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Sample records for human parasite schistosoma

  1. Adult somatic stem cells in the human parasite, Schistosoma mansoni

    PubMed Central

    Collins, James J.; Wang, Bo; Lambrus, Bramwell G.; Tharp, Marla; Iyer, Harini; Newmark, Phillip A.

    2013-01-01

    Summary Schistosomiasis is among the most prevalent human parasitic diseases, affecting more than 200 million people worldwide1. The etiological agents of this disease are trematode flatworms (Schistosoma) that live and lay eggs within the vasculature of the host. These eggs lodge in host tissues, causing inflammatory responses that are the primary cause of morbidity. Because these parasites can live and reproduce within human hosts for decades2, elucidating the mechanisms that promote their longevity is of fundamental importance. Although adult pluripotent stem cells, called neoblasts, drive long-term homeostatic tissue maintenance in long-lived free-living flatworms3,4 (e.g., planarians), and neoblast-like cells have been described in some parasitic tapeworms5, little is known about whether similar cell types exist in any trematode species. Here, we describe a population of neoblast-like cells in the trematode Schistosoma mansoni. These cells resemble planarian neoblasts morphologically and share their ability to proliferate and differentiate into derivatives of multiple germ layers. Capitalizing on available genomic resources6,7 and RNAseq-based gene expression profiling, we find that these schistosome neoblast-like cells express a fibroblast growth factor receptor ortholog. Using RNA interference we demonstrate that this gene is required for the maintenance of these neoblast-like cells. Our observations suggest that adaptation of developmental strategies shared by free-living ancestors to modern-day schistosomes likely contributed to the success of these animals as long-lived obligate parasites. We expect that future studies deciphering the function of these neoblast-like cells will have important implications for understanding the biology of these devastating parasites. PMID:23426263

  2. Whole genome resequencing of the human parasite Schistosoma mansoni reveals population history and effects of selection

    PubMed Central

    Crellen, Thomas; Allan, Fiona; David, Sophia; Durrant, Caroline; Huckvale, Thomas; Holroyd, Nancy; Emery, Aidan M.; Rollinson, David; Aanensen, David M.; Berriman, Matthew; Webster, Joanne P.; Cotton, James A.

    2016-01-01

    Schistosoma mansoni is a parasitic fluke that infects millions of people in the developing world. This study presents the first application of population genomics to S. mansoni based on high-coverage resequencing data from 10 global isolates and an isolate of the closely-related Schistosoma rodhaini, which infects rodents. Using population genetic tests, we document genes under directional and balancing selection in S. mansoni that may facilitate adaptation to the human host. Coalescence modeling reveals the speciation of S. mansoni and S. rodhaini as 107.5–147.6KYA, a period which overlaps with the earliest archaeological evidence for fishing in Africa. Our results indicate that S. mansoni originated in East Africa and experienced a decline in effective population size 20–90KYA, before dispersing across the continent during the Holocene. In addition, we find strong evidence that S. mansoni migrated to the New World with the 16–19th Century Atlantic Slave Trade. PMID:26879532

  3. Whole genome resequencing of the human parasite Schistosoma mansoni reveals population history and effects of selection.

    PubMed

    Crellen, Thomas; Allan, Fiona; David, Sophia; Durrant, Caroline; Huckvale, Thomas; Holroyd, Nancy; Emery, Aidan M; Rollinson, David; Aanensen, David M; Berriman, Matthew; Webster, Joanne P; Cotton, James A

    2016-01-01

    Schistosoma mansoni is a parasitic fluke that infects millions of people in the developing world. This study presents the first application of population genomics to S. mansoni based on high-coverage resequencing data from 10 global isolates and an isolate of the closely-related Schistosoma rodhaini, which infects rodents. Using population genetic tests, we document genes under directional and balancing selection in S. mansoni that may facilitate adaptation to the human host. Coalescence modeling reveals the speciation of S. mansoni and S. rodhaini as 107.5-147.6KYA, a period which overlaps with the earliest archaeological evidence for fishing in Africa. Our results indicate that S. mansoni originated in East Africa and experienced a decline in effective population size 20-90KYA, before dispersing across the continent during the Holocene. In addition, we find strong evidence that S. mansoni migrated to the New World with the 16-19th Century Atlantic Slave Trade. PMID:26879532

  4. A catecholamine transporter from the human parasite Schistosoma mansoni with low affinity for psychostimulants

    PubMed Central

    Larsen, Mads B.; Fontana, Andréia C. K.; Magalhães, Lizandra G.; Rodrigues, Vanderlei; Mortensen, Ole V.

    2011-01-01

    The trematode Schistosoma mansoni is the primary cause of schistosomiasis, a devastating neglected tropical disease that affects 200 million individuals. Identifying novel therapeutic targets for the treatment of schistosomiasis is therefore of great public interest. The catecholamines norepinephrine (NE) and dopamine (DA) are essential for the survival of the parasite as they cause muscular relaxation and a lengthening in the parasite and thereby control movement. Here we characterize a novel dopamine/norepinephrine transporter (SmDAT) gene transcript, from Schistosoma mansoni. The SmDAT is expressed in the adult form and in the sporocyst form (infected snails) of the parasite, and also in the egg and miracidium stage. It is absent in the cercaria stage but curiously a transcript missing the exon encoding transmembrane domain 8 was identified in this stage. Heterologous expression of the cDNA in mammalian cells resulted in saturable, dopamine transport activity with an apparent affinity for dopamine comparable to that of the human dopamine transporter. Efflux experiments reveal notably higher substrate selectivity compared with its mammalian counterparts as amphetamine is a much less potent efflux elicitor against SmDAT compared to the human DAT. Pharmacological characterization of the SmDAT revealed that most human DAT inhibitors including psychostimulants such as cocaine were significantly less potent in inhibiting SmDAT. Like DATs from other simpler organisms the pharmacology for SmDAT was more similar to the human norepinephrine transporter. We were not able to identify other dopamine transporting carriers within the completed parasite genome and we hypothesize that the SmDAT is the only catecholamine transporter in the parasite and could be responsible for not only clearing DA but also NE. PMID:21251927

  5. Reconstructing Colonization Dynamics of the Human Parasite Schistosoma mansoni following Anthropogenic Environmental Changes in Northwest Senegal

    PubMed Central

    Van den Broeck, Frederik; Maes, Gregory E.; Larmuseau, Maarten H. D.; Rollinson, David; Sy, Ibrahima; Faye, Djibril; Volckaert, Filip A. M.; Polman, Katja; Huyse, Tine

    2015-01-01

    Background Anthropogenic environmental changes may lead to ecosystem destabilization and the unintentional colonization of new habitats by parasite populations. A remarkable example is the outbreak of intestinal schistosomiasis in Northwest Senegal following the construction of two dams in the ‘80s. While many studies have investigated the epidemiological, immunological and geographical patterns of Schistosoma mansoni infections in this region, little is known about its colonization history. Methodology/Principal Findings Parasites were collected at several time points after the disease outbreak and genotyped using a 420 bp fragment of the mitochondrial cytochrome c oxidase subunit 1 gene (cox1) and nine nuclear DNA microsatellite markers. Phylogeographic and population genetic analyses revealed the presence of (i) many genetically different haplotypes at the non-recombining mitochondrial marker and (ii) one homogenous S. mansoni genetic group at the recombining microsatellite markers. These results suggest that the S. mansoni population in Northwest Senegal was triggered by intraspecific hybridization (i.e. admixture) between parasites that were introduced from different regions. This would comply with the extensive immigration of infected seasonal agricultural workers from neighboring regions in Senegal, Mauritania and Mali. The spatial and temporal stability of the established S. mansoni population suggests a swift local adaptation of the parasite to the local intermediate snail host Biomphalaria pfeifferi at the onset of the epidemic. Conclusions/Significance Our results show that S. mansoni parasites are very successful in colonizing new areas without significant loss of genetic diversity. Maintaining high levels of diversity guarantees the adaptive potential of these parasites to cope with selective pressures such as drug treatment, which might complicate efforts to control the disease. PMID:26275049

  6. Curupira-1 and Curupira-2, two novel Mutator-like DNA transposons from the genomes of human parasites Schistosoma mansoni and Schistosoma japonicum.

    PubMed

    Jacinto, Daniele S; Muniz, Heloisa Dos Santos; Venancio, Thiago M; Wilson, R Alan; Verjovski-Almeida, Sergio; Demarco, Ricardo

    2011-08-01

    Transposons of the Mutator superfamily have been widely described in plants, but only recently have metazoan organisms been shown to harbour them. In this work we describe novel Mutator superfamily transposons from the genomes of the human parasites Schistosoma mansoni and S. japonicum, which we name Curupira-1 and Curupira-2. Curupira elements do not have Terminal Inverted Repeats (TIRs) at their extremities and generate Target Site Duplications (TSDs) of 9 base pairs. Curupira-2 transposons code for a conserved transposase and SWIM zinc finger domains, while Curupira-1 elements comprise these same domains plus a WRKY zinc finger. Alignment of transcript sequences from both elements back to the genomes indicates that they are subject to splicing to produce mature transcripts. Phylogenetic analyses indicate that these transposons represent a new lineage of metazoan Mutator-like elements with characteristics that are distinct from the recently described Phantom elements. Description of these novel schistosome transposons provides new insights in the evolution of transposable elements in schistosomes. PMID:21756422

  7. Saci-1, -2, and -3 and Perere, Four Novel Retrotransposons with High Transcriptional Activities from the Human Parasite Schistosoma mansoni

    PubMed Central

    DeMarco, Ricardo; Kowaltowski, Andre T.; Machado, Abimael A.; Soares, M. Bento; Gargioni, Cybele; Kawano, Toshie; Rodrigues, Vanderlei; Madeira, Alda M. B. N.; Wilson, R. Alan; Menck, Carlos F. M.; Setubal, João C.; Dias-Neto, Emmanuel; Leite, Luciana C. C.; Verjovski-Almeida, Sergio

    2004-01-01

    Using the data set of 180,000 expressed sequence tags (ESTs) of the blood fluke Schistosoma mansoni generated recently by our group, we identified three novel long-terminal-repeat (LTR)- and one novel non-LTR-expressed retrotransposon, named Saci-1, -2, and -3 and Perere, respectively. Full-length sequences were reconstructed from ESTs and have deduced open reading frames (ORFs) with several uncorrupted features, characterizing them as possible active retrotransposons of different known transposon families. Alignment of reconstructed sequences to available preliminary genome sequence data confirmed the overall structure of the transposons. The frequency of sequenced transposon transcripts in cercariae was 14% of all transcripts from that stage, twofold higher than that in schistosomula and three- to fourfold higher than that in adults, eggs, miracidia, and germ balls. We show by Southern blot analysis, by EST annotation and tallying, and by counting transposon tags from a Social Analysis of Gene Expression library, that the four novel retrotransposons exhibit a 10- to 30-fold lower copy number in the genome and a 4- to 200-fold-higher transcriptional rate per copy than the four previously described S. mansoni retrotransposons. Such differences lead us to hypothesize that there are two different populations of retrotransposons in S. mansoni genome, occupying different niches in its ecology. Examples of retrotransposon fragment inserts were found into the 5′ and 3′ untranslated regions of four different S. mansoni target gene transcripts. The data presented here suggest a role for these elements in the dynamics of this complex human parasite genome. PMID:14990715

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

    SciTech Connect

    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 of 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.

  9. 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

  10. Glycomic Analysis of Life Stages of the Human Parasite Schistosoma mansoni Reveals Developmental Expression Profiles of Functional and Antigenic Glycan Motifs*

    PubMed Central

    Smit, Cornelis H.; van Diepen, Angela; Nguyen, D. Linh; Wuhrer, Manfred; Hoffmann, Karl F.; Deelder, André M.; Hokke, Cornelis H.

    2015-01-01

    Glycans present on glycoproteins and glycolipids of the major human parasite Schistosoma mansoni induce innate as well as adaptive immune responses in the host. To be able to study the molecular characteristics of schistosome infections it is therefore required to determine the expression profiles of glycans and antigenic glycan-motifs during a range of critical stages of the complex schistosome lifecycle. We performed a longitudinal profiling study covering schistosome glycosylation throughout worm- and egg-development using a mass spectrometry-based glycomics approach. Our study revealed that during worm development N-glycans with Galβ1–4(Fucα1–3)GlcNAc (LeX) and core-xylose motifs were rapidly lost after cercariae to schistosomula transformation, whereas GalNAcβ1–4GlcNAc (LDN)-motifs gradually became abundant and predominated in adult worms. LeX-motifs were present on glycolipids up to 2 weeks of schistosomula development, whereas glycolipids with mono- and multifucosylated LDN-motifs remained present up to the adult worm stage. In contrast, expression of complex O-glycans diminished to undetectable levels within days after transformation. During egg development, a rich diversity of N-glycans with fucosylated motifs was expressed, but with α3-core fucose and a high degree of multifucosylated antennae only in mature eggs and miracidia. N-glycan antennae were exclusively LDN-based in miracidia. O-glycans in the mature eggs were also diverse and contained LeX- and multifucosylated LDN, but none of these were associated with miracidia in which we detected only the Galβ1–3(Galβ1–6)GalNAc core glycan. Immature eggs also exhibited short O-glycan core structures only, suggesting that complex fucosylated O-glycans of schistosome eggs are derived primarily from glycoproteins produced by the subshell envelope in the developed egg. Lipid glycans with multifucosylated GlcNAc repeats were present throughout egg development, but with the longer highly

  11. Glycomic Analysis of Life Stages of the Human Parasite Schistosoma mansoni Reveals Developmental Expression Profiles of Functional and Antigenic Glycan Motifs.

