is considered to be one of the most prevalent forms of chronic liver disease in the world due to its complication of liver fibrosis. The demonstration of the pro-fibrogenic role of angiotensin (Ang) II in chronic liver disease brought up the idea that anti-Ang II agents may be effective in improving hepatic fibrosis by either blocking Ang II type 1 (AT1) receptors or inhibiting the angiotensin converting enzyme. Peroxisome proliferator-activated receptors gamma (PPARγ) activation has been also shown to inhibit hepatic stellate cell activation and progression of fibrosis. The present study has aimed at testing the anti-fibrogenic effects of telmisartan; an AT1 receptor blocker and a PPARγ partial agonist, alone or combined with praziquantel (PZQ) on Schistosoma mansoni-induced liver fibrosis in mice. To achieve the aim of the study, two sets of experiments were performed in which telmisartan was initiated at the 5th (set 1) and the 10th (set 2) weeks post infection to assess drug efficacy in both acute and chronic stages of liver fibrosis, respectively. Schistosoma mansoni-infected mice were randomly divided into the following four groups: infected-control (I), telmisartan-treated (II), PZQ-treated (III), and telmisartan+PZQ-treated (IV). In addition, a normal non-infected group was used for comparison. Parasitological (hepatomesenteric worm load and oogram pattern), histopathological, morphometric, immunohistochemical (hepatic expressions of matrix metalloproteinase-2; MMP-2 and tissue inhibitor of metalloproteinase-2; TIMP-2), and biochemical (serum transforming growth factor beta 1; TGF-β1 and liver function tests) studies were performed. Telmisartan failed to improve the parasitological parameters, while it significantly (P<0.05) decreased the mean granuloma diameter, area of fibrosis, and serum TGF-β1. Additionally, telmisartan increased MMP-2 and decreased TIMP-2 hepatic expression. Combined treatment failed to show any additive

Protection by phospholipids of Schistosoma mansoni schistosomula against the action of cytotoxic antibodies and complement.

PubMed

Billecocq, A

1987-09-01

Schistosoma mansoni schistosomula cultured in the presence of phospholipids showed a decreased sensitivity to the lethal complement-mediated action of anti-schistosome antibodies. Phosphatidyl choline, sphingomyelin and phosphatidyl ethanolamine had a protective action on the schistosomula transformed in vitro by passage through the skin or by a mechanical procedure. Phosphatidyl choline acted regardless of its fatty acid composition. Phosphatidyl serine and phosphatidic acid did not protect. Thus, it appears that phospholipids can play a role in parasite resistance to immune attack by cytotoxic antibodies and complement, and that this role is specific to certain phospholipid types.

The role of the immunological background of mice in the genetic variability of Schistosoma mansoni as detected by random amplification of polymorphic DNA.

PubMed

Cossa-Moiane, I L; Mendes, T; Ferreira, T M; Mauricio, I; Calado, M; Afonso, A; Belo, S

2015-11-01

Schistosomiasis is a parasitic disease caused by flatworms of the genus Schistosoma. Among the Schistosoma species known to infect humans, S. mansoni is the most frequent cause of intestinal schistosomiasis in sub-Saharan Africa and South America: the World Health Organization estimates that about 200,000 deaths per year result from schistosomiasis in sub-Saharan Africa alone. The Schistosoma life cycle requires two different hosts: a snail as intermediate host and a mammal as definitive host. People become infected when they come into contact with water contaminated with free-living larvae (e.g. when swimming, fishing, washing). Although S. mansoni has mechanisms for escaping the host immune system, only a minority of infecting larvae develop into adults, suggesting that strain selection occurs at the host level. To test this hypothesis, we compared the Belo Horizonte (BH) strain of S. mansoni recovered from definitive hosts with different immunological backgrounds using random amplification of polymorphic DNA-polymerase chain reaction (RAPD-PCR). Schistosoma mansoni DNA profiles of worms obtained from wild-type (CD1 and C57BL/6J) and mutant (Jα18- / - and TGFβRIIdn) mice were analysed. Four primers produced polymorphic profiles, which can therefore potentially be used as reference biomarkers. All male worms were genetically distinct from females isolated from the same host, with female worms showing more specific fragments than males. Of the four host-derived schistosome populations, female and male adults recovered from TGFβRIIdn mice showed RAPD-PCR profiles that were most similar to each other. Altogether, these data indicate that host immunological backgrounds can influence the genetic diversity of parasite populations.

Effect of a novel benzimidazole derivative in experimental Schistosoma mansoni infection.

PubMed

El Bialy, Serry A; Taman, Amira; El-Beshbishi, Samar N; Mansour, Basem; El-Malky, Mohamed; Bayoumi, Waleed A; Essa, Hassan M

2013-12-01

Currently, praziquantel is the only drug of choice for treatment of schistosomiasis. Reports of praziquantel resistance raise concerns about future control of the disease. Therefore, the search for new schistosomicidal drugs is eminent. In this study, the effect of a novel benzimidazole-derived compound (compound BTP-Iso) was assessed in mice harboring adult Schistosoma mansoni (Egyptian strain). Mice were treated 42 days p.i. with compound BTP-Iso using two treatment regimens (200 or 300 mg/kg). In both regimens, there were significant reductions in the number of recovered S. mansoni worms especially females and in immature ova, in addition to a significant reduction in the number and size of hepatic granulomata. A dose of 300 mg/kg resulted in a significant decrease in intestinal and hepatic tissue egg loads. Effect on schistosomes was confirmed by scanning electron microscopy, where adult worms recovered from mice treated with 200 mg/kg of compound BTP-Iso revealed tegumental alternations, characterised by swelling of tegumental ridges, bleb formation, and mild erosion in male worms; however in females, there were extensive erosion and destruction of the tegumental surface. These promising results may encourage future use of compound BTP-Iso in the treatment of schistosomiasis. However, more research is needed to detect the effect of compound BTP-Iso on early developmental stages of S. mansoni and on other species of human schistosomes.

Long-term dynamics of natural populations of Schistosoma mansoni among Rattus rattus in patchy environment.

PubMed

Théron, A; Pointier, J P; Morand, S; Imbert-Establet, D; Borel, G

1992-04-01

Dynamics of natural populations of Schistosoma mansoni were studied during 8 consecutive years among Rattus rattus populations from 8 transmission sites of the marshy forest focus of Guadeloupe (French West Indies). The schistosome population is over-dispersed (k = 0.119) within the murine hosts and ecological factors linked to the patchy environment may be responsible for such aggregated distribution. Analysis of the spatio-temporal variations in prevalences, intensities and abundances showed limited variations of the infection during the 8 years at the level of the whole parasite population but great spatial heterogeneity at the level of local schistosome populations. Inter-populational genetic variability linked to the degree of adaptation of this human parasite to the murine host may explain differences in transmission dynamics between the local populations of S. mansoni.

Transcriptome analysis of Schistosoma mansoni larval development using serial analysis of gene expression (SAGE).

PubMed

Taft, A S; Vermeire, J J; Bernier, J; Birkeland, S R; Cipriano, M J; Papa, A R; McArthur, A G; Yoshino, T P

2009-04-01

Infection of the snail, Biomphalaria glabrata, by the free-swimming miracidial stage of the human blood fluke, Schistosoma mansoni, and its subsequent development to the parasitic sporocyst stage is critical to establishment of viable infections and continued human transmission. We performed a genome-wide expression analysis of the S. mansoni miracidia and developing sporocyst using Long Serial Analysis of Gene Expression (LongSAGE). Five cDNA libraries were constructed from miracidia and in vitro cultured 6- and 20-day-old sporocysts maintained in sporocyst medium (SM) or in SM conditioned by previous cultivation with cells of the B. glabrata embryonic (Bge) cell line. We generated 21 440 SAGE tags and mapped 13 381 to the S. mansoni gene predictions (v4.0e) either by estimating theoretical 3' UTR lengths or using existing 3' EST sequence data. Overall, 432 transcripts were found to be differentially expressed amongst all 5 libraries. In total, 172 tags were differentially expressed between miracidia and 6-day conditioned sporocysts and 152 were differentially expressed between miracidia and 6-day unconditioned sporocysts. In addition, 53 and 45 tags, respectively, were differentially expressed in 6-day and 20-day cultured sporocysts, due to the effects of exposure to Bge cell-conditioned medium.

Efficacy of Gold Nanoparticles against Nephrotoxicity Induced by Schistosoma mansoni Infection in Mice.

PubMed

Dkhil, Mohamed A; Khalil, Mona F; Bauomy, Amira A; Diab, Marwa Sm; Al-Quraishy, Saleh

2016-11-01

In this study, the ameliorative effects of gold nanoparticles (gold NP) on the renal tissue damage in Schistosoma mansoni (S. mansoni)-infected mice was investigated. High-resolution transmission electron microscopy was used for the characterization of NP. The gold NP at concentrations of 250, 500, and 1000 μg/kg body weight were inoculated into S. mansoni-infected mice. The parasite caused alterations in the histological architecture. Furthermore, it induced a significant reduction in the renal glutathione levels; however, the levels of nitric oxide and malondialdehyde were significantly elevated. The parasite also managed to downregulate KIM-1, NGAL, MCP-1, and TGF-β mRNA expression in infected animals. Notably, gold NP treatment in mice reduced the extent of histological impairment and renal oxidative damage. Gold NP were able to regulate gene expression impaired by S. Mansoni infection. The curative effect of gold NP against renal toxicity in S. mansoni-infected mice is associated with their role as free radical scavengers. Copyright © 2016 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

Diagnostic accuracy and applicability of a PCR system for the detection of Schistosoma mansoni DNA in human urine samples from an endemic area.

PubMed

Enk, Martin Johannes; Oliveira e Silva, Guilherme; Rodrigues, Nilton Barnabé

2012-01-01

Schistosomiasis caused by Schistosoma mansoni, one of the most neglected human parasitoses in Latin America and Africa, is routinely confirmed by microscopic visualization of eggs in stool. The main limitation of this diagnostic approach is its lack of sensitivity in detecting individual low worm burdens and consequently data on infection rates in low transmission settings are little reliable. According to the scientific literature, PCR assays are characterized by high sensitivity and specificity in detecting parasite DNA in biological samples. A simple and cost effective extraction method for DNA of Schistosoma mansoni from urine samples in combination with a conventional PCR assay was developed and applied in an endemic area. This urine based PCR system was tested for diagnostic accuracy among a population of a small village in an endemic area, comparing it to a reference test composed of three different parasitological techniques. The diagnostic parameters revealed a sensitivity of 100%, a specificity of 91.20%, positive and negative predictive values of 86.25% and 100%, respectively, and a test accuracy of 94.33%. Further statistical analysis showed a k index of 0.8806, indicating an excellent agreement between the reference test and the PCR system. Data obtained from the mouse model indicate the infection can be detected one week after cercariae penetration, opening a new perspective for early detection and patient management during this stage of the disease. The data indicate that this innovative PCR system provides a simple to handle and robust diagnostic tool for the detection of S. mansoni DNA from urine samples and a promising approach to overcome the diagnostic obstacles in low transmission settings. Furthermore the principals of this molecular technique, based on the examination of human urine samples may be useful for the diagnosis of other neglected tropical diseases that can be detected by trans-renal DNA.

Socioenvironmental factors associated with Schistosoma mansoni infection and intermediate hosts in an urban area of northeastern Brazil

PubMed Central

Souza, Geza Thais Rangel; Melo, Claudia Moura; Madi, Rubens Riscala; Jeraldo, Verónica de Lourdes Sierpe

2018-01-01

Schistosomiasis, which is caused by trematodes of the genus Schistosoma and by the species Schistosoma mansoni in Brazil, is transmitted primarily by Biomphalaria glabrata mollusks. Infections occur in humans and mollusks in freshwater environments contaminated with feces from infected humans. This study aimed to evaluate potential foci of schistosomiasis based on the identification of infection sites for the snails, factors that increased the human infection probability of S. mansoni infection, and the relationship of the disease with abiotic, biotic, and sociocultural factors. The study was conducted in an urban area on the northeast coast of Brazil; this location was chosen based on the following factors: the presence of B. glabrata, nearby freshwater, and the absence of sewer treatment. A parasitological analysis was performed to evaluate infections of the mollusks and residents inside the perimeter defined by the collection points. Questionnaires were applied to obtain demographic data and to identify behaviors that led to human infection. To verify the contamination of freshwater by human feces, a microbiological analysis of the water was performed at the mollusk collection points to determine the rate of contamination with fecal coliforms. A total of 10,270 B. glabrata mollusks were collected between August 2013 and August 2014, of which 8.8% were positive for S. mansoni; the prevalence ranged from 0 to 34.5% over the study period. A total of 232 coprological samples from the residents were analyzed. The S. mansoni infection prevalence rate was 16.4%, and the S. mansoni parasitic load in the infected residents was 54.9 eggs per gram of feces on average. Males were more affected by the parasite, especially in the 8-17-year-old age range. Thermotolerant coliforms were observed at the mollusk collection sites, which indicated that freshwater and sewage were in continuous contact. This contamination indicated poor sanitary conditions, as was previously observed

Schistosoma mansoni and other intestinal parasitic infections in schoolchildren and vervet monkeys in Lake Ziway area, Ethiopia.

PubMed

Teklemariam, Dejene; Legesse, Mengistu; Degarege, Abraham; Liang, Song; Erko, Berhanu

2018-02-20

To assess Schistosoma mansoni and other intestinal parasitic infections in schoolchildren and vervet monkeys (Chlorocebus aethiops) in Bochessa Village, Ziway, Ethiopia. Fecal specimens from selected schoolchildren and droppings of the vervet monkeys were collected and microscopically examined for intestinal parasites using the Kato-Katz thick smear and formol-ether concentration techniques. The prevalences of S. mansoni, Trichuris trichiura, Ascaris lumbricoides, Enterobius vermicularis, hookworms, Hymenolepis nana and Taenia species among the children were 35.7, 26.9, 24.1, 2.1, 2.1, 1.07 and 2.1%, respectively (by Kato-Katz) and 39.3, 36.1, 35.6, 2.9, 10.0, 4.3, and 2.9%, respectively (by formol-ether concentration). Prevalence of S. mansoni in vervet monkeys ranged from 10 to 20%. B. pfeifferi snails were exposed to S. mansoni miracidia from vervet origin, shed cercariae were then used to infect lab-bred albino mice. Adult worms were harvested from the mice 5 weeks post-exposure to cercariae to establish the schistosome life cycle and confirm the infection in the vervet monkeys. The natural infection of S. mansoni in vervet monkeys suggests that the non-human primate is likely to be implicated in the local transmission of schistosomiasis. Further epidemiological and molecular studies are needed to fully elucidate zoonotic role of non-human primate in the area.

Protective and Anti-Pathology Effects of Sm Fructose-1,6-Bisphosphate Aldolase-Based DNA Vaccine against Schistosoma mansoni by Changing Route of Injection

PubMed Central

Saber, Mohamed; Hammam, Olft; Karim, Amr; Medhat, Amina; Khela, Mamdouh; El-Dabaa, Ehab

2013-01-01

This study aimed to evaluate the efficacy of fructose-1,6-bis phosphate aldolase (SMALDO) DNA vaccination against Schistosoma mansoni infection using different routes of injection. The SMALDO has been cloned into the eukaryotic expression vector pcDNA3.1/V5-His TOPO-TA and was used in injecting Swiss albino mice intramuscularly (IM), subcutaneously (SC), or intraperitoneally (IP) (50 µg/mouse). Mice vaccinated with non-recombinant pcDNA3.1 served as controls. Each group was immunized 4 times at weeks 0, 2, 4, and 6. Two weeks after the last booster dose, all mice groups were infected with 80 S. mansoni cercariae via tail immersion. At week 8 post-infection, animals were sacrificed for assessment of parasitological and histopathological parameters. High anti-SMALDO IgG antibody titers were detected in sera of all vaccinated groups (P<0.01) compared to the control group. Both the IP and SC vaccination routes resulted in a significant reduction in worm burden (46.2% and 28.9%, respectively, P<0.01). This was accompanied by a significant reduction in hepatic and intestinal egg counts (41.7% and 40.2%, respectively, P<0.01) in the IP group only. The number of dead eggs was significantly increased in both IP and IM groups (P<0.01). IP vaccination recorded the highest significant reduction in granuloma number and diameter (54.7% and 29.2%, respectively, P<0.01) and significant increase in dead miracidia (P<0.01). In conclusion, changing the injection route of SMALDO DNA vaccination significantly influenced the efficacy of vaccination. SMALDO DNA vaccination via IP route could be a promising protective and anti-pathology vaccine candidate against S. mansoni infection. PMID:23710082

Protective and anti-pathology effects of Sm fructose-1,6-bisphosphate aldolase-based DNA vaccine against schistosoma mansoni by changing route of injection.

PubMed

Saber, Mohamed; Diab, Tarek; Hammam, Olft; Karim, Amr; Medhat, Amina; Khela, Mamdouh; El-Dabaa, Ehab

2013-04-01

This study aimed to evaluate the efficacy of fructose-1,6-bis phosphate aldolase (SMALDO) DNA vaccination against Schistosoma mansoni infection using different routes of injection. The SMALDO has been cloned into the eukaryotic expression vector pcDNA3.1/V5-His TOPO-TA and was used in injecting Swiss albino mice intramuscularly (IM), subcutaneously (SC), or intraperitoneally (IP) (50 µg/mouse). Mice vaccinated with non-recombinant pcDNA3.1 served as controls. Each group was immunized 4 times at weeks 0, 2, 4, and 6. Two weeks after the last booster dose, all mice groups were infected with 80 S. mansoni cercariae via tail immersion. At week 8 post-infection, animals were sacrificed for assessment of parasitological and histopathological parameters. High anti-SMALDO IgG antibody titers were detected in sera of all vaccinated groups (P<0.01) compared to the control group. Both the IP and SC vaccination routes resulted in a significant reduction in worm burden (46.2% and 28.9%, respectively, P<0.01). This was accompanied by a significant reduction in hepatic and intestinal egg counts (41.7% and 40.2%, respectively, P<0.01) in the IP group only. The number of dead eggs was significantly increased in both IP and IM groups (P<0.01). IP vaccination recorded the highest significant reduction in granuloma number and diameter (54.7% and 29.2%, respectively, P<0.01) and significant increase in dead miracidia (P<0.01). In conclusion, changing the injection route of SMALDO DNA vaccination significantly influenced the efficacy of vaccination. SMALDO DNA vaccination via IP route could be a promising protective and anti-pathology vaccine candidate against S. mansoni infection.

Antigenic cross-reactivity between Schistosoma mansoni and peanut: a role for cross-reactive carbohydrate determinants (CCDs) and implications for the hygiene hypothesis.

PubMed

Igetei, Joseph E; El-Faham, Marwa; Liddell, Susan; Doenhoff, Michael J

2017-04-01

The antigenic reactivity of constituents of Schistosoma mansoni and peanut (Arachis hypogaea) was investigated to determine whether identical antigenic epitopes possessed by both organisms provided a possible explanation for the negative correlation between chronic schistosome infection and atopy to allergens. Aqueous extracts of peanuts were probed in Western immunoblots with rabbit IgG antibodies raised against the egg, cercarial and adult worm stages of S. mansoni. Several molecules in the peanut extract were antigenically reactive with antibodies from the various rabbit anti-schistosome sera. A pair of cross-reactive peanut molecules at ~30 000-33 000 molecular weight was purified and both proteins were identified by mass spectrometric analysis as the peanut allergen Ara h 1. Anti-S. mansoni soluble egg antigen antibodies that were eluted off the peanut molecules reacted with two S. mansoni egg antigens identified by mass spectrometry as IPSE/α-1 and κ-5. Alignments of the amino acid sequences of Ara h 1 and either IPSE/α-1 or κ-5 revealed a low level of peptide sequence identity. Incubation of nitrocellulose paper carrying electrophoresed peanut molecules, six constituents of other allergic plants and S. mansoni egg antigens in a mild solution of sodium metaperiodate before probing with antibodies, inhibited most of the cross-reactivities. The results are consistent with the antigenic cross-reactive epitopes of S. mansoni egg antigens, peanut and other allergic plants being cross-reactive carbohydrate determinants (CCDs). These findings are novel and an explanation based on 'blocking antibodies' could provide an insight for the inverse relationship observed between schistosome infection and allergies. © 2017 John Wiley & Sons Ltd.

Use of recombinant calreticulin and cercarial transformation fluid (CTF) in the serodiagnosis of Schistosoma mansoni.

PubMed

El Aswad, Bahaa El Deen Wade; Doenhoff, Michael J; El Hadidi, Abeer Shawky; Schwaeble, Wilhelm J; Lynch, Nicholas J

2011-03-01

Schistosomiasis is traditionally diagnosed by microscopic detection of ova in stool samples, but this method is labour intensive and its sensitivity is limited by low and variable egg secretion in many patients. An alternative is an ELISA using Schistosoma mansoni soluble egg antigen (SEA) to detect anti-schistosome antibody in patient samples. SEA is a good diagnostic marker in non-endemic regions but is of limited value in endemic regions, mainly because of its high cost and limited specificity. Here we assess seven novel antigens for the detection of S. mansoni antibody in an endemic region (the Northern Nile Delta). Using recombinant S. mansoni calreticulin (CRT) and fragments thereof, anti-CRT antibodies were detected in the majority of 97 patients sera. The diagnostic value of some of these antigens was, however, limited by the presence of cross-reacting antibody in the healthy controls, even those recruited in non-endemic areas. Cercarial transformation fluid (CTF), a supernatant that contains soluble material released by the cercariae upon transformation to the schistosomula, is cheaper and easier to produce than SEA. An ELISA using CTF as the detection antigen had a sensitivity of 89.7% and an estimated specificity of 100% when used in non-endemic regions, matching the performance of the established SEA ELISA. CTF was substantially more specific than SEA for diagnosis in the endemic region, and less susceptible than SEA to cross-reacting antibody in the sera of controls with other protozoan and metazoan infections. Copyright © 2010 Elsevier GmbH. All rights reserved.

A 1,536-Well-Based Kinetic HTS Assay for Inhibitors of Schistosoma mansoni Thioredoxin Glutathione Reductase

PubMed Central

Lea, Wendy A.; Jadhav, Ajit; Rai, Ganesha; Sayed, Ahmed A.; Cass, Cynthia L.; Inglese, James; Williams, David L.; Austin, Christopher P.

2008-01-01

Abstract Schistosomiasis is a major neglected tropical disease that currently affects over 200 million people and leads to over 200,000 annual deaths. Schistosoma mansoni parasites survive in humans in part because of a set of antioxidant enzymes that continuously degrade reactive oxygen species produced by the host. A principal component of this defense system has been recently identified as thioredoxin glutathione reductase (TGR), a parasite-specific enzyme that combines the functions of two human counterparts, glutathione reductase and thioredoxin reductase, and as such this enzyme presents an attractive new target for anti-schistosomiasis drug development. Herein, we present the development of a highly miniaturized and robust screening assay for TGR. The 5-μl final volume assay is based on the Ellman reagent [5,5′-dithiobis(2-nitrobenzoic acid) (DTNB)] and utilizes a high-speed absorbance kinetic read to minimize the effect of dust, absorbance interference, and meniscus variation. This assay is further applicable to the testing of other redox enzymes that utilize DTNB as a model substrate. PMID:18665782

The genomic proliferation of transposable elements in colonizing populations: Schistosoma mansoni in the new world.

PubMed

Wijayawardena, Bhagya K; DeWoody, J Andrew; Minchella, Dennis J

2015-06-01

Transposable elements (TEs) are mobile genes with an inherent ability to move within and among genomes. Theory predicts that TEs proliferate extensively during physiological stress due to the breakdown of TE repression systems. We tested this hypothesis in Schistosoma mansoni, a widespread trematode parasite that causes the human disease schistosomiasis. According to phylogenetic analysis, S. mansoni invaded the new world during the last 500 years. We hypothesized that new world strains of S. mansoni would have more copies of TEs than old world strains due to the physiological stress associated with invasion of the new world. We quantified the copy number of six TEs (Saci-1, Saci-2 and Saci-3, Perere-1, Merlin-sm1, and SmTRC1) in the genome and the transcriptome of old world and new world strains of S. mansoni, using qPCR relative quantification. As predicted, the genomes of new world parasites contain significantly more copies of class I and class II TEs in both laboratory and field strains. However, such differences are not observed in the transcriptome suggesting that either TE silencing mechanisms have reactivated to control the expression of these elements or the presence of inactive truncated copies of TEs.

[Chronobiological studies on effect of cyclosporin A (CsA) against adult male worms of Schistosoma mansoni in vitro].

PubMed

Liu, J; Chappell, L H

1998-01-01

To study the action mode of cyclosporin A (CsA) against Schistosoma mansoni in vitro. MF1 mice were infected with Schistosoma mansoni cercariae for 6 weeks when the adult worms were recovered by portal perfusion. The male worms of S. mansoni recovered were exposed to varying concentrations of CsA at 8, 16, and 24 h in vitro. Drug induced damage to the male worm surface was chrono-biologically observed throughout these experiments by SEM. After the male worms of S. mansoni were incubated with 1 microgram/ml CsA for 8-24 h, the tegument showed swelling of ridges with appearance of holes on their surface and detachment of a part of spines. The above damage of the tegument became more evident in male worms after incubation with 10, 15, 20 micrograms/ml CsA for 8-24 h. Moreover, incubation of male worms with 25 micrograms/ml CsA for 8-24 h resulted in significant deformation and disruption of tegument, rupture of ridges and detachment of spines. The tegumental damage of male worms of S. mansoni was dose- and time-dependent. The antischistosomal action of CsA is direct, the schistosome tegument appears to be the main site for CsA attack.

Known Allergen Structures Predict Schistosoma mansoni IgE-Binding Antigens in Human Infection

PubMed Central

Farnell, Edward J.; Tyagi, Nidhi; Ryan, Stephanie; Chalmers, Iain W.; Pinot de Moira, Angela; Jones, Frances M.; Wawrzyniak, Jakub; Fitzsimmons, Colin M.; Tukahebwa, Edridah M.; Furnham, Nicholas; Maizels, Rick M.; Dunne, David W.

2015-01-01

The IgE response has been associated with both allergic reactions and immunity to metazoan parasites. Recently, we hypothesized that all environmental allergens bear structural homology to IgE-binding antigens from metazoan parasites and that this homology defines the relatively small number of protein families containing allergenic targets. In this study, known allergen structures (Pfam domains) from major environmental allergen families were used to predict allergen-like (SmProfilin, SmVAL-6, SmLipocalin, SmHSP20, Sm triosephosphate isomerase, SmThioredoxin, Sm superoxide dismutase, SmCyclophilin, and Sm phosphoglycerate kinase) and non-allergen-like [Sm dynein light chain (SmDLC), SmAldolase SmAK, SmUbiquitin, and Sm14-3-3] proteins in Schistosoma mansoni. Recombinant antigens were produced in Escherichia coli and IgG1, IgG4, and IgE responses against them measured in a cohort of people (n = 222) infected with S. mansoni. All allergen-like antigens were targeted by IgE responses in infected subjects, whilst IgE responses to the non-allergen-like antigens, SmAK, SmUbiquitin, and Sm14-3-3 were essentially absent being of both low prevalence and magnitude. Two new IgE-binding Pfam domain families, not previously described in allergen family databases, were also found, with prevalent IgE responses against SmDLC (PF01221) and SmAldolase (PF00274). Finally, it was demonstrated that immunoregulatory serological processes typically associated with allergens also occurred in responses to allergen-like proteins in S. mansoni infections, including the production of IgG4 in people responding with IgE and the down-regulation of IgE in response to increased antigen exposure from S. mansoni eggs. This study establishes that structures of known allergens can be used to predict IgE responses against homologous parasite allergen-like molecules (parallergens) and that serological responses with IgE/IgG4 to parallergens mirror those seen against allergens, supporting our

Characterization of antigens from Schistosoma mansoni and construction of a cDNA library for the study of schistosomiasis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bugra, K.

1986-01-01

To examine the antigens of adult Schistosoma mansoni, /sup 35/S-methionine-labelled, detergent-extracted proteins were immunoprecipitated and analyzed on SDS-PAGE. Human infection serum immunoprecipitated 14 polypeptides with M/sub r/'s of 120, 105, 88, 86, 66, 64, 54, 48, 42, 38, 35, 32, 29, and 20 Kd. Upon digestion with endoglycosidase F polypeptides with M/sub r/'s of 120, 105, 54, 48, and 29 appeared to have carbohydrate moieties. Extracts of female and male S. mansoni were analyzed by immunoprecipitation and immunoblotting. Two polypeptides with M/sub r/'s of 86 Kd and 54 Kd were detected only in extracts of males. Polyadenylated RNA was extractedmore » from S. mansoni and translated in rabbit reticulocyte lysates. Among the in vitro translation products, polypeptides with 120, 94, 64, 43, 37, 35, 30, 26 and 22 Kd apparent molecular weights were immunoprecipitated by human infection serum. When the translation products of female worms and male worms were compared, the polypeptides with M/sub r/'s of 94 and 64 Kd were only observed in males.« less

Studies on acquired resistance to Schistosoma mansoni in mice exposed to X-irradiated cercariae

PubMed Central

Perlowagora-Szumlewicz, Alina

1964-01-01

In the first part of this paper current information on acquired resistance to schistosomes is reviewed and related to factors which have led to divergent interpretations of experimental results. The author then reports on and discusses experiments performed by her on the development of challenge infections in mice exposed to X-irradiated cercariae of Schistosoma mansoni. While there is some evidence that resistance to S. mansoni may be developed by such exposure, the author considers present findings equivocal and stresses that further research is needed to clarify the situation. ImagesFIG. 2FIG. 3FIG. 4 PMID:14165059

Kidney lesions in baboons infected with Schistosoma mansoni.

PubMed Central

Houba, V; Sturrock, R F; Butterworth, A E

1977-01-01

Glomerular lesions in baboons (Papio anubis) infected with different dosage regimes of Schistosoma mansoni were studied by immunofluorescence and light microscopy on kidney sections and by countercurrent immunoelectrophoresis on kidney homogenates and tissue eluates. Mild lesions, characterized by focal and segmental deposits of immune complexes, developed in sixty-two out of 103 baboons, irrespective of the intensity and duration of the infection. Severe, diffuse lesions developed in six baboons after prolonged and heavy infections. Adult worm and soluble egg antigens, together with IgM, IgG and C3, were detected in most of the severe lesions and in some of the mild lesions. In some animals, antigens were detected in most of the severe lesions and in some of the mild lesions. In some animals, antigens were detected in acid homogenates and eluates of kidneys which showed no deposits of immunoglobulins or complement. These observations indicate that renal lesions in S. mansoni infections may be attributable to the deposition of immune complexes pre-formed in the circulation. However, the demonstration of antigens alone in some animals may suggest an alternative possibility, namely that antigens are deposited first with a subsequent binding of antibody and complement. PMID:414868

The Compatibility Between Biomphalaria glabrata Snails and Schistosoma mansoni: An Increasingly Complex Puzzle.

PubMed

Mitta, G; Gourbal, B; Grunau, C; Knight, M; Bridger, J M; Théron, A

2017-01-01

This review reexamines the results obtained in recent decades regarding the compatibility polymorphism between the snail, Biomphalaria glabrata, and the pathogen, Schistosoma mansoni, which is one of the agents responsible for human schistosomiasis. Some results point to the snail's resistance as explaining the incompatibility, while others support a "matching hypothesis" between the snail's immune receptors and the schistosome's antigens. We propose here that the two hypotheses are not exclusive, and that the compatible/incompatible status of a particular host/parasite couple probably reflects the balance of multiple molecular determinants that support one hypothesis or the other. Because these genes are involved in a coevolutionary arms race, we also propose that the underlying mechanisms can vary. Finally, some recent results show that environmental factors could influence compatibility. Together, these results make the compatibility between B. glabrata and S. mansoni an increasingly complex puzzle. We need to develop more integrative approaches in order to find targets that could potentially be manipulated to control the transmission of schistosomiasis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Molecular context of Schistosoma mansoni transmission in the molluscan environments: A mini-review.

PubMed

Famakinde, Damilare Olatunji

2017-12-01

Schistosoma mansoni, being transmitted by some freshwater Biomphalaria snails, is a major causative agent of human schistosomiasis. In the absence of effective vaccine and alternative drug designs to fight against the disease, and with the limitations of molluscicide application, developing more efficient strategies to interrupt the snail-mediated parasite transmission is being emphasized as potentially instrumental in the efforts toward schistosomiasis elimination, hence, necessitating thorough and comprehensive understanding of the fundamental mechanisms involved in the transmission process. Based on the current advances, this paper presents a concise exposition of the cellular, biochemical, genetic and immunological dynamics of the complex and statge-by-stage interactions between the parasite and its vector in their aquatic environment. It also highlights the possible crosstalk between the parasite's intracellular cyclic adenosine monophosphate (cAMP) and p38 mitogen-activated protein kinase (p38 MAPK) during the intramolluscan stage. Undoubtedly, decades of intensive investigation have untangled many S. mansoni-B. glabrata complexities, yet many aspects of the parasite-vector cycle which can help define potential control clues await further elucidation. Copyright © 2017 Elsevier B.V. All rights reserved.

Epidemiology of soil-transmitted helminths, Schistosoma mansoni, and haematocrit values among schoolchildren in Ethiopia.

PubMed

Abera, Bayeh; Alem, Genetu; Yimer, Mulat; Herrador, Zaida

2013-03-14

This study aimed to determine the prevalence of intestinal helminths, risk factors and haematocrit values among primary schoolchildren. Across-sectional study was conducted in 12 primary schools in March 2011. Stool samples were randomly selected from 778 children and were microscopically examined using Kato-Katz and formal-ether concentration methods. Haematocrit values were measured using heparinized capillary tubes. The overall prevalence of intestinal helminths was 51.5% (rural = 68.3%, urban = 36.2%). Hookworm spp., Schistosoma mansoni and Schistosoma stercoralis were more prevalent in rural schools, whereas Hymenolepis nana was higher in urban schools (p = 0.0001). With regard to haematocrit, 34% of rural and 21.7% of urban schoolchildren had haematocrit values below the median (40.5%) (p=0.001). Hookworm spp. and S. mansoni infected children had lower haematocrit values than non-infected children (p = 0.001). Lack of footwear was positively associated with intestinal helminths infection in rural schools [OR = 2.5 (95% CI: 1.5-4.1)], and having dirty fingernails and untrimmed fingernails were positively associated with the prevalence of intestinal helminths in urban samples [OR = 1.58 (95% CI: 1.03-2.5)]. The prevalence of soil-transmitted helminths and S. mansoni differs by geographical area of the schools and social determinants. Primary school de-worming and health education on proper hygiene are recommended.

Comparative Evaluation of Anthelmintic Activity of Edible and Ornamental Pomegranate Ethanolic Extracts against Schistosoma mansoni

PubMed Central

Badary, Dalia M.; Sayed, Hesham M. B.; Bayoumi, Soad A. H.; Khalifa, Azza A.; El-Moghazy, Ahmed M.

2016-01-01

Due to the development of praziquantel (PZQ) schistosomes resistant strains, the discovery of new antischistosomal agents is of high priority in research. This work reported the in vitro and in vivo effects of the edible and ornamental pomegranate extracts against Schistosoma mansoni. Leaves and stem bark ethanolic extracts of both dried pomegranates were prepared at 100, 300, and 500 μg/mL for in vitro and 600 and 800 mg/kg for in vivo. Adult worms Schistosoma mansoni in RPMI-1640 medium for in vitro and S. mansoni infected mice for in vivo tests were obtained from Theodor Bilharz Research Institute, Cairo, Egypt. In vitro activity was manifested by significant coupled worms separation, reduction of motor activity, lethality, and ultrastructural tegumental alterations in adult worms. In vivo activity was manifested revealed by significant reduction of hepatic granulomas number and diameter, decreased number of bilharzial eggs in liver tissues, lowered liver inflammatory infiltration, decreased hepatic fibrosis, and inducible nitric oxide synthase (iNOS) expression. Ethanolic stem bark extract of edible pomegranate exhibited highest antischistosomal activities both in vitro and in vivo. Therefore, pomegranate showed a good potential to be used as a promising new candidate for the development of new schistosomicidal agents. PMID:27990425

Functional Mapping of Protein Kinase A Reveals Its Importance in Adult Schistosoma mansoni Motor Activity

PubMed Central

de Saram, Paulu S. R.; Ressurreição, Margarida; Davies, Angela J.; Rollinson, David; Emery, Aidan M.; Walker, Anthony J.

2013-01-01

Cyclic AMP (cAMP)-dependent protein kinase/protein kinase A (PKA) is the major transducer of cAMP signalling in eukaryotic cells. Here, using laser scanning confocal microscopy and ‘smart’ anti-phospho PKA antibodies that exclusively detect activated PKA, we provide a detailed in situ analysis of PKA signalling in intact adult Schistosoma mansoni, a causative agent of debilitating human intestinal schistosomiasis. In both adult male and female worms, activated PKA was consistently found associated with the tegument, oral and ventral suckers, oesophagus and somatic musculature. In addition, the seminal vesicle and gynaecophoric canal muscles of the male displayed activated PKA whereas in female worms activated PKA localized to the ootype wall, the ovary, and the uterus particularly around eggs during expulsion. Exposure of live worms to the PKA activator forskolin (50 µM) resulted in striking PKA activation in the central and peripheral nervous system including at nerve endings at/near the tegument surface. Such neuronal PKA activation was also observed without forskolin treatment, but only in a single batch of worms. In addition, PKA activation within the central and peripheral nervous systems visibly increased within 15 min of worm-pair separation when compared to that observed in closely coupled worm pairs. Finally, exposure of adult worms to forskolin induced hyperkinesias in a time and dose dependent manner with 100 µM forskolin significantly increasing the frequency of gross worm movements to 5.3 times that of control worms (P≤0.001). Collectively these data are consistent with PKA playing a central part in motor activity and neuronal communication, and possibly interplay between these two systems in S. mansoni. This study, the first to localize a protein kinase when exclusively in an activated state in adult S. mansoni, provides valuable insight into the intricacies of functional protein kinase signalling in the context of whole schistosome physiology

Inheritance of Schistosoma mansoni infection incompatibility in Biomphalaria alexandrina snails.

PubMed

El Naga, Iman F Abou; Eissa, Maha M; Mossallam, Shereen F; El-Halim, Safaa I Abd

2010-03-01

In this study, we looked at the inheritance of susceptibility and resistance to Schistosoma mansoni infection in the first generation of crossbred Biomphalaria alexandrina snails. Our ultimate goal is to use such information to develop a biological method of controlling schistosomiasis. We infected laboratory-bred snails with S. mansoni miracidia and examined cercarial shedding to determine susceptibility and resistance. Five parental groups were used: Group I contained 30 susceptible snails, Group II contained 30 resistant snails, Group III contained 15 susceptible and 15 resistant snails, Group IV contained 27 susceptible and three resistant snails and Group V contained three susceptible and 27 resistant snails. The percentage of resistant snails in the resulting progeny varied according to the ratio of susceptible and resistant parents per group; they are 7%, 100%, 68%, 45% and 97% from Groups I, II, III, IV and V, respectively. On increasing the percentage of resistant parent snails, the percentage of resistant progeny increased, while cercarial production in their susceptible progeny decreased.

A comparative study on the anti-schistosomal and hepatoprotective effects of vinpocetine and isosorbide-5-mononitrate on Schistosoma mansoni-infected mice.

PubMed

Alhusseiny, Samar M; El-Beshbishi, Samar N; Hashim, Maha M Abu; El-Nemr, Hosam El-Dein E; Handoussa, Aya E

2017-12-01

Schistosomiasis is a remarkable public health problem in developing countries. Presently, praziquantel is the optional drug for all human schistosomiasis. Owing to the increased praziquantel resistance, there is an urgent need to develop new alternatives. This study aims at determining the anti-schistosomal and/or the hepatoprotective effects of the anti-inflammatory drug; vinpocetine, and the vasodilator and the nitric oxide donor; isosorbide-5-mononitrate, in comparison to praziquantel. In the present research, the therapeutic efficacies of these drugs were assessed in Swiss albino female mice (CD-I strain) experimentally infected with an Egyptian strain of Schistosoma mansoni, using some general, parasitological, and histopathological parameters. In this work, praziquantel significantly reduced worm burden and hepatic egg load, increased the percentage of dead eggs in the small intestine and decreased granuloma count, but did not reduce granuloma diameter. While, either vinpocetine or isosorbide-5-mononitrate monotherapy did not induce significant reduction in the worm count, hepatic egg load or shift in the oogram pattern, but significantly reduced granuloma count and diameter. Moreover, isosorbide-5-mononitrate significantly reduced hepatic inflammation and necrosis. The best results were obtained in the mice groups treated with isosorbide-5-mononitrate combined with praziquantel or vinpocetine. Our results point to vinpocetine and isosorbide-5-mononitrate as a convenient and promising adjuvant to praziquantel for ameliorating schistosomal liver pathology. Further studies are recommended to reveal the actual pathways responsible for the different activities of vinpocetine and isosorbide-5-mononitrate. Copyright © 2017 Elsevier B.V. All rights reserved.

Anti-inflammatory/anti-fibrotic effects of the hepatoprotective silymarin and the schistosomicide praziquantel against Schistosoma mansoni-induced liver fibrosis

PubMed Central

2012-01-01

Background Praziquantel (PZQ) is an isoquinoline derivative (2-cyclohexylcarbonyl-1, 2, 3, 6, 7, 11b-hexahydro-4H-pyrazino{2,1-a}-isoquinoline-4-one), and is currently the drug of choice for all forms of schistosomiasis. Silymarin, a standardized milk thistle extract, of which silibinin is the main component, is known for its hepatoprotective, anti-inflammatory, antioxidant activities, and hepatocyte regeneration. This study investigates the anti-inflammatory/anti-fibrotic effects of silymarin and/or PZQ on schistosomal hepatic fibrosis. Methods Schistosoma mansoni-infected mice were divided into two large groups (I & II), each with four subgroups and were run in parallel. (i) Infected untreated; (ii) treated with silymarin, starting from the 4th (3 weeks before PZQ therapy) or 12th (5 weeks after PZQ therapy) weeks post infection (PI); (iii) treated with PZQ in the 7th week PI; and (iv) treated with silymarin, as group (ii) plus PZQ as group (iii). Comparable groups of uninfected mice run in parallel with the infected groups. Mice of groups I and II were killed 10 and 18 weeks PI, respectively. Hepatic content of hydroxyproline (HYP), serum levels and tissue expression of matrix metalloproteinase-2 (MMP-2), transforming growth factor-β1 (TGF-β1) and number of mast cells were determined. In addition, parasitological, biochemical and histological parameters that reflect disease severity and morbidity were examined. Results Silymarin caused a partial decrease in worm burden; hepatic tissue egg load, with an increase in percentage of dead eggs; modulation of granuloma size, with significant reduction of hepatic HYP content; tissue expression of MMP-2, TGF-β1; number of mast cells, with conservation of hepatic reduced glutathione (GSH). PZQ produced complete eradication of worms, eggs and alleviated liver inflammation and fibrosis. The best results were obtained, in most parameters studied, in groups of mice treated with silymarin in addition to PZQ. Conclusions Our

Eukaryotic Protein Kinases (ePKs) of the Helminth Parasite Schistosoma mansoni

PubMed Central

2011-01-01

Background Schistosomiasis remains an important parasitic disease and a major economic problem in many countries. The Schistosoma mansoni genome and predicted proteome sequences were recently published providing the opportunity to identify new drug candidates. Eukaryotic protein kinases (ePKs) play a central role in mediating signal transduction through complex networks and are considered druggable targets from the medical and chemical viewpoints. Our work aimed at analyzing the S. mansoni predicted proteome in order to identify and classify all ePKs of this parasite through combined computational approaches. Functional annotation was performed mainly to yield insights into the parasite signaling processes relevant to its complex lifestyle and to select some ePKs as potential drug targets. Results We have identified 252 ePKs, which corresponds to 1.9% of the S. mansoni predicted proteome, through sequence similarity searches using HMMs (Hidden Markov Models). Amino acid sequences corresponding to the conserved catalytic domain of ePKs were aligned by MAFFT and further used in distance-based phylogenetic analysis as implemented in PHYLIP. Our analysis also included the ePK homologs from six other eukaryotes. The results show that S. mansoni has proteins in all ePK groups. Most of them are clearly clustered with known ePKs in other eukaryotes according to the phylogenetic analysis. None of the ePKs are exclusively found in S. mansoni or belong to an expanded family in this parasite. Only 16 S. mansoni ePKs were experimentally studied, 12 proteins are predicted to be catalytically inactive and approximately 2% of the parasite ePKs remain unclassified. Some proteins were mentioned as good target for drug development since they have a predicted essential function for the parasite. Conclusions Our approach has improved the functional annotation of 40% of S. mansoni ePKs through combined similarity and phylogenetic-based approaches. As we continue this work, we will

Lot quality assurance sampling for screening communities hyperendemic for Schistosoma mansoni.

PubMed

Rabarijaona, L P; Boisier, P; Ravaoalimalala, V E; Jeanne, I; Roux, J F; Jutand, M A; Salamon, R

2003-04-01

Lot quality assurance sampling (LQAS) was evaluated for rapid low cost identification of communities where Schistosoma mansoni infection was hyperendemic in southern Madagascar. In the study area, S. mansoni infection shows very focused and heterogeneous distribution requiring multifariousness of local surveys. One sampling plan was tested in the field with schoolchildren and several others were simulated in the laboratory. Randomization and stool specimen collection were performed by voluntary teachers under direct supervision of the study staff and no significant problem occurred. As expected from Receiver Operating Characteristic (ROC) curves, all sampling plans allowed correct identification of hyperendemic communities and of most of the hypoendemic ones. Frequent misclassifications occurred for communities with intermediate prevalence and the cheapest plans had very low specificity. The study confirmed that LQAS would be a valuable tool for large scale screening in a country with scarce financial and staff resources. Involving teachers, appeared to be quite feasible and should not lower the reliability of surveys. We recommend that the national schistosomiasis control programme systematically uses LQAS for identification of communities, provided that sample sizes are adapted to the specific epidemiological patterns of S. mansoni infection in the main regions.

Glucose Uptake in the Human Pathogen Schistosoma mansoni Is Regulated Through Akt/Protein Kinase B Signaling.

PubMed

McKenzie, Maxine; Kirk, Ruth S; Walker, Anthony J

2018-06-05

In Schistosoma mansoni, the facilitated glucose transporter SGTP4, which is expressed uniquely in the apical surface tegumental membranes of the parasite, imports glucose from host blood to support its growth, development, and reproduction. However, the molecular mechanisms that underpin glucose uptake in this blood fluke are not understood. In this study we employed techniques including Western blotting, immunolocalization, confocal laser scanning microscopy, pharmacological assays, and RNA interference to functionally characterize and map activated Akt in S mansoni. We find that Akt, which could be activated by host insulin and l-arginine, was active in the tegument layer of both schistosomules and adult worms. Blockade of Akt attenuated the expression and evolution of SGTP4 at the surface of the host-invading larval parasite life-stage, and suppressed SGTP4 expression at the tegument in adults; concomitant glucose uptake by the parasite was also attenuated in both scenarios. These findings shed light on crucial mechanistic signaling processes that underpin the energetics of glucose uptake in schistosomes, which may open up novel avenues for antischistosome drug development.

A constitutively active G protein-coupled acetylcholine receptor regulates motility of larval Schistosoma mansoni.

PubMed

MacDonald, Kevin; Kimber, Michael J; Day, Tim A; Ribeiro, Paula

2015-07-01

The neuromuscular system of helminths controls a variety of essential biological processes and therefore represents a good source of novel drug targets. The neuroactive substance, acetylcholine controls movement of Schistosoma mansoni but the mode of action is poorly understood. Here, we present first evidence of a functional G protein-coupled acetylcholine receptor in S. mansoni, which we have named SmGAR. A bioinformatics analysis indicated that SmGAR belongs to a clade of invertebrate GAR-like receptors and is related to vertebrate muscarinic acetylcholine receptors. Functional expression studies in yeast showed that SmGAR is constitutively active but can be further activated by acetylcholine and, to a lesser extent, the cholinergic agonist, carbachol. Anti-cholinergic drugs, atropine and promethazine, were found to have inverse agonist activity towards SmGAR, causing a significant decrease in the receptor's basal activity. An RNAi phenotypic assay revealed that suppression of SmGAR activity in early-stage larval schistosomulae leads to a drastic reduction in larval motility. In sum, our results provide the first molecular evidence that cholinergic GAR-like receptors are present in schistosomes and are required for proper motor control in the larvae. The results further identify SmGAR as a possible candidate for antiparasitic drug targeting. Copyright © 2015 Elsevier B.V. All rights reserved.

Cardamonin, a schistosomicidal chalcone from Piper aduncum L. (Piperaceae) that inhibits Schistosoma mansoni ATP diphosphohydrolase.

PubMed

de Castro, Clarissa C B; Costa, Poliana S; Laktin, Gisele T; de Carvalho, Paulo H D; Geraldo, Reinaldo B; de Moraes, Josué; Pinto, Pedro L S; Couri, Mara R C; Pinto, Priscila de F; Da Silva Filho, Ademar A

2015-09-15

Schistosomiasis is one of the world's major public health problems, and praziquantel (PZQ) is the only available drug to treat this neglected disease with an urgent demand for new drugs. Recent studies indicated that extracts from Piper aduncum L. (Piperaceae) are active against adult worms of Schistosoma mansoni, the major etiological agent of human schistosomiasis. We investigated the in vitro schistosomicidal activity of cardamonin, a chalcone isolated from the crude extract of P. aduncum. Also, this present work describes, for the first time, the S. mansoni ATP diphosphohydrolase inhibitory activity of cardamonin, as well as, its molecular docking with S. mansoni ATPDase1, in order to investigate its mode of inhibition. In vitro schistosomicidal assays and confocal laser scanning microscopy were used to evaluate the effects of cardamonin on adult schistosomes. Cell viability was measured by MTT assay, and the S. mansoni ATPase activity was determined spectrophotometrically. Identification of the cardamonin binding site and its interactions on S. mansoni ATPDase1 were made by molecular docking experiments. A bioguided fractionation of the crude extract of P. aduncum was carried out, leading to identification of cardamonin as the active compound, along with pinocembrin and uvangoletin. Cardamonin (25, 50, and 100 µM) caused 100% mortality, tegumental alterations, and reduction of oviposition and motor activity of all adult worms of S. mansoni, without affecting mammalian cells. Confocal laser scanning microscopy showed tegumental morphological alterations and changes on the numbers of tubercles of S. mansoni worms in a dose-dependent manner. Cardamonin also inhibited S. mansoni ATP diphosphohydrolase (IC50 of 23.54 µM). Molecular docking studies revealed that cardamonin interacts with the Nucleotide-Binding of SmATPDase 1. The nature of SmATPDase 1-cardamonin interactions is mainly hydrophobic and hydrogen bonding. This report provides evidence for the in vitro

Endogenous growth factor stimulation of hemocyte proliferation induces resistance to Schistosoma mansoni challenge in the snail host.

PubMed

Pila, Emmanuel A; Gordy, Michelle A; Phillips, Valerie K; Kabore, Alethe L; Rudko, Sydney P; Hanington, Patrick C

2016-05-10

Digenean trematodes are a large, complex group of parasitic flatworms that infect an incredible diversity of organisms, including humans. Larval development of most digeneans takes place within a snail (Gastropoda). Compatibility between snails and digeneans is often very specific, such that suitable snail hosts define the geographical ranges of diseases caused by these worms. The immune cells (hemocytes) of a snail are sentinels that act as a crucial barrier to infection by larval digeneans. Hemocytes coordinate a robust and specific immunological response, participating directly in parasite killing by encapsulating and clearing the infection. Hemocyte proliferation and differentiation are influenced by unknown digenean-specific exogenous factors. However, we know nothing about the endogenous control of hemocyte development in any gastropod model. Here, we identify and functionally characterize a progranulin [Biomphalaria glabrata granulin (BgGRN)] from the snail B. glabrata, a natural host for the human blood fluke Schistosoma mansoni Granulins are growth factors that drive proliferation of immune cells in organisms, spanning the animal kingdom. We demonstrate that BgGRN induces proliferation of B. glabrata hemocytes, and specifically drives the production of an adherent hemocyte subset that participates centrally in the anti-digenean defense response. Additionally, we demonstrate that susceptible B. glabrata snails can be made resistant to infection with S. mansoni by first inducing hemocyte proliferation with BgGRN. This marks the functional characterization of an endogenous growth factor of a gastropod mollusc, and provides direct evidence of gain of resistance in a snail-digenean infection model using a defined factor to induce snail resistance to infection.

Evaluation of the sensitivity of IgG and IgM ELISA in detecting Schistosoma mansoni infections in a low endemicity setting.

PubMed

Espirito-Santo, M C C; Sanchez, M C A; Sanchez, A R; Alvarado-Mora, M V; Castilho, V L P; Gonçalves, E M N; Luna, E J A; Gryschek, R C B

2014-12-01

Schistosomiasis is a major public health concern, with 200 million people infected worldwide. In Brazil, this disease has been reported in 19 states, and its prevalence in the city of Barra Mansa in Rio de Janeiro State is 1 %. The parasitological diagnostic methods currently available in these areas lack sensitivity; however, enzyme-linked immunosorbent assays (ELISAs) have been employed successfully for the diagnosis of schistosomiasis by using antibodies against antigens of Schistosoma mansoni adult worms and eggs, and for the detection of circulating antigens. The objective of this study was to determine systematically the prevalence of S. mansoni infection in the peripheral areas of Barra Mansa. A cross-sectional study was conducted from April to December 2011 by using probabilistic sampling that collected 610 fecal samples and 612 serum samples. ELISA-IgG with total extracts and ELISA-IgM with trichloroacetic acid-soluble fractions were employed to detect antibodies against S. mansoni and were compared with the Kato-Katz and Hoffman parasitological techniques. Among the individuals studied, anti-S. mansoni antibodies were detected in 11.16 % (n = 71) by ELISA-IgG and in 20.75 % (n = 132) by ELISA-IgM, while the parasitological techniques showed 0.82 % (n = 5) positivity. The agreement between the two ELISA tests was 85.38 % (n = 543), and 8.65 % (n = 55) of the serum samples showed positive results in both tests. The higher positivity of the ELISA-IgM test corroborates the results of previous reports and indicates that the test may be a useful tool in epidemiological studies, particularly in areas of low endemicity for S. mansoni.

Towards an Understanding of the Function of the Phytochelatin Synthase of Schistosoma mansoni

PubMed Central

Rigouin, Coraline; Nylin, Elyse; Cogswell, Alexis A.; Schaumlöffel, Dirk; Dobritzsch, Dirk; Williams, David L.

2013-01-01

Phytochelatin synthase (PCS) is a protease-like enzyme that catalyzes the production of metal chelating peptides, the phytochelatins, from glutathione (GSH). In plants, algae, and fungi phytochelatin production is important for metal tolerance and detoxification. PCS proteins also function in xenobiotic metabolism by processing GSH S-conjugates. The aim of the present study is to elucidate the role of PCS in the parasitic worm Schistosoma mansoni. Recombinant S. mansoni PCS proteins expressed in bacteria could both synthesize phytochelatins and hydrolyze various GSH S-conjugates. We found that both the N-truncated protein and the N- and C-terminal truncated form of the enzyme (corresponding to only the catalytic domain) work through a thiol-dependant and, notably, metal-independent mechanism for both transpeptidase (phytochelatin synthesis) and peptidase (hydrolysis of GSH S-conjugates) activities. PCS transcript abundance was increased by metals and xenobiotics in cultured adult worms. In addition, these treatments were found to increase transcript abundance of other enzymes involved in GSH metabolism. Highest levels of PCS transcripts were identified in the esophageal gland of adult worms. Taken together, these results suggest that S. mansoni PCS participates in both metal homoeostasis and xenobiotic metabolism rather than metal detoxification as previously suggested and that the enzyme may be part of a global stress response in the worm. Because humans do not have PCS, this enzyme is of particular interest as a drug target for schistosomiasis. PMID:23383357

Influence of Schistosoma mansoni and Hookworm Infection Intensities on Anaemia in Ugandan Villages.

PubMed

Chami, Goylette F; Fenwick, Alan; Bulte, Erwin; Kontoleon, Andreas A; Kabatereine, Narcis B; Tukahebwa, Edridah M; Dunne, David W

2015-01-01

The association of anaemia with intestinal schistosomiasis and hookworm infections are poorly explored in populations that are not limited to children or pregnant women. We sampled 1,832 individuals aged 5-90 years from 30 communities in Mayuge District, Uganda. Demographic, village, and parasitological data were collected. Infection risk factors were compared in ordinal logistic regressions. Anaemia and infection intensities were analyzed in multilevel models, and population attributable fractions were estimated. Household and village-level predictors of Schistosoma mansoni and hookworm were opposite in direction or significant for single infections. S. mansoni was found primarily in children, whereas hookworm was prevalent amongst the elderly. Anaemia was more prevalent in individuals with S. mansoni and increased by 2.86 fold (p-value<0.001) with heavy S. mansoni infection intensity. Individuals with heavy hookworm were 1.65 times (p-value = 0.008) more likely to have anaemia than uninfected participants. Amongst individuals with heavy S. mansoni infection intensity, 32.0% (p-value<0.001) of anaemia could be attributed to S. mansoni. For people with heavy hookworm infections, 23.7% (p-value = 0.002) of anaemia could be attributed to hookworm. A greater fraction of anaemia (24.9%, p-value = 0.002) was attributable to heavy hookworm infections in adults (excluding pregnant women) as opposed to heavy hookworm infections in school-aged children and pregnant women (20.2%, p-value = 0.001). Community-based surveys captured anaemia in children and adults affected by S. mansoni and hookworm infections. For areas endemic with schistosomiasis or hookworm infections, WHO guidelines should include adults for treatment in helminth control programmes.

Influence of Schistosoma mansoni and Hookworm Infection Intensities on Anaemia in Ugandan Villages

PubMed Central

Chami, Goylette F.; Fenwick, Alan; Bulte, Erwin; Kontoleon, Andreas A.; Kabatereine, Narcis B.; Tukahebwa, Edridah M.; Dunne, David W.

2015-01-01

Background The association of anaemia with intestinal schistosomiasis and hookworm infections are poorly explored in populations that are not limited to children or pregnant women. Methods We sampled 1,832 individuals aged 5–90 years from 30 communities in Mayuge District, Uganda. Demographic, village, and parasitological data were collected. Infection risk factors were compared in ordinal logistic regressions. Anaemia and infection intensities were analyzed in multilevel models, and population attributable fractions were estimated. Findings Household and village-level predictors of Schistosoma mansoni and hookworm were opposite in direction or significant for single infections. S. mansoni was found primarily in children, whereas hookworm was prevalent amongst the elderly. Anaemia was more prevalent in individuals with S. mansoni and increased by 2.86 fold (p-value<0.001) with heavy S. mansoni infection intensity. Individuals with heavy hookworm were 1.65 times (p-value = 0.008) more likely to have anaemia than uninfected participants. Amongst individuals with heavy S. mansoni infection intensity, 32.0% (p-value<0.001) of anaemia could be attributed to S. mansoni. For people with heavy hookworm infections, 23.7% (p-value = 0.002) of anaemia could be attributed to hookworm. A greater fraction of anaemia (24.9%, p-value = 0.002) was attributable to heavy hookworm infections in adults (excluding pregnant women) as opposed to heavy hookworm infections in school-aged children and pregnant women (20.2%, p-value = 0.001). Conclusion Community-based surveys captured anaemia in children and adults affected by S. mansoni and hookworm infections. For areas endemic with schistosomiasis or hookworm infections, WHO guidelines should include adults for treatment in helminth control programmes. PMID:26513151

Serotonin Signaling in Schistosoma mansoni: A Serotonin–Activated G Protein-Coupled Receptor Controls Parasite Movement

PubMed Central

Rashid, Mohammed; Ribeiro, Paula

2014-01-01

Serotonin is an important neuroactive substance in all the parasitic helminths. In Schistosoma mansoni, serotonin is strongly myoexcitatory; it potentiates contraction of the body wall muscles and stimulates motor activity. This is considered to be a critical mechanism of motor control in the parasite, but the mode of action of serotonin is poorly understood. Here we provide the first molecular evidence of a functional serotonin receptor (Sm5HTR) in S. mansoni. The schistosome receptor belongs to the G protein-coupled receptor (GPCR) superfamily and is distantly related to serotonergic type 7 (5HT7) receptors from other species. Functional expression studies in transfected HEK 293 cells showed that Sm5HTR is a specific serotonin receptor and it signals through an increase in intracellular cAMP, consistent with a 5HT7 signaling mechanism. Immunolocalization studies with a specific anti-Sm5HTR antibody revealed that the receptor is abundantly distributed in the worm's nervous system, including the cerebral ganglia and main nerve cords of the central nervous system and the peripheral innervation of the body wall muscles and tegument. RNA interference (RNAi) was performed both in schistosomulae and adult worms to test whether the receptor is required for parasite motility. The RNAi-suppressed adults and larvae were markedly hypoactive compared to the corresponding controls and they were also resistant to exogenous serotonin treatment. These results show that Sm5HTR is at least one of the receptors responsible for the motor effects of serotonin in S. mansoni. The fact that Sm5HTR is expressed in nerve tissue further suggests that serotonin stimulates movement via this receptor by modulating neuronal output to the musculature. Together, the evidence identifies Sm5HTR as an important neuronal protein and a key component of the motor control apparatus in S. mansoni. PMID:24453972

Effective classification of the prevalence of Schistosoma mansoni.

PubMed

Mitchell, Shira A; Pagano, Marcello

2012-12-01

To present an effective classification method based on the prevalence of Schistosoma mansoni in the community. We created decision rules (defined by cut-offs for number of positive slides), which account for imperfect sensitivity, both with a simple adjustment of fixed sensitivity and with a more complex adjustment of changing sensitivity with prevalence. To reduce screening costs while maintaining accuracy, we propose a pooled classification method. To estimate sensitivity, we use the De Vlas model for worm and egg distributions. We compare the proposed method with the standard method to investigate differences in efficiency, measured by number of slides read, and accuracy, measured by probability of correct classification. Modelling varying sensitivity lowers the lower cut-off more significantly than the upper cut-off, correctly classifying regions as moderate rather than lower, thus receiving life-saving treatment. The classification method goes directly to classification on the basis of positive pools, avoiding having to know sensitivity to estimate prevalence. For model parameter values describing worm and egg distributions among children, the pooled method with 25 slides achieves an expected 89.9% probability of correct classification, whereas the standard method with 50 slides achieves 88.7%. Among children, it is more efficient and more accurate to use the pooled method for classification of S. mansoni prevalence than the current standard method. © 2012 Blackwell Publishing Ltd.

Schistosoma haematobium hotspots in south Nyanza, western Kenya: prevalence, distribution and co-endemicity with Schistosoma mansoni and soil-transmitted helminths

PubMed Central

2014-01-01

Background Schistosomiasis studies in western Kenya have mainly focused on the intestinal form, with evidence of urinary schistosomiasis remaining anecdotal. Detailed disease mapping has been carried out predominantly along the shores of Lake Victoria, but there is a paucity of information on intestinal and urinary schistosomiasis in inland sites. Methods This cross-sectional survey of 3,487 children aged 7–18 years from 95 schools in south Nyanza, western Kenya determined the prevalence, infection intensity, and geographical distribution of Schistosoma haematobium, evaluating its co-endemicity with Schistosoma mansoni and soil-transmitted helminths (STHs). Helminth eggs were analyzed from single urine (for S. haematobium) and stool (for S. mansoni and STHs) samples by centrifugation and Kato-Katz, respectively. Hematuria was used as a proxy indicator for S. haematobium. Schools and water bodies (ponds, water-points, streams, dams and rivers) were mapped using Geographical Information System and prevalence maps obtained using ArcView GIS Software. Results S. haematobium infections with an overall prevalence of 9.3% (95% CI = 8.4-10.2%) were mostly prevalent in Rachuonyo, 22.4% (95% CI = 19.2-25.9% and 19.7 eggs/10 ml) and Migori, 10.7% (95% CI = 9.2-12.3% and 29.5 eggs/10 ml) districts, particularly around Kayuka pond and Ongoche river respectively. Overall infections correlated with hematuria (r = 0.9, P < 0.0001) and were more likely in boys (P < 0.0001, OR = 0.624). S. mansoni infections with an overall prevalence of 13% (95% CI =11.9-14.1%) were majorly confined along the shores of Lake Victoria. STH infections were homogenously distributed with A. lumbricoides occurring in 5.4% (95% CI = 4.7-6.3%) and T. trichiura in 2.8% (95% CI = 2.3-3.4%) of the children. Although S. mansoni infections were more co-endemic with S. haematobium, only A. lumbricoides infections were positively associated with S. haematobium (P = 0

In vivo effect of single oral dose of artemether against early juvenile stages of Schistosoma mansoni Egyptian strain.

PubMed

El-Beshbishi, Samar N; Taman, Amira; El-Malky, Mohamed; Azab, Manar S; El-Hawary, Amira K; El-Tantawy, Dina A

2013-10-01

The current treatment and control of schistosomiasis, rely on a single drug, praziquantel, although, it has minor activity against juvenile stages of the parasite. Studies have shown that artemether (ART) exhibits effects against juveniles of Schistosoma mansoni Liberian and Puerto Rican strains, Schistosoma japonicum and Schistosoma haematobium. Aiming to assess the in vivo activity of single oral dose of ART against early juvenile stages of S. mansoni Egyptian strain, this study was established. Mice were treated with ART (400 mg/kg) at two time points evenly spaced over the period of larval development (7 and 21 days post-infection; pi), and a third treatment point (day 49 pi) was included to elucidate when susceptibility decreases. Administration of ART on day 7 pi reduced the total worm burden by 85.94%. The greatest reductions were seen when treatment was given on day 21 pi, with total and female worm burden reductions of 91.52% and 90.57%, respectively, and cessation of oviposition. Similar dose given on day 49 pi reduced total worm burden by 55.17% and female worm burden by 66.51%. Moreover, it induced significant reduction in the tissue egg load and significant alterations in the oogram pattern with decreased immature eggs and increased dead eggs. Antipathological activities were evident in significant reductions in granulomata count and diameter. In conclusion, ART exhibits major in vivo schistosomicidal effects against the early larval migratory stages of S. mansoni Egyptian strain, mainly the 21-day old schistosomula, hence preventing disease progression and morbidity. Copyright © 2013 Elsevier Inc. All rights reserved.

Effects of proteasome inhibitor MG-132 on the parasite Schistosoma mansoni

PubMed Central

de Paula, Renato G.; Ornelas, Alice M. M.; Moreira, Érika B. C.; Badoco, Fernanda Rafacho; Magalhães, Lizandra G.; Verjovski-Almeida, Sergio; Rodrigues, Vanderlei

2017-01-01

Proteasome is a proteolytic complex responsible for intracellular protein turnover in eukaryotes, archaea and in some actinobacteria species. Previous work has demonstrated that in Schistosoma mansoni parasites, the proteasome inhibitor MG-132 affects parasite development. However, the molecular targets affected by MG-132 in S. mansoni are not entirely known. Here, we used expression microarrays to measure the genome-wide changes in gene expression of S. mansoni adult worms exposed in vitro to MG-132, followed by in silico functional analyses of the affected genes using Ingenuity Pathway Analysis (IPA). Scanning electron microscopy was used to document changes in the parasites’ tegument. We identified 1,919 genes with a statistically significant (q-value ≤ 0.025) differential expression in parasites treated for 24 h with MG-132, when compared with control. Of these, a total of 1,130 genes were up-regulated and 790 genes were down-regulated. A functional gene interaction network comprised of MG-132 and its target genes, known from the literature to be affected by the compound in humans, was identified here as affected by MG-132. While MG-132 activated the expression of the 26S proteasome genes, it also decreased the expression of 19S chaperones assembly, 20S proteasome maturation, ubiquitin-like NEDD8 and its partner cullin-3 ubiquitin ligase genes. Interestingly, genes that encode proteins related to potassium ion binding, integral membrane component, ATPase and potassium channel activities were significantly down-regulated, whereas genes encoding proteins related to actin binding and microtubule motor activity were significantly up-regulated. MG-132 caused important changes in the worm tegument; peeling, outbreaks and swelling in the tegument tubercles could be observed, which is consistent with interference on the ionic homeostasis in S. mansoni. Finally, we showed the down-regulation of Bax pro-apoptotic gene, as well as up-regulation of two apoptosis

The hepatoprotective activity of blue green algae in Schistosoma mansoni infected mice.

PubMed

Mohamed, Azza H; Osman, Gamalat Y; Salem, Tarek A; Elmalawany, Alshimaa M

2014-10-01

This study aims to evaluate the immunomodulatory effects of a natural product, blue green algae (BGA) (100 mg/kg BW), alone or combined with praziquantel PZQ (250 mg/kg BW) on granulomatous inflammation, liver histopathology, some biochemical and immunological parameters in mice infected with Schistosoma mansoni. Results showed that the diameter and number of egg granuloma were significantly reduced after treatment of S. mansoni-infected mice with BGA, PZQ and their combination. The histopathological alterations observed in the liver of S. mansoni-infected mice were remarkably inhibited after BGA treatments. BGA decreased the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) as well as the level of total protein (TP) while the level of albumin was increased. Treatment of infected mice with BGA, PZQ as well as their combination led to significant elevation in the activities of hepatic antioxidant enzymes glutathione peroxidase (GPX) and glutathione-S-transferase (GST) as compared with control group. Combination of BGA and PZQ resulted in significant reduction in the level of intercellular adhesion molecules-1 (ICAM-1), vascular adhesion molecules-1 (VCAM-1) and tumor necrosis factor-alpha (TNF-α) when compared to those of the S. mansoni-infected group. Overall, BGA significantly inhibited the liver damage accompanied with schistosomiasis, exhibited a potent antioxidant and immunoprotective activities. This study suggests that BGA can be considered as promising for development a complementary and/or alternative medicine against schistosomiasis. Copyright © 2014 Elsevier Inc. All rights reserved.

Resistance to Schistosoma mansoni by transplantation of APO Biomphalaria tenagophila.

PubMed

Barbosa, L; Caldeira, R L; Carvalho, O S; Vidigal, T H D A; Jannotti-Passos, L K; Coelho, P M Z

2006-05-01

Transplantation of the haematopoietic organ from Biomphalaria tenagophila (Taim strain, RS, Brazil), resistant to Schistosoma mansoni, to a highly susceptible strain (Cabo Frio, RJ, Brazil) of the same species, showed in the recipient snails resistance against the trematode, when a successful transplant occurred. The success of transplantation could be confirmed by a typical molecular marker of the Taim strain in haemocytes of the recipients (350 bp detected by PCR-RFLP). The recipient snails which did not present the donor marker in haemocytes (unsuccessful transplantation) were infected with the parasite. The use of an atoxic modelling clay for closing the hole in the transplantation site reduced significantly the mortality caused by bleeding after transplantation procedures.

Transcriptomic responses of Biomphalaria pfeifferi to Schistosoma mansoni: Investigation of a neglected African snail that supports more S. mansoni transmission than any other snail species

PubMed Central

Bu, Lijing; Zhang, Si-Ming; Schilkey, Faye D.; Mkoji, Gerald M.; Loker, Eric S.

2017-01-01

Background Biomphalaria pfeifferi is highly compatible with the widespread human-infecting blood fluke Schistosoma mansoni and transmits more cases of this parasite to people than any other snail species. For these reasons, B. pfeifferi is the world’s most important vector snail for S. mansoni, yet we know relatively little at the molecular level regarding the interactions between B. pfeifferi and S. mansoni from early-stage sporocyst transformation to the development of cercariae. Methodology/Principal findings We sought to capture a portrait of the response of B. pfeifferi to S. mansoni as it occurs in nature by undertaking Illumina dual RNA-Seq on uninfected control B. pfeifferi and three intramolluscan developmental stages (1- and 3-days post infection and patent, cercariae-producing infections) using field-derived west Kenyan specimens. A high-quality, well-annotated de novo B. pfeifferi transcriptome was assembled from over a half billion non-S. mansoni paired-end reads. Reads associated with potential symbionts were noted. Some infected snails yielded fewer normalized S. mansoni reads and showed different patterns of transcriptional response than others, an indication that the ability of field-derived snails to support and respond to infection is variable. Alterations in transcripts associated with reproduction were noted, including for the oviposition-related hormone ovipostatin and enzymes involved in metabolism of bioactive amines like dopamine or serotonin. Shedding snails exhibited responses consistent with the need for tissue repair. Both generalized stress and immune factors immune factors (VIgLs, PGRPs, BGBPs, complement C1q-like, chitinases) exhibited complex transcriptional responses in this compatible host-parasite system. Significance This study provides for the first time a large sequence data set to help in interpreting the important vector role of the neglected snail B. pfeifferi in transmission of S. mansoni, including with an emphasis on

Identification of the Schistosoma mansoni TNF-Alpha Receptor Gene and the Effect of Human TNF-Alpha on the Parasite Gene Expression Profile

PubMed Central

Oliveira, Katia C.; Carvalho, Mariana L. P.; Venancio, Thiago M.; Miyasato, Patricia A.; Kawano, Toshie; DeMarco, Ricardo; Verjovski-Almeida, Sergio

2009-01-01

Background Schistosoma mansoni is the major causative agent of schistosomiasis. The parasite takes advantage of host signals to complete its development in the human body. Tumor necrosis factor-alpha (TNF-α) is a human cytokine involved in skin inflammatory responses, and although its effect on the adult parasite's metabolism and egg-laying process has been previously described, a comprehensive assessment of the TNF-α pathway and its downstream molecular effects is lacking. Methodology/Principal Findings In the present work we describe a possible TNF-α receptor (TNFR) homolog gene in S. mansoni (SmTNFR). SmTNFR encodes a complete receptor sequence composed of 599 amino acids, and contains four cysteine-rich domains as described for TNFR members. Real-time RT-PCR experiments revealed that SmTNFR highest expression level is in cercariae, 3.5 (±0.7) times higher than in adult worms. Downstream members of the known human TNF-α pathway were identified by an in silico analysis, revealing a possible TNF-α signaling pathway in the parasite. In order to simulate parasite's exposure to human cytokine during penetration of the skin, schistosomula were exposed to human TNF-α just 3 h after cercariae-to-schistosomula in vitro transformation, and large-scale gene expression measurements were performed with microarrays. A total of 548 genes with significantly altered expression were detected, when compared to control parasites. In addition, treatment of adult worms with TNF-α caused a significantly altered expression of 1857 genes. Interestingly, the set of genes altered in adults is different from that of schistosomula, with 58 genes in common, representing 3% of altered genes in adults and 11% in 3 h-old early schistosomula. Conclusions/Significance We describe the possible molecular elements and targets involved in human TNF-α effect on S. mansoni, highlighting the mechanism by which recently transformed schistosomula may sense and respond to this host mediator at the

Therapeutic effects of Allium sativum and Allium cepa in Schistosoma mansoni experimental infection.

PubMed

Mantawy, Mona Mohamed; Ali, Hanan Farouk; Rizk, Maha Zaki

2011-01-01

The effects of both garlic (Allium sativum) and onion (Allium cepa) on some biochemical parameters in Schistosoma mansoni infected mice individually and mixed either with or without the currently used drug, praziquantel (PZQ) were investigated. These involved some immunological parameters, namely IgM, IgG, interleukins 2 and 6 (IL-2 and 6) and tumor necrosis factor (TNF-α), some antioxidant enzymes [catalase, superoxide dismutase (SOD) and glutathione peroxidase (GPX)]. In addition, parasitological and histopathological investigations were performed. No changes were observed in the normal control mice treated with dry extract of onion or garlic, individually or mixed, with or without PZQ, compared to the normal healthy control group. Infection with S. mansoni showed an increase in IgG, IgM, IL-2, IL-6, TNF-α and catalase enzyme, accompanied with a decrease in GPX and SOD antioxidant enzyme activities. Remarkable amelioration was noticed in the levels of all the measured parameters in S. mansoni infected mice after administration of the studied extracts. Moreover a significant reduction in worm burden, hepatic and intestinal eggs and oogram count was noticed which was reflected in normalization of liver architecture.

Ultrastructural and cytochemical aspects of Schistosoma mansoni cercaria.

PubMed

Cavalcanti, M G S; Araújo, H R C; Paiva, M H S; Silva, G M; Barbosa, C C G S; Silva, L F; Brayner, F A; Alves, L C

2009-04-01

An alternative to identify the critical processes necessary to the parasite establishment of the host is to focus on the evolutionary stage responsible for the primary invasion, i.e. the infection structure. The objective of this study was to ultrastructurally characterize Schistosoma mansoni cercariae, using cytochemical techniques. In order to identify basic proteins, techniques such as ethanolic phosphotungstic acid (EPTA) and ammoniacal silver staining were used. Calcium sites location was achieved using the Hepler technique and to evidence anionic groups, we used cationic ferritin particles and enzyme treatment with trypsin Vibrio cholerae, chondroitinase and neuraminidase. The EPTA technique highlighted the presence of basic tegument proteins, nucleus and nucleolus from subtegumental cells, inclusion bodies and preacetabular glands. After using ammoniacal silver, we observed a strong staining in all infective larvae, particularly in the nuclei of muscle cells, circular muscle tissue and preacetabular glands. Calcium site locations were shown to be uniform, thereby limiting the inner spaces of the larvae, especially muscle cells. Samples treated with cationized ferritin particles presented strong staining at the cuticular level. Neuraminidase treatment did not alter the stained shape of such particles on the trematode surface. However, trypsin or chondroitinase treatment resulted in absence of staining on the larval surface. This information on the biochemical composition of the infecting S. mansoni larvae provides data for a better understanding of the biology of this parasite and background on the intriguing parasite-host relationship.

Female biased sex-ratio in Schistosoma mansoni after exposure to an allopatric intermediate host strain of Biomphalaria glabrata.

PubMed

Lepesant, Julie M J; Boissier, Jérôme; Climent, Déborah; Cosseau, Céline; Grunau, Christoph

2013-10-01

For parasites that require multiple hosts to complete their development, the interaction with the intermediate host may have an impact on parasite transmission and development in the definitive host. The human parasite Schistosoma mansoni needs two different hosts to complete its life cycle: the freshwater snail Biomphalaria glabrata (in South America) as intermediate host and a human or rodents as final host. To investigate the influence of the host environment on life history traits in the absence of selection, we performed experimental infections of two B. glabrata strains of different geographic origin with the same clonal population of S. mansoni. One B. glabrata strain is the sympatric host and the other one the allopatric host. We measured prevalence in the snail, the cercarial infectivity, sex-ratio, immunopathology in the final host and microsatellite frequencies of individual larvae in three successive generations. We show that, even if the parasite population is clonal based on neutral markers, S. mansoni keeps the capacity of generating phenotypic plasticity and/or variability for different life history traits when confront to an unusual environment, in this study the intermediate host. The most dramatic change was observed in sex-ratio: in average 1.7 times more female cercariae were produced when the parasite developed in an allopatric intermediate host. Copyright © 2013 Elsevier Inc. All rights reserved.

Evaluation of the Anti-schistosomal Effects of Turmeric (Curcuma longa) Versus Praziquantel in Schistosoma mansoni Infected Mice.

PubMed

Hussein, Atef; Rashed, Samia; El Hayawan, Ibrahim; El-Sayed, Rabab; Ali, Hemat

2017-01-01

Curcumin is the major active ingredient of Curcuma longa L. , traditionally known as turmeric and has been shown to exhibit a wide range of pharmacological activities including anti-parasitic effect. However, it is found to be water-insoluble and has low bioavailability. The aim of this study was to explore the potential role of turmeric solved in olive oil either alone or in combination with praziquantel (PZQ) in treatment of schistosomiasis mansoni . The whole turmeric powder suspended in olive oil (as a solvent) is indicated to S. mansoni -infected mice aiming to study its potential therapeutic role, either alone or in combination with PZQ. Turmeric significantly reduced S. mansoni worm burden and complete absence of adult worms achieved in mice treated with combination of turmeric and PZQ. Turmeric has slight non-significant effect on the oogram pattern in all examined S. mansoni infected mice. Turmeric and PZQ found to exert a significant reduction of granuloma size in comparison with control. However, turmeric has a non-significant effect on granuloma number. On the other hand, turmeric or/and PZQ treated mice showed obvious improvement of pathology with mild cloudy swelling and less hydropic degeneration. Turmeric significantly reduced parasite worm burden, granuloma size and consequently the pathology of affected liver, it still far less effective than PZQ.

Schistosoma mansoni reinfection: Analysis of risk factors by classification and regression tree (CART) modeling

PubMed Central

Oliveira-Prado, Roberta; Matoso, Leonardo Ferreira; Veloso, Bráulio M.; Andrade, Gisele; Kloos, Helmut; Bethony, Jeffrey M.; Assunção, Renato M.; Correa-Oliveira, Rodrigo

2017-01-01

Praziquantel (PZQ) is an effective chemotherapy for schistosomiasis mansoni and a mainstay for its control and potential elimination. However, it does not prevent against reinfection, which can occur rapidly in areas with active transmission. A guide to ranking the risk factors for Schistosoma mansoni reinfection would greatly contribute to prioritizing resources and focusing prevention and control measures to prevent rapid reinfection. The objective of the current study was to explore the relationship among the socioeconomic, demographic, and epidemiological factors that can influence reinfection by S. mansoni one year after successful treatment with PZQ in school-aged children in Northeastern Minas Gerais state Brazil. Parasitological, socioeconomic, demographic, and water contact information were surveyed in 506 S. mansoni-infected individuals, aged 6 to 15 years, resident in these endemic areas. Eligible individuals were treated with PZQ until they were determined to be negative by the absence of S. mansoni eggs in the feces on two consecutive days of Kato-Katz fecal thick smear. These individuals were surveyed again 12 months from the date of successful treatment with PZQ. A classification and regression tree modeling (CART) was then used to explore the relationship between socioeconomic, demographic, and epidemiological variables and their reinfection status. The most important risk factor identified for S. mansoni reinfection was their “heavy” infection at baseline. Additional analyses, excluding heavy infection status, showed that lower socioeconomic status and a lower level of education of the household head were also most important risk factors for S. mansoni reinfection. Our results provide an important contribution toward the control and possible elimination of schistosomiasis by identifying three major risk factors that can be used for targeted treatment and monitoring of reinfection. We suggest that control measures that target heavily infected

Small gene family encoding an eggshell (chorion) protein of the human parasite Schistosoma mansoni

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bobek, L.A.; Rekosh, D.M.; Lo Verde, P.T.

1988-08-01

The authors isolated six independent genomic clones encoding schistosome chorion or eggshell proteins from a Schistosoma mansoni genomic library. A linkage map of five of the clones spanning 35 kilobase pairs (kbp) of the S. mansoni genome was constructed. The region contained two eggshell protein genes closely linked, separated by 7.5 kbp of intergenic DNA. The two genes of the cluster were arranged in the same orientation, that is, they were transcribed from the same strand. The sixth clone probably represents a third copy of the eggshell gene that is not contained within the 35-kbp region. The 5- end ofmore » the mRNA transcribed from these genes was defined by primer extension directly off the RNA. The ATCAT cap site sequence was homologous to a silkmoth chorion PuTCATT cap site sequence, where Pu indicates any purine. DNA sequence analysis showed that there were no introns in these genes. The DNA sequences of the three genes were very homologous to each other and to a cDNA clone, pSMf61-46, differing only in three or four nucleotices. A multiple TATA box was located at positions -23 to -31, and a CAAAT sequence was located at -52 upstream of the eggshell transcription unit. Comparison of sequences in regions further upstream with silkmoth and Drosophila sequences revealed very short elements that were shared. One such element, TCACGT, recently shown to be an essential cis-regulatory element for silkmoth chorion gene promoter function, was found at a similar position in all three organisms.« less

Schistosoma mansoni: vaccination of mice with 10-krad-irradiated, cryopreserved schistosomules

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lewis, F.A.; Stirewalt, M.A.; Leef, J.L.

1984-06-01

Protection against a Schistosoma mansoni cercarial challenge was evaluated in mice immunized with a vaccine composed of 10-krad-irradiated, cryopreserved schistosomules. The level of resistance induced in C57B1/6 or NMRI (CV) mice increased with the number of schistosomules injected. Up to 83% reduction in challenge worm burden was achieved when 5000 schistosomules were injected per mouse. Intramuscular injection of the vaccine was superior to subcutaneous. Multiple immunizations, up to 3 at 4-week intervals, did not increase the resistance induced by a single immunization. A high level of protection developed in as little as 2 weeks and was maintained through at leastmore » 12 weeks postimmunization. The vaccine irradiated with 10 krad from either a 60-cobalt or 137-cesium source induced equivalent levels of resistance, and no differences were found in the immunogenicity of vaccines comprised of organisms irradiated as cercariae or as 1- to 3-hr-old schistosomules. These findings are basic to the development of a cryopreserved, live vaccine against schistosomiasis of humans or domestic animals.« less

Identification of Antigenic Glycans from Schistosoma mansoni by Using a Shotgun Egg Glycan Microarray

PubMed Central

Mickum, Megan L.; Prasanphanich, Nina Salinger; Song, Xuezheng; Dorabawila, Nelum; Mandalasi, Msano; Lasanajak, Yi; Luyai, Anthony; Secor, W. Evan; Wilkins, Patricia P.; Van Die, Irma; Smith, David F.; Nyame, A. Kwame

2016-01-01

Infection of mammals by the parasitic helminth Schistosoma mansoni induces antibodies to glycan antigens in worms and eggs, but the differential nature of the immune response among infected mammals is poorly understood. To better define these responses, we used a shotgun glycomics approach in which N-glycans from schistosome egg glycoproteins were prepared, derivatized, separated, and used to generate an egg shotgun glycan microarray. This array was interrogated with sera from infected mice, rhesus monkeys, and humans and with glycan-binding proteins and antibodies to gather information about the structures of antigenic glycans, which also were analyzed by mass spectrometry. A major glycan antigen targeted by IgG from different infected species is the FLDNF epitope [Fucα3GalNAcβ4(Fucα3)GlcNAc-R], which is also recognized by the IgG monoclonal antibody F2D2. The FLDNF antigen is expressed by all life stages of the parasite in mammalian hosts, and F2D2 can kill schistosomula in vitro in a complement-dependent manner. Different antisera also recognized other glycan determinants, including core β-xylose and highly fucosylated glycans. Thus, the natural shotgun glycan microarray of schistosome eggs is useful in identifying antigenic glycans and in developing new anti-glycan reagents that may have diagnostic applications and contribute to developing new vaccines against schistosomiasis. PMID:26883596

Epidemiology of intestinal helminthiasis among school children with emphasis on Schistosoma mansoni infection in Wolaita zone, Southern Ethiopia.

PubMed

Alemayehu, Bereket; Tomass, Zewdneh; Wadilo, Fiseha; Leja, Dawit; Liang, Song; Erko, Berhanu

2017-06-20

Intestinal helminth infections are major parasitic diseases causing public health problems in Ethiopia. Although the epidemiology of these infections are well documented in Ethiopia, new transmission foci for schistosomiasis are being reported in different parts of the country. The objective of this study was to assess the prevalence of Schistosoma mansoni and other intestinal helminth infections among school children and determine the endemicity of schistosomiasis in Wolaita Zone, southern Ethiopia. Cross-sectional parasitological and malacological surveys were conducted by collecting stool samples for microscopic examination and snails for intermediate host identification. Stool samples were collected from 503 children and processed for microscopic examination using Kato-Katz and formalin-ether concentration methods. Snails collected from aquatic environments in the study area were identified to species level and Biomphalaria pfeifferi snails, the intermediate host of S. mansoni,, were individually exposed to artificial light in order to induce cercariae shedding. Cercariae shed from snails were used to infect laboratory-bred Swiss albino mice in order to identify the schistosome to species level. The overall prevalence of intestinal helminth infections was 72.2% among school children. S. mansoni infection prevalence was 58.6%. The prevalence and intensity of S. mansoni infections varied among schools and sex of children. Swimming was the only factor reported to be significantly associated with S. mansoni infection (AOR = 2.954, 95% CI:1.962-4.449). Other intestinal helminth species identified were hookworms (27.6%), Ascaris lumbricoides (8.7%), E. vermicularis (2.8%), Taenia species (2.6%), T. trichiura (1.2%) and H. nana (0.6%). Only B. pfeifferi snails collected from streams shed schistosome cercariae and 792 adult S. mansoni worms were harvested from mice exposed to cercariae shed from B. pfeifferi on the 6th week post-exposure. The present study found high

Improvement of the liver pathology by the aqueous extract and the n-butanol fraction of Sida pilosa Retz in Schistosoma mansoni-infected mice.

PubMed

Jatsa, Hermine Boukeng; Russo, Remo Castro; Pereira, Cintia Aparecida de Jesus; Aguilar, Edenil Costa; Garcia, Cristiana Couto; Araújo, Emília Souza; Oliveira, Jailza Lima Rodrigues; Rodrigues, Vanessa Fernandes; de Oliveira, Vinícius Gustavo; Alvarez-Leite, Jacqueline Isaura; Braga, Fernão Castro; Louis-Albert Tchuem Tchuente; Kamtchouing, Pierre; Negrão-Corrêa, Deborah Aparecida; Teixeira, Mauro Martins

2016-03-02

Sida pilosa Retz (Malvaceae) is a plant used in Africa for the treatment of intestinal helminthiasis, lower abdominal pains and dysmenorrhea. In order to determine the potential use of S. pilosa in the treatment of schistosomiasis mansoni, we evaluated the schistosomicidal, antioxidant and anti-fibrotic properties of the aqueous extract and the n-butanol fraction of its aerial parts. S. pilosa aqueous extract (SpAE) at 100, 200 and 400mg/kg and n-butanol fraction (SpBF) at 50, 100 and 200mg/kg were administered per os to Schistosoma mansoni-infected mice for 4 weeks. Praziquantel (100mg/kg × 5 days) was used as reference drug. After sacrifice, worm burden and egg count, transaminases and proteins levels were evaluated. Malondialdehyde (MDA), lipid hydroperoxydes (LOOH), catalase (CAT), superoxide dismutase (SOD), eosinophil peroxidase (EPO) and myeloperoxidase (MPO) were also measured. The anti-fibrotic effect of the plant was evaluated by the determination of hydroxyproline and γ-interferon (IFN-γ). The treatment of S. mansoni-infected mice by SpAE or SpBF resulted in a moderate reduction of worm burden and egg load in the liver and intestine. Both SpAE and SpBF significantly reversed the increasing liver proteins, MDA, LOOH and CAT levels induced by the infection. Moreover, SOD activity was improved by SpAE and SpBF. Schistosomiasis mansoni considerably increased the EPO (p<0.001) and MPO activities (p<0.001). SpAE treatment significantly reduced EPO and MPO activities at all doses. SpBF failed to reduce the increasing MPO and decreased EPO only at the highest dose. S. mansoni-infection induced an increase in hydroxyproline content (p<0.001) and a decrease in IFN-γ level (p<0.001). Both SpAE and SpBF significantly reduced hepatic hydroxyproline content, while only SpAE (p<0.05) improved IFN-γ level. These results suggest that the liver pathology in schistosomiasis mansoni is improved by S. pilosa aqueous extract, which disclosed a moderate schistosomicidal

Landscape of the spliced leader trans-splicing mechanism in Schistosoma mansoni.

PubMed

Boroni, Mariana; Sammeth, Michael; Gava, Sandra Grossi; Jorge, Natasha Andressa Nogueira; Macedo, Andréa Mara; Machado, Carlos Renato; Mourão, Marina Moraes; Franco, Glória Regina

2018-03-01

Spliced leader dependent trans-splicing (SLTS) has been described as an important RNA regulatory process that occurs in different organisms, including the trematode Schistosoma mansoni. We identified more than seven thousand putative SLTS sites in the parasite, comprising genes with a wide spectrum of functional classes, which underlines the SLTS as a ubiquitous mechanism in the parasite. Also, SLTS gene expression levels span several orders of magnitude, showing that SLTS frequency is not determined by the expression level of the target gene, but by the presence of particular gene features facilitating or hindering the trans-splicing mechanism. Our in-depth investigation of SLTS events demonstrates widespread alternative trans-splicing (ATS) acceptor sites occurring in different regions along the entire gene body, highlighting another important role of SLTS generating alternative RNA isoforms in the parasite, besides the polycistron resolution. Particularly for introns where SLTS directly competes for the same acceptor substrate with cis-splicing, we identified for the first time additional and important features that might determine the type of splicing. Our study substantially extends the current knowledge of RNA processing by SLTS in S. mansoni, and provide basis for future studies on the trans-splicing mechanism in other eukaryotes.

Physiological performance and work capacity of Sudanese cane cutters with Schistosoma mansoni infection.

PubMed

Collins, K J; Brotherhood, R J; Davies, C T; Doré, C; Hackett, A J; Imms, F J; Musgrove, J; Weiner, J S; Amin, M A; El Karim, M; Ismail, H M; Omer, A H; Sukkar, M Y

1976-05-01

Physiological tests of work performance and measurement of field productivity were made in 194 Sudanese cane cutters in order to study the effect of Schistosoma mansoni infection. The cane cutters were selected from two age ranges (16-24 and 25-45 years) and subdivided into three clinical groups: not infected, infected with, and infected without clinical signs of hepatosplenomegaly. Men infected with Schistosoma haemotobium, malaria (blood film), or with hemoglobin levels less than 10 g/100 ml were excluded. There was a statistically significant (P less than 0.002) higher mean hemoglobin concentration in those not infected but the mean difference was less than 1 g/100 ml. Submaximal responses to exercise on a stationary bicycle ergometer, oxygen intake, ventilation, tidal volume, cardiac frequency and estimated maximal aerobic power output calculated both in absolute terms and relative to lean body mass and leg volume were similar in the six groups of cane cutters. No significant differences were found in physique, body composition or in thermoregulatory function tests. The cane cutters were found to have little natural acclimatization to heat in terms of sweating capacity when compared with a group of fully acclimatized Sudanese soldiers. The mean productivity (mean daily weight of cane cut per man) was significantly correlated with the individual's estimated maximum aerobic capacity determined in the laboratory, but not with the degree of S. mansoni infection. The noninfected group was less "efficient" (mean productivity:oxygen intake) during cutting than the infected groups but a larger proportion of the noninfected were in their first season of cutting. There was a positive correlation between the number of seasons' cutting experience and the individual's age, degree of infection and mean productivity. Cane cutters studied in this investigation were a relatively fit, active population from whom the more seriously ill were excluded. These results do not

Evaluation of the Anti-schistosomal Effects of Turmeric (Curcuma longa) Versus Praziquantel in Schistosoma mansoni Infected Mice

PubMed Central

HUSSEIN, Atef; RASHED, Samia; El HAYAWAN, Ibrahim; El-SAYED, Rabab; ALI, Hemat

2017-01-01

Background: Curcumin is the major active ingredient of Curcuma longa L., traditionally known as turmeric and has been shown to exhibit a wide range of pharmacological activities including anti-parasitic effect. However, it is found to be water-insoluble and has low bioavailability. The aim of this study was to explore the potential role of turmeric solved in olive oil either alone or in combination with praziquantel (PZQ) in treatment of schistosomiasis mansoni. Methods: The whole turmeric powder suspended in olive oil (as a solvent) is indicated to S. mansoni-infected mice aiming to study its potential therapeutic role, either alone or in combination with PZQ. Results: Turmeric significantly reduced S. mansoni worm burden and complete absence of adult worms achieved in mice treated with combination of turmeric and PZQ. Turmeric has slight non-significant effect on the oogram pattern in all examined S. mansoni infected mice. Turmeric and PZQ found to exert a significant reduction of granuloma size in comparison with control. However, turmeric has a non-significant effect on granuloma number. On the other hand, turmeric or/and PZQ treated mice showed obvious improvement of pathology with mild cloudy swelling and less hydropic degeneration. Conclusion: Turmeric significantly reduced parasite worm burden, granuloma size and consequently the pathology of affected liver, it still far less effective than PZQ. PMID:29317884

Redox balance mechanisms in Schistosoma mansoni rely on peroxiredoxins and albumin and implicate peroxiredoxins as novel drug targets.

PubMed

Sayed, Ahmed A; Cook, Shawna K; Williams, David L

2006-06-23

Schistosoma mansoni, a causative agent of schistosomiasis, resides in the hepatic portal circulation of their human host up to 30 years without being eliminated by the host immune attack. Production of an antioxidant "firewall," which would neutralize the oxidative assault generated by host immune defenses, is one proposed survival mechanism of the parasite. Schistosomes lack catalase, the main H2O2-neutralizing enzyme of many organisms, and their glutathione peroxidases are in the phospholipid class with poor reactivity toward H2O2. Evidence implicates peroxiredoxins (Prx) as providing the main enzymatic activity to reduce H2O2 in the parasite. Quantitative monitoring of Prx mRNAs during parasite life cycle indicated that Prx proteins are differentially expressed, with highest expression occurring in adult stages (oxidative resistant stages). Incubation of schistosomula with Prx1 double-stranded RNA knocked down total Prx enzymatic activity and resulted in lowered survival of cultured parasites compared with controls demonstrating that Prx are essential parasite proteins. These results represent the first report of lethal gene silencing in Schistosoma. Investigation of downstream effects of Prx silencing revealed an abrupt increase of lipid peroxides and the generation of several oxidized proteins. Using mass spectrometry, parasite albumin and actin were identified as the main oxidized proteins. Gene expression analysis showed that schistosome albumin was induced by oxidative stress. This study highlights Prx proteins as essential parasite proteins and potential new targets for anti-schistosome drug development and albumin as a novel, sacrificial oxidant scavenging protein in parasite redox regulation.

Schistosoma mansoni cercariae swim efficiently by exploiting an elastohydrodynamic coupling

NASA Astrophysics Data System (ADS)

Krishnamurthy, Deepak; Katsikis, Georgios; Bhargava, Arjun; Prakash, Manu

2017-03-01

The motility of many parasites is critical for infecting their host, as exemplified in the transmission cycle of the parasite Schistosoma mansoni. In its human infectious stage, submillimetre-scale forms of the parasite known as cercariae swim in freshwater and infect humans by penetrating the skin. This infection causes schistosomiasis, a disease comparable to malaria in global socio-economic impact. Given that cercariae do not feed and hence have a lifetime of around 12 hours, efficient motility is crucial for schistosomiasis transmission. Despite this, a first-principles understanding of how cercariae swim is lacking. Combining biological experiments, a novel theoretical model and its robotic realization, we show that cercariae use their forked tail to swim against gravity using a novel swimming gait, described here as a `T-swimmer gait'. During this gait, cercariae beat their tail periodically while maintaining an increased flexibility near their posterior and anterior ends. This flexibility allows an interaction between fluid drag and bending resistance--an elastohydrodynamic coupling, to naturally break time-reversal symmetry and enable locomotion at small length scales. Finally, we find that cercariae maintain this flexibility at an optimal regime for efficient swimming. We anticipate that our work sets the ground for linking the swimming of cercariae to disease transmission, and could potentially enable explorations of novel strategies for schistosomiasis control and prevention.

The diterpenoid 7-keto-sempervirol, derived from Lycium chinense, displays anthelmintic activity against both Schistosoma mansoni and Fasciola hepatica.

PubMed

Edwards, Jennifer; Brown, Martha; Peak, Emily; Bartholomew, Barbara; Nash, Robert J; Hoffmann, Karl F

2015-03-01

Two platyhelminths of biomedical and commercial significance are Schistosoma mansoni (blood fluke) and Fasciola hepatica (liver fluke). These related trematodes are responsible for the chronic neglected tropical diseases schistosomiasis and fascioliasis, respectively. As no vaccine is currently available for anti-flukicidal immunoprophylaxis, current treatment is mediated by mono-chemical chemotherapy in the form of mass drug administration (MDA) (praziquantel for schistosomiasis) or drenching (triclabendazole for fascioliasis) programmes. This overreliance on single chemotherapeutic classes has dramatically limited the number of novel chemical entities entering anthelmintic drug discovery pipelines, raising significant concerns for the future of sustainable blood and liver fluke control. Here we demonstrate that 7-keto-sempervirol, a diterpenoid isolated from Lycium chinense, has dual anthelmintic activity against related S. mansoni and F. hepatica trematodes. Using a microtiter plate-based helminth fluorescent bioassay (HFB), this activity is specific (Therapeutic index = 4.2, when compared to HepG2 cell lines) and moderately potent (LD50 = 19.1 μM) against S. mansoni schistosomula cultured in vitro. This anti-schistosomula effect translates into activity against both adult male and female schistosomes cultured in vitro where 7-keto-sempervirol negatively affects motility/behaviour, surface architecture (inducing tegumental holes, tubercle swelling and spine loss/shortening), oviposition rates and egg morphology. As assessed by the HFB and microscopic phenotypic scoring matrices, 7-keto-sempervirol also effectively kills in vitro cultured F. hepatica newly excysted juveniles (NEJs, LD50 = 17.7 μM). Scanning electron microscopy (SEM) evaluation of adult F. hepatica liver flukes co-cultured in vitro with 7-keto-sempervirol additionally demonstrates phenotypic abnormalities including breaches in tegumental integrity and spine loss. 7-keto-sempervirol negatively

Development of a Schistosoma mansoni shotgun O-glycan microarray and application to the discovery of new antigenic schistosome glycan motifs.

PubMed

van Diepen, Angela; van der Plas, Arend-Jan; Kozak, Radoslaw P; Royle, Louise; Dunne, David W; Hokke, Cornelis H

2015-06-01

Upon infection with Schistosoma, antibody responses are mounted that are largely directed against glycans. Over the last few years significant progress has been made in characterising the antigenic properties of N-glycans of Schistosoma mansoni. Despite also being abundantly expressed by schistosomes, much less is understood about O-glycans and antibody responses to these have not yet been systematically analysed. Antibody binding to schistosome glycans can be analysed efficiently and quantitatively using glycan microarrays, but O-glycan array construction and exploration is lagging behind because no universal O-glycanase is available, and release of O-glycans has been dependent on chemical methods. Recently, a modified hydrazinolysis method has been developed that allows the release of O-glycans with free reducing termini and limited degradation, and we applied this method to obtain O-glycans from different S. mansoni life stages. Two-dimensional HPLC separation of 2-aminobenzoic acid-labelled O-glycans generated 362 O-glycan-containing fractions that were printed on an epoxide-modified glass slide, thereby generating the first shotgun O-glycan microarray containing naturally occurring schistosome O-glycans. Monoclonal antibodies and mass spectrometry showed that the O-glycan microarray contains well-known antigenic glycan motifs as well as numerous other, potentially novel, antibody targets. Incubations of the microarrays with sera from Schistosoma-infected humans showed substantial antibody responses to O-glycans in addition to those observed to the previously investigated N- and glycosphingolipid glycans. This underlines the importance of the inclusion of these often schistosome-specific O-glycans in glycan antigen studies and indicates that O-glycans contain novel antigenic motifs that have potential for use in diagnostic methods and studies aiming at the discovery of vaccine targets. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights

Rapid screening for Schistosoma mansoni in western Côte d'Ivoire using a simple school questionnaire.

PubMed Central

Utzinger, J.; N'Goran, E. K.; Ossey, Y. A.; Booth, M.; Traoré, M.; Lohourignon, K. L.; Allangba, A.; Ahiba, L. A.; Tanner, M.; Lengeler, C.

2000-01-01

The distribution of schistosomiasis is focal, so if the resources available for control are to be used most effectively, they need to be directed towards the individuals and/or communities at highest risk of morbidity from schistosomiasis. Rapid and inexpensive ways of doing this are needed, such as simple school questionnaires. The present study used such questionnaires in an area of western Côte d'Ivoire where Schistosoma mansoni is endemic; correctly completed questionnaires were returned from 121 out of 134 schools (90.3%), with 12,227 children interviewed individually. The presence of S. mansoni was verified by microscopic examination in 60 randomly selected schools, where 5047 schoolchildren provided two consecutive stool samples for Kato-Katz thick smears. For all samples it was found that 54.4% of individuals were infected with S. mansoni. Moreover, individuals infected with S. mansoni reported "bloody diarrhoea", "blood in stools" and "schistosomiasis" significantly more often than uninfected children. At the school level, Spearman rank correlation analysis showed that the prevalence of S. mansoni significantly correlated with the prevalence of reported bloody diarrhoea (P = 0.002), reported blood in stools (P = 0.014) and reported schistosomiasis (P = 0.011). Reported bloody diarrhoea and reported blood in stools had the best diagnostic performance (sensitivity: 88.2%, specificity: 57.7%, positive predictive value: 73.2%, negative predictive value: 78.9%). The study, which is probably the largest of its kind ever undertaken in Africa, revealed a moderate diagnostic performance of questionnaires for identifying individuals and/or communities at high risk from S. mansoni. PMID:10812739

Anthelmintic effects of the essential oil of fennel (Foeniculum vulgare Mill., Apiaceae) against Schistosoma mansoni.

PubMed

Wakabayashi, Kamila A L; de Melo, Nathalya I; Aguiar, Daniela P; de Oliveira, Pollyanna F; Groppo, Milton; da Silva Filho, Ademar A; Rodrigues, Vanderlei; Cunha, Wilson R; Tavares, Denise C; Magalhães, Lizandra G; Crotti, Antônio E M

2015-07-01

Foeniculum vulgare Mill. (Apiaceae), known as fennel, is a widespread aromatic herbaceous plant, and its essential oil is used as additive in the food, pharmaceutical, cosmetic, and perfume industries. The in vitro antischistosomal activity and cytotoxic effects against V79 cells of the essential oil of F. vulgare cultivated in southeastern Brazil (FV-EO) was investigated. The FV-EO was obtained by hydrodistillation and characterized by GC-FID and GC/MS analyses. (E)-Anethole (69.8%) and limonene (22.5%) were identified as the major constituents. Its anthelmintic activity against Schistosoma mansoni was evaluated at concentrations of 10, 50, and 100 μg/ml, and it was found to be active against adult S. mansoni worms, although it was less effective than the positive control praziquantel (PZQ) in terms of separation of the coupled pairs, mortality, and decreased motor activity. However, FV-EO elicited an interesting dose-dependent reduction in the number of S. mansoni eggs. On their own, (E)-anethole and the limonene enantiomers were much less effective than FV-EO and PZQ. An XTT-cytotoxicity-based assay evidenced no FV-EO cytotoxicity against V79 cells. In summary, FV-EO displayed moderate in vitro schistosomicidal activity against adult S. mansoni worms, exerted remarkable inhibitory effects on the egg development, and was of low toxicity. Copyright © 2015 Verlag Helvetica Chimica Acta AG, Zürich.

A field survey using LAMP assay for detection of Schistosoma mansoni in a low-transmission area of schistosomiasis in Umbuzeiro, Brazil: Assessment in human and snail samples.

PubMed

Gandasegui, Javier; Fernández-Soto, Pedro; Muro, Antonio; Simões Barbosa, Constança; Lopes de Melo, Fabio; Loyo, Rodrigo; de Souza Gomes, Elainne Christine

2018-03-01

In Brazil, schistosomiasis is a parasitic disease of public health relevance, mainly in poor areas where Schistosoma mansoni is the only human species encountered and Biomphalaria straminea is one of the intermediate host snails. A nested-PCR based on a specific mitochondrial S. mansoni minisatellite DNA region has been successfully developed and applied as a reference method in Brazil for S. mansoni detection, mainly in host snails for epidemiological studies. The amplification efficiency of LAMP is known to be higher than PCR. The present work aimed to assess the utility of our previously described SmMIT-LAMP assay for S. mansoni detection in human stool and snail samples in a low-transmission area of schistosomiasis in the municipality of Umbuzeiro, Paraíba State, Northeast Region of Brazil. A total of 427 human stool samples were collected during June-July 2016 in the municipality of Umbuzeiro and an overall prevalence of 3.04% (13/427) resulted positive by duplicate Kato-Katz thick smear. A total of 1,175 snails identified as Biomphalaria straminea were collected from 14 breeding sites along the Paraíba riverbank and distributed in 46 pools. DNA from human stool samples and pooled snails was extracted using the phenol/chloroform method. When performing the SmMIT-LAMP assay a total of 49/162 (30.24%) stool samples resulted positive, including 12/13 (92.31%) that were Kato-Katz positive and 37/149 (24.83%) previously Kato-Katz negative. By nested-PCR, only 1/46 pooled DNA snail samples was positive. By SmMIT-LAMP assay, the same sample also resulted positive and an additional one was positive from a different breeding site. Data of human and snail surveys were used to build risk maps of schistosomiasis incidence using kernel density analysis. This is the first study in which a LAMP assay was evaluated in both human stool and snail samples from a low-transmission schistosomiasis-endemic area. Our SmMIT-LAMP proved to be much more efficient in detection of S

Rapid detection and identification of four major Schistosoma species by high-resolution melt (HRM) analysis.

PubMed

Li, Juan; Zhao, Guang-Hui; Lin, RuiQing; Blair, David; Sugiyama, Hiromu; Zhu, Xing-Quan

2015-11-01

Schistosomiasis, caused by blood flukes belonging to several species of the genus Schistosoma, is a serious and widespread parasitic disease. Accurate and rapid differentiation of these etiological agents of animal and human schistosomiasis to species level can be difficult. We report a real-time PCR assay coupled with a high-resolution melt (HRM) assay targeting a portion of the nuclear 18S rDNA to detect, identify, and distinguish between four major blood fluke species (Schistosoma japonicum, Schistosoma mansoni, Schistosoma haematobium, and Schistosoma mekongi). Using this system, the Schistosoma spp. was accurately identified and could also be distinguished from all other trematode species with which they were compared. As little as 10(-5) ng genomic DNA from a Schistosoma sp. could be detected. This process is inexpensive, easy, and can be completed within 3 h. Examination of 21 representative Schistosoma samples from 15 geographical localities in seven endemic countries validated the value of the HRM detection assay and proved its reliability. The melting curves were characterized by peaks of 83.65 °C for S. japonicum and S. mekongi, 85.65 °C for S. mansoni, and 85.85 °C for S. haematobium. The present study developed a real-time PCR coupled with HRM analysis assay for detection and differential identification of S. mansoni, S. haematobium, S. japonicum, and S. mekongi. This method is rapid, sensitive, and inexpensive. It has important implications for epidemiological studies of Schistosoma.

Identification of Antigenic Glycans from Schistosoma mansoni by Using a Shotgun Egg Glycan Microarray.

PubMed

Mickum, Megan L; Prasanphanich, Nina Salinger; Song, Xuezheng; Dorabawila, Nelum; Mandalasi, Msano; Lasanajak, Yi; Luyai, Anthony; Secor, W Evan; Wilkins, Patricia P; Van Die, Irma; Smith, David F; Nyame, A Kwame; Cummings, Richard D; Rivera-Marrero, Carlos A

2016-05-01

Infection of mammals by the parasitic helminth Schistosoma mansoni induces antibodies to glycan antigens in worms and eggs, but the differential nature of the immune response among infected mammals is poorly understood. To better define these responses, we used a shotgun glycomics approach in which N-glycans from schistosome egg glycoproteins were prepared, derivatized, separated, and used to generate an egg shotgun glycan microarray. This array was interrogated with sera from infected mice, rhesus monkeys, and humans and with glycan-binding proteins and antibodies to gather information about the structures of antigenic glycans, which also were analyzed by mass spectrometry. A major glycan antigen targeted by IgG from different infected species is the FLDNF epitope [Fucα3GalNAcβ4(Fucα3)GlcNAc-R], which is also recognized by the IgG monoclonal antibody F2D2. The FLDNF antigen is expressed by all life stages of the parasite in mammalian hosts, and F2D2 can kill schistosomula in vitro in a complement-dependent manner. Different antisera also recognized other glycan determinants, including core β-xylose and highly fucosylated glycans. Thus, the natural shotgun glycan microarray of schistosome eggs is useful in identifying antigenic glycans and in developing new anti-glycan reagents that may have diagnostic applications and contribute to developing new vaccines against schistosomiasis. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Morphological Characteristics of Schistosoma mansoni PZQ-Resistant and -Susceptible Strains Are Different in Presence of Praziquantel

PubMed Central

Pinto-Almeida, António; Mendes, Tiago; de Oliveira, Rosimeire Nunes; Corrêa, Sheila de Andrade Penteado; Allegretti, Silmara Marques; Belo, Silvana; Tomás, Ana; Anibal, Fernanda de Freitas; Carrilho, Emanuel; Afonso, Ana

2016-01-01

Schistosomiasis is one of the most common human parasitic diseases whose socioeconomic impact is only surpassed by malaria. Praziquantel (PZQ) is the only drug commercially available for the treatment of all schistosome species causing disease in humans. However, there has been stronger evidences of PZQ-resistance on Schistosoma mansoni and thus it is very important to study the phenotypic characteristics associated with it. The aim of this study was to evaluate morphological alterations in S. mansoni PZQ-resistant adult worms and eggs, by comparing a PZQ- resistant strain obtained under PZQ drug pressure with a PZQ-susceptible strain. For this, scanning electronic microscopy was used to assess tegumental responsiveness of both strains under PZQ exposure, and optical microscopy allowed the monitoring of worms and eggs in the presence of the drug. Those assays showed that PZQ-susceptible worms exposed to the drug had more severe tegumental damages than the resistant one, which had only minor alterations. Moreover, contrary to what occurred in the susceptible strain, resistant worms were viable after PZQ exposure and gradually regaining full motility after removal of the drug. Eggs from resistant strain parasites are considerably smaller than those from susceptible strain. Our results suggest that there might be a difference in the tegument composition of the resistant strain and that worms are less responsive to PZQ. Changes observed in egg morphology might imply alterations in the biology of schistosomes associated to PZQ-resistance, which could impact on transmission and pathology of the disease. Moreover, we propose a hypothetical scenario where there is a different egg tropism of the S. mansoni resistant strain. This study is the first comparing two strains that only differ in their resistance characteristics, which makes it a relevant step in the search for resistance determinants. PMID:27199925

Soil-Transmitted Helminths and Schistosoma mansoni Infections in Ethiopian Orthodox Church Students around Lake Tana, Northwest Ethiopia.

PubMed

Afework Bitew, Aschalew; Abera, Bayeh; Seyoum, Walle; Endale, Befekadu; Kiber, Tibebu; Goshu, Girma; Admass, Addiss

2016-01-01

Soil-transmitted helminths (STH) and Schistosoma mansoni infections are the major neglected tropical diseases that result in serious consequences on health, education and nutrition in children in developing countries. The Ethiopian Orthodox church students, who are called Yekolotemari in Amharic, live in areas with poor sanitation and hygiene. Moreover, they are not included in the national STH control programs. Thus, STH and S. mansoni infections prevalence is unknown. A cross-sectional study was conducted on 384 students in June 2014 to determine STH and S. mansoni infections prevalence. Moreover, the knowledge of students about STH and S. mansoni was assessed. Data on knowledge and clinical symptoms were collected using structured questionnaires via face to face interview. Stool specimens were examined by formol-ether concentration method. The overall prevalence of intestinal helminths infections was 85.9% (95% confidence interval (CI): 82.1-89%). STHs infections prevalence was 65.6% (95% CI: 60.7-70.2%). The prevalence of hookworm, Ascaris lumbricoides and Trichuris trichiura were 31.8% (95% CI: 27.3-36.6%), 29.4% (25-31%) and 3.1% (1.8-5.4%), respectively. On the other hand, S. mansoni prevalence was 14.3% (95% CI: 11.1-18.1%). Majority of students infected with S. mansoni had bloody stool with crud odds-ratio of 2.9 (95% CI: 1.5-5.5). Knowledge assessment showed that 50 (13%) and 18 (4.9%) of the respondents knew about transmission of STH and S. mansoni, respectively. The prevalence of STH and S. mansoni infections were high thus de-worming program should include the students of Ethiopian Orthodox churches. Furthermore, provision and use of sanitary facilities, health education for students to create awareness of parasitic infections and improved personal hygiene should be in place.

Soil-Transmitted Helminths and Schistosoma mansoni Infections in Ethiopian Orthodox Church Students around Lake Tana, Northwest Ethiopia

PubMed Central

Afework Bitew, Aschalew; Abera, Bayeh; Seyoum, Walle; Endale, Befekadu; Kiber, Tibebu; Goshu, Girma; Admass, Addiss

2016-01-01

Background Soil-transmitted helminths (STH) and Schistosoma mansoni infections are the major neglected tropical diseases that result in serious consequences on health, education and nutrition in children in developing countries. The Ethiopian Orthodox church students, who are called Yekolotemari in Amharic, live in areas with poor sanitation and hygiene. Moreover, they are not included in the national STH control programs. Thus, STH and S. mansoni infections prevalence is unknown. Methods A cross-sectional study was conducted on 384 students in June 2014 to determine STH and S. mansoni infections prevalence. Moreover, the knowledge of students about STH and S. mansoni was assessed. Data on knowledge and clinical symptoms were collected using structured questionnaires via face to face interview. Stool specimens were examined by formol-ether concentration method. Results The overall prevalence of intestinal helminths infections was 85.9% (95% confidence interval (CI): 82.1–89%). STHs infections prevalence was 65.6% (95% CI: 60.7–70.2%). The prevalence of hookworm, Ascaris lumbricoides and Trichuris trichiura were 31.8% (95% CI: 27.3–36.6%), 29.4% (25–31%) and 3.1% (1.8–5.4%), respectively. On the other hand, S. mansoni prevalence was 14.3% (95% CI: 11.1–18.1%). Majority of students infected with S. mansoni had bloody stool with crud odds-ratio of 2.9 (95% CI: 1.5–5.5). Knowledge assessment showed that 50 (13%) and 18 (4.9%) of the respondents knew about transmission of STH and S. mansoni, respectively. Conclusions The prevalence of STH and S. mansoni infections were high thus de-worming program should include the students of Ethiopian Orthodox churches. Furthermore, provision and use of sanitary facilities, health education for students to create awareness of parasitic infections and improved personal hygiene should be in place. PMID:27203749

The growth and development of Schistosoma mansoni in mice exposed to sublethal doses of radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aitken, R.; Wilson, R.A.

1989-12-01

The maturation of Schistosoma mansoni was studied in mice exposed to various sublethal doses of radiation. Although the treatment of mice with 500 rads of radiation prior to infection did not alter parasite maturation, doses in excess of 500 rads led to a reduction in worm burden. This could not be attributed to a delay in the arrival of parasites in the hepatic portal system. Worms developing in mice treated with 800 rads commenced egg-laying about 1 wk later than worms in intact mice, and the rate of egg deposition appeared to be lower in irradiated hosts. The data demonstratemore » that exposure of C57BL/6 mice to doses of radiation in excess of 500 rads impairs their ability to carry infections of S. mansoni. The findings do not support the hypothesis that primary worm burdens in the mouse are controlled by a host immune response.« less

Do intestinal parasites interfere with the seroepidemiologic surveillance of Schistosoma mansoni infection?

PubMed Central

Alarcón de Noya, B.; Colmenares, C.; Losada, S.; Fermin, Z.; Masroua, G.; Ruiz, L.; Soto, L.; Noya, O.

1996-01-01

In view of the known cross-reactivity of sera from patients with intestinal parasites to some Schistosoma mansoni antigens, field work was conducted in an area of Venezuela non-endemic for schistosomiasis using the routine immunoenzymatic assay (ELISA) with soluble egg antigen (SEA). False positive reactions represented 15.3% of the total population as determined by SEA-ELISA. SEA-immunoblotting of the false positive sera indicated that protein fractions of 91 and 80 kDa appear to be responsible for cross-reactivity. Sera from hookworm infected individuals produced a higher frequency and intensity of cross-reaction than other sera. SEA-fractions of 105, 54, 46, 42, 32, 25 and 15 kDa were the most specific. Images Fig. 2 PMID:8666077

Current status of soil transmitted helminths and Schistosoma mansoni infection among children in two primary schools in North Gondar, Northwest Ethiopia: a cross sectional study.

PubMed

Mathewos, Biniam; Alemu, Abebe; Woldeyohannes, Desalegn; Alemu, Agersew; Addis, Zelalem; Tiruneh, Moges; Aimero, Mulugeta; Kassu, Afework

2014-02-10

School age children are one of the groups at high risk for intestinal parasitic infections especially in developing countries like Ethiopia as the supply of good quality drinking water and latrine coverage are poor. Though there are previous data on the prevalence of soil transmitted helminths (STHs) and Schistosoma mansoni infection among these high risk groups current status in the study area is unknown. Therefore, the aim of this study was to determine the current prevalence and associated risk factors of STHs and S. mansoni infections among school children. A cross-sectional study was carried out in Gorgora and Chuahit towns, North Gondar Zone, North West Ethiopia from January 20 to February 25, 2012 involving 261 school children. A pre-tested and structured questionnaire was used to collect socio-demographic data and possible risk factors. Stool samples were collected and examined for intestinal parasites using Kato Katz method. Chi-square test was used to see if there is association between sociodemographic factors and other risk factors for STH and S. mansoni infection and odds ratio with 95% CI was computed as measures of association. P < 0.05 was taken as statistically significant. Out of the 261 study participants, 174 (66.7%) were infected with one or more species of intestinal parasites. Ascaris lumbricoides was the predominant isolates (39.8%) followed by Trichuris trichiura (6.1%) and Hookworms (4.9%). Schistosoma mansoni was detected in 33.7% of the children. Among infected individuals, 9.5% were coinfected by S. mansoni and A. lumbricoides and 1.5% with S. mansoni and T. trichiura. Swimming habit (OR: 2.536, 95% CI: 1.122, 5.737, P = 0.022) was significantly associated with S. mansoni infection. The prevalence of STH and S. mansoni was high among school children. This should call for implementation of an integrated strategy to reduce morbidity and control of transmission of STH and S. mansoni.

Current status of soil transmitted helminths and Schistosoma mansoni infection among children in two primary schools in North Gondar, Northwest Ethiopia: a cross sectional study

PubMed Central

2014-01-01

Background School age children are one of the groups at high risk for intestinal parasitic infections especially in developing countries like Ethiopia as the supply of good quality drinking water and latrine coverage are poor. Though there are previous data on the prevalence of soil transmitted helminths (STHs) and Schistosoma mansoni infection among these high risk groups current status in the study area is unknown. Therefore, the aim of this study was to determine the current prevalence and associated risk factors of STHs and S. mansoni infections among school children. Methods A cross-sectional study was carried out in Gorgora and Chuahit towns, North Gondar Zone, North West Ethiopia from January 20 to February 25, 2012 involving 261 school children. A pre-tested and structured questionnaire was used to collect socio-demographic data and possible risk factors. Stool samples were collected and examined for intestinal parasites using Kato Katz method. Chi-square test was used to see if there is association between sociodemographic factors and other risk factors for STH and S. mansoni infection and odds ratio with 95% CI was computed as measures of association. P < 0.05 was taken as statistically significant. Results Out of the 261 study participants, 174 (66.7%) were infected with one or more species of intestinal parasites. Ascaris lumbricoides was the predominant isolates (39.8%) followed by Trichuris trichiura (6.1%) and Hookworms (4.9%). Schistosoma mansoni was detected in 33.7% of the children. Among infected individuals, 9.5% were coinfected by S. mansoni and A. lumbricoides and 1.5% with S. mansoni and T. trichiura. Swimming habit (OR: 2.536, 95% CI: 1.122, 5.737, P = 0.022) was significantly associated with S. mansoni infection. Conclusion The prevalence of STH and S. mansoni was high among school children. This should call for implementation of an integrated strategy to reduce morbidity and control of transmission of STH and S. mansoni. PMID

Effect of praziquantel treatment of Schistosoma mansoni during pregnancy on intensity of infection and antibody responses to schistosome antigens: results of a randomised, placebo-controlled trial

PubMed Central

2009-01-01

Background Praziquantel treatment of schistosomiasis during pregnancy was only recommended in 2002; hence the effects of treatment during pregnancy are not fully known. We have therefore evaluated the effects on infection intensity and the immunological effects of praziquantel treatment against Schistosoma mansoni during pregnancy, compared with treatment after delivery. Methods A nested cohort of 387 Schistosoma mansoni infected women was recruited within a larger trial of de-worming during pregnancy. Women were randomised to receive praziquantel or placebo during pregnancy. All women were treated after delivery. Infection intensity after treatment was assessed by a single Kato-Katz examination of stool samples with duplicate slides and categorised as undetected, light (1–99 eggs per gram (epg)), moderate (100–399 epg) or heavy (≥400 epg). Antibodies against S. mansoni worm and egg antigens were measured by ELISA. Results were compared between women first treated during pregnancy and women first treated after delivery. Results At enrolment, 252 (65.1%) of the women had light infection (median (IQR) epg: 35 (11, 59)), 75 (19.3%) moderate (median (IQR) epg: 179(131, 227)) and 60 (15.5%) had heavy infection (median (IQR) epg: 749 (521, 1169)) with S. mansoni. At six weeks after praziquantel treatment during pregnancy S. mansoni infection was not detectable in 81.9% of the women and prevalence and intensity had decreased to 11.8% light, 4.7% moderate and 1.6% heavy a similar reduction when compared with those first treated after delivery (undetected (88.5%), light (10.6%), moderate (0.9%) and heavy (0%), p = 0.16). Parasite specific antibody levels were lower during pregnancy than after delivery. Praziquantel treatment during pregnancy boosted anti-worm IgG isotypes and to a lesser extent IgE, but these boosts were less pronounced than in women whose treatment was delayed until after delivery. Praziquantel had limited effects on antibodies against egg antigens

Human eosinophils modulate peripheral blood mononuclear cell response to Schistosoma mansoni adult worm antigen in vitro.

PubMed

Tweyongyere, R; Namanya, H; Naniima, P; Cose, S; Tukahebwa, E M; Elliott, A M; Dunne, D W; Wilson, S

2016-08-01

High numbers of eosinophils are observed in parasitic infections and allergic diseases, where they are proposed to be terminally differentiated effector cells that play beneficial role in host defence, or cause harmful inflammatory response. Eosinophils have been associated with killing of schistosomulae in vitro, but there is growing evidence that eosinophils can play additional immuno-regulatory role. Here, we report results of a study that examines peripheral blood mononuclear cell (PBMC) cytokine responses to Schistosoma mansoni adult worm antigen (SWA) when stimulated alone or enriched with autologous eosinophils. Production of the Th-2 type cytokines interleukin (IL)-4, IL-5 and IL-13 was lower (P = 0·017, 0·018 and <0·001, respectively) in PBMC + eosinophil cultures than in PBMC-only cultures stimulated with SWA. Substantial levels of IL-13, IL-10, interferon gamma and tumour necrosis factor alpha were recorded in cultures of eosinophils, but none of these cytokines showed significant association with the observed eosinophil-induced drop in cytokine responses of PBMC. Transwell experiments suggested that the observed effect is due to soluble mediators that downmodulate production of Th-2 type cytokines. This study shows that eosinophils may down-modulate schistosome-specific Th-2 type cytokine responses in S. mansoni-infected individuals. The mechanism of this immune modulation remains to be elucidated. © 2016 The Authors. Parasite Immunology Published by John Wiley & Sons Ltd.

Efficacy and Safety of Praziquantel in Preschool-Aged Children in an Area Co-Endemic for Schistosoma mansoni and S. haematobium

PubMed Central

Coulibaly, Jean T.; N'Gbesso, Yve K.; Knopp, Stefanie; Keiser, Jennifer; N'Goran, Eliézer K.; Utzinger, Jürg

2012-01-01

Background In sub-Saharan Africa the recommended strategy to control schistosomiasis is preventive chemotherapy. Emphasis is placed on school-aged children, but in high endemicity areas, preschool-aged children are also at risk, and hence might need treatment with praziquantel. Since a pediatric formulation (e.g., syrup) is not available outside of Egypt, crushed praziquantel tablets are used, but the efficacy and safety of this treatment regimen is insufficiently studied. Methodology We assessed the efficacy and safety of crushed praziquantel tablets among preschool-aged children (<6 years) in the Azaguié district, south Côte d'Ivoire, where Schistosoma mansoni and S. haematobium coexist. Using a cross-sectional design, children provided two stool and two urine samples before and 3 weeks after treatment. Crushed praziquantel tablets, mixed with water, were administered at a dose of 40 mg/kg. Adverse events were assessed and graded 4 and 24 hours posttreatment by interviewing mothers/guardians. Principal Findings Overall, 160 preschool-aged children had at least one stool and one urine sample examined with duplicate Kato-Katz thick smears and a point-of-care circulating cathodic antigen (POC-CCA) cassette for S. mansoni, and urine filtration for S. haematobium diagnosis before and 3 weeks after praziquantel administration. According to the Kato-Katz and urine filtration results, we found high efficacy against S. mansoni (cure rate (CR), 88.6%; egg reduction rate (ERR), 96.7%) and S. haematobium (CR, 88.9%; ERR, 98.0%). POC-CCA revealed considerably lower efficacy against S. mansoni (CR, 53.8%). Treatment was generally well tolerated, but moderately severe adverse events (i.e., body and face inflammation), were observed in four Schistosoma egg-negative children. Conclusions/Significance Crushed praziquantel administered to preschool-aged children at a dose of 40 mg/kg is efficacious against S. mansoni and S. haematobium in a co-endemic setting of Côte d

Human IgG1 Responses to Surface Localised Schistosoma mansoni Ly6 Family Members Drop following Praziquantel Treatment.

PubMed

Chalmers, Iain W; Fitzsimmons, Colin M; Brown, Martha; Pierrot, Christine; Jones, Frances M; Wawrzyniak, Jakub M; Fernandez-Fuentes, Narcis; Tukahebwa, Edridah M; Dunne, David W; Khalife, Jamal; Hoffmann, Karl F

2015-01-01

The heptalaminate-covered, syncytial tegument is an important anatomical adaptation that enables schistosome parasites to maintain long-term, intravascular residence in definitive hosts. Investigation of the proteins present in this surface layer and the immune responses elicited by them during infection is crucial to our understanding of host/parasite interactions. Recent studies have revealed a number of novel tegumental surface proteins including three (SmCD59a, SmCD59b and Sm29) containing uPAR/Ly6 domains (renamed SmLy6A SmLy6B and SmLy6D in this study). While vaccination with SmLy6A (SmCD59a) and SmLy6D (Sm29) induces protective immunity in experimental models, human immunoglobulin responses to representative SmLy6 family members have yet to be thoroughly explored. Using a PSI-BLAST-based search, we present a comprehensive reanalysis of the Schistosoma mansoni Ly6 family (SmLy6A-K). Our examination extends the number of members to eleven (including three novel proteins) and provides strong evidence that the previously identified vaccine candidate Sm29 (renamed SmLy6D) is a unique double uPAR/Ly6 domain-containing representative. Presence of canonical cysteine residues, signal peptides and GPI-anchor sites strongly suggest that all SmLy6 proteins are cell surface-bound. To provide evidence that SmLy6 members are immunogenic in human populations, we report IgG1 (as well as IgG4 and IgE) responses against two surface-bound representatives (SmLy6A and SmLy6B) within a cohort of S. mansoni-infected Ugandan males before and after praziquantel treatment. While pre-treatment IgG1 prevalence for SmLy6A and SmLy6B differs amongst the studied population (7.4% and 25.3% of the cohort, respectively), these values are both higher than IgG1 prevalence (2.7%) for a sub-surface tegumental antigen, SmTAL1. Further, post-treatment IgG1 levels against surface-associated SmLy6A and SmLy6B significantly drop (p = 0.020 and p < 0.001, respectively) when compared to rising IgG1

Inhibition of Schistosoma mansoni ether-a-go-go related gene-encoded potassium channels leads to hypermotility and impaired egg production.

PubMed

Parker-Manuel, S J; Hahnel, S; Grevelding, C G

2015-11-01

The purpose of this work was to investigate the effect of ether-a-go-go related gene (ERG) potassium channel inhibition on Schistosoma mansoni. Use of dofetilide to block the schistosome ERGs resulted in a striking 'corkscrew' effect. The worms were unable to control their motility; they were hypermotile. The treated worms produced abnormal eggs, some of which consisted of little more than a spine. One of the S. mansoni ERGs (SmERGs), Smp_161140, was chosen for further study by RNAi. The transcript was knocked down to 50% compared to the controls. These RNAi-treated worms demonstrated seizure-like movements. In S. mansoni, as in other organisms, ERG channels seem to play a role in regulating muscle excitability. This work shows that egg production can be greatly reduced by effectively targeting muscle coordination in these important parasites. Copyright © 2015 Elsevier Inc. All rights reserved.

Digenetic larvae in Schistosome snails from El Fayoum, Egypt with detection of Schistosoma mansoni in the snail by PCR.

PubMed

Aboelhadid, Shawky M; Thabet, Marwa; El-Basel, Dayhoum; Taha, Ragaa

2016-09-01

The present study aims to detect the digenetic larvae infections in Bulinus truncatus and Biomphalaria alexandrina snails and also PCR detection of Schistosoma mansoni infection. The snails were collected from different branches of Yousef canal and their derivatives in El Fayoum Governorate. The snails were investigated for infection through induction of cercarial shedding by exposure to light and crushing of the snails. The shed cercariae were S. mansoni, Pharyngeate longifurcate type I and Pharyngeate longifurcate type II from B. alexandrina, while that found in B. truncatus were Schitosoma haematobium and Xiphidiocercaria species cercariae. The seasonal prevalence of infection was discussed. Polymerase chain reaction was used for the detection of S. mansoni in the DNA from field collected infected and non infected snails. The results of PCR showed that the pool of B. alexandrina snails which shed S. mansoni cercariae in the laboratory, gave positive reaction in the samples. Pooled samples of field collected B. alexandrina that showed negative microscopic shedding of cercariae gave negative and positive PCR in a consecutive manner. Accordingly, a latent infection in the snail (negative microscopic) could be detected by using PCR.

Efficacy of oxamniquine and praziquantel in the treatment of Schistosoma mansoni infection: a controlled trial.

PubMed Central

Ferrari, M. L. A.; Coelho, P. M. Z.; Antunes, C. M. F.; Tavares, C. A. P.; da Cunha, A. S.

2003-01-01

OBJECTIVE: To evaluate the therapeutic efficacy of oxamniquine and praziquantel, the two most clinically important schistosomicide drugs, and to compare the accuracy of faecal examination with the accuracy of oogram in testing for Schistosoma mansoni infection. METHODS: In a triple-masked and randomized controlled trial, 106 patients infected with S. mansoni were randomly allocated to one of three statistically homogeneous groups. One group was given 60 mg/kg praziquantel per day for three consecutive days, another was given two daily doses of 10 mg/kg oxamniquine, and the placebo group received starch. Faecal examinations (days 15, 30, 60, 90, 120, 150, and 180 after treatment) and biopsy of rectal mucosa by quantitative oogram (days 30, 60, 120, and 180) were used for the initial diagnosis and for evaluating the degree of cure. The chi2 test and the Kruskal-Wallis test were used to compare variables in the three groups. Survival analysis (Kaplan-Meier) and the log-rank test were used to evaluate the efficacy of the treatments. FINDINGS: The sensitivity of stool examinations ranged from 88.9% to 94.4% when patients presented with >5000 S. mansoni eggs per gram of tissue (oogram); when the number of eggs dropped to <1000 eggs per gram, sensitivity was reduced (range, 22.7-34.0%). When cure was evaluated by stool examination, oxamniquine and praziquantel had cure rates of 90.3% and 100%, respectively. However, when the oogram was used as an indicator of sensitivity, the oxamniquine cure rate dropped dramatically (to 42.4%), whereas the rate for praziquantel remained high, at 96.1%. CONCLUSIONS: Praziquantel was significantly more effective than oxamniquine in treating S. mansoni infection. The oogram was markedly more sensitive than stool examinations in detecting S. mansoni eggs and should be recommended for use in clinical trials with schistosomicides. PMID:12764515

A cyclohexanecarboxamide derivative with inhibitory effects on Schistosoma mansoni cercarial serine protease and penetration of mice skin by the parasite.

PubMed

Bahgat, Mahmoud; Aboul-Enein, Mohamed N; El Azzouny, Aida A; Maghraby, Amany; Ruppel, Andreas; Soliman, Wael M

2009-01-01

A cyclohexanecarboxamide derivative, N-phenyl-N-[1-(piperidine-1-carbonyl)cyclohexyl] benzamide (MNRC-5), was evaluated for its inhibitory effects on Schistosoma mansoni cercarial serine protease activity and cercarial penetration. MNRC-5 exerted an inhibitory effect on S. mansoni cercarial serine protease at serial concentrations of the specific chromogenic substrate Boc-Val-Leu-Gly-Arg-PNA for such enzyme family and the inhibitory coefficient (Ki) value was deduced. Moreover, topical treatment of mice tails with the most potent inhibitory concentration of MNRC-5 formulated in jojoba oil successfully blocked cercarial penetration as demonstrated by a significant reduction (75%; p < 0.05) in the recovered S. mansoni worms from treated mice in comparison to control ones whose tails were painted with jojoba oil base containing no MNRC-5. In addition, the IgM and IgG reactivities to crude S. mansoni cercarial, worm and egg antigens were generally lower in sera from treated infected mice than untreated infected mice. In conclusion, we report on a new serine protease inhibitor capable for blocking penetration of host skin by S. mansoni cercariae as measured by lowering worm burden and decrease in the levels of both IgM and IgG towards different bilharzial antigens upon topical treatment.

Schistosoma mansoni miracidia transformed by particle bombardment infect Biomphalaria glabrata snails and develop into transgenic sporocysts.

PubMed

Heyers, Oliver; Walduck, Anna K; Brindley, Paul J; Bleiss, Wilfrid; Lucius, Richard; Dorbic, Tomislav; Wittig, Burghardt; Kalinna, Bernd H

2003-10-01

Miracidia (and adults) of Schistosoma mansoni which had been subjected to particle bombardment with a plasmid DNA encoding enhanced green fluorescent protein (EGFP) under control of the S. mansoni heat shock protein 70 (HSP70) promoter and termination elements were shown to express the reporter gene. Bombarded miracidia were able to penetrate and establish in Biomphalaria glabrata the intermediate host snail. Gold particles could be detected in the germ balls of parasites in paraffin-sections of snail tissue. The bombarded miracidia were able to develop normally and to transform into mother sporocysts. Reporter gene activity could be determined at 10 days post-infection by RT-PCR in snail tissues, but not by microscopy or Western blot which probably reflected sub-optimal expression levels of constructs. Our findings indicated that it is feasible to return transgenic miracidia to the life cycle, a crucial step for the establishment of a transgenesis system for schistosomes.

The 86-kilodalton antigen from Schistosoma mansoni is a heat-shock protein homologous to yeast HSP-90.

PubMed

Johnson, K S; Wells, K; Bock, J V; Nene, V; Taylor, D W; Cordingley, J S

1989-08-01

We report the sequence of a cDNA clone encoding an 86-kDa polypeptide antigen (p86) from Schistosoma mansoni. Fusion proteins made in Escherichia coli are recognized by human infection sera. The reading frame of this antigen is highly homologous to those of the large heat-shock proteins of Saccharomyces cerevisiae (HSP90) and Drosophila melanogaster (HSP83). mRNA encoding p86 increases in response to heat shock of adult worms, as does HSP70. Comparisons of the sequences of HSP70 and HSP83 homologues show that these two families of heat-shock proteins are not significantly related except for the last four amino acid residues, which are Glu-Glu-Val-Asp in every case. This sequence is not found at the carboxy terminus of any other protein in the current databases.

The Schistosoma mansoni phylome: using evolutionary genomics to gain insight into a parasite's biology.

PubMed

Silva, Larissa Lopes; Marcet-Houben, Marina; Nahum, Laila Alves; Zerlotini, Adhemar; Gabaldón, Toni; Oliveira, Guilherme

2012-11-13

Schistosoma mansoni is one of the causative agents of schistosomiasis, a neglected tropical disease that affects about 237 million people worldwide. Despite recent efforts, we still lack a general understanding of the relevant host-parasite interactions, and the possible treatments are limited by the emergence of resistant strains and the absence of a vaccine. The S. mansoni genome was completely sequenced and still under continuous annotation. Nevertheless, more than 45% of the encoded proteins remain without experimental characterization or even functional prediction. To improve our knowledge regarding the biology of this parasite, we conducted a proteome-wide evolutionary analysis to provide a broad view of the S. mansoni's proteome evolution and to improve its functional annotation. Using a phylogenomic approach, we reconstructed the S. mansoni phylome, which comprises the evolutionary histories of all parasite proteins and their homologs across 12 other organisms. The analysis of a total of 7,964 phylogenies allowed a deeper understanding of genomic complexity and evolutionary adaptations to a parasitic lifestyle. In particular, the identification of lineage-specific gene duplications pointed to the diversification of several protein families that are relevant for host-parasite interaction, including proteases, tetraspanins, fucosyltransferases, venom allergen-like proteins, and tegumental-allergen-like proteins. In addition to the evolutionary knowledge, the phylome data enabled us to automatically re-annotate 3,451 proteins through a phylogenetic-based approach rather than solely sequence similarity searches. To allow further exploitation of this valuable data, all information has been made available at PhylomeDB (http://www.phylomedb.org). In this study, we used an evolutionary approach to assess S. mansoni parasite biology, improve genome/proteome functional annotation, and provide insights into host-parasite interactions. Taking advantage of a proteome

Cross-Reactivity of Schistosoma mansoni Cytosolic Superoxide Dismutase, a Protective Vaccine Candidate, with Host Superoxide Dismutase and Identification of Parasite-Specific B Epitopes

PubMed Central

Carvalho-Queiroz, Claudia; Cook, Rosemary; Wang, Ching C.; Correa-Oliveira, Rodrigo; Bailey, Nicola A.; Egilmez, Nejat K.; Mathiowitz, Edith; LoVerde, Philip T.

2004-01-01

Schistosoma mansoni, an intravascular parasite, has evolved a number of immune evasion mechanisms to establish itself in the host, such as antioxidant enzymes. Our laboratory has demonstrated that the highest levels of certain antioxidant enzymes are found in adult worms, which are the least susceptible to immune killing. Vaccination of mice with naked DNA constructs containing the gene encoding Cu/Zn cytosolic superoxide dismutase (SmCT-SOD) showed significant levels of protection compared to a control group, and our data demonstrate that the adult worms are a target of the immune response that confers resistance in SmCT-SOD DNA-vaccinated mice. Because SmCT-SOD shows significant identity with the human homologue, we evaluated the reactivity of anti-SmCT-SOD antibodies derived from SmCT-SOD-immunized mice and rabbits and from S. mansoni-infected individuals to human superoxide dismutase (hSOD) and SmCT-SOD parasite-specific peptides to assess the potential for autoimmune responses from immunization with the recombinant molecule. In addition, we evaluated the ability of various SmCT-SOD adjuvant-delivered immunizations to induce cross-reactive antibodies. Both mouse and rabbit antibodies generated against SmCT-SOD recognized the denatured form of hSOD. The same antibodies did not recognize nondenatured hSOD. Sera from infected individuals with different clinical forms of schistosomiasis recognized SmCT-SOD but not hSOD. Antibodies from mice immunized with different SmCT-SOD-containing formulations of both DNA and protein were able to recognize SmCT-SOD-derived peptides but not soluble hSOD. All together, these findings serve as a basis for developing a subunit vaccine against schistosomiasis. PMID:15102772

Direct filtration for recovery of Schistosoma mansoni cercariae in the field.

PubMed

Sandt, D G

1973-01-01

The recovery of schistosome cercariae from natural waters has been limited by variations in turbidity and in the accuracy of recovery with different techniques. A modification of the Rowan vacuum paper filtration method employing a battery-operated pumping system, a glass-silicone plate filter, and a specially designed filter holder is described and evaluated. Field tests on St Lucia indicate a mean filtration volume of 12.2 litres per filter at a mean turbidity of 20.3 Jackson turbidity units. Overall, 86% of the volumes filtered per filter were in excess of 6 litres. Particle size, rather than turbidity, was found to be the main factor influencing filter blockage, reading time, and accuracy. Recoveries of 0.01 cercaria (Schistosoma mansoni) per litre sampled were obtained, but the practical limit of the method is considered to be closer to 0.1 cercaria per litre sampled.

Biochemical and Parasitological Studies on the Effect of hUCB-Selected CD34+ Progenitor/Stem Cells in Mice Infected with Schistosoma mansoni

PubMed Central

Abou-Zied, Akram M.; Soliman, Rasha H.; Hefila, Shorouk M.; Imam, Samir A.

2014-01-01

Background and Objectives: Placenta and blood that remained in the umbilical cord is routinely available as a discarded tissue after deliveries and it is free of any legal, moral, ethical or religious objections, providing a high number of multipotent CD34+ progenitor and stem cells. Using ex vivo isolated CD34+ cells from human umbilical cord blood (hUCB) have emerged as promising candidates to treat various diseases, including exogenous pathogenic infections. We have expanded to build a rational approach to study the effect of CD34+ cells after damaged liver tissues by the devastating human parasitic flatworm Schistosoma mansoni. Methods and Results: Experimental studies were conducted in the Department of Zoology, Faculty of Science and Departments of Parasitology and Physiology, Faculty of Medicine, SCU, Egypt. We have studied the impact of ex vivo preparation of CD34+ cells from hUCB on S. mansoni-induced liver fibrosis de novo, and treated for shorter and longer periods in vivo. Ova count, ALT and albumin were measured at specific time interval and histopathological examination of liver was conducted to confirm the biochemical results. The data obtained were statistically analyzed by ANOVA between groups. It was found that the administration of CD34+ cells have modestly reduced liver damage; reduced the S. mansoni infection associated elevation in serum levels of ALT; significantly improved serum levels of albumin and reduced egg granuloma diameter in the livers. Conclusions: We demonstrated that CD34+ cells can markedly ameliorated liver fibrosis in vivo and may be beneficial for therapy to recover organ structure and/or function of S. mansoni-infected mice. PMID:25473447

Prevalence of intestinal parasitic infections among children under five years of age with emphasis on Schistosoma mansoni in Wonji Shoa Sugar Estate, Ethiopia.

PubMed

G/hiwot, Yirgalem; Degarege, Abraham; Erko, Berhanu

2014-01-01

Intestinal parasite infections are major public health problems of children in developing countries causing undernutrition, anemia, intestinal obstruction and mental and physical growth retardation. This study was conducted to assess the prevalence of intestinal helminthic infections among children under five years of age with emphasis on Schistosoma mansoni in Wonji Shoa Sugar Estate, Ethiopia. A cross-sectional parasitological survey was conducted in under-five children living in Wonji Shoa Sugar Estate Ethiopia, April, 2013. Stool samples were collected and examined for intestinal parasites using single Kato-Katz and single Sodium acetate-acetic acid-formalin (SAF) solution concentration methods. Out of 374 children examined using single Kato-Katz and single SAF-concentration methods, 24.3% were infected with at least one intestinal parasite species. About 10.4%, 8.8%, 4.6%, 2.9%, 1.6% and 0.8% of the children were infected with Hymenolepis nana, Schistosoma mansoni, Ascaris lumbricoides, Trichuris trichiura, Enterobius vermicularis and hookworm, respectively. Prevalence of double, triple and quadruple intestinal helminthic infection was 6.4%, 0.54% and 1.1%, respectively. A significant increase in prevalence of S. mansoni (8.3% versus 3.2%) and T. trichiura (2.7% versus 0.5%) infection was observed when determined via the single Kato-Katz method compared to the prevalence of the parasites determined via the single SAF-concentration method. On the other hand, the single SAF-concentration method (9.1%) revealed a significantly higher prevalence of H. nana infection than the single Kato-Katz (1.6%) does. In conclusion, intestinal helminths infections particularly S. mansoni and H. nana were prevalent in under-five children of Wonji Shoa Sugar Estate. Including praziquantel treatment in the deworming program as per the World Health Organization guidelines would be vital to reduce the burden of these diseases in areas where S. mansoni and H. nana infections are

Antiparasitic activity of menadione (vitamin K3) against Schistosoma mansoni in BABL/c mice.

PubMed

Kapadia, Govind J; Soares, Ingrid A O; Rao, G Subba; Badoco, Fernanda R; Furtado, Ricardo A; Correa, Mariana B; Tavares, Denise C; Cunha, Wilson R; Magalhães, Lizandra G

2017-03-01

Schistosomiasis is one of the neglected tropical diseases affecting nearly quarter of a billion people in economically challenged tropical and subtropical countries of the world. Praziquantel (PZQ) is the only drug currently available to treat this parasitic disease in spite being ineffective against juvenile worms and concerns about developing resistance to treat reinfections. Our earlier in vitro viability studies demonstrated significant antiparasitic activity of menadione (MEN) (vitamin K 3 ) against Schistosoma mansoni adult worms. To gain insight into plausible mechanism of antischistosomal activity of MEN, its effect on superoxide anion levels in adult worms were studied in vitro which showed significant increases in both female and male worms. Further confirmation of the deleterious morphological changes in their teguments and organelles were obtained by ultrastructural analysis. Genotoxic and cytotoxic studies in male Swiss mice indicated that MEN was well tolerated at the oral dose of 500mg/kg using the criteria of MNPCE frequency and PCE/RBC ratio in the bone marrow of infected animals. The in vivo antiparasitic activity of MEN was conducted in female BALB/c mice infected with S. mansoni and significant reductions (P<0.001) in total worm burden were observed at single oral doses of 40 and 400mg/kg (48.57 and 61.90%, respectively). Additionally, MEN significantly reduced (P<0.001) the number of eggs in the liver of infected mice by 53.57 and 58.76%, respectively. Similarly, histological analysis of the livers showed a significant reduction (P<0.001) in the diameter of the granulomas. Since MEN is already in use globally as an over-the-counter drug for a variety of common ailments and a dietary supplement with a safety record in par with similar products when used in recommended doses, the above antiparasitic results which compare reasonably well with PZQ, make a compelling case for considering MEN to treat S. mansoni infection in humans. Copyright © 2016

The genome of the blood fluke Schistosoma mansoni

PubMed Central

Berriman, Matthew; Haas, Brian J.; LoVerde, Philip T.; Wilson, R. Alan; Dillon, Gary P.; Cerqueira, Gustavo C.; Mashiyama, Susan T.; Al-Lazikani, Bissan; Andrade, Luiza F.; Ashton, Peter D.; Aslett, Martin A.; Bartholomeu, Daniella C.; Blandin, Gaelle; Caffrey, Conor R.; Coghlan, Avril; Coulson, Richard; Day, Tim A.; Delcher, Art; DeMarco, Ricardo; Djikeng, Appoliniare; Eyre, Tina; Gamble, John A.; Ghedin, Elodie; Gu, Yong; Hertz-Fowler, Christiane; Hirai, Hirohisha; Hirai, Yuriko; Houston, Robin; Ivens, Alasdair; Johnston, David A.; Lacerda, Daniela; Macedo, Camila D.; McVeigh, Paul; Ning, Zemin; Oliveira, Guilherme; Overington, John P.; Parkhill, Julian; Pertea, Mihaela; Pierce, Raymond J.; Protasio, Anna V.; Quail, Michael A.; Rajandream, Marie-Adèle; Rogers, Jane; Sajid, Mohammed; Salzberg, Steven L.; Stanke, Mario; Tivey, Adrian R.; White, Owen; Williams, David L.; Wortman, Jennifer; Wu, Wenjie; Zamanian, Mostafa; Zerlotini, Adhemar; Fraser-Liggett, Claire M.; Barrell, Barclay G.; El-Sayed, Najib M.

2009-01-01

Schistosoma mansoni is responsible for the neglected tropical disease schistosomiasis that affects 210 million people in 76 countries. We report here analysis of the 363 megabase nuclear genome of the blood fluke. It encodes at least 11,809 genes, with an unusual intron size distribution, and novel families of micro-exon genes that undergo frequent alternate splicing. As the first sequenced flatworm, and a representative of the lophotrochozoa, it offers insights into early events in the evolution of the animals, including the development of a body pattern with bilateral symmetry, and the development of tissues into organs. Our analysis has been informed by the need to find new drug targets. The deficits in lipid metabolism that make schistosomes dependent on the host are revealed, while the identification of membrane receptors, ion channels and more than 300 proteases, provide new insights into the biology of the life cycle and novel targets. Bioinformatics approaches have identified metabolic chokepoints while a chemogenomic screen has pinpointed schistosome proteins for which existing drugs may be active. The information generated provides an invaluable resource for the research community to develop much needed new control tools for the treatment and eradication of this important and neglected disease. PMID:19606141

Calmodulins from Schistosoma mansoni: Biochemical analysis and interaction with IQ-motifs from voltage-gated calcium channels.

PubMed

Thomas, Charlotte M; Timson, David J

2018-05-17

The trematode Schistosoma mansoni is a causative agent of schistosomiasis, the second most common parasitic disease of humans after malaria. Calcium homeostasis and calcium-mediated signalling pathways are of particular interest in this species. The drug of choice for treating schistosomiasis, praziquantel, disrupts the regulation of calcium uptake and there is interest in exploiting calcium-mediated processes for future drug discovery. Calmodulin is a calcium sensing protein, present in most eukaryotes. It is a critical regulator of processes as diverse as muscle contraction, cell division and, partly through interaction with voltage-gated calcium channels, intra-cellular calcium concentrations. S. mansoni expresses two highly similar calmodulins - SmCaM1 and SmCaM2. Both proteins interact with calcium, manganese, cadmium (II), iron (II) and lead ions in native gel electrophoresis. These ions also cause conformational changes in the proteins resulting in the exposure of a more hydrophobic surface (as demonstrated by anilinonaphthalene-8-sulfonate fluorescence assays). The proteins are primarily dimeric in the absence of calcium ions, but monomeric in the presence of this ion. Both SmCaM1 and SmCaM2 interact with a peptide corresponding to an IQ-motif derived from the α-subunit of the voltage-gated calcium channel SmCa v 1B (residues 1923-1945). Both proteins bound with slightly higher affinity in the presence of calcium ions. However, there was no difference between the affinities of the two proteins for the peptide. This interaction could be antagonised by chlorpromazine and trifluoperazine, but not praziquantel or thiamylal. Interestingly no interaction could be detected with the other three IQ-motifs identified in S. mansoni voltage-gated ion calcium channels. Copyright © 2018 Elsevier Ltd. All rights reserved.

Schistosoma mansoni miracidial behavior: an assay system for chemostimulation.

PubMed

Sponholtz, G M; Short, R B

1975-04-01

A new system for evaluating the responses of miracidia to chemostimulants is described. The apparatus consists of a translucent plastic block with a center well and a hole in the edge leading to the well. One end of a glass tube, covered with a dialysis membrane, was inserted into the hole. Experimental solutions to be tested were put into the tube and Schistosoma mansoni miracidial behavior was observed in the well on the other side of the permeable membrane. Miracidia were released near the membrane; those which contacted the membrane were scored as to whether they returned (contact with return) or did not return (contact without return) before leaving the field of view. Materials eliciting significantly more contact with return responses than did controls were considered to be stimulatory. In this assay system, snail (Biomphalaria glabrata) conditioned water elicited 75% contact with return as compared to 8% for well water control (P less than 0.05). Tracings from motion pictures showed swimming behavior of miracidia toward snail-conditioned water to be different from behavior toward well water controls. This system permits generation of dilution response curves for chemicals and provides generally quantitative results.

Serum CCL11 (eotaxin-1) and CCL17 (TARC) are serological indicators of multiple helminth infections and are driven by Schistosoma mansoni infection in humans.

PubMed

Geiger, Stefan M; Jardim-Botelho, Anne; Williams, Weston; Alexander, Neal; Diemert, David J; Bethony, Jeffrey M

2013-06-01

To evaluate systemic serum cytokine and chemokine markers for inflammation and Th1/Th2 responses in relation to multiple helminth infections, parasite burden and/or nutritional status of individuals. In a longitudinal study, stool samples from 210 individuals from an area highly endemic for Ascaris lumbricoides, Necator americanus and Schistosoma mansoni were examined before and 12 months after clearance of parasites by chemotherapy. On both occasions, the presence of mono- or multiple infections and intensities of infection were compared with nutritional parameters and with serum cytokines or chemokines as markers for inflammatory, regulatory or Th1- or Th2-type immune responses. Before treatment, we were not able to associate any altered nutritional parameters with increased inflammatory responses, and highest intensities of infection were found in eutrophic participants with multiple infections. In contrast, major changes in serum Th2-type chemokine levels were measured in individuals infected with intestinal helminths and/or S. mansoni, and resulted in significantly higher CCL11 and CCL17 concentrations, both before treatment and after reinfection. The driving force for these elevated type 2 serum chemokine concentrations was an S. mansoni infection and faecal egg counts significantly correlated with serum IL-10 concentrations. © 2013 John Wiley & Sons Ltd.

Biompha-LAMP: A New Rapid Loop-Mediated Isothermal Amplification Assay for Detecting Schistosoma mansoni in Biomphalaria glabrata Snail Host.

PubMed

Gandasegui, Javier; Fernández-Soto, Pedro; Hernández-Goenaga, Juan; López-Abán, Julio; Vicente, Belén; Muro, Antonio

2016-12-01

Schistosomiasis remains one of the most common endemic parasitic diseases affecting over 230 million people worlwide. Schistosoma mansoni is the main species causing intestinal and hepatic schistosomiasis and the fresh water pulmonate snails of the genus Biomphalaria are best known for their role as intermediate hosts of the parasite. The development of new molecular monitoring assays for large-scale screening of snails from transmission sites to detect the presence of schistosomes is an important point to consider for snail control interventions related to schistosomiasis elimination. Our work was focussed on developing and evaluating a new LAMP assay combined with a simple DNA extraction method to detect S. mansoni in experimentally infected snails as a diagnostic tool for field conditions. A LAMP assay using a set of six primers targeting a sequence of S. mansoni ribosomal intergenic spacer 28S-18S rRNA was designed. The detection limit of the LAMP assay was 0.1 fg of S. mansoni DNA at 63°C for 50 minutes. LAMP was evaluated by examining S. mansoni DNA in B. glabrata snails experimentally exposed to miracidia at different times post-exposure: early prepatent period (before cercarial shedding), light infections (snails exposed to a low number of miracidia) and detection of infected snails in pooled samples (within a group of uninfected snails). DNA for LAMP assays was obtained by using a commercial DNA extraction kit or a simple heat NaOH extraction method. We detected S. mansoni DNA in all groups of snails by using no complicated requirement procedure for DNA obtaining. Our LAMP assay, named Biompha-LAMP, is specific, sensitive, rapid and potentially adaptable as a cost-effective method for screening of intermediate hosts infected with S. mansoni in both individual snails and pooled samples. The assay could be suitable for large-scale field surveys for schistosomes control campaigns in endemic areas.

Soil transmitted helminths and schistosoma mansoni infections among school children in Zarima town, northwest Ethiopia.

PubMed

Alemu, Abebe; Atnafu, Asmamaw; Addis, Zelalem; Shiferaw, Yitayal; Teklu, Takele; Mathewos, Biniam; Birhan, Wubet; Gebretsadik, Simon; Gelaw, Baye

2011-07-09

In Ethiopia, because of low quality drinking water supply and latrine coverage, helminths infections are the second most predominant causes of outpatient morbidity. Indeed, there is a scarcity of information on the prevalence of soil transmitted helminths and Schistosomiasis in Ethiopia, special in study area. Therefore, the aim of this study was to determine the prevalence and associated risk factors of soil transmitted helminths and intestinal Schistosomiasis. Cross-sectional study was conducted among 319 school children of Zarima town from April 1 to May 25, 2009. A pre-tested structured questionnaire was used to collect socio-demographic data and possible risk factors exposure. Early morning stool samples were collected and a Kato Katz semi concentration technique was used to examine and count parasitic load by compound light microscope. Data entry and analysis was done using SPSS-15 version and p-value < 0.05 considered statistically significant. Out of 319 study subjects, 263 (82.4%) of the study participants infected with one or more parasites. From soil transmitted helminths, Ascaris lumbricoides was the predominant isolate (22%) followed by Hookworms (19%) and Trichuris trichiura (2.5%). Schistosoma mansoni was also isolated in 37.9% of the study participants. Hookworm and S. mansoni infections showed statistically significant associations with shoe wearing and swimming habit of school children, respectively. Prevalence of soil transmitted helminths (STH) and S.mansoni was high and the diseases were still major health problem in the study area which alerts public health intervention as soon as possible.

Prediction of the potential global distribution for Biomphalaria straminea, an intermediate host for Schistosoma mansoni

PubMed Central

Yang, Ya; Cheng, Wanting; Wu, Xiaoying; Huang, Shaoyu; Deng, Zhuohui; Zeng, Xin; Yang, Yu; Wu, Zhongdao; Chen, Yue; Zhou, Yibiao; Jiang, Qingwu

2018-01-01

Background Schistosomiasis is a snail-borne parasitic disease and is endemic in many tropical and subtropical countries. Biomphalaria straminea, an intermediate host for Schistosoma mansoni, is native to the southeastern part of South America and has established in other regions of South America, Central America and southern China during the last decades. S. mansoni is endemic in Africa, the Middle East, South America and the Caribbean. Knowledge of the potential global distribution of this snail is essential for risk assessment, monitoring, disease prevention and control. Methods and findings A comprehensive database of cross-continental occurrence for B. straminea was compiled to construct ecological models. We used several approaches to investigate the distribution of B. straminea, including direct comparison of climatic conditions, principal component analysis and niche overlap analyses to detect niche shifts. We also investigated the impacts of bioclimatic and human factors, and then used the bioclimatic and footprint layers to predict the potential distribution of B. straminea at global scale. We detected niche shifts accompanying the invasions of B. straminea in the Americas and China. The introduced populations had enlarged its habitats to subtropical regions where annual mean temperature is relatively low. Annual mean temperature, isothermality and temperature seasonality were identified as most important climatic features for the occurrence of B. straminea. Additionally, human factors improved the model prediction (P<0.001). Our model showed that under current climate conditions the snail should mostly be confined to the tropic and subtropic regions, including South America, Central America, Sub-Saharan Africa and Southeast Asia. Conclusions Our results confirmed that niche shifts took place in the invasions of B. straminea, in which bioclimatic and human factors played an important role. Our model predicted the global distribution of B. straminea based

Compounds Derived from the Bhutanese Daisy, Ajania nubigena, Demonstrate Dual Anthelmintic Activity against Schistosoma mansoni and Trichuris muris.

PubMed

Wangchuk, Phurpa; Pearson, Mark S; Giacomin, Paul R; Becker, Luke; Sotillo, Javier; Pickering, Darren; Smout, Michael J; Loukas, Alex

2016-08-01

Whipworms and blood flukes combined infect almost one billion people in developing countries. Only a handful of anthelmintic drugs are currently available to treat these infections effectively; there is therefore an urgent need for new generations of anthelmintic compounds. Medicinal plants have presented as a viable source of new parasiticides. Ajania nubigena, the Bhutanese daisy, has been used in Bhutanese traditional medicine for treating various diseases and our previous studies revealed that small molecules from this plant have antimalarial properties. Encouraged by these findings, we screened four major compounds isolated from A. nubigena for their anthelmintic properties. Here we studied four major compounds derived from A. nubigena for their anthelmintic properties against the nematode whipworm Trichuris muris and the platyhelminth blood fluke Schistosoma mansoni using the xWORM assay technique. Of four compounds tested, two compounds-luteolin (3) and (3R,6R)-linalool oxide acetate (1)-showed dual anthelmintic activity against S. mansoni (IC50 range = 5.8-36.9 μg/mL) and T. muris (IC50 range = 9.7-20.4 μg/mL). Using scanning electron microscopy, we determined luteolin as the most efficacious compound against both parasites and additionally was found effective against the schistosomula, the infective stage of S. mansoni (IC50 = 13.3 μg/mL). Luteolin induced tegumental damage to S. mansoni and affected the cuticle, bacillary bands and bacillary glands of T. muris. Our in vivo assessment of luteolin (3) against T. muris infection at a single oral dosing of 100 mg/kg, despite being significantly (27.6%) better than the untreated control group, was markedly weaker than mebendazole (93.1%) in reducing the worm burden in mice. Among the four compounds tested, luteolin demonstrated the best broad-spectrum activity against two different helminths-T. muris and S. mansoni-and was effective against juvenile schistosomes, the stage that is refractory to the current

Antibody response of Schistosoma mansoni-infected human subjects to the recombinant P28 glutathione-S-transferase and to synthetic peptides.

PubMed

Auriault, C; Gras-Masse, H; Pierce, R J; Butterworth, A E; Wolowczuk, I; Capron, M; Ouma, J H; Balloul, J M; Khalife, J; Neyrinck, J L

1990-09-01

The 28-kilodalton antigen of Schistosoma mansoni has been previously described as having importance as the basis for a potential vaccine. The P28 recombinant molecule and three peptides derived from its primary sequence, namely the 24-43, 115-131, and 140-153 peptides, have been tested to evaluate the humoral responses of Kenyan school children previously classified as susceptible or resistant to reinfection after chemotherapy. We report here that the P28 molecule and two of the peptides studied (peptides 115-131 and 140-153) can be used for detecting specific immunoglobulin G (IgG), IgE, and IgA antibodies. Moreover, the IgG4 response of the susceptible population was significantly greater than that of the resistant group, whereas no differences between the two populations were noticed in total IgG anti-P28 antibodies. This suggested that IgG4 could play a role in the lack of immunity of susceptible patients. A strong IgG3 response restricted to the 140-153 peptide was observed but did not discriminate between the resistant and susceptible populations. In contrast, a marked increase in the IgA response to the 140-153 peptide epitope(s) in sera of the resistant population was noticed. Taken together, these results suggest that the P28 antigen and two of the three peptides selected could give predictive information about the development of the disease or the efficiency of vaccination with P28 as the immunogen.

An association between Schistosoma mansoni worms and an enzymatically-active protease/peptidase in mouse blood.

PubMed

Darani, H Y; Doenhoff, M J

2008-04-01

An enzyme found previously in extracts of adult Schistosoma mansoni worms, that hydrolysed the chromogenic substrate N-acetyl-DL-phenylalanine beta-naphthyl-ester, has here been further investigated and characterized. Evidence that the molecule found in the parasite was antigenically and enzymatically homologous with a constituent of normal mouse plasma has been consolidated using a monospecific serum in immunoelectrophoresis and Western immunoblotting. The molecular size of the enzyme was found to be approximately 70 kDa and it was inhibited by a serine protease inhibitor, but not by inhibitors of other classes of protease. The enzymatic activity found in normal mouse serum was also found in normal rat serum, but not in sera from several other mammalian species.

Chemometric and biological validation of a capillary electrophoresis metabolomic experiment of Schistosoma mansoni infection in mice.

PubMed

Garcia-Perez, Isabel; Angulo, Santiago; Utzinger, Jürg; Holmes, Elaine; Legido-Quigley, Cristina; Barbas, Coral

2010-07-01

Metabonomic and metabolomic studies are increasingly utilized for biomarker identification in different fields, including biology of infection. The confluence of improved analytical platforms and the availability of powerful multivariate analysis software have rendered the multiparameter profiles generated by these omics platforms a user-friendly alternative to the established analysis methods where the quality and practice of a procedure is well defined. However, unlike traditional assays, validation methods for these new multivariate profiling tools have yet to be established. We propose a validation for models obtained by CE fingerprinting of urine from mice infected with the blood fluke Schistosoma mansoni. We have analysed urine samples from two sets of mice infected in an inter-laboratory experiment where different infection methods and animal husbandry procedures were employed in order to establish the core biological response to a S. mansoni infection. CE data were analysed using principal component analysis. Validation of the scores consisted of permutation scrambling (100 repetitions) and a manual validation method, using a third of the samples (not included in the model) as a test or prediction set. The validation yielded 100% specificity and 100% sensitivity, demonstrating the robustness of these models with respect to deciphering metabolic perturbations in the mouse due to a S. mansoni infection. A total of 20 metabolites across the two experiments were identified that significantly discriminated between S. mansoni-infected and noninfected control samples. Only one of these metabolites, allantoin, was identified as manifesting different behaviour in the two experiments. This study shows the reproducibility of CE-based metabolic profiling methods for disease characterization and screening and highlights the importance of much needed validation strategies in the emerging field of metabolomics.

Reversing the Resistance Phenotype of the Biomphalaria glabrata Snail Host Schistosoma mansoni Infection by Temperature Modulation

PubMed Central

Ittiprasert, Wannaporn; Knight, Matty

2012-01-01

Biomphalaria glabrata snails that display either resistant or susceptible phenotypes to the parasitic trematode, Schistosoma mansoni provide an invaluable resource towards elucidating the molecular basis of the snail-host/schistosome relationship. Previously, we showed that induction of stress genes either after heat-shock or parasite infection was a major feature distinguishing juvenile susceptible snails from their resistant counterparts. In order to examine this apparent association between heat stress and snail susceptibility, we investigated the effect of temperature modulation in the resistant snail stock, BS-90. Here, we show that, incubated for up to 4 hrs at 32°C prior to infection, these resistant snails became susceptible to infection, i.e. shedding cercariae at 5 weeks post exposure (PE) while unstressed resistant snails, as expected, remained resistant. This suggests that susceptibility to infection by this resistant snail phenotype is temperature-sensitive (ts). Additionally, resistant snails treated with the Hsp 90 specific inhibitor, geldanamycin (GA) after heat stress, were no longer susceptible to infection, retaining their resistant phenotype. Consistently, susceptible snail phenotypes treated with 100 mM GA before parasite exposure also remained uninfected. These results provide direct evidence for the induction of stress genes (heat shock proteins; Hsp 70, Hsp 90 and the reverse transcriptase [RT] domain of the nimbus non-LTR retrotransposon) in B. glabrata susceptibility to S. mansoni infection and characterize the resistant BS-90 snails as a temperature-sensitive phenotype. This study of reversing snail susceptibility phenotypes to S. mansoni provides an opportunity to directly track molecular pathway(s) that underlie the B. glabrata snail's ability to either sustain or destroy the S. mansoni parasite. PMID:22577362

Reversing the resistance phenotype of the Biomphalaria glabrata snail host Schistosoma mansoni infection by temperature modulation.