    PubMed

    Smit, Cornelis H; van Diepen, Angela; Nguyen, D Linh; Wuhrer, Manfred; Hoffmann, Karl F; Deelder, André M; Hokke, Cornelis H

    2015-07-01

    Glycans present on glycoproteins and glycolipids of the major human parasite Schistosoma mansoni induce innate as well as adaptive immune responses in the host. To be able to study the molecular characteristics of schistosome infections it is therefore required to determine the expression profiles of glycans and antigenic glycan-motifs during a range of critical stages of the complex schistosome lifecycle. We performed a longitudinal profiling study covering schistosome glycosylation throughout worm- and egg-development using a mass spectrometry-based glycomics approach. Our study revealed that during worm development N-glycans with Galβ1-4(Fucα1-3)GlcNAc (LeX) and core-xylose motifs were rapidly lost after cercariae to schistosomula transformation, whereas GalNAcβ1-4GlcNAc (LDN)-motifs gradually became abundant and predominated in adult worms. LeX-motifs were present on glycolipids up to 2 weeks of schistosomula development, whereas glycolipids with mono- and multifucosylated LDN-motifs remained present up to the adult worm stage. In contrast, expression of complex O-glycans diminished to undetectable levels within days after transformation. During egg development, a rich diversity of N-glycans with fucosylated motifs was expressed, but with α3-core fucose and a high degree of multifucosylated antennae only in mature eggs and miracidia. N-glycan antennae were exclusively LDN-based in miracidia. O-glycans in the mature eggs were also diverse and contained LeX- and multifucosylated LDN, but none of these were associated with miracidia in which we detected only the Galβ1-3(Galβ1-6)GalNAc core glycan. Immature eggs also exhibited short O-glycan core structures only, suggesting that complex fucosylated O-glycans of schistosome eggs are derived primarily from glycoproteins produced by the subshell envelope in the developed egg. Lipid glycans with multifucosylated GlcNAc repeats were present throughout egg development, but with the longer highly fucosylated

  12. Carcinogenesis associated with parasites other than Schistosoma, Opisthorchis and Clonorchis: A systematic review.

    PubMed

    Machicado, Claudia; Marcos, Luis A

    2016-06-15

    Only three helminths (Schistosoma haematobium, Opisthorchis viverrini and Clonorchis sinensis) are directly associated with carcinogenesis in humans whereas the role of other parasites in cancer remains unclear. This study aimed to perform a systematic review to identify recent insights in the role of other parasite infections in carcinogenesis. We conducted systematic searches of MEDLINE and EMBASE on July 2015. Our primary outcome was the association between parasitic infections and carcinogenesis. Out of 1,266 studies, 19 were selected for detailed evaluation (eight for helminths and 11 for protozoa). The mechanisms of helminth-induced cancer included chronic inflammation, sustained proliferation, modulation of the host immune system, reprogramming of glucose metabolism and redox signaling, induction of genomic instability and destabilization of suppressor tumor proteins, stimulation of angiogenesis, resisting cell death, and activation of invasion and metastasis. In addition to the current knowledge, the following parasites were found in cancers or tumors: Echinococcus, Strongyloides, Fasciola, Heterakis, Platynosomum and Trichuris. Additional parasites were found in this systematic review that could potentially be associated with cancers or tumors but further evidence is needed to elaborate a cause-effect relationship. PMID:26840624

  13. Involvement of the Cytokine MIF in the Snail Host Immune Response to the Parasite Schistosoma mansoni

    PubMed Central

    Baeza Garcia, Alvaro; Pierce, Raymond J.; Gourbal, Benjamin; Werkmeister, Elisabeth; Colinet, Dominique; Reichhart, Jean-Marc; Dissous, Colette; Coustau, Christine

    2010-01-01

    We have identified and characterized a Macrophage Migration Inhibitory Factor (MIF) family member in the Lophotrochozoan invertebrate, Biomphalaria glabrata, the snail intermediate host of the human blood fluke Schistosoma mansoni. In mammals, MIF is a widely expressed pleiotropic cytokine with potent pro-inflammatory properties that controls cell functions such as gene expression, proliferation or apoptosis. Here we show that the MIF protein from B. glabrata (BgMIF) is expressed in circulating immune defense cells (hemocytes) of the snail as well as in the B. glabrata embryonic (Bge) cell line that has hemocyte-like features. Recombinant BgMIF (rBgMIF) induced cell proliferation and inhibited NO-dependent p53-mediated apoptosis in Bge cells. Moreover, knock-down of BgMIF expression in Bge cells interfered with the in vitro encapsulation of S. mansoni sporocysts. Furthermore, the in vivo knock-down of BgMIF prevented the changes in circulating hemocyte populations that occur in response to an infection by S. mansoni miracidia and led to a significant increase in the parasite burden of the snails. These results provide the first functional evidence that a MIF ortholog is involved in an invertebrate immune response towards a parasitic infection and highlight the importance of cytokines in invertebrate-parasite interactions. PMID:20886098

  14. Schistosoma mansoni: migration potential of normal and radiation attenuated parasites in naive guinea pigs

    SciTech Connect

    Kamiya, H.; McLaren, D.J.

    1987-02-01

    Compressed tissue autoradiography using (75Se)selenomethionine labelled parasites has been used to investigate the migration potential of normal and radiation attenuated cercariae of Schistosoma mansoni in naive guinea pigs. By Day 14 after infection. 44% of normal parasites were detected as reduced silver foci in the liver; this value corresponded well with the number of liver parasites recovered by retrograde perfusion of the hepatic portal system on Day 42 (42% of the challenge). In contrast, cercariae subjected to 50 krad of gamma irradiation failed to migrate out of the skin. The migration capacity of 20 krad irradiated parasites was less severely affected in that about half of the challenge parasites reached the lungs, but virtually none moved to the liver. These data are discussed in relation to the kinetics of immunity induced in guinea pigs by infection or vaccination with normal or radiation attenuated parasites.

  15. New Perspectives on Host-Parasite Interplay by Comparative Transcriptomic and Proteomic Analyses of Schistosoma japonicum

    PubMed Central

    Wang, Sheng-Yue; Cui, Shu-Jian; Chi, Ming; Yan, Qing; Wang, Xin-Rong; Song, Huai-Dong; Xu, Xue-Nian; Wang, Ju-Jun; Zhang, Xiang-Lin; Zhang, Xin; Wang, Zhi-Qin; Xue, Chun-Liang; Brindley, Paul J; McManus, Donald P; Yang, Peng-Yuan; Feng, Zheng; Chen, Zhu; Han, Ze-Guang

    2006-01-01

    Schistosomiasis remains a serious public health problem with an estimated 200 million people infected in 76 countries. Here we isolated ~ 8,400 potential protein-encoding cDNA contigs from Schistosoma japonicum after sequencing circa 84,000 expressed sequence tags. In tandem, we undertook a high-throughput proteomics approach to characterize the protein expression profiles of a number of developmental stages (cercariae, hepatic schistosomula, female and male adults, eggs, and miracidia) and tissues at the host-parasite interface (eggshell and tegument) by interrogating the protein database deduced from the contigs. Comparative analysis of these transcriptomic and proteomic data, the latter including 3,260 proteins with putative identities, revealed differential expression of genes among the various developmental stages and sexes of S. japonicum and localization of putative secretory and membrane antigens, enzymes, and other gene products on the adult tegument and eggshell, many of which displayed genetic polymorphisms. Numerous S. japonicum genes exhibited high levels of identity with those of their mammalian hosts, whereas many others appeared to be conserved only across the genus Schistosoma or Phylum Platyhelminthes. These findings are expected to provide new insights into the pathophysiology of schistosomiasis and for the development of improved interventions for disease control and will facilitate a more fundamental understanding of schistosome biology, evolution, and the host-parasite interplay. PMID:16617374

  16. 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

  17. Structural parameters, molecular properties, and biological evaluation of some terpenes targeting Schistosoma mansoni parasite.

    PubMed

    Mafud, Ana C; Silva, Marcos P N; Monteiro, Daniela C; Oliveira, Maria F; Resende, João G; Coelho, Mayara L; de Sousa, Damião P; Mendonça, Ronaldo Z; Pinto, Pedro L S; Freitas, Rivelilson M; Mascarenhas, Yvonne P; de Moraes, Josué

    2016-01-25

    The use of natural products has a long tradition in medicine, and they have proven to be an important source of lead compounds in the development of new drugs. Among the natural compounds, terpenoids present broad-spectrum activity against infective agents such as viruses, bacteria, fungi, protozoan and helminth parasites. In this study, we report a biological screening of 38 chemically characterized terpenes from different classes, which have a hydroxyl group connected by hydrophobic chain or an acceptor site, against the blood fluke Schistosoma mansoni, the parasite responsible for schistosomiasis mansoni. In vitro bioassays revealed that 3,7-dimethyl-1-octanol (dihydrocitronellol) (10) was the most active terpene (IC50 values of 13-52 μM) and, thus, we investigated its antischistosomal activity in greater detail. Confocal laser scanning microscopy revealed that compound 10 induced severe tegumental damage in adult schistosomes and a correlation between viability and tegumental changes was observed. Furthermore, we compared all the inactive compounds with dihydrocitronellol structurally by using shape and charge modeling. Lipophilicity (miLogP) and other molecular properties (e.g. molecular polar surface area, molecular electrostatic potential) were also calculated. From the 38 terpenes studied, compound 10 is the one with the greatest flexibility, with a sufficient apolar region by which it may interact in a hydrophobic active site. In conclusion, the integration of biological and chemical analysis indicates the potential of the terpene dihydrocitronellol as an antiparasitic agent. PMID:26697994

  18. The tegumental surface membranes of Schistosoma mansoni are enriched in parasite-specific phospholipid species.

    PubMed

    Retra, Kim; deWalick, Saskia; Schmitz, Marion; Yazdanbakhsh, Maria; Tielens, Aloysius G M; Brouwers, Jos F H M; van Hellemond, Jaap J

    2015-08-01

    The complex surface structure of adult Schistosoma mansoni, the tegument, is essential for survival of the parasite. This tegument is syncytial and is covered by two closely-apposed lipid bilayers that form the interactive surface with the host. In order to identify parasite-specific phospholipids present in the tegument, the species compositions of the major glycerophospholipid classes, phosphatidylcholine, phosphatidylserine, phosphatidylethanolamine and phosphatidylinositol, including lysophospholipid species, were analysed in adult S. mansoni worms, isolated tegumental membranes and hamster blood cells. It was shown that there are large differences in species composition in all four phospholipid classes between the membranes of S. mansoni and those of the host blood cells. The species compositions of phosphatidylserine and phosphatidylcholine were strikingly different in the tegument compared with the whole worm. The tegumental membranes are especially enriched in lysophospholipids, predominantly eicosenoic acid (20:1)-containing lyso-phosphatidylserine and lyso-phosphatidylethanolamine species. Furthermore, the tegument was strongly enriched in phosphatidylcholine that contained 5-octadecenoic acid, an unusual fatty acid that is not present in the host. As we have shown previously that lysophospholipids from schistosomes affect the parasite-host interaction, excretion of these tegument-specific phospholipid species was examined in vitro and in vivo. Our experiments demonstrated that these lysophospholipids are not significantly secreted during in vitro incubations and are not detectable in peripheral blood of infected hosts. However, these analyses demonstrated a substantial decrease in PI content of blood plasma from schistosome-infected hamsters, which might indicate that schistosomes influence exosome formation by the host. PMID:25975668

  19. Sexual Preferences in Nutrient Utilization Regulate Oxygen Consumption and Reactive Oxygen Species Generation in Schistosoma mansoni: Potential Implications for Parasite Redox Biology

    PubMed Central

    Oliveira, Matheus P.; Correa Soares, Juliana B. R.; Oliveira, Marcus F.

    2016-01-01

    Schistosoma mansoni, one of the causative agents of human schistosomiasis, has a unique antioxidant network that is key to parasite survival and a valuable chemotherapeutic target. The ability to detoxify and tolerate reactive oxygen species increases along S. mansoni development in the vertebrate host, suggesting that adult parasites are more exposed to redox challenges than young stages. Indeed, adult parasites are exposed to multiple redox insults generated from blood digestion, activated immune cells, and, potentially, from their own parasitic aerobic metabolism. However, it remains unknown how reactive oxygen species are produced by S. mansoni metabolism, as well as their biological effects on adult worms. Here, we assessed the contribution of nutrients and parasite gender to oxygen utilization pathways, and reactive oxygen species generation in whole unpaired adult S. mansoni worms. We also determined the susceptibilities of both parasite sexes to a pro-oxidant challenge. We observed that glutamine and serum importantly contribute to both respiratory and non-respiratory oxygen utilization in adult worms, but with different proportions among parasite sexes. Analyses of oxygen utilization pathways revealed that respiratory rates were high in male worms, which contrast with high non-respiratory rates in females, regardless nutritional sources. Interestingly, mitochondrial complex I-III activity was higher than complex IV specifically in females. We also observed sexual preferences in substrate utilization to sustain hydrogen peroxide production towards glucose in females, and glutamine in male worms. Despite strikingly high oxidant levels and hydrogen peroxide production rates, female worms were more resistant to a pro-oxidant challenge than male parasites. The data presented here indicate that sexual preferences in nutrient metabolism in adult S. mansoni worms regulate oxygen utilization and reactive oxygen species production, which may differently contribute

  20. Sexual Preferences in Nutrient Utilization Regulate Oxygen Consumption and Reactive Oxygen Species Generation in Schistosoma mansoni: Potential Implications for Parasite Redox Biology.

    PubMed

    Oliveira, Matheus P; Correa Soares, Juliana B R; Oliveira, Marcus F

    2016-01-01

    Schistosoma mansoni, one of the causative agents of human schistosomiasis, has a unique antioxidant network that is key to parasite survival and a valuable chemotherapeutic target. The ability to detoxify and tolerate reactive oxygen species increases along S. mansoni development in the vertebrate host, suggesting that adult parasites are more exposed to redox challenges than young stages. Indeed, adult parasites are exposed to multiple redox insults generated from blood digestion, activated immune cells, and, potentially, from their own parasitic aerobic metabolism. However, it remains unknown how reactive oxygen species are produced by S. mansoni metabolism, as well as their biological effects on adult worms. Here, we assessed the contribution of nutrients and parasite gender to oxygen utilization pathways, and reactive oxygen species generation in whole unpaired adult S. mansoni worms. We also determined the susceptibilities of both parasite sexes to a pro-oxidant challenge. We observed that glutamine and serum importantly contribute to both respiratory and non-respiratory oxygen utilization in adult worms, but with different proportions among parasite sexes. Analyses of oxygen utilization pathways revealed that respiratory rates were high in male worms, which contrast with high non-respiratory rates in females, regardless nutritional sources. Interestingly, mitochondrial complex I-III activity was higher than complex IV specifically in females. We also observed sexual preferences in substrate utilization to sustain hydrogen peroxide production towards glucose in females, and glutamine in male worms. Despite strikingly high oxidant levels and hydrogen peroxide production rates, female worms were more resistant to a pro-oxidant challenge than male parasites. The data presented here indicate that sexual preferences in nutrient metabolism in adult S. mansoni worms regulate oxygen utilization and reactive oxygen species production, which may differently contribute

  1. Human EBV-transformed lymphocytes of patients with Schistosoma japonicum infection secrete idiotypically related immunoregulatory antibodies.

    PubMed

    Kresina, T F; Cheever, L W; Chireau, M; Johnson, J; Ramirez, B; Peters, P; Olds, G R

    1992-12-01

    Lymphocytes derived from the peripheral blood of individuals infected with Schistosoma japonica were transformed in vitro with Ebstein-Barr virus (EBV). Serological characterization of antibody molecules revealed both antigen reactive (idiotypic) and anti-idiotypic transformants. One idiotypic EBV transformant, LO2C2, describes a major cross-reactive idiotype associated with anti-antigen binding molecules. Other antibody populations expressing idiotypic cross-reactivity were derived from separate individuals showing shared idiotypy in S. japonicum field study populations in the Republic of Philippines. Both idiotypic and anti-idiotypic molecules suppressed parasite antigen-driven blastogenesis of heterologous human peripheral blood lymphocytes. The data show a serologically related immunoregulatory immune network in patients in the Republic of the Philippines which is serologically distinct from idiotypy expressed in other selected S. japonicum endemic areas in the Far East. PMID:1333380

  2. Biological, biochemical and histopathological features related to parasitic castration of Biomphalaria glabrata infected by Schistosoma mansoni.