PubMed

Ittiprasert, Wannaporn; Knight, Matty

2012-01-01

Biomphalaria glabrata snails that display either resistant or susceptible phenotypes to the parasitic trematode, Schistosoma mansoni provide an invaluable resource towards elucidating the molecular basis of the snail-host/schistosome relationship. Previously, we showed that induction of stress genes either after heat-shock or parasite infection was a major feature distinguishing juvenile susceptible snails from their resistant counterparts. In order to examine this apparent association between heat stress and snail susceptibility, we investigated the effect of temperature modulation in the resistant snail stock, BS-90. Here, we show that, incubated for up to 4 hrs at 32°C prior to infection, these resistant snails became susceptible to infection, i.e. shedding cercariae at 5 weeks post exposure (PE) while unstressed resistant snails, as expected, remained resistant. This suggests that susceptibility to infection by this resistant snail phenotype is temperature-sensitive (ts). Additionally, resistant snails treated with the Hsp 90 specific inhibitor, geldanamycin (GA) after heat stress, were no longer susceptible to infection, retaining their resistant phenotype. Consistently, susceptible snail phenotypes treated with 100 mM GA before parasite exposure also remained uninfected. These results provide direct evidence for the induction of stress genes (heat shock proteins; Hsp 70, Hsp 90 and the reverse transcriptase [RT] domain of the nimbus non-LTR retrotransposon) in B. glabrata susceptibility to S. mansoni infection and characterize the resistant BS-90 snails as a temperature-sensitive phenotype. This study of reversing snail susceptibility phenotypes to S. mansoni provides an opportunity to directly track molecular pathway(s) that underlie the B. glabrata snail's ability to either sustain or destroy the S. mansoni parasite.

Schistosoma mansoni: resistant specific infection-induced gene expression in Biomphalaria glabrata identified by fluorescent-based differential display.

PubMed

Lockyer, Anne E; Noble, Leslie R; Rollinson, David; Jones, Catherine S

2004-01-01

The freshwater tropical snail Biomphalaria glabrata is an intermediate host for Schistosoma mansoni, the causative agent of human intestinal schistosomiasis, and strains differ in their susceptibility to parasite infection. Changes in gene expression in response to parasite infection have been simultaneously examined in a susceptible strain (NHM1742) and a resistant strain (NHM1981) using a newly developed fluorescent-based differential display method. Such RNA profiling techniques allow the examination of changes in gene expression in response to parasite infection, without requiring previous sequence knowledge, or selecting candidate genes that may be involved in the complex neuroendocrine or defence systems of the snail. Thus, novel genes may be identified. Ten transcripts were initially identified, present only in the profiles derived from snails of the resistant strain when exposed to infection. The differential expression of five of these genes, including HSP70 and several novel transcripts with one containing at least two globin-like domains, has been confirmed by semi-quantitative RT-PCR.

Quantitative High-Throughput Screen Identifies Inhibitors of the Schistosoma mansoni Redox Cascade

PubMed Central

Simeonov, Anton; Jadhav, Ajit; Sayed, Ahmed A.; Wang, Yuhong; Nelson, Michael E.; Thomas, Craig J.; Inglese, James; Williams, David L.; Austin, Christopher P.

2008-01-01

Schistosomiasis is a tropical disease associated with high morbidity and mortality, currently affecting over 200 million people worldwide. Praziquantel is the only drug used to treat the disease, and with its increased use the probability of developing drug resistance has grown significantly. The Schistosoma parasites can survive for up to decades in the human host due in part to a unique set of antioxidant enzymes that continuously degrade the reactive oxygen species produced by the host's innate immune response. Two principal components of this defense system have been recently identified in S. mansoni as thioredoxin/glutathione reductase (TGR) and peroxiredoxin (Prx) and as such these enzymes present attractive new targets for anti-schistosomiasis drug development. Inhibition of TGR/Prx activity was screened in a dual-enzyme format with reducing equivalents being transferred from NADPH to glutathione via a TGR-catalyzed reaction and then to hydrogen peroxide via a Prx-catalyzed step. A fully automated quantitative high-throughput (qHTS) experiment was performed against a collection of 71,028 compounds tested as 7- to 15-point concentration series at 5 µL reaction volume in 1536-well plate format. In order to generate a robust data set and to minimize the effect of compound autofluorescence, apparent reaction rates derived from a kinetic read were utilized instead of end-point measurements. Actives identified from the screen, along with previously untested analogues, were subjected to confirmatory experiments using the screening assay and subsequently against the individual targets in secondary assays. Several novel active series were identified which inhibited TGR at a range of potencies, with IC50s ranging from micromolar to the assay response limit (∼25 nM). This is, to our knowledge, the first report of a large-scale HTS to identify lead compounds for a helminthic disease, and provides a paradigm that can be used to jump-start development of novel

In Silico Repositioning-Chemogenomics Strategy Identifies New Drugs with Potential Activity against Multiple Life Stages of Schistosoma mansoni

PubMed Central

Neves, Bruno J.; Braga, Rodolpho C.; Bezerra, José C. B.; Cravo, Pedro V. L.; Andrade, Carolina H.

2015-01-01

Morbidity and mortality caused by schistosomiasis are serious public health problems in developing countries. Because praziquantel is the only drug in therapeutic use, the risk of drug resistance is a concern. In the search for new schistosomicidal drugs, we performed a target-based chemogenomics screen of a dataset of 2,114 proteins to identify drugs that are approved for clinical use in humans that may be active against multiple life stages of Schistosoma mansoni. Each of these proteins was treated as a potential drug target, and its amino acid sequence was used to interrogate three databases: Therapeutic Target Database (TTD), DrugBank and STITCH. Predicted drug-target interactions were refined using a combination of approaches, including pairwise alignment, conservation state of functional regions and chemical space analysis. To validate our strategy, several drugs previously shown to be active against Schistosoma species were correctly predicted, such as clonazepam, auranofin, nifedipine, and artesunate. We were also able to identify 115 drugs that have not yet been experimentally tested against schistosomes and that require further assessment. Some examples are aprindine, gentamicin, clotrimazole, tetrabenazine, griseofulvin, and cinnarizine. In conclusion, we have developed a systematic and focused computer-aided approach to propose approved drugs that may warrant testing and/or serve as lead compounds for the design of new drugs against schistosomes. PMID:25569258

Gestation and breastfeeding in schistosomotic mothers differently modulate the immune response of adult offspring to postnatal Schistosoma mansoni infection

PubMed Central

Santos, Patrícia d‘Emery Alves; de Lorena, Virgínia Maria Barros; Fernandes, Érica de Souza; Sales, Iana Rafaela Fernandes; do Nascimento, Wheverton Ricardo Correia; Gomes, Yara de Miranda; Albuquerque, Mônica Camelo Pessoa de Azevedo; Costa, Vlaudia Maria Assis; de Souza, Valdênia Maria Oliveira

2016-01-01

Schistosoma mansoni antigens in the early life alter homologous and heterologous immunity during postnatal infections. We evaluate the immunity to parasite antigens and ovalbumin (OA) in adult mice born/suckled by schistosomotic mothers. Newborns were divided into: born (BIM), suckled (SIM) or born/suckled (BSIM) in schistosomotic mothers, and animals from noninfected mothers (control). When adults, the mice were infected and compared the hepatic granuloma size and cellularity. Some animals were OA + adjuvant immunised. We evaluated hypersensitivity reactions (HR), antibodies levels (IgG1/IgG2a) anti-soluble egg antigen and anti-soluble worm antigen preparation, and anti-OA, cytokine production, and CD4+FoxP3+T-cells by splenocytes. Compared to control group, BIM mice showed a greater quantity of granulomas and collagen deposition, whereas SIM and BSIM presented smaller granulomas. BSIM group exhibited the lowest levels of anti-parasite antibodies. For anti-OA immunity, immediate HR was suppressed in all groups, with greater intensity in SIM mice accompanied of the remarkable level of basal CD4+FoxP3+T-cells. BIM and SIM groups produced less interleukin (IL)-4 and interferon (IFN)-g. In BSIM, there was higher production of IL-10 and IFN-g, but lower levels of IL-4 and CD4+FoxP3+T-cells. Thus, pregnancy in schistosomotic mothers intensified hepatic fibrosis, whereas breastfeeding diminished granulomas in descendants. Separately, pregnancy and breastfeeding could suppress heterologous immunity; however, when combined, the responses could be partially restored in infected descendants. PMID:26872339

Gestation and breastfeeding in schistosomotic mothers differently modulate the immune response of adult offspring to postnatal Schistosoma mansoni infection.

PubMed

Santos, Patrícia d'Emery Alves; Lorena, Virgínia Maria Barros de; Fernandes, Érica de Souza; Sales, Iana Rafaela Fernandes; Nascimento, Wheverton Ricardo Correia do; Gomes, Yara de Miranda; Albuquerque, Mônica Camelo Pessoa de Azevedo; Costa, Vlaudia Maria Assis; Souza, Valdênia Maria Oliveira de

2016-02-01

Schistosoma mansoni antigens in the early life alter homologous and heterologous immunity during postnatal infections. We evaluate the immunity to parasite antigens and ovalbumin (OA) in adult mice born/suckled by schistosomotic mothers. Newborns were divided into: born (BIM), suckled (SIM) or born/suckled (BSIM) in schistosomotic mothers, and animals from noninfected mothers (control). When adults, the mice were infected and compared the hepatic granuloma size and cellularity. Some animals were OA + adjuvant immunised. We evaluated hypersensitivity reactions (HR), antibodies levels (IgG1/IgG2a) anti-soluble egg antigen and anti-soluble worm antigen preparation, and anti-OA, cytokine production, and CD4+FoxP3+T-cells by splenocytes. Compared to control group, BIM mice showed a greater quantity of granulomas and collagen deposition, whereas SIM and BSIM presented smaller granulomas. BSIM group exhibited the lowest levels of anti-parasite antibodies. For anti-OA immunity, immediate HR was suppressed in all groups, with greater intensity in SIM mice accompanied of the remarkable level of basal CD4+FoxP3+T-cells. BIM and SIM groups produced less interleukin (IL)-4 and interferon (IFN)-g. In BSIM, there was higher production of IL-10 and IFN-g, but lower levels of IL-4 and CD4+FoxP3+T-cells. Thus, pregnancy in schistosomotic mothers intensified hepatic fibrosis, whereas breastfeeding diminished granulomas in descendants. Separately, pregnancy and breastfeeding could suppress heterologous immunity; however, when combined, the responses could be partially restored in infected descendants.

Schistosoma mansoni Infections, Undernutrition and Anaemia among Primary Schoolchildren in Two Onshore Villages in Rorya District, North-Western Tanzania.

PubMed

Munisi, David Zadock; Buza, Joram; Mpolya, Emmanuel A; Kinung'hi, Safari M

2016-01-01

Undernutrition and anaemia remains to be a major public health problem in many developing countries, where they mostly affect children. Intestinal parasitic infections are known to affect both growth and haemoglobin levels. Much has been reported on the impact of geohelminths on anaemia and undernutrition, leaving that of Schistosoma mansoni not well studied. Therefore this study intended to determine the association between S.mansoni infections, anaemia and undernutrition among schoolchildren in Rorya district, Northwestern Tanzania. A cross-sectional study was carried among schoolchildren in two onshore villages namely Busanga and Kibuyi in Rorya district. Single stool specimens were collected from 513 randomly selected schoolchildren and processed for microscopic examination using the Kato-Katz method. Nutritional status was determined by anthropometry. Blood samples were also collected and examined for malaria parasites and haemoglobin levels using the Giemsa stain and HaemoCue methods, respectively. A pretested questionnaire was used to collect socio-demographic data and associated factors. The prevalence of S. mansoni infection and malaria was 84.02% and 9.16%, respectively. Other parasites found were Ascaris lumbricoides (1.36%) and Hookworm (1.36%). The prevalence of stunting and wasting was 38.21% and 14.42%, respectively. The prevalence of anaemia was 29.43%, whereby 0.58% had severe anaemia. S. mansoni infection was not found to be associated with undernutrition or anaemia (p>0.05). The risk of stunting and wasting increased with increasing age (p<0.001). Anaemia was associated with age, sex and village of residence (p<0.05). S.mansoni, undernutrition and anaemia are highly prevalent in the study area. The observed rates of undernutrition and anaemia were seen not to be associated with S.mansoni infection suggesting possibly being a result of poor dietary nutrients. This study suggests that policy makers should consider Rorya district for inclusion into

Soil transmitted helminths and schistosoma mansoni infections among school children in zarima town, northwest Ethiopia

PubMed Central

2011-01-01

Background In Ethiopia, because of low quality drinking water supply and latrine coverage, helminths infections are the second most predominant causes of outpatient morbidity. Indeed, there is a scarcity of information on the prevalence of soil transmitted helminths and Schistosomiasis in Ethiopia, special in study area. Therefore, the aim of this study was to determine the prevalence and associated risk factors of soil transmitted helminths and intestinal Schistosomiasis. Methods Cross-sectional study was conducted among 319 school children of Zarima town from April 1 to May 25, 2009. A pre-tested structured questionnaire was used to collect socio-demographic data and possible risk factors exposure. Early morning stool samples were collected and a Kato Katz semi concentration technique was used to examine and count parasitic load by compound light microscope. Data entry and analysis was done using SPSS-15 version and p-value < 0.05 considered statistically significant. Results Out of 319 study subjects, 263 (82.4%) of the study participants infected with one or more parasites. From soil transmitted helminths, Ascaris lumbricoides was the predominant isolate (22%) followed by Hookworms (19%) and Trichuris trichiura (2.5%). Schistosoma mansoni was also isolated in 37.9% of the study participants. Hookworm and S. mansoni infections showed statistically significant associations with shoe wearing and swimming habit of school children, respectively. Conclusion Prevalence of soil transmitted helminths (STH) and S.mansoni was high and the diseases were still major health problem in the study area which alerts public health intervention as soon as possible. PMID:21740589

Use of Occult Blood Detection Cards for Real-Time PCR-Based Diagnosis of Schistosoma Mansoni Infection

PubMed Central

Schunk, Mirjam; Kebede Mekonnen, Seleshi; Wondafrash, Beyene; Mengele, Carolin; Fleischmann, Erna; Herbinger, Karl-Heinz; Verweij, Jaco J.; Geldmacher, Christof; Bretzel, Gisela; Löscher, Thomas; Zeynudin, Ahmed

2015-01-01

Background In Schistosoma mansoni infection, diagnosis and control after treatment mainly rely on parasitological stool investigations which are laborious and have limited sensitivity. PCR methods have shown equal or superior sensitivity but preservation and storage methods limit their use in the field. Therefore, the use of occult blood detection cards (fecal cards) for easy sampling and storage of fecal samples for further PCR testing was evaluated in a pilot study. Methodology Stool specimens were collected in a highly endemic area for S. mansoni in Ethiopia and submitted in an investigator-blinded fashion to microscopic examination by Kato-Katz thick smear as well as to real-time PCR using either fresh frozen stool samples or stool smears on fecal cards which have been stored at ambient temperature for up to ten months. Principal Findings Out of 55 stool samples, 35 were positive by microscopy, 33 and 32 were positive by PCR of frozen samples and of fecal card samples, respectively. When microscopy was used as diagnostic “gold standard”, the sensitivity of PCR on fresh stool was 94.3% (95%-CI: 86.6; 100) and on fecal cards 91.4% (95%-CI: 82.2; 100). Conclusions The use of fecal cards proved to be a simple and useful method for stool collection and prolonged storage prior to PCR based diagnosis of S. mansoni infection. This technique may be a valuable approach for large scale surveillance and post treatment assessments PMID:26360049

Use of Occult Blood Detection Cards for Real-Time PCR-Based Diagnosis of Schistosoma Mansoni Infection.

PubMed

Schunk, Mirjam; Kebede Mekonnen, Seleshi; Wondafrash, Beyene; Mengele, Carolin; Fleischmann, Erna; Herbinger, Karl-Heinz; Verweij, Jaco J; Geldmacher, Christof; Bretzel, Gisela; Löscher, Thomas; Zeynudin, Ahmed

2015-01-01

In Schistosoma mansoni infection, diagnosis and control after treatment mainly rely on parasitological stool investigations which are laborious and have limited sensitivity. PCR methods have shown equal or superior sensitivity but preservation and storage methods limit their use in the field. Therefore, the use of occult blood detection cards (fecal cards) for easy sampling and storage of fecal samples for further PCR testing was evaluated in a pilot study. Stool specimens were collected in a highly endemic area for S. mansoni in Ethiopia and submitted in an investigator-blinded fashion to microscopic examination by Kato-Katz thick smear as well as to real-time PCR using either fresh frozen stool samples or stool smears on fecal cards which have been stored at ambient temperature for up to ten months. Out of 55 stool samples, 35 were positive by microscopy, 33 and 32 were positive by PCR of frozen samples and of fecal card samples, respectively. When microscopy was used as diagnostic "gold standard", the sensitivity of PCR on fresh stool was 94.3% (95%-CI: 86.6; 100) and on fecal cards 91.4% (95%-CI: 82.2; 100). The use of fecal cards proved to be a simple and useful method for stool collection and prolonged storage prior to PCR based diagnosis of S. mansoni infection. This technique may be a valuable approach for large scale surveillance and post treatment assessments.

In silico analysis of the fucosylation-associated genome of the human blood fluke Schistosoma mansoni: cloning and characterization of the fucosyltransferase multigene family.

PubMed

Peterson, Nathan A; Anderson, Tavis K; Yoshino, Timothy P

2013-01-01

Fucosylated glycans of the parasitic flatworm Schistosoma mansoni play key roles in its development and immunobiology. In the present study we used a genome-wide homology-based bioinformatics approach to search for genes that contribute to fucosylated glycan expression in S. mansoni, specifically the α2-, α3-, and α6-fucosyltransferases (FucTs), which transfer L-fucose from a GDP-L-fucose donor to an oligosaccharide acceptor. We identified and in silico characterized several novel schistosome FucT homologs, including six α3-FucTs and six α6-FucTs, as well as two protein O-FucTs that catalyze the unrelated transfer of L-fucose to serine and threonine residues of epidermal growth factor- and thrombospondin-type repeats. No α2-FucTs were observed. Primary sequence analyses identified key conserved FucT motifs as well as characteristic transmembrane domains, consistent with their putative roles as fucosyltransferases. Most genes exhibit alternative splicing, with multiple transcript variants generated. A phylogenetic analysis demonstrated that schistosome α3- and α6-FucTs form monophyletic clades within their respective gene families, suggesting multiple gene duplications following the separation of the schistosome lineage from the main evolutionary tree. Quantitative decreases in steady-state transcript levels of some FucTs during early larval development suggest a possible mechanism for differential expression of fucosylated glycans in schistosomes. This study systematically identifies the complete repertoire of FucT homologs in S. mansoni and provides fundamental information regarding their genomic organization, genetic variation, developmental expression, and evolutionary history.

Ultrastructural study on Biomphalaria alexandrina haemocytes infected with Schistosoma mansoni in Egypt and its correlation with nitric oxide level.

PubMed

Helal, Eman G; El-Dafrawy, Shadia M; Mohamed, Amira H; Abou-El-Nour, Basma M; Ibrahim, Samah

2014-04-01

Some snails of Biomphalaria alexandrina can resist the infection of Schistosoma mansoni so this study aimed to clearly this mechanism by using light and electron microscopy (EM) and determine the role of Nitric oxide in this mechanism. B. alexandrina snails used in this study were exposed individually to S. mansoni infection according to their response they were classified into susceptible group (shed cercariae) and resistant group (failed to shed cercariae). Snails not exposed to infection were included in this study as control group. Nitric oxide (NO) level was assayed directly in the soluble fraction of B. alexandrina haemolymph supernatants collected from each group of B. alexandrina snails were subjected to NO assay by the Greiss reaction. The level of NO in haemolymph of infected snails was significantly increased (p < 0.001) than both control and non infected snails groups, however, in non infected snails group had significantly (p < 0.05) compared to control group. This study when correlated the changes recognized by EM with NO level the pro apoptotic effect of high level of NO on the haemocytes. Characterization and identification of cell shape of haemocytes in both haemolymph and tissue were examined by light and electron microscopy. Examination of B. alexandrina snail's haemocytes revealed three types of different cells classified according to their shape and granular contents. These cells are granulocytes, amoebocytes and hyalineocytes. Electron microscope study also revealed the important role of granulocytes and amoebocytes as defense mechanism against snail infection. NO is considered an important anti parasite molecule; intra-molluscan stages of parasites switch off host NO defense response.

Biompha-LAMP: A New Rapid Loop-Mediated Isothermal Amplification Assay for Detecting Schistosoma mansoni in Biomphalaria glabrata Snail Host

PubMed Central

Hernández-Goenaga, Juan; López-Abán, Julio; Vicente, Belén; Muro, Antonio

2016-01-01

Background Schistosomiasis remains one of the most common endemic parasitic diseases affecting over 230 million people worlwide. Schistosoma mansoni is the main species causing intestinal and hepatic schistosomiasis and the fresh water pulmonate snails of the genus Biomphalaria are best known for their role as intermediate hosts of the parasite. The development of new molecular monitoring assays for large-scale screening of snails from transmission sites to detect the presence of schistosomes is an important point to consider for snail control interventions related to schistosomiasis elimination. Our work was focussed on developing and evaluating a new LAMP assay combined with a simple DNA extraction method to detect S. mansoni in experimentally infected snails as a diagnostic tool for field conditions. Methodology/Principal findings A LAMP assay using a set of six primers targeting a sequence of S. mansoni ribosomal intergenic spacer 28S-18S rRNA was designed. The detection limit of the LAMP assay was 0.1 fg of S. mansoni DNA at 63°C for 50 minutes. LAMP was evaluated by examining S. mansoni DNA in B. glabrata snails experimentally exposed to miracidia at different times post-exposure: early prepatent period (before cercarial shedding), light infections (snails exposed to a low number of miracidia) and detection of infected snails in pooled samples (within a group of uninfected snails). DNA for LAMP assays was obtained by using a commercial DNA extraction kit or a simple heat NaOH extraction method. We detected S. mansoni DNA in all groups of snails by using no complicated requirement procedure for DNA obtaining. Conclusions/Significance Our LAMP assay, named Biompha-LAMP, is specific, sensitive, rapid and potentially adaptable as a cost-effective method for screening of intermediate hosts infected with S. mansoni in both individual snails and pooled samples. The assay could be suitable for large-scale field surveys for schistosomes control campaigns in endemic

Sublethal toxicity of Roundup to immunological and molecular aspects of Biomphalaria alexandrina to Schistosoma mansoni infection.

PubMed

Mohamed, Azza H

2011-05-01

The present study was performed to elucidate the cellular mechanisms of Biomphalaria alexandrina snails hemocytes against sublethal concentration (10 mg/L) of herbicide Roundup (48% Glyphosate) and/or Schistosoma mansoni infection during 7 days of exposure. Obtained results indicated that herbicide treatment and/or infection led to significant increase (P<0.05) in total hemocytes count during exposure period. Examination of hemocytes monolayers resulted in observation of 3 morphologically different cell types, round small, hyalinocytes and spreading hemocytes. Spreading hemocytes are the dominant, more responsive and highly phagocytic cell type in all experimental groups. Moreover, the exposure to herbicide, infection or both together led to a significant increase (P<0.05) of in vitro phagocytic activity against yeast cells during 7 days of exposure. In addition, flow cytometric analysis of cell cycle and comet assay, resulted in DNA damage in B. alexandrina hemocytes exposed to herbicide and/or S. mansoni infection when compared to control group. The immunological responses as well as molecular aspects in B. alexandrina snails have been proposed as biomarkers of exposure to environmental pollutants. Copyright © 2010 Elsevier Inc. All rights reserved.

Ecotourism as a source of infection with Schistosoma mansoni in Minas Gerais, Brazil.

PubMed

Murta, Felipe Leão Gomes; Massara, Cristiano Lara; Nogueira, Joyce Favacho Cardoso; Dos Santos Carvalho, Omar; de Mendonça, Cristiane Lafetá Furtado; Pinheiro, Viviane Aparecida Oliveira; Enk, Martin Johannes

2016-01-01

In recent years, a new pattern of schistosomiasis transmission has been described which is related to recreational activities associated with rural or ecological tourism and migratory flows and accompanying changes in social dynamics in Brazil. The objective of this report is to describe two schistosomiasis outbreaks that occurred during the practice of rural tourism in Minas Gerais, Brazil, and review this pattern of transmission within the wider context of schistosomiasis control. The first outbreak was characterized by its high infection rate, showing that 59 % of the exposed eco-tourists became positive for infection with Schistosoma mansoni . In addition, all three disease transmitting species of intermediate host snails were found in the area. In the second outbreak, all members of one tourist family were infected and reported contact with water in a well-known tourist area. The malacological survey in the region revealed an infection rate with S. mansoni of 8.3 % among the collected snails. Infection of urban dwellers that report contact with contaminated water associated with ecotourism represents a new pattern of disease transmission and dissemination. The infection with the disease at these occasions finds its expression in outbreaks of acute schistosomiasis among internal tourists to rural areas. Therefore, epidemiological surveillance in endemic areas should be aware of this schistosomiasis transmission pattern, and a multidisciplinary approach, most of all sanitation and health education measures, is required in order increase the efficiency of control strategies.

Schistosome-induced cholangiocyte proliferation and osteopontin secretion correlate with fibrosis and portal hypertension in human and murine schistosomiasis mansoni.

PubMed

Pereira, Thiago A; Syn, Wing-Kin; Machado, Mariana V; Vidigal, Paula V; Resende, Vivian; Voieta, Izabela; Xie, Guanhua; Otoni, Alba; Souza, Márcia M; Santos, Elisângela T; Chan, Isaac S; Trindade, Guilherme V M; Choi, Steve S; Witek, Rafal P; Pereira, Fausto E; Secor, William E; Andrade, Zilton A; Lambertucci, José Roberto; Diehl, Anna Mae

2015-11-01

Schistosomiasis is a major cause of portal hypertension worldwide. It associates with portal fibrosis that develops during chronic infection. The mechanisms by which the pathogen evokes these host responses remain unclear. We evaluated the hypothesis that schistosome eggs release factors that directly stimulate liver cells to produce osteopontin (OPN), a pro-fibrogenic protein that stimulates hepatic stellate cells to become myofibroblasts. We also investigated the utility of OPN as a biomarker of fibrosis and/or severity of portal hypertension. Cultured cholangiocytes, Kupffer cells and hepatic stellate cells were treated with soluble egg antigen (SEA); OPN production was quantified by quantitative reverse transcriptase polymerase chain reaction (qRTPCR) and ELISA; cell proliferation was assessed by BrdU (5-bromo-2'-deoxyuridine). Mice were infected with Schistosoma mansoni for 6 or 16 weeks to cause early or advanced fibrosis. Liver OPN was evaluated by qRTPCR and immunohistochemistry (IHC) and correlated with liver fibrosis and serum OPN. Livers from patients with schistosomiasis mansoni (early fibrosis n=15; advanced fibrosis n=72) or healthy adults (n=22) were immunostained for OPN and fibrosis markers. Results were correlated with plasma OPN levels and splenic vein pressures. SEA-induced cholangiocyte proliferation and OPN secretion (P<0.001 compared with controls). Cholangiocytes were OPN (+) in Schistosoma-infected mice and humans. Liver and serum OPN levels correlated with fibrosis stage (mice: r=0.861; human r=0.672, P=0.0001) and myofibroblast accumulation (mice: r=0.800; human: r=0.761, P=0.0001). Numbers of OPN (+) bile ductules strongly correlated with splenic vein pressure (r=0.778; P=0.001). S. mansoni egg antigens stimulate cholangiocyte proliferation and OPN secretion. OPN levels in liver and blood correlate with fibrosis stage and portal hypertension severity. © 2015 Authors; published by Portland Press Limited.

Countrywide Reassessment of Schistosoma mansoni Infection in Burundi Using a Urine-Circulating Cathodic Antigen Rapid Test: Informing the National Control Program

PubMed Central

Ortu, Giuseppina; Ndayishimiye, Onésime; Clements, Michelle; Kayugi, Donatien; Campbell, Carl H.; Lamine, Mariama Sani; Zivieri, Antonio; Magalhaes, Ricardo Soares; Binder, Sue; King, Charles H.; Fenwick, Alan; Colley, Daniel G.; Jourdan, Peter Mark

2017-01-01

Following implementation of the national control program, a reassessment of Schistosoma mansoni prevalence was conducted in Burundi to determine the feasibility of moving toward elimination. A countrywide cluster-randomized cross-sectional study was performed in May 2014. At least 25 schools were sampled from each of five eco-epidemiological risk zones for schistosomiasis. Fifty randomly selected children 13–14 years of age per school were included for a single urine-circulating cathodic antigen (CCA) rapid test and, in a subset of schools, for duplicate Kato-Katz slide preparation from a single stool sample. A total of 17,331 children from 347 schools were tested using CCA. The overall prevalence of S. mansoni infection, when CCA trace results were considered negative, was 13.5% (zone range [zr] = 4.6–17.8%), and when CCA trace results were considered positive, it was 42.8% (zr = 34.3–49.9%). In 170 schools, prevalence of this infection determined using Kato-Katz method was 1.5% (zr ==0–2.7%). The overall mean intensity of S. mansoni infection determined using Kato-Katz was 0.85 eggs per gram (standard deviation = 10.86). A majority of schools (84%) were classified as non-endemic (prevalence = 0) using Kato-Katz; however, a similar proportion of schools were classified as endemic when CCA trace results were considered negative (85%) and nearly all (98%) were endemic when CCA trace results were considered positive. The findings of this nationwide reassessment using a CCA rapid test indicate that Schistosoma infection is still widespread in Burundi, although its average intensity is probably low. Further evidence is now needed to determine the association between CCA rapid test positivity and low-intensity disease transmission. PMID:28115675

Cloning of the chaperonin t-complex polypeptide 1 gene from Schistosoma mansoni and studies of its expression levels under heat shock and oxidative stress.

PubMed

Campos, E G; Hamdan, F F

2000-03-01

The protein TCP-1 (t-complex polypeptide 1) is a subunit of the hetero-oligomeric complex CCT (chaperonin containing TCP- 1) present in the eukaryotic cytosol. Chaperone function may be critical for the development and survival of the different life stages of Schistosoma mansoni, a parasite that is exposed to drastic environmental changes during its development. We isolated a full-length S. mansoni TCP-1 cDNA (SmTCP-1A) encoding a protein highly homologous with TCP-1. The deduced SmTCP-1A amino-acid sequence shows up to 65% identity with other eukaryotic CCT family members. Semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) analysis revealed that the mRNA expression levels of SmTCP-1A in adult S. mansoni were down-regulated in worms subjected to heat shock and oxidative stress conditions. This down-regulation of SmTCP-1A mRNA may reflect a switch in CCT subunits as an adaptive response to heat shock and oxidative stress conditions.

Comparing the performance of circulating cathodic antigen and Kato-Katz techniques in evaluating Schistosoma mansoni infection in areas with low prevalence in selected counties of Kenya: a cross-sectional study.

PubMed

Okoyo, Collins; Simiyu, Elses; Njenga, Sammy M; Mwandawiro, Charles

2018-04-11

Kato-Katz technique has been the mainstay test in Schistosoma mansoni diagnosis in endemic areas. However, recent studies have documented its poor sensitivity in evaluating Schistosoma mansoni infection especially in areas with lower rates of transmission. It's the primary diagnostic tool in monitoring impact of the Kenya national school based deworming program on infection transmission, but there is need to consider a more sensitive technique as the prevalence reduces. Therefore, this study explored the relationship between results of the stool-based Kato-Katz technique with urine-based point-of-care circulating cathodic antigen (POC-CCA) test in view to inform decision-making by the program in changing from Kato-Katz to POC-CCA test. We used two cross-sectional surveys conducted pre- and post- mass drug administration (MDA) using praziquantel in a representative random sample of children from 18 schools across 11 counties. A total of 1944 children were randomly sampled for the study. Stool and urine samples were tested for S. mansoni infection using Kato-Katz and POC-CCA methods, respectively. S. mansoni prevalence using each technique was calculated and 95% confidence intervals obtained using binomial regression model. Specificity (Sp) and sensitivity (Sn) were determined using 2 × 2 contingency tables and compared using the McNemar's chi-square test. A total of 1899 and 1878 children were surveyed at pre- and post-treatment respectively. S. mansoni infection prevalence was 26.5 and 21.4% during pre- and post-treatment respectively using POC-CCA test, and 4.9 and 1.5% for pre- and post-treatment respectively using Kato-Katz technique. Taking POC-CCA as the gold standard, Kato-Katz was found to have significantly lower sensitivity both at pre- and post-treatment, Sn = 12.5% and Sn = 5.2% respectively, McNemar test χ 2 m  = 782.0, p < 0.001. In overall, the results showed a slight/poor agreement between the two methods, kappa index (k

Compounds Derived from the Bhutanese Daisy, Ajania nubigena, Demonstrate Dual Anthelmintic Activity against Schistosoma mansoni and Trichuris muris

PubMed Central

Pearson, Mark S.; Giacomin, Paul R.; Becker, Luke; Sotillo, Javier; Pickering, Darren

2016-01-01

Background Whipworms and blood flukes combined infect almost one billion people in developing countries. Only a handful of anthelmintic drugs are currently available to treat these infections effectively; there is therefore an urgent need for new generations of anthelmintic compounds. Medicinal plants have presented as a viable source of new parasiticides. Ajania nubigena, the Bhutanese daisy, has been used in Bhutanese traditional medicine for treating various diseases and our previous studies revealed that small molecules from this plant have antimalarial properties. Encouraged by these findings, we screened four major compounds isolated from A. nubigena for their anthelmintic properties. Methodology/Principal Findings Here we studied four major compounds derived from A. nubigena for their anthelmintic properties against the nematode whipworm Trichuris muris and the platyhelminth blood fluke Schistosoma mansoni using the xWORM assay technique. Of four compounds tested, two compounds—luteolin (3) and (3R,6R)-linalool oxide acetate (1)—showed dual anthelmintic activity against S. mansoni (IC50 range = 5.8–36.9 μg/mL) and T. muris (IC50 range = 9.7–20.4 μg/mL). Using scanning electron microscopy, we determined luteolin as the most efficacious compound against both parasites and additionally was found effective against the schistosomula, the infective stage of S. mansoni (IC50 = 13.3 μg/mL). Luteolin induced tegumental damage to S. mansoni and affected the cuticle, bacillary bands and bacillary glands of T. muris. Our in vivo assessment of luteolin (3) against T. muris infection at a single oral dosing of 100 mg/kg, despite being significantly (27.6%) better than the untreated control group, was markedly weaker than mebendazole (93.1%) in reducing the worm burden in mice. Conclusions/Significance Among the four compounds tested, luteolin demonstrated the best broad-spectrum activity against two different helminths—T. muris and S. mansoni—and was

Sustaining the Control of Schistosoma mansoni in Western Côte d'Ivoire: Baseline Findings before the Implementation of a Randomized Trial

PubMed Central

Assaré, Rufin K.; Hürlimann, Eveline; Ouattara, Mamadou; N'Guessan, Nicaise A.; Tian-Bi, Yves-Nathan T.; Yapi, Ahoua; Yao, Patrick K.; Coulibaly, Jean T.; Knopp, Stefanie; N'Goran, Eliézer K.; Utzinger, Jürg

2016-01-01

We report baseline findings before the implementation of a 4-year intervention trial designed to assess the impact of three different school-based treatment schedules with praziquantel to sustain the control of intestinal schistosomiasis. The baseline survey was conducted in 75 schools of western Côte d'Ivoire previously identified with moderate Schistosoma mansoni endemicity (prevalence: 10–24% in children aged 13–14 years). Three stool samples collected over consecutive days were subjected to duplicate Kato-Katz thick smears each. A questionnaire was administered to collect village-specific information that is relevant for schistosomiasis transmission. Overall, 4,953 first graders (aged 5–8 years) and 7,011 school children (aged 9–12 years) had complete parasitologic data. The overall prevalence of S. mansoni was 5.4% among first graders and 22.1% in 9- to 12-year-old children. Open defecation was practiced in all villages. The current baseline findings will be important to better understand the dynamics of S. mansoni prevalence and intensity over the course of this trial that might be governed by village characteristics and specific treatment interventions. PMID:26598571

New insights into the molecular epidemiology and population genetics of Schistosoma mansoni in Ugandan pre-school children and mothers.

PubMed

Betson, Martha; Sousa-Figueiredo, Jose C; Kabatereine, Narcis B; Stothard, J Russell

2013-01-01

Significant numbers of pre-school children are infected with Schistosoma mansoni in sub-Saharan Africa and are likely to play a role in parasite transmission. However, they are currently excluded from control programmes. Molecular phylogenetic studies have provided insights into the evolutionary origins and transmission dynamics of S. mansoni, but there has been no research into schistosome molecular epidemiology in pre-school children. Here, we investigated the genetic diversity and population structure of S. mansoni in pre-school children and mothers living in lakeshore communities in Uganda and monitored for changes over time after praziquantel treatment. Parasites were sampled from children (<6 years) and mothers enrolled in the longitudinal Schistosomiasis Mothers and Infants Study at baseline and at 6-, 12- and 18-month follow-up surveys. 1347 parasites from 35 mothers and 45 children were genotyped by direct sequencing of the cytochrome c oxidase (cox1) gene. The cox1 region was highly diverse with over 230 unique sequences identified. Parasite populations were genetically differentiated between lakes and non-synonymous mutations were more diverse at Lake Victoria than Lake Albert. Surprisingly, parasite populations sampled from children showed a similar genetic diversity to those sampled from mothers, pointing towards a non-linear relationship between duration of exposure and accumulation of parasite diversity. The genetic diversity six months after praziquantel treatment was similar to pre-treatment diversity. Our results confirm the substantial genetic diversity of S. mansoni in East Africa and provide significant insights into transmission dynamics within young children and mothers, important information for schistosomiasis control programmes.

Novel Non-Peptide Inhibitors against SmCL1 of Schistosoma mansoni: In Silico Elucidation, Implications and Evaluation via Knowledge Based Drug Discovery

PubMed Central

Zafar, Atif; Ahmad, Sabahuddin; Rizvi, Asim; Ahmad, Masood

2015-01-01

Schistosomiasis is a major endemic disease known for excessive mortality and morbidity in developing countries. Because praziquantel is the only drug available for its treatment, the risk of drug resistance emphasizes the need to discover new drugs for this disease. Cathepsin SmCL1 is the critical target for drug design due to its essential role in the digestion of host proteins for growth and development of Schistosoma mansoni. Inhibiting the function of SmCL1 could control the wide spread of infections caused by S. mansoni in humans. With this objective, a homology modeling approach was used to obtain theoretical three-dimensional (3D) structure of SmCL1. In order to find the potential inhibitors of SmCL1, a plethora of in silico techniques were employed to screen non-peptide inhibitors against SmCL1 via structure-based drug discovery protocol. Receiver operating characteristic (ROC) curve analysis and molecular dynamics (MD) simulation were performed on the results of docked protein-ligand complexes to identify top ranking molecules against the modelled 3D structure of SmCL1. MD simulation results suggest the phytochemical Simalikalactone-D as a potential lead against SmCL1, whose pharmacophore model may be useful for future screening of potential drug molecules. To conclude, this is the first report to discuss the virtual screening of non-peptide inhibitors against SmCL1 of S. mansoni, with significant therapeutic potential. Results presented herein provide a valuable contribution to identify the significant leads and further derivatize them to suitable drug candidates for antischistosomal therapy. PMID:25933436

Increased human IgE induced by killing Schistosoma mansoni in vivo is associated with pretreatment Th2 cytokine responsiveness to worm antigens.

PubMed

Walter, Klaudia; Fulford, Anthony J C; McBeath, Rowena; Joseph, Sarah; Jones, Frances M; Kariuki, H Curtis; Mwatha, Joseph K; Kimani, Gachuhi; Kabatereine, Narcis B; Vennervald, Birgitte J; Ouma, John H; Dunne, David W

2006-10-15

In schistosomiasis endemic areas, children are very susceptible to postchemotherapy reinfection, whereas adults are relatively resistant. Different studies have reported that schistosome-specific IL-4 and IL-5 responses, or posttreatment worm-IgE levels, correlate with subsequent low reinfection. Chemotherapy kills i.v. worms providing an in vivo Ag challenge. We measured anti-worm (soluble worm Ag (SWA) and recombinant tegumental Ag (rSm22.6)) and anti-egg (soluble egg Ag) Ab levels in 177 Ugandans (aged 7-50) in a high Schistosoma mansoni transmission area, both before and 7 wk posttreatment, and analyzed these data in relation to whole blood in vitro cytokine responses at the same time points. Soluble egg Ag-Ig levels were unaffected by treatment but worm-IgG1 and -IgG4 increased, whereas worm-IgE increased in many but not all individuals. An increase in worm-IgE was mainly seen in >15-year-olds and, unlike in children, was inversely correlated to pretreatment infection intensities, suggesting this response was associated both with resistance to pretreatment infection, as well as posttreatment reinfection. The increases in SWA-IgE and rSm22.6-IgE positively correlated with pretreatment Th2 cytokines, but not IFN-gamma, induced by SWA. These relationships remained significant after allowing for the confounding effects of pretreatment infection intensity, age, and pretreatment IgE levels, indicating a link between SWA-specific Th2 cytokine responsiveness and subsequent increases in worm-IgE. An exceptionally strong relationship between IL-5 and posttreatment worm-IgE levels in < 15-year-olds suggested that the failure of younger children to respond to in vivo Ag stimulation with increased levels of IgE, is related to their lack of pretreatment SWA Th2 cytokine responsiveness.

Systematic Review and Meta-analysis of the Impact of Chemical-Based Mollusciciding for Control of Schistosoma mansoni and S. haematobium Transmission

PubMed Central

King, Charles H.; Sutherland, Laura J.; Bertsch, David

2015-01-01

Background Programs for schistosomiasis control are advancing worldwide, with many benefits noted in terms of disease reduction. Yet risk of reinfection and recurrent disease remain, even in areas with high treatment coverage. In the search for means to better prevent new Schistosoma infections, attention has returned to an older strategy for transmission control, i.e., chemical mollusciciding, to suppress intermediate host snail species responsible for S. mansoni and S. haematobium transmission. The objective of this systematic review and meta-analysis was to summarize prior experience in molluscicide-based control of Bulinus and Biomphalaria spp. snails, and estimate its impact on local human Schistosoma infection. Methodology/Principal Findings The review was registered at inception with PROSPERO (CRD42013006869). Studies were identified by online database searches and hand searches of private archives. Eligible studies included published or unpublished mollusciciding field trials performed before January 2014 involving host snails for S. mansoni or S. haematobium, with a primary focus on the use of niclosamide. Among 63 included papers, there was large variability in terms of molluscicide dosing, and treatment intervals varied from 3–52 weeks depending on location, water source, and type of application. Among 35 studies reporting on prevalence, random effects meta-analysis indicated that, on average, odds of infection were reduced 77% (OR 0.23, CI95% 0.17, 0.31) during the course of mollusciciding, with increased impact if combined with drug therapy, and progressively greater impact over time. In 17 studies reporting local incidence, risk of new infection was reduced 64% (RR 0.36 CI95% 0.25, 0.5), but additional drug treatment did not appear to influence incidence effects. Conclusion/Significance While there are hurdles to implementing molluscicide control, its impact on local transmission is typically strong, albeit incomplete. Based on past experience

Planning schistosomiasis control: investigation of alternative sampling strategies for Schistosoma mansoni to target mass drug administration of praziquantel in East Africa.

PubMed

Sturrock, Hugh J W; Gething, Pete W; Ashton, Ruth A; Kolaczinski, Jan H; Kabatereine, Narcis B; Brooker, Simon

2011-09-01

In schistosomiasis control, there is a need to geographically target treatment to populations at high risk of morbidity. This paper evaluates alternative sampling strategies for surveys of Schistosoma mansoni to target mass drug administration in Kenya and Ethiopia. Two main designs are considered: lot quality assurance sampling (LQAS) of children from all schools; and a geostatistical design that samples a subset of schools and uses semi-variogram analysis and spatial interpolation to predict prevalence in the remaining unsurveyed schools. Computerized simulations are used to investigate the performance of sampling strategies in correctly classifying schools according to treatment needs and their cost-effectiveness in identifying high prevalence schools. LQAS performs better than geostatistical sampling in correctly classifying schools, but at a cost with a higher cost per high prevalence school correctly classified. It is suggested that the optimal surveying strategy for S. mansoni needs to take into account the goals of the control programme and the financial and drug resources available.

SmShb, the SH2-Containing Adaptor Protein B of Schistosoma mansoni Regulates Venus Kinase Receptor Signaling Pathways

PubMed Central

Morel, Marion; Vanderstraete, Mathieu; Cailliau, Katia; Hahnel, Steffen; Grevelding, Christoph G.; Dissous, Colette

2016-01-01

Venus kinase receptors (VKRs) are invertebrate receptor tyrosine kinases (RTKs) formed by an extracellular Venus Fly Trap (VFT) ligand binding domain associated via a transmembrane domain with an intracellular tyrosine kinase (TK) domain. Schistosoma mansoni VKRs, SmVKR1 and SmVKR2, are both implicated in reproductive activities of the parasite. In this work, we show that the SH2 domain-containing protein SmShb is a partner of the phosphorylated form of SmVKR1. Expression of these proteins in Xenopus oocytes allowed us to demonstrate that the SH2 domain of SmShb interacts with the phosphotyrosine residue (pY979) located in the juxtamembrane region of SmVKR1. This interaction leads to phosphorylation of SmShb on tyrosines and promotes SmVKR1 signaling towards the JNK pathway. SmShb transcripts are expressed in all parasite stages and they were found in ovary and testes of adult worms, suggesting a possible colocalization of SmShb and SmVKR1 proteins. Silencing of SmShb in adult S. mansoni resulted in an accumulation of mature sperm in testes, indicating a possible role of SmShb in gametogenesis. PMID:27636711

Characterizing the Biochemical Response to Schistosoma mansoni Infection and Treatment with Praziquantel in Preschool and School Aged Children.

PubMed

Panic, Gordana; Coulibaly, Jean T; Harvey, Nikita; Keiser, Jennifer; Swann, Jonathan

2018-05-21

Schistosomiasis is a widespread chronic neglected tropical disease prevalent mostly in children in under-resourced rural areas. Its pathological effects have been clinically characterized, yet the molecular-level effects are understudied. In this study, the biochemical effects of Schistosoma mansoni infection and praziquantel treatment were studied in 130 preschool aged and 159 school aged infected children and 11 noninfected children in Azaguié, Côte d'Ivoire. Urine samples were collected prior to receiving 20, 40, or 60 mg/kg of praziquantel or a placebo, as well as 24 h post-treatment, and at the 3-week follow up. Urinary metabolic phenotypes were measured using 1 H NMR spectroscopy, and metabolic variation associated with S. mansoni infection and praziquantel administration was identified using multivariate statistical techniques. Discriminatory metabolic signatures were detected between heavily infected and noninfected children at baseline as well as according to the dose of praziquantel administered 24 h post treatment. These signatures were primarily associated with the metabolic activity of the gut microbiota, gut health and growth biomarkers and energy and liver metabolism. These analyses provide insights into the metabolic phenotype of schistosomiasis and treatment with praziquantel in two important demographics.

SmShb, the SH2-Containing Adaptor Protein B of Schistosoma mansoni Regulates Venus Kinase Receptor Signaling Pathways.

PubMed

Morel, Marion; Vanderstraete, Mathieu; Cailliau, Katia; Hahnel, Steffen; Grevelding, Christoph G; Dissous, Colette

2016-01-01

Venus kinase receptors (VKRs) are invertebrate receptor tyrosine kinases (RTKs) formed by an extracellular Venus Fly Trap (VFT) ligand binding domain associated via a transmembrane domain with an intracellular tyrosine kinase (TK) domain. Schistosoma mansoni VKRs, SmVKR1 and SmVKR2, are both implicated in reproductive activities of the parasite. In this work, we show that the SH2 domain-containing protein SmShb is a partner of the phosphorylated form of SmVKR1. Expression of these proteins in Xenopus oocytes allowed us to demonstrate that the SH2 domain of SmShb interacts with the phosphotyrosine residue (pY979) located in the juxtamembrane region of SmVKR1. This interaction leads to phosphorylation of SmShb on tyrosines and promotes SmVKR1 signaling towards the JNK pathway. SmShb transcripts are expressed in all parasite stages and they were found in ovary and testes of adult worms, suggesting a possible colocalization of SmShb and SmVKR1 proteins. Silencing of SmShb in adult S. mansoni resulted in an accumulation of mature sperm in testes, indicating a possible role of SmShb in gametogenesis.

Larval excretory-secretory products from the parasite Schistosoma mansoni modulate HSP70 protein expression in defence cells of its snail host, Biomphalaria glabrata.

PubMed

Zahoor, Zahida; Davies, Angela J; Kirk, Ruth S; Rollinson, David; Walker, Anthony John

2010-09-01

Synthesis of heat shock proteins (HSPs) following cellular stress is a response shared by many organisms. Amongst the HSP family, the approximately 70 kDa HSPs are the most evolutionarily conserved with intracellular chaperone and extracellular immunoregulatory functions. This study focused on the effects of larval excretory-secretory products (ESPs) from the parasite Schistosoma mansoni on HSP70 protein expression levels in haemocytes (defence cells) from its snail intermediate host Biomphalaria glabrata. S. mansoni larval stage ESPs are known to interfere with haemocyte physiology and behaviour. Haemocytes from two different B. glabrata strains, one which is susceptible to S. mansoni infection and one which is resistant, both showed reduced HSP70 protein levels following 1 h challenge with S. mansoni ESPs when compared to unchallenged controls; however, the reduction observed in the resistant strain was less marked. The decline in intracellular HSP70 protein persisted for at least 5 h in resistant snail haemocytes only. Furthermore, in schistosome-susceptible snails infected by S. mansoni for 35 days, haemocytes possessed approximately 70% less HSP70. The proteasome inhibitor, MG132, partially restored HSP70 protein levels in ESP-challenged haemocytes, demonstrating that the decrease in HSP70 was in part due to intracellular degradation. The extracellular signal-regulated kinase (ERK) signalling pathway appears to regulate HSP70 protein expression in these cells, as the mitogen-activated protein-ERK kinase 1/2 (MEK1/2) inhibitor, U0126, significantly reduced HSP70 protein levels. Disruption of intracellular HSP70 protein expression in B. glabrata haemocytes by S. mansoni ESPs may be a strategy employed by the parasite to manipulate the immune response of the intermediate snail host.

Confirmed local endemicity and putative high transmission of Schistosoma mansoni in the Sesse Islands, Lake Victoria, Uganda.

PubMed

Standley, Claire J; Adriko, Moses; Besigye, Fred; Kabatereine, Narcis B; Stothard, Russell J

2011-03-01

The Sesse Islands, in the Ugandan portion of Lake Victoria, have long been considered a low transmission zone for intestinal schistosomiasis. Based on observations of high prevalence of Schistosoma mansoni infection in the northern-most islands of this archipelago, a follow-up survey was conducted to ascertain whether transmission was endemic to this island group, combining parasitological and malacological surveys. Prevalence of intestinal schistosomiasis was again observed to be high, as was intensity of infections which, combined with low reported incidence of treatment, suggests that chemotherapy-based control initiatives are not being maximally effective in this region as high levels of population movement between islands and districts are confounding. The local disease transmission was confirmed by the observations of high abundance of Biomphalaria, as well as field-caught snails shedding S. mansoni cercariae. DNA sequencing of 12 cercariae revealed common mitochondrial cox1 haplotypes, as well as, novel ones, consistent with the high genetic diversity of this parasite in Lake Victoria. Intestinal schistosomiasis is firmly endemic in parts of the Sesse Islands and more broadly, this island group provides an insight into the future challenges to be faced by the Ugandan National Control Programme in regularly reaching these rather remote, inaccessible and largely itinerant communities.

Simultaneous infection of Schistosoma mansoni and S. rodhaini in Biomphalaria glabrata: impact on chronobiology and cercarial behaviour

PubMed Central

Norton, Alice; Rollinson, David; Richards, Louisa; Webster, Joanne

2008-01-01

Background The chances of a schistosome cercaria encountering a suitable definitive host may be enhanced by emergence from the molluscan intermediate host with maximal glycogen stores and by an appropriate chronobiological rhythm. This study aimed to identify and characterize the effects of potential competitive interactions in the snail host Biomphalaria glabrata, between the closely-related Schistosoma mansoni and S. rodhaini, on phenotypic behavioural traits. It was predicted that inter-specific competition would affect chronobiological emergence rhythms and reduce the activity of schistosome swimming behavioural traits. Biomphalaria glabrata snails (120) were exposed to either S. mansoni or S. rodhaini single infections, or a mixed infection of both species simultaneously and the resulting cercarial phenotypic traits were characterised. Cercariae were identified from co-exposed snails by amplification and sequencing of the mitochondrial cytochrome oxidase subunit 1 (CO1). Results S. mansoni and S. rodhaini largely maintained their distinct chronobiological rhythms after mixed exposures and infections. However, inter-specific competition appeared to result in a restriction of the shedding pattern of S. rodhaini and slight shift in the shedding pattern of S. mansoni. Inter-specific competition also significantly lowered hourly cercarial production for both parasite species in comparison to single exposures and infections and reduced cercarial swimming activity. Conclusion Inter-specific competition was shown to influence cercarial production, chronobiology and activity and should therefore be investigated further in field situations to determine the effects of these changes on parasite fitness (incorporating both host finding and infectivity) where these two species overlap. Importantly this competition did not result in a large change in chronobiological emergence of cercariae for either species indicating that it would not have a large influence on the species

Long-term effect of mass chemotherapy, transmission and risk factors for Schistosoma mansoni infection in very low endemic communities of Venezuela.

PubMed

Hofstede, Stefanie N; Tami, Adriana; van Liere, Genevieve A F S; Ballén, Diana; Incani, Renzo N

2014-12-01

The prevalence of Schistosoma mansoni infection in Venezuela has changed from high to low due mostly to successful control activities, including mass chemotherapy and molluscicide applications. This study examined the impact of mass chemotherapy on S. mansoni transmission and risk factors for infection 12 years after administration of praziquantel in Venezuela. Two relatively isolated rural communities were studied, one with snail control (Manuare) and the second without (Los Naranjos). A cross-sectional survey of randomly selected households included 226 (Manuare) and 192 (Los Naranjos) consenting participants. S. mansoni prevalence was determined using a combination of coprological (Kato-Katz) and serological (circumoval precipitin test, alkaline phosphatase immunoassay and Western blot) tests. Data on epidemiological and socioeconomic risk factors were obtained through individual structured interviews. Univariate analysis and multivariate logistic regression models identified independent risk factors for infection. Water sites were examined for the presence of Biomphalaria glabrata snails. Only one participant was positive by coprology. The overall prevalences according to the combined tests were 32.7% in Manuare and 26.6% in Los Naranjos. Lower prevalences (12.7% in Manuare and 13.2% in Los Naranjos) were found in children <12 years of age representing those born after mass chemotherapy. Social demographic variables associated with infection in both communities were older age (>25 years), contact with specific water sites, and being a farmer/non-specialised worker. Mass treatment with praziquantel applied once to endemic communities led to an important and long-lasting sustained reduction of S. mansoni infections independent of the application of snail control. A degree of low active transmission of S. mansoni persisted in the treated areas which was associated with similar factors in both communities. Copyright © 2014 Elsevier B.V. All rights reserved.

Potential effect of the medicinal plants Calotropis procera, Ficus elastica and Zingiber officinale against Schistosoma mansoni in mice.

PubMed

Seif el-Din, Sayed H; El-Lakkany, Naglaa M; Mohamed, Mona A; Hamed, Manal M; Sterner, Olov; Botros, Sanaa S

2014-02-01

Calotropis procera (Ait.) R. Br. (Asclepiadaceae), Ficus elastica Roxb. (Moraceae) and Zingiber officinale Roscoe (Zingiberaceae) have been traditionally used to treat many diseases. The antischistosomal activity of these plant extracts was evaluated against Schistosoma mansoni. Male mice exposed to 80 ± 10 cercariae per mouse were divided into two batches. The first was divided into five groups: (I) infected untreated, while groups from (II-V) were treated orally (500 mg/kg for three consecutive days) by aqueous stem latex and flowers of C. procera, latex of F. elastica and ether extract of Z. officinale, respectively. The second batch was divided into four comparable groups (except Z. officinale-treated group) similarly treated as the first batch in addition to the antacid ranitidine (30 mg/kg) 1 h before extract administration. Safety, worm recovery, tissues egg load and oogram pattern were assessed. Calotropis procera latex and flower extracts are toxic (50-70% mortality) even in a small dose (250 mg/kg) before washing off their toxic rubber. Zingiber officinale extract insignificantly decrease (7.26%) S. mansoni worms. When toxic rubber was washed off and ranitidine was used, C. procera (stem latex and flowers) and F. elastica extracts revealed significant S. mansoni worm reductions by 45.31, 53.7 and 16.71%, respectively. Moreover, C. procera extracts produced significant reductions in tissue egg load (∼34-38.5%) and positively affected oogram pattern. The present study may be useful to supplement information with regard to C. procera and F. elastica antischistosomal activity and provide a basis for further experimental trials.

Schistosoma egg-induced liver pathology resolution by Sm-p80-based schistosomiasis vaccine in baboons.

PubMed

Le, Loc; Molehin, Adebayo J; Nash, Stewart; Sennoune, Souad R; Ahmad, Gul; Torben, Workineh; Zhang, Weidong; Siddiqui, Afzal A

2018-05-05

Schistosomiasis remains a serious chronic debilitating hepato-intestinal disease. Current control measures based on mass drug administration are inadequate due to sustained re-infection rates, low treatment coverage and emergence of drug resistance. Hence, there is an urgent need for a schistosomiasis vaccine for disease control. In this study, we assessed the anti-pathology efficacy of Schistosoma mansoni large subunit of calpain (Sm-p80)-based vaccine against schistosomiasis caused by infections with Schistosoma mansoni in baboons. We also evaluated the disease transmission-blocking potential of Sm-p80 vaccine. Immunisations with Sm-p80-based vaccine resulted in significant reduction of hepatic egg load in vaccinated baboons (67.7% reduction, p = 0.0032) when compared to the control animals, indicative of reduction in pathology. There was also a significant reduction in sizes of egg-induced granulomas in baboons immunised with Sm-p80 vaccine compared to their control counterparts. Egg hatching rate analysis revealed an overall 85.6% reduction (p = 0.0018) in vaccinated animals compared to the controls, highlighting the potential role of Sm-p80 vaccine in disease transmission. The findings on anti-pathology efficacy and transmission-blocking potential presented in this study have formed the basis for a large-scale double-blinded baboon experiment that is currently underway. Copyright © 2018 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.

Comparing Diagnostic Accuracy of Kato-Katz, Koga Agar Plate, Ether-Concentration, and FLOTAC for Schistosoma mansoni and Soil-Transmitted Helminths

PubMed Central

Glinz, Dominik; Silué, Kigbafori D.; Knopp, Stefanie; Lohourignon, Laurent K.; Yao, Kouassi P.; Steinmann, Peter; Rinaldi, Laura; Cringoli, Giuseppe; N'Goran, Eliézer K.; Utzinger, Jürg

2010-01-01

Background Infections with schistosomes and soil-transmitted helminths exert a considerable yet underappreciated economic and public health burden on afflicted populations. Accurate diagnosis is crucial for patient management, drug efficacy evaluations, and monitoring of large-scale community-based control programs. Methods/Principal Findings The diagnostic accuracy of four copromicroscopic techniques (i.e., Kato-Katz, Koga agar plate, ether-concentration, and FLOTAC) for the detection of Schistosoma mansoni and soil-transmitted helminth eggs was compared using stool samples from 112 school children in Côte d'Ivoire. Combined results of all four methods served as a diagnostic ‘gold’ standard and revealed prevalences of S. mansoni, hookworm, Trichuris trichiura, Strongyloides stercoralis and Ascaris lumbricoides of 83.0%, 55.4%, 40.2%, 33.9% and 28.6%, respectively. A single FLOTAC from stool samples preserved in sodium acetate-acetic acid-formalin for 30 or 83 days showed a higher sensitivity for S. mansoni diagnosis (91.4%) than the ether-concentration method on stool samples preserved for 40 days (85.0%) or triplicate Kato-Katz using fresh stool samples (77.4%). Moreover, a single FLOTAC detected hookworm, A. lumbricoides and T. trichiura infections with a higher sensitivity than any of the other methods used, but resulted in lower egg counts. The Koga agar plate method was the most accurate diagnostic assay for S. stercoralis. Conclusion/Significance We have shown that the FLOTAC method holds promise for the diagnosis of S. mansoni. Moreover, our study confirms that FLOTAC is a sensitive technique for detection of common soil-transmitted helminths. For the diagnosis of S. stercoralis, the Koga agar plate method remains the method of choice. PMID:20651931

Larval excretory-secretory products from the parasite Schistosoma mansoni modulate HSP70 protein expression in defence cells of its snail host, Biomphalaria glabrata

PubMed Central

Zahoor, Zahida; Davies, Angela J.; Kirk, Ruth S.; Rollinson, David

2010-01-01

Synthesis of heat shock proteins (HSPs) following cellular stress is a response shared by many organisms. Amongst the HSP family, the ∼70 kDa HSPs are the most evolutionarily conserved with intracellular chaperone and extracellular immunoregulatory functions. This study focused on the effects of larval excretory-secretory products (ESPs) from the parasite Schistosoma mansoni on HSP70 protein expression levels in haemocytes (defence cells) from its snail intermediate host Biomphalaria glabrata. S. mansoni larval stage ESPs are known to interfere with haemocyte physiology and behaviour. Haemocytes from two different B. glabrata strains, one which is susceptible to S. mansoni infection and one which is resistant, both showed reduced HSP70 protein levels following 1 h challenge with S. mansoni ESPs when compared to unchallenged controls; however, the reduction observed in the resistant strain was less marked. The decline in intracellular HSP70 protein persisted for at least 5 h in resistant snail haemocytes only. Furthermore, in schistosome-susceptible snails infected by S. mansoni for 35 days, haemocytes possessed approximately 70% less HSP70. The proteasome inhibitor, MG132, partially restored HSP70 protein levels in ESP-challenged haemocytes, demonstrating that the decrease in HSP70 was in part due to intracellular degradation. The extracellular signal-regulated kinase (ERK) signalling pathway appears to regulate HSP70 protein expression in these cells, as the mitogen-activated protein-ERK kinase 1/2 (MEK1/2) inhibitor, U0126, significantly reduced HSP70 protein levels. Disruption of intracellular HSP70 protein expression in B. glabrata haemocytes by S. mansoni ESPs may be a strategy employed by the parasite to manipulate the immune response of the intermediate snail host. PMID:20182834

Reduction in transmission of Schistosoma mansoni by a four-year focal mollusciciding programme against Biomphalaria glabrata in Saint Lucia.

PubMed

Prentice, M A; Jordan, P; Bartholomew, R K; Grist, E

1981-01-01

The effect of transmission of Schistosoma mansoni of a focal snail control programme was investigated over four years amongst approximately 1250 people living in five communities in the steep-sided Soufriere river valley, St. Lucia, West Indies. Bayer 6076 was applied from constant flow drip cans to 12 stream sections at a target dose of 8 mg/litre clonitralide every four weeks. Only proven and potential transmission sites were treated; marsh habitats, where Biomphalaria glabrata were widespread, were ignored. In the stream snail numbers were reduced by 94% in the first year and by 100% thereafter. Incidence of new S. mansoni infections amongst children fell from 18% in the last year before control to 6% and 9% after three and four years respectively. Amongst children and adults in the four years of control the conversion/reversion ratio declined leading to a lowering of the over-all prevalence from 40% to 22%. Parasitologically the results were similar to those of a previously evaluated area-wide mollusciciding programme. The mean annual cost per person protected was US $2.60. This figure is atypically high because the topography of the area severely limited the population size.

Schistosoma mansoni infection causes oxidative stress and alters receptor for advanced glycation endproduct (RAGE) and tau levels in multiple organs in mice.

PubMed

de Oliveira, Ramatis Birnfeld; Senger, Mario Roberto; Vasques, Laura Milan; Gasparotto, Juciano; dos Santos, João Paulo Almeida; Pasquali, Matheus Augusto de Bittencourt; Moreira, José Claudio Fonseca; Silva, Floriano Paes; Gelain, Daniel Pens

2013-04-01

Schistosomiasis is a parasitic disease caused by trematode worms from the Schistosoma genus and is characterized by high rates of morbidity. The main organs affected in this pathology, such as liver, kidneys and spleen, are shifted to a pro-oxidant state in the course of the infection. Here, we compared oxidative stress parameters of liver, kidney and spleen with other organs affected by schistosomiasis - heart, brain cortex and lungs. The results demonstrated that mice infected with Schistosoma mansoni had altered non-enzymatic antioxidant status in lungs and brain, increased carbonyl levels in lungs, and a moderate level of oxidative stress in heart. A severe redox imbalance in liver and kidneys and decreased non-enzymatic antioxidant capacity in spleen were also observed. Superoxide dismutase and catalase activities were differently modulated in liver, kidney and heart, and we found that differences in Superoxide dismutase 2 and catalase protein content may be responsible for these differences. Lungs had decreased receptor for advanced glycation endproduct expression and the brain cortex presented altered tau expression and phosphorylation levels, suggesting important molecular changes in these tissues, as homeostasis of these proteins is widely associated with the normal function of their respective organs. We believe that these results demonstrate for the first time that changes in the redox profile and expression of tissue-specific proteins of organs such as heart, lungs and brain are observed in early stages of S. mansoni infection. Copyright © 2013 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

Schistosoma mansoni: assessment of effects of oleic acid, cercarial age and water temperature on parasite-host attraction.

PubMed

Lee, Vivien S T; Burgess, Jefferey L; Sterling, Charles R; Lutz, Eric A

2013-09-01

Although the lifecycle of Schistosoma spp. and pathophysiology of schistosomiasis have been established, the mechanism by which cercariae find their host is not well understood. Speculatively, host infection by random and accidental host contact is not as biologically plausible as a biochemical mechanism of mammalian attraction. A few studies have indicated that biochemical cues and temperature gradients may play a role in host identification, attraction and attachment triggers. This study aimed to elucidate these mechanisms more specifically through evaluation of biochemical, age and temperature influences leading to Schistosoma mansoni cercariae attraction and attachment behaviors. Oleic acid, a common unsaturated free fatty acid in the outer layer of human skin, was tested for cercariae attraction across biologically relevant concentrations. Influence of media type (beeswax, nail varnish and agar), age-dependent behavior variability and environmentally appropriate temperatures (22 and 30 °C) were also evaluated. Results indicated that oleic acid at concentrations of 0.3, 0.9 and 1.8 g/mL in beeswax significantly increased median attachment to media (median attachment of 7.50%, 4.20% and 3.71%, respectively, P<0.001), compared with plain beeswax, with maximal attachment of 30.30% at 0.3g/mL of oleic acid. In media containing 0.3 g/mL of oleic acid, cercarial attachment was highest for freshly emerged cercariae to 5h post-emergence, with a significant decrease in attachment behavior at 10h post-emergence (P<0.01). Aquatic temperature at which cercariae were exposed to media did not yield significant results (P value >0.05). Biochemical, age and environmental factors influencing cercarial host attraction and attachment behavior have been elucidated by this study. This information will inform further development of devices for environmental surveillance and potentially improve cercarial exposure prevention strategies. Copyright © 2013 Australian Society for

Schistosoma mansoni and soil-transmitted helminths among preschool-aged children in Chuahit, Dembia district, Northwest Ethiopia: prevalence, intensity of infection and associated risk factors.

PubMed

Alemu, Agersew; Tegegne, Yalewayker; Damte, Demekech; Melku, Mulugeta

2016-05-23

Intestinal schistosomiasis and soil-transmitted helminthiasis are the major public health problems globally. Compared with any other age group, pre-school aged children and school-aged children are the most exposed. There are few studies showing the burden of intestinal schistosomiasis, and soil-transmitted helminthiasis among pre-school aged children in Ethiopia. Hence, this study aimed to assess the prevalence of schistosoma mansoni and soil-transmitted helminths and associated risk factors among preschool aged children of Chuahit and surrounding Kebeles, Northwest Ethiopia. A community based cross sectional study was conducted from February 2 to March 27 2015. Four hundred one preschool-aged children were included in the study by using two stage cluster sampling technique. Pretested structured questionnaire was employed to collected data via face-to-face interview technique. A single stool specimen was collected, and a portion of the sample was processed by Kato Katz method. Of the total children, 141 (35.2 %) harbored one or more intestinal helminthes. Schistosoma mansoni was found in 45 (11.2 %) of preschool age children. Ascaris lumbricoides was the predominant isolate, 77 (19.2 %) followed by S. mansoni, 45 (11.2 %). The least parasites isolated were Tania species, 2 (0.5 %). After adjusting for other variables, being mothers who did not have the habit of washing hands after toilet (AOR = 7.3, 95%CI: 2.97-17.95), being occupationally housewife mothers (AOR = 8.9, 95%CI: 2.27-25.4), using protected spring water as a main family source of water (AOR = 3.9, 95%CI: 1.2-12.3) and child habit of not wearing shoe (AOR = 1.91, 95%CI: 1.01-3.64) were significantly associated with high prevalence of soil-transmitted helminthiasis among preschool-age children in Chuahit. The current study showed that relatively higher level of STH and S. mansoni among preschool-aged children in Chuahit. This finding calls for a need of public health education

The Substrate-free and -bound Crystal Structures of the Duplicated Taurocyamine Kinase from the Human Parasite Schistosoma mansoni*

PubMed Central

Merceron, Romain; Awama, Ayman M.; Montserret, Roland; Marcillat, Olivier; Gouet, Patrice

2015-01-01

The taurocyamine kinase from the blood fluke Schistosoma mansoni (SmTK) belongs to the phosphagen kinase (PK) family and catalyzes the reversible Mg2+-dependent transfer of a phosphoryl group between ATP and taurocyamine. SmTK is derived from gene duplication, as are all known trematode TKs. Our crystallographic study of SmTK reveals the first atomic structure of both a TK and a PK with a bilobal structure. The two unliganded lobes present a canonical open conformation and interact via their respective C- and N-terminal domains at a helix-mediated interface. This spatial arrangement differs from that observed in true dimeric PKs, in which both N-terminal domains make contact. Our structures of SmTK complexed with taurocyamine or l-arginine compounds explain the mechanism by which an arginine residue of the phosphagen specificity loop is crucial for substrate specificity. An SmTK crystal was soaked with the dead end transition state analog (TSA) components taurocyamine-NO32−-MgADP. One SmTK monomer was observed with two bound TSAs and an asymmetric conformation, with the first lobe semiclosed and the second closed. However, isothermal titration calorimetry and enzyme kinetics experiments showed that the two lobes function independently. A small angle x-ray scattering model of SmTK-TSA in solution with two closed active sites was generated. PMID:25837252

Schistosoma mansoni infection of juvenile Biomphalaria glabrata induces a differential stress response between resistant and susceptible snails.

PubMed

Ittiprasert, Wannaporn; Nene, Rahul; Miller, André; Raghavan, Nithya; Lewis, Fred; Hodgson, Jacob; Knight, Matty

2009-11-01

Schistosomes develop successfully in susceptible snails but are encapsulated and killed in resistant ones. Mechanism(s) shaping these outcomes involves the parasites ability to evade the snail's defenses. RNA analysis from resistant (BS-90), non-susceptible (LAC2) and susceptible (NMRI) juvenile Biomphalaria glabrata to Schistosoma mansoni revealed that stress-related genes, heat shock protein 70 (Hsp 70) and reverse transcriptase (RT), were dramatically co-induced early in susceptible snails, but not in resistant/non-susceptible ones. These transcripts were, however, down regulated upon exposure to irradiated parasites although penetration behavior of irradiated vs. normal parasites were the same, indicating that Hsp 70 and RT regulation was elicited by infection and not injury. Understanding molecular events involved in stress response transcriptional regulation of Hsp 70 in juvenile snails could pave a way towards the identification of genes involved in schistosome/snail interactions.

Cross-Reactivity between Schistosoma mansoni Antigens and the Latex Allergen Hev b 7: Putative Implication of Cross-Reactive Carbohydrate Determinants (CCDs)

PubMed Central

Doenhoff, Michael J.; El-Faham, Marwa; Liddell, Susan; Fuller, Heidi R.; Stanley, Ronald G.; Schramm, Gabriele; Igetei, Joseph E.

2016-01-01

IgG antibodies produced by rabbits immunized against S. mansoni antigens cross-reacted with aqueous soluble constituents of a variety of allergens. The antibody cross-reactivity was largely sensitive to degradation by treatment of the target antigens with sodium meta-periodate, suggesting the cross-reactivity was due to carbohydrate determinants that were common to both the schistosome and the allergens (CCDs). The reaction between the rabbit antibodies and a 43 kDa molecule in a rubber latex extract was analysed further: tandem mass spectrometry identified the latex molecule as allergen Hev b 7. Rabbit anti-schistosome IgG antibodies purified by acid-elution from solid-phase latex Hev b 7 reacted with the S. mansoni egg antigens IPSE/alpha-1 and kappa-5 and cercarial antigens SPO-1 and a fatty acid-binding protein. Moreover, purified anti-S. mansoni egg, latex cross-reactive antibodies reacted with antigenic constituents of some fruits, a result of potential relevance to the latex-fruit syndrome of allergic reactions. We propose that IgG anti-schistosome antibodies that cross-react with allergens may be able to block IgE-induced allergic reactions and thus provide a possible explanation for the hygiene hypothesis. PMID:27467385

Efficient trans-cleavage by the Schistosoma mansoni SMα1 hammerhead ribozyme in the extreme thermophile Thermus thermophilus

PubMed Central

Vazquez-Tello, Alejandro; Castán, Pablo; Moreno, Renata; Smith, James M.; Berenguer, José; Cedergren, Robert

2002-01-01

The catalytic hammerhead structure has been found in association with repetitive DNA from several animals, including salamanders, crickets and schistosomes, and functions to process in cis the long multimer transcripts into monomer RNA in vivo. The cellular role of these repetitive elements and their transcripts is unknown. Moreover, none of these natural hammerheads have been shown to trans-cleave a host mRNA in vivo. We analyzed the cis- and trans-cleavage properties of the hammerhead ribozyme associated with the SMα DNA family from the human parasite Schistosoma mansoni. The efficiency of trans-cleavage of a target RNA in vitro was affected mainly by both the temperature-dependent chemical step and the ribozyme–product dissociation step. The optimal temperature for trans-cleavage was 70°C. This result was confirmed when both the SMα1 ribozyme and the target RNA were expressed in the extreme thermophile Thermus thermophilus. Moreover, SMα1 RNA showed a remarkable thermostability, equal or superior to that of the most stable RNAs in this species, suggesting that SMα1 RNA has been selected for stability. Computer analysis predicts that the monomer and multimer transcripts fold into highly compact secondary structures, which may explain their exceptional stability in vivo. PMID:11917021

Host Defense Versus Immunosuppression: Unisexual Infection With Male or Female Schistosoma mansoni Differentially Impacts the Immune Response Against Invading Cercariae.

PubMed

Sombetzki, Martina; Koslowski, Nicole; Rabes, Anne; Seneberg, Sonja; Winkelmann, Franziska; Fritzsche, Carlos; Loebermann, Micha; Reisinger, Emil C

2018-01-01

Infection with the intravascular diecious trematode Schistosoma spp . remains a serious tropical disease and public health problem in the developing world, affecting over 258 million people worldwide. During chronic Schistosoma mansoni infection, complex immune responses to tissue-entrapped parasite eggs provoke granulomatous inflammation which leads to serious damage of the liver and intestine. The suppression of protective host immune mechanisms by helminths promotes parasite survival and benefits the host by reducing tissue damage. However, immune-suppressive cytokines may reduce vaccine-induced immune responses. By combining a single-sex infection system with a murine air pouch model, we were able to demonstrate that male and female schistosomes play opposing roles in modulating the host's immune response. Female schistosomes suppress early innate immune responses to invading cercariae in the skin and upregulate anergy-associated genes. In contrast, male schistosomes trigger strong innate immune reactions which lead to a reduction in worm and egg burden in the liver. Our data suggest that the female worm is a neglected player in the dampening of the host's immune defense system and is therefore a promising target for new immune modulatory therapies.

Evaluation of the CCA Immuno-Chromatographic Test to Diagnose Schistosoma mansoni in Minas Gerais State, Brazil

PubMed Central

Silveira, Alda Maria Soares; Costa, Emanuele Gama Dutra; Ray, Debalina; Suzuki, Brian M.; Hsieh, Michael H.; Fraga, Lucia Alves de Oliveira; Caffrey, Conor R.

2016-01-01

Background The Kato-Katz (KK) stool smear is the standard test for the diagnosis of Schistosoma mansoni infection, but suffers from low sensitivity when infections intensities are moderate to low. Thus, misdiagnosed individuals remain untreated and contribute to the disease transmission, thereby forestalling public health efforts to move from a modality of disease control to one of elimination. As an alternative, the urine-based diagnosis of schistosomiasis mansoni via the circulating cathodic antigen immuno-chromatographic test (CCA-ICT) has been extensively evaluated in Africa with the conclusion that it may replace the KK test in areas where prevalences are moderate or high. Methods and Findings The objective was to measure the performance of the CCA-ICT in a sample study population composed of residents from non-endemic and endemic areas for schistosomiasis mansoni in two municipalities of Minas Gerais state, Brazil. Volunteers (130) were classified into three infection status groups based on duplicate Kato-Katz thick smears from one stool sample (2KK test): 41 negative individuals from non-endemic areas, 41 negative individuals from endemic areas and 48 infected individuals from endemic areas. Infection status was also determined by the CCA-ICT and infection exposure by antibody ELISA (enzyme-linked immunosorbent assay) to S. mansoni soluble egg antigen (SEA) and soluble (adult) worm antigen preparation (SWAP). Sensitivity and specificity were influenced by whether the trace score visually adjudicated in the CCA-ICT was characterized as positive or negative for S. mansoni infection. An analysis of a two-graph receiver operating characteristic was performed to change the cutoff point. When the trace score was interpreted as a positive rather than as a negative result, the specificity decreased from 97.6% to 78.0% whereas sensitivity increased from 68.7% to 85.4%. A significantly positive correlation between the CCA-ICT scores and egg counts was identified (r

Fecal occult blood and fecal calprotectin as point-of-care markers of intestinal morbidity in Ugandan children with Schistosoma mansoni infection.

PubMed

Bustinduy, Amaya L; Sousa-Figueiredo, José C; Adriko, Moses; Betson, Martha; Fenwick, Alan; Kabatereine, Narcis; Stothard, J Russell

2013-11-01

Calprotectin is a calcium-binding cytoplasmic protein found in neutrophils and increasingly used as a marker of bowel inflammation. Fecal occult blood (FOB) is also a dependable indicator of bowel morbidity. The objective of our study was to determine the applicability of these tests as surrogate markers of Schistosoma mansoni intestinal morbidity before and after treatment with praziquantel (PZQ). 216 children (ages 3-9 years old) from Buliisa District in Lake Albert, Uganda were examined and treated with PZQ at baseline in October 2012 with 211 of them re-examined 24 days later for S. mansoni and other soil transmitted helminths (STH). POC calprotectin and FOB assays were performed at both time points on a subset of children. Associations between the test results and infection were analysed by logistic regression. Fecal calprotectin concentrations of 150-300 µg/g were associated with S. mansoni egg patent infection both at baseline and follow up (OR: 12.5 P = 0.05; OR: 6.8 P = 0.02). FOB had a very strong association with baseline anemia (OR: 9.2 P = 0.03) and medium and high egg intensity schistosomiasis at follow up (OR: 6.6 P = 0.03; OR: 51.3 P = 0.003). Both tests were strongly associated with heavy intensity S. mansoni infections. There was a significant decrease in FOB and calprotectin test positivity after PZQ treatment in those children who had egg patent schistosomiasis at baseline. Both FOB and calprotectin rapid assays were found to correlate positively and strongly with egg patent S. mansoni infection with a positive ameloriation response after PZQ treatment indicative of short term reversion of morbidity. Both tests were appropriate for use in the field with excellent operational performance and reliability. Due to its lower-cost which makes its scale-up of use affordable, FOB could be immediately adopted as a monitoring tool for PC campaigns for efficacy evaluation before and after treatment.

Molecular Characterization of the Schistosoma mansoni Zinc Finger Protein SmZF1 as a Transcription Factor

PubMed Central

D'Astolfo, Diego S.; Cardoso, Fernanda C.; Rajão, Matheus A.; Mourão, Marina M.; Gava, Elisandra; Oliveira, Sérgio C.; Macedo, Andréa M.; Machado, Carlos R.; Pena, Sérgio D. J.; Kitten, Gregory T.; Franco, Glória R.

2009-01-01

Background During its development, the parasite Schistosoma mansoni is exposed to different environments and undergoes many morphological and physiological transformations as a result of profound changes in gene expression. Characterization of proteins involved in the regulation of these processes is of importance for the understanding of schistosome biology. Proteins containing zinc finger motifs usually participate in regulatory processes and are considered the major class of transcription factors in eukaryotes. It has already been shown, by EMSA (Eletrophoretic Mobility Shift Assay), that SmZF1, a S. mansoni zinc finger (ZF) protein, specifically binds both DNA and RNA oligonucleotides. This suggests that this protein might act as a transcription factor in the parasite. Methodology/Principal Findings In this study we extended the characterization of SmZF1 by determining its subcellular localization and by verifying its ability to regulate gene transcription. We performed immunohistochemistry assays using adult male and female worms, cercariae and schistosomula to analyze the distribution pattern of SmZF1 and verified that the protein is mainly detected in the cells nuclei of all tested life cycle stages except for adult female worms. Also, SmZF1 was heterologously expressed in mammalian COS-7 cells to produce the recombinant protein YFP-SmZF1, which was mainly detected in the nucleus of the cells by confocal microscopy and Western blot assays. To evaluate the ability of this protein to regulate gene transcription, cells expressing YFP-SmZF1 were tested in a luciferase reporter system. In this system, the luciferase gene is downstream of a minimal promoter, upstream of which a DNA region containing four copies of the SmZF1 putative best binding site (D1-3DNA) was inserted. SmZF1 increased the reporter gene transcription by two fold (p≤0.003) only when its specific binding site was present. Conclusion Taken together, these results strongly support the hypothesis

Epigenetic modulation, stress and plasticity in susceptibility of the snail host, Biomphalaria glabrata, to Schistosoma mansoni infection.

PubMed

Knight, Matty; Ittiprasert, Wannaporn; Arican-Goktas, Halime D; Bridger, Joanna M

2016-06-01

Blood flukes are the causative agent of schistosomiasis - a major neglected tropical disease that remains endemic in numerous countries of the tropics and sub-tropics. During the past decade, a concerted effort has been made to control the spread of schistosomiasis, using a drug intervention program aimed at curtailing transmission. These efforts notwithstanding, schistosomiasis has re-emerged in southern Europe, raising concerns that global warming could contribute to the spread of this disease to higher latitude countries where transmission presently does not take place. Vaccines against schistosomiasis are not currently available and reducing transmission by drug intervention programs alone does not prevent reinfection in treated populations. These challenges have spurred awareness that new interventions to control schistosomiasis are needed, especially since the World Health Organization hopes to eradicate the disease by 2025. For one of the major species of human schistosomes, Schistosoma mansoni, the causative agent of hepatointestinal schistosomiasis in Africa and the Western Hemisphere, freshwater snails of the genus Biomphalaria serve as the obligate intermediate host of this parasite. To determine mechanisms that underlie parasitism by S. mansoni of Biomphalaria glabrata, which might be manipulated to block the development of intramolluscan larval stages of the parasite, we focused effort on the impact of schistosome infection on the epigenome of the snail. Results to date reveal a complex relationship, manifested by the ability of the schistosome to manipulate the snail genome, including the expression of specific genes. Notably, the parasite subverts the stress response of the host to ensure productive parasitism. Indeed, in isolates of B. glabrata native to central and South America, susceptible to infection with S. mansoni, the heat shock protein 70 (Bg-HSP70) gene of this snail is rapidly relocated in the nucleus and transcribed to express HSP70

In silico analysis of the fucosylation-associated genome of the human blood fluke Schistosoma mansoni: cloning and characterization of the enzymes involved in GDP-L-fucose synthesis and Golgi import

PubMed Central

2013-01-01

Background Carbohydrate structures of surface-expressed and secreted/excreted glycoconjugates of the human blood fluke Schistosoma mansoni are key determinants that mediate host-parasite interactions in both snail and mammalian hosts. Fucose is a major constituent of these immunologically important glycans, and recent studies have sought to characterize fucosylation-associated enzymes, including the Golgi-localized fucosyltransferases that catalyze the transfer of L-fucose from a GDP-L-fucose donor to an oligosaccharide acceptor. Importantly, GDP-L-fucose is the only nucleotide-sugar donor used by fucosyltransferases and its availability represents a bottleneck in fucosyl-glycotope expression. Methods A homology-based genome-wide bioinformatics approach was used to identify and molecularly characterize the enzymes that contribute to GDP-L-fucose synthesis and Golgi import in S. mansoni. Putative functions were further investigated through molecular phylogenetic and immunocytochemical analyses. Results We identified homologs of GDP-D-mannose-4,6-dehydratase (GMD) and GDP-4-keto-6-deoxy-D-mannose-3,5-epimerase-4-reductase (GMER), which constitute a de novo pathway for GDP-L-fucose synthesis, in addition to a GDP-L-fucose transporter (GFT) that putatively imports cytosolic GDP-L-fucose into the Golgi. In silico primary sequence analyses identified characteristic Rossman loop and short-chain dehydrogenase/reductase motifs in GMD and GMER as well as 10 transmembrane domains in GFT. All genes are alternatively spliced, generating variants of unknown function. Observed quantitative differences in steady-state transcript levels between miracidia and primary sporocysts may contribute to differential glycotope expression in early larval development. Additionally, analyses of protein expression suggest the occurrence of cytosolic GMD and GMER in the ciliated epidermal plates and tegument of miracidia and primary sporocysts, respectively, which is consistent with previous

In silico analysis of the fucosylation-associated genome of the human blood fluke Schistosoma mansoni: cloning and characterization of the enzymes involved in GDP-L-fucose synthesis and Golgi import.