    PubMed

    Faro, Marta Julia; Perazzini, Mariana; Corrêa, Lygia dos Reis; Mello-Silva, Clélia Christina; Pinheiro, Jairo; Mota, Ester Maria; de Souza, Samaly; de Andrade, Zilton; Júnior, Arnaldo Maldonado

    2013-06-01

    Parasitic castration in the snail-trematode relationship can be understood as any change in the reproductive function of the snail that is due to interference by the developing larvae inside the snail that leads to the reduction or complete disruption of egg-laying activity. This study was designed to observe the parasitic castration of Biomphalaria glabrata infected with Schistosoma mansoni during both the pre-patent and patent periods. The effect of infection on snail fecundity and fertility, growth rate and survival was studied during the 62 days following miracidia exposure. An integrated approach was employed that used biochemical and histological tools over the same period. To study the effect of infection on reproduction, we individually exposed 30 snails to 5 miracidia each and tracked their fertility and fecundity. For our histopathological studies, 50 snails were exposed to 20 miracidia each, and for our histochemical studies, 50 snails were exposed to 5 miracidia each. An equal number of uninfected snails were used as a control for each group. The B. glabrata exposed to the BH strain of S. mansoni showed 50% positivity for cercarial shedding. Both the experimental and control groups showed 100% survival. The pre-patent period lasted until 39 days after exposure to miracidia. Exposed snails that showed cercarial shedding exhibited higher growth rates than either exposed snails that did not demonstrate cercarial shedding or uninfected controls. Exposed snails without cercarial shedding and uninfected controls showed no differences in the reproductive parameters evaluated during the patent period; snails experiencing cercarial shedding showed a reduction in fecundity and fertility. These snails began to lay eggs only after the 50th day post miracidia exposure. The haemolymph glucose levels showed an oscillating pattern that decreased during periods of greater mobilisation of energy by the larvae and was accompanied by a depletion of glycogen in the

  3. Venus Kinase Receptors Control Reproduction in the Platyhelminth Parasite Schistosoma mansoni

    PubMed Central

    Cailliau, Katia; Morel, Marion; Hahnel, Steffen; Leutner, Silke; Beckmann, Svenja; Grevelding, Christoph G.; Dissous, Colette

    2014-01-01

    The Venus Kinase Receptor (VKR) is a single transmembrane molecule composed of an intracellular tyrosine kinase domain close to that of insulin receptor and an extracellular Venus Flytrap (VFT) structure similar to the ligand binding domain of many class C G Protein Coupled Receptors. This receptor tyrosine kinase (RTK) was first discovered in the platyhelminth parasite Schistosoma mansoni, then in a large variety of invertebrates. A single vkr gene is found in most genomes, except in S. mansoni in which two genes Smvkr1 and Smvkr2 exist. VKRs form a unique family of RTKs present only in invertebrates and their biological functions are still to be discovered. In this work, we show that SmVKRs are expressed in the reproductive organs of S. mansoni, particularly in the ovaries of female worms. By transcriptional analyses evidence was obtained that both SmVKRs fulfill different roles during oocyte maturation. Suppression of Smvkr expression by RNA interference induced spectacular morphological changes in female worms with a strong disorganization of the ovary, which was dominated by the presence of primary oocytes, and a defect of egg formation. Following expression in Xenopus oocytes, SmVKR1 and SmVKR2 receptors were shown to be activated by distinct ligands which are L-Arginine and calcium ions, respectively. Signalling analysis in Xenopus oocytes revealed the capacity of SmVKRs to activate the PI3K/Akt/p70S6K and Erk MAPK pathways involved in cellular growth and proliferation. Additionally, SmVKR1 induced phosphorylation of JNK (c-Jun N-terminal kinase). Activation of JNK by SmVKR1 was supported by the results of yeast two-hybrid experiments identifying several components of the JNK pathway as specific interacting partners of SmVKR1. In conclusion, these results demonstrate the functions of SmVKR in gametogenesis, and particularly in oogenesis and egg formation. By eliciting signalling pathways potentially involved in oocyte proliferation, growth and migration

  4. 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

  5. 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

  6. Human TNF-α induces differential protein phosphorylation in Schistosoma mansoni adult male worms.

    PubMed

    Oliveira, Katia C; Carvalho, Mariana L P; Bonatto, José Matheus C; Schechtman, Debora; Verjovski-Almeida, Sergio

    2016-02-01

    Schistosoma mansoni and its vertebrate host have a complex and intimate connection in which several molecular stimuli are exchanged and affect both organisms. Human tumor necrosis factor alpha (hTNF-α), a pro-inflammatory cytokine, is known to induce large-scale gene expression changes in the parasite and to affect several parasite biological processes such as metabolism, egg laying, and worm development. Until now, the molecular mechanisms for TNF-α activity in worms are not completely understood. Here, we aimed at exploring the effect of hTNF-α on S. mansoni protein phosphorylation by 2D gel electrophoresis followed by a quantitative analysis of phosphoprotein staining and protein identification by mass spectrometry. We analyzed three biological replicates of adult male worms exposed to hTNF-α and successfully identified 32 protein spots with a statistically significant increase in phosphorylation upon in vitro exposure to hTNF-α. Among the differentially phosphorylated proteins, we found proteins involved in metabolism, such as glycolysis, galactose metabolism, urea cycle, and aldehyde metabolism, as well as proteins related to muscle contraction and to cytoskeleton remodeling. The most differentially phosphorylated protein (30-fold increase in phosphorylation) was 14-3-3, whose function is known to be modulated by phosphorylation, belonging to a signal transduction protein family that regulates a variety of processes in all eukaryotic cells. Further, 75% of the identified proteins are known in mammals to be related to TNF-α signaling, thus suggesting that TNF-α response may be conserved in the parasite. We propose that this work opens new perspectives to be explored in the study of the molecular crosstalk between host and pathogen. PMID:26547565

  7. Effect of different stages of Schistosoma mansoni infection on the parasite burden and immune response to Strongyloides venezuelensis in co-infected mice.

    PubMed

    de Rezende, Michelle Carvalho; Araújo, Emília Souza; Moreira, João Marcelo Peixoto; Rodrigues, Vanessa Fernandes; Rodrigues, Jailza Lima; Pereira, Cíntia A de Jesus; Negrão-Corrêa, Deborah

    2015-12-01

    Multiple schistosome and soil-transmitted nematode infections are frequently reported in human populations living in tropical areas of developing countries. In addition to exposure factors, the host immune response plays an important role in helminth control and morbidity in hosts with multiple infections; however, these aspects are difficult to evaluate in human populations. In the current study, female Swiss mice were simultaneously co-infected with Strongyloides venezuelensis and Schistosoma mansoni or infected with St. venezuelensis at 2, 4, or 14 weeks after Sc. mansoni infection. The simultaneously infected mice showed a similar parasite burden for St. venezuelensis compared with mono-infected mice. In contrast, there was a significant reduction of St. venezuelensis burden (primarily during the migration of the larvae) in mice that were previously infected with Sc. mansoni at the acute or chronic phase. Independent of the stage of Sc. mansoni infection, the St. venezuelensis co-infection was capable of inducing IL-4 production in the small intestine, increasing the IgE concentration in the serum and increasing eosinophilia in the lungs and intestine. This result suggests that the nematode infection stimulates local type 2 immune responses independently of the schistosomiasis stage. Moreover, previous Sc. mansoni infection stimulated early granulocyte infiltration in the lungs and trematode-specific IgM and IgG1 production that recognized antigens from St. venezuelensis infective larvae; these immune responses would act in the early control of St. venezuelensis larvae. Our data suggest that the effect of multiple helminth infections on host susceptibility and morbidity largely depends on the species of parasite and the immune response. PMID:26350380

  8. A Schistosoma protein, Sh-TOR, is a novel inhibitor of complement which binds human C2.

    PubMed

    Inal, J M; Sim, R B

    2000-03-24

    Human complement regulatory (also called inhibitory) proteins control misdirected attack of complement against autologous cells. Trypanosome and schistosome parasites which survive in the host vascular system also possess regulators of human complement. We have shown Sh-TOR, a protein with three predicted transmembrane domains, located on the Schistosoma parasite surface, to be a novel complement regulatory receptor. The N-terminal extracellular domain, Sh-TOR-ed1, binds the complement protein C2 from human serum and specifically interacts with the C2a fragment. As a result Sh-TOR-ed1 pre-incubated with C2 inhibits classical pathway (CP)-mediated haemolysis of sheep erythrocytes in a dose-dependent manner. In CP-mediated complement activation, C2 normally binds to C4b to form the CP C3 convertase and Sh-TOR-ed1 has short regions of sequence identity with a segment of human C4b. We propose the more appropriate name for TOR of CRIT (complement C2 receptor inhibitory trispanning). PMID:10734221

  9. The role played by alternative splicing in antigenic variability in human endo-parasites

    PubMed Central

    2014-01-01

    Endo-parasites that affect humans include Plasmodium, the causative agent of malaria, which remains one of the leading causes of death in human beings. Despite decades of research, vaccines to this and other endo-parasites remain elusive. This is in part due to the hyper-variability of the parasites surface proteins. Generally these surface proteins are encoded by a large family of genes, with only one being dominantly expressed at certain life stages. Another layer of complexity can be introduced through the alternative splicing of these surface proteins. The resulting isoforms may differ from each other with regard to cell localisation, substrate affinities and functions. They may even differ in structure to the extent that they are no longer recognised by the host’s immune system. In many cases this leads to changes in the N terminus of these proteins. The geographical localisation of endo-parasitic infections around the tropics and the highest incidences of HIV-1 infection in the same areas, adds a further layer of complexity as parasitic infections affect the host immune system resulting in higher HIV infection rates, faster disease progression, and an increase in the severity of infections and complications in HIV diagnosis. This review discusses some examples of parasite surface proteins that are alternatively spliced in trypanosomes, Plasmodium and the parasitic worm Schistosoma as well as what role alternate splicing may play in the interaction between HIV and these endo-parasites. PMID:24472559

  10. Partnering Parasites: Evidence of Synergism between Heavy Schistosoma haematobium and Plasmodium Species Infections in Kenyan Children

    PubMed Central

    Florey, Lia S.; King, Charles H.; Van Dyke, Melissa K.; Muchiri, Eric M.; Mungai, Peter L.; Zimmerman, Peter A.; Wilson, Mark L.

    2012-01-01

    Background Residents of resource-poor tropical countries carry heavy burdens of concurrent parasitic infections, leading to high rates of morbidity and mortality. This study was undertaken to help identify the social and environmental determinants of multiple parasite infection in one such community. Methodology/Principal Findings Residents of Kingwede, Kenya aged 8 years and older were tested for presence and intensity of S. haematobium and Plasmodium spp. infections in a cross-sectional, household-based, community survey. Using General Estimating Equation (GEE) models, social and environmental determinants associated with patterns of co-infection were identified, with age being one of the most important factors. Children had 9.3 times the odds of co-infection compared to adults (95%CI = 5.3–16.3). Even after controlling for age, socio-economic position, and other correlates of co-infection, intense concomitant infections with the two parasites were found to cluster in a subset of individuals: the odds of heavy vs. light S. haematobium infection increased with increasing Plasmodium infection intensity suggesting the importance of unmeasured biological factors in determining intensity of co-infection. Conclusions/Significance Children in this community are more likely to be infected with multiple parasites than are adults and should therefore be targeted for prevention and control interventions. More importantly, heavy infections with multiple parasite species appear to cluster within a subset of individuals. Further studies focusing on these most vulnerable people are warranted. PMID:22848765

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

    SciTech Connect

    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 of 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.

  12. Initial experiences with praziquantel in the treatment of human infections due to Schistosoma haematobium

    PubMed Central

    Davis, A.; Biles, J. E.; Ulrich, A.-M.

    1979-01-01

    Initial studies of the tolerance and efficacy of praziquantel in the treatment of human infections due to Schistosoma haematobium were conducted at the WHO Tropical Diseases Research Centre, Ndola, Zambia. The first stage of the trial was a double-blind assessment against placebo of the tolerance and efficacy of oral doses of 1×20, 2×20, or 3×20 mg/kg in patients with a minimum schistosome egg excretion of 50 per random 10-ml sample of urine. Later a single-blind trial was carried out of the efficacy of three oral doses, each of 20 mg/kg, given at 4-hour intervals, or of a single oral dose of 50 mg/kg. In 79 young Zambians with S. haematobium infections (and often other parasitic infections), patient tolerance to the drug was very good, only minor post-treatment symptoms of intermittent epigastric pain, anorexia, and headache being noted, all of short duration. No changes of clinical relevance were detected in the results of a battery of haematological and biochemical tests. Post-treatment eosinophilia occurred in 42% of drug-treated patients but also in 30% of those given placebo. Serial electrocardiograms revealed no changes of significance. At six months after treatment, of 73 patients followed up, only 1 case of parasitological failure was detected. At one year, 66 (83.5%) of 79 patients with S. haematobium infection were followed up and 2 (2.5%) parasitological failures were detected. Two years after treatment, 45 (57%) of 79 patients with S. haematobium showed negative urines, 7 (9%) had positive hatching tests, and 27 (34%) were absent. PMID:396053

  13. Human schistosomiasis: Schistosoma mansoni antigen detection in renal glomeruli.

    PubMed

    Hoshino-Shimizu, S; De Brito, T; Kanamura, H Y; Canto, A L; Silva, A O; Campos, A R; Penna, D O; Da Silva, L C

    1976-01-01

    Twelve kidney, five biopsy and seven necropsy specimens, all from schistosomiasis mansoni patients were studied by light and immunoflurescent microscopy in an attempt to detect antigen in the glomerular walls. Deposits of IgM, IgG,I gA, IgE, complement C3 and fibrinogen were observered in most cases. Antigen was successfully detected in two cases(one biopsy and one necropsy specimen), both exhibiting proliferative glomerulonephritis. The only clinical manifestation was a slight proteinuria. IgG antibodies eluted from the sutopsy kidney homogenates showed specific binding mostly to Schistosoma mansoni gut, thus spggesting that the fixed antibodies (eluates) are, at least partially, consituted by antibodies similar to the anti-circulating antigen. These data reinfroce the hypothesis that renal injury in schistosomiasis is mediated through an immune complex disease. PMID:65811

  14. Differential transcriptomic responses of Biomphalaria glabrata (Gastropoda, Mollusca) to bacteria and metazoan parasites, Schistosoma mansoni and Echinostoma paraensei (Digenea, Platyhelminthes).