PubMed

Peterson, Nathan A; Anderson, Tavis K; Wu, Xiao-Jun; Yoshino, Timothy P

2013-07-09

Carbohydrate structures of surface-expressed and secreted/excreted glycoconjugates of the human blood fluke Schistosoma mansoni are key determinants that mediate host-parasite interactions in both snail and mammalian hosts. Fucose is a major constituent of these immunologically important glycans, and recent studies have sought to characterize fucosylation-associated enzymes, including the Golgi-localized fucosyltransferases that catalyze the transfer of L-fucose from a GDP-L-fucose donor to an oligosaccharide acceptor. Importantly, GDP-L-fucose is the only nucleotide-sugar donor used by fucosyltransferases and its availability represents a bottleneck in fucosyl-glycotope expression. A homology-based genome-wide bioinformatics approach was used to identify and molecularly characterize the enzymes that contribute to GDP-L-fucose synthesis and Golgi import in S. mansoni. Putative functions were further investigated through molecular phylogenetic and immunocytochemical analyses. We identified homologs of GDP-D-mannose-4,6-dehydratase (GMD) and GDP-4-keto-6-deoxy-D-mannose-3,5-epimerase-4-reductase (GMER), which constitute a de novo pathway for GDP-L-fucose synthesis, in addition to a GDP-L-fucose transporter (GFT) that putatively imports cytosolic GDP-L-fucose into the Golgi. In silico primary sequence analyses identified characteristic Rossman loop and short-chain dehydrogenase/reductase motifs in GMD and GMER as well as 10 transmembrane domains in GFT. All genes are alternatively spliced, generating variants of unknown function. Observed quantitative differences in steady-state transcript levels between miracidia and primary sporocysts may contribute to differential glycotope expression in early larval development. Additionally, analyses of protein expression suggest the occurrence of cytosolic GMD and GMER in the ciliated epidermal plates and tegument of miracidia and primary sporocysts, respectively, which is consistent with previous localization of highly

Parasite and vertebrate host genetic heterogeneity determine the outcome of infection by Schistosoma mansoni.

PubMed

Nino Incani, R; Morales, G; Cesari, I M

2001-02-01

Intraspecific variation in Schistosoma mansoni infection and modulation of its expression by vertebrate host genetics was studied by evaluation of some biological parameters of the infection in BALB/c and C57BL/6 mice infected with one Brazilian (BH) and two Venezuelan (YT and SM) laboratory strains of the parasite. Mice infected with 60 cercariae of each parasite strain were euthanized at 5, 6, 8, and 12 weeks. Parameters recorded included the number of adult worms recovered by portal perfusion (infectivity); the number of eggs in the feces, the intestine, and the liver; and the ability of the eggs to cross the intestine, expressed as a quotient of the number of eggs in the intestine versus the feces. Results showed that the parasite appeared to determine the infectivity, the sex ratio, the onset and timing of oviposition, the number of eggs produced, initial egg laying toward the liver, and the ability to cross the intestinal wall. In this sense the BH strain appeared to be the most efficient and the SM strain, the most delayed; the YT strain was intermediate, although closer to the SM strain. On the other hand, the host appeared to influence the susceptibility to infection, the fecundity, and the percentage of eggs distributed in the liver and in the intestine during the chronic stage. In this sense, although they have been shown to be less susceptible to infection than BALB/c mice, C57BL/6 mice permit more eggs to be produced and exhibit similar numbers of eggs in the intestine and the liver at certain time points. It appears from these results that parasite genetics is essential for the outcome of infection with S. mansoni, but some characteristics may be quantitatively modulated by host genetics.

Anthelmintic Activity of Crude Extract and Essential Oil of Tanacetum vulgare (Asteraceae) against Adult Worms of Schistosoma mansoni

PubMed Central

Godinho, Loyana Silva; Aleixo de Carvalho, Lara Soares; Barbosa de Castro, Clarissa Campos; Dias, Mirna Meana; Pinto, Priscila de Faria; Crotti, Antônio Eduardo Miller; Pinto, Pedro Luiz Silva; de Moraes, Josué; Da Silva Filho, Ademar A.

2014-01-01

Schistosomiasis, a parasitic disease caused by trematode flatworms of the genus Schistosoma, affects more than 200 million people worldwide, and its control is dependent on a single drug, praziquantel. Tanacetum vulgare (Asteraceae) is used in folk medicine as a vermifuge. This study aimed to investigate the in vitro schistosomicidal activity of the crude extract (TV) and the essential oil (TV-EO) from the aerial parts of T. vulgare. TV-EO was obtained by hydrodistillation and analyzed by GC/MS, which allowed the identification of β-thujone (84.13%) as the major constituent. TV and TV-EO, at 200 μg/mL, decreased motor activity and caused 100% mortality of all adult worms. At 100 and 50 μg/mL, only TV caused death of all adult worms, while TV-EO was inactive. TV (200 μg/mL) was also able to reduce viability and decrease production of developed eggs. Confocal laser scanning microscopy showed morphological alterations in the tegument of the S. mansoni surface after incubation with TV (50 and 100 μg/mL). Quantitative analysis on the schistosomes tegument showed that TV caused changes in the numbers of tubercles of S. mansoni male worms in a dose-dependent manner. The findings suggest that T. vulgare is a potential source of schistosomicidal compounds. PMID:24672320

Transcriptional Changes in Schistosoma mansoni during Early Schistosomula Development and in the Presence of Erythrocytes

PubMed Central

Gobert, Geoffrey N.; Tran, Mai H.; Moertel, Luke; Mulvenna, Jason; Jones, Malcolm K.; McManus, Donald P.; Loukas, Alex

2010-01-01

Background Schistosomes cause more mortality and morbidity than any other human helminth, but control primarily relies on a single drug that kills adult worms. The newly transformed schistosomulum stage is susceptible to the immune response and is a target for vaccine development and rational drug design. Methodology/Principal Findings To identify genes which are up-regulated during the maturation of Schistosoma mansoni schistosomula in vitro, we cultured newly transformed parasites for 3 h or 5 days with and without erythrocytes and compared their transcriptional profiles using cDNA microarrays. The most apparent changes were in the up-regulation of genes between 3 h and 5 day schistosomula involved in blood feeding, tegument and cytoskeletal development, cell adhesion, and stress responses. The most highly up-regulated genes included a tegument tetraspanin Sm-tsp-3 (1,600-fold up-regulation), a protein kinase, a novel serine protease and serine protease inhibitor, and intestinal proteases belonging to distinct mechanistic classes. The inclusion of erythrocytes in the culture medium resulted in a general but less pronounced increase in transcriptional activity, with the highest up-regulation of genes involved in iron metabolism, proteolysis, and transport of fatty acids and sugars. Conclusions We have identified the genes that are up-regulated during the first 5 days of schistosomula development in vitro. Using a combination of gene silencing techniques and murine protection studies, some of these highly up-regulated transcripts can be targeted for future development of new vaccines and drugs. PMID:20161728

The sex lives of parasites: investigating the mating system and mechanisms of sexual selection of the human pathogen Schistosoma mansoni.

PubMed

Steinauer, Michelle L

2009-08-01

The mating systems of internal parasites are inherently difficult to investigate although they have important implications for the evolutionary biology of the species, disease epidemiology, and are important considerations for control measures. Using parentage analyses, three topics concerning the mating biology of Schistosoma mansoni were investigated: the number of mates per adult male and female, variance in reproductive success among individuals, and the potential role for sexual selection on male body size and also mate choice for genetically dissimilar individuals. Results indicated that schistosomes were mostly monogamous, and evidence of only one mate change occurred over a period of 5-6 weeks. One male was polygynous and contained two females in its gynecophoral canal although offspring were only detected for one of the females. Even though they were primarily monogamous and the sex ratio near even, reproductive success was highly variable, indicating a potential role for sexual selection. Male body size was positively related to reproductive success, consistent with sexual selection via male-male competition and female choice for large males. However, relatedness of pairs was not associated with their reproductive success. Finally, genetically identical individuals differed significantly in their reproductive output and identical males in their body size, indicating important partner and environmental effects on these traits.

Choline incorporation by Schistosoma mansoni: distribution of choline metabolites during development and after sexual differentiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ancelin, M.L.; Torpier, G.; Vial, H.J.

1987-06-01

Choline metabolism was investigated in Schistosoma mansoni during the main phases of its development, namely, schistosomula, 11- and 15-day-old worms, and adults. At the physiological choline concentration used in the assay (20 microM), betaine was, along with phosphatidylcholine, one of the most abundant choline metabolites, revealing considerable choline oxidation activity. Very little radioactivity was associated with CDP-choline, whereas a sustained incorporation into phosphocholine occurred. These results provide good evidence that CTP:phosphocholine cytidylyltransferase plays a regulatory role in the de novo pathway of phosphatidylcholine biosynthesis. During development, the incorporation of choline into its various metabolites was maximal in 11-day-old worms. Atmore » this stage, the oxidative pathway predominated over the Kennedy pathway, whereas at all other stages the de novo phosphatidylcholine biosynthesis was predominant. Furthermore, choline incorporation into betaine was much more important in the adult female worm than in the male, indicating a major difference in choline incorporation and distribution between the 2 sexes of the adult worms.« less

Effect of clinically approved HDAC inhibitors on Plasmodium, Leishmania and Schistosoma parasite growth.

PubMed

Chua, Ming Jang; Arnold, Megan S J; Xu, Weijun; Lancelot, Julien; Lamotte, Suzanne; Späth, Gerald F; Prina, Eric; Pierce, Raymond J; Fairlie, David P; Skinner-Adams, Tina S; Andrews, Katherine T

2017-04-01

Malaria, schistosomiasis and leishmaniases are among the most prevalent tropical parasitic diseases and each requires new innovative treatments. Targeting essential parasite pathways, such as those that regulate gene expression and cell cycle progression, is a key strategy for discovering new drug leads. In this study, four clinically approved anti-cancer drugs (Vorinostat, Belinostat, Panobinostat and Romidepsin) that target histone/lysine deacetylase enzymes were examined for in vitro activity against Plasmodium knowlesi, Schistosoma mansoni, Leishmania amazonensis and L. donovani parasites and two for in vivo activity in a mouse malaria model. All four compounds were potent inhibitors of P. knowlesi malaria parasites (IC 50 9-370 nM), with belinostat, panobinostat and vorinostat having 8-45 fold selectivity for the parasite over human neonatal foreskin fibroblast (NFF) or human embryonic kidney (HEK 293) cells, while romidepsin was not selective. Each of the HDAC inhibitor drugs caused hyperacetylation of P. knowlesi histone H4. None of the drugs was active against Leishmania amastigote or promastigote parasites (IC 50  > 20 μM) or S. mansoni schistosomula (IC 50  > 10 μM), however romidepsin inhibited S. mansoni adult worm parings and egg production (IC 50 ∼10 μM). Modest in vivo activity was observed in P. berghei infected mice dosed orally with vorinostat or panobinostat (25 mg/kg twice daily for four days), with a significant reduction in parasitemia observed on days 4-7 and 4-10 after infection (P < 0.05), respectively. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

The extracellular release of Schistosoma mansoni HMGB1 nuclear protein is mediated by acetylation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Coutinho Carneiro, Vitor; Moraes Maciel, Renata de; Caetano de Abreu da Silva, Isabel

2009-12-25

Schistosoma mansoni HMGB1 (SmHMGB1) was revealed to be a substrate for the parasite histone acetyltransferases SmGCN5 and SmCBP1. We found that full-length SmHMGB1, as well as its HMG-box B (but not HMG-box A) were acetylated in vitro by SmGCN5 and SmCBP1. However, SmCBP1 was able to acetylate both substrates more efficiently than SmGCN5. Interestingly, the removal of the C-terminal acidic tail of SmHMGB1 (SmHMGB1{Delta}C) resulted in increased acetylation of the protein. We showed by mammalian cell transfection assays that SmHMGB1 and SmHMGB1{Delta}C were transported from the nucleus to the cytoplasm after sodium butyrate (NaB) treatment. Importantly, after NaB treatment, SmHMGB1more » was also present outside the cell. Together, our data suggest that acetylation of SmHMGB1 plays a role in cellular trafficking, culminating with its secretion to the extracellular milieu. The possible role of SmHMGB1 acetylation in the pathogenesis of schistosomiasis is discussed.« less

Schistosoma mansoni: radiation dose and morphologic integrity of schistosomules as factors for an effective cryopreserved live vaccine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lewis, F.A.; Stirewalt, M.; Leef, J.L.

1984-01-01

The effectiveness of a cryopreserved, irradiated schistosomule vaccine against an homologous Schistosoma mansoni cercarial challenge was tested in C57B1/6 mice. Highly significant levels of protection developed consistently when mice were immunized with the vaccine irradiated at 10-20 Krad, i.e., doses below that considered optimal for irradiated cercariae (50 Krad). Cryopreserved schistosomules irradiated at 10 or 20 Krad induced greater levels of protection than did schistosomules irradiated at 2, 5, 30, or 50 Krad. Protective immunity developed as early as 3 weeks post-immunization. When immunizing inocula were injected at various times post-thaw, or when schistosomule subpopulations of normal-appearing, damaged or deadmore » organisms were injected, those populations which had appeared to sustain the least degree of damage were those most capable of stimulating protective immunity. These findings highlight the hazards of extrapolating conditions considered standard for an irradiated cercarial vaccine to one in which cryopreservation, for storage of the schistosomules, is an added stress.« less

Effect of diazinon and/or praziquantel on selected protein aspects in healthy and Schistosoma mansoni infected mice.

PubMed

Hanna, Laila S; Medhat, Amina M; Abdel-Menem, Hanan A

2003-04-01

In Egypt, schistosomiasis is still a major public health problem and praziquantel is the drug of choice for its treatment, whereas diazinon is globally used as an insecticide for controlling pests. They adversely affect the environment. Therefore, the authors studied the effect of 1/20 LD50 diazinon given orally to healthy and Schistosoma mansoni infected mice for 5 successive days up to 9 and 17 weeks coupled with a therapeutic dose (2 x 500 mg/kg Bwt) of praziquantel, 2 weeks before sacrificing. The results showed that non significant differences were obtained from total proteins, albumin, globulins, and albumin/globulin ratio. However, significant differences were revealed from alpha1-, alpha2-, beta1-, beta2-, and gamma-globubins in addition to plasma ceruloplasmin. Diazinon changed the levels of alpha2-, beta1-, and gamma-globubins, while diazinon coupled with schistosomiasis affected the levels of most studied parameters. Consequently, exposure to insecticides should be avoided specially in the rural areas where schistosomiasis is still endemic.

Schistosomicidal Activity of Alkyl-phenols from the Cashew Anacardium occidentale against Schistosoma mansoni Adult Worms.

PubMed

Alvarenga, Tavane A; de Oliveira, Pollyanna F; de Souza, Julia M; Tavares, Denise C; Andrade E Silva, Márcio L; Cunha, Wilson R; Groppo, Milton; Januário, Ana H; Magalhães, Lizandra G; Pauletti, Patrícia M

2016-11-23

Bioassay-guided study of the ethanol extract from the cashew Anacardium occidentale furnished cardol triene (1), cardol diene (2), anacardic acid triene (3), cardol monoene (4), anacardic acid diene (5), 2-methylcardol triene (6), and 2-methylcardol diene (7). 1D- and 2D-NMR experiments and HRMS analysis confirmed the structures of compounds 1-7. Compounds 2 and 7 were active against Schistosoma mansoni adult worms in vitro, with LC 50 values of 32.2 and 14.5 μM and selectivity indices of 6.1 and 21.2, respectively. Scanning electron microscopy of the tegument of male worms in the presence of compound 7 at 25 μM after 24 h of incubation showed severe damage as well as peeling and reduction in the number of spine tubercles. Transmission electron microscopy analyses revealed swollen mitochondrial membrane, vacuoles, and altered tegument in worms incubated with compound 2 (25 μM after 24 h). Worms incubated with compound 7 (25 μM after 24 h) had lysed interstitial tissue, degenerated mitochondria, and drastically altered tegument. Together, the results indicated that compound 7 presents promising in vitro schistosomicidal activity.

Schistosoma mansoni: interactive effects of irradiation and cryopreservation on parasite maturation and immunization of mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

James, E.R.; Dobinson, A.R.

1984-06-01

Mechanically transformed schistosomula of Schistosoma mansoni were irradiated with levels of 60Co irradiation between 2.5 and 54 krad, cryopreserved by the two-step addition of ethanediol and rapid cooling technique, and were injected intramuscularly into groups of mice which were perfused 40 days later. The schistosomula were either irradiated and then cryopreserved (IC) or cryopreserved and then irradiated in the frozen state (CI). Development into adult worms was prevented with 4 krad for IC schistosomula, but for CI schistosomula a small number of worms (1.6%) was recovered using 8.8 krad. A dose of 4 krad was sufficient to prevent development ofmore » unfrozen controls (I), but for schistosomula irradiated while exposed to ethanediol (EI), a dose of 7 krad was required. Using the different protocols, the peak levels of protection against a challenge infection were achieved with 9 (IC) and 16 krad (CI), compared to 20 krad for unfrozen schistosomula (I) reported previously. The highest level of protection (65%) was achieved with CI schistosomula. Possible interactions between the radioprotective and damaging effects of cryopreservation are discussed.« less

Long-term frozen storage of urine samples: a trouble to get PCR results in Schistosoma spp. DNA detection?

PubMed

Fernández-Soto, Pedro; Velasco Tirado, Virginia; Carranza Rodríguez, Cristina; Pérez-Arellano, José Luis; Muro, Antonio

2013-01-01

Human schistosomiasis remains a serious worldwide public health problem. At present, a sensitive and specific assay for routine diagnosis of schistosome infection is not yet available. The potential for detecting schistosome-derived DNA by PCR-based methods in human clinical samples is currently being investigated as a diagnostic tool with potential application in routine schistosomiasis diagnosis. Collection of diagnostic samples such as stool or blood is usually difficult in some populations. However, urine is a biological sample that can be collected in a non-invasive method, easy to get from people of all ages and easy in management, but as a sample for PCR diagnosis is still not widely used. This could be due to the high variability in the reported efficiency of detection as a result of the high variation in urine samples' storage or conditions for handling and DNA preservation and extraction methods. We evaluate different commercial DNA extraction methods from a series of long-term frozen storage human urine samples from patients with parasitological confirmed schistosomiasis in order to assess the PCR effectiveness for Schistosoma spp. detection. Patients urine samples were frozen for 18 months up to 7 years until use. Results were compared with those obtained in PCR assays using fresh healthy human urine artificially contaminated with Schistosoma mansoni DNA and urine samples from mice experimentally infected with S. mansoni cercariae stored frozen for at least 12 months before use. PCR results in fresh human artificial urine samples using different DNA based extraction methods were much more effective than those obtained when long-term frozen human urine samples were used as the source of DNA template. Long-term frozen human urine samples are probably not a good source for DNA extraction for use as a template in PCR detection of Schistosoma spp., regardless of the DNA method of extraction used.

Transduction of Schistosoma mansoni by vesicular stomatitis virus glycoprotein-pseudotyped Moloney murine leukemia retrovirus.

PubMed

Kines, Kristine J; Mann, Victoria H; Morales, Maria E; Shelby, Bryan D; Kalinna, Bernd H; Gobert, Geoffrey N; Chirgwin, Sharon R; Brindley, Paul J

2006-04-01

Retroviral transduction of cultured schistosomes offers a potential means to establish transgenic lines of schistosomes and thereby to facilitate the elucidation of schistosome gene function and expression. The Moloney murine leukemia retroviral (MMLV) vector pLNHX was modified to incorporate EGFP or luciferase reporter genes under control of schistosome endogenous gene promoters from the spliced leader RNA and HSP70 genes. These constructs and a plasmid encoding vesicular stomatitis virus glycoprotein (VSVG) were utilized along with GP2-293 cells to produce replication incompetent retrovirus particles pseudotyped with the VSVG envelope. Exposure of several developmental stages, including sporocysts, of Schistosoma mansoni to these virions was facilitated by incubation with polybrene and/or by centrifugation. The early stages of binding and uptake of virus to the parasite tegument were demonstrated by the immunofluorescence colocalization of VSVG envelope and retroviral capsid proteins. Southern hybridization analysis indicated the integration of proviral forms of the MMLV constructs in genomic DNA isolated from the virus exposed schistosomes. Furthermore, analysis of RNA isolated from virus treated parasites demonstrated the presence of transcripts encoding reporter transgenes. Together these results indicated productive transduction by VSVG pseudotyped MMLV of cultured schistosomes, and suggest a tractable route forward towards heritable schistosome transgenesis.

Deposition and maturation of eggs of Schistosoma mansoni in vitro: importance of fatty acids in serum-free media.

PubMed

Newport, G R; Weller, T H

1982-03-01

A serum-free medium which supports miracidial development in some eggs deposited by adult Schistosoma mansoni in vitro is described. Derivation of the medium involved examination of the supportiveness of nine chemically defined media, selection of one promoting the highest degree of worm oviposition, and supplementation of the latter with various serum fractions. The serum fraction supporting egg maturation was nondialyzable, and precipitated at 50-60% ammonium sulfate saturation. This fraction could be replaced by bovine serum albumin; however, the supportive activity disappeared if this material was delipidated. Addition of soybean lecithin, or stearic acid, to fatty-acid-free, albumin-supplemented media yielded intermediate results, while similar addition of other nonesterified fatty acids proved non stimulatory. A fatty acid mixture, rich in stearic acid, was then developed which, when added to delipidated-albumin supplemented media, supported a degree of egg development comparable to that obtained with media supplemented with 8% newborn calf serum.

Ionotropic Receptors Identified within the Tentacle of the Freshwater Snail Biomphalaria glabrata, an Intermediate Host of Schistosoma mansoni

PubMed Central

Liang, Di; Wang, Tianfang; Rotgans, Bronwyn A.; McManus, Donald P.; Cummins, Scott F.

2016-01-01

Biomphalaria glabrata (B. glabrata) is an air-breathing aquatic mollusc found in freshwater habitats across the Western Hemisphere. It is most well-known for its recognized capacity to act as a major intermediate host for Schistosoma mansoni, the human blood fluke parasite. Ionotropic receptors (IRs), a variant family of the ionotropic glutamate receptors (iGluR), have an evolutionary ancient function in detecting odors to initiate chemosensory signaling. In this study, we applied an array of methods towards the goal of identifying IR-like family members in B. glabrata, ultimately revealing two types, the iGluR and IR. Sequence alignment showed that three ligand-binding residues are conserved in most Biomphalaria iGluR sequences, while the IRs did exhibit a variable pattern, lacking some or all known glutamate-interactingresidues, supporting their distinct classification from the iGluRs. We show that B. glabrata contains 7 putative IRs, some of which are expressed within its chemosensory organs. To further investigate a role for the more ancient IR25a type in chemoreception, we tested its spatial distribution pattern within the snail cephalic tentacle by in situ hybridization. The presence of IR25a within presumptive sensory neurons supports a role for this receptor in olfactory processing, contributing to our understanding of the molecular pathways that are involved in Biomphalaria olfactory processing. PMID:27253696

Ionotropic Receptors Identified within the Tentacle of the Freshwater Snail Biomphalaria glabrata, an Intermediate Host of Schistosoma mansoni.

PubMed

Liang, Di; Wang, Tianfang; Rotgans, Bronwyn A; McManus, Donald P; Cummins, Scott F

2016-01-01

Biomphalaria glabrata (B. glabrata) is an air-breathing aquatic mollusc found in freshwater habitats across the Western Hemisphere. It is most well-known for its recognized capacity to act as a major intermediate host for Schistosoma mansoni, the human blood fluke parasite. Ionotropic receptors (IRs), a variant family of the ionotropic glutamate receptors (iGluR), have an evolutionary ancient function in detecting odors to initiate chemosensory signaling. In this study, we applied an array of methods towards the goal of identifying IR-like family members in B. glabrata, ultimately revealing two types, the iGluR and IR. Sequence alignment showed that three ligand-binding residues are conserved in most Biomphalaria iGluR sequences, while the IRs did exhibit a variable pattern, lacking some or all known glutamate-interactingresidues, supporting their distinct classification from the iGluRs. We show that B. glabrata contains 7 putative IRs, some of which are expressed within its chemosensory organs. To further investigate a role for the more ancient IR25a type in chemoreception, we tested its spatial distribution pattern within the snail cephalic tentacle by in situ hybridization. The presence of IR25a within presumptive sensory neurons supports a role for this receptor in olfactory processing, contributing to our understanding of the molecular pathways that are involved in Biomphalaria olfactory processing.

Schistosoma mansoni Tegument (Smteg) Induces IL-10 and Modulates Experimental Airway Inflammation.

PubMed

Marinho, Fábio Vitarelli; Alves, Clarice Carvalho; de Souza, Sara C; da Silva, Cintia M G; Cassali, Geovanni D; Oliveira, Sergio C; Pacifico, Lucila G G; Fonseca, Cristina T

2016-01-01

Previous studies have demonstrated that S. mansoni infection and inoculation of the parasite eggs and antigens are able to modulate airways inflammation induced by OVA in mice. This modulation was associated to an enhanced production of interleukin-10 and to an increased number of regulatory T cells. The S. mansoni schistosomulum is the first stage to come into contact with the host immune system and its tegument represents the host-parasite interface. The schistosomula tegument (Smteg) has never been studied in the context of modulation of inflammatory disorders, although immune evasion mechanisms take place in this phase of infection to guarantee the persistence of the parasite in the host. The aim of this study was to evaluate the Smteg ability to modulate inflammation in an experimental airway inflammation model induced by OVA and to characterize the immune factors involved in this modulation. To achieve the objective, BALB/c mice were sensitized with ovalbumin (OVA) and then challenged with OVA aerosol after Smteg intraperitoneal inoculation. Protein extravasation and inflammatory cells were assessed in bronchoalveolar lavage and IgE levels were measured in serum. Additionally, lungs were excised for histopathological analyses, cytokine measurement and characterization of the cell populations. Inoculation with Smteg led to a reduction in the protein levels in bronchoalveolar lavage (BAL) and eosinophils in both BAL and lung tissue. In the lung tissue there was a reduction in inflammatory cells and collagen deposition as well as in IL-5, IL-13, IL-25 and CCL11 levels. Additionally, a decrease in specific anti-OVA IgE levels was observed. The reduction observed in these inflammatory parameters was associated with increased levels of IL-10 in lung tissues. Furthermore, Smteg/asthma mice showed high percentage of CD11b+F4/80+IL-10+ and CD11c+CD11b+IL-10+ cells in lungs. Taken together, these findings demonstrate that S. mansoni schistosomula tegument can modulates

Purification of a chymotrypsin-like enzyme present on adult Schistosoma mansoni worms from infected mice and its characterization as a host carboxylesterase.

PubMed

Igetei, Joseph E; Liddell, Susan; El-Faham, Marwa; Doenhoff, Michael J

2016-04-01

A serine protease-like enzyme found in detergent extracts of Schistosoma mansoni adult worms perfused from infected mice has been purified from mouse blood and further characterized. The enzyme is approximately 85 kDa and hydrolyses N-acetyl-DL-phenylalanine β-naphthyl-ester, a chromogenic substrate for chymotrypsin-like enzymes. The enzyme from S. mansoni worms appears to be antigenically and enzymatically similar to a molecule that is present in normal mouse blood and so is seemingly host-derived. The enzyme was partially purified by depleting normal mouse serum of albumin using sodium chloride and cold ethanol, followed by repeated rounds of purification by one-dimensional sodium dodecyl sulphate polyacrylamide gel electrophoresis. The purified material was subjected to tandem mass spectrometry and its derived peptides found to belong to mouse carboxylesterase 1C. Its ability to hydrolyse α- or β-naphthyl acetates, which are general esterase substrates, has been confirmed. A similar carboxylesterase was purified and characterized from rat blood. Additional evidence to support identification of the enzyme as a carboxylesterase has been provided. Possible roles of the enzyme in the mouse host-parasite relationship could be to ease the passage of worms through the host's blood vessels and/or in immune evasion.

Worm Proteins of Schistosoma mansoni Reduce the Severity of Experimental Chronic Colitis in Mice by Suppressing Colonic Proinflammatory Immune Responses

PubMed Central

Heylen, Marthe; Ruyssers, Nathalie E.; De Man, Joris G.; Timmermans, Jean-Pierre; Pelckmans, Paul A.; Moreels, Tom G.; De Winter, Benedicte Y.

2014-01-01

Although helminthic therapy as a possible new option to treat inflammatory bowel disease is a well-established concept by now, the search for immunomodulatory helminth-derived compounds and their mechanisms of action is still ongoing. We investigated the therapeutic potential and the underlying immunological mechanisms of Schistosoma mansoni soluble worm proteins (SmSWP) in an adoptive T cell transfer mouse model of chronic colitis. Both a curative and a preventive treatment protocol were included in this study. The curative administration of SmSWP (started when colitis was established), resulted in a significant improvement of the clinical disease score, colonoscopy, macroscopic and microscopic inflammation score, colon length and myeloperoxidase activity. The therapeutic potential of the preventive SmSWP treatment (started before colitis was established), was less pronounced compared with the curative SmSWP treatment but still resulted in an improved clinical disease score, body weight loss, colon length and microscopic inflammation score. Both the curative and preventive SmSWP treatment downregulated the mRNA expression of the proinflammatory cytokines IFN-γ and IL-17A and upregulated the mRNA expression of the anti-inflammatory cytokine IL-4 in the colon at the end of the experiment. This colonic immunomodulatory effect of SmSWP could not be confirmed at the protein level. Moreover, the effect of SmSWP appeared to be a local colonic phenomenon, since the flow cytometric T cell characterization of the mesenteric lymph nodes and the cytokine measurements in the serum did not reveal any effect of SmSWP treatment. In conclusion, SmSWP treatment reduced the severity of colitis in the adoptive transfer mouse model via the suppression of proinflammatory cytokines and the induction of an anti-inflammatory response in the colon. PMID:25313594

Atypical properties of a conventional calcium channel beta subunit from the platyhelminth Schistosoma mansoni.

PubMed

Salvador-Recatalà, Vicenta; Schneider, Toni; Greenberg, Robert M

2008-03-26

The function of voltage-gated calcium (Cav) channels greatly depends on coupling to cytoplasmic accessory beta subunits, which not only promote surface expression, but also modulate gating and kinetic properties of the alpha1 subunit. Schistosomes, parasitic platyhelminths that cause schistosomiasis, express two beta subunit subtypes: a structurally conventional beta subunit and a variant beta subunit with unusual functional properties. We have previously characterized the functional properties of the variant Cavbeta subunit. Here, we focus on the modulatory phenotype of the conventional Cavbeta subunit (SmCavbeta) using the human Cav2.3 channel as the substrate for SmCavbeta and the whole-cell patch-clamp technique. The conventional Schistosoma mansoni Cavbeta subunit markedly increases Cav2.3 currents, slows macroscopic inactivation and shifts steady state inactivation in the hyperpolarizing direction. However, currents produced by Cav2.3 in the presence of SmCavbeta run-down to approximately 75% of their initial amplitudes within two minutes of establishing the whole-cell configuration. This suppressive effect was independent of Ca2+, but dependent on intracellular Mg2+-ATP. Additional experiments revealed that SmCavbeta lends the Cav2.3/SmCavbeta complex sensitivity to Na+ ions. A mutant version of the Cavbeta subunit lacking the first forty-six amino acids, including a string of twenty-two acidic residues, no longer conferred sensitivity to intracellular Mg2+-ATP and Na+ ions, while continuing to show wild type modulation of current amplitude and inactivation of Cav2.3. The data presented in this article provide insights into novel mechanisms employed by platyhelminth Cavbeta subunits to modulate voltage-gated Ca2+ currents that indicate interactions between the Ca2+ channel complex and chelated forms of ATP as well as Na+ ions. These results have potentially important implications for understanding previously unknown mechanisms by which platyhelminths and

Specific Schistosoma mansoni rat T cell clones. I. Generation and functional analysis in vitro and in vivo.

PubMed

Pestel, J; Dissous, C; Dessaint, J P; Louis, J; Engers, H; Capron, A

1985-06-01

In an attempt to determine the role of schistosome-specific T cells in the immune mechanisms developed during schistosomiasis, Schistosoma mansoni-specific T cells and clones were generated in vitro and some of their functions analyzed in vitro and in vivo in the fischer rat model. The data presented here can be summarized as follows: a) Lymph node cells (LNC) from rats primed with the excretory/secretory antigens-incubation products (IPSm) of adult worms proliferate in vitro only in response to the homologous schistosome antigens and not to unrelated antigens (Ag) such as ovalbumin (OVA) or Dipetalonema viteae and Fasciola hepatica parasite extracts. b) After in vitro restimulation of the primed LNC population with IPSm in the presence of antigen-presenting cells (APC) and maintenance in IL 2-containing medium, the frequency of IPSm-specific T cells is increased and the T cells can be restimulated only in the presence of APC possessing the same major histocompatibility complex (MHC) antigens. c) Following appropriate limiting dilution assays (LDA) (1 cell/well), 10 IPSm-specific T cell clones were obtained, and two of four maintained in culture were tested for their helper activity because they expressed only the W3/13+ W3/25+ surface phenotypes. d) The two highly proliferating IPSm-specific T cell clones (G5 and E23) exhibit an IPSm-dependent helper activity, as shown by the increase in IgG production by IPSm-primed B cells. e) IPSm-T cell clone (G5) as well as IPSm-T cell lines when injected in S. mansoni-infested rats can exert an in vivo helper activity, which is characterized by an accelerated production of IgG antibodies specific for the previously identified 30 to 40 kilodaltons (kd) schistosomula surface antigens (Ag). As recent studies have demonstrated that rat monoclonal antibodies recognize some incubation products of adult S. mansoni as well as one of the 30 to 40 kd schistosomula surface antigens, and taking into account the fact that the T cell

DNA barcoding of schistosome cercariae reveals a novel sub-lineage within Schistosoma rodhaini from Ngamba Island Chimpanzee Sanctuary, Lake Victoria.

PubMed

Standley, C J; Stothard, J R

2012-10-01

While Schistosoma rodhaini is typically considered a parasite of small mammals and is very scantly distributed in the Lake Victoria basin, it is known to hybridize with the more widespread Schistosoma mansoni, the causative agent of intestinal schistosomiasis. As part of broader parasitological and malacological surveys for S. mansoni across Lake Victoria, schistosome cercariae were harvested from a field-caught Biomphalaria choanomphala taken on Ngamba Island Chimpanzee Sanctuary, Uganda. Upon DNA barcoding, these cercariae were found to be a mixture of both S. rodhaini and S. mansoni, with further phylogenetic analysis revealing a hitherto unknown sub-lineage within S. rodhaini. Despite repeated sampling for eggs and miracidia from both chimpanzees and staff on Ngamba Island Sanctuary, detection of S. rodhaini within local definitive hosts awaits additional efforts, which should be mindful of a potential host role of spotted-necked otters.

Definition of the complete Schistosoma mansoni hemoglobinase mRNA sequence and gene expression in developing parasites.

PubMed

el Meanawy, M A; Aji, T; Phillips, N F; Davis, R E; Salata, R A; Malhotra, I; McClain, D; Aikawa, M; Davis, A H

1990-07-01

Schistosoma mansoni uses a variety of proteases termed hemoglobinases to obtain nutrition from host globin. Previous reports have characterized cDNAs encoding 1 of these enzymes. However, these sequences did not define the primary structures of the mRNA and protein. The complete sequence of the 1390 base mRNA has now been determined. It encodes a 50 kDa primary translation product. In vitro translations coupled with immunoprecipitations and Western blots of parasite lysates allowed visualization of the 50 kDa form. Production of the 31 kDa mature hemoglobinase from the 50 kDa species involves removal of both NH2 and COOH terminal residues from the primary translation product. Expression of hemoglobinase mRNA and protein was examined during larval parasite development. Low levels were observed in young schistosomula. After 6-9 days in culture, high hemoglobinase levels were seen which correlated with the onset of red blood cell feeding. Immunoelectron microscopy was employed to examine hemoglobinase location and function. In adult worms the enzyme was associated with the gut lumen and gut epithelium. In cercariae, the protease was observed in the head gland, suggesting new roles for the protease.

In vitro schistosomicidal and antiviral activities of Arctium lappa L. (Asteraceae) against Schistosoma mansoni and Herpes simplex virus-1.

PubMed

Dias, Mirna Meana; Zuza, Ohana; Riani, Lorena R; de Faria Pinto, Priscila; Pinto, Pedro Luiz Silva; Silva, Marcos P; de Moraes, Josué; Ataíde, Ana Caroline Z; de Oliveira Silva, Fernanda; Cecílio, Alzira Batista; Da Silva Filho, Ademar A

2017-10-01

Schistosomiasis and herpes diseases represent serious issues to the healthcare systems, infecting a large number of people worldwide, mainly in developing countries. Arctium lappa L. (Asteraceae), known as "bardana" and "burdock", is a medicinal plant popularly used for several purposes, including as antiseptic. In this study, we evaluated the in vitro schistosomicidal and antiherpes activities of the crude extract of A. lappa, which have not yet been described. Fruits of A. lappa L. were extracted by maceration with ethanol: H 2 O (96:4 v/v) in order to obtain the hydroalcoholic extract of A. lappa (AL). In vitro schistosomicidal assays were assessed against adult worms of Schistosoma mansoni, while the in vitro antiviral activity of AL was evaluated on replication of Herpes simplex virus type-1 (HSV-1). Cell viability was measured by MTT assay, using Vero cells and chemical composition of AL was determined by qualitative UPLC-ESI-QTOF-MS analysis. UPLC-ESI-QTOF-MS analysis of AL revealed the presence of dibenzylbutyrolactone lignans, such as arctiin and arctigenin. Results showed that AL was not cytotoxic to Vero cells even when tested at 400μg/mL. qPCR results indicated a significant viral load decreased for all tested concentrations of AL (400, 50, and 3.125μg/mL), which showed similar antiviral effect to acyclovir (50μg/mL) when tested at 400μg/mL. Also, AL (400, 200, and 100μg/mL) caused 100% mortality and significantly reduction on motor activity of all adult worms of S. mansoni. Confocal laser scanning microscopy showed tegumental morphological alterations and changes on the numbers of tubercles of S. mansoni worms in a dose-dependent manner after treatment with AL. This report provides the first evidence for the in vitro schistosomicidal and antiherpes activities of AL, opening the route to further schistosomicidal and antiviral studies with AL and their compounds, especially lignans. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Antioxidant and schistosomicidal effect of Allium sativum and Allium cepa against Schistosoma mansoni different stages.

PubMed

Mantawy, M M; Aly, H F; Zayed, N; Fahmy, Z H

2012-07-01

The schistosomicidal properties of garlic (Allium sativum) and onion (Allium cepa) powder were tested in vitro against Schistosoma mansoni miracidia, schistosomula, cercaria and adult worms. Results indicate their strong biocidal effects against all stages of the parasite and also show scavenging inhibitory effect on 2,2-diphenyl-1-picrylhydrazyl (DPPH) and nitric oxide (NO). In the present work, the in vivo effects of A. sativum and A. cepa on lipid peroxide and some antioxidant enzymes; thioredoxin reductase (TrxR), sorbitol dehydrogenase (SDH), superoxide dismutase (SOD), catalase (CAT) and glutathione reductase (GR) (as they have a crucial role in host protection against invading parasite) were also studied. The data demonstrate that, there was a significant inhibition in SOD, CAT, GR, TrxR and SDH in infected liver while, significant elevation was detected in lipid peroxide as compared to the normal control. The current resultS clearly revealed that, the used both edible plants enhance the host antioxidant system indicated by lowering in lipid peroxide and stimulation of SOD, CAT, GR, TrxR and SDH enzyme levels. Enhancement of such enzymes using A. sativum and A. cepa could in turn render the parasite vulnerable to damage by the host and may play a role in the antischistosomal potency of the used food ingredients.

Sm14 of Schistosoma mansoni in Fusion with Tetanus Toxin Fragment C Induces Immunoprotection against Tetanus and Schistosomiasis in Mice

PubMed Central

Abreu, Patrícia A. E.; Miyasato, Patrícia A.; Vilar, Mônica M.; Dias, Waldely O.; Ho, Paulo L.; Tendler, Míriam; Nascimento, Ana L. T. O.

2004-01-01

We have constructed vectors that permit the expression in Escherichia coli of Schistosoma mansoni fatty acid-binding protein 14 (Sm14) in fusion with the nontoxic, but highly immunogenic, tetanus toxin fragment C (TTFC). The recombinant six-His-tagged proteins were purified by nickel affinity chromatography and used in immunization and challenge assays. Animals inoculated with TTFC in fusion with or coadministered with Sm14 showed high levels of tetanus toxin antibodies, while animals inoculated with Sm14 in fusion with or coadministered with TTFC showed high levels of Sm14 antibodies. In both cases, there were no changes in the type of immune response (Th2) obtained with the fusion proteins compared to those obtained with the nonfused proteins. Mice immunized with the recombinant proteins (TTFC in fusion with or coadministered with Sm14) survived the challenge with tetanus toxin and did not show any symptoms of the disease. Control animals inoculated with either phosphate-buffered saline (PBS) or Sm14 died with severe symptoms of tetanus after 24 h. Mice immunized with the recombinant proteins (Sm14 in fusion with or coadministered with TTFC) showed a 50% reduction in worm burden when they were challenged with S. mansoni cercariae, while control animals inoculated with either PBS or TTFC were not protected. The results show that the expression of other antigens in fusion at the carboxy terminus of TTFC is feasible for the development of a multivalent recombinant vaccine. PMID:15385496

Prototypic chromatin insulator cHS4 protects retroviral transgene from silencing in Schistosoma mansoni

PubMed Central

Suttiprapa, Sutas; Rinaldi, Gabriel; Brindley, Paul J.

2011-01-01

Vesicular stomatitis virus glycoprotein (VSVG) pseudotyped murine leukemia virus (MLV) virions can transduce schistosomes, leading to chromosomal integration of reporter transgenes. To develop VSVG-MLV for functional genomics in schistosomes, the influence of the chicken β-globin cHS4 element, a prototypic chromatin insulator, on transgene expression was examined. Plasmid pLNHX encoding the MLV 5′- and 3′-Long Terminal Repeats (LTRs) flanking the neomycin phosphotransferase gene (neo) was modified to include, within the U3 region of the 3′-LTR, active components of cHS4 insulator, the 250 bp core fused to the 400 bp 3′-region. Cultured larvae of Schistosoma mansoni were transduced with virions from producer cells transfected with control or cHS4-bearing plasmids. Schistosomules transduced with cHS4 virions expressed two to 20 times higher levels of neo than controls, while carrying comparable numbers of integrated proviral transgenes. The findings not only demonstrated that cHS4 was active in schistosomes but also they represent the first report of activity of cHS4 in any Lophotrochozoan species, which has significant implications for evolutionary conservation of heterochromatin regulation. The findings advance prospects for transgenesis in functional genomics of the schistosome genome to discover intervention targets because they provide the means to enhance and extend transgene activity including for vector based RNA interference. PMID:21918820

Differences in the number of hemocytes in the snail host Biomphalaria tenagophila, resistant and susceptible to Schistosoma mansoni infection.

PubMed

Oliveira, A L D; Levada, P M; Zanotti-Magalhaes, E M; Magalhães, L A; Ribeiro-Paes, J T

2010-12-21

The relationships between schistosomiasis and its intermediate host, mollusks of the genus Biomphalaria, have been a concern for decades. It is known that the vector mollusk shows different susceptibility against parasite infection, whose occurrence depends on the interaction between the forms of trematode larvae and the host defense cells. These cells are called amebocytes or hemocytes and are responsible for the recognition of foreign bodies and for phagocytosis and cytotoxic reactions. The defense cells mediate the modulation of the resistant and susceptible phenotypes of the mollusk. Two main types of hemocytes are found in the Biomphalaria hemolymph: the granulocytes and the hyalinocytes. We studied the variation in the number (kinetics) of hemocytes for 24 h after exposing the parasite to genetically selected and non-selected strains of Biomphalaria tenagophila, susceptible or not to infection by Schistosoma mansoni. The differences were analyzed referred to the variations in the number of hemocytes in mollusks susceptible or not to infection by S. mansoni. The hemolymph of the selected and non-selected snails was collected, and hemocytes were counted using a Neubauer chamber at six designated periods: 0 h (control, non-exposed individuals), 2 h, 6 h, 12 h, 18 h and, 24 h after parasite exposure. Samples of hemolymph of five selected mollusks and five non-selected mollusks were separately used at each counting time. There was a significant variation in the number of hemocytes between the strains, which indicates that defense cells have different behaviors in resistant and susceptible mollusks.

Multivariable Regression Analysis in Schistosoma mansoni-Infected Individuals in the Sudan Reveals Unique Immunoepidemiological Profiles in Uninfected, egg+ and Non-egg+ Infected Individuals.

PubMed

Elfaki, Tayseer Elamin Mohamed; Arndts, Kathrin; Wiszniewsky, Anna; Ritter, Manuel; Goreish, Ibtisam A; Atti El Mekki, Misk El Yemen A; Arriens, Sandra; Pfarr, Kenneth; Fimmers, Rolf; Doenhoff, Mike; Hoerauf, Achim; Layland, Laura E

2016-05-01

In the Sudan, Schistosoma mansoni infections are a major cause of morbidity in school-aged children and infection rates are associated with available clean water sources. During infection, immune responses pass through a Th1 followed by Th2 and Treg phases and patterns can relate to different stages of infection or immunity. This retrospective study evaluated immunoepidemiological aspects in 234 individuals (range 4-85 years old) from Kassala and Khartoum states in 2011. Systemic immune profiles (cytokines and immunoglobulins) and epidemiological parameters were surveyed in n = 110 persons presenting patent S. mansoni infections (egg+), n = 63 individuals positive for S. mansoni via PCR in sera but egg negative (SmPCR+) and n = 61 people who were infection-free (Sm uninf). Immunoepidemiological findings were further investigated using two binary multivariable regression analysis. Nearly all egg+ individuals had no access to latrines and over 90% obtained water via the canal stemming from the Atbara River. With regards to age, infection and an egg+ status was linked to young and adolescent groups. In terms of immunology, S. mansoni infection per se was strongly associated with increased SEA-specific IgG4 but not IgE levels. IL-6, IL-13 and IL-10 were significantly elevated in patently-infected individuals and positively correlated with egg load. In contrast, IL-2 and IL-1β were significantly lower in SmPCR+ individuals when compared to Sm uninf and egg+ groups which was further confirmed during multivariate regression analysis. Schistosomiasis remains an important public health problem in the Sudan with a high number of patent individuals. In addition, SmPCR diagnostics revealed another cohort of infected individuals with a unique immunological profile and provides an avenue for future studies on non-patent infection states. Future studies should investigate the downstream signalling pathways/mechanisms of IL-2 and IL-1β as potential diagnostic markers in order to

Multivariable Regression Analysis in Schistosoma mansoni-Infected Individuals in the Sudan Reveals Unique Immunoepidemiological Profiles in Uninfected, egg+ and Non-egg+ Infected Individuals

PubMed Central

Wiszniewsky, Anna; Ritter, Manuel; Goreish, Ibtisam A.; Atti El Mekki, Misk El Yemen A.; Arriens, Sandra; Pfarr, Kenneth; Fimmers, Rolf; Doenhoff, Mike; Hoerauf, Achim; Layland, Laura E.

2016-01-01

Background In the Sudan, Schistosoma mansoni infections are a major cause of morbidity in school-aged children and infection rates are associated with available clean water sources. During infection, immune responses pass through a Th1 followed by Th2 and Treg phases and patterns can relate to different stages of infection or immunity. Methodology This retrospective study evaluated immunoepidemiological aspects in 234 individuals (range 4–85 years old) from Kassala and Khartoum states in 2011. Systemic immune profiles (cytokines and immunoglobulins) and epidemiological parameters were surveyed in n = 110 persons presenting patent S. mansoni infections (egg+), n = 63 individuals positive for S. mansoni via PCR in sera but egg negative (SmPCR+) and n = 61 people who were infection-free (Sm uninf). Immunoepidemiological findings were further investigated using two binary multivariable regression analysis. Principal Findings Nearly all egg+ individuals had no access to latrines and over 90% obtained water via the canal stemming from the Atbara River. With regards to age, infection and an egg+ status was linked to young and adolescent groups. In terms of immunology, S. mansoni infection per se was strongly associated with increased SEA-specific IgG4 but not IgE levels. IL-6, IL-13 and IL-10 were significantly elevated in patently-infected individuals and positively correlated with egg load. In contrast, IL-2 and IL-1β were significantly lower in SmPCR+ individuals when compared to Sm uninf and egg+ groups which was further confirmed during multivariate regression analysis. Conclusions/Significance Schistosomiasis remains an important public health problem in the Sudan with a high number of patent individuals. In addition, SmPCR diagnostics revealed another cohort of infected individuals with a unique immunological profile and provides an avenue for future studies on non-patent infection states. Future studies should investigate the downstream signalling pathways

Evidence for Integrin - Venus Kinase Receptor 1 Alliance in the Ovary of Schistosoma mansoni Females Controlling Cell Survival.

PubMed

Gelmedin, Verena; Morel, Marion; Hahnel, Steffen; Cailliau, Katia; Dissous, Colette; Grevelding, Christoph G

2017-01-01

In metazoan integrin signaling is an important process of mediating extracellular and intracellular communication processes. This can be achieved by cooperation of integrins with growth factor receptors (GFRs). Schistosoma mansoni is a helminth parasite inducing schistosomiasis, an infectious disease of worldwide significance for humans and animals. First studies on schistosome integrins revealed their role in reproductive processes, being involved in spermatogenesis and oogenesis. With respect to the roles of eggs for maintaining the parasite´s life cycle and for inducing the pathology of schistosomiasis, elucidating reproductive processes is of high importance. Here we studied the interaction of the integrin receptor Smβ-Int1 with the venus kinase receptor SmVKR1 in S. mansoni. To this end we cloned and characterized SmILK, SmPINCH, and SmNck2, three putative bridging molecules for their role in mediating Smβ-Int1/SmVKR1 cooperation. Phylogenetic analyses showed that these molecules form clusters that are specific for parasitic platyhelminths as it was shown for integrins before. Transcripts of all genes colocalized in the ovary. In Xenopus oocytes germinal vesicle breakdown (GVBD) was only induced if all members were simultaneously expressed. Coimmunoprecipitation results suggest that a Smβ-Int1-SmILK-SmPINCH-SmNck2-SmVKR1 complex can be formed leading to the phosphorylation and activation of SmVKR1. These results indicate that SmVKR1 can be activated in a ligand-independent manner by receptor-complex interaction. RNAi and inhibitor studies to knock-down SmILK as a representative complex member concurrently revealed effects on the extracellular matrix surrounding the ovary and oocyte localization within the ovary, oocyte survival, and egg production. By TUNEL assays, confocal laser scanning microscopy (CLSM), Caspase-3 assay, and transcript profiling of the pro-apoptotic BCL-2 family members BAK/BAX we obtained first evidence for roles of this signaling

Change in children's school behavior after mass administration of praziquantel for Schistosoma mansoni infection in endemic areas of western Kenya: A pilot study using the Behavioral Assessment System for Children (BASC-2).

PubMed

Musuva, Rosemary; Shen, Ye; Wei, Xianjue; Binder, Sue; Ivy, Julianne A; Secor, W Evan; Montgomery, Susan P; King, Charles H; Mwinzi, Pauline N M

2017-01-01

Schistosomiasis is a parasite-related chronic inflammatory condition that can cause anemia, decreased growth, liver abnormalities, and deficits in cognitive functioning among children. This study used the Behavior Assessment System for Children (BASC-2) to collect data on thirty-six 9-12 year old school-attending children's behavioral profiles in an Schistosoma mansoni-endemic area of western Kenya, before and after treatment with praziquantel for S. mansoni infection. BASC-2 T scores were significantly reduced post-treatment (p < 0.05) for each of the 'negative' behavior categories including externalizing problems (hyperactivity, aggression, and conduct problems that are disruptive in nature), internalizing problems (anxiety, depression, somatization, atypicality, and withdrawal), school problems (academic difficulties, included attention problems and learning problems), and the composite behavioral symptoms index (BSI), signifying improved behavior. While the observed improvement in the 'positive' behavior category of adaptive skills (adaptability, functional communication, social skills, leadership, and study skills) was not statistically significant, there were significant improvements in two adaptive skills subcategories: social skills and study skills. Results of this study suggest that children have better school-related behaviors without heavy S. mansoni infection, and that infected children's behaviors, especially disruptive problem behaviors, improve significantly after praziquantel treatment.

Decline in transmission of schistosomiasis mansoni in Oman.

PubMed

Al Abaidani, Idris; Al-Abri, Seif; Shaban, Mahmoud; Ghugey, Satish L; Al Kathery, Salem; Al-Mashikhi, Khalid; Garba, Amadou; Gabrielli, Albis Francesco

2016-12-12

Intestinal schistosomiasis due to Schistosoma mansoni was first reported in Oman in 1979. We describe the trend in parasitological and serological prevalence of human infection with S. mansoni in the endemic area over the period 1982-2014, and the compliance of data generated by the national monitoring and evaluation system with schistosomiasis elimination criteria set by the Ministry of Health of Oman. Parasitological and serological assessments were carried out on population (mainly children) living in the area at risk for schistosomiasis in Dhofar, the country's only endemic Governorate, for a period of over 30 years. Kato-Katz thick smear and Indirect Haemagglutination Assay were the techniques employed. Data indicate a progressive decline in prevalence of S. mansoni throughout the 1980s and the 1990s, a recrudescence in the early 2000s, and a more marked decrease following the implementation of six rounds of mass treatment with praziquantel from 2007 to 2013. Latest parasitological prevalence (2011) was 0%, while latest serological prevalence (2014) was 0.11%. Transmission of schistosomiasis has reached very low levels in Oman. Elimination criteria established by the Ministry of Health of Oman (parasitological prevalence ≤ 1% and serological prevalence ≤ 5%) have been met since 2008. Further investigations are required to assess whether interruption of transmission has been achieved in some or all foci, in view of the establishment of a formal verification process under the auspices of WHO.

Long-Term Frozen Storage of Urine Samples: A Trouble to Get PCR Results in Schistosoma spp. DNA Detection?

PubMed Central

Fernández-Soto, Pedro; Velasco Tirado, Virginia; Carranza Rodríguez, Cristina; Pérez-Arellano, José Luis; Muro, Antonio

2013-01-01

Background Human schistosomiasis remains a serious worldwide public health problem. At present, a sensitive and specific assay for routine diagnosis of schistosome infection is not yet available. The potential for detecting schistosome-derived DNA by PCR-based methods in human clinical samples is currently being investigated as a diagnostic tool with potential application in routine schistosomiasis diagnosis. Collection of diagnostic samples such as stool or blood is usually difficult in some populations. However, urine is a biological sample that can be collected in a non-invasive method, easy to get from people of all ages and easy in management, but as a sample for PCR diagnosis is still not widely used. This could be due to the high variability in the reported efficiency of detection as a result of the high variation in urine samples’ storage or conditions for handling and DNA preservation and extraction methods. Methodology/Principal Findings We evaluate different commercial DNA extraction methods from a series of long-term frozen storage human urine samples from patients with parasitological confirmed schistosomiasis in order to assess the PCR effectiveness for Schistosoma spp. detection. Patientś urine samples were frozen for 18 months up to 7 years until use. Results were compared with those obtained in PCR assays using fresh healthy human urine artificially contaminated with Schistosoma mansoni DNA and urine samples from mice experimentally infected with S. mansoni cercariae stored frozen for at least 12 months before use. PCR results in fresh human artificial urine samples using different DNA based extraction methods were much more effective than those obtained when long-term frozen human urine samples were used as the source of DNA template. Conclusions/Significance Long-term frozen human urine samples are probably not a good source for DNA extraction for use as a template in PCR detection of Schistosoma spp., regardless of the DNA method of

Schistosoma mansoni Infection Can Jeopardize the Duration of Protective Levels of Antibody Responses to Immunizations against Hepatitis B and Tetanus Toxoid.

PubMed

Riner, Diana K; Ndombi, Eric M; Carter, Jennifer M; Omondi, Amos; Kittur, Nupur; Kavere, Emmy; Korir, Harrison K; Flaherty, Briana; Karanja, Diana; Colley, Daniel G

2016-12-01

Schistosomiasis is a disease of major public health importance in sub-Saharan Africa. Immunoregulation begins early in schistosome infection and is characterized by hyporesponsiveness to parasite and bystander antigens, suggesting that a schistosome infection at the time of immunization could negatively impact the induction of protective vaccine responses. This study examined whether having a Schistosoma mansoni infection at the time of immunization with hepatitis B and tetanus toxoid (TT) vaccines impacts an individual's ability to achieve and maintain protective antibody levels against hepatitis B surface antigen or TT. Adults were recruited from Kisumu Polytechnic College in Western Kenya. At enrollment, participants were screened for schistosomiasis and soil transmitted helminths (STHs) and assigned to groups based on helminth status. The vaccines were then administered and helminth infections treated a week after the first hepatitis B boost. Over an 8 month period, 3 blood specimens were obtained for the evaluation of humoral and cytokine responses to the vaccine antigens and for immunophenotyping. 146 individuals were available for final analysis and 26% were S. mansoni positive (Sm+). Schistosomiasis did not impede the generation of initial minimum protective antibody levels to either hepatitis B or TT vaccines. However, median hepatitis B surface antibody levels were significantly lower in the Sm+ group after the first boost and remained lower, but not significantly lower, following praziquantel (PZQ) treatment and final boost. In addition, 8 months following TT boost and 7 months following PZQ treatment, Sm+ individuals were more likely to have anti-TT antibody levels fall below levels considered optimal for long term protection. IL-5 levels in response to in vitro TT stimulation of whole blood were significantly higher in the Sm+ group at the 8 month time period as well. Individuals with schistosomiasis at the start the immunizations were capable of

Schistosoma mansoni Infection Can Jeopardize the Duration of Protective Levels of Antibody Responses to Immunizations against Hepatitis B and Tetanus Toxoid

PubMed Central

Riner, Diana K.; Ndombi, Eric M.; Carter, Jennifer M.; Omondi, Amos; Kittur, Nupur; Kavere, Emmy; Korir, Harrison K.; Flaherty, Briana; Karanja, Diana; Colley, Daniel G.

2016-01-01

Background Schistosomiasis is a disease of major public health importance in sub-Saharan Africa. Immunoregulation begins early in schistosome infection and is characterized by hyporesponsiveness to parasite and bystander antigens, suggesting that a schistosome infection at the time of immunization could negatively impact the induction of protective vaccine responses. This study examined whether having a Schistosoma mansoni infection at the time of immunization with hepatitis B and tetanus toxoid (TT) vaccines impacts an individual’s ability to achieve and maintain protective antibody levels against hepatitis B surface antigen or TT. Methods Adults were recruited from Kisumu Polytechnic College in Western Kenya. At enrollment, participants were screened for schistosomiasis and soil transmitted helminths (STHs) and assigned to groups based on helminth status. The vaccines were then administered and helminth infections treated a week after the first hepatitis B boost. Over an 8 month period, 3 blood specimens were obtained for the evaluation of humoral and cytokine responses to the vaccine antigens and for immunophenotyping. Results 146 individuals were available for final analysis and 26% were S. mansoni positive (Sm+). Schistosomiasis did not impede the generation of initial minimum protective antibody levels to either hepatitis B or TT vaccines. However, median hepatitis B surface antibody levels were significantly lower in the Sm+ group after the first boost and remained lower, but not significantly lower, following praziquantel (PZQ) treatment and final boost. In addition, 8 months following TT boost and 7 months following PZQ treatment, Sm+ individuals were more likely to have anti-TT antibody levels fall below levels considered optimal for long term protection. IL-5 levels in response to in vitro TT stimulation of whole blood were significantly higher in the Sm+ group at the 8 month time period as well. Conclusions Individuals with schistosomiasis at the

Infection with Schistosoma mansoni has an Effect on Quality of Life, but not on Physical Fitness in Schoolchildren in Mwanza Region, North-Western Tanzania: A Cross-Sectional Study

PubMed Central

Kinung’hi, Safari; Magnussen, Pascal; Kaatano, Godfrey

2016-01-01

Background Infection with Schistosoma mansoni negatively impact children’s physical health and may influence their general well-being. The aim of this study was to investigate the effect of S. mansoni infections on a panel of morbidity indicators with emphasis on quality of life (PedsQL; measured in four different dimensions) and physical fitness (measured as VO2 max) among 572 schoolchildren aged 7–8 years. Methodology/Principal findings Prevalence of S. mansoni infections was 58.7%, with an arithmetic mean (95% CI) among positives of 207.3 (169.2–245.4) eggs per gram (epg). Most infections were light (56.5%), while 16.4% had heavy infections. Girls had significantly higher arithmetic mean intensities (95% CI) than boys (247.4 (189.2–305.6) vs. 153.2 (110.6–195.8); P = 0.004). A total of 30.1% were anaemic with no sex difference. Stunting and wasting was found in less than 10% of the population. There was no association between S. mansoni prevalence or intensities and the following parameters: anthropometry, anaemia, liver or spleen pathology in neither univariable nor multivariable linear regression analyses. However, in univariable analyses children with S. mansoni infection had a significantly lower score in emotional PedsQL (95% CI) than uninfected (77.3 (74.5–80.1) vs. 82.7 (79.9–85.5); P = 0.033) and infected children had a higher VO2 max (95% CI) compared to uninfected (51.4 (51.0–51.8) vs. 50.8 (50.3–51.3); P = 0.042). In multivariable linear regression analyses, age, S. mansoni infection, haemoglobin and VO2 max were significant predictors for emotional PedsQL while significant predictors for VO2 max were physical PedsQL, height, age and haemoglobin. S. mansoni infection was thus not retained in the multivariable regression analyses on VO2 max. Conclusions/Significance Of the measured morbidity parameters, S. mansoni infection had a significant effect on the emotional dimension of quality of life, but not on physical fitness. If Peds

Quality control of Kato slide counts for Schistosoma mansoni: a review of 12 years' experience in Kenya.

PubMed Central

Sturrock, R. F.; Ouma, J. H.; Kariuki, H. C.; Thiongo, F. W.; Koech, D. K.; Butterworth, A. E.

1997-01-01

A total of 19 annual or biannual audits were performed over a 12-year period by an independent microscopist on randomized subsamples of Kato slides examined for Schistosoma mansoni eggs by Kenyan microscopists from the Division of Vector-borne Diseases (DVBD). The recounts were invariably lower than the originals owing to some deterioration of the preparations between counts, but the two were strongly correlated: significant regressions of recounts on counts taking up 80-90% of the observed variance. Observer bias differed significantly between microscopists but remained stable over time, whereas repeatability of recounts on counts dropped slightly in periods of maximum work load but did not vary systematically with time. Approximately 7% of the counts and recounts disagreed on the presence or absence of eggs, but less than a third of these were negatives that were found positive on recount. False negatives dropped to 1.3% if duplicate counts were considered. The performance of the Kenyan microscopists was remarkably high and consistent throughout the 12-year period. This form of quality control is suitable for projects where limited funds preclude full-time supervisors using more sophisticated systems. PMID:9447781

Is PCR the Next Reference Standard for the Diagnosis of Schistosoma in Stool? A Comparison with Microscopy in Senegal and Kenya.

PubMed

Meurs, Lynn; Brienen, Eric; Mbow, Moustapha; Ochola, Elizabeth A; Mboup, Souleymane; Karanja, Diana M S; Secor, W Evan; Polman, Katja; van Lieshout, Lisette

2015-01-01

The current reference test for the detection of S. mansoni in endemic areas is stool microscopy based on one or more Kato-Katz stool smears. However, stool microscopy has several shortcomings that greatly affect the efficacy of current schistosomiasis control programs. A highly specific multiplex real-time polymerase chain reaction (PCR) targeting the Schistosoma internal transcriber-spacer-2 sequence (ITS2) was developed by our group a few years ago, but so far this PCR has been applied mostly on urine samples. Here, we performed more in-depth evaluation of the ITS2 PCR as an alternative method to standard microscopy for the detection and quantification of Schistosoma spp. in stool samples. Microscopy and PCR were performed in a Senegalese community (n = 197) in an area with high S. mansoni transmission and co-occurrence of S. haematobium, and in Kenyan schoolchildren (n = 760) from an area with comparatively low S. mansoni transmission. Despite the differences in Schistosoma endemicity the PCR performed very similarly in both areas; 13-15% more infections were detected by PCR when comparing to microscopy of a single stool sample. Even when 2-3 stool samples were used for microscopy, PCR on one stool sample detected more infections, especially in people with light-intensity infections and in children from low-risk schools. The low prevalence of soil-transmitted helminthiasis in both populations was confirmed by an additional multiplex PCR. The ITS2-based PCR was more sensitive than standard microscopy in detecting Schistosoma spp. This would be particularly useful for S. mansoni detection in low transmission areas, and post-control settings, and as such improve schistosomiasis control programs, epidemiological research, and quality control of microscopy. Moreover, it can be complemented with other (multiplex real-time) PCRs to detect a wider range of helminths and thus enhance effectiveness of current integrated control and elimination strategies for neglected

Thioredoxin Glutathione Reductase as a Novel Drug Target: Evidence from Schistosoma japonicum

PubMed Central

Xie, ShuYing; Qian, ChunYan; Wang, Jie; Zhang, Wei; Yin, XuRen; Hua, ZiChun; Yu, ChuanXin

2012-01-01

Background Schistosomiasis remains a major public health concern affecting billions of people around the world. Currently, praziquantel is the only drug of choice for treatment of human schistosomiasis. The emergence of drug resistance to praziquantel in schistosomes makes the development of novel drugs an urgent task. Thioredoxin glutathione reductase (TGR) enzymes in Schistosoma mansoni and some other platyhelminths have been identified as alternative targets. The present study was designed to confirm the existense and the potential value of TGR as a target for development of novel antischistosomal agents in Schistosoma japonicum, a platyhelminth endemic in Asia. Methods and Findings After cloning the S. japonicum TGR (SjTGR) gene, the recombinant SjTGR selenoprotein was purified and characterized in enzymatic assays as a multifunctional enzyme with thioredoxin reductase (TrxR), glutathione reductase (GR) and glutaredoxin (Grx) activities. Immunological and bioinformatic analyses confirmed that instead of having separate TrxR and GR proteins in mammalian, S. japonicum only encodes TGR, which performs the functions of both enzymes and plays a critical role in maintaining the redox balance in this parasite. These results were in good agreement with previous findings in Schistosoma mansoni and some other platyhelminths. Auranofin, a known inhibitor against TGR, caused fatal toxicity in S. japonicum adult worms in vitro and reduced worm and egg burdens in S. japonicum infected mice. Conclusions Collectively, our study confirms that a multifunctional enzyme SjTGR selenoprotein, instead of separate TrxR and GR enzymes, exists in S. japonicum. Furthermore, TGR may be a potential target for development of novel agents against schistosomes. This assumption is strengthened by our demonstration that the SjTGR is an essential enzyme for maintaining the thiol-disulfide redox homeostasis of S. japonicum. PMID:22384025

Interventions for treating schistosomiasis mansoni.

PubMed

Saconato, H; Atallah, A

2000-01-01

Schistosomiasis is a parasite that is carried by freshwater snails. The intestinal form infects the intestine, liver and spleen and can be fatal. The objective of this review was to assess the effects of oxamniquine or praziquantel for treating Schistosomiasis mansoni We searched the Cochrane Infectious Diseases Group trials register, the Cochrane Controlled Trials Register, Medline, Lilacs and reference lists of articles. The Revista da Sociedade Brasileira de Medicina Tropical and Brazilian Tropical Medicine Congress abstracts were handsearched Randomised and quasi-randomised trials comparing oxamniquine and/or praziquantel to placebo for the treatment of Schistosomiasis mansoni. Two reviewers independently assessed trial quality and extracted data. Thirteen trials met the inclusion criteria. Praziquantel and oxamniquine were effective in curing Schistosoma mansoni infection when compared to placebo. In Africa, praziquantel 40 mg/Kg is more effective than oxamniquine 15 mg/Kg in individuals older than 14 years (OR 3.54, 95%CI 1.70, 7.38), but no difference was found when compared with oxamniquine 30 mg/Kg (OR 0.29, 95%CI 0.08, 1.01). In Brazil, praziquantel was equally effective when compared with oxamniquine in individuals older than 14 years (OR 1.70, 95%CI 0.83, 3.49). Both drugs appear safe. There was no difference in reinfection rate between zinc supplementation and placebo (OR 0.82, 95%CI 0.47, 1.41). IPraziquantel and oxamniquine both appear to be effective for the treatment of Schistosomiasis mansoni, although lower doses of oxamniquine (less than 30 milligrams per kilogram) may not be as effective.

Anthelmintic activity in vitro and in vivo of Baccharis trimera (Less) DC against immature and adult worms of Schistosoma mansoni.

PubMed

de Oliveira, Rosimeire Nunes; Rehder, Vera Lúcia Garcia; Oliveira, Adriana Silva Santos; Jeraldo, Veronica de Lourdes Sierpe; Linhares, Arício Xavier; Allegretti, Silmara Marques

2014-04-01

Although its efficiency against all Schistosoma species, praziquantel (PZQ) shows low efficacy against schistosomula and juvenile stages. The potential for development of resistance to PZQ has justified the search for new alternative chemotherapies. In this scenario, studies to new formulations, more comprehensive and without adverse effects, are being conducted. One viable and promising treatment is the study of medicinal plants as a new approach to the experimental treatment for Schistosomiasis. Amongst all the variety of the medicinal species studied, we can highlight Baccharis trimera (Less) DC, known as "Carqueja-amarga". This paper not only describes the effect of crude dichloromethane extract (DE) and aqueous fraction (AF) obtained from B. trimera, in vitro but also is the first one that investigates the in vivo efficacy of B. trimera against schistosomula, juvenile and adult worms of Schistosoma mansoni BH strain. In the experiment, mice were treated with DE, AF and PZQ (40 and 200mg/kg) over the period of larval development (3 and 30 post-infection; pi), and adult worms (60days post-infection; pi). The in vitro results show that the DE and AF effects are dose-dependents, being the 130μg/mL the most effective one in a shorter period of incubation. The exposure of the in vitro samples over adult parasites were able to inhibit 100% of the oviposition in females. Likewise caused the mortality of the parasites with morphological alterations on the tegument, on the suckers, oral and acetabulum, in both males and females after 6-72h of exposure. Additionally, the in vivo treatments against juvenile and adult infection were more effective compared to the control group untreated. Administrations of AF and DE in day 30pi (juvenile worms) show female worm total burden reductions of 75% and 68% respectively. At the same period of infection reductions of respectively 98% and 97% egg/g in the faeces were seen. In relation to the different egg developmental stages

A new focus of schistosomiasis mansoni in Hayk town, northeastern Ethiopia.

PubMed

Amsalu, Gashaw; Mekonnen, Zeleke; Erko, Berhanu

2015-02-03

The endemicity of human schistosomiasis has long been established in Ethiopia, and new foci have also been continuously reported.The objective of this study was to determine the transmission and magnitude of schistosomiasis in Hayk area, northeastern Ethiopia. A cross sectional parasitological survey involving 384 school children was conducted for intestinal schistosomiasis between January and March 2010 in two primary schools in Hayk area, northeastern Ethiopia. The stool samples were processed for microscopic examination using Kato-Katz technique. Malacological survey and observation on human water contact activities were also carried out. Snails were checked for schistosome infection by shedding and lab-bred mice were exposed to the cercariae shed from Biomphalaria pfeifferi en masse. Adult Schistosoma mansoni worms were harvested from the mice after 45 days of exposure to the schistosome cercariae. The overall prevalence and intensity of intestinal schistosomiasis among school children in Hayk Number 1 and Hayk Number 2 Primary Schools was found to be 45% and 161 epg, respectively. The prevalence of infection had relationship with age and sex. Males were more infected than females. Children in the age group 15-19 years had the highest infection rate, followed by 10-14 and 5-9 years age group. Schistosome infection in Biomphalaria pfeifferi was 3.2%. Schistosome infection was also established in laboratory-bred mice and adult Schistosoma mansoni worms were harvested. The observed intestinal schistosomiasis with prevalence of 45% among young children, collection of schistosome infected Biomphalaria pfeifferi, and the establishment of lab infection in mice showed that transmission of intestinal schistosomiasis is taking place in the area. Preventive chemotherapy with praziquantel should be immediately put in place to reduce morbidity and interrupt transmission of schistosomiasis in the area.

Comparison of individual and pooled stool samples for the assessment of intensity of Schistosoma mansoni and soil-transmitted helminth infections using the Kato-Katz technique.

PubMed

Kure, Ashenafi; Mekonnen, Zeleke; Dana, Daniel; Bajiro, Mitiku; Ayana, Mio; Vercruysse, Jozef; Levecke, Bruno

2015-09-24

Our group has recently provided a proof-of-principle for the examination of pooled stool samples using McMaster technique as a strategy for the rapid assessment of intensity of soil-transmitted helminth infections (STH, Ascaris lumbricoides, Trichuris trichiura and hookworm). In the present study we evaluated this pooling strategy for the assessment of intensity of both STH and Schistosoma mansoni infections using the Kato-Katz technique. A cross-sectional survey was conducted in 360 children aged 5-18 years from six schools in Jimma Zone (southwest Ethiopia). We performed faecal egg counts (FECs) in both individual and pooled samples (pools sizes of 5, 10 and 20) to estimate the number of eggs per gram of stool (EPG) using the Kato-Katz technique. We also assessed the time to screen both individual and pooled samples. Except for hookworms, there was a significant correlation (correlation coefficient = 0.53-0.95) between the mean of individual FECs and the FECs of pooled samples for A. lumbricoides, T. trichiura and S. mansoni, regardless of the pool size. Mean FEC were 2,596 EPG, 125 EPG, 47 EPG, and 41 EPG for A. lumbricoides, T. trichiura, S. mansoni and hookworm, respectively. There was no significant difference in FECs between the examination of individual and pooled stool samples, except for hookworms. For this STH, pools of 10 resulted in a significant underestimation of infection intensity. The total time to obtain individual FECs was 65 h 5 min. For pooled FECs, this was 19 h 12 min for pools of 5, 14 h 39 min for pools of 10 and 12 h 42 min for pools of 20. The results indicate that pooling of stool sample holds also promise as a rapid assessment of infections intensity for STH and S. mansoni using the Kato-Katz technique. In this setting, the time in the laboratory was reduced by 70 % when pools of 5 instead of individual stool samples were screened.

Biomphalaria glabrata transcriptome: cDNA microarray profiling identifies resistant- and susceptible-specific gene expression in haemocytes from snail strains exposed to Schistosoma mansoni

PubMed Central

Lockyer, Anne E; Spinks, Jenny; Kane, Richard A; Hoffmann, Karl F; Fitzpatrick, Jennifer M; Rollinson, David; Noble, Leslie R; Jones, Catherine S

2008-01-01

Background Biomphalaria glabrata is an intermediate snail host for Schistosoma mansoni, one of the important schistosomes infecting man. B. glabrata/S. mansoni provides a useful model system for investigating the intimate interactions between host and parasite. Examining differential gene expression between S. mansoni-exposed schistosome-resistant and susceptible snail lines will identify genes and pathways that may be involved in snail defences. Results We have developed a 2053 element cDNA microarray for B. glabrata containing clones from ORESTES (Open Reading frame ESTs) libraries, suppression subtractive hybridization (SSH) libraries and clones identified in previous expression studies. Snail haemocyte RNA, extracted from parasite-challenged resistant and susceptible snails, 2 to 24 h post-exposure to S. mansoni, was hybridized to the custom made cDNA microarray and 98 differentially expressed genes or gene clusters were identified, 94 resistant-associated and 4 susceptible-associated. Quantitative PCR analysis verified the cDNA microarray results for representative transcripts. Differentially expressed genes were annotated and clustered using gene ontology (GO) terminology and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analysis. 61% of the identified differentially expressed genes have no known function including the 4 susceptible strain-specific transcripts. Resistant strain-specific expression of genes implicated in innate immunity of invertebrates was identified, including hydrolytic enzymes such as cathepsin L, a cysteine proteinase involved in lysis of phagocytosed particles; metabolic enzymes such as ornithine decarboxylase, the rate-limiting enzyme in the production of polyamines, important in inflammation and infection processes, as well as scavenging damaging free radicals produced during production of reactive oxygen species; stress response genes such as HSP70; proteins involved in signalling, such as importin 7 and copine 1

Biomphalaria glabrata transcriptome: cDNA microarray profiling identifies resistant- and susceptible-specific gene expression in haemocytes from snail strains exposed to Schistosoma mansoni.

PubMed

Lockyer, Anne E; Spinks, Jenny; Kane, Richard A; Hoffmann, Karl F; Fitzpatrick, Jennifer M; Rollinson, David; Noble, Leslie R; Jones, Catherine S

2008-12-29

Biomphalaria glabrata is an intermediate snail host for Schistosoma mansoni, one of the important schistosomes infecting man. B. glabrata/S. mansoni provides a useful model system for investigating the intimate interactions between host and parasite. Examining differential gene expression between S. mansoni-exposed schistosome-resistant and susceptible snail lines will identify genes and pathways that may be involved in snail defences. We have developed a 2053 element cDNA microarray for B. glabrata containing clones from ORESTES (Open Reading frame ESTs) libraries, suppression subtractive hybridization (SSH) libraries and clones identified in previous expression studies. Snail haemocyte RNA, extracted from parasite-challenged resistant and susceptible snails, 2 to 24 h post-exposure to S. mansoni, was hybridized to the custom made cDNA microarray and 98 differentially expressed genes or gene clusters were identified, 94 resistant-associated and 4 susceptible-associated. Quantitative PCR analysis verified the cDNA microarray results for representative transcripts. Differentially expressed genes were annotated and clustered using gene ontology (GO) terminology and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analysis. 61% of the identified differentially expressed genes have no known function including the 4 susceptible strain-specific transcripts. Resistant strain-specific expression of genes implicated in innate immunity of invertebrates was identified, including hydrolytic enzymes such as cathepsin L, a cysteine proteinase involved in lysis of phagocytosed particles; metabolic enzymes such as ornithine decarboxylase, the rate-limiting enzyme in the production of polyamines, important in inflammation and infection processes, as well as scavenging damaging free radicals produced during production of reactive oxygen species; stress response genes such as HSP70; proteins involved in signalling, such as importin 7 and copine 1, cytoplasmic intermediate

Significant variance in genetic diversity among populations of Schistosoma haematobium detected using microsatellite DNA loci from a genome-wide database.

PubMed

Glenn, Travis C; Lance, Stacey L; McKee, Anna M; Webster, Bonnie L; Emery, Aidan M; Zerlotini, Adhemar; Oliveira, Guilherme; Rollinson, David; Faircloth, Brant C

2013-10-17

Urogenital schistosomiasis caused by Schistosoma haematobium is widely distributed across Africa and is increasingly being targeted for control. Genome sequences and population genetic parameters can give insight into the potential for population- or species-level drug resistance. Microsatellite DNA loci are genetic markers in wide use by Schistosoma researchers, but there are few primers available for S. haematobium. We sequenced 1,058,114 random DNA fragments from clonal cercariae collected from a snail infected with a single Schistosoma haematobium miracidium. We assembled and aligned the S. haematobium sequences to the genomes of S. mansoni and S. japonicum, identifying microsatellite DNA loci across all three species and designing primers to amplify the loci in S. haematobium. To validate our primers, we screened 32 randomly selected primer pairs with population samples of S. haematobium. We designed >13,790 primer pairs to amplify unique microsatellite loci in S. haematobium, (available at http://www.cebio.org/projetos/schistosoma-haematobium-genome). The three Schistosoma genomes contained similar overall frequencies of microsatellites, but the frequency and length distributions of specific motifs differed among species. We identified 15 primer pairs that amplified consistently and were easily scored. We genotyped these 15 loci in S. haematobium individuals from six locations: Zanzibar had the highest levels of diversity; Malawi, Mauritius, Nigeria, and Senegal were nearly as diverse; but the sample from South Africa was much less diverse. About half of the primers in the database of Schistosoma haematobium microsatellite DNA loci should yield amplifiable and easily scored polymorphic markers, thus providing thousands of potential markers. Sequence conservation among S. haematobium, S. japonicum, and S. mansoni is relatively high, thus it should now be possible to identify markers that are universal among Schistosoma species (i.e., using DNA sequences

Potential effects of Cramoll 1,4 lectin on murine Schistosomiasis mansoni.

PubMed

Melo, Cristiane Moutinho Lagos de; de Lima, Amanda Lucena Rosendo; Beltrão, Eduardo Isidoro Carneiro; Cavalcanti, Carmelita C Bezerra; de Melo-Júnior, Mário Ribeiro; Montenegro, Silvia Maria L; Coelho, Luana Cassandra B Barroso; Correia, Maria Tereza dos Santos; Carneiro-Leão, Ana Maria dos Anjos

2011-05-01

Cratylia mollis is a natural forage plant from the Northeast of Brazil. C. mollis seed lectin (Cramoll) containing molecular forms 1 and 4 (Cramoll 1,4) has shown anti-inflammatory and wound-healing activities. This work analyzed the effect of Cramoll 1,4 on experimental schistosomiasis in mice. Experimental groups (n=15/group) were composed of female albino Swiss mice, which were subcutaneously and caudally infected with Schistosoma mansoni (BH strain, 100 cercariae/mouse) and were treated with an intraperitoneal dose after infection as follows: (1) Cramoll 1,4 (50 mg kg(-1) single dose - after 40 days of infection), (2) Cramoll 1,4 (7 mg kg(-1) daily dose - for 7 days after infection) and control (untreated mice). Mice were sacrificed 8 weeks after infection and adult worms were recovered from the portal-hepatic system. Livers were fixed in 10% (v/v) formaldehyde/0.15M NaCl and tissue sections were processed for haematoxilin and Masson's trichrome stainings. Mice infected subcutaneously harboured no or very few worms and hence the effect of Cramoll 1,4 could not be assessed. Results (P≤0.05) were obtained with Cramoll 1,4 using the two treatments, with reduction of: egg excretion (79 and 80%), adult worm recovery (71 and 79%) and liver granulomas (40 and 73.5%) in relation to control. This study showed the potential anti-helminthic activity of Cramoll 1,4 when tested against Schistosomiasis mansoni infection in mice. Copyright © 2011 Elsevier B.V. All rights reserved.

The potential role of Morus alba leaves extract on the brain of mice infected with Schistosoma mansoni.

PubMed

Bauomy, Amira A

2014-01-01

Schistosomiasis is a neglected tropical disease which is associated with neuropsychiatric and neuropathological disorders. Herein, the main goal of the presented work is to investigate the effect of Morus alba leaves extract in mice brain infected with Schistosoma mansoni. Since, the resistance of Schistosomes to antischistosomal drug (praziquantel) has been examined, schistosomiasis induced brain oxidative stress as evidenced by the decrease of glutathione level, total antioxidant capacity and the activity of catalase significantly, while a significant elevation in the levels of nitrite/nitrate and malondialdhyde. In addition, the infection resulted in neurochemical disturbances, the main inhibitory amino acid, γ- aminobutyric acid level was decreased. In contrast, the level of chloride ions and acetylcholine esterase activity were significantly increased. Moreover, the histopathological section showed some impairments in the brain. The treatment with Morus alba leaves extract ameliorated the induced disturbances in schistosome-infected mice where the levels of non-enzymatic and enzymatic antioxidants were elevated. On the other hand, the levels of nitrite/nitrate and malondialdhyde were significantly reduced. Likewise, treatment of mice with Morus alba leaves extract improved the altered levels of γ- aminobutyric acid level and chloride ion. Also, it improved the recorded impairments of the histopathological section in the brain of schistosome infected mice.

Ultrastructural analysis of β-lapachone-induced surface membrane damage in male adult Schistosoma mansoni BH strain worms.

PubMed

Aires, André de Lima; Ximenes, Eulália Camelo Pessoa Azevedo; Silva, Renata Alexandre Ramos; Barbosa, Vanessa Xavier; Góes, Alexandre José da Silva; Peixoto, Christina Alves; Souza, Valdênia Maria Oliveira; Albuquerque, Mônica Camelo Pessôa de Azevedo

2014-07-01

The present study provides, for the first time, conclusions on the in vitro schistosomicidal properties of β-lap. Adult male Schistosoma mansoni worms of the BH strain were used for the study. Motility, mortality, cell viability and alterations in the tegument were employed as schistosomicidal parameters. Alterations in motility were observed 6h after incubation in concentrations of 50 and 100 μM. β-lap decreased significantly the worm viability, reducing the formation of formazan in 17.7%, 27.4% and 54.8% at concentrations of 25, 50 and 100 μM, respectively. Mortality in concentrations of 50 and 100 μM was of 67% and 100%, respectively, after 24h. The death of the parasite was preceded by progressive surface membrane damage, characterized by tegument peeling, spine reduction and erosion, blister formation and rupture, and the emergence of holes. In addition to this, in the anterior portion, intense general edema, areas of cracking with a wrinkled surface, furrows and a fibrous appearance were also observed. The results of the present study thus provide a sound basis for further in-depth studies of the schistosomicidal properties of β-lap, both in the laboratory and in the field. Copyright © 2014 Elsevier Inc. All rights reserved.