    PubMed

    Adema, Coen M; Hanington, Patrick C; Lun, Cheng-Man; Rosenberg, George H; Aragon, Anthony D; Stout, Barbara A; Lennard Richard, Mara L; Gross, Paul S; Loker, Eric S

    2010-01-01

    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 12h post-wounding, exposure to Gram negative or Gram positive bacteria (Escherichia coli and Micrococcus luteus, respectively), or infection with compatible trematode parasites (Schistosoma mansoni or Echinostoma 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)

  15. Palaeoparasitology - Human Parasites in Ancient Material.

    PubMed

    Araújo, Adauto; Reinhard, Karl; Ferreira, Luiz Fernando

    2015-01-01

    Parasite finds in ancient material launched a new field of science: palaeoparasitology. Ever since the pioneering studies, parasites were identified in archaeological and palaeontological remains, some preserved for millions of years by fossilization. However, the palaeoparasitological record consists mainly of parasites found specifically in human archaeological material, preserved in ancient occupation sites, from prehistory until closer to 2015. The results include some helminth intestinal parasites still commonly found in 2015, such as Ascaris lumbricoides, Trichuris trichiura and hookworms, besides others such as Amoebidae and Giardia intestinalis, as well as viruses, bacteria, fungi and arthropods. These parasites as a whole provide important data on health, diet, climate and living conditions among ancient populations. This chapter describes the principal findings and their importance for knowledge on the origin and dispersal of infectious diseases. PMID:26597072

  16. Suppression of the Insulin Receptors in Adult Schistosoma japonicum Impacts on Parasite Growth and Development: Further Evidence of Vaccine Potential.

    PubMed

    You, Hong; Gobert, Geoffrey N; Cai, Pengfei; Mou, Rong; Nawaratna, Sujeevi; Fang, Guofu; Villinger, Francois; McManus, Donald P

    2015-05-01

    To further investigate the importance of insulin signaling in the growth, development, sexual maturation and egg production of adult schistosomes, we have focused attention on the insulin receptors (SjIRs) of Schistosoma japonicum, which we have previously cloned and partially characterised. We now show, by Biolayer Interferometry, that human insulin can bind the L1 subdomain (insulin binding domain) of recombinant (r)SjIR1 and rSjIR2 (designated SjLD1 and SjLD2) produced using the Drosophila S2 protein expression system. We have then used RNA interference (RNAi) to knock down the expression of the SjIRs in adult S. japonicum in vitro and show that, in addition to their reduced transcription, the transcript levels of other important downstream genes within the insulin pathway, associated with glucose metabolism and schistosome fecundity, were also impacted substantially. Further, a significant decrease in glucose uptake was observed in the SjIR-knockdown worms compared with luciferase controls. In vaccine/challenge experiments, we found that rSjLD1 and rSjLD2 depressed female growth, intestinal granuloma density and faecal egg production in S. japonicum in mice presented with a low dose challenge infection. These data re-emphasize the potential of the SjIRs as veterinary transmission blocking vaccine candidates against zoonotic schistosomiasis japonica in China and the Philippines. PMID:25961574

  17. Suppression of the Insulin Receptors in Adult Schistosoma japonicum Impacts on Parasite Growth and Development: Further Evidence of Vaccine Potential

    PubMed Central

    You, Hong; Gobert, Geoffrey N.; Cai, Pengfei; Mou, Rong; Nawaratna, Sujeevi; Fang, Guofu; Villinger, Francois; McManus, Donald P.

    2015-01-01

    To further investigate the importance of insulin signaling in the growth, development, sexual maturation and egg production of adult schistosomes, we have focused attention on the insulin receptors (SjIRs) of Schistosoma japonicum, which we have previously cloned and partially characterised. We now show, by Biolayer Interferometry, that human insulin can bind the L1 subdomain (insulin binding domain) of recombinant (r)SjIR1 and rSjIR2 (designated SjLD1 and SjLD2) produced using the Drosophila S2 protein expression system. We have then used RNA interference (RNAi) to knock down the expression of the SjIRs in adult S. japonicum in vitro and show that, in addition to their reduced transcription, the transcript levels of other important downstream genes within the insulin pathway, associated with glucose metabolism and schistosome fecundity, were also impacted substantially. Further, a significant decrease in glucose uptake was observed in the SjIR-knockdown worms compared with luciferase controls. In vaccine/challenge experiments, we found that rSjLD1 and rSjLD2 depressed female growth, intestinal granuloma density and faecal egg production in S. japonicum in mice presented with a low dose challenge infection. These data re-emphasize the potential of the SjIRs as veterinary transmission blocking vaccine candidates against zoonotic schistosomiasis japonica in China and the Philippines. PMID:25961574

  18. Human immune responses to Schistosoma mansoni vaccine candidate antigens.

    PubMed

    Ribeiro de Jesus, A; Araújo, I; Bacellar, O; Magalhães, A; Pearce, E; Harn, D; Strand, M; Carvalho, E M

    2000-05-01

    To determine the naturally occurring immunological responses to the Schistosoma mansoni antigens paramyosin, IrV-5, Sm-23 (MAP-3), and triose phosphate isomerase (MAP-4), a total of 119 subjects from an area of endemicity for schistosomiasis, including "resistant" subjects (n = 17) were evaluated. Specific immunoglobulin G1 (IgG1), IgG2, IgG3, IgG4, and IgA levels for each of the antigens and the cytokine profile in culture supernatants from antigen-stimulated peripheral blood mononuclear cells (PBMC) were determined. Although all the subjects had a high degree of contaminated water exposure, their infection levels were variable (0 to 1,128 eggs/g of stool). There were direct correlations between infection levels and levels of SWAP- and paramyosin-specific IgG1 and IgG4 (P < 0.05). However, an inverse correlation between infection levels and specific IgG2 to IrV-5 (P < 0.01) was observed. The evaluation of the cytokine profile (interleukin 5 [IL-5], IL-10, gamma interferon [IFN-gamma], and tumor necrosis factor alpha) in response to these antigens showed inverse correlations between the degree of infection and IFN-gamma levels in PBMC supernatants stimulated with paramyosin (P < 0.05) and IrV-5 (P < 0.01). Additionally, inverse correlations between the degree of infection and IL-5 levels in MAP-3- and MAP-4-stimulated PBMC supernatants (P < 0.01) were found. Logistic regression analysis was performed to adjust the results of cytokine profile by age. IL-5 production in MAP-3-stimulated PBMC supernatants was associated with lower infection levels (odds ratio = 11.2 [95% confidence interval, 2.7 to 45.8]). PMID:10768975

  19. Purification and characterization of 3-hydroxymethylglutaryl-coenzyme A reductase of Schistosoma mansoni: regulation of parasite enzyme activity differs from mammalian host.

    PubMed

    Chen, G Z; Foster, L; Bennett, J L

    1991-07-01

    The enzyme 3-hydroxymethylglutaryl-CoA (HMG-CoA) reductase plays a critical role in regulating the production of cholesterol, dolichols, and ubiquinones in mammals. The inhibition of this enzyme in Schistosoma mansoni is accompanied by a cessation of egg production by the female parasite and a reduced ability of the parasite to properly glycoslyate their proteins. Furthermore, we recently demonstrated that mevinolin, if given continuously over a period of 10-14 days, is a potent antischistosomal drug. In this paper, we describe the properties of purified HMG-CoA reductase from S. mansoni. Using affinity chromatography, we were able to obtain a 417-fold purification of the enzyme which had Km values similar to the rat enzyme for HMG-CoA and NADPH. The Ki value for mevinolin, a potent and selective inhibitor of the rat reductase (Ki = 0.6 nM), was significantly higher (Ki = 46 nM) for the schistosome enzyme. SDS-PAGE and HPLC of the purified enzyme resulted in the appearance of a single protein, which had a molecular weight (66,000) in the range reported for the rat enzyme. Parasite reductase activity, unlike that of its host, did not display a circadian rhythm. Furthermore, agents which elevate (cholestyramine) or decrease (cholesterol) mammalian reductase activity had no effect on the parasite enzyme. Our results suggest that the mechanism which regulates production of the parasite's enzyme may differ from its mammalian host. PMID:1905241

  20. Drug repurposing and human parasitic protozoan diseases

    PubMed Central

    Andrews, Katherine T.; Fisher, Gillian; Skinner-Adams, Tina S.

    2014-01-01

    Parasitic diseases have an enormous health, social and economic impact and are a particular problem in tropical regions of the world. Diseases caused by protozoa and helminths, such as malaria and schistosomiasis, are the cause of most parasite related morbidity and mortality, with an estimated 1.1 million combined deaths annually. The global burden of these diseases is exacerbated by the lack of licensed vaccines, making safe and effective drugs vital to their prevention and treatment. Unfortunately, where drugs are available, their usefulness is being increasingly threatened by parasite drug resistance. The need for new drugs drives antiparasitic drug discovery research globally and requires a range of innovative strategies to ensure a sustainable pipeline of lead compounds. In this review we discuss one of these approaches, drug repurposing or repositioning, with a focus on major human parasitic protozoan diseases such as malaria, trypanosomiasis, toxoplasmosis, cryptosporidiosis and leishmaniasis. PMID:25057459

  1. Parasites as probes for prehistoric human migrations?

    PubMed

    Araujo, Adauto; Reinhard, Karl J; Ferreira, Luiz Fernando; Gardner, Scott L

    2008-03-01

    Host-specific parasites of humans are used to track ancient migrations. Based on archaeoparasitology, it is clear that humans entered the New World at least twice in ancient times. The archaeoparasitology of some intestinal parasites in the New World points to migration routes other than the Bering Land Bridge. Helminths have been found in mummies and coprolites in North and South America. Hookworms (Necator and Ancylostoma), whipworms (Trichuris trichiura) and other helminths require specific conditions for life-cycle completion. They could not survive in the cold climate of the northern region of the Americas. Therefore, humans would have lost some intestinal parasites while crossing Beringia. Evidence is provided here from published data of pre-Columbian sites for the peopling of the Americas through trans-oceanic or costal migrations. PMID:18262843

  2. Schistosoma mansoni Infection in Preschool-Aged Children: Development of Immunoglobulin E and Immunoglobulin G4 Responses to Parasite Allergen-Like Proteins

    PubMed Central

    Pinot de Moira, Angela; Sousa-Figueiredo, Jose C.; Jones, Frances M.; Fitzsimmons, Colin M.; Betson, Martha; Kabatereine, Narcis B.; Stothard, J. Russell; Dunne, David W.

    2013-01-01

    Specific immunoglobulin E (IgE) responses are upregulated during chronic schistosome infection and during allergy. These responses are tightly regulated during schistosomiasis. We have previously shown that IgE regulation depends on the extent and length of exposure to individual parasite allergen-like proteins. Here we compare the development of IgE and immunoglobulin G4 (IgG4) responses to the differentially expressed allergen-like proteins SmTAL1 and SmTAL2 among preschool-aged children from 2 villages with different levels of Schistosoma mansoni transmission. We found a lack of SmTAL1 responsiveness among all children, but evidence for IgG4-dependent IgE-SmTAL2 desensitization in both villages, occurring earlier among children from the village where the level of transmission was greater. Findings provide insights into the development and regulation of allergic-type immune responses. PMID:23125445

  3. Predicting frequency distribution and influence of sociodemographic and behavioral risk factors of Schistosoma mansoni infection and analysis of co-infection with intestinal parasites.

    PubMed

    Rollemberg, Carla V V; Silva, Marília M B L; Rollemberg, Karla C; Amorim, Fábio R; Lessa, Nayanna M N; Santos, Marcos D S; Souza, Acácia M B; Melo, Enaldo V; Almeida, Roque P; Silva, Ângela M; Werneck, Guilherme L; Santos, Mario A; Almeida, José A P; Jesus, Amélia R

    2015-01-01

    Geospatial analysis was used to study the epidemiology of Schistosoma mansoni, intestinal parasites and co-infections in an area (Ilha das Flores) in Sergipe, Brazil. We collected individually georeferenced sociodemographic, behavioral and parasitological data from 500 subjects, analyzed them by conventional statistics, and produced risk maps by Kernel estimation. The prevalence rates found were: S. mansoni (24.0%), Trichuris trichiura (54.8%), Ascaris lumbricoides (49.2%), Hookworm (17.6%) and Entamoeba histolytica (7.0%). Only 59/500 (11.8%) individuals did not present any of these infections, whereas 279/500 (55.8%) were simultaneously infected by three or more parasites. We observed associations between S. mansoni infection and various variables such as male gender, being rice farmer or fisherman, low educational level, low income, water contact and drinking untreated water. The Kernel estimator indicated that high-risk areas coincide with the poorest regions of the villages as well as with the part of the villages without an adequate sewage system. We also noted associations between both A. lumbricoides and hookworm infections with low education and low income. A. lumbricoides infection and T. trichiura infection were both associated with drinking untreated water and residential open-air sewage. These findings call for an integrated approach to effectively control multiple parasitic infections. PMID:26054512

  4. Prevalence of Intestinal Parasitic Infections among Children under Five Years of Age with Emphasis on Schistosoma mansoni in Wonji Shoa Sugar Estate, Ethiopia

    PubMed Central

    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

  5. 21 CFR 866.3600 - Schistosoma spp. serological reagents.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... serum. The identification aids in the diagnosis of schistosomiasis caused by parasitic flatworms of the genus Schistosoma. Schistosomiasis is characterized by a variety of acute and chronic infections....

  6. 21 CFR 866.3600 - Schistosoma spp. serological reagents.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... serum. The identification aids in the diagnosis of schistosomiasis caused by parasitic flatworms of the genus Schistosoma. Schistosomiasis is characterized by a variety of acute and chronic infections....

  7. 21 CFR 866.3600 - Schistosoma spp. serological reagents.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... serum. The identification aids in the diagnosis of schistosomiasis caused by parasitic flatworms of the genus Schistosoma. Schistosomiasis is characterized by a variety of acute and chronic infections....

  8. 21 CFR 866.3600 - Schistosoma spp. serological reagents.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... serum. The identification aids in the diagnosis of schistosomiasis caused by parasitic flatworms of the genus Schistosoma. Schistosomiasis is characterized by a variety of acute and chronic infections....

  9. 21 CFR 866.3600 - Schistosoma spp. serological reagents.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... serum. The identification aids in the diagnosis of schistosomiasis caused by parasitic flatworms of the genus Schistosoma. Schistosomiasis is characterized by a variety of acute and chronic infections....

  10. Synthesis of a sugar-based thiosemicarbazone series and structure-activity relationship versus the parasite cysteine proteases rhodesain, cruzain, and Schistosoma mansoni cathepsin B1.