Rapid assessment of Schistosoma mansoni: the validity, applicability and cost-effectiveness of the Lot Quality Assurance Sampling method in Uganda

PubMed Central

Brooker, Simon; Kabatereine, Narcis B.; Myatt, Mark; Stothard, J. Russell; Fenwick, Alan

2007-01-01

Summary Rapid and accurate identification of communities at highest risk of morbidity from schistosomiasis is key for sustainable control. Although school questionnaires can effectively and inexpensively identify communities with a high prevalence of Schistosoma haematobium, parasitological screening remains the preferred option for S. mansoni. To help reduce screening costs, we investigated the validity of Lot Quality Assurance Sampling (LQAS) in classifying schools according categories of S. mansoni prevalence in Uganda, and explored its applicability and cost-effectiveness. First, we evaluated several sampling plans using computer simulation and then field tested one sampling plan in 34 schools in Uganda. Finally, cost-effectiveness of different screening and control strategies (including mass treatment without prior screening) was determined, and sensitivity analysis undertaken to assess the effect of infection levels and treatment costs. In identifying schools with prevalence ≥50%, computer simulations showed that LQAS had high levels of sensitivity and specificity (>90%) at sample sizes <20. The method also provides an ability to classify communities into three prevalence categories. Field testing showed that LQAS where 15 children were sampled had excellent diagnostic performance (sensitivity: 100%, specificity: 96.4%, positive predictive value: 85.7% and negative predictive value: 92.3%). Screening using LQAS was more cost-effective than mass treating all schools (US$ 218 vs. US$ 482 / high prevalence school treated). Threshold analysis indicated that parasitological screening and mass treatment would become equivalent for settings where prevalence exceeds 50% in 75% of schools and for treatment costs of US$ 0.19 per schoolchild. We conclude that, in Uganda, LQAS provides a rapid, valid, and cost-effective method for guiding decision makers in allocating finite resources for the control of schistosomiasis. PMID:15960703

Rapid assessment of Schistosoma mansoni: the validity, applicability and cost-effectiveness of the Lot Quality Assurance Sampling method in Uganda.

PubMed

Brooker, Simon; Kabatereine, Narcis B; Myatt, Mark; Russell Stothard, J; Fenwick, Alan

2005-07-01

Rapid and accurate identification of communities at highest risk of morbidity from schistosomiasis is key for sustainable control. Although school questionnaires can effectively and inexpensively identify communities with a high prevalence of Schistosoma haematobium, parasitological screening remains the preferred option for S. mansoni. To help reduce screening costs, we investigated the validity of Lot Quality Assurance Sampling (LQAS) in classifying schools according to categories of S. mansoni prevalence in Uganda, and explored its applicability and cost-effectiveness. First, we evaluated several sampling plans using computer simulation and then field tested one sampling plan in 34 schools in Uganda. Finally, cost-effectiveness of different screening and control strategies (including mass treatment without prior screening) was determined, and sensitivity analysis undertaken to assess the effect of infection levels and treatment costs. In identifying schools with prevalences > or =50%, computer simulations showed that LQAS had high levels of sensitivity and specificity (>90%) at sample sizes <20. The method also provides an ability to classify communities into three prevalence categories. Field testing showed that LQAS where 15 children were sampled had excellent diagnostic performance (sensitivity: 100%, specificity: 96.4%, positive predictive value: 85.7% and negative predictive value: 92.3%). Screening using LQAS was more cost-effective than mass treating all schools (US$218 vs. US$482/high prevalence school treated). Threshold analysis indicated that parasitological screening and mass treatment would become equivalent for settings where prevalence > or =50% in 75% of schools and for treatment costs of US$0.19 per schoolchild. We conclude that, in Uganda, LQAS provides a rapid, valid and cost-effective method for guiding decision makers in allocating finite resources for the control of schistosomiasis.

Proteome analysis of the cardiac and pericardial tissue of Biomphalaria tenagophila populations susceptible and resistant to Schistosoma mansoni infection.

PubMed

Jannotti-Passos, Liana K; Andrade, Hélida M; Caldeira, Roberta L; Romanha, Alvaro J; Murta, Silvane M F; Chapeaurouge, Donat A; Perales, Jonas; Coelho, Paulo Marcos Z; Carvalho, Omar S

2008-03-01

For a better comprehension of the parasite-host interaction, proteins expressed by the cardiac and pericardial tissues were compared between susceptible (Cabo Frio) and resistant (Taim) Biomphalaria tenagophila populations, challenged (c) and non-challenged (nc) with Schistosoma mansoni. Proteins were separated by two-dimensional gel electrophoresis (2DE) and stained with Coomassie blue. A total of 146 and 135 spots were observed in Cabo Frio (CFnc) and in Taim (Tnc) non-challenged populations, respectively, whereas 153 spots were detected in both Cabo Frio (CFc) and Taim (Tc) challenged populations. Regarding comparisons between CFnc and CFc, the numbers of exclusive spots obtained were one and nine, respectively, whereas Tnc yielded 17 and Tc eight exclusive spots. By comparing the total of spots in CF (nc+c) with T (nc+c) populations, we obtained: four exclusive spots for CFc; zero for CFnc; four for Tc and; one for Tnc. A quantitative comparison (reason>2.5) of the total spots of CF (nc+c) with T (nc+c) populations allowed us to distinguish five more intense spots for Tc, 14 for Tnc, 15 for CFnc and 11 for CFc. In the CFnc population, two proteins were identified: actin and ATP synthase alpha chain; in the CFc population, four proteins: actin, calmodulin, HSP70, and dehydrogenase; in the Tnc population, five proteins: matrilin, HSP70, actin, ATP synthase alpha chain and intermediate filament of the protein; and in the Tc population, three proteins: actin, alpha-S1 casein and ATP synthase alpha chain. Out of a total of 79 spots, only nine proteins were identified due to the low number of available nucleotide sequences in the GenBank. Nevertheless, knowing proteins regarded as differentially expressed is indispensable for hitherto unidentified genes implicated in B. tenagophila resistance and or susceptibility to S. mansoni infection.

Antischistosomal activity of ginger (Zingiber officinale) against Schistosoma mansoni harbored in C57 mice.

PubMed

Mostafa, Osama M S; Eid, Refaat A; Adly, Mohamed A

2011-08-01

The repeated chemotherapy of schistosomiasis has resulted in the emergence of drug-resistant schistosome strains. The development of such resistance has drawn the attention of many authors to alternative drugs. Many medicinal plants were studied to investigate their antischistosomal potency. The present work aimed to evaluate antischistosomal activity of crude aqueous extract of ginger against Schistosoma mansoni. Sixteen mice of C57 strain were exposed to 100 ± 10 cercariae per mouse by the tail immersion method; the mice were divided into two groups: untreated group and ginger-treated one. All mice were sacrificed at the end of 10th week post-infection. Worm recovery and egg counting in the hepatic tissues and faeces were determined. Surface topography of the recovered worms was studied by scanning electron microscopy. Histopathological examination of liver and intestine was done using routine histological procedures. The worm burden and the egg density in liver and faeces of mice treated with ginger were fewer than in non-treated ones. Scanning electron microscopical examination revealed that male worms recovered from mice treated with ginger lost their normal surface architecture, since its surface showed partial loss of tubercles' spines, extensive erosion in inter-tubercle tegumental regions and numerous small blebs around tubercles. Histopathological data indicated a reduction in the number and size of granulomatous inflammatory infiltrations in the liver and intestine of treated mice compared to non-treated mice. The results of the present work suggested that ginger has antischistosomal activities and provided a basis for subsequent experimental and clinical trials.

Integrated multi-omic analyses in Biomphalaria-Schistosoma dialogue reveal the immunobiological significance of FREP-SmPoMuc interaction.

PubMed

Portet, Anaïs; Pinaud, Silvain; Tetreau, Guillaume; Galinier, Richard; Cosseau, Céline; Duval, David; Grunau, Christoph; Mitta, Guillaume; Gourbal, Benjamin

2017-10-01

The fresh water snail Biomphalaria glabrata is one of the vectors of the trematode pathogen Schistosoma mansoni, which is one of the agents responsible of human schistosomiasis. In this host-parasite interaction, co-evolutionary dynamic results into an infectivity mosaic known as compatibility polymorphism. Integrative approaches including large scale molecular approaches have been conducted in recent years to improve our understanding of the mechanisms underlying compatibility. This review presents the combination of integrated Multi-Omic approaches leading to the discovery of two repertoires of polymorphic and/or diversified interacting molecules: the parasite antigens S. mansoni polymorphic mucins (SmPoMucs) and the B. glabrata immune receptors fibrinogen-related proteins (FREPs). We argue that their interactions may be major components for defining the compatible/incompatible status of a specific snail/schistosome combination. Copyright © 2017 Elsevier Ltd. All rights reserved.

Comparative in vivo antioxidant levels in Schistosoma mansoni infected mice treated with praziquantel or the essential oil of Melaleuca armillaris leaves.

PubMed

Rizk, M; Ibrahim, N; El-Rigal, N

2012-10-15

Plant extracts are continuously investigated for their extensive inclusion of biologically active constituents that exert therapeutic activities against many diseases. The aim of this study was to assess the antioxidant/anti-schistosomal activities of the essential oil of the fresh leaves of Melaleuca armillaris (M. armillaris) compared to Praziquantel (PZQ) on normal and Schistosoma mansoni-infected mice. The oil was isolated by hydrodistillation and analyzed by gas chromatography/mass spectrometry (GC/MS). The oil was rich in 1,8-cineole (33.93%), terpinen-4-ol (18.79%), limonene (10.37%) and B-pinene (6.59%). M. armillaris oil (150 mg kg(-1), orally) was administered from the second week post infection twice per week for six weeks. PZQ (500 mg kg(-1), orally) was administered for two successive days 8 weeks post infection and mice sacrificed one week later. Total protein, Malondialdehyde (MDA), Glutathione (GSH), vitamins C and E, the antioxidant enzymes catalase and superoxide dismutase, as well as liver weights and liver/body weight were determined in the liver tissues. Results showed that, both treatments significantly ameliorated the disturbed levels ofGSH and MDA in infected mice. Both vitamins were significantly elevated after treatment with the oil while a significant increase in catalase accompanied by a pronounced decrease in SOD were obtained after treatment with PZQ. Both treatments markedly improved liver and body weights in infected mice compared to the infected-untreated ones. In conclusion, natural plant sources may be used as promising alternative agents to chemical drugs for schistosomiasis treatment, since the latter may result in drug-induced resistance arising from repeated use.

Evaluation of the Schistosoma mansoni Y-box-binding protein (SMYB1) potential as a vaccine candidate against schistosomiasis.

PubMed

Dias, Sílvia R C; Boroni, Mariana; Rocha, Elizângela A; Dias, Thomaz L; de Laet Souza, Daniela; Oliveira, Fabrício M S; Bitar, Mainá; Macedo, Andrea M; Machado, Carlos R; Caliari, Marcelo V; Franco, Glória R

2014-01-01

Schistosomiasis is a neglected tropical disease, and after malaria, is the second most important tropical disease in public health. A vaccine that reduces parasitemia is desirable to achieve mass treatment with a low cost. Although potential antigens have been identified and tested in clinical trials, no effective vaccine against schistosomiasis is available. Y-box-binding proteins (YBPs) regulate gene expression and participate in a variety of cellular processes, including transcriptional and translational regulation, DNA repair, cellular proliferation, drug resistance, and stress responses. The Schistosoma mansoni ortholog of the human YB-1, SMYB1, is expressed in all stages of the parasite life cycle. Although SMYB1 binds to DNA or RNA oligonucleotides, immunohistochemistry assays demonstrated that it is primarily localized in the cytoplasm of parasite cells. In addition, SMYB1 interacts with a protein involved in mRNA processing, suggesting that SMYB1 functions in the turnover, transport, and/or stabilization of RNA molecules during post-transcriptional gene regulation. Here we report the potential of SMYB1 as a vaccine candidate. We demonstrate that recombinant SMYB1 stimulates the production of high levels of specific IgG1 antibodies in a mouse model. The observed levels of specific IgG1 and IgG2a antibodies indicate an actual protection against cercariae challenge. Animals immunized with rSMYB1 exhibited a 26% reduction in adult worm burden and a 28% reduction in eggs retained in the liver. Although proteins from the worm tegument are considered optimal targets for vaccine development, this study demonstrates that unexposed cytoplasmic proteins can reduce the load of intestinal worms and the number of eggs retained in the liver.

Biochemical changes after subchronic and chronic interaction of Schistosoma mansoni infection in Swiss albino mice with two specific compounds.

PubMed

Hanna, Laila S; Medhat, Amina M; Abdel-Menem, Hanan A

2003-04-01

In Egypt, infection with Schistosoma mansoni (S.m.) and residues of pesticides have been considered as major environmental pollutants that adversely affect health. Effects of diazinon (DZN) and/or praziquantel (PZQ) on the levels of plasma triiodothyronine (T3), thyroxine (T4), activities of brain acetylcholinesterase (AchE) and liver alanine aminotransferase (ALT) in addition to blood reduced glutathione (GSH) in healthy and S.m. infected mice were investigated after 9 and 17 weeks of either infection or intoxication with DZN. Triiodothyronine showed significant differences among the different treatments. The group of mice treated with PZQ showed the highest levels of T3 at both time intervals. Thyroxine level showed significant differences between the two time intervals. The lowest levels of T4 were observed in the infected-PZQ group at week 17. The maximum inhibition of brain AchE activity was noticed in DZN-PZQ treated group after 9 and 17 weeks. The different treatments significantly reduced the activities of liver ALT. The highest decrease was recorded in the infected-DZN-PZQ group at week 9. All treatments significantly lowered the levels of blood GSH after 9 weeks.

Controlled Chaos of Polymorphic Mucins in a Metazoan Parasite (Schistosoma mansoni) Interacting with Its Invertebrate Host (Biomphalaria glabrata)

PubMed Central

Roger, Emmanuel; Grunau, Christoph; Pierce, Raymond J.; Hirai, Hirohisa; Gourbal, Benjamin; Galinier, Richard; Emans, Rémi; Cesari, Italo M.; Cosseau, Céline; Mitta, Guillaume

2008-01-01

Invertebrates were long thought to possess only a simple, effective and hence non-adaptive defence system against microbial and parasitic attacks. However, recent studies have shown that invertebrate immunity also relies on immune receptors that diversify (e.g. in echinoderms, insects and mollusks (Biomphalaria glabrata)). Apparently, individual or population-based polymorphism-generating mechanisms exists that permit the survival of invertebrate species exposed to parasites. Consequently, the generally accepted arms race hypothesis predicts that molecular diversity and polymorphism also exist in parasites of invertebrates. We investigated the diversity and polymorphism of parasite molecules (Schistosoma mansoni Polymorphic Mucins, SmPoMucs) that are key factors for the compatibility of schistosomes interacting with their host, the mollusc Biomphalaria glabrata. We have elucidated the complex cascade of mechanisms acting both at the genomic level and during expression that confer polymorphism to SmPoMuc. We show that SmPoMuc is coded by a multi-gene family whose members frequently recombine. We show that these genes are transcribed in an individual-specific manner, and that for each gene, multiple splice variants exist. Finally, we reveal the impact of this polymorphism on the SmPoMuc glycosylation status. Our data support the view that S. mansoni has evolved a complex hierarchical system that efficiently generates a high degree of polymorphism—a “controlled chaos”—based on a relatively low number of genes. This contrasts with protozoan parasites that generate antigenic variation from large sets of genes such as Trypanosoma cruzi, Trypanosoma brucei and Plasmodium falciparum. Our data support the view that the interaction between parasites and their invertebrate hosts are far more complex than previously thought. While most studies in this matter have focused on invertebrate host diversification, we clearly show that diversifying mechanisms also exist on

High prevalence of Schistosoma mansoni and other intestinal parasites among elementary school children in Southwest Ethiopia: a cross-sectional study.

PubMed

Jejaw, Ayalew; Zemene, Endalew; Alemu, Yayehirad; Mengistie, Zemenu

2015-07-02

Intestinal parasitic infections (IPIs) pose significant public health challenges in school children in developing countries. The aim of this study is to determine prevalence of intestinal parasites among elementary school children in Mizan-Aman town, southwest Ethiopia. Institution-based cross-sectional study involving 460 elementary school children in Mizan-Aman Town was conducted from May to June 2013. The school children were selected using multistage sampling technique. Data on demography and predisposing factors of IPIs were collected using pretested questionnaire. Moreover, single stool specimen was examined microscopically after wet mount and formol-ether sedimentation concentration procedures. Infection intensity of Schistosoma mansoni and soil-transmitted helminths (STHs) was estimated using Kato-Katz egg counting method. Age of the children ranged from 5 to 17 years. Overall, 76.7% (95%CI: 72.8-80.6) of the children harbored at least one species of intestinal parasite. Eight species of intestinal parasites were detected with S. mansoni (44.8%) and Ascaris lumbricoides (28.7%) being predominant. Helminths and pathogenic intestinal protozoa were detected in 73.9 and 7.8% of the children, respectively. After adjusting for other variables, age between 5 and 9 years (AOR, 2.6, 95%CI, 1.552-4.298), male gender (AOR, 2.1, 95%CI, 1.222-3.526), attending public school (AOR, 0.1, 95%CI, 0.060-0.256), using river/well water (AOR, 2.4, 95%CI, 0.912-6.191), irregular washing of hands before meal (AOR, 0.5, 95%CI, 0.254-0.865), consuming street food (AOR, 2.3, 95%CI, 1.341-3.813) and raw vegetables (AOR, 2.7, 95%CI, 1.594-4.540) were significantly associated with IPIs in the study participants. Prevalence of intestinal parasites among the school children was high. Deworming of the school children and continuous follow up is required.

Interpreting ambiguous 'trace' results in Schistosoma mansoni CCA Tests: Estimating sensitivity and specificity of ambiguous results with no gold standard.

PubMed

Clements, Michelle N; Donnelly, Christl A; Fenwick, Alan; Kabatereine, Narcis B; Knowles, Sarah C L; Meité, Aboulaye; N'Goran, Eliézer K; Nalule, Yolisa; Nogaro, Sarah; Phillips, Anna E; Tukahebwa, Edridah Muheki; Fleming, Fiona M

2017-12-01

The development of new diagnostics is an important tool in the fight against disease. Latent Class Analysis (LCA) is used to estimate the sensitivity and specificity of tests in the absence of a gold standard. The main field diagnostic for Schistosoma mansoni infection, Kato-Katz (KK), is not very sensitive at low infection intensities. A point-of-care circulating cathodic antigen (CCA) test has been shown to be more sensitive than KK. However, CCA can return an ambiguous 'trace' result between 'positive' and 'negative', and much debate has focused on interpretation of traces results. We show how LCA can be extended to include ambiguous trace results and analyse S. mansoni studies from both Côte d'Ivoire (CdI) and Uganda. We compare the diagnostic performance of KK and CCA and the observed results by each test to the estimated infection prevalence in the population. Prevalence by KK was higher in CdI (13.4%) than in Uganda (6.1%), but prevalence by CCA was similar between countries, both when trace was assumed to be negative (CCAtn: 11.7% in CdI and 9.7% in Uganda) and positive (CCAtp: 20.1% in CdI and 22.5% in Uganda). The estimated sensitivity of CCA was more consistent between countries than the estimated sensitivity of KK, and estimated infection prevalence did not significantly differ between CdI (20.5%) and Uganda (19.1%). The prevalence by CCA with trace as positive did not differ significantly from estimates of infection prevalence in either country, whereas both KK and CCA with trace as negative significantly underestimated infection prevalence in both countries. Incorporation of ambiguous results into an LCA enables the effect of different treatment thresholds to be directly assessed and is applicable in many fields. Our results showed that CCA with trace as positive most accurately estimated infection prevalence.

Estimating the prevalence and intensity of Schistosoma mansoni infection among rural communities in Western Tanzania: The influence of sampling strategy and statistical approach

PubMed Central

Bakuza, Jared S.; Denwood, Matthew J.; Nkwengulila, Gamba

2017-01-01

Background Schistosoma mansoni is a parasite of major public health importance in developing countries, where it causes a neglected tropical disease known as intestinal schistosomiasis. However, the distribution of the parasite within many endemic regions is currently unknown, which hinders effective control. The purpose of this study was to characterize the prevalence and intensity of infection of S. mansoni in a remote area of western Tanzania. Methodology/Principal findings Stool samples were collected from 192 children and 147 adults residing in Gombe National Park and four nearby villages. Children were actively sampled in local schools, and adults were sampled passively by voluntary presentation at the local health clinics. The two datasets were therefore analysed separately. Faecal worm egg count (FWEC) data were analysed using negative binomial and zero-inflated negative binomial (ZINB) models with explanatory variables of site, sex, and age. The ZINB models indicated that a substantial proportion of the observed zero FWEC reflected a failure to detect eggs in truly infected individuals, meaning that the estimated true prevalence was much higher than the apparent prevalence as calculated based on the simple proportion of non-zero FWEC. For the passively sampled data from adults, the data were consistent with close to 100% true prevalence of infection. Both the prevalence and intensity of infection differed significantly between sites, but there were no significant associations with sex or age. Conclusions/Significance Overall, our data suggest a more widespread distribution of S. mansoni in this part of Tanzania than was previously thought. The apparent prevalence estimates substantially under-estimated the true prevalence as determined by the ZINB models, and the two types of sampling strategies also resulted in differing conclusions regarding prevalence of infection. We therefore recommend that future surveillance programmes designed to assess risk

Crystal structure of a Schistosoma mansoni septin reveals the phenomenon of strand slippage in septins dependent on the nature of the bound nucleotide.

PubMed

Zeraik, Ana E; Pereira, Humberto M; Santos, Yuri V; Brandão-Neto, José; Spoerner, Michael; Santos, Maiara S; Colnago, Luiz A; Garratt, Richard C; Araújo, Ana P U; DeMarco, Ricardo

2014-03-14

Septins are filament-forming GTP-binding proteins involved in important cellular events, such as cytokinesis, barrier formation, and membrane remodeling. Here, we present two crystal structures of the GTPase domain of a Schistosoma mansoni septin (SmSEPT10), one bound to GDP and the other to GTP. The structures have been solved at an unprecedented resolution for septins (1.93 and 2.1 Å, respectively), which has allowed for unambiguous structural assignment of regions previously poorly defined. Consequently, we provide a reliable model for functional interpretation and a solid foundation for future structural studies. Upon comparing the two complexes, we observe for the first time the phenomenon of a strand slippage in septins. Such slippage generates a front-back communication mechanism between the G and NC interfaces. These data provide a novel mechanistic framework for the influence of nucleotide binding to the GTPase domain, opening new possibilities for the study of the dynamics of septin filaments.

Combined immunization using DNA-Sm14 and DNA-Hsp65 increases CD8+ memory T cells, reduces chronic pathology and decreases egg viability during Schistosoma mansoni infection

PubMed Central

2014-01-01

Background Schistosomiasis is one of the most important neglected diseases found in developing countries and affects 249 million people worldwide. The development of an efficient vaccination strategy is essential for the control of this disease. Previous work showed partial protection induced by DNA-Sm14 against Schistosoma mansoni infection, whereas DNA-Hsp65 showed immunostimulatory properties against infectious diseases, autoimmune diseases, cancer and antifibrotic properties in an egg-induced granuloma model. Methods C57BL/6 mice received 4 doses of DNA-Sm14 (100 μg/dose) and DNA-Hsp65 (100 μg/dose), simultaneously administrated, or DNA-Sm14 alone, once a week, during four weeks. Three groups were included: 1- Control (no immunization); 2- DNA-Sm14; 3- DNA-Sm14/DNA-Hsp65. Two weeks following last immunization, animals were challenged subcutaneously with 30 cercariae. Fifteen, 48 and 69 days after infection splenocytes were collected to evaluate the number of CD8+ memory T cells (CD44highCD62low) using flow cytometry. Forty-eight days after challenge adult worms were collected by portal veins perfusion and intestines were collected to analyze the intestinal egg viability. Histological, immunohistochemical and soluble quantification of collagen and α-SMA accumulation were performed on the liver. Results In the current work, we tested a new vaccination strategy using DNA-Sm14 with DNA-Hsp65 to potentiate the protection against schistosomiasis. Combined vaccination increased the number of CD8+ memory T cells and decreased egg viability on the intestinal wall of infected mice. In addition, simultaneous vaccination with DNA-Sm14/DNA-Hsp65 reduced collagen and α-SMA accumulation during the chronic phase of granuloma formation. Conclusion Simultaneous vaccination with DNA-Sm14/DNA-Hsp65 showed an immunostimulatory potential and antifibrotic property that is associated with the reduction of tissue damage on Schistosoma mansoni experimental infection. PMID

Efficient Ligation of the Schistosoma Hammerhead Ribozyme †

PubMed Central

Canny, Marella D.; Jucker, Fiona M.; Pardi, Arthur

2011-01-01

The hammerhead ribozyme from Schistosoma mansoni is the best characterized of the natural hammerhead ribozymes. Biophysical, biochemical, and structural studies have shown that the formation of the loop-loop tertiary interaction between stems I and II alters the global folding, cleavage kinetics, and conformation of the catalytic core of this hammerhead, leading to a ribozyme that is readily cleaved under physiological conditions. This study investigates the ligation kinetics and the internal equilibrium between cleavage and ligation for the Schistosoma hammerhead. Single turnover kinetic studies on a construct where the ribozyme cleaves and ligates substrate(s) in trans showed up to 23% ligation when starting from fully cleaved products. This was achieved by a ~2,000-fold increase in the rate of ligation compared to a minimal hammerhead without the loop-loop tertiary interaction, yielding an internal equilibrium that ranges from 2–3 at physiological Mg2+ ion concentrations (0.1 –1 mM). Thus, the natural Schistosoma hammerhead ribozyme is almost as efficient at ligation as it is at cleavage. The results here are consistent with a model where formation of the loop-loop tertiary interaction leads to a higher population of catalytically active molecules, and where formation of this tertiary interaction has a much larger effect on the ligation than the cleavage activity of the Schistosoma hammerhead ribozyme. PMID:17319693

Recovery of primary sporocysts in vivo in the Schistosoma mansoni/Biomphalaria glabrata model using a simple fixation method suitable for extraction of genomic DNA and RNA.

PubMed

Allienne, Jean-François; Théron, André; Gourbal, Benjamin

2011-09-01

Detailed studies of host/parasite interactions are currently limited because in situ gene sequencing or monitoring of parasite gene expression is so far limited to genes presenting a high loci copy number in the Schistosome genome or a high level of expression. Indeed, how to investigate the host parasite molecular interplay when parasites are not directly accessible in vivo? Here we describe a method to circumvent this problem and to analyze DNA and RNA of Schistosoma mansoni during the interaction with its intermediate snail host Biomphalaria glabrata. We propose a technique for improved DNA and RNA extraction from the intra-molluscan stage of the parasite recovered after fixation of infected snails in Raillet-Henry solution. The extractions can be used for genetic analysis, transcription studies and microsatellite genotyping. Copyright © 2011 Elsevier Inc. All rights reserved.

A comparative epidemiologic study of specific antibodies (IgM and IgA) and parasitological findings in an endemic area of low transmission of schistosoma mansoni.

PubMed

Kanamura, H Y; Dias, L C; da Silva, R M; Glasser, C M; Patucci, R M; Vellosa, S A; Antunes, J L

1998-01-01

The diagnostic potential of circulating IgM and IgA antibodies against Schistosoma mansoni gut-associated antigens detected by the immunofluorescence test (IFT) on adult worm paraffin sections was evaluated comparatively to the fecal parasitological method, for epidemiological purposes in low endemic areas for schistosomiasis. Blood samples were collected on filter paper from two groups of schoolchildren living in two different localities of the municipality of Itariri (São Paulo, Brazil) with different histories and prevalences of schistosomiasis. The parasitological and serological data were compared to those obtained for another group of schoolchildren from a non-endemic area for schistosomiasis. The results showed poor sensitivity of the parasitological method in detecting individuals with low worm burden and indicate the potential of the serological method as an important tool to be incorporated into schistosomiasis control and vigilance programs for determining the real situation of schistosomiasis in low endemic areas.

Prophylactic effect of artemether on human schistosomiasis mansoni among Egyptian children: A randomized controlled trial.

PubMed

Elmorshedy, Hala; Tanner, Marcel; Bergquist, Robert N; Sharaf, Soraya; Barakat, Rashida

2016-06-01

A double-blind, randomized controlled trial was conducted in an endemic focus for Schistosoma mansoni in Kafr El-Sheikh Governorate, Northern Nile Delta, Egypt, to evaluate the prophylactic effect of artemether (ART) given in conjunction with praziquantel (PZQ). The study encompassed 913 primary school children randomly assigned to two treatment groups PZQ/ART and PZQ/ART-placebo. At baseline, both groups received 40 mg/kg body weight of PZQ twice four weeks apart, after which one group received 6 mg/kg body weight of ART every 3 weeks in 5 cycles during the transmission season and the other group received ART-placebo. At the end of the study, prevalence of infection among the PZQ/ART was approximately half that of the PZQ/ART-placebo group, i.e. 6.7% versus 11.6%, and incidence of new infections for the PZQ/ART was 2.7% versus 6.5% for the PZQ/ART-placebo. In conclusion, PZQ/ART combined therapy might be considered as an adjunct measure against human schistosomiasis, by specifically reducing transmission and therefore contribute to disease elimination. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Time series analysis of the transcriptional responses of Biomphalaria glabrata throughout the course of intramolluscan development of Schistosoma mansoni and Echinostoma paraensei

PubMed Central

Hanington, Patrick C.; Lun, Cheng-Man; Adema, Coen M; Loker, Eric S

2010-01-01

Successful colonization of a compatible snail host by a digenetic trematode miracidium initiates a complex, proliferative development program requiring weeks to reach culmination in the form of production of cercariae which, once started, may persist for the remainder of the life span of the infected snail. How are such proliferative and invasive parasites able to circumvent host defenses and establish chronic infections? Using a microarray designed to monitor the internal defense and stress-related responses of the freshwater snail Biomphalaria glabrata, we have undertaken a time course study to monitor snail responses following exposure to two different trematode species to which the snail is susceptible: the medically important Schistosoma mansoni, exemplifying sporocyst production in its larval development, or Echinostoma paraensei, representing an emphasis on rediae production in its larval development. We sampled eight time points (0.5, 1, 2, 4, 8, 16 and 32 days p.i.) that cover the period required for cercariae to be produced. Following exposure to S. mansoni, there was a preponderance of up-regulated over down-regulated array features through 2 days p.i. but by 4 days p.i. and thereafter, this pattern was strongly reversed. For E. paraensei, there was a preponderance of down-regulated array features over up-regulated features at even 0.5 days p.i., a pattern that persists throughout the course of infection except for 1 day p.i., when up-regulated array features slightly outnumbered down-regulated features. Examination of particular array features revealed several that were up-regulated by both parasites early in the course of infection and one, fibrinogen related protein 4 (FREP 4), that remained significantly elevated throughout the course of infection with either parasite, effectively serving as a marker of infection. Many defense-related transcripts were persistently down-regulated, including several fibrinogen-containing lectins and homologs of

Schistosoma mansoni Phosphoenolpyruvate Carboxykinase, a Novel Egg Antigen: Immunological Properties of the Recombinant Protein and Identification of a T-Cell Epitope

PubMed Central

Asahi, Hiroko; Osman, Ahmed; Cook, Rosemary M.; LoVerde, Philip T.; Stadecker, Miguel J.

2000-01-01

In schistosomiasis mansoni, hepatic granulomatous inflammation surrounding parasite eggs is mediated by CD4+ T helper (Th) cells sensitized to schistosomal egg antigens (SEA). We previously showed that a prominent lymphoproliferative response of CD4+ Th cells from schistosome-infected C57BL/6 (BL/6) mice was directed against a 62-kDa component of SEA. A partial amino acid sequence of the 62-kDa component was found to be identical with one present in the enzyme phosphoenolpyruvate carboxykinase (PEPCK). Based on this sequence, a cDNA clone containing the entire coding region of PEPCK was identified, and the full recombinant Schistosoma mansoni PEPCK (rSm-PEPCK) of 626 amino acids was purified from a prokaryotic expression system. rSm-PEPCK strongly stimulated a specific T-cell hybridoma, 4E6, as well as CD4+ Th cells from SEA-immunized BL/6 mice and from infected BL/6, CBA, and BALB/c mice. In the infected mice, rSm-PEPCK elicited significant gamma interferon production as well as, to a lesser extent, production of interleukin-2 and -5. In BL/6 and BALB/c mice, the CD4+ Th cell response to rSm-PEPCK was greater than that directed against the egg antigen Sm-p40; conversely, CBA mice responded better to Sm-p40 than to Sm-PEPCK. A 12-amino-acid region (residues 398 to 409: DKSKDPKAHPNS) was demonstrated to contain a T-cell epitope; synthetic peptides containing this epitope significantly stimulated specific hybridoma 4E6 and polyclonal CD4+ Th cells. The identification and characterization of immunogenic egg components will contribute to the understanding and possible control of T-cell-mediated schistosomal disease. PMID:10816489

Schistosoma mansoni: is acquired immunity induced by highly x-irradiated cercariae dependent on the size of the challenging dose

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hsue, S.Y.; Hsue, H.F.; Osborne, J.W.

1982-04-01

A high degree of immunity, as shown by a 91% reduction of the number of worms recovered was found in five groups of mice that were immunized five times with highly X-irradiated cercariae and then challenged with 10, 20, 50, 100, or 500 normal Schistosoma mansoni cercariae. The results indicated that there were no significant differences in worm reduction in immunized mice challenged with different numbers of cercariae; consequently the immunity induced by this immunization method did not appear to be challenge-dose-dependent. However, the results also showed that when immunized mice were challenged with 500, 100, 50, 20, and 10more » cercariae, 0, 13, 26, 56, and 68%, respectively, of the experimental animals were free of worms. Thus, the percentage of worm-negative cases increased as the number of challenge cercariae decreased. When viewed in this manner, the acquired immunity may be considered challenge-dose-dependent as well. If this method of vaccination is used for schistosomiasis control, we may anticipate that in both hypo- and hyperendemic areas, the intensity of infection and the severity of the disease will be reduced owing to a reduction in worms burdens, and in hypoendemic areas, there will be a number of worm-free cases.« less

Schistosoma mansoni venom allergen-like protein 4 (SmVAL4) is a novel lipid-binding SCP/TAPS protein that lacks the prototypical CAP motifs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kelleher, Alan; Darwiche, Rabih; Rezende, Wanderson C.

2014-08-01

The first structure of an S. mansoni venom allergen-like protein is presented. Schistosomiasis is a parasitic disease that affects over 200 million people. Vaccine candidates have been identified, including Schistosoma mansoni venom allergen-like proteins (SmVALs) from the SCP/TAPS (sperm-coating protein/Tpx/antigen 5/pathogenesis related-1/Sc7) superfamily. The first SmVAL structure, SmVAL4, was refined to a resolution limit of 2.16 Å. SmVAL4 has a unique structure that could not be predicted from homologous structures, with longer loops and an unusual C-terminal extension. SmVAL4 has the characteristic α/β-sandwich and central SCP/TAPS cavity. Furthermore, SmVAL4 has only one of the signature CAP cavity tetrad amino-acid residuesmore » and is missing the histidines that coordinate divalent cations such as Zn{sup 2+} in other SCP/TAPS proteins. SmVAL4 has a cavity between α-helices 1 and 4 that was observed to bind lipids in tablysin-15, suggesting the ability to bind lipids. Subsequently, SmVAL4 was shown to bind cholesterol in vitro. Additionally, SmVAL4 was shown to complement the in vivo sterol-export phenotype of yeast mutants lacking their endogenous CAP proteins. Expression of SmVAL4 in yeast cells lacking endogenous CAP function restores the block in sterol export. These studies suggest an evolutionarily conserved lipid-binding function shared by CAP proteins such as SmVAL4 and yeast CAP proteins such as Pry1.« less

Clinical, parasitological and immunological features of canal cleaners hyper-exposed to Schistosoma mansoni in the Sudan

PubMed Central

SATTI, M Z; SULAIMAN, S M; HOMEIDA, M M A; YOUNIS, S A; GHALIB, H W

1996-01-01

The present work was a longitudinal study on Schistosoma mansoni infection in occupationally hyperexposed canal cleaners in the Sudan and the influence of therapy on the parasitological and humoral immune parameters. Chronically infected canal cleaners (n = 28) were more resistant to reinfection (Fisher's exact test, P < 0.05) than newly recruited canal cleaners (n = 17). Chronically infected canal cleaners had a significantly higher degree of Symmers' fibrosis (χ2 = 19.1, P < 0.0001), significantly larger portal vein diameter (P < 0.05) and enlarged spleen (χ2 = 4.2, P < 0.05) than recently infected, newly recruited canal cleaners. ELISA was used to detect IgG, IgA and IgM in response to whole worm homogenate (WWH) and cercarial homogenate (CH). Chronically infected canal cleaners had significantly higher IgG to WWH antigen than newly recruited canal cleaners and normally exposed individuals (P < 0.05), while both chronically infected and newly recruited canal cleaners had higher IgG levels to CH antigen than normally exposed individuals (P < 0.05). The newly recruited canal cleaners had a significantly higher IgM level to CH antigen than chronically infected canal cleaners (P < 0.05). The IgG level to WWH antigen increased significantly after treatment in newly recruited canal cleaners and normally exposed individuals (P < 0.05). The IgA level to CH antigen increased significantly after treatment in the chronically infected group (P < 0.05). Comparison of the serological parameters between the different study groups with regards to infection and treatment is discussed. PMID:9099926

Praziquantel decreases fecundity in Schistosoma mansoni adult worms that survive treatment: evidence from a laboratory life-history trade-offs selection study.

PubMed

Lamberton, Poppy H L; Faust, Christina L; Webster, Joanne P

2017-06-16

Mass drug administration of praziquantel is the World Health Organization's endorsed control strategy for schistosomiasis. A decade of annual treatments across sub-Saharan Africa has resulted in significant reductions of infection prevalence and intensity levels, although 'hotspots' remain. Repeated drug treatments place strong selective pressures on parasites, which may affect life-history traits that impact transmission dynamics. Understanding drug treatment responses and the evolution of such traits can help inform on how to minimise the risk of drug resistance developing, maximise sustainable control programme success, and improve diagnostic protocols. We performed a four-generation Schistosoma mansoni praziquantel selection experiment in mice and snails. We used three S. mansoni lines: a praziquantel-resistant isolate (R), a praziquantel-susceptible isolate (S), and a co-infected line (RS), under three treatment regimens: untreated, 25 mg/kg praziquantel, or 50 mg/kg praziquantel. Life-history traits, including parasite adult-worm establishment, survival, reproduction (fecundity), and associated morbidity, were recorded in mice across all four generations. Predictor variables were tested in a series of generalized linear mixed effects models to determine which factors had a significant influence on parasite life-history traits in definitive hosts under different selection regimes. Praziquantel pressure significantly reduced adult-worm burdens across all generations and isolates, including within R-lines. However, previous drug treatment resulted in an increase in adult-worm establishment with increasing generation from P1 to F3. The highest worm numbers were in the co-infected RS line. Praziquantel treatment decreased adult-worm burden, but had a larger negative impact on the mean daily number of miracidia, a proxy for fecundity, across all three parasite isolates. Our predicted cost of resistance was not supported by the traits we measured within the

Plasmodium falciparum Infection Status among Children with Schistosoma in Sub-Saharan Africa: A Systematic Review and Meta-analysis

PubMed Central

Degarege, Abraham; Degarege, Dawit; Veledar, Emir; Erko, Berhanu; Nacher, Mathieu; Beck-Sague, Consuelo M.; Madhivanan, Purnima

2016-01-01

Background It has been suggested that Schistosoma infection may be associated with Plasmodium falciparum infection or related reduction in haemoglobin level, but the nature of this interaction remains unclear. This systematic review synthesized evidence on the relationship of S. haematobium or S. mansoni infection with the occurrence of P. falciparum malaria, Plasmodium density and related reduction in haemoglobin level among children in sub-Saharan Africa (SSA). Methodology/Principal findings A systematic review in according with PRISMA guidelines was conducted. All published articles available in PubMed, Embase, Cochrane library and CINAHL databases before May 20, 2015 were searched without any limits. Two reviewers independently screened, reviewed and assessed all the studies. Cochrane Q and Moran’s I2 were used to assess heterogeneity and the Egger test was used to examine publication bias. The summary odds ratio (OR), summary regression co-efficient (β) and 95% confidence intervals (CI) were estimated using a random-effects model. Out of 2,920 citations screened, 12 articles (five cross-sectional, seven prospective cohort) were eligible to be included in the systematic review and 11 in the meta-analysis. The 12 studies involved 9,337 children in eight SSA countries. Eight studies compared the odds of asymptomatic/uncomplicated P. falciparum infection, two studies compared the incidence of uncomplicated P. falciparum infection, six studies compared P. falciparum density and four studies compared mean haemoglobin level between children infected and uninfected with S. haematobium or S. mansoni. Summary estimates of the eight studies based on 6,018 children showed a higher odds of asymptomatic/uncomplicated P. falciparum infection in children infected with S. mansoni or S. haematobium compared to those uninfected with Schistosoma (summary OR: 1.82; 95%CI: 1.41, 2.35; I2: 52.3%). The increase in odds of asymptomatic/uncomplicated P. falciparum infection among

CK2 phosphorylation of Schistosoma mansoni HMGB1 protein regulates its cellular traffic and secretion but not its DNA transactions.

PubMed

de Abreu da Silva, Isabel Caetano; Carneiro, Vitor Coutinho; Maciel, Renata de Moraes; da Costa, Rodrigo Furtado Madeiro; Furtado, Daniel Rodrigues; de Oliveira, Francisco Meirelles Bastos; da Silva-Neto, Mário Alberto Cardoso; Rumjanek, Franklin David; Fantappié, Marcelo Rosado

2011-01-01

The helminth Schistosoma mansoni parasite resides in mesenteric veins where fecundated female worms lay hundred of eggs daily. Some of the egg antigens are trapped in the liver and induce a vigorous granulomatous response. High Mobility Group Box 1 (HMGB1), a nuclear factor, can also be secreted and act as a cytokine. Schistosome HMGB1 (SmHMGB1) is secreted by the eggs and stimulate the production of key cytokines involved in the pathology of schistosomiasis. Thus, understanding the mechanism of SmHMGB1 release becomes mandatory. Here, we addressed the question of how the nuclear SmHMGB1 can reach the extracellular space. We showed in vitro and in vivo that CK2 phosphorylation was involved in the nucleocytoplasmic shuttling of SmHMGB1. By site-directed mutagenesis we mapped the two serine residues of SmHMGB1 that were phosphorylated by CK2. By DNA bending and supercoiling assays we showed that CK2 phosphorylation of SmHMGB1 had no effect in the DNA binding activities of the protein. We showed by electron microscopy, as well as by cell transfection and fluorescence microscopy that SmHMGB1 was present in the nucleus and cytoplasm of adult schistosomes and mammalian cells. In addition, we showed that treatments of the cells with either a phosphatase or a CK2 inhibitor were able to enhance or block, respectively, the cellular traffic of SmHMGB1. Importantly, we showed by confocal microscopy and biochemically that SmHMGB1 is significantly secreted by S. mansoni eggs of infected animals and that SmHMGB1 that were localized in the periovular schistosomotic granuloma were phosphorylated. We showed that secretion of SmHMGB1 is regulated by phosphorylation. Moreover, our results suggest that egg-secreted SmHMGB1 may represent a new egg antigen. Therefore, the identification of drugs that specifically target phosphorylation of SmHMGB1 might block its secretion and interfere with the pathogenesis of schistosomiasis.

Developing a mathematical model for the evaluation of the potential impact of a partially efficacious vaccine on the transmission dynamics of Schistosoma mansoni in human communities.

PubMed

Stylianou, Andria; Hadjichrysanthou, Christoforos; Truscott, James E; Anderson, Roy M

2017-06-17

There is currently no vaccine available to protect humans against infection with the schistosome digenean parasites, although candidate formulations for Schistosoma mansoni are under trial in animal models, including rodents and primates. Current strategies for the control of infection are based on mass drug administration (MDA) targeted at school-aged children of age 5 to 14 years. This approach is unlikely to eliminate exposure to infection except in settings with very low levels of transmission. A deterministic mathematical model for the transmission dynamics of the parasite is described and employed to investigate community level outcomes. The model is defined to encompass two different delivery strategies for the vaccination of the population, namely, infant (cohort) and mass vaccination. However, in this paper the focus is on vaccination delivered in a cohort immunisation programme where infants are immunised within the first year of life before acquiring infection. An analysis of the parasite's transmission dynamics following the administration of a partially protective vaccine is presented. The vaccine acts on parasite mortality, fecundity or/and establishment. A vaccine with an efficacy of over 60% can interrupt transmission in low and moderate transmission settings. In higher transmission intensity areas, greater efficacy or higher infant vaccination coverage is required. Candidate vaccines that act either on parasite mortality, fecundity or establishment within the human host, can be similarly effective. In all cases, however, the duration of protection is important. The community level impact of vaccines with all modes of action, declines if vaccine protection is of a very short duration. However, durations of protection of 5-10 years or more are sufficient, with high coverage and efficacy levels, to halt transmission. The time taken to break transmission may be 18 years or more after the start of the cohort vaccination, depending on the intensity of

Re-evaluation of schistosomiasis mansoni in Minas Gerais, Brazil. III. "Noroeste de Minas" mesoregion.

PubMed

Carvalho, O S; Massara, C L; Guerra, H L; Campos, Y R; Caldeira, R L; Chaves, A; Katz, N

1998-01-01

This study was conducted to assess the presence of schistosomiasis mansoni in the "Noroeste de Minas" mesoregion, an area considered non-endemic. A malacologic survey and parasitologic stool examinations were undertaken in 13 municipalities of the mesoregion. A sample of 3,283 primary school students was submitted to fecal examination by the Kato-Katz method. A total of 3,627 planorbids was collected and examined. The molluscs were identified as Biomphalaria straminea in seven municipalities (Unaí, Bonfinópolis de Minas, Paracatu, Jaão Pinheiro, Vazante, Lagamar and Lagoa Grande) and as Biomphalaria peregrina in one (Presidente Olegário). All planorbids were negative for Schistosoma mansoni. Four students were diagnosed with schistosomiasis in the municipalities of Buritis, Formoso, Paracatu and Unaí, but none of these cases was considered autochthonous. The data obtained indicate that the "Noroeste de Minas" mesoregion continues to be non-endemic for schistosomiasis mansoni, although the presence of intermediate hosts associated with parasitized individuals emphasizes the need for epidemiological surveillance of schistosomiasis in this mesoregion.

Use of Molecular Methods for the Rapid Mass Detection of Schistosoma mansoni (Platyhelminthes: Trematoda) in Biomphalaria spp. (Gastropoda: Planorbidae)

PubMed Central

Jannotti-Passos, Liana Konovaloffi; Dos Santos Carvalho, Omar

2017-01-01

The low stringency-polymerase chain reaction (LS-PCR) and loop-mediated isothermal amplification (LAMP) assays were used to detect the presence of S. mansoni DNA in (1) Brazilian intermediate hosts (Biomphalaria glabrata, B. straminea, and B. tenagophila) with patent S. mansoni infections, (2) B. glabrata snails with prepatent S. mansoni infections, (3) various mixtures of infected and noninfected snails; and (4) snails infected with other trematode species. The assays showed high sensitivity and specificity and could detect S. mansoni DNA when one positive snail was included in a pool of 1,000 negative specimens of Biomphalaria. These molecular approaches can provide a low-cost, effective, and rapid method for detecting the presence of S. mansoni in pooled samples of field-collected Biomphalaria. These assays should aid mapping of transmission sites in endemic areas, especially in low prevalence regions and improve schistosomiasis surveillance. It will be a useful tool to monitor low infection rates of snails in areas where control interventions are leading towards the elimination of schistosomiasis. PMID:28246533

HIV-1 vaccine-specific responses induced by Listeria vector vaccines are maintained in mice subsequently infected with a model helminth parasite, Schistosoma mansoni.

PubMed

Shollenberger, Lisa M; Bui, Cac T; Paterson, Yvonne; Nyhoff, Lindsay; Harn, Donald A

2013-11-19

In areas co-endemic for helminth parasites and HIV/AIDS, infants are often administered vaccines prior to infection with immune modulatory helminth parasites. Systemic Th2 biasing and immune suppression caused by helminth infection reduces cell-mediated responses to vaccines such as tetanus toxoid and BCG. Therefore, we asked if infection with helminthes post-vaccination, alters already established vaccine induced immune responses. In our model, mice are vaccinated against HIV-1 Gag using a Listeria vaccine vector (Lm-Gag) in a prime-boost manner, then infected with the human helminth parasite Schistosoma mansoni. This allows us to determine if established vaccine responses are maintained or altered after helminth infection. Our second objective asked if helminth infection post-vaccination alters the recipient's ability to respond to a second boost. Here we compared responses between uninfected mice, schistosome infected mice, and infected mice that were given an anthelminthic, which occurred coincident with the boost or four weeks prior, as well as comparing to un-boosted mice. We report that HIV-1 vaccine-specific responses generated by Listeria vector HIV-1 vaccines are maintained following subsequent chronic schistosome infection, providing further evidence that Listeria vector vaccines induce potent vaccine-specific responses that can withstand helminth infection. We also were able to demonstrate that administration of a second Listeria boost, which markedly enhanced the immune response, was minimally impacted by schistosome infection, or anthelminthic therapy. Surprisingly, we also observed enhanced antibody responses to HIV Gag in vaccinated mice subsequently infected with schistosomes. Copyright © 2013 Elsevier Ltd. All rights reserved.

Interpreting ambiguous ‘trace’ results in Schistosoma mansoni CCA Tests: Estimating sensitivity and specificity of ambiguous results with no gold standard

PubMed Central

Donnelly, Christl A.; Fenwick, Alan; Kabatereine, Narcis B.; Knowles, Sarah C. L.; Meité, Aboulaye; N'Goran, Eliézer K.; Nalule, Yolisa; Nogaro, Sarah; Phillips, Anna E.; Tukahebwa, Edridah Muheki; Fleming, Fiona M.

2017-01-01

Background The development of new diagnostics is an important tool in the fight against disease. Latent Class Analysis (LCA) is used to estimate the sensitivity and specificity of tests in the absence of a gold standard. The main field diagnostic for Schistosoma mansoni infection, Kato-Katz (KK), is not very sensitive at low infection intensities. A point-of-care circulating cathodic antigen (CCA) test has been shown to be more sensitive than KK. However, CCA can return an ambiguous ‘trace’ result between ‘positive’ and ‘negative’, and much debate has focused on interpretation of traces results. Methodology/Principle findings We show how LCA can be extended to include ambiguous trace results and analyse S. mansoni studies from both Côte d’Ivoire (CdI) and Uganda. We compare the diagnostic performance of KK and CCA and the observed results by each test to the estimated infection prevalence in the population. Prevalence by KK was higher in CdI (13.4%) than in Uganda (6.1%), but prevalence by CCA was similar between countries, both when trace was assumed to be negative (CCAtn: 11.7% in CdI and 9.7% in Uganda) and positive (CCAtp: 20.1% in CdI and 22.5% in Uganda). The estimated sensitivity of CCA was more consistent between countries than the estimated sensitivity of KK, and estimated infection prevalence did not significantly differ between CdI (20.5%) and Uganda (19.1%). The prevalence by CCA with trace as positive did not differ significantly from estimates of infection prevalence in either country, whereas both KK and CCA with trace as negative significantly underestimated infection prevalence in both countries. Conclusions Incorporation of ambiguous results into an LCA enables the effect of different treatment thresholds to be directly assessed and is applicable in many fields. Our results showed that CCA with trace as positive most accurately estimated infection prevalence. PMID:29220354

The acceptability and safety of praziquantel alone and in combination with mebendazole in the treatment of Schistosoma mansoni and soil-transmitted helminthiasis in children aged 1-4 years in Uganda.

PubMed

Namwanje, Harriet; Kabatereine, Narcis B; Olsen, Annette

2011-10-01

There is limited information on the acceptability and safety of praziquantel for treatment of schistosomiasis in children below the age of four years. In addition, although mebendazole has been extensively used together with praziquantel against infections with schistosomiasis and soil-transmitted helminthiasis (STH) in school-aged children, no specific acceptability or safety studies have been published on this drug combination in younger children. A randomized clinical trial was conducted to determine the safety of praziquantel alone and in combination with mebendazole in the treatment of Schistosoma mansoni and STH in children aged 1 to 4 years. A total of 596 children from Bwondha fishing community in Mayuge district and Wang-Kado fishing community in Nebbi district were investigated using duplicate Kato-Katz thick smears of two stool samples and 130 (21·8%) were found infected with S. mansoni. Of these, 19·2% (25) had heavy intensity of infections. Of the infected children, 82 were included and randomised into praziquantel (40 mg/kg) + mebendazole (500 mg) or praziquantel (40 mg/kg) alone. Many symptoms were reported before treatment while very few were reported after treatment and all on treatment day. No serious adverse events were reported or observed after treatment. Praziquantel with or without mebendazole was well tolerated in small children in the study area.

Regulation of HSP70 gene expression during the life cycle of the parasitic helminth Schistosoma mansoni.

PubMed

Neumann, S; Ziv, E; Lantner, F; Schechter, I

1993-03-01

Analyses of RNA from different developmental stages of Schistosoma mansoni showed stage-specific expression of heat-shock protein 70 (hsp70), which is regulated by a developmental program and by stress. The developmental program, common to hsp70 and other genes (e.g. paramyosin), refers to constitutive expression in miracidia sporocyst and adult worm but not in cercariae, and to the termination of hsp70 gene transcription during sporocyst/cercaria transformation. Stress induction, specific to hsp70, refers to transient accumulation of high levels of hsp70 mRNA during cercariae/schistosomula transformation and in adult worms after heat shock (42 degrees C). Cercariae/schistosomula transformation can be visualized as a physiological stress involving shifts in temperature (23-37 degrees C) and in salt concentration (from water to isotonic medium), as well as removal of tails from cercariae to yield isolated bodies that transform into schistosomula. It was found that temperature is an important factor, but not sufficient for strong induction of the hsp70 genes of schistosomula. Tail removal is an obligatory step for full induction of the hsp70 genes of schistosomula, in response to a temperature shift from 23-37 degrees C. The hsp70 genes in cercariae and isolated tails do not respond to stimuli (salt and temperature increases) that strongly activate the genes in isolated bodies (i.e., schistosomula). We speculate that the hsp70 genes in intact cercariae are not inducible because the tails can produce inhibitory signals that diffuse to the bodies and suppress their hsp70 genes. This hypothesis is useful to explain the termination of hsp70 gene transcription during sporocyst/cercaria transformation by the inhibitory effect of the growing tail.

Immunohistochemical Investigations of Treatment with Ro 13-3978, Praziquantel, Oxamniquine, and Mefloquine in Schistosoma mansoni-Infected Mice

PubMed Central

Panic, Gordana; Ruf, Marie-Thérèse

2017-01-01

ABSTRACT To date, there is only one drug in use, praziquantel, to treat more than 250 million people afflicted with schistosomiasis, a debilitating parasitic disease. The aryl hydantoin Ro 13-3978 is a promising drug candidate with in vivo activity superior to that of praziquantel against both adult and juvenile Schistosoma mansoni organisms. Given the drug's contrasting low activity in vitro and the timing of its onset of action in vivo, it was postulated that immune-assisted parasite clearance could contribute to the drug's in vivo activity. We undertook histopathological studies to investigate this hypothesis. Infected mice were treated with an effective dose of Ro 13-3978 (100 mg/kg of body weight) and were dissected before and after the drug's in vivo onset of action. The veins and livers were excised, paraffin-embedded, and sectioned, and macrophages (IBA-1), neutrophils (Neutro), B cells (CD45R), and T cells (CD3) were stained by immunohistochemistry. For comparison, samples from infected untreated mice and mice treated with effective doses of praziquantel (400 mg/kg), oxamniquine (200 mg/kg), and mefloquine (200 mg/kg) were examined. At 24 h after treatment with Ro 13-3978, significant macrophage recruitment to the veins was observed, along with a modest increase in circulating B cells, and at 48 h, neutrophils and T cells are also present. Treatment with praziquantel and oxamniquine showed similar patterns of recruitment but with comparatively higher cellular levels, whereas mefloquine treatment resulted in minimal cell recruitment until 3 days posttreatment. Our study sheds light on the immediate immune responses to antischistosomal treatment in mice and provides further insight into immune effector mechanisms of schistosome clearance. PMID:28971860

Octopamine-signaling in the metazoan pathogen, Schistosoma mansoni: localization, small-molecule screening and opportunities for drug development.

PubMed

El-Sakkary, Nelly; Chen, Steven; Arkin, Michelle R; Caffrey, Conor R; Ribeiro, Paula

2018-06-20

Schistosomiasis is a tropical disease caused by a flatworm trematode parasite that infects over 240 million people worldwide. Treatment and control of the disease rely on just one drug, praziquantel. The possibility of drug resistance coupled with praziquantel's variable efficacy encourages the identification of new drugs and drug targets. Disruption of neuromuscular homeostasis in parasitic worms is a validated strategy for drug development. However, in schistosomes, much remains to be understood about the organization of the nervous system, its component neurotransmitters and potential for drug discovery. Using synapsin as a neuronal marker, we map the central and peripheral nervous systems in the Schistosoma mansoni adult and schistosomulum (post-infective larva). We discover the widespread presence of octopamine (OA), a tyrosine-derived and invertebrate-specific neurotransmitter involved in neuromuscular coordination. OA-labeling facilitated the discovery of two pairs of ganglia in the brain of the adult schistosome rather than the one pair thus far reported for this or other trematodes. In quantitative phenotypic assays, OA and structurally-related tyrosine-derived phenolamine and catecholamine neurotransmitters differentially modulated schistosomulum motility and length. Similarly, from a screen of 28 drug agonists and antagonists of tyrosine derivative-signaling, certain drugs that act on OA and dopamine receptors induced robust and sometimes complex concentration-dependent effects on schistosome motility and length, including at concentrations achievable in vivo The present data advance our knowledge of the organization of the nervous system in this globally important pathogen and identify a number of drugs that interfere with tyrosine-derived signaling, one or more of which may provide the basis for a new chemotherapeutic approach to treat schistosomiasis. © 2018. Published by The Company of Biologists Ltd.

Anti- Schistosomular Activity of Human Monocytes/Macrophages in Response to Interleukin-3 and Granulocyte-Macrophage Colonystimulating Factor Stimulation

PubMed Central

Nissimov, L.; Lengy, J.; Keisari, Y.

1994-01-01

Human monocytes, co-incubated for 7 days in culture with GM-CSF or IL-3 but not with IFN-γ, exerted a variable schistosotnulicidal effect on Schistosoma mansoni parasites when grown in 96-well round-bottomed plates but not in flat-bottomed plates. Addition of LPS or IFN-γ or both, for the last 48 h did not enhance the cidal effect. Addition of LPS but not IFN-γ to the pre-incubated cells with GM-CSF or IL-3 markedly stimulated TNF-α production by the cells but not their cidal activity. The variable cidal effects obtained with the monocytes/macrophages from different donors suggest that these effects may be genetically predetermined and are possibly linked to blood group markers or to MHC class I or II antigens. PMID:18475576

Rates and intensity of re-infection with human helminths after treatment and the influence of individual, household, and environmental factors in a Brazilian community.

PubMed

Cundill, Bonnie; Alexander, Neal; Bethony, Jeff M; Diemert, David; Pullan, Rachel L; Brooker, Simon

2011-09-01

This study quantifies the rate and intensity of re-infection with human hookworm and Schistosoma mansoni infection 12 months following successful treatment, and investigates the influence of socio-economic, geographical and environmental factors. A longitudinal study of 642 individuals aged over 5 years was conducted in Minas Gerais State, Brazil from June 2004 to March 2006. Risk factors were assessed using interval censored regression for the rate and negative binomial regression for intensity. The crude rate and intensity of hookworm re-infection was 0·21 per year (95% confidence interval (CI) 0·15-0·29) and 70·9 epg (95% CI 47·2-106·6). For S. mansoni the rate was 0·06 per year (95% CI 0·03-0·10) and intensity 6·51 epg (95% CI 3·82-11·11). Rate and intensity of re-infection with hookworm were highest among males and positively associated with previous infection status, absence of a toilet and house structure. Rate and intensity of S. mansoni re-infection were associated with previous infection status as well as geographical, environmental and socio-economic factors. The implications of findings for the design of anti-helminth vaccine trials are discussed.

Advancing a vaccine to prevent human schistosomiasis.

PubMed

Merrifield, Maureen; Hotez, Peter J; Beaumier, Coreen M; Gillespie, Portia; Strych, Ulrich; Hayward, Tara; Bottazzi, Maria Elena

2016-06-03

Several candidate human schistosomiasis vaccines are in different stages of preclinical and clinical development. The major targets are Schistosoma haematobium (urogenitial schistosomiasis) and Schistosoma mansoni (intestinal schistosomiasis) that account for 99% of the world's 252 million cases, with 90% of these cases in Africa. Two recombinant S. mansoni vaccines - Sm-TSP-2 and Sm-14 are in Phase 1 trials, while Smp80 (calpain) is undergoing testing in non-human primates. Sh28GST, also known as Bilhvax is in advanced clinical development for S. haematobium infection. The possibility remains that some of these vaccines may cross-react to target both schistosome species. These vaccines were selected on the basis of their protective immunity in preclinical challenge models, through human immune-epidemiological studies or both. They are being advanced through a combination of academic research institutions, non-profit vaccine product development partnerships, biotechnology companies, and developing country vaccine manufacturers. In addition, new schistosome candidate vaccines are being identified through bioinformatics, OMICs approaches, and moderate throughput screening, although the full potential of reverse vaccinology for schistosomiasis has not yet been realized. The target product profiles of these vaccines vary but many focus on vaccinating children, in some cases following mass treatment with praziquantel, also known as vaccine-linked chemotherapy. Several regulatory pathways have been proposed, some of which rely on World Health Organization prequalification. Copyright © 2016 World Health Organization. Published by Elsevier Ltd.. All rights reserved.

Praziquantel in a Clay Nanoformulation Shows More Bioavailability and Higher Efficacy against Murine Schistosoma mansoni Infection

PubMed Central

Mohamed, Wael S.; Nasr, Hanaa E.; El-Lakkany, Naglaa M.; Seif el-Din, Sayed H.; Botros, Sanaa S.

2015-01-01

Consideration of existing compounds always simplifies and shortens the long and difficult process of discovering new drugs specifically for diseases of developing countries, an approach that may add to the significant potential cost savings. This study focused on improving the biological characteristics of the already-existing antischistosomal praziquantel (PZQ) by incorporating it into montmorillonite (MMT) clay as a delivery carrier to overcome its known bioavailability drawbacks. The oral bioavailability of a PZQ-MMT clay nanoformulation and its in vivo efficacy against Schistosoma mansoni were investigated. The PZQ-MMT clay nanoformulation provided a preparation with a controlled release rate, a decrease in crystallinity, and an appreciable reduction in particle size. Uninfected and infected mice treated with PZQ-MMT clay showed 3.61- and 1.96-fold and 2.16- and 1.94-fold increases, respectively, in area under the concentration-time curve from 0 to 8 h (AUC0–8) and maximum concentration of drug in serum (Cmax), with a decrease in elimination rate constant (kel) by 2.84- and 1.35-fold and increases in the absorption rate constant (ka) and half-life (t1/2e) by 2.11- and 1.51-fold and 2.86- and 1.34-fold, respectively, versus the corresponding conventional PZQ-treated groups. This improved bioavailability has been expressed in higher efficacy of the drug, where the dose necessary to kill 50% of the worms was reduced by >3-fold (PZQ 50% effective dose [ED50] was 20.25 mg/kg of body weight for PZQ-MMT clay compared to 74.07 mg/kg for conventional PZQ), with significant reduction in total tissue egg load and increase in total immature, mature, and dead eggs in most of the drug-treated groups. This formulation showed better bioavailability, enhanced antischistosomal efficacy, and a safer profile despite the longer period of residence in the systemic circulation. Although the conventional drug's toxicity was not examined, animal mortality rates were not different

MiR-277/4989 regulate transcriptional landscape during juvenile to adult transition in the parasitic helminth Schistosoma mansoni

PubMed Central

van Dongen, Stijn; Collins, Julie; Quintais, Leonor; Ribeiro, Diogo M.; Sessler, Florian; Hunt, Martin; Rinaldi, Gabriel; Collins, James J.; Enright, Anton J.; Berriman, Matthew

2017-01-01

Schistosomes are parasitic helminths that cause schistosomiasis, a disease affecting circa 200 million people, primarily in underprivileged regions of the world. Schistosoma mansoni is the most experimentally tractable schistosome species due to its ease of propagation in the laboratory and the high quality of its genome assembly and annotation. Although there is growing interest in microRNAs (miRNAs) in trematodes, little is known about the role these molecules play in the context of developmental processes. We use the completely unaware “miRNA-blind” bioinformatics tool Sylamer to analyse the 3’-UTRs of transcripts differentially expressed between the juvenile and adult stages. We show that the miR-277/4989 family target sequence is the only one significantly enriched in the transition from juvenile to adult worms. Further, we describe a novel miRNA, sma-miR-4989 showing that its proximal genomic location to sma-miR-277 suggests that they form a miRNA cluster, and we propose hairpin folds for both miRNAs compatible with the miRNA pathway. In addition, we found that expression of sma-miR-277/4989 miRNAs are up-regulated in adults while their predicted targets are characterised by significant down-regulation in paired adult worms but remain largely undisturbed in immature “virgin” females. Finally, we show that sma-miR-4989 is expressed in tegumental cells located proximal to the oesophagus gland and also distributed throughout the male worms’ body. Our results indicate that sma-miR-277/4989 might play a dominant role in post-transcriptional regulation during development of juvenile worms and suggest an important role in the sexual development of female schistosomes. PMID:28542189

Latent class analysis to evaluate performance of point-of-care CCA for low-intensity Schistosoma mansoni infections in Burundi.

PubMed

Clements, Michelle N; Corstjens, Paul L A M; Binder, Sue; Campbell, Carl H; de Dood, Claudia J; Fenwick, Alan; Harrison, Wendy; Kayugi, Donatien; King, Charles H; Kornelis, Dieuwke; Ndayishimiye, Onesime; Ortu, Giuseppina; Lamine, Mariama Sani; Zivieri, Antonio; Colley, Daniel G; van Dam, Govert J

2018-02-23

Kato-Katz examination of stool smears is the field-standard method for detecting Schistosoma mansoni infection. However, Kato-Katz misses many active infections, especially of light intensity. Point-of-care circulating cathodic antigen (CCA) is an alternative field diagnostic that is more sensitive than Kato-Katz when intensity is low, but interpretation of CCA-trace results is unclear. To evaluate trace results, we tested urine and stool specimens from 398 pupils from eight schools in Burundi using four approaches: two in Burundi and two in a laboratory in Leiden, the Netherlands. In Burundi, we used Kato-Katz and point-of-care CCA (CCAB). In Leiden, we repeated the CCA (CCAL) and also used Up-Converting Phosphor Circulating Anodic Antigen (CAA). We applied Bayesian latent class analyses (LCA), first considering CCA traces as negative and then as positive. We used the LCA output to estimate validity of the prevalence estimates of each test in comparison to the population-level infection prevalence and estimated the proportion of trace results that were likely true positives. Kato-Katz yielded the lowest prevalence (6.8%), and CCAB with trace considered positive yielded the highest (53.5%). There were many more trace results recorded by CCA in Burundi (32.4%) than in Leiden (2.3%). Estimated prevalence with CAA was 46.5%. LCA indicated that Kato-Katz had the lowest sensitivity: 15.9% [Bayesian Credible Interval (BCI): 9.2-23.5%] with CCA-trace considered negative and 15.0% with trace as positive (BCI: 9.6-21.4%), implying that Kato-Katz missed approximately 85% of infections. CCAB underestimated disease prevalence when trace was considered negative and overestimated disease prevalence when trace was considered positive, by approximately 12 percentage points each way, and CAA overestimated prevalence in both models. Our results suggest that approximately 52.2% (BCI: 37.8-5.8%) of the CCAB trace readings were true infections. Whether measured in the laboratory or the

Simplification and Standardization of Dot-ELISA for Human Schistosomiasis Mansoni

DTIC Science & Technology

1987-01-01

Cross-reactivity between the S. mansoni antigen and human fascioliasis sera was noticed in 2 out of 8 patient sera. Good correlation between the...small tients with fascioliasis were tested, 2 gave weakly positive reactions with SWAP, but none cross- reacted with SEA. TABLE I. Comparison between...other editions a;. obsolete ... .,.. UNCLASSIFIED UNCLASSIEDE 17/88 (Contd.) 19. fascioliasis sera was noticed in 2 out of 8 patient sera. Good

Evaluation of oral therapy on Mansonial Schistosomiasis using single dose of Balanites aegyptiaca fruits and praziquantel.

PubMed

Koko, W S; Abdalla, H S; Galal, M; Khalid, H S

2005-01-01

The efficacy of Balanites aegyptiaca fruit mesocarp was compared with praziquantel in mice infected with Sudanese strain of Schistosoma mansoni. Infected mice were given a single dose of 200 mg/kg body weight of B. aegyptiaca fruit mesocarp and 200 mg/kg b.w. of praziquantel after 6 weeks from the onset of the infection. A significant reduction was observed in EPG (egg count per gram of faeces), eggs burden in tissues and recovery of adult worms (P<0.05) for both the plant and the drug-treated animals.

Elucidation of the in vitro and in vivo activities of bridged 1,2,4-trioxolanes, bridged 1,2,4,5-tetraoxanes, tricyclic monoperoxides, silyl peroxides, and hydroxylamine derivatives against Schistosoma mansoni.

PubMed

Cowan, Noemi; Yaremenko, Ivan A; Krylov, Igor B; Terent'ev, Alexander O; Keiser, Jennifer

2015-08-15

Praziquantel is currently the only drug available to treat schistosomiasis. Since drug resistance would be a major barrier for the increasing global attempts to eliminate schistosomiasis as a public health problem, efforts should go hand in hand with the discovery of novel treatment options. Synthetic peroxides might offer a good direction since their antischistosomal activity has been demonstrated in the laboratory. We studied 19 bridged 1,2,4,5-tetraoxanes, 2 tricyclic monoperoxides, 11 bridged 1,2,4-trioxolanes, 12 silyl peroxides, and 4 hydroxylamine derivatives against newly transformed schistosomula (NTS) and adult Schistosoma mansoni in vitro. Schistosomicidal compounds were tested for cytotoxicity followed by in vivo studies of the most promising compounds. Tricyclic monoperoxides, trioxolanes, and tetraoxanes revealed the highest in vitro activity against NTS (IC50s 0.4-20.2 μM) and adult schistosomes (IC50s 1.8-22.8 μM). Tetraoxanes showed higher cytotoxicity than antischistosomal activity. Selected trioxolane and tricyclic monoperoxides were tested in mice harboring an adult S. mansoni infection. The highest activity was observed for two trioxolanes, which showed moderate worm burden reductions (WBR) of 44.3% and 42.9% (p>0.05). Complexation of the compounds with β-cyclodextrin with the aim to improve solubility and gastrointestinal absorption did not increase in vivo antischistosomal efficacy. The high in vitro antischistosomal activity of trioxolanes and tricyclic monoperoxides is a promising basis for future investigations, with the focus on improving in vivo efficacy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Evaluating a point-of-care circulating cathodic antigen test (POC-CCA) to detect Schistosoma mansoni infections in a low endemic area in north-eastern Brazil.

PubMed

Bezerra, Fernando Schemelzer Moraes; Leal, Joames Kauffimann Freitas; Sousa, Mariana Silva; Pinheiro, Marta Cristhiany Cunha; Ramos, Alberto Novaes; Silva-Moraes, Vanessa; Katz, Naftale

2018-06-01

Schistosomiasis is still a public health problem in Brazil. The Kato-Katz test is the most frequently used diagnostic method for Schistosoma mansoni infection. However, it lacks sensitivity in areas of low prevalence. We have assessed the positivity rate of S. mansoni infection in Bananeiras, a village on Capistrano, Ceara, Brazil by performing a point-of-care test in urine to determine the circulating cathodic antigens (POC-CCA), and we compared the findings with those of the Kato-Katz technique for egg detection in stool and an enzyme-linked immunosorbent assay for specific antibodies against adult worms (SWAP-ELISA) in serum before treatment (baseline). Additionally, the POC-CCA and Kato-Katz test results were compared at one and two years post-treatment, and only POC-CCA strips were utilised for follow-up testing on urine samples at 3-6 weeks. Only one sample of stool and urine was collected per event. Overall, 258 individuals were investigated at the baseline. The POC-CCA test detected 10 (3.9%) positive cases; however, this amount increased to 30 (11.6%) when considering trace readings as positive (t + ), whereas the Kato-Katz method found only 4 (1.6%) positive cases and the SWAP-ELISA detected 105 (40.7%) positive cases. The consistency observed between a single POC-CCA (t + ) or (t-) and the Kato-Katz (three slides) was poor (Kappa indexes <0.20). The highest positivity rate as determined by CCA and Kato-Katz was found in adults. At the baseline, a praziquantel treatment was administered to all individuals regardless of their infection status. According to the POC-CCA test, 93% of the previous positive cases became negative by the third week after the treatment; this rate reached 100% at the sixth week assessment. The follow-up showed that of the 175 individuals evaluated at one year post-treatment, only one (0.6%) showed 'trace' results, and all the individuals were negative for eggs in the stool. At two years, all 185 examined individuals were

The small RNA complement of adult Schistosoma haematobium.

PubMed

Stroehlein, Andreas J; Young, Neil D; Korhonen, Pasi K; Hall, Ross S; Jex, Aaron R; Webster, Bonnie L; Rollinson, David; Brindley, Paul J; Gasser, Robin B

2018-05-01

Blood flukes of the genus Schistosoma cause schistosomiasis-a neglected tropical disease (NTD) that affects more than 200 million people worldwide. Studies of schistosome genomes have improved our understanding of the molecular biology of flatworms, but most of them have focused largely on protein-coding genes. Small non-coding RNAs (sncRNAs) have been explored in selected schistosome species and are suggested to play essential roles in the post-transcriptional regulation of genes, and in modulating flatworm-host interactions. However, genome-wide small RNA data are currently lacking for key schistosomes including Schistosoma haematobium-the causative agent of urogenital schistosomiasis of humans. MicroRNAs (miRNAs) and other sncRNAs of male and female adults of S. haematobium and small RNA transcription levels were explored by deep sequencing, genome mapping and detailed bioinformatic analyses. In total, 89 transcribed miRNAs were identified in S. haematobium-a similar complement to those reported for the congeners S. mansoni and S. japonicum. Of these miRNAs, 34 were novel, with no homologs in other schistosomes. Most miRNAs (n = 64) exhibited sex-biased transcription, suggestive of roles in sexual differentiation, pairing of adult worms and reproductive processes. Of the sncRNAs that were not miRNAs, some related to the spliceosome (n = 21), biogenesis of other RNAs (n = 3) or ribozyme functions (n = 16), whereas most others (n = 3798) were novel ('orphans') with unknown functions. This study provides the first genome-wide sncRNA resource for S. haematobium, extending earlier studies of schistosomes. The present work should facilitate the future curation and experimental validation of sncRNA functions in schistosomes to enhance our understanding of post-transcriptional gene regulation and of the roles that sncRNAs play in schistosome reproduction, development and parasite-host cross-talk.

Redesign of Schistosoma mansoni NAD+ catabolizing enzyme : the active site H103W mutation restores ADP-ribosyl cyclase activity†

PubMed Central

Kuhn, Isabelle; Kellenberger, Esther; Rognan, Didier; Lund, Frances E.; Muller-Steffner, Hélène; Schuber, Francis

2008-01-01

Schistosoma mansoni NAD(P)+ catabolizing enzyme (SmNACE) is a new member of the ADP-ribosyl cyclase family. In contrast to all the other enzymes which are involved in the production of metabolites that elicit Ca2+ mobilization, SmNACE is virtually unable to transform NAD+ into the second messenger cyclic ADP-ribose (cADPR). Sequence alignments revealed that one of four conserved residues within the active site of these enzymes was replaced in SmNACE by a histidine (His103) instead of the highly conserved tryptophan. To find out whether the inability of SmNACE to catalyze the canonical ADP-ribosyl cyclase reaction is linked to this change we have replaced His103 with a tryptophan. The H103W mutation in SmNACE was indeed found to restore ADP-ribosyl cyclase activity as cADPR amounts for 7% of the reaction products, i.e., a value larger than observed for other members of this family such as CD38. Introduction of a Trp103 residue provides some of the binding characteristics of mammalian ADP-ribosyl cyclases such as increased affinity for Cibacron blue and slow-binding inhibition by araF-NAD+. Homology modeling of wild-type and H103W mutant three-dimensional structures, and docking of substrates within the active sites, provide new insight into the catalytic mechanism of SmNACE. Both residue side chains share similar roles in the nicotinamide-ribose bond cleavage step leading to an E.ADP-ribosyl reaction intermediate. They diverge however in the evolution of this intermediate; His103 provides a more polar environment favoring the accessibility to water and hydrolysis leading to ADP-ribose at the expense of the intramolecular cyclization pathway resulting in cADPR. PMID:17002287

Species dependent impact of helminth-derived antigens on human macrophages infected with Mycobacterium tuberculosis: Direct effect on the innate anti-mycobacterial response

PubMed Central

Singh, Susmita K.; McKay, Derek M.

2017-01-01

Background In countries with a high prevalence of tuberculosis there is high coincident of helminth infections that might worsen disease outcome. While Mycobacterium tuberculosis (Mtb) gives rise to a pro-inflammatory Th1 response, a Th2 response is typical of helminth infections. A strong Th2 response has been associated with decreased protection against tuberculosis. Principal findings We investigated the direct effect of helminth-derived antigens on human macrophages, hypothesizing that helminths would render macrophages less capable of controlling Mtb. Measuring cytokine output, macrophage surface markers with flow cytometry, and assessing bacterial replication and phagosomal maturation revealed that antigens from different species of helminth directly affect macrophage responses to Mtb. Antigens from the tapeworm Hymenolepis diminuta and the nematode Trichuris muris caused an anti-inflammatory response with M2-type polarization, reduced macrophage phagosome maturation and ability to activate T cells, along with increased Mtb burden, especially in T. muris exposed cells which also induced the highest IL-10 production upon co-infection. However, antigens from the trematode Schistosoma mansoni had the opposite effect causing a decrease in IL-10 production, M1-type polarization and increased control of Mtb. Conclusion We conclude that, independent of any adaptive immune response, infection with helminth parasites, in a species-specific manner can influence the outcome of tuberculosis by either enhancing or diminishing the bactericidal function of macrophages. PMID:28192437

Comparison of Th1- and Th2-associated immune reactivities stimulated by single versus multiple vaccination of mice with irradiated Schistosoma mansoni cercariae

DOE Office of Scientific and Technical Information (OSTI.GOV)

Caulada-Benedetti, Z.; Al-Zamel, F.; Sher, A.

1991-03-01

Mice immunized against Schistosoma mansoni by a single percutaneous exposure to radiation-attenuated parasite larvae demonstrate partial resistance to challenge infection that has been shown to correlate with development of cell-mediated immunity, whereas mice hyperimmunized by multiple exposure to attenuated larvae produce antibodies capable of transferring partial protection to naive recipients. Measurement of Ag-specific lymphokine responses in these animals suggested that the difference in resistance mechanisms may be due to the differential induction of Th subset response by the two immunization protocols. Thus, upon Ag stimulation, singly immunized mice predominantly demonstrated responses associated with Th1 reactivity, including IL-2 and IFN-gamma production,more » whereas multiply immunized animals showed increased IL-5, IL-4, and IgG1 antibody production associated with enhanced Th2 response. These responses demonstrated some degree of organ compartmentalization, with splenocytes demonstrating higher Th1-related lymphokine production and cells from draining lymph nodes showing stronger proliferation and Th2 type reactivity. However, hyperimmunized mice also continued to demonstrate substantial Th1-associated immune reactivity. Moreover, in vivo Ag challenge elicited activated larvacidal macrophages in hyperimmunized animals. These observations indicate that protective cell-mediated mechanisms associated with induction of CD4+ Th1 cell reactivity predominate in singly vaccinated mice. Further vaccination stimulates Th2 responses, such as enhanced IgG1 production, that may also contribute to protective immunity.« less

In Vitro Assessment of Anthelmintic Activities of Rauwolfia vomitoria (Apocynaceae) Stem Bark and Roots against Parasitic Stages of Schistosoma mansoni and Cytotoxic Study

PubMed Central

Bosompem, Kwabena Mante; Anyan, William Kofi; Owusu, Kofi Baffour-Awuah; Tettey, Mabel Deladem; Kissi, Felicia Amanfo; Appiah, Alfred Ampomah; Penlap Beng, Veronique; Nyarko, Alexander Kwadwo

2017-01-01

Schistosomiasis is a Neglected Tropical Diseases which can be prevented with mass deworming chemotherapy. The reliance on a single drug, praziquantel, is a motivation for the search of novel antischistosomal compounds. This study investigated the anthelmintic activity of the stem bark and roots of Rauwolfia vomitoria against two life stages of Schistosoma mansoni. Both plant parts were found to be active against cercariae and adult worms. Within 2 h of exposure all cercariae were killed at a concentration range of 62.5–1000 µg/mL and 250–1000 µg/mL of R. vomitoria stem bark and roots, respectively. The LC50 values determined for the stem bark after 1 and 2 h of exposure were 207.4 and 61.18 µg/mL, respectively. All adult worms exposed to the concentrations range of 250–1000 µg/mL for both plant parts died within 120 h of incubation. The cytotoxic effects against HepG2 and Chang liver cell assessed using MTT assay method indicated that both plant extracts which were inhibitory to the proliferation of cell lines with IC50 > 20 μg/mL appear to be safe. This report provides the first evidence of in vitro schistosomicidal potency of R. vomitoria with the stem bark being moderately, but relatively, more active and selective against schistosome parasites. This suggests the presence of promising medicinal constituent(s). PMID:28348881

High Throughput Screening Identifies Novel Lead Compounds with Activity against Larval, Juvenile and Adult Schistosoma mansoni

PubMed Central

Gardner, J. Mark F.; Bell, Andrew S.; Parkinson, Tanya; Bickle, Quentin

2016-01-01

An estimated 600 million people are affected by the helminth disease schistosomiasis caused by parasites of the genus Schistosoma. There is currently only one drug recommended for treating schistosomiasis, praziquantel (PZQ), which is effective against adult worms but not against the juvenile stage. In an attempt to identify improved drugs for treating the disease, we have carried out high throughput screening of a number of small molecule libraries with the aim of identifying lead compounds with balanced activity against all life stages of Schistosoma. A total of almost 300,000 compounds were screened using a high throughput assay based on motility of worm larvae and image analysis of assay plates. Hits were screened against juvenile and adult worms to identify broadly active compounds and against a mammalian cell line to assess cytotoxicity. A number of compounds were identified as promising leads for further chemical optimization. PMID:27128493

Synthesis and evaluation of 1,4-naphthoquinone ether derivatives as SmTGR inhibitors and new anti-schistosomal drugs.

PubMed

Johann, Laure; Belorgey, Didier; Huang, Hsin-Hung; Day, Latasha; Chessé, Matthieu; Becker, Katja; Williams, David L; Davioud-Charvet, Elisabeth

2015-08-01

Investigations regarding the chemistry and mechanism of action of 2-methyl-1,4-naphthoquinone (or menadione) derivatives revealed 3-phenoxymethyl menadiones as a novel anti-schistosomal chemical series. These newly synthesized compounds (1-7) and their difluoromethylmenadione counterparts (8, 9) were found to be potent and specific inhibitors of Schistosoma mansoni thioredoxin-glutathione reductase (SmTGR), which has been identified as a potential target for anti-schistosomal drugs. The compounds were also tested in enzymic assays using both human flavoenzymes, i.e. glutathione reductase (hGR) and selenium-dependent human thioredoxin reductase (hTrxR), to evaluate the specificity of the inhibition. Structure-activity relationships as well as physico- and electro-chemical studies showed a high potential for the 3-phenoxymethyl menadiones to inhibit SmTGR selectively compared to hGR and hTrxR enzymes, in particular those bearing an α-fluorophenol methyl ether moiety, which improves anti-schistosomal action. Furthermore, the (substituted phenoxy)methyl menadione derivative (7) displayed time-dependent SmTGR inactivation, correlating with unproductive NADPH-dependent redox cycling of SmTGR, and potent anti-schistosomal action in worms cultured ex vivo. In contrast, the difluoromethylmenadione analog 9, which inactivates SmTGR through an irreversible non-consuming NADPH-dependent process, has little killing effect in worms cultured ex vivo. Despite ex vivo activity, none of the compounds tested was active in vivo, suggesting that the limited bioavailability may compromise compound activity. Therefore, future studies will be directed toward improving pharmacokinetic properties and bioavailability. © 2015 FEBS.