    PubMed

    Fonseca, Nayara Cristina; da Cruz, Luana Faria; da Silva Villela, Filipe; do Nascimento Pereira, Glaécia Aparecida; de Siqueira-Neto, Jair Lage; Kellar, Danielle; Suzuki, Brian M; Ray, Debalina; de Souza, Thiago Belarmino; Alves, Ricardo José; Sales Júnior, Policarpo Ademar; Romanha, Alvaro José; Murta, Silvane Maria Fonseca; McKerrow, James H; Caffrey, Conor R; de Oliveira, Renata Barbosa; Ferreira, Rafaela Salgado

    2015-05-01

    The pressing need for better drugs against Chagas disease, African sleeping sickness, and schistosomiasis motivates the search for inhibitors of cruzain, rhodesain, and Schistosoma mansoni CB1 (SmCB1), the major cysteine proteases from Trypanosoma cruzi, Trypanosoma brucei, and S. mansoni, respectively. Thiosemicarbazones and heterocyclic analogues have been shown to be both antitrypanocidal and inhibitory against parasite cysteine proteases. A series of compounds was synthesized and evaluated against cruzain, rhodesain, and SmCB1 through biochemical assays to determine their potency and structure-activity relationships (SAR). This approach led to the discovery of 6 rhodesain, 4 cruzain, and 5 SmCB1 inhibitors with 50% inhibitory concentrations (IC50s) of ≤ 10 μM. Among the compounds tested, the thiosemicarbazone derivative of peracetylated galactoside (compound 4i) was discovered to be a potent rhodesain inhibitor (IC50 = 1.2 ± 1.0 μM). The impact of a range of modifications was determined; removal of thiosemicarbazone or its replacement by semicarbazone resulted in virtually inactive compounds, and modifications in the sugar also diminished potency. Compounds were also evaluated in vitro against the parasites T. cruzi, T. brucei, and S. mansoni, revealing active compounds among this series. PMID:25712353

  11. Synthesis of a Sugar-Based Thiosemicarbazone Series and Structure-Activity Relationship versus the Parasite Cysteine Proteases Rhodesain, Cruzain, and Schistosoma mansoni Cathepsin B1

    PubMed Central

    Fonseca, Nayara Cristina; da Cruz, Luana Faria; da Silva Villela, Filipe; do Nascimento Pereira, Glaécia Aparecida; de Siqueira-Neto, Jair Lage; Kellar, Danielle; Suzuki, Brian M.; Ray, Debalina; de Souza, Thiago Belarmino; Alves, Ricardo José; Júnior, Policarpo Ademar Sales; Romanha, Alvaro José; Murta, Silvane Maria Fonseca; McKerrow, James H.; Caffrey, Conor R.; de Oliveira, Renata Barbosa

    2015-01-01

    The pressing need for better drugs against Chagas disease, African sleeping sickness, and schistosomiasis motivates the search for inhibitors of cruzain, rhodesain, and Schistosoma mansoni CB1 (SmCB1), the major cysteine proteases from Trypanosoma cruzi, Trypanosoma brucei, and S. mansoni, respectively. Thiosemicarbazones and heterocyclic analogues have been shown to be both antitrypanocidal and inhibitory against parasite cysteine proteases. A series of compounds was synthesized and evaluated against cruzain, rhodesain, and SmCB1 through biochemical assays to determine their potency and structure-activity relationships (SAR). This approach led to the discovery of 6 rhodesain, 4 cruzain, and 5 SmCB1 inhibitors with 50% inhibitory concentrations (IC50s) of ≤10 μM. Among the compounds tested, the thiosemicarbazone derivative of peracetylated galactoside (compound 4i) was discovered to be a potent rhodesain inhibitor (IC50 = 1.2 ± 1.0 μM). The impact of a range of modifications was determined; removal of thiosemicarbazone or its replacement by semicarbazone resulted in virtually inactive compounds, and modifications in the sugar also diminished potency. Compounds were also evaluated in vitro against the parasites T. cruzi, T. brucei, and S. mansoni, revealing active compounds among this series. PMID:25712353

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

    PubMed

    Abruzzi, Amy; Fried, Bernard

    2011-01-01

    This review examines coinfection of selected species of Schistosoma with bacteria, protozoa and helminths and focuses on the effects of the coinfection on the hosts. The review is based mainly on tables that contain the salient information on the coinfecting organisms in vertebrate hosts. Further explanation and clarification of the tables are given in the text. A table is also provided that gives synoptic information on the 37 species in the 19 genera considered in this review. Coinfection studies with Schistosoma species and the other organisms were considered in six tables plus the accompanying text. Considerations of the Schistosoma interactions with another species of organism include studies on coinfection with Plasmodium, with protozoa other than Plasmodium; with Salmonella, with bacteria other than Salmonella; and with Fasciola, with helminths other than Fasciola. Numerous factors were found to influence the effects of coinfection on the vertebrate host, including organisms and hosts used in the studies, order and time interval between the first and the second infection, studies on natural versus experimental hosts, dosage of the infectious agents, strains and pedigrees of the parasites, age of hosts at time of exposure to the infectious agents and age of hosts at the time of necropsy. Overall, a prior infection with Schistosoma, particularly a patent infection, often has an effect on the subsequent infection by a protozoan, bacterium or other helminth. In relatively few cases, a prior infection with Schistosoma decreased the severity of the subsequent infection as with Helicobacter pylori, Fasciola hepatica, Echinostoma or Plasmodium, the latter only exhibiting this behaviour when coinfected with Schistosoma haematobium. More often, however, a prior infection with Schistosoma increased the severity of the second infection as with Leishmania, Toxoplasma gondii, Entamoeba histolytica, Staphylococcus aureus or Salmonella. In some of these coinfection studies

  13. 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 Central

    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. PMID:25897665

  14. Diagnostic Accuracy and Applicability of a PCR System for the Detection of Schistosoma mansoni DNA in Human Urine Samples from an Endemic Area

    PubMed Central

    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. PMID:22701733

  15. 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. PMID:22701733

  16. Ectopic Schistosoma mansoni Eggs Inside a Lipoma.

    PubMed

    Sabino, Kelly Renata; Nunes, Maurício Buzelin; Petroianu, Andy

    2016-01-01

    Ectopic schistosomiasis is uncommon and tends to occur when the parasite's eggs or adult forms are located far from their normal site. This report presents the first described case of ectopic Schistosoma mansoni eggs inside a subcutaneous lipoma far from the tissues of this worm's life cycle and with no connection to either portal veins or any other vascular system. These eggs were found inside giant cells surrounded by inflammatory cells. In conclusion, in humans, ectopic S. mansoni eggs can be found far from the tissues of the described life cycle of this worm, with no connection to portal veins or other blood vessels used for their migration. PMID:26598562

  17. Biology Today: Parasites and Human Ecology.

    ERIC Educational Resources Information Center

    Flannery, Maura C.

    1984-01-01

    Offers various reasons why the study of parasites and the diseases they cause should be incorporated into classroom biology discussions. Examples of several parasitic diseases and their ecological significance are provided. (JN)

  18. 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

  19. Invertebrate host-parasite relationships: convergent evolution of a tropomyosin epitope between Schistosoma sp., Fasciola hepatica, and certain pulmonate snails.

    PubMed

    Weston, D; Allen, B; Thakur, A; LoVerde, P T; Kemp, W M

    1994-05-01

    Monoclonal antibodies (mAb) directed against Schistosoma mansoni tropomyosin isoform, SMTM (Xu et al. Experimental Parasitology 69, 373-392, 1989), were used to test for cross-reactivity with Biomphalaria glabrata antigens. One mAb (1F10) recognized antigens of 39, 41, and 80 kDa in a snail head/foot antigen preparation but not a hepatopancreas antigen preparation. Another mAb (1C1) cross-reacted with a 39-kDa antigen in the head/foot extract but not in the hepatopancreas extract. Epitope mapping revealed the 1F10 epitope to be between amino acids 135 and 188 of both Bg39 (Dissous et al. Molecular and Biochemical Parasitology 43, 245-256, 1990) and BgTMII (Weston and Kemp, Experimental Parasitology 76, 358-370, 1993), while the 1C1 epitope was located between amino acids 189 and 213 of BgTMII. Various invertebrate species, including members from Trematoda, Pulmonata, Annelida, and Arthropoda, were tested for cross-reactivity with the monoclonal antibodies. While the 1F10 mAb displayed broad invertebrate cross-reactivity, the 1C1 mAb cross-reactivity was restricted to schistosomes, F. hepatica, and the pulmonate snails B. glabrata and Physa sp. PMID:7512930

  20. Tissue Transglutaminase-Regulated Transformed Growth Factor-β1 in the Parasite Links Schistosoma japonicum Infection with Liver Fibrosis

    PubMed Central

    Tang, Juanjuan; Zhu, Xunmin; Zhao, Jingjing; Fung, Mingchiu; Li, Yinyan; Gao, Zhiyan; Yan, Suikai; Li, Xiaomin; Ji, Xiaofang; Su, Fang; Li, Zi

    2015-01-01

    Transforming growth factor (TGF-β1) is among the strongest factors of liver fibrogenesis, but its association with Schistosoma-caused liver fibrosis is controversial. Tissue transglutaminase (tTG) is the principal enzyme controlling TGF-β1 maturation and contributes to Sj-infected liver fibrosis. Here we aim to explore the consistency between tTG and TGF-β1 and TGF-β1 source and its correlation with liver fibrosis after Sj-infection. TGF-β1 was upregulated at weeks 6 and 8 upon liver fibrosis induction. During tTG inhibition, TGF-β1 level decreased in sera and liver of infected mice. TGF-β1 showed positive staining in liver containing Sj adult worms and eggs. TGF-β1 was also detected in Sj adult worm sections, soluble egg antigen and Sj adult worm antigen, and adult worms' culture medium. The TGF-β1 mature peptide cDNA sequence and its extended sequence were amplified through RT-PCR and RACE-PCR using adult worms as template, and sequence is analyzed and loaded to NCBI GenBank (number GQ338152.1). TGF-β1 transcript in Sj eggs was higher than in adult worms. In Sj-infected liver, transcriptional level of TGF-β1 from Sj, but not mouse liver, correlated with liver fibrosis extent. This study provides evidence that tTG regulates TGF-β1 and illustrates the importance of targeting tTG in treating Sj infection-induced fibrosis. PMID:26199461

  1. Schistosoma haematobium in Guinea-Bissau: unacknowledged morbidity due to a particularly neglected parasite in a particularly neglected country.

    PubMed

    Botelho, Monica C; Machado, Ana; Carvalho, André; Vilaça, Manuela; Conceição, Orquídea; Rosa, Fernanda; Alves, Helena; Richter, Joachim; Bordalo, Adriano Agostinho

    2016-04-01

    Schistosomiasis is the major neglected tropical helminthic disease worldwide. Current knowledge on the epidemiology of schistosomiasis in Guinea-Bissau is scarce and regarding to the absence of Schistosoma haematobium (S.h.). Therefore, a pilot study was undertaken to assess the prevalence and morbidity due to S.h. infection in randomly selected 90 children and adolescents aged 6 to 15 years. Prevalence of S.h. infection was 20.00 % (18/90). Microhematuria was observed in 61.11 % (11/18) of S.h.-egg-excreting vs. 37.50 % (27/72) of non-S.h.-egg-excreting children p ≤ 0.01. Body mass index (BMI) was less than 15 kg/m(2) in 52/90 (57.78 %) of all children and adolescents, but this proportion increased to 66.67 % (12/18) in S.h.-infected children who were more frequently stunted and wasted than in non-infected children. The mean weight-for-age Z score (WAZ) was reduced in S.h. infected as compared to non-infected children (-1.48 ± 1.08 SD vs. -0.80 ± 1.11 SD; p ≤ 0.01). To our knowledge, this is the first epidemiologic report on S. haematobium infection in Guinea-Bissau since 22 years. Even in this relatively small study sample, it appears that S. haematobium, besides the well-known symptoms such as hematuria, leads to significant, albeit commonly unacknowledged morbidity such as stunting and wasting. These observations underscore the notion that this vulnerable but neglected population urgently needs to be targeted for implementation of measures for treatment and control. PMID:26755362

  2. Identification of in vivo protein phosphorylation sites in human pathogen Schistosoma japonicum by a phosphoproteomic approach.

    PubMed

    Luo, Rong; Zhou, Chunjing; Lin, Jiaojiao; Yang, Dehao; Shi, Yaojun; Cheng, Guofeng

    2012-01-01

    Schistosome is the causative agent of human schistosomiasis and related animal disease. Reversible protein phosphorylation plays a key role in signaling processing that are vital for a cell and organism. However, it remains to be undercharacterized in schistosomes. In the present study, we characterized in vivo protein phosphorylation events in different developmental stages (schistosomula and adult worms) of Schistosoma japonicum by using microvolume immobilized metal-ion affinity chromatography (IMAC) pipette tips coupled to nanoLC-ESI-MS/MS. In total, 127 distinct phosphorylation sites were identified in 92 proteins in S. japonicum. A comparison of the phosphopeptides identified between the schistosomula and the adult worms revealed 30 phosphoproteins co-detected in both of the two worms. These proteins included several signal molecules and enzymes such as 14-3-3 protein, cysteine string protein, heat shock protein 90, epidermal growth factor receptor pathway substrate 8, proliferation-associated protein 2G4, peptidyl-prolyl isomerase G, phosphofructokinase and thymidylate kinase. Additionally, the phosphorylation sites were examined for phosphorylation specific motif and evolutionarily conservation. The study represents the first attempt to determine in vivo protein phosphorylation in S. japonicum by using a phosphoproteomic approach. The results by providing an inventory of phosphorylated proteins may facilitate to further understand the mechanisms involved in schistosome development and growth, and then may result in the development of novel vaccine candidates and drug targets for schistosomiasis control. PMID:22036931

  3. Association Between Schistosoma haematobium Exposure and Human Immunodeficiency Virus Infection Among Females in Mozambique.

    PubMed

    Brodish, Paul Henry; Singh, Kavita

    2016-05-01

    Recent evidence suggests an association between human immunodeficiency virus (HIV) and female genital schistosomiasis (FGS) in sub-Saharan Africa, especially in Mozambique, South Africa, Tanzania, and Zimbabwe. Women with FGS have increased numbers of HIV target cells and cell receptors in genital and blood compartments, potentially increasing the risk of HIV transmission per sexual exposure, and the association may explain the high female:male ratio of HIV prevalence unique to sub-Saharan Africa. We investigate this association in Mozambique by linking two georeferenced, high-quality secondary data sources on HIV prevalence and Schistosoma haematobium: the AIDS Indicator Survey, and the Global Neglected Tropical Diseases (GNTD) open-source database, respectively. We construct a schistosomiasis exposure covariate indicating women reporting "unimproved" daily drinking water sources and living no more than 2-5 km from high-endemic global positioning system (GPS) coordinates in the GNTD. In logistic regression analyses predicting HIV-positive status, we show that exposure increases the odds of HIV-positive status by three times, controlling for demographic and sexual risk factors. PMID:26976893

  4. Diagnostic significance of Schistosoma mansoni proteins Sm31 and Sm32 in human schistosomiasis in an endemic area in Egypt.