Effect of Ketoconazole, a Cytochrome P450 Inhibitor, on the Efficacy of Quinine and Halofantrine against Schistosoma mansoni in Mice

PubMed Central

Sabra, Abdel-Nasser Abdel-Aal; Hammam, Olfat Ali; El-Lakkany, Naglaa Mohamed

2013-01-01

The fear that schistosomes will become resistant to praziquantel (PZQ) motivates the search for alternatives to treat schistosomiasis. The antimalarials quinine (QN) and halofantrine (HF) possess moderate antischistosomal properties. The major metabolic pathway of QN and HF is through cytochrome P450 (CYP) 3A4. Accordingly, this study investigates the effects of CYP3A4 inhibitor, ketoconazole (KTZ), on the antischistosomal potential of these quinolines against Schistosoma mansoni infection by evaluating parasitological, histopathological, and biochemical parameters. Mice were classified into 7 groups: uninfected untreated (I), infected untreated (II), infected treated orally with PZQ (1,000 mg/kg) (III), QN (400 mg/kg) (IV), KTZ (10 mg/kg)+QN as group IV (V), HF (400 mg/kg) (VI), and KTZ (as group V)+HF (as group VI) (VII). KTZ plus QN or HF produced more inhibition (P<0.05) in hepatic CYP450 (85.7% and 83.8%) and CYT b5 (75.5% and 73.5%) activities, respectively, than in groups treated with QN or HF alone. This was accompanied with more reduction in female (89.0% and 79.3%), total worms (81.4% and 70.3%), and eggs burden (hepatic; 83.8%, 66.0% and intestinal; 68%, 64.5%), respectively, and encountering the granulomatous reaction to parasite eggs trapped in the liver. QN and HF significantly (P<0.05) elevated malondialdehyde levels when used alone or with KTZ. Meanwhile, KTZ plus QN or HF restored serum levels of ALT, albumin, and reduced hepatic glutathione (KTZ+HF) to their control values. KTZ enhanced the therapeutic antischistosomal potential of QN and HF over each drug alone. Moreover, the effect of KTZ+QN was more evident than KTZ+HF. PMID:23710083

Reprint Accession List 1979. Number 9.

DTIC Science & Technology

1980-01-01

2(8153):1184-1185, 1979 Acc. No. 1202 BARSOUM, R.S., BASSILY, S., SOLIMAN, M.M., RAMZY, M.F., MILAD, M. and HASSABALLA, A-M.: Renal Amyloidosis and...Number PARASITOLOGY Schistosoma mansoni 1185, 1195 Schistosoma mansoni infection in hamsters 1188 PATHOLOGY Renal Amyloidosis 1202 RADIOLOGY The effect

Human Schistosomiasis: Clinical Perspective: Review

PubMed Central

Barsoum, Rashad S.; Esmat, Gamal; El-Baz, Tamer

2013-01-01

The clinical manifestations of schistosomiasis pass by acute, sub acute and chronic stages that mirror the immune response to infection. The later includes in succession innate, TH1 and TH2 adaptive stages, with an ultimate establishment of concomitant immunity. Some patients may also develop late complications, or suffer the sequelae of co-infection with other parasites, bacteria or viruses. Acute manifestations are species-independent; occur during the early stages of invasion and migration, where infection-naivety and the host’s racial and genetic setting play a major role. Sub acute manifestations occur after maturity of the parasite and settlement in target organs. They are related to the formation of granulomata around eggs or dead worms, primarily in the lower urinary tract with Schistosoma haematobium, and the colon and rectum with Schistosoma mansoni, Schistosoma japonicum, Schistosoma intercalatum and Schistosoma mekongi infection. Secondary manifestations during this stage may occur in the kidneys, liver, lungs or other ectopic sites. Chronic morbidity is attributed to the healing of granulomata by fibrosis and calcification at the sites of oval entrapment, deposition of schistosomal antigen-antibody complexes in the renal glomeruli or the development of secondary amyloidosis. Malignancy may complicate the chronic lesions in the urinary bladder or colon. Co-infection with salmonella or hepatitis viruses B or C may confound the clinical picture of schistosomiasis, while the latter may have a negative impact on the course of other co-infections as malaria, leishmaniasis and HIV. Prevention of schistosomiasis is basically geared around education and periodic mass treatment, an effective vaccine being still experimental. Praziquantel is the drug of choice in the treatment of active infection by any species, with a cure rate of 80%. Other antischistosomal drugs include metrifonate for S. haematobium, oxamniquine for S. mansoni and Artemether and, possibly

21 CFR 866.3600 - Schistosoma spp. serological reagents.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Schistosoma spp. serological reagents. 866.3600 Section 866.3600 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3600 Schistosoma...

21 CFR 866.3600 - Schistosoma spp. serological reagents.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Schistosoma spp. serological reagents. 866.3600 Section 866.3600 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3600 Schistosoma...

21 CFR 866.3600 - Schistosoma spp. serological reagents.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Schistosoma spp. serological reagents. 866.3600 Section 866.3600 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3600 Schistosoma...

21 CFR 866.3600 - Schistosoma spp. serological reagents.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Schistosoma spp. serological reagents. 866.3600 Section 866.3600 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3600 Schistosoma...

21 CFR 866.3600 - Schistosoma spp. serological reagents.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Schistosoma spp. serological reagents. 866.3600 Section 866.3600 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3600 Schistosoma...

Sm10.3, a Member of the Micro-Exon Gene 4 (MEG-4) Family, Induces Erythrocyte Agglutination In Vitro and Partially Protects Vaccinated Mice against Schistosoma mansoni Infection

PubMed Central

Martins, Vicente P.; Morais, Suellen B.; Pinheiro, Carina S.; Assis, Natan R. G.; Figueiredo, Barbara C. P.; Ricci, Natasha D.; Alves-Silva, Juliana; Caliari, Marcelo V.; Oliveira, Sergio C.

2014-01-01

Background The parasitic flatworm Schistosoma mansoni is a blood fluke that causes schistosomiasis. Current schistosomiasis control strategies are mainly based on chemotherapy, but many researchers believe that the best long-term strategy to control disease is a combination of drug treatment and immunization with an anti-schistosome vaccine. Numerous antigens that are expressed at the interface between the parasite and the mammalian host have been assessed. Among the most promising molecules are the proteins present in the tegument and digestive tract of the parasite. Methodology/Principal Findings In this study, we evaluated the potential of Sm10.3, a member of the micro-exon gene 4 (MEG-4) family, for use as part of a recombinant vaccine. We confirmed by real-time PCR that Sm10.3 was expressed at all stages of the parasite life cycle. The localization of Sm10.3 on the surface and lumen of the esophageal and intestinal tract in adult worms and lung-stage schistosomula was confirmed by confocal microscopy. We also show preliminary evidence that rSm10.3 induces erythrocyte agglutination in vitro. Immunization of mice with rSm10.3 induced a mixed Th1/Th2-type response, as IFN-γ, TNF-α, and low levels of IL-5 were detected in the supernatant of cultured splenocytes. The protective effect conferred by vaccination with rSm10.3 was demonstrated by 25.5–32% reduction in the worm burden, 32.9–43.6% reduction in the number of eggs per gram of hepatic tissue, a 23.8% reduction in the number of granulomas, an 11.8% reduction in the area of the granulomas and a 39.8% reduction in granuloma fibrosis. Conclusions/Significance Our data suggest that Sm10.3 is a potential candidate for use in developing a multi-antigen vaccine to control schistosomiasis and provide the first evidence for a possible role for Sm10.3 in the blood feeding process. PMID:24651069

Sm10.3, a member of the micro-exon gene 4 (MEG-4) family, induces erythrocyte agglutination in vitro and partially protects vaccinated mice against Schistosoma mansoni infection.

PubMed

Martins, Vicente P; Morais, Suellen B; Pinheiro, Carina S; Assis, Natan R G; Figueiredo, Barbara C P; Ricci, Natasha D; Alves-Silva, Juliana; Caliari, Marcelo V; Oliveira, Sergio C

2014-03-01

The parasitic flatworm Schistosoma mansoni is a blood fluke that causes schistosomiasis. Current schistosomiasis control strategies are mainly based on chemotherapy, but many researchers believe that the best long-term strategy to control disease is a combination of drug treatment and immunization with an anti-schistosome vaccine. Numerous antigens that are expressed at the interface between the parasite and the mammalian host have been assessed. Among the most promising molecules are the proteins present in the tegument and digestive tract of the parasite. In this study, we evaluated the potential of Sm10.3, a member of the micro-exon gene 4 (MEG-4) family, for use as part of a recombinant vaccine. We confirmed by real-time PCR that Sm10.3 was expressed at all stages of the parasite life cycle. The localization of Sm10.3 on the surface and lumen of the esophageal and intestinal tract in adult worms and lung-stage schistosomula was confirmed by confocal microscopy. We also show preliminary evidence that rSm10.3 induces erythrocyte agglutination in vitro. Immunization of mice with rSm10.3 induced a mixed Th1/Th2-type response, as IFN-γ, TNF-α, and low levels of IL-5 were detected in the supernatant of cultured splenocytes. The protective effect conferred by vaccination with rSm10.3 was demonstrated by 25.5-32% reduction in the worm burden, 32.9-43.6% reduction in the number of eggs per gram of hepatic tissue, a 23.8% reduction in the number of granulomas, an 11.8% reduction in the area of the granulomas and a 39.8% reduction in granuloma fibrosis. Our data suggest that Sm10.3 is a potential candidate for use in developing a multi-antigen vaccine to control schistosomiasis and provide the first evidence for a possible role for Sm10.3 in the blood feeding process.

Prevalence of intestinal helminth infection among school children in Maksegnit and Enfranz Towns, northwestern Ethiopia, with emphasis on Schistosoma mansoni infection.

PubMed

Gashaw, Fikru; Aemero, Mulugeta; Legesse, Mengistu; Petros, Beyene; Teklehaimanot, Tilahun; Medhin, Girmay; Berhe, Nega; Mekonnen, Yalemtsehay; Erko, Berhanu

2015-10-31

Schistosomiasis is endemic in Ethiopia and previously unknown transmission foci have been reported from time to time in different parts of the country. Further surveys are required in areas where endemicity of the disease is not known to cover them with control program if transmission is taking place. This study, therefore, aims to assess the magnitude of schistosomiasis mansoni and soil-transmitted helminthiasis in Maksegnit and Enfranz Towns, northwestern Ethiopia. Cross-sectional parasitological and malacological surveys were conducted in three schools found in Maksegnit and Enfranz Towns. Stool specimens were collected from 550 randomly selected school children (age range 5 to 17 years) and processed for microscopic examination using Kato-Katz method (single smear per stool sample). Malacological survey was conducted in Gumara and Garno Rivers found in the study areas. Biomphalaria pfeifferi snails collected from the two rivers were individually exposed to artificial light in order to induce cercarial shedding. Laboratory-bred Swiss albino mice were exposed to the cercariae and definite identification of the schistosome species was made based on morphology. The overall prevalence of S. mansoni infection was found to be 49%; however, it varied by schools, with Selam having 60.7%, and Maksegnit Number 1 and 2 having 45.8 and 39.6%, respectively. The respective mean intensity of S. mansoni infection among school children in Selam, Maksegnit Number 1 and Maksegnit Number 2 Schools were 243, 194 and 183 eggs per gram of stool (epg). In all the study areas there was no difference in prevalence of S. mansoni infection in relation to age, however, the prevalence varied by sex, with males having highest prevalence (54.5% vs 44.1%) (p = 0.012). Adult S. mansoni worms were harvested from mice exposed to cercariae shed from B. pfeifferi on the 6(th) week post-exposure. The prevalence of Ascaris lumbricoides single infection was 16.5% while its co-infection with S

Histone deacetylase inhibition modulates histone acetylation at gene promoter regions and affects genome-wide gene transcription in Schistosoma mansoni

PubMed Central

Anderson, Letícia; Gomes, Monete Rajão; daSilva, Lucas Ferreira; Pereira, Adriana da Silva Andrade; Mourão, Marina M.; Romier, Christophe; Pierce, Raymond

2017-01-01

Background Schistosomiasis is a parasitic disease infecting hundreds of millions of people worldwide. Treatment depends on a single drug, praziquantel, which kills the Schistosoma spp. parasite only at the adult stage. HDAC inhibitors (HDACi) such as Trichostatin A (TSA) induce parasite mortality in vitro (schistosomula and adult worms), however the downstream effects of histone hyperacetylation on the parasite are not known. Methodology/Principal findings TSA treatment of adult worms in vitro increased histone acetylation at H3K9ac and H3K14ac, which are transcription activation marks, not affecting the unrelated transcription repression mark H3K27me3. We investigated the effect of TSA HDACi on schistosomula gene expression at three different time points, finding a marked genome-wide change in the transcriptome profile. Gene transcription activity was correlated with changes on the chromatin acetylation mark at gene promoter regions. Moreover, combining expression data with ChIP-Seq public data for schistosomula, we found that differentially expressed genes having the H3K4me3 mark at their promoter region in general showed transcription activation upon HDACi treatment, compared with those without the mark, which showed transcription down-regulation. Affected genes are enriched for DNA replication processes, most of them being up-regulated. Twenty out of 22 genes encoding proteins involved in reducing reactive oxygen species accumulation were down-regulated. Dozens of genes encoding proteins with histone reader motifs were changed, including SmEED from the PRC2 complex. We targeted SmEZH2 methyltransferase PRC2 component with a new EZH2 inhibitor (GSK343) and showed a synergistic effect with TSA, significantly increasing schistosomula mortality. Conclusions/Significance Genome-wide gene expression analyses have identified important pathways and cellular functions that were affected and may explain the schistosomicidal effect of TSA HDACi. The change in expression

Genetic Manipulation of Schistosoma haematobium, the Neglected Schistosome

PubMed Central

Rinaldi, Gabriel; Okatcha, Tunika I.; Popratiloff, Anastas; Ayuk, Mary A.; Suttiprapa, Sutas; Mann, Victoria H.; Liang, Yung-san; Lewis, Fred A.; Loukas, Alex; Brindley, Paul J.

2011-01-01

Background Minimal information on the genome and proteome of Schistosoma haematobium is available, in marked contrast to the situation with the other major species of human schistosomes for which draft genome sequences have been reported. Accordingly, little is known about functional genomics in S. haematobium, including the utility or not of RNA interference techniques that, if available, promise to guide development of new interventions for schistosomiasis haematobia. Methods/Findings Here we isolated and cultured developmental stages of S. haematobium, derived from experimentally infected hamsters. Targeting different developmental stages, we investigated the utility of soaking and/or square wave electroporation in order to transfect S. haematobium with nucleic acid reporters including Cy3-labeled small RNAs, messenger RNA encoding firefly luciferase, and short interfering RNAs (siRNAs). Three hours after incubation of S. haematobium eggs in 50 ng/µl Cy3-labeled siRNA, fluorescent foci were evident indicating that labeled siRNA had penetrated into miracidia developing within the egg shell. Firefly luciferase activity was detected three hours after square wave electroporation of the schistosome eggs and adult worms in 150 ng/µl of mRNA. RNA interference knockdown (silencing) of reporter luciferase activity was seen following the introduction of dsRNA specific for luciferase mRNA in eggs, schistosomules and mixed sex adults. Moreover, introduction of an endogenous gene-specific siRNA into adult schistosomes silenced transcription of tetraspanin 2 (Sh-tsp-2), the apparent orthologue of the Schistosoma mansoni gene Sm-tsp-2 which encodes the surface localized structural and signaling protein Sm-TSP-2. Together, knockdown of reporter luciferase and Sh-tsp-2 indicated the presence of an intact RNAi pathway in S. haematobium. Also, we employed laser scanning confocal microscopy to view the adult stages of S. haematobium. Conclusions These findings and approaches

Sustaining Control of Schistosomiasis Mansoni in Western Côte d’Ivoire: Results from a SCORE Study, One Year after Initial Praziquantel Administration

PubMed Central

Assaré, Rufin K.; Tian-Bi, Yves-Nathan T.; Yao, Patrick K.; N’Guessan, Nicaise A.; Ouattara, Mamadou; Yapi, Ahoua; Coulibaly, Jean T.; Meïté, Aboulaye; Hürlimann, Eveline; Knopp, Stefanie; Utzinger, Jürg; N’Goran, Eliézer K.

2016-01-01

Background The Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) has launched several large-scale trials to determine the best strategies for gaining and sustaining control of schistosomiasis and transitioning toward elimination. In Côte d’Ivoire, a 5-year cluster-randomized trial is being implemented in 75 schools to sustain the control of schistosomiasis mansoni. We report Schistosoma mansoni infection levels in children one year after the initial school-based treatment (SBT) with praziquantel and compare with baseline results to determine the effect of the intervention. Methodology The baseline cross-sectional survey was conducted in late 2011/early 2012 and the first follow-up in May 2013. Three consecutive stool samples were collected from 9- to 12-year-old children in 75 schools at baseline and 50 schools at follow-up. Stool samples were subjected to duplicate Kato-Katz thick smears. Directly observed treatment (DOT) coverage of the SBT was assessed and the prevalence and intensity of S. mansoni infection compared between baseline and follow-up. Principal Findings The S. mansoni prevalence in the 75 schools surveyed at baseline was 22.1% (95% confidence interval (CI): 19.5–24.4%). The DOT coverage was 84.2%. In the 50 schools surveyed at baseline and one year after treatment, the overall prevalence of S. mansoni infection decreased significantly from 19.7% (95% CI: 18.5–20.8%) to 12.8% (95% CI: 11.9–13.8%), while the arithmetic mean S. mansoni eggs per gram of stool (EPG) among infected children slightly increased from 92.2 EPG (95% CI: 79.2–105.3 EPG) to 109.3 EPG (95% CI: 82.7–135.9 EPG). In two of the 50 schools, the prevalence increased significantly, despite a DOT coverage of >75%. Conclusions/Significance One year after the initial SBT, the S. mansoni prevalence had decreased. Despite this positive trend, an increase was observed in some schools. Moreover, the infection intensity among S. mansoni-infected children

Comparison of self-reported and observed water contact in an S. mansoni endemic village in Brazil.

PubMed

Friedman, J F; Kurtis, J D; McGarvey, S T; Fraga, A L; Silveira, A; Pizziolo, V; Gazzinelli, G; LoVerde, P; Corrêa-Oliveira, R

2001-03-30

Estimates of exposure are critical for immuno-epidemiologic and intervention studies in human schistosomiasis. Direct observation of human water contact patterns is both costly and time consuming. To address these issues, we determined whether individuals residing in a Schistosoma mansoni endemic village in Brazil could accurately self-report their water contact patterns. We compared the results of a water contact questionnaire to the present gold standard, direct observation of water contact in 86 volunteers, aged 8--29. We administered a survey to estimate volunteers' frequency and type of water contact and directly measured each volunteers' water contact patterns during 5 weeks of detailed water contact observations. We found a poor correlation between self reported frequency of contact and directly observed exposure (rho=0.119, P=NS). The questionnaire data was supplemented by information about average body surface area of exposure and duration of contact for specific activities derived from observations of this cohort. This 'supplemented questionnaire' data was significantly correlated with their exposure index (rho=0.227, P=0.05). It provides a starting point from which questionnaires may develop to provide a more cost-effective and less labor intensive method of assessing water contact exposure at the level of the individual.

Coinfection of Schistosoma (Trematoda) with bacteria, protozoa and helminths.

PubMed

Abruzzi, Amy; Fried, Bernard

2011-01-01

, the increased severity of the subsequent infection was associated with a specific, prolonged form of the disease in humans, which has implications for patient treatment and recovery. Additional research is needed, particularly on Schistosoma coinfections which currently have a small body of research and are current problems in human populations. Examples of such Schistosoma interactions include the genera of Mycobacteria, Leishmania, Staphylococcus, Necator and Strongyloides. Hopefully, future studies will elucidate valuable new information on the interesting subject of coinfection of Schistosoma with other organisms. Copyright © 2011 Elsevier Ltd. All rights reserved.

Pharmacological manipulation of the chronic granulomatous reactions in the livers of mice infected with schistosomiasis.

PubMed

Rainsford, K D

1985-01-01

The severe granulomatous reactions in the liver which occur following infestation by adult Schistosoma mansonii are largely initiated by invading eosinophils and monocytes. The present studies were designed to investigate the possibility that (a) anti-inflammatory drugs could be employed beneficially to attenuate the liver granulomatous reactions in schistosomiasis, and (b) that part of the therapeutic effects of anti-schistosomal (AS) drugs might be due to possible influences on arachidonate metabolism. Therefore the effects were determined of (a) AS as compared with NSAI drugs on eicosanoid metabolism in isolated human peripheral leucocyte populations, and (b) electron-microscopic changes in the livers of mice infected with Schistosoma mansoni in response to AS and/or NSAI drugs. Of the AS drugs only praziquantel (10-100 microM) inhibited 5-HETE production by the 5-lipoxygenase pathway. No effects were observed of this or the other AS drugs on prostaglandin production. In S. mansoni infected mice, praziquantel (250 mg/kg/d), given orally with indomethacin (5 mg/kg/d) for 5 days did not improve the inflammatory reactions around worms or eggs of schistosomes. Furthermore, both indomethacin (5 mg/kg/d) alone and benoxaprofen (20 mg/kg/d for 5 days) elicited liver changes suggestive of specific liver damage by these drugs. These results suggest that liver pathology may be enhanced by NSAI drugs perhaps as a consequence of the liver metabolism of these drugs being compromised. Their use to modify inflammatory reactions at the peak of liver schistosome infections may thus be contraindicated.

HPLC-ESI-MS Characterization of Certain Polyphenolic Compounds of Carica papaya L. Fruit Extracts and Evaluation of Their Potential Against Murine Schistosomiasis mansoni.

PubMed

Abdel-Lateef, Ezzat El-Sayed; Rabia, Ibrahim Aly; El-Sayed, Mortada Mohamed; Abdel-Hameed, El-Sayed Saleh

2018-04-10

The in vivo antischistosomal activities of Carica papaya L. extracts were evaluated and the characterization of the active secondary metabolites of the defatted methanolic extract was performed using HPLC-ESI-MS. The plant fruit powders were extracted with 85% methanol and fractionated using organic solvents. The in vivo antischistosomal effects of the methanolic extracts and its fractions, as well as the assessment of the relationship between the antischistosomal activity of these plant extracts and oxidative stress, was determined. In addition, the defatted methanolic extract was characterized by HPLC-ESI-MS analysis. The number of worms, ova, and the Oogram pattern displayed typical Schistosoma mansoni pathology 8 weeks after infection in mice. Treatment of the infected group with the defatted methanolic extracts significantly decreased worm burden, immature ova and mature ova, while increasing the percentage of dead ova in vivo. The butanol fraction was the most effective fraction reducing worm burden by 77%, ova count in the intestine by 76% and in the liver by 80%, and significantly decreased immature and mature ova ( P <0.001) compared to the infected group. Additionally, the defatted methanolic extracts improved the reduced glutathione and malondialdehyde levels in hepatic tissues in the treated groups compared to the infected group. The HPLC-ESI-MS analysis of the Carica papaya defatted methanolic extract revealed the presence of several polyphenolic compounds. Carica papaya fruit extracts are rich with phenolic acids and flavonoids and show a significant effect against S. mansoni infections which may be used alternative to PZQ as anti-schistosomal drug against schistosomiasis. © Georg Thieme Verlag KG Stuttgart · New York.

Anti-schistosomal activity of cyclosporin A: studies on murine spleen cells and the influence of a cyclosporin antagonist on resistance to infection.

PubMed Central

Brannan, L R; Chappell, L H; Woo, J; Thomson, A W

1989-01-01

Mice were treated with 5-day courses of cyclosporin A (CsA) around the time of infection with Schistosoma mansoni. Recovery of lung-stage worms 4-8 days post-infection (p.i.) was substantially reduced (80%) and no sexually mature adults were recovered from the hepatic portal system at 7 weeks p.i. Flow cytometric analysis of spleen cells from CsA-treated animals during the period of maximal parasite attrition revealed transient reductions in CD3+ and CD4+ cells and in the CD4+: CD8+ ratio compared with drug vehicle-treated, infected controls. No significant numerical changes in B cells, macrophages or eosinophils were detected relative to vehicle-treated infected mice. Transfer of spleen cells from CsA-treated donors 8 days after infection failed to confer increased resistance to S. mansoni infection on untreated recipients. Moreover, concomitant administration of CsA and an inducer of interleukin-2 production (ADA-202-718) did not interfere with the anti-schistosomal effect of CsA. Despite our incomplete understanding of the in vivo properties of CsA and reports of its paradoxical effects on immune responses, these new data indicate that the influence of CsA in schistosomiasis is unlikely to be mediated by modulation of host cell mediated immunity. This contrasts with certain other anti-parasitic effects of CsA which appear to be mediated by an action on T cells. PMID:2503438

RESISTANCE PRODUCED IN MICE BY EXPOSURE TO IRRADIATED SCHISTOSOMA MANSONI CERCARIAE

DOE Office of Scientific and Technical Information (OSTI.GOV)

Radke, M.G.; Sadun, E.H.

1963-04-01

Studies were undertaken to determine whether gamma irradiation of cercariae might provide a means of investigating some of the mechanisms involved in the acquired resistance to schistosomiasis. Control mice received 200 nonirradiated cercariae, and other groups received the same number of cercariae that had been exposed to 6 different doses of Co/sup 60/ gamma irradiation varying from 1000--20000 rep. Eight weeks later the worms recovered were counted. Doses of 4000 rep or higher completely inhibited the development of schistosomes. A few stunted and underdeveloped worms were found in some of the mice receiving cercariae irradiated at 2500 and 3000 rep.more » Some adult schistosomes were observed in the groups receiving 1500 and 2000 rep and eggs were found in the liver but not in the stools of some mice. However, all of the mice exposed to cercariae irradiated with 1000 rep had eggs in liver and stools. The worm burden decreased regularly with increasing dosages up to 3000 rep, beyond which no worms were found at necropsy. The decrease in the number of worms mice acquired was linear only when cercariae were exposed from 1000to 2000 rep, however, even beyond such dosages, it followed a straight line when the logarithm of irradiation dose was plotied. Acquired resistance to S. mansoni was observed in mice following a previous exposure to irradiated cercariae. (TCO)« less

The burden, pattern and factors that contribute to periportal fibrosis in HIV-infected patients in an S. mansoni endemic rural Uganda.

PubMed

Ocama, Ponsiano; Opio, Kenneth Christopher; Seremba, Emmanuel; Ajal, Paul; Apica, Betty Stephanie; Aginya, Emmanuel Odongo

2017-06-01

Both Human Immunodeficiency Virus (HIV) and S.mansoni infections are common in Uganda and can cause liver disease. No study has determined co-infection significance in Uganda. We carried out a study on the burden, pattern and factors that contribute to peri-portal fibrosis (PPF) in HIV infected patients attending a Primary healthcare setting at Pakwach. We conducted a cross-sectional study in the HIV clinic at Pakwach health centre IV. Data on demographics, contact with the Nile, CD4 + cell count, ART and alcohol use were collected. Urinary Circulating Cathodic Antigen (CCA), was done for S. Mansoni detection. Liver scan was done for presence and pattern of PPF. HBsAg testing was performed on all participants. Data was analyzed using Stata Version 10. We enrolled 299 patients, median age 39 years (IQR 16), most were female, 210 (73%). Overall, 206 (68.9%) had PPF, majority 191 (92.7%) had pattern c, either alone (63 participants) or in combination with pattern d (128 participants). Age of 30-50 years was significantly associated with PPF (OR 2.28 p-value-0.003). We found high prevalence of S. mansoni and PPF in the HIV infected population and age was a significant factor for PPF. We recommend all HIV infected patients be examined routinely for S. mansoni infection for early anti-schistosomal treatment.

Parasitic Helminths: New Weapons against Immunological Disorders

PubMed Central

Osada, Yoshio; Kanazawa, Tamotsu

2010-01-01

The prevalence of allergic and autoimmune diseases is increasing in developed countries, possibly due to reduced exposure to microorganisms in childhood (hygiene hypothesis). Epidemiological and experimental evidence in support of this hypothesis is accumulating. In this context, parasitic helminths are now important candidates for antiallergic/anti-inflammatory agents. Here we summarize antiallergic/anti-inflammatory effects of helminths together along with our own study of the effects of Schistosoma mansoni on Th17-dependent experimental arthritis. We also discuss possible mechanisms of helminth-induced suppression according to the recent advances of immunology. PMID:20169100

Parasitic helminths: new weapons against immunological disorders.

PubMed

Osada, Yoshio; Kanazawa, Tamotsu

2010-01-01

The prevalence of allergic and autoimmune diseases is increasing in developed countries, possibly due to reduced exposure to microorganisms in childhood (hygiene hypothesis). Epidemiological and experimental evidence in support of this hypothesis is accumulating. In this context, parasitic helminths are now important candidates for antiallergic/anti-inflammatory agents. Here we summarize antiallergic/anti-inflammatory effects of helminths together along with our own study of the effects of Schistosoma mansoni on Th17-dependent experimental arthritis. We also discuss possible mechanisms of helminth-induced suppression according to the recent advances of immunology.

Schistosoma Infection and Schistosoma-Derived Products Modulate the Immune Responses Associated with Protection against Type 2 Diabetes

PubMed Central

Tang, Chun-Lian; Liu, Zhi-Ming; Gao, Yan Ru; Xiong, Fei

2018-01-01

Studies on parasite-induced immunoregulatory mechanisms could contribute to the development of new therapies for inflammatory diseases such as type 2 diabetes (T2D), which is a chronic inflammatory disease characterized by persistent elevated glucose levels due to insulin resistance. The association between previous Schistosoma infection and T2D has been confirmed—Schistosoma infection and Schistosoma-derived products modulate the immune system, including innate and acquired immune responses, contributing to T2D disease control. Schistosoma infections and Schistosoma-derived molecules affect the immune cell composition in adipose tissue, dampening inflammation and improving glucose tolerance. This protective role includes the polarization of immune cells to alternatively activated macrophages, dendritic cells, eosinophils, and group 2 innate lymphoid cells. Furthermore, Schistosoma infection and Schistosoma products are effective for the treatment of T2D, as they increase the number of type 2 helper T cells (Th2) and regulatory T cells (Tregs) and decrease type 1 helper T cells (Th1) and type 17 helper T cells (Th17) cells. Thus, our aim was to comprehensively review the mechanism through which Schistosoma infection and Schistosoma products modulate the immune response against T2D. PMID:29387059

Schistosoma Infection and Schistosoma-Derived Products Modulate the Immune Responses Associated with Protection against Type 2 Diabetes.

PubMed

Tang, Chun-Lian; Liu, Zhi-Ming; Gao, Yan Ru; Xiong, Fei

2017-01-01

Studies on parasite-induced immunoregulatory mechanisms could contribute to the development of new therapies for inflammatory diseases such as type 2 diabetes (T2D), which is a chronic inflammatory disease characterized by persistent elevated glucose levels due to insulin resistance. The association between previous Schistosoma infection and T2D has been confirmed- Schistosoma infection and Schistosoma -derived products modulate the immune system, including innate and acquired immune responses, contributing to T2D disease control. Schistosoma infections and Schistosoma -derived molecules affect the immune cell composition in adipose tissue, dampening inflammation and improving glucose tolerance. This protective role includes the polarization of immune cells to alternatively activated macrophages, dendritic cells, eosinophils, and group 2 innate lymphoid cells. Furthermore, Schistosoma infection and Schistosoma products are effective for the treatment of T2D, as they increase the number of type 2 helper T cells (Th2) and regulatory T cells (Tregs) and decrease type 1 helper T cells (Th1) and type 17 helper T cells (Th17) cells. Thus, our aim was to comprehensively review the mechanism through which Schistosoma infection and Schistosoma products modulate the immune response against T2D.

[Discovery of a focus of intestinal bilharziasis in te Republic of Djibouti].

PubMed

Koeck, J L; Modica, C; Tual, F; Czarnecki, E; Fabre, R; Merle, C; Montfort, F; Jouvenin, N; Cavallo, J D

1999-01-01

An unprecedented pocket of intestinal schistosomiasis was discovered in the Republic of Djibouti in 1997. The first cases were diagnosed in French and Djiboutian tourists who presented initial symptoms of bilharzian infection after bathing in the fresh-water basin under Hassan Gari Bira Falls, near Randa. Seventeen cases were subsequently confirmed by detection of anti-schistosome antibodies using indirect hemagglutination (IH) and indirect immunofluorescence (IIF) and/or detection of Schistosoma mansoni eggs in the stool. Further testing was performed in 35 village inhabitants, mostly children, who had been exposed by bathing in the basin. The IH reaction was positive in 28 patients (80 p. 100) including 17 (49 p. 100) with levels greater than 1/64. In 92 p. 100 of cases, IH findings were confirmed by IIF which indicated that association with hypereosinophilia was common. Schistosoma mansoni eggs were found in stools from 7 patients (19 p. 100) who generally displayed mild hypereosinophilia. Information concerning the zone of risk was distributed and control measures were undertaken as widely as possible in Djibouti and abroad.

Protein Translation Enzyme lysyl-tRNA Synthetase Presents a New Target for Drug Development against Causative Agents of Loiasis and Schistosomiasis.

PubMed

Sharma, Arvind; Sharma, Manmohan; Yogavel, Manickam; Sharma, Amit

2016-11-01

Helminth parasites are an assemblage of two major phyla of nematodes (also known as roundworms) and platyhelminths (also called flatworms). These parasites are a major human health burden, and infections caused by helminths are considered under neglected tropical diseases (NTDs). These infections are typified by limited clinical treatment options and threat of drug resistance. Aminoacyl-tRNA synthetases (aaRSs) are vital enzymes that decode genetic information and enable protein translation. The specific inhibition of pathogen aaRSs bores well for development of next generation anti-parasitics. Here, we have identified and annotated aaRSs and accessory proteins from Loa loa (nematode) and Schistosoma mansoni (flatworm) to provide a glimpse of these protein translation enzymes within these parasites. Using purified parasitic lysyl-tRNA synthetases (KRSs), we developed series of assays that address KRS enzymatic activity, oligomeric states, crystal structure and inhibition profiles. We show that L. loa and S. mansoni KRSs are potently inhibited by the fungal metabolite cladosporin. Our co-crystal structure of Loa loa KRS-cladosporin complex reveals key interacting residues and provides a platform for structure-based drug development. This work hence provides a new direction for both novel target discovery and inhibitor development against eukaryotic pathogens that include L. loa and S. mansoni.

Protein Translation Enzyme lysyl-tRNA Synthetase Presents a New Target for Drug Development against Causative Agents of Loiasis and Schistosomiasis

PubMed Central

Yogavel, Manickam; Sharma, Amit

2016-01-01

Helminth parasites are an assemblage of two major phyla of nematodes (also known as roundworms) and platyhelminths (also called flatworms). These parasites are a major human health burden, and infections caused by helminths are considered under neglected tropical diseases (NTDs). These infections are typified by limited clinical treatment options and threat of drug resistance. Aminoacyl-tRNA synthetases (aaRSs) are vital enzymes that decode genetic information and enable protein translation. The specific inhibition of pathogen aaRSs bores well for development of next generation anti-parasitics. Here, we have identified and annotated aaRSs and accessory proteins from Loa loa (nematode) and Schistosoma mansoni (flatworm) to provide a glimpse of these protein translation enzymes within these parasites. Using purified parasitic lysyl-tRNA synthetases (KRSs), we developed series of assays that address KRS enzymatic activity, oligomeric states, crystal structure and inhibition profiles. We show that L. loa and S. mansoni KRSs are potently inhibited by the fungal metabolite cladosporin. Our co-crystal structure of Loa loa KRS-cladosporin complex reveals key interacting residues and provides a platform for structure-based drug development. This work hence provides a new direction for both novel target discovery and inhibitor development against eukaryotic pathogens that include L. loa and S. mansoni. PMID:27806050

The Schistosoma Granuloma: Friend or Foe?

PubMed Central

Hams, Emily; Aviello, Gabriella; Fallon, Padraic G.

2013-01-01

Infection of man with Schistosoma species of trematode parasite causes marked chronic morbidity. Individuals that become infected with Schistosomes may develop a spectrum of pathology ranging from mild cercarial dermatitis to severe tissue inflammation, in particular within the liver and intestines, which can lead to life threatening hepatosplenomegaly. It is well established that the etiopathology during schistosomiasis is primarily due to an excessive or unregulated inflammatory response to the parasite, in particular to eggs that become trapped in various tissue. The eggs forms the foci of a classical type 2 granulomatous inflammation, characterized by an eosinophil-rich, CD4+ T helper (Th) 2 cell dominated infiltrate with additional infiltration of alternatively activated macrophages (M2). Indeed the sequela of the type 2 perioval granuloma is marked fibroblast infiltration and development of fibrosis. Paradoxically, while the granuloma is the cause of pathology it also can afford some protection, whereby the granuloma minimizes collateral tissue damage in the liver and intestines. Furthermore, the parasite is exquisitely reliant on the host to mount a granulomatous reaction to the eggs as this inflammatory response facilitates the successful excretion of the eggs from the host. In this focused review we will address the conundrum of the S. mansoni granuloma acting as both friend and foe in inflammation during infection. PMID:23596444

Exploring molecular variation in Schistosoma japonicum in China.

PubMed

Young, Neil D; Chan, Kok-Gan; Korhonen, Pasi K; Min Chong, Teik; Ee, Robson; Mohandas, Namitha; Koehler, Anson V; Lim, Yan-Lue; Hofmann, Andreas; Jex, Aaron R; Qian, Baozhen; Chilton, Neil B; Gobert, Geoffrey N; McManus, Donald P; Tan, Patrick; Webster, Bonnie L; Rollinson, David; Gasser, Robin B

2015-12-01

Schistosomiasis is a neglected tropical disease that affects more than 200 million people worldwide. The main disease-causing agents, Schistosoma japonicum, S. mansoni and S. haematobium, are blood flukes that have complex life cycles involving a snail intermediate host. In Asia, S. japonicum causes hepatointestinal disease (schistosomiasis japonica) and is challenging to control due to a broad distribution of its snail hosts and range of animal reservoir hosts. In China, extensive efforts have been underway to control this parasite, but genetic variability in S. japonicum populations could represent an obstacle to eliminating schistosomiasis japonica. Although a draft genome sequence is available for S. japonicum, there has been no previous study of molecular variation in this parasite on a genome-wide scale. In this study, we conducted the first deep genomic exploration of seven S. japonicum populations from mainland China, constructed phylogenies using mitochondrial and nuclear genomic data sets, and established considerable variation between some of the populations in genes inferred to be linked to key cellular processes and/or pathogen-host interactions. Based on the findings from this study, we propose that verifying intraspecific conservation in vaccine or drug target candidates is an important first step toward developing effective vaccines and chemotherapies against schistosomiasis.

Anti-CD25 monoclonal antibody enhances the protective efficacy of Schistosoma japonicum GST vaccine via inhibition of CD4+CD25+Foxp3+ regulatory T cells.

PubMed

Tang, Chun-Lian; Yang, Jin; Cheng, Liang-Yu; Cheng, Lan-Fang; Liu, Zhi-Ming

2017-10-01

The effect of anti-CD25 monoclonal antibody (anti-CD25 mAb) on the protection efficacy of Schistosoma japonicum 26 kDa GST (glutathione-S-transferase) vaccine was evaluated. Mice were immunized with GST before infection with S. japonicum cercariae and then injected with anti-CD25 mAb. The worm reduction rate was promoted from 24.18% in mice with GST immunization to 47.09% in mice with GST plus anti-CD25 mAb. Compared with the control group, the percentages of splenic CD4 + CD25 + Foxp3 + regulatory T cells (Tregs) were significantly lower after administration of anti-CD25 mAb; meanwhile, elevated levels of IFN-γ and IL-2 were secreted by splenocytes. These results indicate that the poor protective efficacy of the GST vaccine against S. japonicum results from the presence of CD4 + CD25 + Foxp3 + Tregs, while anti-CD25 mAb can partially block CD4 + CD25 + Foxp3 + Tregs and thus enhance the protective efficacy of the GST vaccine.

Schistosoma real-time PCR as diagnostic tool for international travellers and migrants.

PubMed

Cnops, Lieselotte; Tannich, Egbert; Polman, Katja; Clerinx, Jan; Van Esbroeck, Marjan

2012-10-01

To evaluate the use of a genus-specific PCR that combines high sensitivity with the detection of different Schistosoma species for diagnosis in international travellers and migrants in comparison to standard microscopy. The genus-specific real-time PCR was developed to target the 28S ribosomal RNA gene of the major human Schistosoma species. It was validated for analytical specificity and reproducibility and demonstrated an analytical sensitivity of 0.2 eggs per gram of faeces. Its diagnostic performance was further evaluated on 152 faecal, 32 urine and 38 serum samples from patients presenting at the outpatient clinic of the Institute of Tropical Medicine in Antwerp (Belgium). We detected Schistosoma DNA in 76 faecal (50.0%) and five urine (15.6%) samples of which, respectively, nine and one were not detected by standard microscopy. Only two of the 38 serum samples of patients with confirmed schistosomiasis were positive with the presently developed PCR. Sequence analysis on positive faecal samples allowed identification of the Schistosoma species complex. The real-time PCR is highly sensitive and may offer added value in diagnosing imported schistosomiasis. The genus-specific PCR can detect all schistosome species that are infectious to humans and performs very well with faeces and urine, but not in serum. © 2012 Blackwell Publishing Ltd.

Biomphalaria alexandrina in Egypt: past, present and future.

PubMed

Abou-El-Naga, Iman F

2013-09-01

The African species of Biomphalaria appeared as a result of the relatively recent west-to-east trans-Atlantic dispersal of the Biomphalaria glabrata-like taxon. In Egypt, Biomphalaria alexandrina is the intermediate host for Schistosoma mansoni. Biomphalaria alexandrina originated in the area between Alexandria and Rosetta and has historically been confined to the Nile Delta. Schistosoma mansoni reached Egypt via infected slaves and baboons from the Land of Punt through migrations that occurred as early as the Vth Dynasty. The suggestion of the presence of Schistosoma mansoni infection in Lower Egypt during Pharaonic times is discussed despite the fact that that there is no evidence of such infection in Egyptian mummies. It is only recently that Biomphalaria alexandrina colonized the Egyptian Nile from the Delta to Lake Nasser. This change was likely due to the construction of huge water projects, the development of new water resources essential for land reclamation projects and the movement of refugees from the Suez Canal zone to the Delta and vice versa. The situation with respect to Biomphalaria in Egypt has become complicated in recent years by the detection of Biomphalaria glabrata and a hybrid between both species; however, follow-up studies have demonstrated the disappearance of such species within Egypt. The National Schistosoma Control Program has made great strides with respect to the eradication of schistosoma; however, there has unfortunately been a reemergence of Schistosoma mansoni resistant to praziquantel. There are numerous factors that may influence the prevalence of snails in Egypt, including the construction of water projects, the increase in reclaimed areas, global climate change and pollution. Thus, continued field studies in addition to the cooperation of several scientists are needed to obtain an accurate representation of the status of this species. In addition, the determination of the genome sequence for Biomphalaria alexandrina and the

Risk factors for schistosomiasis in an urban area in northern Côte d'Ivoire.

PubMed

M'Bra, Richard K; Kone, Brama; Yapi, Yapi G; Silué, Kigbafori D; Sy, Ibrahima; Vienneau, Danielle; Soro, Nagnin; Cissé, Guéladio; Utzinger, Jürg

2018-05-18

Schistosomiasis is a water-based disease transmitted by trematodes belonging to the genus Schistosoma. The aim of this study was to assess the relationship between the prevalence of schistosomiasis and access to water, sanitation and hygiene (WASH) and environmental and socioeconomic factors in the city of Korhogo, northern Côte d'Ivoire. A cross-sectional study including 728 randomly selected households was conducted in Korhogo in March 2015. The heads of the households were interviewed about access to WASH and environmental and socioeconomic factors. All children abed between 5 and 15 years living in the households were selected to provide stool and urine samples for parasitological diagnosis of Schistosoma mansoni and Schistosoma haematobium infection. The relationship between infection with S. mansoni and potential risk factors was analysed by a mixed logistic regression model with 'household' as a random factor. Likelihood ratio tests were used to identify factors that were significantly associated with a Schistosoma spp. infection. The overall prevalence of schistosomiasis among school-aged children in Korhogo was 1.9% (45/2341) composed of 0.3% (3/1248) S. haematobium and 3.5% (42/1202) S. mansoni. Due to the low prevalence of S. haematobium infection, risk factor analysis was limited to S. mansoni. Boys were 7.8 times more likely to be infected with S. mansoni than girls. Children between 10 and 15 years of age were 3.8 times more likely to be infected than their younger counterparts aged 5-10 years. Moreover, living in a house further away from a water access point (odds ratio [OR] = 0.29, 95% confidence interval [CI]: 0.13-0.70) and abstaining from swimming in open freshwater bodies (OR = 0.16, 95% CI: 0.04-0.56) were significantly associated with decreased odds of S. mansoni infection. The socioeconomic status did not appear to influence the prevalence of S. mansoni. A strategy to reduce the incidence of schistosomiasis should focus on

Species-Specific Serological Detection for Schistosomiasis by Serine Protease Inhibitor (SERPIN) in Multiplex Assay.

PubMed

Tanigawa, Chihiro; Fujii, Yoshito; Miura, Masashi; Nzou, Samson Muuo; Mwangi, Anne Wanjiru; Nagi, Sachiyo; Hamano, Shinjiro; Njenga, Sammy M; Mbanefo, Evaristus Chibunna; Hirayama, Kenji; Mwau, Matilu; Kaneko, Satoshi

2015-01-01

Both Schistosoma mansoni and Schistosoma haematobium cause schistosomiasis in sub-Saharan Africa. We assessed the diagnostic value of selected Schistosoma antigens for the development of a multiplex serological immunoassay for sero-epidemiological surveillance. Diagnostic ability of recombinant antigens from S. mansoni and S. haematobium was assessed by Luminex multiplex immunoassay using plasma from school children in two areas of Kenya, endemic for different species of schistosomiasis. S. mansoni serine protease inhibitor (SERPIN) and Sm-RP26 showed significantly higher reactivity to patient plasma as compared to the control group. Sm-Filamin, Sm-GAPDH, Sm-GST, Sm-LAP1, Sm-LAP2, Sm-Sm31, Sm-Sm32 and Sm-Tropomyosin did not show difference in reactivity between S. mansoni infected and uninfected pupils. Sm-RP26 was cross-reactive to plasma from S. haematobium patients, whereas Sm-SERPIN was species-specific. Sh-SEPRIN was partially cross-reactive to S. mansoni infected patients. ROC analysis for Sm-RP26, Sm-SERPIN and Sh-SERPIN showed AUC values of 0.833, 0.888 and 0.947, respectively. Using Spearman's rank correlation coefficient analysis, we also found significant positive correlation between the number of excreted eggs and median fluorescence intensity (MFI) from the multiplex immunoassays for Sm-SERPIN (ρ = 0.430, p-value = 0.003) and Sh-SERPIN (ρ = 0.433, p-value = 0.006). Sm-SERPIN is a promising species-specific diagnostic antigen. Sh-SEPRIN was partially cross-reactive to S. mansoni infected patients. SERPINs showed correlation with the number of excreted eggs. These indicate prospects for inclusion of SERPINs in the multiplex serological immunoassay system.

Helminth Genomics: The Implications for Human Health

PubMed Central

Brindley, Paul J.; Mitreva, Makedonka; Ghedin, Elodie; Lustigman, Sara

2009-01-01

More than two billion people (one-third of humanity) are infected with parasitic roundworms or flatworms, collectively known as helminth parasites. These infections cause diseases that are responsible for enormous levels of morbidity and mortality, delays in the physical development of children, loss of productivity among the workforce, and maintenance of poverty. Genomes of the major helminth species that affect humans, and many others of agricultural and veterinary significance, are now the subject of intensive genome sequencing and annotation. Draft genome sequences of the filarial worm Brugia malayi and two of the human schistosomes, Schistosoma japonicum and S. mansoni, are now available, among others. These genome data will provide the basis for a comprehensive understanding of the molecular mechanisms involved in helminth nutrition and metabolism, host-dependent development and maturation, immune evasion, and evolution. They are likely also to predict new potential vaccine candidates and drug targets. In this review, we present an overview of these efforts and emphasize the potential impact and importance of these new findings. PMID:19855829

24-nor-ursodeoxycholic acid ameliorates inflammatory response and liver fibrosis in a murine model of hepatic schistosomiasis.

PubMed

Sombetzki, Martina; Fuchs, Claudia D; Fickert, Peter; Österreicher, Christoph H; Mueller, Michaela; Claudel, Thierry; Loebermann, Micha; Engelmann, Robby; Langner, Cord; Sahin, Emine; Schwinge, Dorothee; Guenther, Nina D; Schramm, Christoph; Mueller-Hilke, Brigitte; Reisinger, Emil C; Trauner, Michael

2015-04-01

Intrahepatic granuloma formation and fibrosis characterize the pathological features of Schistosoma mansoni infection. Based on previously observed substantial anti-fibrotic effects of 24-nor-ursodeoxycholic acid (norUDCA) in Abcb4/Mdr2(-/-) mice with cholestatic liver injury and biliary fibrosis, we hypothesized that norUDCA improves inflammation-driven liver fibrosis in S. mansoni infection. Adult NMRI mice were infected with 50 S. mansoni cercariae and after 12 weeks received either norUDCA- or ursodeoxycholic acid (UDCA)-enriched diet (0.5% wt/wt) for 4 weeks. Bile acid effects on liver histology, serum biochemistry, key regulatory cytokines, hepatic hydroxyproline content as well as granuloma formation were compared to naive mice and infected controls. In addition, effects of norUDCA on primary T-cell activation/proliferation and maturation of the antigen-presenting-cells (dendritic cells, macrophages) were determined in vitro. UDCA as well as norUDCA attenuated the inflammatory response in livers of S. mansoni infected mice, but exclusively norUDCA changed cellular composition and reduced size of hepatic granulomas as well as TH2-mediated hepatic fibrosis in vivo. Moreover, norUDCA affected surface expression level of major histocompatibility complex (MHC) class II of macrophages and dendritic cells as well as activation/proliferation of T-lymphocytes in vitro, whereas UDCA had no effect. This study demonstrates pronounced anti-inflammatory and anti-fibrotic effects of norUDCA compared to UDCA in S. mansoni induced liver injury, and indicates that norUDCA directly represses antigen presentation of antigen presenting cells and subsequent T-cell activation in vitro. Therefore, norUDCA represents a promising drug for the treatment of this important cause of liver fibrosis. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Refolding of the recombinant protein Sm29, a step toward the production of the vaccine candidate against schistosomiasis.

PubMed

Chura-Chambi, Rosa M; Nakajima, Erika; de Carvalho, Roberta R; Miyasato, Patricia A; Oliveira, Sergio C; Morganti, Ligia; Martins, Elizabeth A L

2013-12-01

Schistosomiasis is an important parasitic disease, with about 240 million people infected worldwide. Humans and animals can be infected, imposing an enormous social and economic burden. The only drug available for chemotherapy, praziquantel, does not control reinfections, and an efficient vaccine for prophylaxis is still missing. However, the tegumental protein Sm29 of Schistosoma mansoni was shown to be a promising antigen to compose an anti-schistosomiasis vaccine. Though, recombinant Sm29 is expressed in Escherichia coli as insoluble inclusion bodies requiring an efficient process of refolding, thus, hampering its production in large scale. We present in this work studies to refold the recombinant Sm29 using high hydrostatic pressure, a mild condition to dissociate aggregated proteins, leading to refolding on a soluble conformation. Our studies resulted in high yield of rSm29 (73%) as a stably soluble and structured protein. The refolded antigen presented protective effect against S. mansoni development in immunized mice. We concluded that the refolding process by application of high hydrostatic pressure succeeded, and the procedure can be scaled-up, allowing industrial production of Sm29. Copyright © 2013 Elsevier B.V. All rights reserved.

Whole-genome sequence of Schistosoma haematobium.

PubMed

Young, Neil D; Jex, Aaron R; Li, Bo; Liu, Shiping; Yang, Linfeng; Xiong, Zijun; Li, Yingrui; Cantacessi, Cinzia; Hall, Ross S; Xu, Xun; Chen, Fangyuan; Wu, Xuan; Zerlotini, Adhemar; Oliveira, Guilherme; Hofmann, Andreas; Zhang, Guojie; Fang, Xiaodong; Kang, Yi; Campbell, Bronwyn E; Loukas, Alex; Ranganathan, Shoba; Rollinson, David; Rinaldi, Gabriel; Brindley, Paul J; Yang, Huanming; Wang, Jun; Wang, Jian; Gasser, Robin B

2012-01-15

Schistosomiasis is a neglected tropical disease caused by blood flukes (genus Schistosoma; schistosomes) and affecting 200 million people worldwide. No vaccines are available, and treatment relies on one drug, praziquantel. Schistosoma haematobium has come into the spotlight as a major cause of urogenital disease, as an agent linked to bladder cancer and as a predisposing factor for HIV/AIDS. The parasite is transmitted to humans from freshwater snails. Worms dwell in blood vessels and release eggs that become embedded in the bladder wall to elicit chronic immune-mediated disease and induce squamous cell carcinoma. Here we sequenced the 385-Mb genome of S. haematobium using Illumina-based technology at 74-fold coverage and compared it to sequences from related parasites. We included genome annotation based on function, gene ontology, networking and pathway mapping. This genome now provides an unprecedented resource for many fundamental research areas and shows great promise for the design of new disease interventions.

Organism-like formation of Schistosoma hemozoin and its function suggest a mechanism for anti-malarial action of artemisinin

PubMed Central

Sun, Jun; Li, Chen; Wang, Suwen

2016-01-01

The current theories of antimalarial mechanism of artemisinin are inadequate to fully explain the observed effects. In our study, “organism-like” formation of Schistosoma hemozoin granules by attaching to and utilizing erythrocytes to form new ones was observed. This indicates that heme iron is transferred from erythrocytes to hemozoin granules during their formation. However, as a disposal product of heme detoxification, these granules are not completely expelled from the Schistosoma gut, but decomposed again between microvilli in the posterior portion of the gut to transfer iron to eggs. Based on the function of iron transport supported by our observation of the unique process of Schistosoma hemozoin formation, here we propose a new viewpoint of antimalarial mechanism of artemisinin, which emphasizes the final outcome, i.e., interference of iron utilization in parasites by artemisinin, instead of focusing on the mode of interaction between artemisinin and heme or hemozoin. This suggests that artemisinin and its endoperoxides derivatives likely hit the Achilles’ heel of hemozoin-producing and iron-dependent organisms. PMID:27694940

Efficacy of soluble glycoprotein fraction from Allium sativum purified by size exclusion chromatography on murine Schistosomiasis mansoni.

PubMed

Aly, Ibrahim; Taher, Eman E; El-Sayed, Hoda; Mohammed, Faten A; ELnain, Gehan; Hamad, Rabab S; Bayoumy, Elsayed M

2017-06-01

In this work, the efficiency of crude MeOH extracts and soluble glycoprotein fraction of Allium sativum purified by size-exclusion chromatography (SEC) on parasitological, histopathological and some biochemical parameters in Schistosoma mansoni infected mice were investigated. Animals were infected by tail immersion with 100 cercariae/each mouse and divided into five groups in addition to the normal control. The results revealed a significant decrease in mean worm burden in all treated mice especially in the group treated with soluble glycoprotein fraction of A. sativum as compared to infected non-treated control with the disappearance of female worms. Administration of the studied extracts revealed remarkable amelioration in the levels of all the measured parameters in S. mansoni infected mice. In addition, treatment of mice with crude A. sativum MeOH extract and soluble glycoprotein fraction of A. sativum decreased significantly the activities of studied enzymes as compared to the infected untreated group. The highest degrees of enhancement in pathological changes was observed in the treated one with soluble glycoprotein fraction of A. sativum compared to the infected group represented by small sized, late fibro-cellular granuloma, the decrease in cellular constituents and degenerative changes in eggs. In conclusion, A. sativum treatment had effective schistosomicidal activities, through reduction of worm burden and tissue eggs, especially when it was given in purified glycoprotein fraction. Moreover, the soluble glycoprotein fraction of A. sativum largely modulates both the size and the number of granulomas. Copyright © 2017 Elsevier Ltd. All rights reserved.

HIV Target Cells in Schistosoma haematobium-Infected Female Genital Mucosa

PubMed Central

Jourdan, Peter Mark; Holmen, Sigve Dhondup; Gundersen, Svein Gunnar; Roald, Borghild; Kjetland, Eyrun Floerecke

2011-01-01

The parasite Schistosoma haematobium frequently causes genital lesions in women and could increase the risk of human immunodeficiency virus (HIV) transmission. This study quantifies the HIV target cells in schistosome-infected female genital mucosa. Cervicovaginal biopsies with and without schistosomiasis were immunostained for quantification of CD4+ T lymphocytes (CD3, CD8), macrophages (CD68), and dendritic Langerhans cells (S100 protein). We found significantly higher densities of genital mucosal CD4+ T lymphocytes and macrophages surrounding schistosome ova compared with cervicovaginal mucosa without ova (P = 0.034 and P = 0.018, respectively). We found no increased density of Langerhans cells (P = 0.25). This study indicates that S. haematobium may significantly increase the density of HIV target cells (CD4+ T lymphocytes and macrophages) in the female genitals, creating a beneficial setting for HIV transmission. Further studies are needed to confirm these findings and to evaluate the effect of anti-schistosomal treatment on female genital schistosomiasis. PMID:22144444

Sensitivity and specificity of the circulating cathodic antigen rapid urine test in the diagnosis of Schistosomiasis mansoni infection and evaluation of morbidity in a low- endemic area in Brazil.

PubMed

Ferreira, Fernanda Teixeira; Fidelis, Thiago André; Pereira, Thiago Almeida; Otoni, Alba; Queiroz, Leonardo Campos; Amâncio, Frederico Figueiredo; Antunes, Carlos Maurício; Lambertucci, José Roberto

2017-01-01

The Kato-Katz technique is the standard diagnostic test for Schistosoma mansoni infection in rural areas. However, the utility of this method is severely limited by the day-to-day variability in host egg excretion in the stool. In high-transmission areas, the point-of-care circulating cathodic antigen (POC-CCA) urine assay has proven to be a reliable test. However, investigations of the reliability of the POC-CCA assay in low-transmission regions are under way. This study aimed to evaluate the sensitivity and specificity of the POC-CCA assay and the morbidity of schistosomiasis in a low-endemic area in Brazil. Pains City is a low-transmission zone for schistosomiasis. A total of 300 subjects aged 7-76 years were randomly selected for the POC-CCA cassette test. For S. mansoni diagnosis, three stool samples on six slides were compared with one urine sample for each subject. The sensitivity and specificity in the absence of a gold standard were calculated using latent class analysis. Clinical examinations and abdominal ultrasounds were performed in 181 volunteers to evaluate morbidity associated with schistosomiasis. The sensitivity and specificity of the Kato-Katz technique were 25.6% and 94.6%, respectively. By contrast, the sensitivity and specificity of the POC-CCA assay were 68.1% and 72.8%, respectively. Hepatosplenic schistosomiasis was diagnosed in two patients (1.1%). Overall, the POC-CCA urine assay proved to be a useful test for diagnosing S. mansoni in a low-endemic area in Brazil. Severe clinical forms of schistosomiasis can be present even in such low-endemic areas.

Epidemiology of human fascioliasis and intestinal parasitosis among schoolchildren in Lake Tana Basin, northwest Ethiopia.

PubMed

Fentie, Tsegaw; Erqou, Sebhat; Gedefaw, Molla; Desta, Almaw

2013-08-01

Parasitic diseases are the second most frequent cause of outpatient morbidity in Ethiopia. A cross-sectional study was conducted in Lake Tana Basin, northwest Ethiopia, from November 2007 to February 2008, to assess the magnitude and associated risk factors for parasitic diseases, including human fascioliasis. We examined 520 stool samples from randomly selected schoolchildren in six schools by microscopy. Rapid sedimentation and Kato-Katz techniques were used to detect and count Fasciola and Schistosoma eggs. The formol-ether concentration method was used for the identification of other helminth eggs, larvae and cysts of protozoan parasites. The overall prevalence of intestinal parasitic infections was 71.3% (95% CI 67.3-75.1%). Hookworm was the predominant intestinal parasite (23.5%, 95% CI 19.8-27.1%), followed by Ascaris lumbricoides (18.5%, 95% CI 15.2-21.9%) and Schistosoma mansoni (16.7%, 95% CI 13.5-19.9%). One hundred and sixty-three (31.4%) children had multiple parasitic infections. The most relevant finding was a prevalence of Fasciola spp. of 3.3% in an area where only sporadic cases have been reported previously. The risk of Fasciola spp. infection was significantly associated with raw vegetable consumption, use of unsafe drinking water sources, irrigation practices and sheep and/or cattle ownership. Irrigation practices, male gender, raw vegetable consumption and use of unsafe drinking water sources were risk factors for S. mansoni infection. A high prevalence of parasitic infections among children in the region was found, including a relatively high prevalence of Fasciola spp. infection. Epidemiological studies on the magnitude of parasitic infections in different regions will enable high-risk communities to be identified and allow for planning of appropriate interventions.

Whole genome analysis of a schistosomiasis-transmitting freshwater snail

PubMed Central

Adema, Coen M.; Hillier, LaDeana W.; Jones, Catherine S.; Loker, Eric S.; Knight, Matty; Minx, Patrick; Oliveira, Guilherme; Raghavan, Nithya; Shedlock, Andrew; do Amaral, Laurence Rodrigues; Arican-Goktas, Halime D.; Assis, Juliana G.; Baba, Elio Hideo; Baron, Olga L.; Bayne, Christopher J.; Bickham-Wright, Utibe; Biggar, Kyle K.; Blouin, Michael; Bonning, Bryony C.; Botka, Chris; Bridger, Joanna M.; Buckley, Katherine M.; Buddenborg, Sarah K.; Lima Caldeira, Roberta; Carleton, Julia; Carvalho, Omar S.; Castillo, Maria G.; Chalmers, Iain W.; Christensens, Mikkel; Clifton, Sandra; Cosseau, Celine; Coustau, Christine; Cripps, Richard M.; Cuesta-Astroz, Yesid; Cummins, Scott F.; di Stefano, Leon; Dinguirard, Nathalie; Duval, David; Emrich, Scott; Feschotte, Cédric; Feyereisen, Rene; FitzGerald, Peter; Fronick, Catrina; Fulton, Lucinda; Galinier, Richard; Gava, Sandra G.; Geusz, Michael; Geyer, Kathrin K.; Giraldo-Calderón, Gloria I.; de Souza Gomes, Matheus; Gordy, Michelle A.; Gourbal, Benjamin; Grunau, Christoph; Hanington, Patrick C.; Hoffmann, Karl F.; Hughes, Daniel; Humphries, Judith; Jackson, Daniel J.; Jannotti-Passos, Liana K.; de Jesus Jeremias, Wander; Jobling, Susan; Kamel, Bishoy; Kapusta, Aurélie; Kaur, Satwant; Koene, Joris M.; Kohn, Andrea B.; Lawson, Dan; Lawton, Scott P; Liang, Di; Limpanont, Yanin; Liu, Sijun; Lockyer, Anne E.; Lovato, TyAnna L.; Ludolf, Fernanda; Magrini, Vince; McManus, Donald P.; Medina, Monica; Misra, Milind; Mitta, Guillaume; Mkoji, Gerald M.; Montague, Michael J.; Montelongo, Cesar; Moroz, Leonid L.; Munoz-Torres, Monica C.; Niazi, Umar; Noble, Leslie R.; Oliveira, Francislon S.; Pais, Fabiano S.; Papenfuss, Anthony T.; Peace, Rob; Pena, Janeth J.; Pila, Emmanuel A.; Quelais, Titouan; Raney, Brian J.; Rast, Jonathan P.; Rollinson, David; Rosse, Izinara C.; Rotgans, Bronwyn; Routledge, Edwin J.; Ryan, Kathryn M.; Scholte, Larissa L. S.; Storey, Kenneth B.; Swain, Martin; Tennessen, Jacob A.; Tomlinson, Chad; Trujillo, Damian L.; Volpi, Emanuela V.; Walker, Anthony J.; Wang, Tianfang; Wannaporn, Ittiprasert; Warren, Wesley C.; Wu, Xiao-Jun; Yoshino, Timothy P.; Yusuf, Mohammed; Zhang, Si-Ming; Zhao, Min; Wilson, Richard K.

2017-01-01

Biomphalaria snails are instrumental in transmission of the human blood fluke Schistosoma mansoni. With the World Health Organization's goal to eliminate schistosomiasis as a global health problem by 2025, there is now renewed emphasis on snail control. Here, we characterize the genome of Biomphalaria glabrata, a lophotrochozoan protostome, and provide timely and important information on snail biology. We describe aspects of phero-perception, stress responses, immune function and regulation of gene expression that support the persistence of B. glabrata in the field and may define this species as a suitable snail host for S. mansoni. We identify several potential targets for developing novel control measures aimed at reducing snail-mediated transmission of schistosomiasis. PMID:28508897

Human plasma lipid modulation in schistosomiasis mansoni depends on apolipoprotein E polymorphism.

PubMed

Martins da Fonseca, Caíque Silveira; Pimenta Filho, Adenor Almeida; dos Santos, Bianka Santana; da Silva, César Augusto; Domingues, Ana Lúcia Coutinho; Owen, James Stuart; Lima, Vera Lúcia de Menezes

2014-01-01

Schistosomiasis mansoni is a parasitic liver disease, which causes several metabolic disturbances. Here, we evaluate the influence of Apolipoprotein E (APOE) gene polymorphism, a known modulator of lipid metabolism, on plasma lipid levels in patients with hepatosplenic schistosomiasis. Blood samples were used for APOE genotyping and to measure total cholesterol (TC), LDL-C, HDL-C and triglycerides. Schistosomiasis patients had reduced TC, LDL-C and triglycerides (25%, 38% and 32% lower, respectively; P<0.0001) compared to control individuals, whereas HDL-C was increased (10% higher; P = 0.0136). Frequency of the common alleles, ε2, ε3 and ε4, was similar (P = 0.3568) between controls (n = 108) and patients (n = 84), implying that APOE genotype did not affect susceptibility to the advanced stage of schistosomiasis. Nevertheless, while patient TC and LDL-C levels were significantly reduced for each allele (except TC in ε2 patients), changes in HDL-C and triglycerides were noted only for the less common ε2 and ε4 alleles. The most striking finding, however, was that accepted regulation of plasma lipid levels by APOE genotype was disrupted by schistosomiasis. Thus, while ε2 controls had higher TC and LDL-C than ε3 carriers, these parameters were lower in ε2 versus ε3 patients. Similarly, the inverse relationship of TG levels in controls (ε2>ε3>ε4) was absent in patients (ε2 or ε4>ε3), and the increase in HDL-C of ε2 or ε4 patients compared to ε3 patients was not seen in the control groups. We confirm that human schistosomiasis causes dyslipidemia and report for the first time that certain changes in plasma lipid and lipoprotein levels depend on APOE gene polymorphism. Importantly, we also concluded that S. mansoni disrupts the expected regulation of plasma lipids by the different ApoE isoforms. This finding suggests ways to identify new metabolic pathways affected by schistosomiasis and also potential molecular targets to treat

Differential transcriptomic responses of Biomphalaria glabrata (Gastropoda, Mollusca) to bacteria and metazoan parasites, Schistosoma mansoni and Echinostoma paraensei (Digenea, Platyhelminthes)

PubMed Central

Adema, Coen M; Hanington, Patrick C.; Lun, Cheng-Man; Rosenberg, George H.; Aragon, Anthony D; Stout, Barbara A; Richard, Mara L. Lennard; Gross, Paul S.; Loker, Eric S

2009-01-01

A 70-mer oligonucleotide-based microarray (1152 features) that emphasizes stress and immune responses factors was constructed to study transcriptomic responses of the snail Biomphalaria glabrata to different immune challenges. In addition to sequences with relevant putative ID and Gene Ontology (GO) annotation, the array features non-immune factors and unknown B. glabrata ESTs for functional gene discovery. The transcription profiles of B. glabrata (3 biological replicates, each a pool of 5 snails) were recorded at 12 hours post wounding, exposure to Gram negative or Gram positive bacteria (Escherichia coli and Micrococcus luteus, respectively), or infection with compatible trematode parasites (S. mansoni or E. paraensei, 20 miracidia/snail), relative to controls, using universal reference RNA. The data were subjected to Significance Analysis for Microarrays (SAM), with a false positive rate (FPR) ≤10%. Wounding yielded a modest differential expression profile (27 up/21 down) with affected features mostly dissimilar from other treatments. Partially overlapping, yet distinct expression profiles were recorded from snails challenged with E. coli (83 up/20 down) or M. luteus (120 up/42 down), mostly showing up-regulation of defense and stress-related features. Significantly altered expression of selected immune features indicates that B. glabrata detects and responds differently to compatible trematodes. Echinostoma paraensei infection was associated mostly with down regulation of many (immune-) transcripts (42 up/68 down), whereas S. mansoni exposure yielded a preponderance of up-regulated features (140 up/23 down), with only few known immune genes affected. These observations may reflect the divergent strategies developed by trematodes during their evolution as specialized pathogens of snails to negate host defense responses. Clearly, the immune defenses of B. glabrata distinguish and respond differently to various immune challenges. PMID:19962194

Spatial distribution and risk factors of Schistosoma haematobium and hookworm infections among schoolchildren in Kwale, Kenya

PubMed Central

Chadeka, Evans Asena; Nagi, Sachiyo; Sunahara, Toshihiko; Cheruiyot, Ngetich Benard; Bahati, Felix; Ozeki, Yuriko; Inoue, Manabu; Osada-Oka, Mayuko; Okabe, Mayuko; Hirayama, Yukio; Changoma, Mwatasa; Adachi, Keishi; Mwende, Faith; Kikuchi, Mihoko; Nakamura, Risa; Kalenda, Yombo Dan Justin; Kaneko, Satoshi; Hirayama, Kenji; Shimada, Masaaki; Ichinose, Yoshio; Njenga, Sammy M.; Matsumoto, Sohkichi

2017-01-01

Background Large-scale schistosomiasis control programs are implemented in regions with diverse social and economic environments. A key epidemiological feature of schistosomiasis is its small-scale heterogeneity. Locally profiling disease dynamics including risk factors associated with its transmission is essential for designing appropriate control programs. To determine spatial distribution of schistosomiasis and its drivers, we examined schoolchildren in Kwale, Kenya. Methodology/Principal findings We conducted a cross-sectional study of 368 schoolchildren from six primary schools. Soil-transmitted helminths and Schistosoma mansoni eggs in stool were evaluated by the Kato-Katz method. We measured the intensity of Schistosoma haematobium infection by urine filtration. The geometrical mean intensity of S. haematobium was 3.1 eggs/10 ml urine (school range, 1.4–9.2). The hookworm geometric mean intensity was 3.2 eggs/g feces (school range, 0–17.4). Heterogeneity in the intensity of S. haematobium and hookworm infections was evident in the study area. To identify factors associated with the intensity of helminth infections, we utilized negative binomial generalized linear mixed models. The intensity of S. haematobium infection was associated with religion and socioeconomic status (SES), while that of hookworm infection was related to SES, sex, distance to river and history of anthelmintic treatment. Conclusions/Significance Both S. haematobium and hookworm infections showed micro-geographical heterogeneities in this Kwale community. To confirm and explain our observation of high S. haematobium risk among Muslims, further extensive investigations are necessary. The observed small scale clustering of the S. haematobium and hookworm infections might imply less uniform strategies even at finer scale for efficient utilization of limited resources. PMID:28863133

Evaluation of sodium fluoride toxicity in Schistosoma infected snails: assessment of antioxidants, antiapoptotic, hypoprotein and hypocholesterol activities.

PubMed

Koriem, Khaled M M; Shamsuri, Radziyah B; Ubaidillah, Asliza M

2016-12-01

The snails' tissues represents an intermediate or secondary host for Schistosoma sporocysts where, germ cells within the secondary sporocyst begin to divide to produce thousands of cercariae capable of infecting humans. The aim of the study was to evaluate the toxicity of sodium fluoride in Schistosoma snails' tissue homogenates. A total number of 264 different Schistosoma snails were collected from eight drainage water resources and divided into control uninfected and infected snails; where infected snails divided into four group; the first group without any treatment while second, third and fourth groups immersed in 25, 50 and 100 mg sodium fluoride/L during the period of 4 weeks then the snails' hemolymph and tissue homogenates were prepared to evaluate the snail' tissue antioxidants, protein content, lipid profile and apoptosis. The results obtained revealed that superoxide dismutase, glutathione- S -transferase, glutathione peroxidase, catalase, reduced glutathione, glutathione reductase levels were decreased while malondialdehyde, protein carbonyl, total protein, albumin, globulin, cholesterol, low density lipoprotein and triglycerides levels were increased in Schistosoma infected snails' tissues. Schistosoma also induced apoptosis in snails' tissues homogenates. Sodium fluoride restores all the above parameters to approach the control uninfected snails levels. In conclusion, sodium fluoride inhibits oxidative stress and apoptosis produced in Schistosoma infected snails and consequently it is be useful to be used in Schistosoma infection inhibition where sodium fluoride at higher dose was more effective than the lower two doses.

Molluscicidal effect of fenitrothion and anilofos on Lymnaea natalensis and Biomphalaria alexandrina snails and on the free larval stages of Schistosoma mansoni.

PubMed

Tantawy, Ahmed A

2006-08-01

Psticides; fenitrothion and anilofos (aniloguard) were testd as molluscicides against Lymnaea natalensis and Biomplhalaria alexandrina. The LC10 & LC90 of fenitrothion was 0.12 & 0.21 ppm for L. nalalensis and 0.17 & .26 ppm for B. alexandrina, respectively. The LC50 & LC90 anilofos was 2.61 & 6.47 ppm for Lymnaea and 3.07 & 8.6 ppm for Biomphalaria. The effect of sublethal concentrations (LC0, LC5 & C10) of Feni-rothion on B. alexandrina growth rate, eggs hatchability and on free larval stages of Schistosonma mansoni (miracidia & cerca-riae) were studied. The results obtained showed that sublethal concentrations of fenitrothion caused reduction in growth rate of B. alexandrina and reduction in the hatchibility of snails eggs. The mortality rates of miracidia and cercariae were elevated by increasing both the concentrations of fenitrothion and the time of exposure. The results showed that fenitrothion was more toxic to the free larval stages of S. mansoni than to their snails. The results showed a significant reduction in total protein of treated snails when compared with controls in haemolymph while there was an increase of protein contents of the tissue. The AlkP enzyme activity was slightly increased in the haemolymph of experimental groups than the control and in the tissues the values were significantly higher when compared with control. ALT enzyme activity in haemolymph of experimental groups was higher than controls while its activity in tissue was lower. AST enzyme activity was higher in haemolymph and tissue of experimental groups than in controls.

[Research progress of molecular genetic analysis in Schistosoma variation].

PubMed

Zheng, Su-Yue; Li, Fei

2014-02-01

The development of molecular biology techniques makes important contributions to the researches of heritable variation of Schistosoma. In recent years, the molecular genetic analysis in the Schistosoma variation researches mainly includes the restriction fragment length polymorphism (RFLP), random amplified polymorphism technology (RAPD), microsatellite anchored PCR (SSR-PCR), and polymerase reaction single-strand conformation polymorphism (PCR-SSCP). This article reviews the research progress of molecular genetic analysis in Schistosoma variation in recent years.

Homology modeling of parasite histone deacetylases to guide the structure-based design of selective inhibitors.

PubMed

Melesina, Jelena; Robaa, Dina; Pierce, Raymond J; Romier, Christophe; Sippl, Wolfgang

2015-11-01

Histone deacetylases (HDACs) are promising epigenetic targets for the treatment of various diseases, including cancer and neurodegenerative disorders. There is evidence that they can also be addressed to treat parasitic infections. Recently, the first X-ray structure of a parasite HDAC was published, Schistosoma mansoni HDAC8, giving structural insights into its inhibition. However, most of the targets from parasites of interest still lack this structural information. Therefore, we prepared homology models of relevant parasitic HDACs and compared them to human and S. mansoni HDACs. The information about known S. mansoni HDAC8 inhibitors and compounds that affect the growth of Trypanosoma, Leishmania and Plasmodium species was used to validate the models by docking and molecular dynamics studies. Our results provide analysis of structural features of parasitic HDACs and should be helpful for selecting promising candidates for biological testing and for structure-based optimisation of parasite-specific inhibitors. Copyright © 2015 Elsevier Inc. All rights reserved.

Regulation of Schistosoma mansoni development and reproduction by the mitogen-activated protein kinase signaling pathway.

PubMed

Andrade, Luiza Freire de; Mourão, Marina de Moraes; Geraldo, Juliana Assis; Coelho, Fernanda Sales; Silva, Larissa Lopes; Neves, Renata Heisler; Volpini, Angela; Machado-Silva, José Roberto; Araujo, Neusa; Nacif-Pimenta, Rafael; Caffrey, Conor R; Oliveira, Guilherme

2014-06-01

Protein kinases are proven targets for drug development with an increasing number of eukaryotic Protein Kinase (ePK) inhibitors now approved as drugs. Mitogen-activated protein kinase (MAPK) family members connect cell-surface receptors to regulatory targets within cells and influence a number of tissue-specific biological activities such as cell proliferation, differentiation and survival. However, the contributions of members of the MAPK pathway to schistosome development and survival are unclear. We employed RNA interference (RNAi) to elucidate the functional roles of five S. mansoni genes (SmCaMK2, SmJNK, SmERK1, SmERK2 and SmRas) involved in MAPK signaling pathway. Mice were injected with post-infective larvae (schistosomula) subsequent to RNAi and the development of adult worms observed. The data demonstrate that SmJNK participates in parasite maturation and survival of the parasites, whereas SmERK are involved in egg production as infected mice had significantly lower egg burdens with female worms presenting underdeveloped ovaries. Furthermore, it was shown that the c-fos transcription factor was overexpressed in parasites submitted to RNAi of SmERK1, SmJNK and SmCaMK2 indicating its putative involvement in gene regulation in this parasite's MAPK signaling cascade. We conclude that MAPKs proteins play important roles in the parasite in vivo survival, being essential for normal development and successful survival and reproduction of the schistosome parasite. Moreover SmERK and SmJNK are potential targets for drug development.

Helminth antigens counteract a rapid high-fat diet-induced decrease in adipose tissue eosinophils.

PubMed

van den Berg, Susan M; van Dam, Andrea D; Kusters, Pascal J H; Beckers, Linda; den Toom, Myrthe; van der Velden, Saskia; Van den Bossche, Jan; van Die, Irma; Boon, Mariëtte R; Rensen, Patrick C N; Lutgens, Esther; de Winther, Menno P J

2017-10-01

Brown adipose tissue (BAT) activation and white adipose tissue (WAT) beiging can increase energy expenditure and have the potential to reduce obesity and associated diseases. The immune system is a potential target in mediating brown and beige adipocyte activation. Type 2 and anti-inflammatory immune cells contribute to metabolic homeostasis within lean WAT, with a prominent role for eosinophils and interleukin (IL)-4-induced anti-inflammatory macrophages. We determined eosinophil numbers in epididymal WAT (EpAT), subcutaneous WAT (ScAT) and BAT after 1 day, 3 days or 1 week of high-fat diet (HFD) feeding in C57Bl/6 mice. One day of HFD resulted in a rapid drop in eosinophil numbers in EpAT and BAT, and after 3 days, in ScAT. In an attempt to restore this HFD-induced drop in adipose tissue eosinophils, we treated 1-week HFD-fed mice with helminth antigens from Schistosoma mansoni or Trichuris suis and evaluated whether the well-known protective metabolic effects of helminth antigens involves BAT activation or beiging. Indeed, antigens of both helminth species induced high numbers of eosinophils in EpAT, but failed to induce beiging. In ScAT, Schistosoma mansoni antigens induced mild eosinophilia, which was accompanied by slightly more beiging. No effects were observed in BAT. To study type 2 responses on brown adipocytes directly, T37i cells were stimulated with IL-4. This increased Ucp1 expression and strongly induced the production of eosinophil chemoattractant CCL11 (+26-fold), revealing that brown adipocytes themselves can attract eosinophils. Our findings indicate that helminth antigen-induced eosinophilia fails to induce profound beiging of white adipocytes. © 2017 Society for Endocrinology.

[Pathogen identification of 10 suspected cases of sparganosis mansoni].

PubMed

Zeng, Qing-Ren; He, Mei; Wang, Fang; Zhang, Zu-Ping; Su, Zhan-San; Zhou, Jun; Liu, Bao-An; Lan, Zhi-Hua; Hu, Mian-Juan; Cai, Li-Ting

2012-06-30

To diagnose 10 cases of clinically suspected cases of sparganosis mansoni by pathogen identification. In the period from August 2009 to August 2011, 10 biopsy specimens were obtained from 10 patients of four hospitals to identify the pathogen. Among the 10 cases, 4 cases showed abdominal subcutaneous mass, 3 showed eyelid swelling, 1 displayed brain lesions, 1 showed pulmonary mass, and 1 showed pleural effusion. There was one parasite each from three patients with eyelid swelling, and one patient with abdominal subcutaneous mass, which were observed by naked eye and microscope morphologically and histologically. Specimens from other six cases were examined by microscope after paraffin embedding, sectioning, and HE staining. For further identification, the parasite biopsy tissue specimens were detected by immunohistochemistry with Sparganum mansoni-immunized rabbit serum as the primary antibody. Three intact worms, from three patients with eyelid swelling, showed typical S. mansoni morphological characteristics. One residue parasite from the abdominal subcutaneous mass showed network structures and full of calcareous corpuscles in the body under microscope same as that of S. mansoni. The histological structure in three of the six sections showed typically the body wall with folds, which was dense, thick and deeply eosine stained, part of the tegument outside was covered by micro-hairs. In the worm body there was net-like loose structure and calcareous corpuscles without cavity. The structure of the other three worm sections was atypical. The six worm sections were positive by immunohistochemical detection. The 10 clinically suspected cases are diagnosed as sparganosis mansoni.

The hidden epidemic of schistosomiasis in recent African immigrants and asylum seekers to Italy.

PubMed

Beltrame, Anna; Buonfrate, Dora; Gobbi, Federico; Angheben, Andrea; Marchese, Valentina; Monteiro, Geraldo Badona; Bisoffi, Zeno

2017-08-01

The prevalence of schistosomiasis among recent refugees from sub-Saharan Africa in Italy is unknown. This is a retrospective review of African immigrants screened at Centre for Tropical Diseases of Negrar from March 2014 to February 2016. Of the 373 immigrants tested, 34% were positive at least at one schistosomiasis test. The proportion of positive ELISA serology was 103/373 (27.6%). At microscopy, infected subjects were 65/373 (17.4%), (51% Schistosoma haematobium, 38% Schistosoma mansoni, 11% both). CCA antigen for S. mansoni was positive in 47/373 individuals (12.6%). We found a particularly high positivity rate in subjects from Mali (72.1%) and Ivory Coast (48%). This "hidden epidemic" of schistosomiasis cannot be longer neglected, considering the risk of severe complications, and the effective and inexpensive treatment available.

Detection of early and single infections of Schistosoma japonicum in the intermediate host snail, Oncomelania hupensis, by PCR and loop-mediated isothermal amplification (LAMP) assay.

PubMed

Kumagai, Takashi; Furushima-Shimogawara, Rieko; Ohmae, Hiroshi; Wang, Tian-Ping; Lu, Shaohong; Chen, Rui; Wen, Liyong; Ohta, Nobuo

2010-09-01

Polymerase chain reaction (PCR) with the specific primer set amplifying 28S ribosomal DNA (rDNA) of Schistosoma japonicum was able to detect genomic DNA of S. japonicum, but not S. mansoni, at 100 fg. This procedure enabled us to detect the DNA from a single miracidium and a snail infected with one miracidium at just 1 day after infection. We compared these results with those from loop-mediated isothermal amplification (LAMP) targeting 28S rDNA and found similar results. The LAMP could amplify the specific DNA from a group of 100 normal snails mixed with one infected snail A PCR screening of infected snails from endemic regions in Anhui Province revealed schistosomal DNA even in snails found negative by microscopy. PCR and LAMP show promise for monitoring the early infection rate in snails, and they may be useful for predicting the risk of infection in the endemic places.

Schistosomiasis

PubMed Central

Tucker, Matthew S.; Karunaratne, Laksiri B.; Lewis, Fred A.; Freitas, Tori C.; Liang, Yung-san

2014-01-01

Schistosomiasis is the second most important parasitic disease in the world in terms of public health impact. Globally, it is estimated that the disease affects over 200 million people and is responsible for 200,000 deaths each year. The three major schistosomes infecting humans are Schistosoma mansoni, S. japonicum, and S. haematobium. Much immunological research has focused on schistosomiasis because of the pathological effects of the disease, which include liver fibrosis and bladder dysfunction. This Unit covers a wide range of aspects of maintaining the life cycles of these parasites, including preparation of schistosome egg antigen, maintenance of intermediate snail hosts, infection of the definitive and intermediate hosts, and others. The Unit primariiy focues on S. mansoni, but also includes coverage of S. japonicum and S. haematobium life cycles. PMID:18432750

Purinergic P2Y12 Receptor Activation in Eosinophils and the Schistosomal Host Response.

PubMed

Muniz, Valdirene S; Baptista-Dos-Reis, Renata; Benjamim, Claudia F; Mata-Santos, Hilton A; Pyrrho, Alexandre S; Strauch, Marcelo A; Melo, Paulo A; Vicentino, Amanda R R; Silva-Paiva, Juliana; Bandeira-Melo, Christianne; Weller, Peter F; Figueiredo, Rodrigo T; Neves, Josiane S

2015-01-01

Identifying new target molecules through which eosinophils secrete their stored proteins may reveal new therapeutic approaches for the control of eosinophilic disorders such as host immune responses to parasites. We have recently reported the expression of the purinergic P2Y12 receptor (P2Y12R) in human eosinophils; however, its functional role in this cell type and its involvement in eosinophilic inflammation remain unknown. Here, we investigated functional roles of P2Y12R in isolated human eosinophils and in a murine model of eosinophilic inflammation induced by Schistosoma mansoni (S. mansoni) infection. We found that adenosine 5'-diphosphate (ADP) induced human eosinophils to secrete eosinophil peroxidase (EPO) in a P2Y12R dependent manner. However, ADP did not interfere with human eosinophil apoptosis or chemotaxis in vitro. In vivo, C57Bl/6 mice were infected with cercariae of the Belo Horizonte strain of S. mansoni. Analyses performed 55 days post infection revealed that P2Y12R blockade reduced the granulomatous hepatic area and the eosinophilic infiltrate, collagen deposition and IL-13/IL-4 production in the liver without affecting the parasite oviposition. As found for humans, murine eosinophils also express the P2Y12R. P2Y12R inhibition increased blood eosinophilia, whereas it decreased the bone marrow eosinophil count. Our results suggest that P2Y12R has an important role in eosinophil EPO secretion and in establishing the inflammatory response in the course of a S. mansoni infection.

A Schistosoma haematobium-specific real-time PCR for diagnosis of urogenital schistosomiasis in serum samples of international travelers and migrants.

PubMed

Cnops, Lieselotte; Soentjens, Patrick; Clerinx, Jan; Van Esbroeck, Marjan

2013-01-01

Diagnosis of urogenital schistosomiasis by microscopy and serological tests may be elusive in travelers due to low egg load and the absence of seroconversion upon arrival. There is need for a more sensitive diagnostic test. Therefore, we developed a real-time PCR targeting the Schistosoma haematobium-specific Dra1 sequence. The PCR was evaluated on urine (n = 111), stool (n = 84) and serum samples (n = 135), and one biopsy from travelers and migrants with confirmed or suspected schistosomiasis. PCR revealed a positive result in 7/7 urine samples, 11/11 stool samples and 1/1 biopsy containing S. haematobium eggs as demonstrated by microscopy and in 22/23 serum samples from patients with a parasitological confirmed S. haematobium infection. S. haematobium DNA was additionally detected by PCR in 7 urine, 3 stool and 5 serum samples of patients suspected of having schistosomiasis without egg excretion in urine and feces. None of these suspected patients demonstrated other parasitic infections except one with Blastocystis hominis and Entamoeba cyst in a fecal sample. The PCR was negative in all stool samples containing S. mansoni eggs (n = 21) and in all serum samples of patients with a microscopically confirmed S. mansoni (n = 22), Ascaris lumbricoides (n = 1), Ancylostomidae (n = 1), Strongyloides stercoralis (n = 1) or Trichuris trichuria infection (n = 1). The PCR demonstrated a high specificity, reproducibility and analytical sensitivity (0.5 eggs per gram of feces). The real-time PCR targeting the Dra1 sequence for S. haematobium-specific detection in urine, feces, and particularly serum, is a promising tool to confirm the diagnosis, also during the acute phase of urogenital schistosomiasis.

DNA Vaccine Encoding the Chimeric Form of Schistosoma mansoni Sm-TSP2 and Sm29 Confers Partial Protection against Challenge Infection

PubMed Central

Gonçalves de Assis, Natan Raimundo; Batistoni de Morais, Suellen; Figueiredo, Bárbara Castro Pimentel; Ricci, Natasha Delaqua; de Almeida, Leonardo Augusto; da Silva Pinheiro, Carina; Martins, Vicente de Paulo; Oliveira, Sergio Costa

2015-01-01

Schistosomiasis is an important parasitic disease worldwide that affects more than 207 million people in 76 countries and causes approximately 250,000 deaths per year. The best long-term strategy to control schistosomiasis is through immunization combined with drug treatment. Due to the ability of DNA vaccines to generate humoral and cellular immune responses, such vaccines are considered a promising approach against schistosomiasis. Sm29 and tetraspanin-2 (Sm-TSP2) are two proteins that are located in the S. mansoni tegument of adult worms and schistosomula and induce high levels of protection through recombinant protein immunization. In this study, we transfected BHK-21 cells with plasmids encoding Sm29, Sm-TSP2 or a chimera containing both genes. Using RT-PCR analysis and western blot, we confirmed that the DNA vaccine constructs were transcribed and translated, respectively, in BHK-21 cells. After immunization of mice, we evaluated the reduction in worm burden. We observed worm burden reductions of 17-22%, 22%, 31-32% and 24-32% in animals immunized with the pUMVC3/Sm29, pUMVC3/SmTSP-2, pUMVC3/Chimera and pUMVC3/Sm29 + pUMVC3/SmTSP-2 plasmids, respectively. We evaluated the humoral response elicited by DNA vaccines, and animals immunized with pUMVC3/Sm29 and pUMVC3/Sm29 + pUMVC3/SmTSP-2 showed higher titers of anti-Sm29 antibodies. The cytokine profile produced by the spleen cells of immunized mice was then evaluated. We observed higher production of Th1 cytokines, such as TNF-α and IFN-γ, in vaccinated mice and no significant production of IL-4 and IL-5. The DNA vaccines tested in this study showed the ability to generate a protective immune response against schistosomiasis, probably through the production of Th1 cytokines. However, future strategies aiming to optimize the protective response induced by a chimeric DNA construct need to be developed. PMID:25942636

21 CFR 660.50 - Anti-Human Globulin.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 7 2014-04-01 2014-04-01 false Anti-Human Globulin. 660.50 Section 660.50 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS ADDITIONAL STANDARDS FOR DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Anti-Human Globulin § 660.50 Anti-Human...

21 CFR 660.50 - Anti-Human Globulin.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 7 2011-04-01 2010-04-01 true Anti-Human Globulin. 660.50 Section 660.50 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS ADDITIONAL STANDARDS FOR DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Anti-Human Globulin § 660.50 Anti-Human...

21 CFR 660.50 - Anti-Human Globulin.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 7 2013-04-01 2013-04-01 false Anti-Human Globulin. 660.50 Section 660.50 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS ADDITIONAL STANDARDS FOR DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Anti-Human Globulin § 660.50 Anti-Human...

21 CFR 660.50 - Anti-Human Globulin.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 7 2012-04-01 2012-04-01 false Anti-Human Globulin. 660.50 Section 660.50 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS ADDITIONAL STANDARDS FOR DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Anti-Human Globulin § 660.50 Anti-Human...

Screening trematodes for novel intervention targets: a proteomic and immunological comparison of Schistosoma haematobium, Schistosoma bovis and Echinostoma caproni

PubMed Central

HIGÓN, MELISSA; COWAN, GRAEME; NAUSCH, NORMAN; CAVANAGH, DAVID; OLEAGA, ANA; TOLEDO, RAFAEL; STOTHARD, J. RUSSELL; ANTÚNEZ, ORETO; MARCILLA, ANTONIO; BURCHMORE, RICHARD; MUTAPI, FRANCISCA

2011-01-01

SUMMARY With the current paucity of vaccine targets for parasitic diseases, particularly those in childhood, the aim of this study was to compare protein expression and immune cross-reactivity between the trematodes Schistosoma haematobium, S. bovis and Echinostoma caproni in the hope of identifying novel intervention targets. Native adult parasite proteins were separated by 2-dimensional gel electrophoresis and identified through electrospray ionisation tandem mass spectrometry to produce a reference gel. Proteins from differential gel electrophoresis analyses of the three parasite proteomes were compared and screened against sera from hamsters infected with S. haematobium and E. caproni following 2-dimensional Western blotting. Differential protein expression between the three species was observed with circa 5% of proteins from S. haematobium showing expression up-regulation compared to the other two species. There was 91% similarity between the proteomes of the two Schistosoma species and 81% and 78·6% similarity between S. haematobium and S. bovis versus E. caproni, respectively. Although there were some common cross-species antigens, species-species targets were revealed which, despite evolutionary homology, could be due to phenotypic plasticity arising from different host-parasite relationships. Nevertheless, this approach helps to identify novel intervention targets which could be used as broad-spectrum candidates for future use in human and veterinary vaccines. PMID:21729355

Chicken egg yolk antibodies (IgY) for detecting circulating antigens of Schistosoma japonicum.

PubMed

Cai, Yu-Chun; Guo, Jian; Chen, Shao-Hong; Tian, Li-Guang; Steinmann, Peter; Chen, Mu-Xin; Li, Hao; Ai, Lin; Chen, Jia-Xu

2012-09-01

IgY isolated from egg yolk has been widely used in immunodiagnostic tests, including tests to detect circulating antigen (soluble egg antigen or SEA) of Schistosoma japonicum. A sandwich ELISA was established using a combination of anti-S. japonicum SEA-IgY polyclonal antibodies and IgM monoclonal antibodies. To explore sensitivity and specificity of the sandwich ELISA, serum samples from 43 patients infected with S. japonicum were tested. All acute cases and 91.3% of the chronic cases showed a positive reaction. Only 5% of the control sera from healthy persons gave a positive response. Cross-reactions with antibodies to nine other parasites were rare. The developed immunoassay is reasonably sensitive and specific. It could be used for field research and treatment efficacy assessments. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Targeting histone deacetylase inhibitors for anti-malarial therapy.

PubMed

Andrews, Katherine T; Tran, Thanh N; Wheatley, Nicole C; Fairlie, David P

2009-01-01

It is now clear that histone acetylation plays key roles in regulating gene transcription in both eukaryotes and prokaryotes, the acetylated form inducing gene expression while deacetylation silences genes. Recent studies have identified roles for histone acetyltransferases (HATs) and/or histone deacetylases (HDACs) in a number of parasites including Entamoeba histolytica, Toxoplasma gondii, Schistosoma mansoni, Cryptosporidium sp., Leishmania donovani, Neospora caninum, and Plasmodium falciparum. Here we survey fairly limited efforts to date in profiling antimalarial activities of HDAC inhibitors, showing that such compounds are potent inhibitors of the growth of P. falciparum in vitro and in vivo. Most of the compounds evaluated so far have borne a zinc-binding hydroxamate group that tends to be metabolized in vivo, and thus new zinc-binding groups need to be incorporated into second generation inhibitors in order to mask the catalytic zinc in the active site of HDACs. Also the development of compounds that are selective for parasitic HDACs over mammalian HDACs is still in relative infancy and it will take some time to derive antiparasitic HDAC inhibitor compounds with minimal toxicity for the host and acceptable pharmacokinetic and pharmacodynamic profiles for human treatment. Nevertheless, results to date suggest that HDAC inhibitor development represents a promising new approach to the potential treatment of parasitic infections, including those induced by malaria protozoa, and may offer new therapeutic targets within increasingly drug-resistant malarial parasites.

Artemether as adjuvant therapy to praziquantel in murine Egyptian schistosomiasis mansoni.

PubMed

Mahmoud, M R; Botros, S S

2005-02-01

We investigated the activity of artemether (ART) against different developmental stages of schistosomes alone and in addition to praziquantel (PZQ). ART was administered orally (400 mg/kg) 4 and 6 wk postinfection (PI), 4 and 5 wk PI, or 4 or 6 wk PI alone and in addition to oral PZQ (500 x 2 mg/kg) 6 wk PI. Mice were killed in parallel to infected untreated controls 8 wk PI. Parasitological parameters and histological changes in the liver were studied. ART given 4 and 6 wk PI reduced worm burdens by 59 and 55% and tissue egg load by 96 and 90%, respectively. Moreover, eggs in different developmental stages were not found. The reduction in worm and egg burden (63 and 58%, and 96 and 99%, respectively) in mice treated with ART 4 and 5 wk or 4 and 6 wk PI was comparable with that in ART-treated mice at 4 or 6 wk PI. Compared with PZQ alone, combined treatment of PZQ and ART (4 and 5 wk or 4 and 6 wk PI) did not enhance worm eradication, but there was a complete absence of parasite eggs. Livers revealed no granulomata when ART was given 4 and 5 wk or 4 and 6 wk PI, with minimal central necrosis in those treated 4 and 6 wk PI. In conclusion, combined treatment of ART (4 and 6 wk PI) and PZQ resulted in >90% worm eradication and amelioration of Schistosoma mansoni eggs from the tissues, with minor histological changes in the liver.

Angiogenesis and parasitic helminth-associated neovascularization.

PubMed

Dennis, Roger D; Schubert, Uwe; Bauer, Christian

2011-04-01

Successful metazoan parasitism, among many other factors, requires a supply of nutrients and the removal of waste products. There is a prerequisite for a parasite-defined vasculature. The angiogenic mechanism(s) involved presumably depend on the characteristics of the tissue- and vascular system-dwelling, parasitic helminths. Simplistically, 2 possibilities or a combination of both have been considered in this review. The multifactorial induction of parasitic helminth-associated neovascularization could arise through, either a host-, a parasite- or a host-/parasite-dependent, angiogenic switch. Most studies appear to support the first and third hypotheses, but evidence exists for the intrahepatic cestode Echinococcus multilocularis, the free-living nematode Caenorhabditis elegans and the intravascular trematode Schistosoma mansoni for the second inference. In contrast, the nematode anti-coagulant protein NAPc2 from adult Ancylostoma caninum is also an anti-angiogenic factor.

Migrating microbes: what pathogens can tell us about population movements and human evolution.

PubMed

Houldcroft, Charlotte J; Ramond, Jean-Baptiste; Rifkin, Riaan F; Underdown, Simon J

2017-08-01

The biology of human migration can be observed from the co-evolutionary relationship with infectious diseases. While many pathogens are brief, unpleasant visitors to human bodies, others have the ability to become life-long human passengers. The story of a pathogen's genetic code may, therefore, provide insight into the history of its human host. The evolution and distribution of disease in Africa is of particular interest, because of the deep history of human evolution in Africa, the presence of a variety of non-human primates, and tropical reservoirs of emerging infectious diseases. This study explores which pathogens leave traces in the archaeological record, and whether there are realistic prospects that these pathogens can be recovered from sub-Saharan African archaeological contexts. Three stories are then presented of germs on a journey. The first is the story of HIV's spread on the back of colonialism and the railway networks over the last 150 years. The second involves the spread of Schistosoma mansoni, a parasite which shares its history with the trans-Atlantic slave trade and the origins of fresh-water fishing. Finally, we discuss the tantalising hints of hominin migration and interaction found in the genome of human herpes simplex virus 2. Evidence from modern African pathogen genomes can provide data on human behaviour and migration in deep time and contribute to the improvement of human quality-of-life and longevity.

Streptozotocin (STZ) and schistosomiasis mansoni change the biodistribution of radiopharmaceutical sodium (99m)Tc-pertechnetate in mice.

PubMed

Góes, Vanessa Coelho; Neves, Renata Heisler; Arnóbio, Adriano; Bernardo-Filho, Mario; Machado-Silva, José Roberto

2016-09-01

Technetium-99m ((99m)Tc) is a radionuclide commonly used in nuclear medicine to obtain (99m)Tc-radiopharmaceuticals, which can be used to evaluate either physiological processes or changes related to diseases. It is also used in some experimental studies. Streptozotocin (STZ) administration to rodents causes lesions in very early stages and induces severe and permanent diabetes. Most morbidity of schistosomiasis mansoni is attributed to a granulomatous inflammatory response and associated liver fibrosis. This study was designed to investigate whether STZ administration and schistosomiasis modify the biodistribution of the radiopharmaceutical sodium (99m)Tc-pertechnetate. Adult female mice were infected by exposure to 100Schistosoma mansoni cercariae (BH strain, Belo Horizonte, Brazil) and euthanized after nine weeks. STZ was administered by a single intraperitoneal injection of 100mg/kg body weight, 3 or 15days before euthanasia. Each animal received 100μl of sodium (Na) (99m)Tc-pertechnetate ((99m)TcO4(-)) (740kBq). The animals were divided into four groups: A, uninfected; B, infected; C, uninfected + STZ; and D, infected + STZ. Blood, brain, thyroid, heart, lungs, liver, spleen, pancreas and kidneys were removed. The radioactivity was counted and the percentage of the injected dose of Na(99m)TcO4 per gram of the organ (% ID/g) was determined. Three days after the STZ injection, there was a decrease of Na(99m)TcO4 uptake by the liver, lungs, pancreas and kidneys (p<0.05) in group D when compared with group A. After 15days, the decrease of Na(99m)TcO4 uptake occurred also in the brain, thyroid, heart, spleen and blood (p<0.05) in group D. We demonstrated modifications on the biodistribution of Na(99m)TcO4 due to STZ administration and schistosomiasis, possibly due to physiological alterations in some organs. The biodistribution of radiopharmaceutical Na(99m)TcO4 should be carefully evaluated in subjects with diabetes and/or schistosomiasis infection. Copyright �

Identification of lead chemotherapeutic agents from medicinal plants against blood flukes and whipworms.

PubMed

Wangchuk, Phurpa; Giacomin, Paul R; Pearson, Mark S; Smout, Michael J; Loukas, Alex

2016-08-30

Schistosomiasis and trichuriasis are two of the most common neglected tropical diseases (NTD) that affect almost a billion people worldwide. There is only a limited number of effective drugs to combat these NTD. Medicinal plants are a viable source of parasiticides. In this study, we have investigated six of the 19 phytochemicals isolated from two Bhutanese medicinal plants, Corydalis crispa and Pleurospermum amabile, for their anthelmintic properties. We used the xWORM technique and Scanning Electron Microscope-based imaging to determine the activity of the compounds. Of the six compounds tested, isomyristicin and bergapten showed significant anthelmintic activity against Schistosoma mansoni and Trichuris muris with bergapten being the most efficacious compound one against both parasites (S. mansoni IC50 = 8.6 μg/mL and T. muris IC50 = 10.6 μg/mL) and also against the schistosomulum stage of S. mansoni. These two compounds induced tegumental damage to S. mansoni and affected the cuticle, bacillary bands and bacillary glands of T. muris. The efficacy against multiple phylogenetically distinct parasites and different life stages, especially the schistosomulum where praziquantel is ineffective, makes isomyristicin and bergapten novel scaffolds for broad-spectrum anthelmintic drug development that could be used for the control of helminths infecting humans and animals.

Non-equilibrium plasma prevention of Schistosoma japonicum transmission

NASA Astrophysics Data System (ADS)

Wang, Xing-Quan; Wang, Feng-Peng; Chen, Wei; Huang, Jun; Bazaka, Kateryna; Ostrikov, Kostya (Ken)

2016-10-01

Schistosoma japonicum is a widespread human and animal parasite that causes intestinal and hepatosplenic schistosomiasis linked to colon, liver and bladder cancers, and anemia. Estimated 230 million people are currently infected with Schistosoma spp, with 779 million people at risk of contracting the parasite. Infection occurs when a host comes into contact with cercariae, a planktonic larval stage of the parasite, and can be prevented by inactivating the larvae, commonly by chemical treatment. We investigated the use of physical non-equilibrium plasma generated at atmospheric pressure using custom-made dielectric barrier discharge reactor to kill S. japonicum cercariae. Survival rate decreased with treatment time and applied power. Plasmas generated in O2 and air gas discharges were more effective in killing S. japonicum cercariae than that generated in He, which is directly related to the mechanism by which cercariae are inactivated. Reactive oxygen species, such as O atoms, abundant in O2 plasma and NO in air plasma play a major role in killing of S. japonicum cercariae via oxidation mechanisms. Similar level of efficacy is also shown for a gliding arc discharge plasma jet generated in ambient air, a system that may be more appropriate for scale-up and integration into existing water treatment processes.

Co-Infection With Intestinal Helminths Markedly Reduces Proinflammatory Cytokines And Disease Severity In Natural And Induced High-Pathology Schistosomiasis

USDA-ARS?s Scientific Manuscript database

Infection with the trematode helminth Schistosoma mansoni results in a parasite egg-induced, CD4 T cell-mediated, hepato-intestinal granulomatous and fibrosing inflammation that varies greatly in severity, with a higher frequency of milder forms typical in endemic areas. One possible explanation is...

Helminths and Cancers From the Evolutionary Perspective.

PubMed

Scholte, Larissa L S; Pascoal-Xavier, Marcelo A; Nahum, Laila A

2018-01-01

Helminths include free-living and parasitic Platyhelminthes and Nematoda which infect millions of people worldwide. Some Platyhelminthes species of blood flukes ( Schistosoma haematobium, Schistosoma japonicum , and Schistosoma mansoni ) and liver flukes ( Clonorchis sinensis and Opisthorchis viverrini ) are known to be involved in human cancers. Other helminths are likely to be carcinogenic. Our main goals are to summarize the current knowledge of human cancers caused by Platyhelminthes, point out some helminth and human biomarkers identified so far, and highlight the potential contributions of phylogenetics and molecular evolution to cancer research. Human cancers caused by helminth infection include cholangiocarcinoma, colorectal hepatocellular carcinoma, squamous cell carcinoma, and urinary bladder cancer. Chronic inflammation is proposed as a common pathway for cancer initiation and development. Furthermore, different bacteria present in gastric, colorectal, and urogenital microbiomes might be responsible for enlarging inflammatory and fibrotic responses in cancers. Studies have suggested that different biomarkers are involved in helminth infection and human cancer development; although, the detailed mechanisms remain under debate. Different helminth proteins have been studied by different approaches. However, their evolutionary relationships remain unsolved. Here, we illustrate the strengths of homology identification and function prediction of uncharacterized proteins from genome sequencing projects based on an evolutionary framework. Together, these approaches may help identifying new biomarkers for disease diagnostics and intervention measures. This work has potential applications in the field of phylomedicine (evolutionary medicine) and may contribute to parasite and cancer research.

[Study on an intervention model of "schools without infected students with schistosoma japonica" in heavy endemic areas].

PubMed

Chen, Hai-ying; Hu, Guang-han; Song, Kuang-yu; Xiong, Zhi-wei; Wan, Bao-ping; Yang, Ping-yi; Hu, Jia; Peng, Guo-hua; Hu, Wei-Chen; Fu, Guo-Lan

2010-10-01

To study an intervention model of "schools without infected students with schistosoma japonica", to control and prevent students from schistosoma infection. Twelve primary schools of four heavy endemic counties (districts) with schistosomiasis in the Poyang Lake areas were selected as the study fields, of which, ten schools were the experimental groups, and the other two schools were the control groups by cluster random sampling. All enrolment students were the target population. The baseline survey was carried out in 2005, and an intervention model, "information dissemination + behavior participation + behavior encouragement", was applied in the experiment groups in 2006 - 2008, then the effect of intervention was assessed. Before intervention (2005), the anti-schistosomiasis knowledge awareness rate of experimental and control groups were 14.75% (324/2196) and 16.58% (91/549), and the different was not significant (χ(2) = 1.14, P > 0.05); the rate of accurate attitude of anti-schistosomiasis were 14.71% (323/2196) and 11.84% (65/549) in experimental and control groups, and the difference was not significant (χ(2) = 2.98, P > 0.05); the rate of contacting infected water were 15.44% (18 988/122 976) and 15.03% (4622/30 744) in experimental and control group and the difference was not significant (χ(2) = 3.13, P > 0.05); and the infection rate of schistosomiasis of experiment control groups were 9.65% (212/2196) and 10.56% (58/549), the difference was not significant (χ(2) = 0.41, P > 0.05). After one year intervention (2006), the anti-schistosomiasis knowledge awareness rate of experimental and control groups were 97.79% (2032/2078) and 18.11% (98/541), and the different was significant (χ(2) = 1794.31, P < 0.01); the rate of accurate attitude of anti-schistosomiasis were 99.09% (2059/2078) and 13.49% (73/541) in experimental and control group, and the difference was significant (χ(2) = 2077.45, P < 0.01). After 1 - 3 years intervention (2006 - 2008), there

Tropical Diseases Screening in Immigrant Patients with Human Immunodeficiency Virus Infection in Spain

PubMed Central

Salvador, Fernando; Molina, Israel; Sulleiro, Elena; Burgos, Joaquín; Curran, Adrián; den Eynde, Eva Van; Villar del Saz, Sara; Navarro, Jordi; Crespo, Manuel; Ocaña, Inma; Ribera, Esteve; Falcó, Vicenç; Pahissa, Albert

2013-01-01

Latent parasitic infections can reactivate because of immunosuppression. We conducted a prospective observational study of all human immunodeficiency virus (HIV)–infected immigrants who visited the Infectious Diseases Department of the Hospital Universitari Vall d'Hebron, Barcelona, Spain, during June 2010–May 2011. Screening of the most prevalent tropical diseases (intestinal parasitosis, Chagas disease, leishmaniasis, malaria, schistosomiasis, and strongyloidiasis) was performed according to geographic origin. A total of 190 patients were included: 141 (74.2%) from Latin America, 41 (21.6%) from sub-Saharan Africa, and 8 (4.2%) from northern Africa. Overall, 36.8% (70 of 190) of the patients had at least one positive result for any parasitic disease: 5 patients with positive Trypanosoma cruzi serology, 11 patients with positive Schistosoma mansoni serology, 35 patients with positive Strongyloides stercoralis serology, 7 patients with positive Leishmania infantum serology, intestinal parasitosis were detected in 37 patients, malaria was diagnosed in one symptomatic patient. We propose a screening and management strategy of latent parasitic infections in immigrant patients infected with HIV. PMID:23509119

Tropical diseases screening in immigrant patients with human immunodeficiency virus infection in Spain.

PubMed

Salvador, Fernando; Molina, Israel; Sulleiro, Elena; Burgos, Joaquín; Curran, Adrián; Van den Eynde, Eva; Villar del Saz, Sara; Navarro, Jordi; Crespo, Manuel; Ocaña, Inma; Ribera, Esteve; Falcó, Vicenç; Pahissa, Albert

2013-06-01

Latent parasitic infections can reactivate because of immunosuppression. We conducted a prospective observational study of all human immunodeficiency virus (HIV)-infected immigrants who visited the Infectious Diseases Department of the Hospital Universitari Vall d'Hebron, Barcelona, Spain, during June 2010-May 2011. Screening of the most prevalent tropical diseases (intestinal parasitosis, Chagas disease, leishmaniasis, malaria, schistosomiasis, and strongyloidiasis) was performed according to geographic origin. A total of 190 patients were included: 141 (74.2%) from Latin America, 41 (21.6%) from sub-Saharan Africa, and 8 (4.2%) from northern Africa. Overall, 36.8% (70 of 190) of the patients had at least one positive result for any parasitic disease: 5 patients with positive Trypanosoma cruzi serology, 11 patients with positive Schistosoma mansoni serology, 35 patients with positive Strongyloides stercoralis serology, 7 patients with positive Leishmania infantum serology, intestinal parasitosis were detected in 37 patients, malaria was diagnosed in one symptomatic patient. We propose a screening and management strategy of latent parasitic infections in immigrant patients infected with HIV.

Helminth-induced arginase-1 exacerbates lung inflammation and disease severity in tuberculosis.

PubMed

Monin, Leticia; Griffiths, Kristin L; Lam, Wing Y; Gopal, Radha; Kang, Dongwan D; Ahmed, Mushtaq; Rajamanickam, Anuradha; Cruz-Lagunas, Alfredo; Zúñiga, Joaquín; Babu, Subash; Kolls, Jay K; Mitreva, Makedonka; Rosa, Bruce A; Ramos-Payan, Rosalio; Morrison, Thomas E; Murray, Peter J; Rangel-Moreno, Javier; Pearce, Edward J; Khader, Shabaana A

2015-12-01

Parasitic helminth worms, such as Schistosoma mansoni, are endemic in regions with a high prevalence of tuberculosis (TB) among the population. Human studies suggest that helminth coinfections contribute to increased TB susceptibility and increased rates of TB reactivation. Prevailing models suggest that T helper type 2 (Th2) responses induced by helminth infection impair Th1 immune responses and thereby limit Mycobacterium tuberculosis (Mtb) control. Using a pulmonary mouse model of Mtb infection, we demonstrated that S. mansoni coinfection or immunization with S. mansoni egg antigens can reversibly impair Mtb-specific T cell responses without affecting macrophage-mediated Mtb control. Instead, S. mansoni infection resulted in accumulation of high arginase-1-expressing macrophages in the lung, which formed type 2 granulomas and exacerbated inflammation in Mtb-infected mice. Treatment of coinfected animals with an antihelminthic improved Mtb-specific Th1 responses and reduced disease severity. In a genetically diverse mouse population infected with Mtb, enhanced arginase-1 activity was associated with increased lung inflammation. Moreover, in patients with pulmonary TB, lung damage correlated with increased serum activity of arginase-1, which was elevated in TB patients coinfected with helminths. Together, our data indicate that helminth coinfection induces arginase-1-expressing type 2 granulomas, thereby increasing inflammation and TB disease severity. These results also provide insight into the mechanisms by which helminth coinfections drive increased susceptibility, disease progression, and severity in TB.

Identification of lead chemotherapeutic agents from medicinal plants against blood flukes and whipworms

PubMed Central

Wangchuk, Phurpa; Giacomin, Paul R.; Pearson, Mark S.; Smout, Michael J.; Loukas, Alex

2016-01-01

Schistosomiasis and trichuriasis are two of the most common neglected tropical diseases (NTD) that affect almost a billion people worldwide. There is only a limited number of effective drugs to combat these NTD. Medicinal plants are a viable source of parasiticides. In this study, we have investigated six of the 19 phytochemicals isolated from two Bhutanese medicinal plants, Corydalis crispa and Pleurospermum amabile, for their anthelmintic properties. We used the xWORM technique and Scanning Electron Microscope-based imaging to determine the activity of the compounds. Of the six compounds tested, isomyristicin and bergapten showed significant anthelmintic activity against Schistosoma mansoni and Trichuris muris with bergapten being the most efficacious compound one against both parasites (S. mansoni IC50 = 8.6 μg/mL and T. muris IC50 = 10.6 μg/mL) and also against the schistosomulum stage of S. mansoni. These two compounds induced tegumental damage to S. mansoni and affected the cuticle, bacillary bands and bacillary glands of T. muris. The efficacy against multiple phylogenetically distinct parasites and different life stages, especially the schistosomulum where praziquantel is ineffective, makes isomyristicin and bergapten novel scaffolds for broad-spectrum anthelmintic drug development that could be used for the control of helminths infecting humans and animals. PMID:27572696

Detection of intestinal parasites on field-grown strawberries in the Federal District of Brazil.

PubMed

Silva, Sandra Regina Morais da; Maldonade, Iriani Rodrigues; Ginani, Verônica Cortez; Lima, Sônia Alves; Mendes, Vinícios Silveira; Azevedo, Maria Lidiane Ximendes; Gurgel-Gonçalves, Rodrigo; Machado, Eleuza Rodrigues

2014-01-01

This study evaluated the presence of pathogenic human parasites on field-grown strawberries in the Federal District of Brazil. A total of 48 samples of strawberries and 48 soil samples from 16 properties were analyzed. Contaminated strawberries were detected in 56% of the properties. Schistosoma mansoni, Ascaris lumbricoides or Ascaris suum, Balantidium coli, Endolimax nana, and Entamoeba spp. were detected. Soil was contaminated with Entamoeba spp., Entamoeba coli, Strongyloides spp., Ancylostomatidae, and Hymenolepis nana. Producers should be instructed on the safe handling of strawberries in order to reduce the incidence of strawberries that are contaminated with enteroparasites.

Population genetics of Schistosoma japonicum within the Philippines suggest high levels of transmission between humans and dogs.

PubMed

Rudge, James W; Carabin, Hélène; Balolong, Ernesto; Tallo, Veronica; Shrivastava, Jaya; Lu, Da-Bing; Basáñez, María-Gloria; Olveda, Remigio; McGarvey, Stephen T; Webster, Joanne P

2008-01-01

Schistosoma japonicum, which remains a major public health problem in the Philippines and mainland China, is the only schistosome species for which zoonotic transmission is considered important. While bovines are suspected as the main zoonotic reservoir in parts of China, the relative contributions of various non-human mammals to S. japonicum transmission in the Philippines remain to be determined. We examined the population genetics of S. japonicum in the Philippines in order to elucidate transmission patterns across host species and geographic areas. S. japonicum miracidia (hatched from eggs within fecal samples) from humans, dogs, pigs and rats, and cercariae shed from snail-intermediate hosts, were collected across two geographic areas of Samar Province. Individual isolates were then genotyped using seven multiplexed microsatellite loci. Wright's F(ST) values and phylogenetic trees calculated for parasite populations suggest a high frequency of parasite gene-flow across definitive host species, particularly between dogs and humans. Parasite genetic differentiation between areas was not evident at the definitive host level, possibly suggesting frequent import and export of infections between villages, although there was some evidence of geographic structuring at the snail-intermediate host level. These results suggest very high levels of transmission across host species, and indicate that the role of dogs should be considered when planning control programs. Furthermore, a regional approach to treatment programs is recommended where human migration is extensive.

[The occurrence of Biomphalaria straminea (Pulmonata: Planorbidae) on an aquaculture farm of IBAMA in Uberlândia, MG. Instituto Brasileiro do Meio Ambiente a dos Recursos Naturais Renováveis].

PubMed

Silveira, E de P; Marçal Júnior, O; Machado, M I

1997-01-01

This work evaluates the occurrence of freshwater snails in the IBAMA's fish breeding station in Uberlândia, Minas Gerais State. We verified the presence of Biomphalaria straminea in 39.5% of all breeding tanks. None of the snails were infected by Schistosoma mansoni, but further investigation should be done in the area.

Projecting the Long-Term Impact of School- or Community-Based Mass-Treatment Interventions for Control of Schistosoma Infection

PubMed Central

Wang, Xiaoxia; Gurarie, David; Mungai, Peter L.; Muchiri, Eric M.; Kitron, Uriel; King, Charles H.

2012-01-01

Background Schistosomiasis remains a significant health burden in many areas of the world. Morbidity control, focused on limiting infection intensity through periodic delivery of anti-schistosomal medicines, is the thrust of current World Health Organization guidelines (2006) for reduction of Schistosoma-related disease. A new appreciation of the lifetime impact of repeated Schistosoma infection has directed attention toward strategies for greater suppression of parasite infection per se, with the goal of transmission interruption. Variations in drug schedules involving increased population coverage and/or treatment frequency are now undergoing field trials. However, their relative effectiveness in long-term infection suppression is presently unknown. Methodology/Principal Findings Our study used available field data to calibrate advanced network models of village-level Schistosoma transmission to project outcomes of six different community- or school age-based programs, as compared to the impact of current 2006 W.H.O. recommended control strategies. We then scored the number of years each of 10 typical villages would remain below 10% infection prevalence (a practicable level associated with minimal prevalence of disease). All strategies that included four annual treatments effectively reduced community prevalence to less than 10%, while programs having yearly gaps (‘holidays’) failed to reach this objective in half of the communities. Effective post-program suppression of infection prevalence persisted in half of the 10 villages for 7–10 years, whereas in five high-risk villages, program effects on prevalence lasted zero to four years only. Conclusions/Significance At typical levels of treatment adherence (60 to 70%), current WHO recommendations will likely not achieve effective suppression of Schistosoma prevalence unless implemented for ≥6 years. Following more aggressive 4 year annual intervention, some communities may be able to continue without

Population Genetics of Schistosoma japonicum within the Philippines Suggest High Levels of Transmission between Humans and Dogs

PubMed Central

Rudge, James W.; Carabin, Hélène; Balolong, Ernesto; Tallo, Veronica; Shrivastava, Jaya; Lu, Da-Bing; Basáñez, María-Gloria; Olveda, Remigio; McGarvey, Stephen T.; Webster, Joanne P.

2008-01-01

Background Schistosoma japonicum, which remains a major public health problem in the Philippines and mainland China, is the only schistosome species for which zoonotic transmission is considered important. While bovines are suspected as the main zoonotic reservoir in parts of China, the relative contributions of various non-human mammals to S. japonicum transmission in the Philippines remain to be determined. We examined the population genetics of S. japonicum in the Philippines in order to elucidate transmission patterns across host species and geographic areas. Methodology/Principal Findings S. japonicum miracidia (hatched from eggs within fecal samples) from humans, dogs, pigs and rats, and cercariae shed from snail-intermediate hosts, were collected across two geographic areas of Samar Province. Individual isolates were then genotyped using seven multiplexed microsatellite loci. Wright's FST values and phylogenetic trees calculated for parasite populations suggest a high frequency of parasite gene-flow across definitive host species, particularly between dogs and humans. Parasite genetic differentiation between areas was not evident at the definitive host level, possibly suggesting frequent import and export of infections between villages, although there was some evidence of geographic structuring at the snail–intermediate host level. Conclusions/Significance These results suggest very high levels of transmission across host species, and indicate that the role of dogs should be considered when planning control programs. Furthermore, a regional approach to treatment programs is recommended where human migration is extensive. PMID:19030225

Schistosomiasis in Zambia: a systematic review of past and present experiences.

PubMed

Kalinda, Chester; Chimbari, Moses J; Mukaratirwa, Samson

2018-04-30

The speedy rate of change in the environmental and socio-economics factors may increase the incidence, prevalence and risk of schistosomiasis infections in Zambia. However, available information does not provide a comprehensive understanding of the biogeography and distribution of the disease, ecology and population dynamics of intermediate host snails. The current study used an information-theoretical approach to understand the biogeography and prevalence schistosomiasis and identified knowledge gaps that would be useful to improve policy towards surveillance and eradication of intermediate hosts snails in Zambia. To summarise the existing knowledge and build on past and present experiences of schistosomiasis epidemiology for effective disease control in Zambia, a systematic search of literature for the period 2000-2017 was done on PubMed, Google Scholar and EBSCOhost. Using the key words: 'Schistosomiasis', 'Biomphalaria', 'Bulinus', 'Schistosoma mansoni', 'Schistosoma haematobium', and 'Zambia', in combination with Booleans terms 'AND' and 'OR', published reports/papers were obtained and reviewed independently for inclusion. Thirteen papers published in English that fulfilled the inclusion criteria were selected for the final review. The papers suggest that the risk of infection has increased over the years and this has been attributed to environmental, socio-economic and demographic factors. Furthermore, schistosomiasis is endemic in many parts of the country with infection due to Schistosoma haematobium being more prevalent than that due to S. mansoni. This review also found that S. haematobium was linked to genital lesions, thus increasing risks of contracting other diseases such as HIV and cervical cancer. For both S. haematobium and S. mansoni, environmental, socio-economic, and demographic factors were influential in the transmission and prevalence of the disease and highlight the need for detailed knowledge on ecological modelling and mapping the

SjTat-TPI facilitates adaptive T-cell responses and reduces hepatic pathology during Schistosoma japonicum infection in BALB/c mice.

PubMed

Zhang, Wenyue; Luo, Xiaofeng; Zhang, Fan; Zhu, Yuxiao; Yang, Bingya; Hou, Min; Xu, Zhipeng; Yu, Chuanxin; Chen, Yingying; Chen, Lin; Ji, Minjun

2015-12-30

Schistosomiasis is a kind of parasitic zoonoses which causes serious damage to public health and social development. China is one of the countries most affected by Schistosoma japonicum and an effective vaccine is still needed. In this study, we adopted Tat-mediated protein transduction technology to investigate the impact of different antigen presented approaches on host's immune response and the potential protection against Schistosoma japonicum infection. We successfully constructed the recombinant S. japonicum triosephosphate isomerase, Tat-TPI, as a vaccine candidate. Whether injected with Tat-TPI in foot pad or vaccinated with Tat-TPI in the back subcutaneously for three times, the draining popliteal lymph nodes and spleen both developed a stronger CD8(+)T response (Tc1) in mice. Not only that, but it also helped CD4(+)T cells to produce more IFN-γ than TPI immunisation. In addition, it could boost IgG production, especially IgG1 subclass. Most importantly, Tat-TPI immunisation led to the significant smaller area of a single egg granuloma in the livers as compared with TPI-vaccinated or control groups. However, the anti-infection efficiency induced by Tat-TPI was still restricted. This study indicated that immunisation with Tat-fused TPI could contribute to enhance CD4(+)T-cell response and decrease hepatic egg granulomatous area after S. japonicum infection though it did not achieve our expected protection against Schistosoma japonicum infection. The optimal vaccine strategy warrants further research.

In vitro antischistosomal activity of venom from the Egyptian snake Cerastes cerastes.

PubMed

Hassan, Ehssan Ahmed; Abdel-Rahman, Mohamed Ahmed; Ibrahim, Mohamed Moussa; Soliman, Maha Farid Mohamed

2016-01-01

We studied the potential in vitro antischistosomal activity of Cerastes cerastes venom on adult Schistosoma mansoni worms. Live specimens of the horned viper snake, C. cerastes were collected from the Aswan Governorate (Egypt). Venom was collected from snakes by manual milking. Worms of S. mansoni were obtained from infected hamsters by perfusion and isolated from blood using phosphate buffer. Mortality rates of worms were monitored after 3 days of exposure to snake venom at LC50 and various sublethal concentrations (10, 5, 2.5µg/ml). Scanning electron microscopy was used to investigate tegumental changes in treated worms after exposure to LC50 doses of venom. The LC50 of C. cerastes venom was 21.5µg/ml. The effect of C. cerastes venom on Schistosoma worms varied according to their sex. The mortality rate of male and female worms after 48-h exposure was 83.3% and 50%, respectively. LC50 of C. cerastes venom induced mild to severe tegumental damage in Schistosoma worms in the form of destruction of the oral sucker, shrinkage and erosion of the tegument, and loss of some tubercle spines. The present study demonstrated that C. cerastes venom exerts potential in vitro antischistosomal activity in a time and dose-dependent manner. These results may warrant further investigations to develop novel schistosomicidal agents from C. cerastes snake venom.

Large-scale determinants of intestinal schistosomiasis and intermediate host snail distribution across Africa: does climate matter?

PubMed

Stensgaard, Anna-Sofie; Utzinger, Jürg; Vounatsou, Penelope; Hürlimann, Eveline; Schur, Nadine; Saarnak, Christopher F L; Simoonga, Christopher; Mubita, Patricia; Kabatereine, Narcis B; Tchuem Tchuenté, Louis-Albert; Rahbek, Carsten; Kristensen, Thomas K

2013-11-01

The geographical ranges of most species, including many infectious disease agents and their vectors and intermediate hosts, are assumed to be constrained by climatic tolerances, mainly temperature. It has been suggested that global warming will cause an expansion of the areas potentially suitable for infectious disease transmission. However, the transmission of infectious diseases is governed by a myriad of ecological, economic, evolutionary and social factors. Hence, a deeper understanding of the total disease system (pathogens, vectors and hosts) and its drivers is important for predicting responses to climate change. Here, we combine a growing degree day model for Schistosoma mansoni with species distribution models for the intermediate host snail (Biomphalaria spp.) to investigate large-scale environmental determinants of the distribution of the African S. mansoni-Biomphalaria system and potential impacts of climatic changes. Snail species distribution models included several combinations of climatic and habitat-related predictors; the latter divided into "natural" and "human-impacted" habitat variables to measure anthropogenic influence. The predictive performance of the combined snail-parasite model was evaluated against a comprehensive compilation of historical S. mansoni parasitological survey records, and then examined for two climate change scenarios of increasing severity for 2080. Future projections indicate that while the potential S. mansoni transmission area expands, the snail ranges are more likely to contract and/or move into cooler areas in the south and east. Importantly, we also note that even though climate per se matters, the impact of humans on habitat play a crucial role in determining the distribution of the intermediate host snails in Africa. Thus, a future contraction in the geographical range size of the intermediate host snails caused by climatic changes does not necessarily translate into a decrease or zero-sum change in human

Decline in infection-related morbidities following drug-mediated reductions in the intensity of Schistosoma infection: A systematic review and meta-analysis

PubMed Central

Andrade, Gisele; Bertsch, David J.; Gazzinelli, Andrea

2017-01-01

Background Since 1984, WHO has endorsed drug treatment to reduce Schistosoma infection and its consequent morbidity. Cross-sectional studies suggest pre-treatment correlation between infection intensity and risk for Schistosoma-related pathology. However, evidence also suggests that post-treatment reduction in intensity may not reverse morbidity because some morbidities occur at all levels of infection, and some reflect permanent tissue damage. The aim of this project was to systematically review evidence on drug-based control of schistosomiasis and to develop a quantitative estimate of the impact of post-treatment reductions in infection intensity on prevalence of infection-associated morbidity. Methodology/Principal findings This review was registered at inception with PROSPERO (CRD42015026080). Studies that evaluated morbidity before and after treatment were identified by online searches and searches of private archives. Post-treatment odds ratios or standardized mean differences were calculated for each outcome, and these were correlated to treatment-related egg count reduction ratios (ERRs) by meta-regression. A greater ERR correlated with greater reduction in odds of most morbidities. Random effects meta-analysis was used to derive summary estimates: after treatment of S. mansoni and S. japonicum, left-sided hepatomegaly was reduced by 54%, right-sided hepatomegaly by 47%, splenomegaly by 37%, periportal fibrosis by 52%, diarrhea by 53%, and blood in stools by 75%. For S. haematobium, hematuria was reduced by 92%, proteinuria by 90%, bladder lesions by 86%, and upper urinary tract lesions by 72%. There were no consistent changes in portal dilation or hemoglobin levels. In sub-group analysis, age, infection status, region, parasite species, and interval to follow-up were associated with meaningful differences in outcome. Conclusion/Significance While there are challenges to implementing therapy for schistosomiasis, and praziquantel therapy is not fully

Helminth-induced arginase-1 exacerbates lung inflammation and disease severity in tuberculosis

PubMed Central

Monin, Leticia; Griffiths, Kristin L.; Lam, Wing Y.; Gopal, Radha; Kang, Dongwan D.; Ahmed, Mushtaq; Rajamanickam, Anuradha; Cruz-Lagunas, Alfredo; Zúñiga, Joaquín; Babu, Subash; Kolls, Jay K.; Mitreva, Makedonka; Rosa, Bruce A.; Ramos-Payan, Rosalio; Morrison, Thomas E.; Murray, Peter J.; Rangel-Moreno, Javier; Pearce, Edward J.; Khader, Shabaana A.

2015-01-01

Parasitic helminth worms, such as Schistosoma mansoni, are endemic in regions with a high prevalence of tuberculosis (TB) among the population. Human studies suggest that helminth coinfections contribute to increased TB susceptibility and increased rates of TB reactivation. Prevailing models suggest that T helper type 2 (Th2) responses induced by helminth infection impair Th1 immune responses and thereby limit Mycobacterium tuberculosis (Mtb) control. Using a pulmonary mouse model of Mtb infection, we demonstrated that S. mansoni coinfection or immunization with S. mansoni egg antigens can reversibly impair Mtb-specific T cell responses without affecting macrophage-mediated Mtb control. Instead, S. mansoni infection resulted in accumulation of high arginase-1–expressing macrophages in the lung, which formed type 2 granulomas and exacerbated inflammation in Mtb-infected mice. Treatment of coinfected animals with an antihelminthic improved Mtb-specific Th1 responses and reduced disease severity. In a genetically diverse mouse population infected with Mtb, enhanced arginase-1 activity was associated with increased lung inflammation. Moreover, in patients with pulmonary TB, lung damage correlated with increased serum activity of arginase-1, which was elevated in TB patients coinfected with helminths. Together, our data indicate that helminth coinfection induces arginase-1–expressing type 2 granulomas, thereby increasing inflammation and TB disease severity. These results also provide insight into the mechanisms by which helminth coinfections drive increased susceptibility, disease progression, and severity in TB. PMID:26571397

PROPERTIES OF VARIOUS ANTI-γ-GLOBULIN FACTORS IN HUMAN SERA

PubMed Central

Harboe, Morten; Rau, Barbara; Aho, Kimmo

1965-01-01

The serological and physicochemical properties of the following three forms of human anti-γ-globulin factors were compared: (a) rheumatoid factors; (b) Milgrom type anti-γ-globulin factors; and (c) factors directed against an antigen in human γG-globulin that is hidden in the intact molecule and revealed by enzymatic digestion at low pH. The property common to these factors is ability to interact with human γG-globulin; they are distinguishable because they react with different antigenic groups on this molecule. In all of five sera, the Milgrom type anti-γ-globulin factors were γM-globulins. They reacted with various human γG-globulin antibodies but failed to interact with γM-globulin type antibodies in agglutination and absorption experiments. When isolated from other anti-γ-globulin factors, they agglutinated red cells coated with intact anti-Rh antibodies, but failed to react with cells cells coated with pepsin-digested anti-Rh antibody. These observations indicate that the agglutinator reacts with the crystallizable, inert fragment of γG-globulin. Anti-γ-globulin activity directed against an antigen in human γG-globulin revealed by pepsin digestion was demonstrated in γG-, γA-, and γM-globulins. This anti-γ-globulin factor could be absorbed by antigen-antibody precipitates containing human antibody, which shows that the hidden antigen in human γG-globulin is revealed not only by enzymatic digestion at low pH, but also when γG-globulin is present as antibody in an antigen-antibody precipitate. Rheumatoid factors and Milgrom type anti-γ-globulin factors were also absorbed by antigen-antibody precipitates containing human antibody. The results indicate that the three distinct forms of antiγ-globulin factors may all be produced as a result of antigenic stimulation by autologous antigen-antibody complexes. PMID:14276773

Experimental Design and Methods for Development of Diagnostic Assays for Schistosomiasis Using Monoclonal Antibodies.

DTIC Science & Technology

1983-08-25

solium, Echinococcus granulosus , Entamoeba histolytica, or Wucher erTra-bancr--ofti. The S. mansoni glycoproteins that were immunoprecipitated by sera...Sera from patients or experimental animals infected with Schistosoma, Fasciola hepatica, Trichinella spiralis, Taenia solium, Echinococcus ... granulosus , or Paragonimus westermani cross-react in diag-nostic assays with antigens derived from schistosomes, whether as whole organisms (1-4), crude

In vivo T cell depletion regulates resistance and morbidity in murine schistosomiasis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Phillips, S.M.; Linette, G.P.; Doughty, B.L.

1987-08-01

These studies assessed the roles of subpopulations of T lymphocytes in inducing and modulating resistance to schistosomiasis and thereby influencing subsequent morbidity. C57BL/6 mice were depleted in vivo of Lyt-1+, Lyt-2+, and L3T4+ cells by the daily administration of monoclonal antibodies. The development of protective immunity, induced by exposure to irradiated Schistosoma mansoni cercariae as expressed in depleted animals, was compared to that demonstrated in undepleted, normal, and congenitally athymic C57BL/6 mice. The development of morbidity was determined by spleen weight, portal pressure and reticuloendothelial system activity. The results indicated that depletion of specific subpopulations of T lymphocytes minimally affectedmore » the primary development of parasites; however, depletion strongly influenced the development of resistance to the parasite and subsequent morbidity due to infection. Depletion of T lymphocytes by anti-Lyt-1+ or anti-L3T4+ antibody decreased the development of resistance, antibody and delayed-type hypersensitivity directed against schistosome antigens. Morbidity due to disease was increased. Depletion of Lyt-2+ cells produced opposite changes with augmented resistance and reduced morbidity. Congenitally athymic mice developed minimal resistance and morbidity. Moreover, resistance was inversely related to the morbidity shown by a given animal. These studies indicate that the development of protective immunity to S. mansoni cercariae is regulated by discrete subpopulations of T lymphocytes. The feasibility of decreasing morbidity by increasing specific immunologically mediated resistance is suggested.« less

Immunoprotection of Mice against Schistosomiasis Mansoni Using Solubilized Membrane Antigens

PubMed Central

Sulbarán, Guidenn; Noya, Oscar; Brito, Beatríz; Ballén, Diana E.; Cesari, Italo M.

2013-01-01

Background Schistosomiasis continues to be one of the most prevalent parasitic diseases in the world. Despite the existence of a highly effective antischistosome drug, the disease is spreading into new areas, and national control programs do not arrive to complete their tasks particularly in low endemic areas. The availability of a vaccine could represent an additional component to chemotherapy. Experimental vaccination studies are however necessary to identify parasite molecules that would serve as vaccine candidates. In the present work, C57BL/6 female mice were subcutaneously immunized with an n-butanol extract of the adult worm particulate membranous fraction (AWBE) and its protective effect against a S. mansoni challenge infection was evaluated. Methodology and Findings Water-saturated n-butanol release into the aqueous phase a set of membrane-associated (glyco)proteins that are variably recognized by antibodies in schistosome-infected patients; among the previously identified AWBE antigens there is Alkaline Phosphatase (SmAP) which has been associated with resistance to the infection in mice. As compared to control, a significantly lower number of perfuse parasites was obtained in the immunized/challenged mouse group (P<0.05, t test); and consequently, a lower number of eggs and granulomas (with reduced sizes), overall decreasing pathology. Immunized mice produced high levels of sera anti-AWBE IgG recognizing antigens of ∼190-, 130-, 98-, 47-, 28-23, 14-, and 9-kDa. The ∼130-kDa band (the AP dimer) exhibited in situ SmAP activity after addition of AP substrate and the activity was not apparently inhibited by host antibodies. A preliminary proteomic analysis of the 25-, 27-, and 28-kDa bands in the immunodominant 28–23 kDa region suggested that they are composed of actin. Conclusions Immunization with AWBE induced the production of specific antibodies to various adult worm membrane molecules (including AP) and a partial (43%) protection against a

Perceptions about interventions to control schistosomiasis among the Lake Victoria island communities of Koome, Uganda.

PubMed

Sanya, Richard E; Tumwesige, Edward; Elliott, Alison M; Seeley, Janet

2017-10-01

Praziquantel-based mass treatment is the main approach to controlling schistosomiasis mansoni in endemic areas. Interventions such as provision and use of safe water, minimising contact with infested water, disposal of stool in latrines and snail control provide key avenues to break the transmission cycle and can sustain the benefits of mass treatment in the long term. Efforts are also being made to develop a schistosomiasis vaccine which, if effective, might reduce the incidence of re-infection after treatment. However, any interventions deployed need to be acceptable to, and sustainable by, the target communities. In this qualitative study, we investigated the perceptions of six Lake Victoria island communities of Koome, Uganda, about interventions to control Schistosoma mansoni infection and their willingness to participate in Schistosoma vaccine trials. Thirty-two in-depth interviews, 12 key informant interviews and 10 focus group discussions were conducted. Data were analysed using a thematic content approach. Intestinal schistosomiasis was not regarded as a serious health problem because a mass treatment programme is in place. However, the communities lack safe water sources and latrines. Mass treatment with praziquantel, safe water supplies and use of toilets were deemed the most acceptable interventions by the participants. The communities are willing to participate in Schistosoma vaccine trials. Knowledge of a community's perception about interventions to control schistosomiasis can be valuable to policy makers and programme implementers intending to set up interventions co-managed by the community members. In this study, the views of the Lake Victoria island communities of Koome are presented. This study also provides data to guide further work on alternative interventions such as Schistosoma vaccine trials in these communities.

Praziquantel Treatment in Trematode and Cestode Infections: An Update

PubMed Central

2013-01-01

Status and emerging issues in the use of praziquantel for treatment of human trematode and cestode infections are briefly reviewed. Since praziquantel was first introduced as a broadspectrum anthelmintic in 1975, innumerable articles describing its successful use in the treatment of the majority of human-infecting trematodes and cestodes have been published. The target trematode and cestode diseases include schistosomiasis, clonorchiasis and opisthorchiasis, paragonimiasis, heterophyidiasis, echinostomiasis, fasciolopsiasis, neodiplostomiasis, gymnophalloidiasis, taeniases, diphyllobothriasis, hymenolepiasis, and cysticercosis. However, Fasciola hepatica and Fasciola gigantica infections are refractory to praziquantel, for which triclabendazole, an alternative drug, is necessary. In addition, larval cestode infections, particularly hydatid disease and sparganosis, are not successfully treated by praziquantel. The precise mechanism of action of praziquantel is still poorly understood. There are also emerging problems with praziquantel treatment, which include the appearance of drug resistance in the treatment of Schistosoma mansoni and possibly Schistosoma japonicum, along with allergic or hypersensitivity reactions against praziquantel treatment. To cope with and overcome these problems, combined use of drugs, i.e., praziquantel and other newly introduced compounds such as triclabendazole, artemisinins, and tribendimidine, is being tried. PMID:24265948

Quantitative assessment of the impact of partially protective anti-schistosomiasis vaccines

PubMed Central

Ndeffo Mbah, Martial; Galvani, Alison

2017-01-01

Background Mass drug administration (MDA) of praziquantel has been the intervention of choice against schistosomiasis but with limited success in interrupting the transmission. The development of anti-Schistosoma vaccines is underway. Our objective is to quantify the population-level impact of anti-Schistosoma vaccines when administered alone and in combination with mass drug administration (MDA) and determine factors in vaccine design and public health implementation that optimize vaccination role in schistosomiasis control and elimination. Methods and findings We developed a deterministic compartmental model simulation of schistosomiasis transmission in a high-risk Kenyan community, including stratification by age, parasite burden, and vaccination status. The modeled schistosomiasis vaccines differed in terms of vaccine duration of protection (durability) and three biological efficacies. These are vaccine susceptibility effect (SE) of reducing person’s susceptibility to Schistosoma acquisition, vaccine mortality effect (ME) of reducing established worm burden and vaccine fecundity effect (FE) of reducing egg release by mature worms. We quantified the population-level impact of vaccination over two decades under diverse vaccination schemes (childhood vs. mass campaigns), with different age-targeting scenarios, different risk settings, and with combined intervention with MDA. We also assessed the sensitivity of our predictions to uncertainties in model parameters. Over two decades, our base case vaccine with 80% SE, FE, and ME efficacies, 10 years’ durability, provided by mass vaccination every 10 years, reduced host prevalence, mean intensity, incidence, and patent snail prevalence to 31%, 20 eggs/10-ml sample/person, 0.87 worm/person-year, and 0.74%, from endemic-state values of 71%, 152, 3.3, and 0.98%, respectively. Lower impact was found when coverage did not encompass all potential contaminators, and childhood-only vaccination schemes showed delayed and

Quantitative assessment of the impact of partially protective anti-schistosomiasis vaccines.

PubMed

Alsallaq, Ramzi A; Gurarie, David; Ndeffo Mbah, Martial; Galvani, Alison; King, Charles

2017-04-01

Mass drug administration (MDA) of praziquantel has been the intervention of choice against schistosomiasis but with limited success in interrupting the transmission. The development of anti-Schistosoma vaccines is underway. Our objective is to quantify the population-level impact of anti-Schistosoma vaccines when administered alone and in combination with mass drug administration (MDA) and determine factors in vaccine design and public health implementation that optimize vaccination role in schistosomiasis control and elimination. We developed a deterministic compartmental model simulation of schistosomiasis transmission in a high-risk Kenyan community, including stratification by age, parasite burden, and vaccination status. The modeled schistosomiasis vaccines differed in terms of vaccine duration of protection (durability) and three biological efficacies. These are vaccine susceptibility effect (SE) of reducing person's susceptibility to Schistosoma acquisition, vaccine mortality effect (ME) of reducing established worm burden and vaccine fecundity effect (FE) of reducing egg release by mature worms. We quantified the population-level impact of vaccination over two decades under diverse vaccination schemes (childhood vs. mass campaigns), with different age-targeting scenarios, different risk settings, and with combined intervention with MDA. We also assessed the sensitivity of our predictions to uncertainties in model parameters. Over two decades, our base case vaccine with 80% SE, FE, and ME efficacies, 10 years' durability, provided by mass vaccination every 10 years, reduced host prevalence, mean intensity, incidence, and patent snail prevalence to 31%, 20 eggs/10-ml sample/person, 0.87 worm/person-year, and 0.74%, from endemic-state values of 71%, 152, 3.3, and 0.98%, respectively. Lower impact was found when coverage did not encompass all potential contaminators, and childhood-only vaccination schemes showed delayed and lower impact. In lower prevalence

Population genetics of the Schistosoma snail host Bulinus truncatus in Egypt.

PubMed

Zein-Eddine, Rima; Djuikwo-Teukeng, Félicité F; Dar, Yasser; Dreyfuss, Gilles; Van den Broeck, Frederik

2017-08-01

The tropical freshwater snail Bulinus truncatus serves as an important intermediate host of several human and cattle Schistosoma species in many African regions. Despite some ecological and malacological studies, there is no information on the genetic diversity of B. truncatus in Egypt. Here, we sampled 70-100 snails in ten localities in Upper Egypt and the Nile Delta. Per locality, we sequenced 10 snails at a partial fragment of the cytochrome c oxidase subunit 1 gene (cox1) and we genotyped 25-30 snails at six microsatellite markers. A total of nine mitochondrial haplotypes were detected, of which five were unique to the Nile Delta and three were unique to Upper Egypt, indicating that snail populations may have evolved independently in both regions. Bayesian clustering and hierarchical F-statistics using microsatellite markers further revealed strong population genetic structure at the level of locality. Observed heterozygosity was much lower compared to what is expected under random mating, which could be explained by high selfing rates, population size reductions and to a lesser extent by the Wahlund effect. Despite these observations, we found signatures of gene flow and cross-fertilization, even between snails from the Nile Delta and Upper Egypt, indicating that B. truncatus can travel across large distances in Egypt. These observations could have serious consequences for disease epidemiology, as it means that infected snails from one region could rapidly and unexpectedly spark a new epidemic in another distant region. This could be one of the factors explaining the rebound of human Schistosoma infections in the Nile Delta, despite decades of sustained schistosomiasis control. Copyright © 2017 Elsevier B.V. All rights reserved.

Brain magnetic resonance imaging findings in young patients with hepatosplenic schistosomiasis mansoni without overt symptoms.

PubMed

Manzella, Adonis; Borba-Filho, Paulo; Brandt, Carlos T; Oliveira, Keyla

2012-06-01

The purpose of this study was to describe the brain magnetic resonance imaging (MRI) findings in young patients with hepatosplenic schistosomiasis mansoni without overt neurologic manifestations. This study included 34 young persons (age range = 9-25 years) with hepatosplenic schistosomiasis mansoni who had been previously treated. Patients were scanned on a 1.5-T system that included multiplanar pre-contrast and post-contrast sequences, and reports were completed by two radiologists after a consensus review. Twenty (58.8%) patients had MRI signal changes that were believed to be related to schistosomiasis mansoni. Twelve of the 20 patients had small focal hyperintensities on T2WI in the cerebral white matter, and eight patients had symmetric hyperintense basal ganglia on T1WI. There was a high frequency of brain MRI signal abnormalities in this series. Although not specific, these findings may be related to schistosomiasis.

Biotechnological advances in the diagnosis, species differentiation and phylogenetic analysis of Schistosoma spp.

PubMed

Zhao, Guang-Hui; Li, Juan; Blair, David; Li, Xiao-Yan; Elsheikha, Hany M; Lin, Rui-Qing; Zou, Feng-Cai; Zhu, Xing-Quan

2012-01-01

Schistosomiasis is a serious parasitic disease caused by blood-dwelling flukes of the genus Schistosoma. Throughout the world, schistosomiasis is associated with high rates of morbidity and mortality, with close to 800 million people at risk of infection. Precise methods for identification of Schistosoma species and diagnosis of schistosomiasis are crucial for an enhanced understanding of parasite epidemiology that informs effective antiparasitic treatment and preventive measures. Traditional approaches for the diagnosis of schistosomiasis include etiological, immunological and imaging techniques. Diagnosis of schistosomiasis has been revolutionized by the advent of new molecular technologies to amplify parasite nucleic acids. Among these, polymerase chain reaction-based methods have been useful in the analysis of genetic variation among Schistosoma spp. Mass spectrometry is now extending the range of biological molecules that can be detected. In this review, we summarize traditional, non-DNA-based diagnostic methods and then describe and discuss the current and developing molecular techniques for the diagnosis, species differentiation and phylogenetic analysis of Schistosoma spp. These exciting techniques provide foundations for further development of more effective and precise approaches to differentiate schistosomes and diagnose schistosomiasis in the clinic, and also have important implication for exploring novel measures to control schistosomiasis in the near future. Copyright © 2012 Elsevier Inc. All rights reserved.

Refined stratified-worm-burden models that incorporate specific biological features of human and snail hosts provide better estimates of Schistosoma diagnosis, transmission, and control.

PubMed

Gurarie, David; King, Charles H; Yoon, Nara; Li, Emily

2016-08-04

Schistosoma parasites sustain a complex transmission process that cycles between a definitive human host, two free-swimming larval stages, and an intermediate snail host. Multiple factors modify their transmission and affect their control, including heterogeneity in host populations and environment, the aggregated distribution of human worm burdens, and features of parasite reproduction and host snail biology. Because these factors serve to enhance local transmission, their inclusion is important in attempting accurate quantitative prediction of the outcomes of schistosomiasis control programs. However, their inclusion raises many mathematical and computational challenges. To address these, we have recently developed a tractable stratified worm burden (SWB) model that occupies an intermediate place between simpler deterministic mean worm burden models and the very computationally-intensive, autonomous agent models. To refine the accuracy of model predictions, we modified an earlier version of the SWB by incorporating factors representing essential in-host biology (parasite mating, aggregation, density-dependent fecundity, and random egg-release) into demographically structured host communities. We also revised the snail component of the transmission model to reflect a saturable form of human-to-snail transmission. The new model allowed us to realistically simulate overdispersed egg-test results observed in individual-level field data. We further developed a Bayesian-type calibration methodology that accounted for model and data uncertainties. The new model methodology was applied to multi-year, individual-level field data on S. haematobium infections in coastal Kenya. We successfully derived age-specific estimates of worm burden distributions and worm fecundity and crowding functions for children and adults. Estimates from the new SWB model were compared with those from the older, simpler SWB with some substantial differences noted. We validated our new SWB

Akt-mediated anti-apoptotic effects of substance P in Anti-Fas-induced apoptosis of human tenocytes

PubMed Central

Backman, Ludvig J; Danielson, Patrik

2013-01-01

Substance P (SP) and its receptor, the neurokinin-1 receptor (NK-1 R), are expressed by human tenocytes, and they are both up-regulated in cases of tendinosis, a condition associated with excessive apoptosis. It is known that SP can phosphorylate/activate the protein kinase Akt, which has anti-apoptotic effects. This mechanism has not been studied for tenocytes. The aims of this study were to investigate if Anti-Fas treatment is a good apoptosis model for human tenocytes in vitro, if SP protects from Anti-Fas-induced apoptosis, and by which mechanisms SP mediates an anti-apoptotic response. Anti-Fas treatment resulted in a time- and dose-dependent release of lactate dehydrogenase (LDH), i.e. induction of cell death, and SP dose-dependently reduced the Anti-Fas-induced cell death through a NK-1 R specific pathway. The same trend was seen for the TUNEL assay, i.e. SP reduced Anti-Fas-induced apoptosis via NK-1 R. In addition, it was shown that SP reduces Anti-Fas-induced decrease in cell viability as shown with crystal violet assay. Protein analysis using Western blot confirmed that Anti-Fas induces cleavage/activation of caspase-3 and cleavage of PARP; both of which were inhibited by SP via NK-1 R. Finally, SP treatment resulted in phosphorylation/activation of Akt as shown with Western blot, and it was confirmed that the anti-apoptotic effect of SP was, at least partly, induced through the Akt-dependent pathway. In conclusion, we show that SP reduces Anti-Fas-induced apoptosis in human tenocytes and that this anti-apoptotic effect of SP is mediated through NK-1 R and Akt-specific pathways. PMID:23577779

Perceptions about interventions to control schistosomiasis among the Lake Victoria island communities of Koome, Uganda

PubMed Central

Tumwesige, Edward; Elliott, Alison M.; Seeley, Janet

2017-01-01

Background Praziquantel-based mass treatment is the main approach to controlling schistosomiasis mansoni in endemic areas. Interventions such as provision and use of safe water, minimising contact with infested water, disposal of stool in latrines and snail control provide key avenues to break the transmission cycle and can sustain the benefits of mass treatment in the long term. Efforts are also being made to develop a schistosomiasis vaccine which, if effective, might reduce the incidence of re-infection after treatment. However, any interventions deployed need to be acceptable to, and sustainable by, the target communities. Methods In this qualitative study, we investigated the perceptions of six Lake Victoria island communities of Koome, Uganda, about interventions to control Schistosoma mansoni infection and their willingness to participate in Schistosoma vaccine trials. Thirty-two in-depth interviews, 12 key informant interviews and 10 focus group discussions were conducted. Data were analysed using a thematic content approach. Findings Intestinal schistosomiasis was not regarded as a serious health problem because a mass treatment programme is in place. However, the communities lack safe water sources and latrines. Mass treatment with praziquantel, safe water supplies and use of toilets were deemed the most acceptable interventions by the participants. The communities are willing to participate in Schistosoma vaccine trials. Conclusion/Significance Knowledge of a community’s perception about interventions to control schistosomiasis can be valuable to policy makers and programme implementers intending to set up interventions co-managed by the community members. In this study, the views of the Lake Victoria island communities of Koome are presented. This study also provides data to guide further work on alternative interventions such as Schistosoma vaccine trials in these communities. PMID:28968470

Akt-mediated anti-apoptotic effects of substance P in Anti-Fas-induced apoptosis of human tenocytes.

PubMed

Backman, Ludvig J; Danielson, Patrik

2013-06-01

Substance P (SP) and its receptor, the neurokinin-1 receptor (NK-1 R), are expressed by human tenocytes, and they are both up-regulated in cases of tendinosis, a condition associated with excessive apoptosis. It is known that SP can phosphorylate/activate the protein kinase Akt, which has anti-apoptotic effects. This mechanism has not been studied for tenocytes. The aims of this study were to investigate if Anti-Fas treatment is a good apoptosis model for human tenocytes in vitro, if SP protects from Anti-Fas-induced apoptosis, and by which mechanisms SP mediates an anti-apoptotic response. Anti-Fas treatment resulted in a time- and dose-dependent release of lactate dehydrogenase (LDH), i.e. induction of cell death, and SP dose-dependently reduced the Anti-Fas-induced cell death through a NK-1 R specific pathway. The same trend was seen for the TUNEL assay, i.e. SP reduced Anti-Fas-induced apoptosis via NK-1 R. In addition, it was shown that SP reduces Anti-Fas-induced decrease in cell viability as shown with crystal violet assay. Protein analysis using Western blot confirmed that Anti-Fas induces cleavage/activation of caspase-3 and cleavage of PARP; both of which were inhibited by SP via NK-1 R. Finally, SP treatment resulted in phosphorylation/activation of Akt as shown with Western blot, and it was confirmed that the anti-apoptotic effect of SP was, at least partly, induced through the Akt-dependent pathway. In conclusion, we show that SP reduces Anti-Fas-induced apoptosis in human tenocytes and that this anti-apoptotic effect of SP is mediated through NK-1 R and Akt-specific pathways. © 2013 The Authors Journal of Cellular and Molecular Medicine Published by Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

The origin and dispersion of human parasitic diseases in the old world (Africa, Europe and Madagascar).

PubMed

Nozais, Jean-Pierre

2003-01-01

The ancestors of present-day man (Homo sapiens sapiens) appeared in East Africa some three and a half million years ago (Australopithecs), and then migrated to Europe, Asia, and later to the Americas, thus beginning the differentiation process. The passage from nomadic to sedentary life took place in the Middle East in around 8000 BC. Wars, spontaneous migrations and forced migrations (slave trade) led to enormous mixtures of populations in Europe and Africa and favoured the spread of numerous parasitic diseases with specific strains according to geographic area. The three human plasmodia (Plasmodium falciparum, P. vivax, and P. malariae) were imported from Africa into the Mediterranean region with the first human migrations, but it was the Neolithic revolution (sedentarisation, irrigation, population increase) which brought about actual foci for malaria. The reservoir for Leishmania infantum and L. donovani--the dog--has been domesticated for thousands of years. Wild rodents as reservoirs of L. major have also long been in contact with man and probably were imported from tropical Africa across the Sahara. L. tropica, by contrast, followed the migrations of man, its only reservoir. L. infantum and L. donovani spread with man and his dogs from West Africa. Likewise, for thousands of years, the dog has played an important role in the spread and the endemic character of hydatidosis through sheep (in Europe and North Africa) and dromadary (in the Sahara and North Africa). Schistosoma haematobium and S. mansoni have existed since prehistoric times in populations living in or passing through the Sahara. These populations then transported them to countries of Northern Africa where the specific, intermediary hosts were already present. Madagascar was inhabited by populations of Indonesian origin who imported lymphatic filariosis across the Indian Ocean (possibly of African origin since the Indonesian sailors had spent time on the African coast before reaching Madagascar

Arginase activity in peripheral blood of patients with intestinal schistosomiasis, Wonji, Central Ethiopia.

PubMed

Getaneh, A; Tamrat, A; Tadesse, K

2015-07-01

Morbidity and mortality caused by schistosomiasis usually results from immunopathology. But the underlying mechanisms are not yet clearly understood. Th2-type immune response is thought to be dominant during chronic schistosomiasis, and upregulation of arginase-I is one component of this milieu. A cohort study was conducted to assess arginase activity in peripheral blood of humans with intestinal schistosomiasis in Wonji-Shoa Sugar Estate, Central Ethiopia. Laboratory-confirmed 30 Schistosoma mansoni-infected patients and 18 apparently healthy controls were recruited. Faecal egg count was carried out by Kato-Katz technique. Plasma and peripheral blood mononuclear cells (PBMCs) were isolated from whole blood. Activity of arginase in plasma and PBMC lysates was measured, and results were compared with that of controls. Twenty-one of 30 patients had light infection, whereas moderate and heavy intensity infections were observed in eight and only one patient(s), respectively. A significant increase in both PBMC (patients: 59.96 + 82.99, controls: 25.44 + 24.6 mU/mg protein, P < 0.0001) and plasma (patients: 1.61 + 2.19, controls: 0.31 + 0.73 mU/mL plasma, P < 0.0001) arginase activity was observed during human S. mansoni infection. Arginase activity increases in peripheral blood of patients with intestinal schistosomiasis. © 2015 John Wiley & Sons Ltd.

Studies on heterologous immunity in schistosomiasis*

PubMed Central

Amin, M. A.; Nelson, G. S.; Saoud, M. F. A.

1968-01-01

Previous studies on heterologous immunity in mice have indicated that Schistosoma bovis and S. mattheei could be used to limit the severity of infection resulting from subsequent challenge by S. mansoni. These observations have now been extended to study the immunizing effect in rhesus monkeys of both S. mattheei and S. bovis. The bovine schistosomes were shown to be relatively non-pathogenic in rhesus monkeys. Immunization with 1000-2000 cercariae resulted in a marked reduction in the pathogenic effect of subsequent challenge with S. mansoni. This effect was demonstrated by a decrease in the worm load and tissue egg densities in 10 immunized monkeys as compared with 5 control animals. There was no correlation between fluorescent antibody titres and the intensity of infection or the degree of acquired immunity. There was a cross-reaction between S. mansoni and the bovine schistosomes. It is suggested that natural heterologous immunity (zooprophylaxis) may be of considerable epidemiological importance in determining the severity of schistosomiasis in man. PMID:4970323

Existence of host-related DNA sequences in the schistosome genome.

PubMed

Iwamura, Y; Irie, Y; Kominami, R; Nara, T; Yasuraoka, K

1991-06-01

DNA sequences homologous to the mouse intracisternal A particle and endogenous type C retrovirus were detected in the DNAs of Schistosoma japonicum adults and S. mansoni eggs. Furthermore, other kinds of repetitive sequences in the host genome such as mouse type 1 Alu sequence (B1), mouse type 2 Alu sequence (B2) and mo-2 sequence, a mouse mini-satellite, were also detected in the DNAs from adults and eggs of S. japonicum and eggs of S. mansoni. Almost all of the sequences described above were absent in the DNAs of S. mansoni adults. The DNA fingerprints of schistosomes, using the mo-2 sequence, were indistinguishable from each other and resembled those of their murine hosts. Moreover, the mo-2 sequence was hypermethylated in the DNAs of schistosomes and its amount was variable in them. These facts indicate that host-related sequences are actually present in schistosomes and that the mo-2 repetitive sequence exists probably in extra-chromosome.

Anti-leukemic activity and tolerability of anti-human CD47 monoclonal antibodies

PubMed Central

Pietsch, E C; Dong, J; Cardoso, R; Zhang, X; Chin, D; Hawkins, R; Dinh, T; Zhou, M; Strake, B; Feng, P-H; Rocca, M; Santos, C Dos; Shan, X; Danet-Desnoyers, G; Shi, F; Kaiser, E; Millar, H J; Fenton, S; Swanson, R; Nemeth, J A; Attar, R M

2017-01-01

CD47, a broadly expressed cell surface protein, inhibits cell phagocytosis via interaction with phagocyte-expressed SIRPα. A variety of hematological malignancies demonstrate elevated CD47 expression, suggesting that CD47 may mediate immune escape. We discovered three unique CD47-SIRPα blocking anti-CD47 monoclonal antibodies (mAbs) with low nano-molar affinity to human and cynomolgus monkey CD47, and no hemagglutination and platelet aggregation activity. To characterize the anti-cancer activity elicited by blocking CD47, the mAbs were cloned into effector function silent and competent Fc backbones. Effector function competent mAbs demonstrated potent activity in vitro and in vivo, while effector function silent mAbs demonstrated minimal activity, indicating that blocking CD47 only leads to a therapeutic effect in the presence of Fc effector function. A non-human primate study revealed that the effector function competent mAb IgG1 C47B222-(CHO) decreased red blood cells (RBC), hematocrit and hemoglobin by >40% at 1 mg/kg, whereas the effector function silent mAb IgG2σ C47B222-(CHO) had minimal impact on RBC indices at 1 and 10 mg/kg. Taken together, our findings suggest that targeting CD47 is an attractive therapeutic anti-cancer approach. However, the anti-cancer activity observed with anti-CD47 mAbs is Fc effector dependent as are the side effects observed on RBC indices. PMID:28234345

Anti-tumor immunity induced by an anti-idiotype antibody mimicking human Her-2/neu.

PubMed

Mohanty, Kartik; Saha, Asim; Pal, Smarajit; Mallick, Palash; Chatterjee, Sunil K; Foon, Kenneth A; Bhattacharya-Chatterjee, Malaya

2007-07-01

Our goal is to apply an anti-idiotype (Id) antibody based vaccine approach for the treatment of Her-2/neu-positive human cancer. Amplification and/or over-expression of Her-2/neu occur in multiple human malignancies and are associated with poor prognosis. Her-2/neu proto-oncogene is a suitable target for cancer immunotherapy. We have developed and characterized a murine monoclonal anti-Id antibody, 6D12 that mimics a specific epitope of Her-2/neu and can be used as a surrogate antigen for Her-2/neu. In this study, the efficacy of 6D12 as a tumor vaccine was evaluated in a murine tumor model. Immunization of immunocompetent C57BL/6 mice with 6D12 conjugated to keyhole limpet hemocyanin and mixed with Freund's adjuvant or 6D12 combined with the adjuvant QS21 induced anti-6D12 as well as anti-Her-2/neu immunity. Her-2/neu-positive human breast carcinoma cells, SK-BR-3 reacted with immunized mice sera as determined by ELISA and flow cytometry. Flow cytometry analysis also demonstrated strong reactivity of immunized mice sera with human Her-2/neu transfected EL4 cells (EL4-Her-2), but no reactivity with nontransfected parental EL4 cells. Antibody dependent cellular cytotoxicity against EL4-Her-2 cells was also observed in presence of immune sera. Mice immunized with 6D12 were protected against a challenge with lethal doses of EL4-Her-2 cells, whereas no protection was observed against parental EL4 cells or when mice were immunized with an unrelated anti-Id antibody and challenged with EL4-Her-2 cells. These data suggest that anti-Id 6D12 vaccine can induce protective Her-2/neu specific antitumor immunity and may serve as a potential network antigen for the treatment of patients with Her-2/neu-positive tumors.

Prevalence of schistosome antibodies with hepatosplenic signs and symptoms among patients from Kaoma, Western Province, Zambia.

PubMed

Payne, Lara; Turner-Moss, Eleanor; Mutengo, Mable; Asombang, Akwi W; Kelly, Paul

2013-08-30

Schistosomiasis is a major cause of morbidity and mortality, with over 200 million people infected worldwide. Eighty-five percent of cases are in Africa. The hepatosplenic form develops over time by an immune reaction to trapped Schistosoma mansoni eggs in the portal system leading to liver fibrosis, portal hypertension and oesophageal varices. Most patients presenting to the University Teaching Hospital in Lusaka with oesophageal varices, come from Western province, but no formal studies have been carried out in this area assessing the burden of hepatosplenic pathology. We aimed to define the extent of the problem in Kaoma district, western Zambia, and to correlate signs and symptoms with serology. A symptom questionnaire, demographic survey and physical examination was conducted amongst patients presenting to Kaoma district outpatient clinics. To assess the prevalence of Schistosoma mansoni infections, blood was collected and screened for the presence of Schistosoma antibodies using Enzyme linked immunosorbent assay (ELISA). Of the 110 patients screened, 97 (88%) were ELISA positive. Forty-six percent (51/110) reported haematochezia and 7% experienced haematemesis (8/110). On physical examination 27% (30/110) hepatomegaly and 17% (30/110) splenomegaly was observed amongst participants but there were few correlations between serology and signs/symptoms. On questioning 68% (75/110) of participants knew nothing about schistosomiasis transmission. Our serological and clinical data indicate a very heavy burden of schistosomiasis-related portal hypertension. Our evidence highlights a need for mass treatment in Kaoma to address and prevent extensive pathology of hepatosplenic schistosomiasis. Safe water and health education throughout Western Province are clearly also important.

Distribution of intermediate host snails of schistosomiasis and fascioliasis in relation to environmental factors during the dry season in the Tchologo region, Côte d'Ivoire

NASA Astrophysics Data System (ADS)

Krauth, Stefanie J.; Wandel, Nathalie; Traoré, Seïdinan I.; Vounatsou, Penelope; Hattendorf, Jan; Achi, Louise Y.; McNeill, Kristopher; N'Goran, Eliézer K.; Utzinger, Jürg

2017-10-01

Snail-borne trematodiases, such as fascioliasis and schistosomiasis, belong to the neglected tropical diseases; yet, millions of people and livestock are affected. The spatial and temporal distribution of intermediate host snails plays an important role in the epidemiology and control of trematodiases. Snail distribution is influenced by numerous environmental and anthropomorphic factors. The aim of this study was to assess the distribution and constitution of the snail fauna during the dry season in constructed and natural water bodies in the Tchologo region, northern Côte d'Ivoire, and to relate these findings to environmental factors and human infections. Snails were collected using standard procedures and environmental parameters were assessed from a total of 50 water bodies in and around 30 randomly selected villages. A canonical correspondence analysis was performed to establish the relationship between snail occurrence and environmental factors. Furthermore, a total of 743 people from the same 30 villages and nearby settlements were invited for stool and urine examination for the diagnosis of Fasciola spp., Schistosoma haematobium and Schistosoma mansoni. Snails of medical importance of the genera Biomphalaria, Bulinus, Lymnaea and Physa were found. Differences in snail occurrence from sites sampled in December 2014 and snails sampled in February 2015, as well as between the northern and southern part of the study area, were revealed. Various environmental factors, such as temperature and human activities, were related to the occurrence of intermediate host snail species in the region. Only 2.3% of human participants tested positive for schistosomiasis, while no Fasciola eggs were found in stool samples. We conclude that intermediate host snails of Fasciola and Schistosoma co-occur in water bodies in the Tchologo region and that the distribution of these snails correlates not only with environmental factors, but also with the presence of humans and animals

Chimpanzees Immunized with Recombinant Soluble CD4 Develop Anti-Self CD4 Antibody Responses with Anti-Human Immunodeficiency Virus Activity

NASA Astrophysics Data System (ADS)

Watanabe, Mamoru; Boyson, Jonathan E.; Lord, Carol I.; Letvin, Norman L.

1992-06-01

In view of the efficiency with which human immunodeficiency virus replication can be blocked in vitro with anti-CD4 antibodies, the elicitation of an anti-CD4 antibody response through active immunization might represent a useful therapeutic strategy for AIDS. Here we demonstrate that immunization of chimpanzees with recombinant soluble human CD4 elicited an anti-CD4 antibody response. The elicited antibody bound self CD4 on digitonin-treated but not freshly isolated lymphocytes. Nevertheless, this antibody blocked human immunodeficiency virus replication in chimpanzee and human lymphocytes. These observations suggest that immunization with recombinant soluble CD4 from human immunodeficiency virus-infected humans may be feasible and therapeutically beneficial.