    PubMed

    El-Sayed, L H; Ghoneim, H; Demian, S R; El-Sayed, M H; Tawfik, N M; Sakr, I; Abou-Basha, L M; Renganathan, E; Klinkert, M Q; Abou-Rawash, N

    1998-09-01

    We performed a series of ELISAs to evaluate the diagnostic significance of two Schistosoma mansoni proteins, Sm31 (cysteine proteinase, cathepsin B) and Sm32 (asparaginyl endopeptidase). Our study populations were chosen from two villages in an endemic area close to Alexandria. Using fusion proteins MS2-Sm31 and MS2-Sm32 as antigens, 70% and 78.9%, respectively, of patient sera from 134 parasitologically confirmed cases reacted positively. The percentage of seropositivity increased to 84.5% when parasite-derived proteins Sm31 and Sm32 were used. The serum levels of antibodies to these two proteins in recombinant or native forms do not correlate with intensity of infection and hence are detected even when egg counts are low, which makes proteins Sm31 and Sm32 useful antigens in the identification of S. mansoni infected cases, particularly in endemic areas in Egypt. PMID:9754667

  5. Cholinergic components of nervous system of Schistosoma mansoni and S. haematobium (Digenea: Schistosomatidae).

    PubMed

    Reda, Enayat S; El-Shabasy, Eman A; Said, Ashraf E; Mansour, Mohamed F A; Saleh, Mai A

    2016-08-01

    A comparison has been made for the first time between the cholinergic components of the nervous system of important human digeneans namely Schistosoma mansoni and Schistosoma haematobium from infected hamster (Cricentus auratus) in Egypt. In each parasite, the central nervous system consists of two cerebral ganglia and three pairs of nerve cords (ventral, lateral, and dorsal) linked together by some transverse connectives and numerous ring commissures. Peripheral cholinergic innervation was detected in oral and ventral suckers and in some parts of female reproductive system in both species, but there were some differences. The possible functions of some of these nervous components are discussed. PMID:27130318

  6. Serodiagnosis of Schistosoma mansoni infections in an endemic area of Burkina Faso: performance of several immunological tests with different parasite antigens.

    PubMed

    Sorgho, Hermann; Bahgat, Mahmoud; Poda, Jean-Noel; Song, Wenjian; Kirsten, Christa; Doenhoff, Michael J; Zongo, Issaka; Ouédraogo, Jean-Bosco; Ruppel, Andreas

    2005-02-01

    The performance of indirect haemagglutination assays (IHA), enzyme-linked immunosorbent assays (ELISA) and indirect immunofluorescent antibody tests (IFAT) were compared with 450 sera from a Schistosoma mansoni-endemic area in Burkina Faso. All participants in this survey provided at least one sample each of stool, urine and serum. From those with an egg-negative Kato-Katz thick smear, a second stool sample was examined. IHA was based on either extracts of adult S. mansoni worms (SmIHA) or S. japonicum egg antigen (SjIHA). For ELISA, three antigen preparations were used, namely: (i) soluble S. mansoni adult worm antigens (SWAP); (ii) soluble S. mansoni egg antigens (SEA); and (iii) a cationic exchange fraction of S. mansoni eggs (CEF6). IFAT was performed with S. mansoni male worm sections. Among the egg-excretors, the sensitivity of ELISA was high and egg antigens performed slightly better (SEA, 96%; CEF6, 97%) than worm antigen (94%). Sensitivity of IHA was satisfactory with homologous (Sm, >85%), but not heterologous (Sj, 56%) parasite antigen. In IFAT, the parenchyma-associated fluorescence showed high sensitivity (95%), but gut-associated fluorescence, which is known to be a sensitive diagnostic marker for schistosome-infected European travelers, was observed only in 76% of a sub-sample of 100 of the endemic sera. Among sera from egg-negative individuals, many gave positive reactions in several or all of the tests employed. These reactions (formally "false positive") are considered to represent true infections, since chemotherapy had not yet been delivered to this population. For the purpose of further surveys in Burkina Faso or other resource-poor settings, we suggest IHA as an accurate diagnostic test and propose to further improve its performance by including egg rather than worm antigens. PMID:15652331

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

    PubMed Central

    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

    Background 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. Methodology/Principal Findings 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

  8. A combined proteomic and immunologic approach for the analysis of Schistosoma mansoni cercariae and adult worm protein extracts and the detection of one of the vaccine candidates, Sm28GST, from a Venezuelan parasite isolate.

    PubMed

    Losada, Sandra; Sabatier, Laurence; Hammann, Philippe; Guillier, Christelle; Matos, César; Bermúdez, Henry; Lorenzo, María Angelita; Noya, Oscar

    2011-06-01

    Understanding the mode of Schistosoma mansoni larval invasion and the mechanism of immune evasion utilized by larvae and adult worms is essential for a rational development of vaccines or drugs to prevent or cure the disease. This parasite has a very complex molecular organization in all parasite stages, and identifying the major parasite proteins would give clues to schistosome metabolism and to the interaction of the parasite with the host immune system. Our goal was the evaluation of the protein parasite repertoire using a proteomic approach, and the characterization of protein extracts from two different parasite stages of a Venezuelan isolate, such as cercariae and adult worms, previously performed by other authors in some other strains. A comparison among authors was made. Besides, we aimed to identify different isoforms of one of the vaccine candidates, the gluthation-S-transferase protein (Sm28GST), by 2D SDS-PAGE and mass spectrometry, and to achieve its immunologic detection using sera from rabbits immunized with synthetic peptides derived from the Sm28GST protein. These techniques allowed the identification of some of the target molecules of the protective immune response that are being evaluated as potential members of a multi-component and multi-stage anti-S. mansoni vaccine and to clarify if the selected peptides induce antibodies that are able to recognize different isoforms of the Sm28GST. PMID:21866785

  9. Monoclonal antibody-based dipstick assay: a reliable field applicable technique for diagnosis of Schistosoma mansoni infection using human serum and urine samples.

    PubMed

    Demerdash, Zeinab; Mohamed, Salwa; Hendawy, Mohamed; Rabia, Ibrahim; Attia, Mohy; Shaker, Zeinab; Diab, Tarek M

    2013-02-01

    A field applicable diagnostic technique, the dipstick assay, was evaluated for its sensitivity and specificity in diagnosing human Schistosoma mansoni infection. A monoclonal antibody (mAb) against S. mansoni adult worm tegumental antigen (AWTA) was employed in dipstick and sandwich ELISA for detection of circulating schistosome antigen (CSA) in both serum and urine samples. Based on clinical and parasitological examinations, 60 S. mansoni-infected patients, 30 patients infected with parasites other than schistosomiasis, and 30 uninfected healthy individuals were selected. The sensitivity and specificity of dipstick assay in urine samples were 86.7% and 90.0%, respectively, compared to 90.0% sensitivity and 91.7% specificity of sandwich ELISA. In serum samples, the sensitivity and specificity were 88.3% and 91.7% for dipstick assay vs. 91.7% and 95.0% for sandwich ELISA, respectively. The diagnostic efficacy of dipstick assay in urine and serum samples was 88.3% and 90.0%, while it was 90.8% and 93.3% for sandwich ELISA, respectively. The diagnostic indices of dipstick assay and ELISA either in serum or in urine were statistically comparable (P>0.05). In conclusion, the dipstick assay offers an alternative simple, rapid, non-invasive technique in detecting CSA or complement to stool examinations especially in field studies. PMID:23467705

  10. Mobile phones and malaria: modeling human and parasite travel

    PubMed Central

    Buckee, Caroline O.; Wesolowski, Amy; Eagle, Nathan; Hansen, Elsa; Snow, Robert W.

    2013-01-01

    Human mobility plays an important role in the dissemination of malaria parasites between regions of variable transmission intensity. Asymptomatic individuals can unknowingly carry parasites to regions where mosquito vectors are available, for example, undermining control programs and contributing to transmission when they travel. Understanding how parasites are imported between regions in this way is therefore an important goal for elimination planning and the control of transmission, and would enable control programs to target the principal sources of malaria. Measuring human mobility has traditionally been difficult to do on a population scale, but the widespread adoption of mobile phones in low-income settings presents a unique opportunity to directly measure human movements that are relevant to the spread of malaria. Here, we discuss the opportunities for measuring human mobility using data from mobile phones, as well as some of the issues associated with combining mobility estimates with malaria infection risk maps to meaningfully estimate routes of parasite importation. PMID:23478045

  11. 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. PMID:25128879

  12. 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

  13. Environmental, genetic and immunological factors in human resistance to Schistosoma mansoni.

    PubMed

    Dessein, A J; Couissinier, P; Demeure, C; Rihet, P; Kohlstaedt, S; Carneiro-Carvalho, D; Ouattara, M; Goudot-Crozel, V; Dessein, H; Bourgois, A

    1992-08-01

    The design of programs for the control of endemies requires the knowledge of the principal factors that determine parasite transmission and infection levels in exposed populations. In the studies summarized in this article, the role of environmental and host specific factors in the infection by S. mansoni have been evaluated. It is shown that a limited number of factors actually influences infection intensity: water contacts, age, and sex were shown to account for 20 to 25% of infection variance, while 35 to 40% of it was accounted for by the effect of a major codominant gene. A remarkable fact is the important weighting (around 55% of the variance) of factors (the major gene and age) that influence human capacities of resistance. This observation strongly supports control measures aimed at increasing human resistance, such as vaccination. The effect of age on the development of resistance has now been observed in several studies on S. mansoni or S. haematobium. It is, therefore, a constant finding in schistosomiasis infections that resistance develops extremely slowly requiring a long period of exposure to the parasite and repeated infections. These studies provide strong incentives to increase efforts in the evaluation of the immune response of subjects living in endemic areas. Such evaluations are necessary to define vaccine and vaccination programs, and they are also urgently needed to evaluate the effects of chemotherapy on the development of immunity in children and adolescents, as well as on the persistence of protective immunity in adults. Immunological studies begin to provide a clearer picture of the role of acquired immunity in human protection against S. mansoni. It is increasingly clear that the slow development of resistance in children, as well as its alteration in certain age groups, are related to the maturation of parasite specific immunity and its alteration by specific immune factors. Thus, the development of resistance is associated with the

  14. Human facial beauty : Averageness, symmetry, and parasite resistance.

    PubMed

    Thornhill, R; Gangestad, S W

    1993-09-01

    It is hypothesized that human faces judged to be attractive by people possess two features-averageness and symmetry-that promoted adaptive mate selection in human evolutionary history by way of production of offspring with parasite resistance. Facial composites made by combining individual faces are judged to be attractive, and more attractive than the majority of individual faces. The composites possess both symmetry and averageness of features. Facial averageness may reflect high individual protein heterozygosity and thus an array of proteins to which parasites must adapt. Heterozygosity may be an important defense of long-lived hosts against parasites when it occurs in portions of the genome that do not code for the essential features of complex adaptations. In this case heterozygosity can create a hostile microenvironment for parasites without disrupting adaptation. Facial bilateral symmetry is hypothesized to affect positive beauty judgments because symmetry is a certification of overall phenotypic quality and developmental health, which may be importantly influenced by parasites. Certain secondary sexual traits are influenced by testosterone, a hormone that reduces immunocompetence. Symmetry and size of the secondary sexual traits of the face (e.g., cheek bones) are expected to correlate positively and advertise immunocompetence honestly and therefore to affect positive beauty judgments. Facial attractiveness is predicted to correlate with attractive, nonfacial secondary sexual traits; other predictions from the view that parasite-driven selection led to the evolution of psychological adaptations of human beauty perception are discussed. The view that human physical attractiveness and judgments about human physical attractiveness evolved in the context of parasite-driven selection leads to the hypothesis that both adults and children have a species-typical adaptation to the problem of identifying and favoring healthy individuals and avoiding parasite

  15. The machinery underlying malaria parasite virulence is conserved between rodent and human malaria parasites

    PubMed Central

    De Niz, Mariana; Ullrich, Ann-Katrin; Heiber, Arlett; Blancke Soares, Alexandra; Pick, Christian; Lyck, Ruth; Keller, Derya; Kaiser, Gesine; Prado, Monica; Flemming, Sven; del Portillo, Hernando; Janse, Chris J.; Heussler, Volker; Spielmann, Tobias

    2016-01-01

    Sequestration of red blood cells infected with the human malaria parasite Plasmodium falciparum in organs such as the brain is considered important for pathogenicity. A similar phenomenon has been observed in mouse models of malaria, using the rodent parasite Plasmodium berghei, but it is unclear whether the P. falciparum proteins known to be involved in this process are conserved in the rodent parasite. Here we identify the P. berghei orthologues of two such key factors of P. falciparum, SBP1 and MAHRP1. Red blood cells infected with P. berghei parasites lacking SBP1 or MAHRP1a fail to bind the endothelial receptor CD36 and show reduced sequestration and virulence in mice. Complementation of the mutant P. berghei parasites with the respective P. falciparum SBP1 and MAHRP1 orthologues restores sequestration and virulence. These findings reveal evolutionary conservation of the machinery underlying sequestration of divergent malaria parasites and support the notion that the P. berghei rodent model is an adequate tool for research on malaria virulence. PMID:27225796

  16. The machinery underlying malaria parasite virulence is conserved between rodent and human malaria parasites.

    PubMed

    De Niz, Mariana; Ullrich, Ann-Katrin; Heiber, Arlett; Blancke Soares, Alexandra; Pick, Christian; Lyck, Ruth; Keller, Derya; Kaiser, Gesine; Prado, Monica; Flemming, Sven; Del Portillo, Hernando; Janse, Chris J; Heussler, Volker; Spielmann, Tobias

    2016-01-01

    Sequestration of red blood cells infected with the human malaria parasite Plasmodium falciparum in organs such as the brain is considered important for pathogenicity. A similar phenomenon has been observed in mouse models of malaria, using the rodent parasite Plasmodium berghei, but it is unclear whether the P. falciparum proteins known to be involved in this process are conserved in the rodent parasite. Here we identify the P. berghei orthologues of two such key factors of P. falciparum, SBP1 and MAHRP1. Red blood cells infected with P. berghei parasites lacking SBP1 or MAHRP1a fail to bind the endothelial receptor CD36 and show reduced sequestration and virulence in mice. Complementation of the mutant P. berghei parasites with the respective P. falciparum SBP1 and MAHRP1 orthologues restores sequestration and virulence. These findings reveal evolutionary conservation of the machinery underlying sequestration of divergent malaria parasites and support the notion that the P. berghei rodent model is an adequate tool for research on malaria virulence. PMID:27225796

  17. Polymorphic microsatellites in the human bloodfluke, Schistosoma japonicum, identified using a genomic resource

    PubMed Central

    2011-01-01

    Re-emergence of schistosomiasis in regions of China where control programs have ceased requires development of molecular-genetic tools to track gene flow and assess genetic diversity of Schistosoma populations. We identified many microsatellite loci in the draft genome of Schistosoma japonicum using defined search criteria and selected a subset for further analysis. From an initial panel of 50 loci, 20 new microsatellites were selected for eventual optimization and application to a panel of worms from endemic areas. All but one of the selected microsatellites contain simple tri-nucleotide repeats. Moderate to high levels of polymorphism were detected. Numbers of alleles ranged from 6 to 14 and observed heterozygosity was always >0.6. The loci reported here will facilitate high resolution population-genetic studies on schistosomes in re-emergent foci. PMID:21299863

  18. A Miniaturized Screen of a Schistosoma mansoni Serotonergic G Protein-Coupled Receptor Identifies Novel Classes of Parasite-Selective Inhibitors

    PubMed Central

    Chan, John D.; McCorvy, John D.; Acharya, Sreemoyee; Day, Timothy A.; Roth, Bryan L.; Marchant, Jonathan S.

    2016-01-01

    Schistosomiasis is a tropical parasitic disease afflicting ~200 million people worldwide and current therapy depends on a single drug (praziquantel) which exhibits several non-optimal features. These shortcomings underpin the need for next generation anthelmintics, but the process of validating physiologically relevant targets (‘target selection’) and pharmacologically profiling them is challenging. Remarkably, even though over a quarter of current human therapeutics target rhodopsin-like G protein coupled receptors (GPCRs), no library screen of a flatworm GPCR has yet been reported. Here, we have pharmacologically profiled a schistosome serotonergic GPCR (Sm.5HTR) implicated as a downstream modulator of PZQ efficacy, in a miniaturized screening assay compatible with high content screening. This approach employs a split luciferase based biosensor sensitive to cellular cAMP levels that resolves the proximal kinetics of GPCR modulation in intact cells. Data evidence a divergent pharmacological signature between the parasitic serotonergic receptor and the closest human GPCR homolog (Hs.5HTR7), supporting the feasibility of optimizing parasitic selective pharmacophores. New ligands, and chemical series, with potency and selectivity for Sm.5HTR over Hs.5HTR7 are identified in vitro and validated for in vivo efficacy against schistosomules and adult worms. Sm.5HTR also displayed a property resembling irreversible inactivation, a phenomenon discovered at Hs.5HTR7, which enhances the appeal of this abundantly expressed parasite GPCR as a target for anthelmintic ligand design. Overall, these data underscore the feasibility of profiling flatworm GPCRs in a high throughput screening format competent to resolve different classes of GPCR modulators. Further, these data underscore the promise of Sm.5HTR as a chemotherapeutically vulnerable node for development of next generation anthelmintics. PMID:27187180

  19. A Miniaturized Screen of a Schistosoma mansoni Serotonergic G Protein-Coupled Receptor Identifies Novel Classes of Parasite-Selective Inhibitors.

    PubMed

    Chan, John D; McCorvy, John D; Acharya, Sreemoyee; Johns, Malcolm E; Day, Timothy A; Roth, Bryan L; Marchant, Jonathan S

    2016-05-01

    Schistosomiasis is a tropical parasitic disease afflicting ~200 million people worldwide and current therapy depends on a single drug (praziquantel) which exhibits several non-optimal features. These shortcomings underpin the need for next generation anthelmintics, but the process of validating physiologically relevant targets ('target selection') and pharmacologically profiling them is challenging. Remarkably, even though over a quarter of current human therapeutics target rhodopsin-like G protein coupled receptors (GPCRs), no library screen of a flatworm GPCR has yet been reported. Here, we have pharmacologically profiled a schistosome serotonergic GPCR (Sm.5HTR) implicated as a downstream modulator of PZQ efficacy, in a miniaturized screening assay compatible with high content screening. This approach employs a split luciferase based biosensor sensitive to cellular cAMP levels that resolves the proximal kinetics of GPCR modulation in intact cells. Data evidence a divergent pharmacological signature between the parasitic serotonergic receptor and the closest human GPCR homolog (Hs.5HTR7), supporting the feasibility of optimizing parasitic selective pharmacophores. New ligands, and chemical series, with potency and selectivity for Sm.5HTR over Hs.5HTR7 are identified in vitro and validated for in vivo efficacy against schistosomules and adult worms. Sm.5HTR also displayed a property resembling irreversible inactivation, a phenomenon discovered at Hs.5HTR7, which enhances the appeal of this abundantly expressed parasite GPCR as a target for anthelmintic ligand design. Overall, these data underscore the feasibility of profiling flatworm GPCRs in a high throughput screening format competent to resolve different classes of GPCR modulators. Further, these data underscore the promise of Sm.5HTR as a chemotherapeutically vulnerable node for development of next generation anthelmintics. PMID:27187180

  20. Helminth parasite proteomics: from experimental models to human infections

    PubMed Central

    MUTAPI, FRANCISCA

    2012-01-01

    SUMMARY Schistosomiasis is a major human helminth infection endemic in developing countries. Urogenital schistosomiasis, caused by S. haematobium, is the most prevalent human schistosome disease in sub-Saharan Africa. Currently control of schistosome infection is by treatment of infected people with the anthelmintic drug praziquantel, but there are calls for continued efforts to develop a vaccine against the parasites. In order for successful vaccine development, it is necessary to understand the biology and molecular characteristics of the parasite. Ultimately, there is need to understand the nature and dynamics of the relationship between the parasite and the natural host. Thus, my studies have focused on molecular characterization of different parasite stages and integrating this information with quantitative approaches to investigate the nature and development of protective immunity against schistosomes in humans. Proteomics has proved a powerful tool in these studies allowing the proteins expressed by the parasite to be characterized at a molecular and immunological level. In this review, the application of proteomic approaches to understanding the human-schistosome relationship as well as testing specific hypotheses on the nature and development of schistosome-specific immune responses is discussed. The contribution of these approaches to informing schistosome vaccine development is highlighted. PMID:22455721

  1. 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. PMID:27169695

  2. New Frontiers in Schistosoma Genomics and Transcriptomics

    PubMed Central

    Nahum, Laila A.; Mourão, Marina M.; Oliveira, Guilherme

    2012-01-01

    Schistosomes are digenean blood flukes of aves and mammals comprising 23 species. Some species are causative agents of human schistosomiasis, the second major neglected disease affecting over 230 million people worldwide. Modern technologies including the sequencing and characterization of nucleic acids and proteins have allowed large-scale analyses of parasites and hosts, opening new frontiers in biological research with potential biomedical and biotechnological applications. Nuclear genomes of the three most socioeconomically important species (S. haematobium, S. japonicum, and S. mansoni) have been sequenced and are under intense investigation. Mitochondrial genomes of six Schistosoma species have also been completely sequenced and analysed from an evolutionary perspective. Furthermore, DNA barcoding of mitochondrial sequences is used for biodiversity assessment of schistosomes. Despite the efforts in the characterization of Schistosoma genomes and transcriptomes, many questions regarding the biology and evolution of this important taxon remain unanswered. This paper aims to discuss some advances in the schistosome research with emphasis on genomics and transcriptomics. It also aims to discuss the main challenges of the current research and to point out some future directions in schistosome studies. PMID:23227308

  3. Control of human parasitic diseases: Context and overview.

    PubMed

    Molyneux, David H

    2006-01-01

    The control of parasitic diseases of humans has been undertaken since the aetiology and natural history of the infections was recognized and the deleterious effects on human health and well-being appreciated by policy makers, medical practitioners and public health specialists. However, while some parasitic infections such as malaria have proved difficult to control, as defined by a sustained reduction in incidence, others, particularly helminth infections can be effectively controlled. The different approaches to control from diagnosis, to treatment and cure of the clinically sick patient, to control the transmission within the community by preventative chemotherapy and vector control are outlined. The concepts of eradication, elimination and control are defined and examples of success summarized. Overviews of the health policy and financing environment in which programmes to control or eliminate parasitic diseases are positioned and the development of public-private partnerships as vehicles for product development or access to drugs for parasite disease control are discussed. Failure to sustain control of parasites may be due to development of drug resistance or the failure to implement proven strategies as a result of decreased resources within the health system, decentralization of health management through health-sector reform and the lack of financial and human resources in settings where per capita government expenditure on health may be less than $US 5 per year. However, success has been achieved in several large-scale programmes through sustained national government investment and/or committed donor support. It is also widely accepted that the level of investment in drug development for the parasitic diseases of poor populations is an unattractive option for pharmaceutical companies. The development of partnerships to specifically address this need provides some hope that the intractable problems of the treatment regimens for the trypanosomiases and

  4. Human Adaptation to the Parasitic Environment

    PubMed Central

    Dudley, Sheldon F.

    1929-01-01

    Man, in contact with the pathogens in his environment, responds by developing immunity with or without symptomatic illness. The incidence of infectious disease in a community depends on the parasitic factor or “infection pressure,” and the host factor, “herd immunity,” i.e., the resistance of the community as a whole to the infection. Environment is only a secondary factor which alters the relative values of the two primary factors. Morbidity varies directly as the “infection pressure,” and inversely as the “herd immunity.” The great difficulty heretofore has been to separate the two factors expressing morbidity. In diphtheria, to some extent, this is now possible by means of the Schick test. By using clues gained from the study of diphtheria, and examining the age-incidence, severity, and fatality, of other infections under various environmental conditions, the hypothesis is reached that herd-immunity increases with the herd's past experience of the bacterial causes of most, if not all, infectious diseases. This immunity may be acquired latently, without illness, and, even if not always enough to prevent symptomatic infection, may be such that severity and fatality are decreased. The process is an example of the general biological mechanism by which the members of a species acquire adaptative variations more suitable to the environment. Of recent years air-borne droplet infections have caused less fatality and trouble to the English herd than a century ago. The manifold increase of the density and of the motion in the English herd must have greatly raised the average infection-pressure, but since severity of clinical disease has diminished and incidence has not increased in proportion, the herd-immunity of the English must have outstripped the increase of infection-pressure, i.e., the herd has become more closely adapted to its bacterial environment. It must not, however, be forgotten that adaptive fluctuations in parasitic characters must also

  5. Schistosome serine protease inhibitors: parasite defense or homeostasis?

    PubMed Central

    Lopez Quezada, Landys A.; McKerrow, James H.

    2016-01-01

    Serpins are a structurally conserved family of macromolecular inhibitors found in numerous biological systems. The completion and annotation of the genomes of Schistosoma mansoni and Schistosoma japonicum has enabled the identification by phylogenetic analysis of two major serpin clades. S. mansoni shows a greater multiplicity of serpin genes, perhaps reflecting adaptation to infection of a human host. Putative targets of schistosome serpins can be predicted from the sequence of the reactive center loop (RCL). Schistosome serpins may play important roles in both post-translational regulation of schistosome-derived proteases, as well as parasite defense mechanisms against the action of host proteases. PMID:21670886

  6. Structural bioinformatics study of PNP from Schistosoma mansoni.

    PubMed

    da Silveira, Nelson José Freitas; Uchôa, Hugo Brandão; Canduri, Fernanda; Pereira, José Henrique; Camera, João Carlos; Basso, Luiz Augusto; Palma, Mário Sergio; Santos, Diógenes Santiago; de Azevedo, Walter Filgueira

    2004-09-10

    The parasite Schistosoma mansoni lacks the de novo pathway for purine biosynthesis and depends on salvage pathways for its purine requirements. Schistosomiasis is endemic in 76 countries and territories and amongst the parasitic diseases ranks second after malaria in terms of social and economic impact and public health importance. The PNP is an attractive target for drug design and it has been submitted to extensive structure-based design. The atomic coordinates of the complex of human PNP with inosine were used as template for starting the modeling of PNP from S. mansoni complexed with inosine. Here we describe the model for the complex SmPNP-inosine and correlate the structure with differences in the affinity for inosine presented by human and S. mansoni PNPs. PMID:15313179

  7. Human parasitic protozoan infection to infertility: a systematic review.

    PubMed

    Shiadeh, Malihe Nourollahpour; Niyyati, Maryam; Fallahi, Shirzad; Rostami, Ali

    2016-02-01

    Protozoan parasitic diseases are endemic in many countries worldwide, especially in developing countries, where infertility is a major burden. It has been reported that such infections may cause infertility through impairment in male and female reproductive systems. We searched Medline, PubMed, and Scopus databases and Google scholar to identify the potentially relevant studies on protozoan parasitic infections and their implications in human and animal model infertility. Literature described that some of the protozoan parasites such as Trichomonas vaginalis may cause deformities of the genital tract, cervical neoplasia, and tubal and atypical pelvic inflammations in women and also non-gonoccocal urethritis, asthenozoospermia, and teratozoospermia in men. Toxopalasma gondii could cause endometritis, impaired folliculogenesis, ovarian and uterine atrophy, adrenal hypertrophy, vasculitis, and cessation of estrus cycling in female and also decrease in semen quality, concentration, and motility in male. Trypanosoma cruzi inhibits cell division in embryos and impairs normal implantation and development of placenta. Decrease in gestation rate, infection of hormone-producing glands, parasite invasion of the placenta, and overproduction of inflammatory cytokines in the oviducts and uterine horns are other possible mechanisms induced by Trypanosoma cruzi to infertility. Plasmodium spp. and Trypanosoma brucei spp. cause damage in pituitary gland, hormonal disorders, and decreased semen quality. Entamoeba histolytica infection leads to pelvic pain, salpingitis, tubo-ovarian abscess, and genital ulcers. Cutaneous and visceral leishmaniasis can induce genital lesion, testicular amyloidosis, inflammation of epididymis, prostatitis, and sperm abnormality in human and animals. In addition, some epidemiological studies have reported that rates of protozoan infections in infertile patients are higher than healthy controls. The current review indicates that protozoan parasitic

  8. Parasites

    MedlinePlus

    ... CME and CNE for clinicians... Parasitic Disease and Malaria Strategic Priorities: 2015—2020... Cyclosporiasis: Most U.S. cases ... R S T U V W X Y Z Malaria An ancient disease that affects millions of people ...

  9. Affinities between Asian non-human Schistosoma species, the S. indicum group, and the African human schistosomes.

    PubMed

    Agatsuma, T; Iwagami, M; Liu, C X; Rajapakse, R P V J; Mondal, M M H; Kitikoon, V; Ambu, S; Agatsuma, Y; Blair, D; Higuchi, T

    2002-03-01

    Schistosoma species have traditionally been arranged in groups based on egg morphology, geographical origins, and the genus or family of snail intermediate host. One of these groups is the 'S. indicum group' comprising species from Asia that use pulmonate snails as intermediate hosts. DNA sequences were obtained from the four members of this group (S. indicum, S. spindale, S. nasale and S. incognitum) to provide information concerning their phylogenetic relationships with other Asian and African species and species groups. The sequences came from the second internal transcribed spacer (ITS2) of the ribosomal gene repeat, part of the 28S ribosomal RNA gene (28S), and part of the mitochondrial cytochrome c oxidase subunit 1 (CO1) gene. Tree analyses using both distance and parsimony methods showed the S. indicum group not to be monophyletic. Schistosoma indicum, S. spindale and S. nasale were clustered among African schistosomes, while S. incognitum was placed as sister to the African species (using ITS2 and 28S nucleotide sequences and CO1 amino acid sequences), or as sister to all other species of Schistosoma (CO1 nucleotide sequences). Based on the present molecular data, a scenario for the evolution of the S. indicum group is discussed. PMID:12018199

  10. In Vitro and In Vivo Activities of Arachidonic Acid against Schistosoma mansoni and Schistosoma haematobium▿

    PubMed Central

    El Ridi, Rashika; Aboueldahab, Marwa; Tallima, Hatem; Salah, Mohamed; Mahana, Noha; Fawzi, Samia; Mohamed, Shadia H.; Fahmy, Omar M.