Geographic strain differentiation of Schistosoma japonicum in the Philippines using microsatellite markers

PubMed Central

Moendeg, Kharleezelle J.; Angeles, Jose Ma M.; Nakao, Ryo; Leonardo, Lydia R.; Fontanilla, Ian Kendrich C.; Goto, Yasuyuki; Kirinoki, Masashi; Villacorte, Elena A.; Rivera, Pilarita T.; Inoue, Noboru; Chigusa, Yuichi

2017-01-01

Background Microsatellites have been found to be useful in determining genetic diversities of various medically-important parasites which can be used as basis for an effective disease management and control program. In Asia and Africa, the identification of different geographical strains of Schistosoma japonicum, S. haematobium and S. mansoni as determined through microsatellites could pave the way for a better understanding of the transmission epidemiology of the parasite. Thus, the present study aims to apply microsatellite markers in analyzing the populations of S. japonicum from different endemic areas in the Philippines for possible strain differentiation. Methodology/ Principal findings Experimental mice were infected using the cercariae of S. japonicum collected from infected Oncomelania hupensis quadrasi snails in seven endemic municipalities. Adult worms were harvested from infected mice after 45 days of infection and their DNA analyzed against ten previously characterized microsatellite loci. High genetic diversity was observed in areas with high endemicity. The degree of genetic differentiation of the parasite population between endemic areas varies. Geographical separation was considered as one of the factors accounting for the observed difference between populations. Two subgroups have been observed in one of the study sites, suggesting that co-infection with several genotypes of the parasite might be present in the population. Clustering analysis showed no particular spatial structuring between parasite populations from different endemic areas. This result could possibly suggest varying degrees of effects of the ongoing control programs and the existing gene flow in the populations, which might be attributed to migration and active movement of infected hosts from one endemic area to another. Conclusions/ Significance Based on the results of the study, it is reasonable to conclude that genetic diversity could be one possible criterion to assess the

Rigidity and resistance of larval- and adult schistosomes-medium interface

DOE Office of Scientific and Technical Information (OSTI.GOV)

Migliardo, Federica, E-mail: fmigliardo@unime.it; Tallima, Hatem; El Ridi, Rashika

Graphical abstract: - Highlights: • Schistosoma larvae and worms are studied by neutron scattering. • Measurements on larvae were repeated after one day and by increasing temperature. • The flexibility properties of larvae and adult parasites are compared. • The parasite rigidity is related to their resistance to the hostile environment. • Insight into the parasite defense mechanisms to the immune system attack is achieved. - Abstract: Schistosomiasis is second only to malaria in prevalence and severity, and is still a major health problem in many tropical countries worldwide with about 200–300 million cases and with more than 800 millionmore » people at risk of infection. Based on these data, the World Health Organization recommends fostering research efforts for understanding at any level the mechanisms of the infection and then decreasing the social and economical impact of schistosomiasis. A key role is played by the parasite apical lipid membrane, which is entirely impervious to the surrounding elements of the immune system. We have previously demonstrated that the interaction between schistosomes and surrounding medium is governed by a parasite surface membrane sphingomyelin-based hydrogen barrier. In the present article, the elastic contribution to the total motion as a function of the exchanged wave-vector Q and the mean square displacement values for Schistosoma mansoni larvae and worms and Schistosomahaematobium worms have been evaluated by quasi elastic neutron scattering (QENS). The results point out that S. mansoni larvae show a smaller mean square displacement in comparison to S. mansoni and S. haematobium worms. These values increased by repeating the measurements after one day. These differences, which are analogous to those observed for the diffusion coefficient we previously evaluated, are interpreted in terms of rigidity of the parasite-medium interaction. S. mansoni larvae are the most rigid systems, while S. haematobium worms are

Closing the praziquantel treatment gap: new steps in epidemiological monitoring and control of schistosomiasis in African infants and preschool-aged children

PubMed Central

STOTHARD, J. RUSSELL; SOUSA-FIGUEIREDO, JOSÉ C.; BETSON, MARTHA; GREEN, HELEN K.; SETO, EDMUND Y. W.; GARBA, AMADOU; SACKO, MOUSSA; MUTAPI, FRANCISCA; VAZ NERY, SUSANA; AMIN, MUTAMAD A.; MUTUMBA-NAKALEMBE, MARGARET; NAVARATNAM, ANNALAN; FENWICK, ALAN; KABATEREINE, NARCIS B.; GABRIELLI, ALBIS F.; MONTRESOR, ANTONIO

2011-01-01

SUMMARY Where very young children come into contact with water containing schistosome cercariae, infections occur and schistosomiasis can be found. In high transmission environments, where mothers daily bathe their children with environmentally drawn water, many infants and preschool-aged children have schistosomiasis. This ‘new’ burden, inclusive of co-infections with Schistosoma haematobium and Schistosoma mansoni, is being formally explored as infected children are not presently targeted to receive praziquantel (PZQ) within current preventive chemotherapy campaigns. Thus an important PZQ treatment gap exists whereby infected children might wait up to 4–5 years before receiving first treatment in school. International treatment guidelines, set within national treatment platforms, are presently being modified to provide earlier access to medication(s). Although detailed pharmacokinetic studies are needed, to facilitate pragmatic dosing in the field, an extended ‘dose pole’ has been devised and epidemiological monitoring has shown that administration of PZQ (40 mg/kg), in either crushed tablet or liquid suspension, is both safe and effective in this younger age-class; drug efficacy, however, against S. mansoni appears to diminish after repeated rounds of treatment. Thus use of PZQ should be combined with appropriate health education/water hygiene improvements for both child and mother to bring forth a more enduring solution. PMID:21861945

Anti-oxidative and anti-genotoxic effects of methanolic extract of Mentha pulegium on human lymphocyte culture.

PubMed

Alpsoy, Lokman; Sahin, Hilal; Karaman, Seyda

2011-08-01

In the present work, methanolic extract of Mentha pulegium from Erzurum, Turkey, was used in order to report the results of anti-oxidant capacity, anti-oxidant activity and anti-genotoxic effects. The total antioxidant capacity and total phenolic content were measured by using CUPRAC, ABTS and Folin-Ciocalteu colorimetric methods. The total phenolic content was higher than the total antioxidant capacity (for the results of both the CUPRAC and ABTS methods) of methanolic extract of M pulegium (ME). Also, we evaluated the anti-oxidant enzyme activity such as superoxide dismutase (SOD) and glutation peroxidase, total glutation (GSH) and malondialdehyde (MDA) in human lymphocyte culture. In CCl₄-treated group, the activity of SOD, glutathione peroxidase (GPx) and GSH decreased significantly and the level of MDA increased significantly. A significant increase in the activity of SOD, GPx and the level of GSH were seen when supplemented with ME to CCl₄-treated group. Furthermore, a significant decrease in the level of MDA was observed when compared with CCl₄ alone treated group. In addition, anti-genotoxic effect of ME was studied by using sister chromatid exchange (SCE) method. As a result, ME has shown anti-genotoxic effect depend on anti-oxidative effect on human lymphocyte culture.

Approaches to genotyping individual miracidia of Schistosoma japonicum

PubMed Central

Xiao, Ning; Remais, Justin V.; Brindley, Paul J.; Qiu, Dong-chuan; Carlton, Elizabeth J.; Li, Rong-zhi; Lei, Yang; Blair, David

2013-01-01

Molecular genetic tools are needed to address questions as to the source and dynamics of transmission of the human blood fluke Schistosoma japonicum in regions where human infections have re-emerged, and to characterize infrapopulations in individual hosts. The life-stage that interests us as a target for collecting genotypic data is the miracidium, a very small larval stage that consequently yields very little DNA for analysis. Here, we report the successful development of a multiplex format permitting genotyping of 17 microsatellite loci in four sequential multiplex reactions using a single miracidium held on a Whatman Classic FTA indicating card. This approach was successful after short storage periods, but after long storage (>4 years) considerable difficulty was encountered in multiplex genotyping, necessitating the use of whole genome amplification (WGA) methods. WGA applied to cards stored for long periods of time resulted in sufficient DNA for accurate and repeatable genotyping. Trials and tests of these methods, as well as application to some field-collected samples, are reported, along with discussion of the potential insights to be gained from such techniques. These include recognition of sibships among miracidia from a single host, and inference of the minimum number of worm pairs that might be present in a host. PMID:24013341

Approaches to genotyping individual miracidia of Schistosoma japonicum.

PubMed

Xiao, Ning; Remais, Justin V; Brindley, Paul J; Qiu, Dong-Chuan; Carlton, Elizabeth J; Li, Rong-Zhi; Lei, Yang; Blair, David

2013-12-01

Molecular genetic tools are needed to address questions as to the source and dynamics of transmission of the human blood fluke Schistosoma japonicum in regions where human infections have reemerged, and to characterize infrapopulations in individual hosts. The life stage that interests us as a target for collecting genotypic data is the miracidium, a very small larval stage that consequently yields very little DNA for analysis. Here, we report the successful development of a multiplex format permitting genotyping of 17 microsatellite loci in four sequential multiplex reactions using a single miracidium held on a Whatman Classic FTA indicating card. This approach was successful after short storage periods, but after long storage (>4 years), considerable difficulty was encountered in multiplex genotyping, necessitating the use of whole genome amplification (WGA) methods. WGA applied to cards stored for long periods of time resulted in sufficient DNA for accurate and repeatable genotyping. Trials and tests of these methods, as well as application to some field-collected samples, are reported, along with the discussion of the potential insights to be gained from such techniques. These include recognition of sibships among miracidia from a single host, and inference of the minimum number of worm pairs that might be present in a host.

Understanding the interaction between human serum albumin and anti-bacterial/ anti-cancer compounds.

PubMed

Rehman, Md Tabish; Khan, Asad U

2015-01-01

Human serum albumin (HSA) is the most important carrier of exogenous and endogenous molecules in human plasma. Understanding and characterizing the interaction of drugs with HSA has attracted enormous research interests from decades. The nature and magnitude of these bindings have direct consequence on drug delivery, pharmacokinetics, pharmacodynamics, therapeutic efficacy and drug designing. An overview of HSA and antibacterial/ anti-cancer ligands interaction is the need of the hour as these drugs together constitute more than half of the total drug consumption in the world. In this review, the information on the number of binding sites, binding strength, the nature of binding interactions and the location of binding sites of such drugs on the HSA are summarised. The effect of such drugs on the overall conformation, stability and function of HSA is also reviewed. This review will help to gain useful insights into the significance of the binding of anti-bacterial and anti-cancer drugs with plasma protein and the effect of binding on its overall distribution and pharmacological activities.

Immunogenicity of the irradiated Schistosoma mansoni schistosomula vaccine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Othman, M.I.

1986-01-01

This work was initiated to investigate the immunogenicity of the irradiated schistosomula vaccine with respect to its: ability to protect against challenge infection; ability to induce antibody responses in Western blot (WB) assay; and the antibodies' ability to kill the parasites; ultrastructural changes of the vaccine organism's tegument; antibody binding to their surface in immunofluorescence (IFA) and immunoelectron microscopic (IEM) assays and surface antigen recognition with different sera in WB. Irradiated schistosomula, freshly prepared or cultured up to 48 hours, were able to induce significant levels of protection (27%-67%). however, irradiated cercariae offered greater protection (52%-72%). Vaccination of mice withmore » irradiated schistosomula, led to higher antibody responses to adult freeze-thaw (AFT) and schistosomula membrane extract (SME) antigens with respect to to time and number of recognized antigens.« less

Inconsistent Protective Efficacy and Marked Polymorphism Limits the Value of Schistosoma japonicum Tetraspanin-2 as a Vaccine Target

PubMed Central

Zhang, Wenbao; Li, Jun; Duke, Mary; Jones, Malcolm K.; Kuang, Ling; Zhang, Jianfeng; Blair, David; Li, Yuesheng; McManus, Donald P.

2011-01-01

Background Schistosoma mansoni tetraspanin 2 (Sm-TSP-2) has been shown to be strongly recognized by IgG1 and IgG3 antibodies from individuals putatively resistant to schistosome infection, but not chronically infected people, and to induce high levels of protection against challenge infection in the murine model of schistosomiasis. Amplification by PCR of homologous sequences from male and female S. japonicum worms showed the presence of 7 different clusters or subclasses of S. japonicum TSP-2. We determined the protective efficacy of one subclass – Sj-TSP-2e. Methodology/Principal Findings Following the alignment of 211 cDNAs, we identified 7 clusters encoding S. japonicum TSP-2 (Sj-TSP-2) based on sequence variation in the large extracellular loop (LEL) region with differing frequency of transcription in male and female worms. Quantitative PCR analysis revealed elevated expression of Sj-TSP-2 in adult worms compared with other life cycle stages. We expressed in E. coli the LEL region of one of the clusters which exhibited a high frequency of transcription in female worms, and showed the purified recombinant protein (Sj-TSP-2e) was recognised by 43.1% of sera obtained from confirmed schistosomiasis japonica patients. Vaccination of mice with the recombinant protein induced high levels of IgG1 and IgG2 antibodies, but no consistent protective efficacy against challenge infection was elicited in three independent trials. Conclusions/Significance The highly polymorphic nature of the Sj-TSP-2 gene at the transcriptional level may limit the value of Sj-TSP-2 as a target for future S. japonicum vaccine development. PMID:21655308

Understanding global changes of the liver proteome during murine schistosomiasis using a label-free shotgun approach.

PubMed

Campos, Jonatan Marques; Neves, Leandro Xavier; de Paiva, Nívia Carolina Nogueira; de Oliveira E Castro, Renata Alves; Casé, Ana Helena; Carneiro, Cláudia Martins; Andrade, Milton Hércules Guerra; Castro-Borges, William

2017-01-16

Schistosomiasis is an endemic disease affecting over 207 million people worldwide caused by helminth parasites of the genus Schistosoma. In Brazil the disease is responsible for the loss of up to 800 lives annually, resulting from the desabilitating effects of this chronic condition. In this study, we infected Balb/c mice with Schistosoma mansoni and analysed global changes in the proteomic profile of soluble liver proteins. Our shotgun analyses revealed predominance of up-regulation of proteins at 5weeks of infection, coinciding with the onset of egg laying, and a remarkable down-regulation of liver constituents at 7weeks, when severe tissue damage is installed. Representatives of glycolytic enzymes and stress response (in particular at the endoplasmic reticulum) were among the most differentially expressed molecules found in the infected liver. Collectively, our data contribute over 70 molecules not previously reported to be found at altered levels in murine schistosomiasis to further exploration of their potential as biomarkers of the disease. Moreover, understanding their intricate interaction using bioinformatics approach can potentially bring clarity to unknown mechanisms linked to the establishment of this condition in the vertebrate host. To our knowledge, this study refers to the first shotgun proteomic analysis to provide an inventory of the global changes in the liver soluble proteome caused by Schistosoma mansoni in the Balb/c model. It also innovates by yielding data on quantification of the identified molecules as a manner to clarify and give insights into the underlying mechanisms for establishment of Schistosomiasis, a neglected tropical disease with historical prevalence in Brazil. Copyright © 2016 Elsevier B.V. All rights reserved.

Respiratory Syncytial Virus (RSV) Pulmonary Infection in Humanized Mice Induces Human Anti-RSV Immune Responses and Pathology

PubMed Central

Sharma, Anurag; Wu, Wenzhu; Sung, Biin; Huang, Jing; Tsao, Tiffany; Li, Xiangming; Gomi, Rika; Tsuji, Moriya

2016-01-01

ABSTRACT Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract disease, which causes high rates of morbidity and mortality in infants and the elderly. Models of human RSV pulmonary disease are needed to better understand RSV pathogenesis and to assess the efficacy of RSV vaccines. We assessed the RSV-specific human innate, humoral, and cellular immune responses in humanized mice (mice with a human immune system [HIS mice]) with functional human CD4+ T and B cells. These mice were generated by introduction of HLA class II genes, various human cytokines, and human B cell activation factor into immunodeficient NOD scid gamma (NSG) mice by the use of an adeno-associated virus vector, followed by engraftment of human hematopoietic stem cells. During the first 3 days of infection, HIS mice lost more weight and cleared RSV faster than NSG mice. Human chemokine (C-C motif) ligand 3 (CCL3) and human interleukin-1β (IL-1β) expression was detected in the RSV-infected HIS mice. The pathological features induced by RSV infection in HIS mice included peribronchiolar inflammation, neutrophil predominance in the bronchioalveolar lavage fluid, and enhanced airway mucus production. Human anti-RSV IgG and RSV-neutralizing antibodies were detected in serum and human anti-RSV mucosal IgA was detected in bronchioalveolar lavage fluid for up to 6 weeks. RSV infection induced an RSV-specific human gamma interferon response in HIS mouse splenocytes. These results indicate that human immune cells can induce features of RSV lung disease, including mucus hyperplasia, in murine lungs and that HIS mice can be used to elicit human anti-RSV humoral and cellular immunity. IMPORTANCE Infections with respiratory syncytial virus (RSV) are common and can cause severe lung disease in infants and the elderly. The lack of a suitable animal model with disease features similar to those in humans has hampered efforts to predict the efficacy of novel anti-RSV therapies and

21 CFR 660.50 - Anti-Human Globulin.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Globulin. (a) Proper name and definition. The proper name of this product shall be Anti-Human Globulin... in tissue cultures or in secondary hosts. [50 FR 5579, Feb. 11, 1985, as amended at 65 FR 77499, Dec...

Spatial co-distribution of neglected tropical diseases in the East African Great Lakes region: revisiting the justification for integrated control

PubMed Central

Clements, Archie C. A.; Deville, Marie-Alice; Ndayishimiye, Onésime; Brooker, Simon; Fenwick, Alan

2010-01-01

Summary OBJECTIVE To determine spatial patterns of co-endemicity of schistosomiasis mansoni and the soil-transmitted helminths (STHs) Ascaris lumbricoides, Trichuris trichiura and hookworm in the Great Lakes region of East Africa, to help plan integrated neglected tropical disease programmes in this region. METHOD Parasitological surveys were conducted in Uganda, Tanzania, Kenya and Burundi in 28 213 children in 404 schools. Bayesian geostatistical models were used to interpolate prevalence of these infections across the study area. Interpolated prevalence maps were overlaid to determine areas of co-endemicity. RESULTS In the Great Lakes region, prevalence was 18.1% for Schistosoma mansoni, 50.0% for hookworm, 6.8% for A. lumbricoides and 6.8% for T. trichiura. Hookworm infection was ubiquitous, whereas S. mansoni, A. lumbricoides and T. trichiura were highly focal. Most areas were endemic (prevalence ≥10%) or hyperendemic (prevalence ≥50%) for one or more STHs, whereas endemic areas for schistosomiasis mansoni were restricted to foci adjacent large perennial water bodies. CONCLUSION Because of the ubiquity of hookworm, treatment programmes are required for STH throughout the region but efficient schistosomiasis control should only be targeted at limited high-risk areas. Therefore, integration of schistosomiasis with STH control is only indicated in limited foci in East Africa. PMID:20409287

Protocol and baseline data for a multi-year cohort study of the effects of different mass drug treatment approaches on functional morbidities from schistosomiasis in four African countries.

PubMed

Shen, Ye; King, Charles H; Binder, Sue; Zhang, Feng; Whalen, Christopher C; Evan Secor, W; Montgomery, Susan P; Mwinzi, Pauline N M; Olsen, Annette; Magnussen, Pascal; Kinung'hi, Safari; Phillips, Anna E; Nalá, Rassul; Ferro, Josefo; Aurelio, H Osvaldo; Fleming, Fiona; Garba, Amadou; Hamidou, Amina; Fenwick, Alan; Campbell, Carl H; Colley, Daniel G

2017-09-29

The Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) focus is on randomized trials of different approaches to mass drug administration (MDA) in endemic countries in Africa. Because their studies provided an opportunity to evaluate the effects of mass treatment on Schistosoma-associated morbidity, nested cohort studies were developed within SCORE's intervention trials to monitor changes in a suite of schistosomiasis disease outcomes. This paper describes the process SCORE used to select markers for prospective monitoring and the baseline prevalence of these morbidities in four parallel cohort studies. In July 2009, SCORE hosted a discussion of the potential impact of MDA on morbidities due to Schistosoma infection that might be measured in the context of multi-year control. Candidate markers were reviewed and selected for study implementation. Baseline data were then collected from cohorts of children in four country studies: two in high endemic S. mansoni sites (Kenya and Tanzania), and two in high endemic S. haematobium sites (Niger and Mozambique), these cohorts to be followed prospectively over 5 years. At baseline, 62% of children in the S. mansoni sites had detectable eggs in their stool, and 10% had heavy infections (≥ 400 eggs/g feces). Heavy S. mansoni infections were found to be associated with increased baseline risk of anemia, although children with moderate or heavy intensity infections had lower risk of physical wasting. Prevalence of egg-positive infection in the combined S. haematobium cohorts was 27%, with 5% of individuals having heavy infection (≥50 eggs/10 mL urine). At baseline, light intensity S. haematobium infection was associated with anemia and with lower scores in the social domain of health-related quality-of-life (HRQoL) assessed by Pediatric Quality of Life Inventory. Our consensus on practical markers of Schistosoma-associated morbidity indicated that height, weight, hemoglobin, exercise tolerance, HRQo

Schistosomiasis Prevalence and Intensity of Infection in Latin America and the Caribbean Countries, 1942-2014: A Systematic Review in the Context of a Regional Elimination Goal

PubMed Central

2016-01-01

Background In 2012 the World Health Assembly adopted resolution WHA65.21 on elimination of schistosomiasis, calling for increased investment in schistosomiasis control and support for countries to initiate elimination programs. This study aims to analyze prevalence and intensity of Schistosoma mansoni infection in children in Latin America and the Caribbean countries and territories (LAC), at the second administrative level or lower. Methodology A systematic review of schistosomiasis prevalence and intensity of infection was conducted by searching at PubMed, LILACS and EMBASE. Experts on the topic were informally consulted and institutional web pages were reviewed (PAHO/WHO, Ministries of Health). Only SCH infection among children was registered because it can be a ‘proxi-indicator’ of recent transmission by the time the study is conducted. Principal Findings One hundred thirty two full-text articles met the inclusion criteria and provided 1,242 prevalence and 199 intensity of infection data points. Most of them were from Brazil (69.7%). Only Brazil published studies after 2001, showing several 'hot spots' with high prevalence. Brazil, Venezuela, Suriname and Saint Lucia need to update the epidemiological status of schistosomiasis to re-design their national programs and target the elimination of Schistosoma mansoni transmission by 2020. In Antigua and Barbuda, Dominican Republic, Guadeloupe, Martinique, Montserrat and Puerto Rico schistosomiasis transmission may be interrupted. However the compilation of an elimination dossier and follow-up surveys, per WHO recommendations, are needed to verify that status. Hence, the burden of subtle SCH chronic infection may be still present and even high in countries that may have eliminated transmission. Heterogeneity in the methodologies used for monitoring and evaluating the progress of the schistosomiasis programs was found, making cross-national and chronological comparisons difficult. Conclusions There is a need for

Schistosomiasis Prevalence and Intensity of Infection in Latin America and the Caribbean Countries, 1942-2014: A Systematic Review in the Context of a Regional Elimination Goal.

PubMed

Zoni, Ana Clara; Catalá, Laura; Ault, Steven K

2016-03-01

In 2012 the World Health Assembly adopted resolution WHA65.21 on elimination of schistosomiasis, calling for increased investment in schistosomiasis control and support for countries to initiate elimination programs. This study aims to analyze prevalence and intensity of Schistosoma mansoni infection in children in Latin America and the Caribbean countries and territories (LAC), at the second administrative level or lower. A systematic review of schistosomiasis prevalence and intensity of infection was conducted by searching at PubMed, LILACS and EMBASE. Experts on the topic were informally consulted and institutional web pages were reviewed (PAHO/WHO, Ministries of Health). Only SCH infection among children was registered because it can be a 'proxi-indicator' of recent transmission by the time the study is conducted. One hundred thirty two full-text articles met the inclusion criteria and provided 1,242 prevalence and 199 intensity of infection data points. Most of them were from Brazil (69.7%). Only Brazil published studies after 2001, showing several 'hot spots' with high prevalence. Brazil, Venezuela, Suriname and Saint Lucia need to update the epidemiological status of schistosomiasis to re-design their national programs and target the elimination of Schistosoma mansoni transmission by 2020. In Antigua and Barbuda, Dominican Republic, Guadeloupe, Martinique, Montserrat and Puerto Rico schistosomiasis transmission may be interrupted. However the compilation of an elimination dossier and follow-up surveys, per WHO recommendations, are needed to verify that status. Hence, the burden of subtle SCH chronic infection may be still present and even high in countries that may have eliminated transmission. Heterogeneity in the methodologies used for monitoring and evaluating the progress of the schistosomiasis programs was found, making cross-national and chronological comparisons difficult. There is a need for updating the schistosomiasis status in the historically

An interesting finding in the uterine cervix: Schistosoma hematobium calcified eggs.

PubMed

Toller, Alexia; Scopin, Ana Carolina; Apfel, Vanessa; Prigenzi, Karla Calaça Kabbach; Tso, Fernanda Kesselring; Focchi, Gustavo Rubino de Azevedo; Speck, Neila; Ribalta, Julisa

2015-01-01

Schistosoma hematobium infection is an endemic parasitic disease in Africa, which is frequently associated with urinary schistosomiasis. The parasite infection causes epithelial changes and disruption, facilitating the infection by the human papilloma virus and human immunodeficiency virus (HIV). The authors report the case of a 44-year-old African HIV-positive woman who presented an abnormal routine Pap smear. Colposcopy examination revealed dense acetowhite micropapillary epithelium covering the ectocervix, iodine-negative, an erosion area in endocervical canal, and atypical vessels. Histologic examination of the surgical specimens showed numerous calcified schistosome eggs (probably S. hematobium) and a high-grade cervical intraepithelial neoplasia. The relation between S. hematobium infection and bladder cancer is well known; however, this relationship with cervical cancer remains controversial. The symptoms of schistosomiasis of the female genital tract are rather non-specific, and are often misdiagnosed with other pelvic diseases. The familiarity of health professionals with schistosomiasis of the female genital tract is less than expected, even in endemic regions. Therefore, great awareness of this differential diagnosis in routine gynecological practice is of paramount importance.

Schistosome egg antigens, including the glycoprotein IPSE/alpha-1, trigger the development of regulatory B cells

PubMed Central

Veninga, Henrike; van der Vlugt, Luciën E. P. M.; Voskamp, Astrid; Boon, Louis; Westerhof, Lotte B.; Smits, Hermelijn H.

2017-01-01

Infection with the helminth Schistosoma (S.) mansoni drives the development of interleukin (IL)-10-producing regulatory B (Breg) cells in mice and man, which have the capacity to reduce experimental allergic airway inflammation and are thus of high therapeutic interest. However, both the involved antigen and cellular mechanisms that drive Breg cell development remain to be elucidated. Therefore, we investigated whether S. mansoni soluble egg antigens (SEA) directly interact with B cells to enhance their regulatory potential, or act indirectly on B cells via SEA-modulated macrophage subsets. Intraperitoneal injections of S. mansoni eggs or SEA significantly upregulated IL-10 and CD86 expression by marginal zone B cells. Both B cells as well as macrophages of the splenic marginal zone efficiently bound SEA in vivo, but macrophages were dispensable for Breg cell induction as shown by macrophage depletion with clodronate liposomes. SEA was internalized into acidic cell compartments of B cells and induced a 3-fold increase of IL-10, which was dependent on endosomal acidification and was further enhanced by CD40 ligation. IPSE/alpha-1, one of the major antigens in SEA, was also capable of inducing IL-10 in naïve B cells, which was reproduced by tobacco plant-derived recombinant IPSE. Other major schistosomal antigens, omega-1 and kappa-5, had no effect. SEA depleted of IPSE/alpha-1 was still able to induce Breg cells indicating that SEA contains more Breg cell-inducing components. Importantly, SEA- and IPSE-induced Breg cells triggered regulatory T cell development in vitro. SEA and recombinant IPSE/alpha-1 also induced IL-10 production in human CD1d+ B cells. In conclusion, the mechanism of S. mansoni-induced Breg cell development involves a direct targeting of B cells by SEA components such as the secretory glycoprotein IPSE/alpha-1. PMID:28753651

Geographical distribution of human Schistosoma japonicum infection in The Philippines: tools to support disease control and further elimination

PubMed Central

Magalhães, Ricardo J Soares; Salamat, Maria Sonia; Leonardo, Lydia; Gray, Darren J; Carabin, Hélène; Halton, Kate; McManus, Donald P; Williams, Gail M; Rivera, Pilarita; Saniel, Ofelia; Hernandez, Leda; Yakob, Laith; McGarvey, Stephen; Clements, Archie

2015-01-01

Schistosoma japonicum infection is believed to be endemic in 28 of the 80 provinces of The Philippines and the most recent data on schistosomiasis prevalence have shown considerable variability between provinces. In order to increase the efficient allocation of parasitic disease control resources in the country, we aimed to describe the small-scale spatial variation in S. japonicum prevalence across The Philippines, quantify the role of the physical environment in driving the spatial variation of S. japonicum, and develop a predictive risk map of S. japonicum infection. Data on S. japonicum infection from 35,754 individuals across the country were geolocated at the barangay level and included in the analysis. The analysis was then stratified geographically for the regions of Luzon, the Visayas and Mindanao. Zero-inflated binomial Bayesian geostatistical models of S. japonicum prevalence were developed and diagnostic uncertainty was incorporated. Results of the analysis show that in the three regions, males and individuals aged ≥ 20 years had significantly higher prevalence of S. japonicum compared with females and children < 5 years. The role of the environmental variables differed between regions of The Philippines. Schistosoma japonicum infection was widespread in the Visayas whereas it was much more focal in Luzon and Mindanao. This analysis revealed significant spatial variation in the prevalence of S. japonicum infection in The Philippines. This suggests that a spatially targeted approach to schistosomiasis interventions, including mass drug administration, is warranted. When financially possible, additional schistosomiasis surveys should be prioritized for areas identified to be at high risk but which were under-represented in our dataset. PMID:25128879

Bovine lactoferricin is anti-inflammatory and anti-catabolic in human articular cartilage and synovium.

PubMed

Yan, Dongyao; Chen, Di; Shen, Jie; Xiao, Guozhi; van Wijnen, Andre J; Im, Hee-Jeong

2013-02-01

Bovine lactoferricin (LfcinB) is a multi-functional peptide derived from proteolytic cleavage of bovine lactoferrin. LfcinB was found to antagonize the biological effects mediated by angiogenic growth factors such as vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF-2) in endothelial cells. However, the effect of LfcinB on human articular cartilage remained unknown. Here, our findings demonstrate that LfcinB restored the proteoglycan loss promoted by catabolic factors (interleukin-1β) IL-1β and FGF-2 in vitro and ex vivo. Mechanistically, LfcinB attenuated the effects of IL-1β and FGF-2 on the expression of cartilage-degrading enzymes (MMP-1, MMP-3, and MMP-13), destructive cytokines (IL-1β and IL-6), and inflammatory mediators (iNOS and TLR2). LfcinB induced protective cytokine expression (IL-4 and IL-10), and downregulated aggrecanase basal expression. LfcinB specifically activated ERK MAPK and Akt signaling pathways, which may account for its anti-inflammatory activity. We also revealed that LfcinB exerted similar protective effects on human synovial fibroblasts challenged by IL-1β, with minimal cytotoxicity. Collectively, our results suggest that LfcinB possesses potent anti-catabolic and anti-inflammatory bioactivities in human articular tissues, and may be utilized for the prevention and/or treatment of OA in the future. Copyright © 2012 Wiley Periodicals, Inc.

The epidemiology of schistosomiasis mansoni and soil-transmitted helminths in elementary school children from the South Gondar Zone of the Amhara National Regional State, Ethiopia.

PubMed

Jemaneh, L

2000-04-01

In a cross-sectional survey undertaken in 22 communities of 6 districts in the South Gondar Zone of the Amhara National Regional State, 2279 school children had their stools examined for schistosomiasis mansoni and soil-transmitted helminths using the Kato-Katz technique. Overall the prevalence rates were 16.4%, 28.9%, 9.5% and 12.9% for S. mansoni, A. lumbricoides, T. trichiura and the hookworms, respectively. S. mansoni infection was registered from 14 of the 22 communities, in more than 60% of which the prevalence was over 20%. Infection with A. lumbricoides was noted in 20 schools and except in three schools the prevalence was above 20%. T. trichiura infection was found in 19 of the 22 schools with prevalence rates from 1.7% to 20.0%. Infection due to the hookworms was recorded in 17 schools, in 40% of which the prevalence was 20% or more. Generally communities of the western districts of the zone had higher infection rates of schistosomiasis mansoni and soil-transmitted helminthiasis as compared to those in the eastern districts. The presence of S. mansoni foci in 9 communities is reported for the first time. In general neither sex nor age were related to prevalence or intensity of infection. Forty nine percent of the examined children had one or more types of helminths, of which 32.5%, 13.3% and 2.4% were single, double and triple infections, respectively. A. lumbricoides commonly occurred with the other helminths. Multiplicity of infection was not sex related. 14.6%, 28.4%, 8.3% and 12.1% of the children had moderate or heavy infections of schistosomiasis mansoni, ascariasis, trichuriasis and hookworms, respectively.

Use of AN Eosinophil Specific Monoclonal Antibody in Assessing Eosinophil Function.

NASA Astrophysics Data System (ADS)

Minkoff, Marjorie Sue

A monoclonal antibody to an eosinophil specific determinant is very important in assessing eosinophil function during helminthic infection. Eosinophils induced by Schistosoma mansoni infection in BALB/c mice were used to induce C57B1/6 immunocytes for production of hybridomas secreting eosinophil monoclonal antibodies. These antibodies were shown to react with an eosinophil surface epitope but not with neutrophils or macrophages as determined by ELISA, immunodiffusion, immunofluorescence, and immunoblot assay. Affinity chromatography with eosinophil chemotactic factor-sepharose consistently selected out a { rm M_ R} 67,000 protein from solubilized eosinophil membrane antigens but not from neutrophil and macrophage antigens. In vitro studies showed that the eosinophil-specific monoclonal antibodies abrogated antibody-dependent eosinophil -mediated killing of S. mansoni schistosomula using mouse, rat or human eosinophils. Neutrophil and macrophage killing activities were unaffected. The monoclonal antibodies effected complement-dependent lysis of mouse and rat eosinophils but not of human eosinophils. ECF-treated eosinophils showed enhanced killing of schistosomula which was blocked by the monoclonal antibody. Murine and human eosinophils preincubated with monoclonal antibody exhibited decreased chemotaxis to ECF at optimal chemotactic concentrations. The monoclonal antibody also blocked eosinophil binding to ECF- sepharose beads. In vivo induction of peripheral blood eosinophilia by injection of S. mansoni eggs was suppressed by injections of monoclonal antibodies 2CD13 and 2QD45 in mouse and rat experimental models. Eosinophilia induced by keyhole limpet hemocyanin- cyclophosphamide treatment was also suppressed by monoclonal antibody in both murine and rat systems. Pulmonary granulomas in mice given egg injection and monoclonal antibody were smaller and contained fewer eosinophils than those granulomas from mice given eggs only. In immuno-biochemical studies, the

Trichuris suis-induced modulation of human dendritic cell function is glycan-mediated.

PubMed

Klaver, Elsenoor J; Kuijk, Loes M; Laan, Lisa C; Kringel, Helene; van Vliet, Sandra J; Bouma, Gerd; Cummings, Richard D; Kraal, Georg; van Die, Irma

2013-03-01

Human monocyte-derived dendritic cells (DCs) show remarkable phenotypic changes upon direct contact with soluble products (SPs) of Trichuris suis, a pig whipworm that is experimentally used in therapies to ameliorate inflammation in patients with Crohn's disease and multiple sclerosis. These changes may contribute to the observed induction of a T helper 2 (Th2) response and the suppression of Toll-like receptor (TLR)-induced Th1 and Th17 responses by human DCs primed with T. suis SPs. Here it is demonstrated that glycans of T. suis SPs contribute significantly to the suppression of the lipopolysaccharide (LPS)-induced expression in DCs of a broad variety of cytokines and chemokines, including important pro-inflammatory mediators such as TNF-α, IL-6, IL-12, lymphotoxin α (LTA), C-C Motif Ligand (CCL)2, C-X-C Motif Ligands (CXCL)9 and CXCL10. In addition, the data show that human DCs strongly bind T. suis SP-glycans via the C-type lectin receptors (CLRs) mannose receptor (MR) and DC-specific ICAM-3-grabbing non-integrin (DC-SIGN). The interaction of DCs with T. suis glycans likely involves mannose-type glycans, rather than fucosylated glycans, which differs from DC binding to soluble egg antigens of the human worm parasite, Schistosoma mansoni. In addition, macrophage galactose-type lectin (MGL) recognises T. suis SPs, which may contribute to the interaction with immature DCs or other MGL-expressing immune cells such as macrophages. The interaction of T. suis glycans with CLRs of human DCs may be essential for the ability of T. suis to suppress a pro-inflammatory phenotype of human DCs. The finding that the T. suis-induced modulation of human DC function is glycan-mediated is novel and indicates that helminth glycans contribute to the dampening of inflammation in a wide range of human inflammatory diseases. Copyright © 2012 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

Predominant antitumor effects by fully human anti-TRAIL-receptor2 (DR5) monoclonal antibodies in human glioma cells in vitro and in vivo

PubMed Central

Nagane, Motoo; Shimizu, Saki; Mori, Eiji; Kataoka, Shiro; Shiokawa, Yoshiaki

2010-01-01

Tumor necrosis factor–related apoptosis-inducing ligand (TRAIL/Apo2 L) preferentially induces apoptosis in human tumor cells through its cognate death receptors DR4 or DR5, thereby being investigated as a potential agent for cancer therapy. Here, we applied fully human anti-human TRAIL receptor monoclonal antibodies (mAbs) to specifically target one of death receptors for TRAIL in human glioma cells, which could also reduce potential TRAIL-induced toxicity in humans. Twelve human glioma cell lines treated with several fully human anti-human TRAIL receptor mAbs were sensitive to only anti-DR5 mAbs, whereas they were totally insensitive to anti-DR4 mAb. Treatment with anti-DR5 mAbs exerted rapid cytotoxicity and lead to apoptosis induction. The cellular sensitivity was closely associated with cell-surface expression of DR5. Expression of c-FLIPL, Akt, and Cyclin D1 significantly correlated with sensitivity to anti-DR5 mAbs. Primary cultures of glioma cells were also relatively resistant to anti-DR5 mAbs, exhibiting both lower DR5 and higher c-FLIPL expression. Downregulation of c-FLIPL expression resulted in the sensitization of human glioma cells to anti-DR5 mAbs, whereas overexpression of c-FLIPL conferred resistance to anti-DR5 mAb. Treatment of tumor-burden nude mice with the direct agonist anti-DR5 mAb KMTR2 significantly suppressed growth of subcutaneous glioma xenografts leading to complete regression. Similarly, treatment of nude mice bearing intracerebral glioma xenografts with KMTR2 significantly elongated lifespan without tumor recurrence. These results suggest that DR5 is the predominant TRAIL receptor mediating apoptotic signals in human glioma cells, and sensitivity to anti-DR5 mAbs was determined at least in part by the expression level of c-FLIPL and Akt. Specific targeting of death receptor pathway through DR5 using fully human mAbs might provide a novel therapeutic strategy for intractable malignant gliomas. PMID:20511188

Localization of Tyrosine Hydroxylase-like Immunoreactivity in the Nervous Systems of Biomphalaria glabrata and Biomphalaria alexandrina, Intermediate Hosts for Schistosomiasis

PubMed Central

Vallejo, Deborah; Habib, Mohammed R.; Delgado, Nadia; Vaasjo, Lee O.; Croll, Roger P.; Miller, Mark W.

2014-01-01

Planorbid snails of the genus Biomphalaria are major intermediate hosts for the digenetic trematode parasite Schistosoma mansoni. Evidence suggests that levels of the neurotransmitter dopamine (DA) are reduced during the course of S. mansoni multiplication and transformation within the snail. This investigation used immunohistochemical methods to localize tyrosine hydroxylase (TH), the rate-limiting enzyme in the biosynthesis of catecholamines, in the nervous system of Biomphalaria. The two species examined, Biomphalaria glabrata and Biomphalaria alexandrina, are the major intermediate hosts for S. mansoni in sub-Saharan Africa, where more than 90% of global cases of human intestinal schistosomiasis occur. TH-like immunoreactive (THli) neurons were distributed throughout the central nervous system (CNS) and labeled fibers were present in all commissures, connectives, and nerves. Some asymmetries were observed, including a large distinctive neuron (LPeD1) in the pedal ganglion described previously in several pulmonates. The majority of TH-like immunoreactive neurons were detected in the peripheral nervous system (PNS), especially in lip and foot regions of the anterior integument. Independent observations supporting the dopaminergic phenotype of THli neurons included 1) block of LPeD1 synaptic signaling by the D2/3 antagonist sulpiride, and 2) the similar localization of aqueous aldehyde (FaGlu) induced fluorescence. The distribution of THli neurons indicates that, as in other gastropods, dopamine functions as a sensory neurotransmitter and in the regulation of feeding and reproductive behaviors in Biomphalaria. It is hypothesized that infection could stimulate transmitter release from dopaminergic sensory neurons and that dopaminergic signaling could contribute to modifications of both host and parasite behavior. PMID:24477836

Recombinant production, crystallization and preliminary structural characterization of Schistosoma japonicum profilin

PubMed Central

Vervaet, Nele; Kallio, Juha Pekka; Meier, Susanne; Salmivaara, Emilia; Eberhardt, Maike; Zhang, Shuangmin; Sun, Xi; Wu, Zhongdao; Kursula, Petri; Kursula, Inari

2013-01-01

Helminthic parasites of the genus Schistosoma contain a tegumental membrane, which is of crucial importance for modulation of the host immune response and parasite survival. The actin cytoskeleton plays an important role in the function of the tegument. Profilins are among the most important proteins regulating actin dynamics. Schistosoma japonicum possesses one profilin-like protein, which has been characterized as a potential vaccine candidate. Notably, profilins are highly immunogenic molecules in many organisms. Here, the profilin from S. japonicum was expressed, purified and crystallized. A native data set to 1.91 Å resolution and a single-wavelength anomalous diffraction (SAD) data set to a resolution of 2.2 Å were collected. The crystals belonged to space group P212121, with unit-cell parameters a = 31.82, b = 52.17, c = 59.79 Å and a = 35.29, b = 52.15, c = 59.82 Å, respectively. PMID:24192365

Recombinant production, crystallization and preliminary structural characterization of Schistosoma japonicum profilin.

PubMed

Vervaet, Nele; Kallio, Juha Pekka; Meier, Susanne; Salmivaara, Emilia; Eberhardt, Maike; Zhang, Shuangmin; Sun, Xi; Wu, Zhongdao; Kursula, Petri; Kursula, Inari

2013-11-01

Helminthic parasites of the genus Schistosoma contain a tegumental membrane, which is of crucial importance for modulation of the host immune response and parasite survival. The actin cytoskeleton plays an important role in the function of the tegument. Profilins are among the most important proteins regulating actin dynamics. Schistosoma japonicum possesses one profilin-like protein, which has been characterized as a potential vaccine candidate. Notably, profilins are highly immunogenic molecules in many organisms. Here, the profilin from S. japonicum was expressed, purified and crystallized. A native data set to 1.91 Å resolution and a single-wavelength anomalous diffraction (SAD) data set to a resolution of 2.2 Å were collected. The crystals belonged to space group P2(1)2(1)2(1), with unit-cell parameters a = 31.82, b = 52.17, c = 59.79 Å and a = 35.29, b = 52.15, c = 59.82 Å, respectively.

Geographical distribution of human Schistosoma japonicum infection in The Philippines: tools to support disease control and further elimination.

PubMed

Soares Magalhães, Ricardo J; Salamat, Maria Sonia; Leonardo, Lydia; Gray, Darren J; Carabin, Hélène; Halton, Kate; McManus, Donald P; Williams, Gail M; Rivera, Pilarita; Saniel, Ofelia; Hernandez, Leda; Yakob, Laith; McGarvey, Stephen; Clements, Archie

2014-11-01

Schistosoma japonicum infection is believed to be endemic in 28 of the 80 provinces of The Philippines and the most recent data on schistosomiasis prevalence have shown considerable variability between provinces. In order to increase the efficient allocation of parasitic disease control resources in the country, we aimed to describe the small-scale spatial variation in S. japonicum prevalence across The Philippines, quantify the role of the physical environment in driving the spatial variation of S. japonicum, and develop a predictive risk map of S. japonicum infection. Data on S. japonicum infection from 35,754 individuals across the country were geo-located at the barangay level and included in the analysis. The analysis was then stratified geographically for the regions of Luzon, the Visayas and Mindanao. Zero-inflated binomial Bayesian geostatistical models of S. japonicum prevalence were developed and diagnostic uncertainty was incorporated. Results of the analysis show that in the three regions, males and individuals aged ⩾20years had significantly higher prevalence of S. japonicum compared with females and children <5years. The role of the environmental variables differed between regions of The Philippines. Schistosoma japonicum infection was widespread in the Visayas whereas it was much more focal in Luzon and Mindanao. This analysis revealed significant spatial variation in the prevalence of S. japonicum infection in The Philippines. This suggests that a spatially targeted approach to schistosomiasis interventions, including mass drug administration, is warranted. When financially possible, additional schistosomiasis surveys should be prioritised for areas identified to be at high risk but which were under-represented in our dataset. Copyright © 2014 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

[Reinfections and the development of schistosomal periportal fibrosis in the murine model].

PubMed

Santos, A B; de Souza, M M; Andrade, Z A

2000-01-01

Experimental pipestem fibrosis of the liver developed more frequently (69.2%) in mice submitted to repeated infections with Schistosoma mansoni, than with single infection (11.1%). The counting of eggs in the liver revealed no significant differences between the two experimental groups. Although the reason why multiple infections favor the development of pipestem fibrosis has not been elucidated, the data obtained represent an experimental support to clinico-epidemiological claims that repeated infections play a role in pathogenesis of hepatosplenic schistosomiasis

Schistosomiasis in school-age children in Burkina Faso after a decade of preventive chemotherapy

PubMed Central

Ouedraogo, Hamado; Drabo, François; Zongo, Dramane; Bagayan, Mohamed; Bamba, Issouf; Pima, Tiba; Yago-Wienne, Fanny; Toubali, Emily

2016-01-01

Abstract Objective To assess the impact of a decade of biennial mass administration of praziquantel on schistosomiasis in school-age children in Burkina Faso. Methods In 2013, in a national assessment based on 22 sentinel sites, 3514 school children aged 7–11 years were checked for Schistosoma haematobium and Schistosoma mansoni infection by the examination of urine and stool samples, respectively. We analysed the observed prevalence and intensity of infections and compared these with the relevant results of earlier surveys in Burkina Faso. Findings S. haematobium was detected in 287/3514 school children (adjusted prevalence: 8.76%, range across sentinel sites: 0.0–56.3%; median: 2.5%). The prevalence of S. haematobium infection was higher in the children from the Centre-Est, Est and Sahel regions than in those from Burkina Faso’s other eight regions with sentinel sites (P < 0.001). The adjusted arithmetic mean intensity of S. haematobium infection, among all children, was 6.0 eggs per 10 ml urine. Less than 1% of the children in six regions had heavy S. haematobium infections – i.e. at least 50 eggs per 10 ml urine – but such infections were detected in 8.75% (28/320) and 11.56% (37/320) of the children from the Centre-Est and Sahel regions, respectively. Schistosoma mansoni was only detected in two regions and 43 children – i.e. 1 (0.31%) of the 320 from Centre-Sud and 42 (8.75%) of the 480 from Hauts Bassins. Conclusion By mass use of preventive chemotherapy, Burkina Faso may have eliminated schistosomiasis as a public health problem in eight regions and controlled schistosome-related morbidity in another three regions. PMID:26769995

Detection of schistosomiasis in an area directly affected by the São Francisco River large-scale water transposition project in the Northeast of Brazil.

PubMed

Silva, José Damião da; Pinheiro, Marta Cristhiany Cunha; Sousa, Mariana Silva; Gomes, Vivian da Silva; Castro, Issis Maria Nogueira de; Ramos, Alberto Novaes; Bezerra, Fernando Schemelzer de Moraes

2017-01-01

The development of the São Francisco River Integration Project [Projeto de Integração do Rio São Francisco (PISF)] in the State of Ceará, Brazil, has resulted in environmental and socioeconomic changes with potential risks to public health. We aimed to determine the presence of Schistosoma mansoni infections in schoolchildren (aged 7-14 years) and workers from the construction site in an area under the direct influence of the PISF in the municipality of Brejo Santo-CE, to aid in the prevention and control of schistosomiasis. We conducted a cross-sectional study using two S. mansoni-detection methods: detection of S. mansoni eggs by the Kato-Katz parasitological method in stool samples (assessed in triplicate for each sample) and S. mansoni circulating cathodic antigen by the point-of-care immunochromatographic rapid test (POC-CCA) in urine. In general, the positivity rates for S. mansoni detection were 1.9% (2/106) among schoolchildren and 2.9% (4/138) among workers. No child had evidence of S. mansoni eggs in their stools; 1.9% tested positive by the POC-CCA method. Among workers, two (1.4%) tested positive by the Kato-Katz test and three (2.2%) by the POC-CCA test. If the POC-CCA test results that were scored as traces were considered negative, then the positivity rates dropped to 0.9% and 0.7% for schoolchildren and workers, respectively. The active transmission of schistosomiasis in a region covered by the PISF was recognized, reinforcing the necessity to consolidate surveillance and control actions, as well as structural sanitation measures to reverse the social determinants of the disease.

State-space forecasting of Schistosoma haematobium time-series in Niono, Mali.

PubMed

Medina, Daniel C; Findley, Sally E; Doumbia, Seydou

2008-08-13

Much of the developing world, particularly sub-Saharan Africa, exhibits high levels of morbidity and mortality associated with infectious diseases. The incidence of Schistosoma sp.-which are neglected tropical diseases exposing and infecting more than 500 and 200 million individuals in 77 countries, respectively-is rising because of 1) numerous irrigation and hydro-electric projects, 2) steady shifts from nomadic to sedentary existence, and 3) ineffective control programs. Notwithstanding the colossal scope of these parasitic infections, less than 0.5% of Schistosoma sp. investigations have attempted to predict their spatial and or temporal distributions. Undoubtedly, public health programs in developing countries could benefit from parsimonious forecasting and early warning systems to enhance management of these parasitic diseases. In this longitudinal retrospective (01/1996-06/2004) investigation, the Schistosoma haematobium time-series for the district of Niono, Mali, was fitted with general-purpose exponential smoothing methods to generate contemporaneous on-line forecasts. These methods, which are encapsulated within a state-space framework, accommodate seasonal and inter-annual time-series fluctuations. Mean absolute percentage error values were circa 25% for 1- to 5-month horizon forecasts. The exponential smoothing state-space framework employed herein produced reasonably accurate forecasts for this time-series, which reflects the incidence of S. haematobium-induced terminal hematuria. It obliquely captured prior non-linear interactions between disease dynamics and exogenous covariates (e.g., climate, irrigation, and public health interventions), thus obviating the need for more complex forecasting methods in the district of Niono, Mali. Therefore, this framework could assist with managing and assessing S. haematobium transmission and intervention impact, respectively, in this district and potentially elsewhere in the Sahel.

Herbicide trials in the snail habitats of the Egypt 49 project*

PubMed Central

Dawood, Ismail K.; Farooq, M.; Dazo, B. C.; Miguel, Luis C.; Unrau, G. O.

1965-01-01

The molluscan hosts of Schistosoma haematobium, Schistosoma mansoni and Fasciola spp. have been found to flourish in association with certain submersed, floating and emergent weeds in the irrigation system of the Egypt 49 project area. The efficacy of acrolein in killing Potamogeton crispus, an important submersed weed, has been previously established. The present paper deals with field trials of different herbicides, alone or combined, against the other predominant types of floating and emergent weeds—Eichhornia crassipes, Panicum repens, Typha ungustata and Scirpus inclinatus. The trials showed that some of the herbicides are effective and have economic advantages over the manual removal of weeds, besides eliminating the health hazard involved in manual removal. Laboratory tests showed that the herbicides also have ovicidal properties. Aquatic-weed control by the use of appropriate herbicides as an adjunct to molluscicides is therefore advocated. PMID:14310915

Anti-complement activities of human breast-milk.

PubMed

Ogundele, M O

1999-08-01

It has long been observed that the human milk possesses significant anti-inflammatory properties, while simultaneously protecting the infant against many intestinal and respiratory pathogens. There is, however, a paucity of information on the degree and extent of this anti-inflammatory activity. In the present study, the inhibitory effects of different fractions of human milk on serum complement activity were analysed. Colostrum and milk samples from healthy voluntary lactating donors at different postpartum ages were obtained and pooled normal human serum was used as source of complement in a modified CH50 assay. Inherent complement activity in human milk was also investigated by measuring the deposition of an activated C3 fragment on a serum-sensitive bacteria, and by haemolytic assays. Most whole- and defatted-milk samples consistently showed a dose-dependent inhibition of the serum complement activity. This inhibition was greater in mature milk compared to transitional milk samples. It was enhanced by inactivation of milk complement, and diminished by centrifugation of milk samples, which partly removed fat and larger protein components including casein micelles. Inherent complement activity in human milk was also demonstrated by haemolysis of sensitised sheep erythrocytes and deposition of C3 fragments on solid-phase bacteria. These activities were highest in the colostrum and gradually decreased as lactation proceeded. Several natural components abundant in the fluid phase of the human breast-milk have been shown to be inhibitors of complement activation in vitro. Their physiological significance probably reside in their ability to prevent inflammatory-induced tissue damage of the delicate immature gastrointestinal tract of the new-born as well as the mammary gland itself, which may arise from ongoing complement activation.

Enhancing Schistosomiasis Control Strategy for Zimbabwe: Building on Past Experiences

PubMed Central

Chimbari, Moses J.

2012-01-01

Schistosoma haematobium and Schistosoma mansoni are prevalent in Zimbabwe to levels that make schistosomiasis a public health problem. Following three national surveys to map the disease prevalence, a national policy on control of schistosomiasis and soil transmitted helminths is being developed. This paper reviews the experiences that Zimbabwe has in the area of schistosomiasis control with a view to influence policy. A case study approach to highlight key experiences and outcomes was adopted. The benefits derived from intersectoral collaboration that led to the development of a model irrigation scheme that incorporates schistosomiasis control measures are highlighted. Similarly, the benefits of using plant molluscicides and fish and duck biological agents (Sargochromis codringtonii and Cairina moschata) are highlighted. Emphasis was also placed on the importance of utilizing locally developed water and sanitation technologies and the critical human resource base in the area of schistosomiasis developed over years. After synthesis of the case studies presented, it was concluded that while there is a need to follow the WHO recommended guidelines for schistosomiasis control it is important to develop a control strategy that is informed by work already done in the country. The importance of having a policy and local guidelines for schistosomiasis control is emphasized. PMID:22655171

Serological approaches for the diagnosis of schistosomiasis - A review.

PubMed

Hinz, Rebecca; Schwarz, Norbert G; Hahn, Andreas; Frickmann, Hagen

2017-02-01

Schistosomiasis is a common disease in endemic areas of Sub-Saharan Africa, South America and Asia. It is rare in Europe, mainly imported from endemic countries due to travelling or human migration. Available methods for the diagnosis of schistosomiasis comprise microscopic, molecular and serological approaches, with the latter detecting antigens or antibodies associated with Schistosoma spp. infection. The serological approach is a valuable screening tool in low-endemicity settings and for travel medicine, though the interpretation of any diagnostic results requires knowledge of test characteristics and a patient's history. Specific antibody detection by most currently used assays is only possible in a relatively late stage of infection and does not allow for the differentiation of acute from previous infections for therapeutic control or the discrimination between persisting infection and re-infection. Throughout the last decades, new target antigens have been identified, and assays with improved performance and suitability for use in the field have been developed. For numerous assays, large-scale studies are still required to reliably characterise assay characteristics alone and in association with other available methods for the diagnosis of schistosomiasis. Apart from S. mansoni, S. haematobium and S. japonicum, for which most available tests were developed, other species of Schistosoma that occur less frequently need to be taken into account. This narrative review describes and critically discusses the results of published studies on the evaluation of serological assays that detect antibodies against different Schistosoma species of humans. It provides insights into the diagnostic performance and an overview of available assays and their suitability for large-scale use or individual diagnosis, and thus sets the scene for serological diagnosis of schistosomiasis and the interpretation of results. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All

Anti-liver-kidney microsome antibody type 1 recognizes human cytochrome P450 db1.

PubMed

Gueguen, M; Yamamoto, A M; Bernard, O; Alvarez, F

1989-03-15

Anti-liver-kidney microsome antibody type 1 (LKM1), present in the sera of a group of children with autoimmune hepatitis, was recently shown to recognize a 50 kDa protein identified as rat liver cytochromes P450 db1 and db2. High homology between these two members of the rat P450 IID subfamily and human P450 db1 suggested that anti-LKM1 antibody is directed against this human protein. To test this hypothesis, a human liver cDNA expression library in phage lambda GT-11 was screened using rat P450 db1 cDNA as a probe. Two human cDNA clones were found to be identical to human P450 db1 by restriction mapping. Immunoblot analysis using as antigen, the purified fusion protein from one of the human cDNA clones showed that only anti-LKM1 with anti-50 kDa reactivity recognized the fusion protein. This fusion protein was further used to develop an ELISA test that was shown to be specific for sera of children with this disease. These results: 1) identify the human liver antigen recognized by anti-LKM1 auto-antibodies as cytochrome P450 db1, 2) allow to speculate that mutation on the human P450 db1 gene could alter its expression in the hepatocyte and make it auto-antigenic, 3) provide a simple and specific diagnostic test for this disease.

New phytochemicals as potential human anti-aging compounds: Reality, promise, and challenges.

PubMed

Corrêa, Rúbia C G; Peralta, Rosane M; Haminiuk, Charles W I; Maciel, Giselle Maria; Bracht, Adelar; Ferreira, Isabel C F R

2018-04-13

Aging is an inevitable process influenced by genetic, lifestyle, and environmental factors. Indirect evidence shows that several phytochemicals can have anti-aging capabilities, although direct evidence in this field is still limited. This report aims to provide a critical review on aspects related to the use of novel phytochemicals as anti-aging agents, to discuss the obstacles found when performing most anti-aging study protocols in humans, and to analyze future perspectives. In addition to the extensively studied resveratrol, epicatechin, quercetin, and curcumin, new phytochemicals have been reported to act as anti-aging agents, such as the amino acid L-theanine isolated from green tea, and the lignans arctigenin and matairesinol isolated from Arctium lappa seeds. Furthermore, this review discusses the application of several new extracts rich in phytochemicals with potential use in anti-aging therapies. Finally, this review also discusses the most important biomarkers to test anti-aging interventions, the necessity of conducting epidemiological studies and the need of clinical trials with adequate study protocols for humans.

Gene Gun Bombardment with DNA-Coated Golden Particles Enhanced the Protective Effect of a DNA Vaccine Based on Thioredoxin Glutathione Reductase of Schistosoma japonicum

PubMed Central

Cao, Yan; Zhao, Bin; Han, Yanhui; Zhang, Juan; Li, Xuezhen; Qiu, Chunhui; Wu, Xiujuan; Hong, Yang; Ai, Dezhou; Lin, Jiaojiao; Fu, Zhiqiang

2013-01-01

Schistosomiasis, caused by infection with Schistosoma species, remains an important parasitic zoonosis. Thioredoxin glutathione reductase of Schistosoma japonicum (SjTGR) plays an important role in the development of the parasite and for its survival. Here we present a recombinant plasmid DNA vaccine, pVAX1/SjTGR, to estimate its protection against S. japonicum in BALB/c mice. The DNA vaccine administrated by particle bombardment induced higher protection than by intramuscular injection. All animals vaccinated with pVAX1/SjTGR developed significant specific anti-SjTGR antibodies than control groups. Moreover, animals immunized by gene gun exhibited a splenocyte proliferative response, with an increase in IFN-γ and IL-4. The recombinant plasmid administrated by gene gun achieved a medium protective efficacy of 27.83–38.83% (P < 0.01) of worm reduction and 40.38–44.51% (P < 0.01) of liver egg count reduction. It suggests that different modes of administering a DNA vaccine can influence the protective efficacy induced by the vaccine. Interestingly, from the enzymatic activity results, we found that worms obtained from pVAX1/SjTGR-vaccinated animals expressed lower enzymatic activity than the control group and the antibodies weakened the enzymatic activity of SjTGR in vitro, too. It implies that the high-level antibodies may contribute to the protective effects. PMID:23509820

State–Space Forecasting of Schistosoma haematobium Time-Series in Niono, Mali

PubMed Central

Medina, Daniel C.; Findley, Sally E.; Doumbia, Seydou

2008-01-01

Background Much of the developing world, particularly sub-Saharan Africa, exhibits high levels of morbidity and mortality associated with infectious diseases. The incidence of Schistosoma sp.—which are neglected tropical diseases exposing and infecting more than 500 and 200 million individuals in 77 countries, respectively—is rising because of 1) numerous irrigation and hydro-electric projects, 2) steady shifts from nomadic to sedentary existence, and 3) ineffective control programs. Notwithstanding the colossal scope of these parasitic infections, less than 0.5% of Schistosoma sp. investigations have attempted to predict their spatial and or temporal distributions. Undoubtedly, public health programs in developing countries could benefit from parsimonious forecasting and early warning systems to enhance management of these parasitic diseases. Methodology/Principal Findings In this longitudinal retrospective (01/1996–06/2004) investigation, the Schistosoma haematobium time-series for the district of Niono, Mali, was fitted with general-purpose exponential smoothing methods to generate contemporaneous on-line forecasts. These methods, which are encapsulated within a state–space framework, accommodate seasonal and inter-annual time-series fluctuations. Mean absolute percentage error values were circa 25% for 1- to 5-month horizon forecasts. Conclusions/Significance The exponential smoothing state–space framework employed herein produced reasonably accurate forecasts for this time-series, which reflects the incidence of S. haematobium–induced terminal hematuria. It obliquely captured prior non-linear interactions between disease dynamics and exogenous covariates (e.g., climate, irrigation, and public health interventions), thus obviating the need for more complex forecasting methods in the district of Niono, Mali. Therefore, this framework could assist with managing and assessing S. haematobium transmission and intervention impact, respectively, in this

Accuracy of Mobile Phone and Handheld Light Microscopy for the Diagnosis of Schistosomiasis and Intestinal Protozoa Infections in Côte d’Ivoire

PubMed Central

Coulibaly, Jean T.; Ouattara, Mamadou; D’Ambrosio, Michael V.; Fletcher, Daniel A.; Keiser, Jennifer; Utzinger, Jürg; N’Goran, Eliézer K.

2016-01-01

Background Handheld light microscopy using compact optics and mobile phones may improve the quality of health care in resource-constrained settings by enabling access to prompt and accurate diagnosis. Methodology Laboratory technicians were trained to operate two handheld diagnostic devices (Newton Nm1 microscope and a clip-on version of the mobile phone-based CellScope). The accuracy of these devices was compared to conventional light microscopy for the diagnosis of Schistosoma haematobium, S. mansoni, and intestinal protozoa infection in a community-based survey in rural Côte d’Ivoire. One slide of 10 ml filtered urine and a single Kato-Katz thick smear from 226 individuals were subjected to the Newton Nm1 microscope and CellScope for detection of Schistosoma eggs and compared to conventional microscopy. Additionally, 121 sodium acetate-acetic acid-formalin (SAF)-fixed stool samples were examined by the Newton Nm1 microscope and compared to conventional microscopy for the diagnosis of intestinal protozoa. Principal Findings The prevalence of S. haematobium, S. mansoni, Giardia intestinalis, and Entamoeba histolytica/E. dispar, as determined by conventional microscopy, was 39.8%, 5.3%, 20.7%, and 4.9%, respectively. The Newton Nm1 microscope had diagnostic sensitivities for S. mansoni and S. haematobium infection of 91.7% (95% confidence interval (CI) 59.8–99.6%) and 81.1% (95% CI 71.2–88.3%), respectively, and specificities of 99.5% (95% CI 97.0–100%) and 97.1% (95% CI 92.2–99.1%), respectively. The CellScope demonstrated sensitivities for S. mansoni and S. haematobium of 50.0% (95% CI 25.4–74.6%) and 35.6% (95% CI 25.9–46.4%), respectively, and specificities of 99.5% (95% CI 97.0–100%) and 100% (95% CI 86.7–100%), respectively. For G. intestinalis and E. histolytica/E. dispar, the Newton Nm1 microscope had sensitivity of 84.0% (95% CI 63.1–94.7%) and 83.3% (95% CI 36.5–99.1%), respectively, and 100% specificity. Conclusions

Accuracy of Mobile Phone and Handheld Light Microscopy for the Diagnosis of Schistosomiasis and Intestinal Protozoa Infections in Côte d'Ivoire.

PubMed

Coulibaly, Jean T; Ouattara, Mamadou; D'Ambrosio, Michael V; Fletcher, Daniel A; Keiser, Jennifer; Utzinger, Jürg; N'Goran, Eliézer K; Andrews, Jason R; Bogoch, Isaac I

2016-06-01

Handheld light microscopy using compact optics and mobile phones may improve the quality of health care in resource-constrained settings by enabling access to prompt and accurate diagnosis. Laboratory technicians were trained to operate two handheld diagnostic devices (Newton Nm1 microscope and a clip-on version of the mobile phone-based CellScope). The accuracy of these devices was compared to conventional light microscopy for the diagnosis of Schistosoma haematobium, S. mansoni, and intestinal protozoa infection in a community-based survey in rural Côte d'Ivoire. One slide of 10 ml filtered urine and a single Kato-Katz thick smear from 226 individuals were subjected to the Newton Nm1 microscope and CellScope for detection of Schistosoma eggs and compared to conventional microscopy. Additionally, 121 sodium acetate-acetic acid-formalin (SAF)-fixed stool samples were examined by the Newton Nm1 microscope and compared to conventional microscopy for the diagnosis of intestinal protozoa. The prevalence of S. haematobium, S. mansoni, Giardia intestinalis, and Entamoeba histolytica/E. dispar, as determined by conventional microscopy, was 39.8%, 5.3%, 20.7%, and 4.9%, respectively. The Newton Nm1 microscope had diagnostic sensitivities for S. mansoni and S. haematobium infection of 91.7% (95% confidence interval (CI) 59.8-99.6%) and 81.1% (95% CI 71.2-88.3%), respectively, and specificities of 99.5% (95% CI 97.0-100%) and 97.1% (95% CI 92.2-99.1%), respectively. The CellScope demonstrated sensitivities for S. mansoni and S. haematobium of 50.0% (95% CI 25.4-74.6%) and 35.6% (95% CI 25.9-46.4%), respectively, and specificities of 99.5% (95% CI 97.0-100%) and 100% (95% CI 86.7-100%), respectively. For G. intestinalis and E. histolytica/E. dispar, the Newton Nm1 microscope had sensitivity of 84.0% (95% CI 63.1-94.7%) and 83.3% (95% CI 36.5-99.1%), respectively, and 100% specificity. Handheld diagnostic devices can be employed in community-based surveys in resource

Prospective European-wide multicentre study on a blood based real-time PCR for the diagnosis of acute schistosomiasis.

PubMed

Wichmann, Dominic; Poppert, Sven; Von Thien, Heidrun; Clerinx, Joannes; Dieckmann, Sebastian; Jensenius, Mogens; Parola, Philippe; Richter, Joachim; Schunk, Mirjam; Stich, August; Zanger, Philipp; Burchard, Gerd D; Tannich, Egbert

2013-01-30

Acute schistosomiasis constitutes a rare but serious condition in individuals experiencing their first prepatent Schistosoma infection. To circumvent costly and time-consuming diagnostics, an early and rapid diagnosis is required. So far, classic diagnostic tools such as parasite microscopy or serology lack considerable sensitivity at this early stage of Schistosoma infection. To validate the use of a blood based real-time polymerase chain reaction (PCR) test for the detection of Schistosoma DNA in patients with acute schistosomiasis who acquired their infection in various endemic regions we conducted a European-wide prospective study in 11 centres specialized in travel medicine and tropical medicine. Patients with a history of recent travelling to schistosomiasis endemic regions and freshwater contacts, an episode of fever (body temperature ≥38.5°C) and an absolute or relative eosinophil count of ≥700/μl or 10%, were eligible for participation. PCR testing with DNA extracted from serum was compared with results from serology and microscopy. Of the 38 patients with acute schistosomiasis included into the study, PCR detected Schistosoma DNA in 35 patients at initial presentation (sensitivity 92%). In contrast, sensitivity of serology (enzyme immunoassay and/or immunofluorescence assay) or parasite microscopy was only 70% and 24%, respectively. For the early diagnosis of acute schistosomiasis, real-time PCR for the detection of schistosoma DNA in serum is more sensitive than classic diagnostic tools such as serology or microscopy, irrespective of the region of infection. Generalization of the results to all Schistosoma species may be difficult as in the study presented here only eggs of S. mansoni were detected by microscopy. A minimum amount of two millilitre of serum is required for sufficient diagnostic accuracy.

Cell Death and Reproductive Regression in Female Schistosoma mansoni

PubMed Central

Galanti, Sarah E.; Huang, Stanley Ching-Cheng; Pearce, Edward J.

2012-01-01

The vitellarium is a highly proliferative organ, producing cells which are incorporated along with a fertilized ovum into the schistosome egg. Vitellarial growth fails to occur in virgin female schistosomes in single sex (female-only) infections, and involution of this tissue, which is accompanied by physical shrinkage of the entire worm, occurs when mature females sexually regress upon removal from their male partners. We have found that upon removal from their hosts into tissue culture, female parasites regress whether they are mated or not, but that cessation of egg production and a decline in expression of the vitelline gene p14 is delayed by mating. We used BrdU labeling to investigate whether there was a loss of proliferation in the vittelarium that might account for regression and found that the proliferation rate declined equally in paired and singled females once placed into culture. However, TUNEL staining and Caspase 3 activity measurements indicate that the loss of vitrellarial cellularity associated with regression is associated with profound apoptotic vitelline cell death, which is not apparent in the vitellaria of paired females immediately ex vivo, and which develops in vitro regardless of whether males are present or not. Furthermore, primordial vitellaria in virgin females have a high frequency of apoptotic cells but are characterized by a proliferation rate that is indistinguishable from that in fully developed vitellaria in mature paired females. Taken together, our data suggest that the vitelline proliferation rate is independent of pairing status. In contrast, the survival of vitelline cells, and therefore the development of the vitellarium, is highly male-dependent. Both processes are negatively affected by removal from the host regardless of whether male worms are present or not, and are unsustainable using standard tissue culture approaches. PMID:22363825

Epidemiological Interactions between Urogenital and Intestinal Human Schistosomiasis in the Context of Praziquantel Treatment across Three West African Countries

PubMed Central

Knowles, Sarah C. L.; Webster, Bonnie L.; Garba, Amadou; Sacko, Moussa; Diaw, Oumar T.; Fenwick, Alan; Rollinson, David; Webster, Joanne P.

2015-01-01

Background In many parts of sub-Saharan Africa, urogenital and intestinal schistosomiasis co-occur, and mixed species infections containing both Schistosoma haematobium and S. mansoni can be common. During co-infection, interactions between these two species are possible, yet the extent to which such interactions influence disease dynamics or the outcome of control efforts remains poorly understood. Methodology/Principal Findings Here we analyse epidemiological data from three West African countries co-endemic for urogenital and intestinal schistosomiasis (Senegal, Niger and Mali) to test whether the impact of praziquantel (PZQ) treatment, subsequent levels of re-infection or long-term infection dynamics are altered by co-infection. In all countries, positive associations between the two species prevailed at baseline: infection by one species tended to predict infection intensity for the other, with the strength of association varying across sites. Encouragingly, we found little evidence that co-infection influenced PZQ efficacy: species-specific egg reduction rates (ERR) and cure rates (CR) did not differ significantly with co-infection, and variation in treatment success was largely geographical. In Senegal, despite positive associations at baseline, children with S. mansoni co-infection at the time of treatment were less intensely re-infected by S. haematobium than those with single infections, suggesting competition between the species may occur post-treatment. Furthermore, the proportion of schistosome infections attributable to S. mansoni increased over time in all three countries examined. Conclusions/Significance These findings suggest that while co-infection between urinary and intestinal schistosomes may not directly affect PZQ treatment efficacy, competitive interspecific interactions may influence epidemiological patterns of re-infection post-treatment. While re-infection patterns differed most strongly according to geographic location, interspecific

Serine Proteases of Parasitic Helminths

PubMed Central

Yang, Yong; Wen, Yun jun; Cai, Ya Nan; Vallée, Isabelle; Boireau, Pascal; Liu, Ming Yuan; Cheng, Shi Peng

2015-01-01

Serine proteases form one of the most important families of enzymes and perform significant functions in a broad range of biological processes, such as intra- and extracellular protein metabolism, digestion, blood coagulation, regulation of development, and fertilization. A number of serine proteases have been identified in parasitic helminths that have putative roles in parasite development and nutrition, host tissues and cell invasion, anticoagulation, and immune evasion. In this review, we described the serine proteases that have been identified in parasitic helminths, including nematodes (Trichinella spiralis, T. pseudospiralis, Trichuris muris, Anisakis simplex, Ascaris suum, Onchocerca volvulus, O. lienalis, Brugia malayi, Ancylostoma caninum, and Steinernema carpocapsae), cestodes (Spirometra mansoni, Echinococcus granulosus, and Schistocephalus solidus), and trematodes (Fasciola hepatica, F. gigantica, and Schistosoma mansoni). Moreover, the possible biological functions of these serine proteases in the endogenous biological phenomena of these parasites and in the host-parasite interaction were also discussed. PMID:25748703

Variation in the expression of macrophage Fc epsilon receptors in relation to experimental rat schistosome infection.

PubMed

Pestel, J; Joseph, M; Dessaint, J P; Capron, A

1988-01-01

The relationship between IgE and rat peritoneal macrophages during the course of Schistosoma mansoni infection was examined. Immune macrophages exhibited an IgE-dependent schistosomulicidal activity mainly between the 5th and the 7th weeks. At this period the percentages of anti-IgE rosettes whose variations appeared consecutive to the variations in the serum IgE level were higher. Following incubation in a serum-free medium immune macrophages could release membrane-associated IgE, to a certain extent, and consequently formed rosettes with IgE-coated erythrocytes, indicating the existence of Fc epsilon receptors. Thus, in terms of rosettes, their number varied in the course of the disease. In fact IgE-rich serum (i.e. at day 42) as IgE molecules could induce this macrophage Fc epsilon receptor. Moreover when transferred to syngeneic rats in association with parasite-specific IgE Fc epsilon R2+ macrophages led to some protection against challenge infection. All the data reported here emphasize the determining role of macrophages and IgE in immunity to schistosomiasis.

Circulating antigen tests and urine reagent strips for diagnosis of active schistosomiasis in endemic areas.

PubMed

Ochodo, Eleanor A; Gopalakrishna, Gowri; Spek, Bea; Reitsma, Johannes B; van Lieshout, Lisette; Polman, Katja; Lamberton, Poppy; Bossuyt, Patrick M M; Leeflang, Mariska M G

2015-03-11

Point-of-care (POC) tests for diagnosing schistosomiasis include tests based on circulating antigen detection and urine reagent strip tests. If they had sufficient diagnostic accuracy they could replace conventional microscopy as they provide a quicker answer and are easier to use. To summarise the diagnostic accuracy of: a) urine reagent strip tests in detecting active Schistosoma haematobium infection, with microscopy as the reference standard; and b) circulating antigen tests for detecting active Schistosoma infection in geographical regions endemic for Schistosoma mansoni or S. haematobium or both, with microscopy as the reference standard. We searched the electronic databases MEDLINE, EMBASE, BIOSIS, MEDION, and Health Technology Assessment (HTA) without language restriction up to 30 June 2014. We included studies that used microscopy as the reference standard: for S. haematobium, microscopy of urine prepared by filtration, centrifugation, or sedimentation methods; and for S. mansoni, microscopy of stool by Kato-Katz thick smear. We included studies on participants residing in endemic areas only. Two review authors independently extracted data, assessed quality of the data using QUADAS-2, and performed meta-analysis where appropriate. Using the variability of test thresholds, we used the hierarchical summary receiver operating characteristic (HSROC) model for all eligible tests (except the circulating cathodic antigen (CCA) POC for S. mansoni, where the bivariate random-effects model was more appropriate). We investigated heterogeneity, and carried out indirect comparisons where data were sufficient. Results for sensitivity and specificity are presented as percentages with 95% confidence intervals (CI). We included 90 studies; 88 from field settings in Africa. The median S. haematobium infection prevalence was 41% (range 1% to 89%) and 36% for S. mansoni (range 8% to 95%). Study design and conduct were poorly reported against current standards. Tests for S

Prevalence of Schistosomes and Soil-Transmitted Helminths and Morbidity Associated with Schistosomiasis among Adult Population in Lake Victoria Basin, Tanzania.

PubMed

Siza, Julius E; Kaatano, Godfrey M; Chai, Jong-Yil; Eom, Keeseon S; Rim, Han-Jong; Yong, Tai-Soon; Min, Duk-Young; Chang, Su Young; Ko, Yunsuk; Changalucha, John M

2015-10-01

The objective of this study was to carry out a community survey on schistosomiais and soil-transmitted helminth (STH) infections in order to suggest feasible and effective intervention strategies in Lake Victoria basin, Tanzania. A total of 37 communities selected from 23 districts of the 4 regions in the Lake Victoria basin of Tanzania were involved in the study. From each of the selected locality, 50 adult community members, 25 males and 25 females, were recruited for the study. Each study participant was requested to submit stool and urine specimens. From each stool specimen, duplicate Kato-Katz thick smears were prepared and microscopically examined for Schistosoma mansoni and STH eggs. Urine specimens were processed by the filtration technique and microscopically examined for Schistosoma haematobium eggs. Ultrasound examination for morbidity due to schistosomiasis was performed. Mass treatment was done using praziquantel and albendazole for schistosome and STHs infections, respectively. Out of 1,606 adults who provided stool specimens, 199 (12.4%) were positive for S. mansoni, 349 (21.7%) for hookworms, 133 (8.3%) for Ascaris lumbricoides, and 33 (2.0%) for Trichuris trichiura. Out of 1,400 participants who provided urine specimens, 25 (1.8%) were positive for S. haematobium eggs. Because of the co-endemicity of these afflictions and their impact on vulnerable population groups, the helminthiasis could be simultaneously treated with 2 drugs, praziquantel for schistosomiasis and albendazole for STHs.

Schistosoma japonicum: susceptibility of neonate mice born to infected and noninfected mothers following subsequent challenge.

PubMed

Zhao, F; Huang, X; Hou, X; Deng, Y; Wu, M; Guan, F; Liu, W; Li, Y; Lei, J

2013-01-01

This study was to investigate the differences between neonate mice born to Schistosoma japonicum-infected mothers and those born to noninfected mothers in subsequent challenge. The intensity of infection (evidenced by worm burden and liver egg burden) and liver immunopathology (number and size of liver granulomas) were significantly reduced in neonates from infected mothers (I.M.) compared with neonates from noninfected mothers (N.M.). Anti-soluble worm antigen of S. japonicum (SWA) IgG could be detected in sera of neonates from I.M. (N.N./I.M.) at 1 week after delivery, remained a plateau for 2 weeks and gradually decreased until 8 weeks of age. Parasite-specific IgM was not detected in sera from N.N./I.M. at any time after delivery. At 6 weeks after infection, the level of anti-SWA IgG in infected neonates from I.M. (I.N./I.M.) was significantly higher than that of infected neonates from N.M. (I.N./N.M.). In addition, production of IFN-γ, IL-12 and TGF-β by cultured splenocytes from I.N./I.M. was significantly increased, while the level of IL-4 was significantly decreased when compared to those from I.N./N.M.. These data demonstrate that congenital exposure to schistosomiasis japonica may render neonatal mice born to I.M. less susceptible to subsequent challenge and result in down-regulation of both infection intensity and immunopathology. © 2013 John Wiley & Sons Ltd.

Detection of Schistosoma Antibodies and exploration of associated factors among local residents around Inlay Lake, Southern Shan State, Myanmar.

PubMed

Soe, Htin Zaw; Oo, Cho Cho; Myat, Tin Ohn; Maung, Nay Soe

2017-03-01

Schistosomiasis is a chronic parasitic disease caused by blood flukes (trematode worms) of the genus Schistosoma. Its transmission has been reported in 78 countries affecting at least 258 million people world-wide. It was documented that S. japonicum species was prevalent in Shan State, Myanmar, but the serological study was not conducted yet. General objective of the present study was to detect schistosoma antibodies and explore associated factors among local residents living around Inlay Lake, Nyaung Shwe Township, and Southern Shan State, Myanmar. An exploratory and cross-sectional analytic study was conducted among local residents (n = 315) in selected rural health center (RHC) areas from December 2012 through June 2013. The participants were interviewed with pretested semi-structured questionnaires and their blood samples (serum) were tested using Schistosomiasis Serology Microwell ELISA test kits (sensitivity 100% and specificity 85%) which detected IgG antibodies but could not distinguish between a new and past infection. Data collected were analysed by SPSS software 16.0 and associations of variables were determined by Chi-squared test with a significant level set at 0.05. Schistosoma seroprevalence (IgG) in study area was found to be 23.8% (95% CI: 18.8-28.8%). The present study is the first and foremost study producing serological evidence of schistosoma infection-one of the neglected tropical diseases-in local people of Myanmar. The factors significantly associated with seropositivity were being male [OR = 2.6 (95% CI: 1.5-4.49), P < 0.001], residence [OR = 3.41 (95% CI: 1.6-7.3), P < 0.05 for Khaung Daing vs. Min Chaung] and education levels [OR = 4.5 (95% CI: 1.18-17.16), P < 0.05 for illiterate/3Rs level vs. high/graduate and OR = 3.16 (95% CI: 1.26-7.93), P < 0.05 for primary/middle level vs. high/graduate] all factors classically associated with risk of schistosoma infection. None of the behavioural factors tested

Bovine lactoferricin, an antimicrobial peptide, is anti-inflammatory and anti-catabolic in human articular cartilage and synovium

PubMed Central

Yan, Dongyao; Chen, Di; Shen, Jie; Xiao, Guozhi; van Wijnen, Andre J; Im, Hee-Jeong

2012-01-01

Bovine lactoferricin (LfcinB) is a multi-functional peptide derived from proteolytic cleavage of bovine lactoferrin. LfcinB was found to antagonize the biological effects mediated by angiogenic growth factors such as vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF-2) in endothelial cells. However, the effect of LfcinB on human articular cartilage remained unknown. Here, our findings demonstrate that LfcinB restored the proteoglycan loss promoted by catabolic factors (interleukin-1 β) IL-1β and FGF-2 in vitro and ex vivo. Mechanistically, LfcinB attenuated the effects of IL-1β and FGF-2 on the expression of cartilage-degrading enzymes (MMP-1, MMP-3, and MMP-13), destructive cytokines (IL-1β and IL-6), and inflammatory mediators (iNOS and TLR2). LfcinB induced protective cytokine expression (IL-4 and IL-10), and downregulated aggrecanase basal expression. LfcinB specifically activated ERK MAPK and Akt signaling pathways, which may account for its anti-inflammatory activity. We also revealed that LfcinB exerted similar protective effects on human synovial fibroblasts challenged by IL-1β, with minimal cytotoxicity. Collectively, our results suggest that LfcinB possesses potent anti-catabolic and anti-inflammatory bioactivities in human articular tissues, and may be utilized for the prevention and/or treatment of OA in the future. PMID:22740381

Evaluation of Loop-Mediated Isothermal Amplification Suitable for Molecular Monitoring of Schistosome-Infected Snails in Field Laboratories

PubMed Central

Hamburger, Joseph; Abbasi, Ibrahim; Kariuki, Curtis; Wanjala, Atsabina; Mzungu, Elton; Mungai, Peter; Muchiri, Eric; King, Charles H.

2013-01-01

We previously described loop-mediated isothermal amplification (LAMP) for detection of Schistosoma haematobium and S. mansoni DNA in infected snails. In the present study, we adapted the LAMP assay for application in field laboratories in schistosomiasis-endemic areas. Isolation of DNA was simplified by blotting snail tissue (extracted in NaOH/sodium dodecyl sulfate) onto treated membranes, which enabled preservation at ambient temperatures. A ready-mix of LAMP reagents, suitable for shipment at ambient temperature and storage in minimal refrigeration, was used. Local survey teams without experience in molecular biology acquired operational expertise with this test within a few hours. Fifty-four field-caught snails were tested locally by LAMP and 59 were tested at similar conditions in Jerusalem. The LAMP results were consistent with those of a polymerase chain reaction; only four samples showed false-negative results. Results indicate that LAMP assays are suitable for detection of S. haematobium and S. mansoni in low-technology parasitology laboratories in which schistosomiasis elimination activities are undertaken. PMID:23208875

Current status of schistosomiasis and soil-transmitted helminthiasis in Beyla and Macenta Prefectures, Forest Guinea.

PubMed

Hodges, Mary; Koroma, Manso M; Baldé, Mamadou S; Turay, Hamid; Fofanah, Ibrahim; Divall, Mark J; Winkler, Mirko S; Zhang, Yaobi

2011-11-01

A cross-sectional survey was undertaken in children aged 9-14 years in Beyla and Macenta Prefectures, Forest Guinea. Stool samples were examined by Kato-Katz and urine samples were examined by the centrifugation method. The overall prevalence and intensity of infection was 66.2% and 462.4 eggs per gram of faeces (epg) for Schistosoma mansoni, 21.0% and 17.8 eggs per 10ml of urine for S. haematobium, 51.2% and 507.5 epg for hookworm, 8.1% and 89.1 epg for Ascaris lumbricoides and 2.4% and 16.7 epg for Trichuris trichiura. The overall prevalence of schistosomiasis (S. mansoni and/or S. haematobium) was 70.7%. The prevalence of schistosomiasis was similar to those reported in the 1990s in the region; however, the prevalence of soil-transmitted helminths has since fallen. These findings illustrate the need for schistosomiasis control in Guinea. Copyright © 2011 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.

Assessment of schistosomiasis in the Dominican Republic.