    2010-01-01

    The development of arachidonic acid (ARA) for treatment of schistosomiasis is an entirely novel approach based on a breakthrough discovery in schistosome biology revealing that activation of parasite tegument-bound neutral sphingomyelinase (nSMase) by unsaturated fatty acids, such as ARA, induces exposure of parasite surface membrane antigens to antibody binding and eventual attrition of developing schistosomula and adult worms. Here, we demonstrate that 5 mM ARA leads to irreversible killing of ex vivo 1-, 3-, 4-, 5-, and 6-week-old Schistosoma mansoni and 9-, 10-, and 12-week-old Schistosoma haematobium worms within 3 to 4 h, depending on the parasite age, even when the worms were maintained in up to 50% fetal calf serum. ARA-mediated worm attrition was prevented by nSMase inhibitors, such as CaCl2 and GW4869. Scanning and transmission electron microscopy revealed that ARA-mediated worm killing was associated with spine destruction, membrane blebbing, and disorganization of the apical membrane structure. ARA-mediated S. mansoni and S. haematobium worm attrition was reproduced in vivo in a series of 6 independent experiments using BALB/c or C57BL/6 mice, indicating that ARA in a pure form (Sigma) or included in infant formula (Nestle) consistently led to 40 to 80% decrease in the total worm burden. Arachidonic acid is already marketed for human use in the United States and Canada for proper development of newborns and muscle growth of athletes; thus, ARA has potential as a safe and cost-effective addition to antischistosomal therapy. PMID:20479203

  11. Myeloradiculitis: a rare event in schistosoma infection.

    PubMed

    Wichmann, D; Hofmann, C; Sudeck, H; Burchard, G-D; Moser, A

    2006-12-01

    Schistosomiasis a parasitic disease caused by trematodes is widely distributed in (sub-)tropical countries. Depending on the species the infection manifests clinically as gastrointestinal (preferentially Schistosoma mansoni and S. japonicum) or urinary (preferentially S. haematobium) disorders. Here we present an uncommon case of myeloradiculitis leading to bladder palsy and sensory loss at the lower limbs. PMID:17180592

  12. Schistosoma hematobium-associated glomerulopathy

    PubMed Central

    Seck, S. M.; Sarr, M. L.; Dial, M. C.; Ka, E. F.

    2011-01-01

    Schistosomiasis is the second most devastating tropical parasitic disease worldwide and is responsible for many urological complications. However, glomerular injury is a rare complication mainly described with Schistosoma mansoni. We report a case of membranoproliferative glomerulonephritis (MPGN) associated with Schistosoma hematobium infection in a young Senegalese boy living in a rural area. Clinical presentation was with steroid-resistant with nephrotic syndrome. Renal biopsy showed type 1 MPGN with the presence of S. hematobium eggs surrounded by a gigantocellular granuloma. Despite therapy with antihelminthic and immunosuppressive drugs, evolution was characterized by progression to end-stage renal disease over 1 year. More efforts should be made on the prevention and early detection of schistosomiasis among at-risk populations. PMID:21886983

  13. Schistosoma-associated Salmonella resist antibiotics via specific fimbrial attachments to the flatworm

    PubMed Central

    2011-01-01

    Background Schistosomes are parasitic helminths that infect humans through dermo-invasion while in contaminated water. Salmonella are also a common water-borne human pathogen that infects the gastrointestinal tract via the oral route. Both pathogens eventually enter the systemic circulation as part of their respective disease processes. Concurrent Schistosoma-Salmonella infections are common and are complicated by the bacteria adhering to adult schistosomes present in the mesenteric vasculature. This interaction provides a refuge in which the bacterium can putatively evade antibiotic therapy and anthelmintic monotherapy can lead to a massive release of occult Salmonella. Results Using a novel antibiotic protection assay, our results reveal that Schistosoma-associated Salmonella are refractory to eight different antibiotics commonly used to treat salmonellosis. The efficacy of these antibiotics was decreased by a factor of 4 to 16 due to this association. Salmonella binding to schistosomes occurs via a specific fimbrial protein (FimH) present on the surface on the bacterium. This same fimbrial protein confers the ability of Salmonella to bind to mammalian cells. Conclusions Salmonella can evade certain antibiotics by binding to Schistosoma. As a result, effective bactericidal concentrations of antibiotics are unfortunately above the achievable therapeutic levels of the drugs in co-infected individuals. Salmonella-Schistosoma binding is analogous to the adherence of Salmonella to cells lining the mammalian intestine. Perturbing this binding is the key to eliminating Salmonella that complicate schistosomiasis. PMID:21711539

  14. The affinity of magnetic microspheres for Schistosoma eggs.

    PubMed

    Candido, Renata R F; Favero, Vivian; Duke, Mary; Karl, Stephan; Gutiérrez, Lucía; Woodward, Robert C; Graeff-Teixeira, Carlos; Jones, Malcolm K; St Pierre, Timothy G

    2015-01-01

    Schistosomiasis is a chronic parasitic disease of humans, with two species primarily causing the intestinal infection: Schistosoma mansoni and Schistosoma japonicum. Traditionally, diagnosis of schistosomiasis is achieved through direct visualisation of eggs in faeces using techniques that lack the sensitivity required to detect all infections, especially in areas of low endemicity. A recently developed method termed Helmintex™ is a very sensitive technique for detection of Schistosoma eggs and exhibits 100% sensitivity at 1.3 eggs per gram of faeces, enough to detect even low-level infections. The Helminthex™ method is based on the interaction of magnetic microspheres and schistosome eggs. Further understanding the underlying egg-microsphere interactions would enable a targeted optimisation of egg-particle binding and may thus enable a significant improvement of the Helmintex™ method and diagnostic sensitivity in areas with low infection rates. We investigated the magnetic properties of S. mansoni and S. japonicum eggs and their interactions with microspheres with different magnetic properties and surface functionalization. Eggs of both species exhibited higher binding affinity to the magnetic microspheres than the non-magnetic microspheres. Binding efficiency was further enhanced if the particles were coated with streptavidin. Schistosoma japonicum eggs bound more microspheres compared with S. mansoni. However, distinct differences within eggs of each species were also observed when the distribution of the number of microspheres bound per egg was modelled with double Poisson distributions. Using this approach, both S. japonicum and S. mansoni eggs fell into two groups, one having greater affinity for magnetic microspheres than the other, indicating that not all eggs of a species exhibit the same binding affinity. Our observations suggest that interaction between the microspheres and eggs is more likely to be related to surface charge-based electrostatic

  15. Can the common brain parasite, Toxoplasma gondii, influence human culture?

    PubMed Central

    Lafferty, Kevin D

    2006-01-01

    The latent prevalence of a long-lived and common brain parasite, Toxoplasma gondii, explains a statistically significant portion of the variance in aggregate neuroticism among populations, as well as in the ‘neurotic’ cultural dimensions of sex roles and uncertainty avoidance. Spurious or non-causal correlations between aggregate personality and aspects of climate and culture that influence T. gondii transmission could also drive these patterns. A link between culture and T. gondii hypothetically results from a behavioural manipulation that the parasite uses to increase its transmission to the next host in the life cycle: a cat. While latent toxoplasmosis is usually benign, the parasite's subtle effect on individual personality appears to alter the aggregate personality at the population level. Drivers of the geographical variation in the prevalence of this parasite include the effects of climate on the persistence of infectious stages in soil, the cultural practices of food preparation and cats as pets. Some variation in culture, therefore, may ultimately be related to how climate affects the distribution of T. gondii, though the results only explain a fraction of the variation in two of the four cultural dimensions, suggesting that if T. gondii does influence human culture, it is only one among many factors. PMID:17015323

  16. Photosensitized inactivation of infectious blood-borne human parasites

    NASA Astrophysics Data System (ADS)

    Judy, Millard M.; Sogandares-Bernal, Franklin M.; Matthews, James Lester

    1995-05-01

    Blood-borne viruses and protozoan parasites that are infectious to humans pose risk world-wide of infection transmission through blood and blood product transfusion. Blood-borne infectious viruses include human immunodeficiency virus (HIV-I), which causes AIDS; hepatitis C virus, which can cause chronic hepatitis; and cytomegalovirus, which can be dangerous to immunocompromised patients, e.g., the newborn, transplant recipients, and AIDS patients. Infectious blood-borne protozoan parasites include Trypanosoma cruzi, which causes Chagas' disease, endemic throughout Central and South America; the Trypanosoma species causing African sleeping sickness endemic in Central Africa; and Plasmodium falciparum, which causes malignant and increasingly drug- resistant human malaria prevalent throughout the tropics. Some researchers have focused on using photosensitizers to inactivate HIV-I and other viruses in whole blood, packed red cells, and platelet concentrates without compromising blood product function. Our group previously has reported photosensitized in vitro inactivation of P. falciparum and the mouse malaria organism Plasmodium berghei in whole blood using hematoporphyrin derivative (HPD) and of T. cruzi using benzoporphyrin derivatives BPDMA and BPDDA, dihematoporphyrin ether (DHE), and hydroxyethylvinyldeuteroporphyrin (HEVD). These results suggest that continued investigation is warranted to evaluate the potential for photosensitized inactivation of blood-borne parasites in blood banking.

  17. Preliminary trials with praziquantel in human infections due to Schistosoma mansoni

    PubMed Central

    Katz, N.; Rocha, R.S.; Chaves, A.

    1979-01-01

    As part of a programme of multicentre trials of the tolerance and therapeutic effect of praziquantel, clinical trials were carried out in Brazil in patients with active Schistosoma mansoni infections, each of whom had a minimum geometric mean egg output of 100 eggs per gram of faeces calculated from multiple pretreatment stool examinations. The first stage was a double-blind assessment of tolerance and efficacy of oral doses of 1 × 20, 2 × 20, or 3 × 20 mg of praziquantel per kg of body weight. Subsequently, single-blind trials explored the effects of 3 × 20 mg/kg at 4-hourly intervals, and a single dose of 50 mg/kg. Side effects increased in frequency as dosage increased. Nausea, epigastric pain, headache, dizziness, and drowsiness were all noted but their severity was mild or moderate and they disappeared in 48 hours. In general, monitoring laboratory tests showed little change. Following a stringent parasitological follow-up, 96% of 28 patients followed at 1 year after treatment with either 3 × 20 mg/kg or 1 × 50 mg/kg were cured. Praziquantel seems to be a very promising drug against S. mansoni and further clinical trials should be strongly encouraged. PMID:396054

  18. Development and behavior of cultured Schistosoma mansoni fed on human erythrocyte ghosts.

    PubMed

    Basch, P F

    1984-09-01

    Schistosomula and adults of Schistosoma mansoni were grown from cercariae in cultures differing only in the treatment of the red blood cells fed to the organisms. "Pink ghosts," containing about 5% of the original hemoglobin, were produced by hemolysis in water; "white ghosts" with no detectable hemoglobin were made in 5 mM phosphate buffer, pH 8. Early growth and development were more rapid and vigorous, and pairs formed more readily when pink ghosts, rather than intact erythrocytes were fed. Schistosomula remained stunted and undeveloped when fed with white ghosts. Attempts at reconstitution of the latter by addition of hemoglobin, concentrated erythrocyte lysate, or pressure-liquefied pink ghosts did not restore growth-promoting activity. Pink ghost-fed worms, particularly paired males, attached to the dish bottom by their acetabulum and oral sucker and travelled by an active looping motion. Substrates of collagen or fibrin or a mammalian cell monolayer did not affect this behavior. Such attachment and locomotion are interpreted as instinctive migratory behavior of schistosomes. PMID:6486300

  19. Ape parasite origins of human malaria virulence genes.

    PubMed

    Larremore, Daniel B; Sundararaman, Sesh A; Liu, Weimin; Proto, William R; Clauset, Aaron; Loy, Dorothy E; Speede, Sheri; Plenderleith, Lindsey J; Sharp, Paul M; Hahn, Beatrice H; Rayner, Julian C; Buckee, Caroline O

    2015-01-01

    Antigens encoded by the var gene family are major virulence factors of the human malaria parasite Plasmodium falciparum, exhibiting enormous intra- and interstrain diversity. Here we use network analysis to show that var architecture and mosaicism are conserved at multiple levels across the Laverania subgenus, based on var-like sequences from eight single-species and three multi-species Plasmodium infections of wild-living or sanctuary African apes. Using select whole-genome amplification, we also find evidence of multi-domain var structure and synteny in Plasmodium gaboni, one of the ape Laverania species most distantly related to P. falciparum, as well as a new class of Duffy-binding-like domains. These findings indicate that the modular genetic architecture and sequence diversity underlying var-mediated host-parasite interactions evolved before the radiation of the Laverania subgenus, long before the emergence of P. falciparum. PMID:26456841

  20. Fungal, Viral, and Parasitic Pneumonias Associated with Human Immunodeficiency Virus.

    PubMed

    Skalski, Joseph H; Limper, Andrew H

    2016-04-01

    Respiratory illness is an important cause of morbidity and mortality in patients with human immunodeficiency virus (HIV). The spectrum of pulmonary disease that can affect patients with HIV is wide and includes opportunistic infection with many fungal, viral, and parasitic organisms. This article reviews the clinical presentation; approach to diagnosis; and management of fungal, viral, and parasitic pneumonias that can develop in patients with HIV including respiratory disease caused by Aspergillus, Cryptococcus, Histoplasma, Coccidioides, Cytomegalovirus, Toxoplasma, and Strongyloides. Because clinical symptoms and radiographic patterns are often insensitive at distinguishing these pulmonary infections, this review particularly focuses on specific host risk factors and diagnostic testing to consider when approaching HIV patients with respiratory illness. PMID:26974302

  1. Ape parasite origins of human malaria virulence genes

    PubMed Central

    Larremore, Daniel B.; Sundararaman, Sesh A.; Liu, Weimin; Proto, William R.; Clauset, Aaron; Loy, Dorothy E.; Speede, Sheri; Plenderleith, Lindsey J.; Sharp, Paul M.; Hahn, Beatrice H.; Rayner, Julian C.; Buckee, Caroline O.

    2015-01-01

    Antigens encoded by the var gene family are major virulence factors of the human malaria parasite Plasmodium falciparum, exhibiting enormous intra- and interstrain diversity. Here we use network analysis to show that var architecture and mosaicism are conserved at multiple levels across the Laverania subgenus, based on var-like sequences from eight single-species and three multi-species Plasmodium infections of wild-living or sanctuary African apes. Using select whole-genome amplification, we also find evidence of multi-domain var structure and synteny in Plasmodium gaboni, one of the ape Laverania species most distantly related to P. falciparum, as well as a new class of Duffy-binding-like domains. These findings indicate that the modular genetic architecture and sequence diversity underlying var-mediated host-parasite interactions evolved before the radiation of the Laverania subgenus, long before the emergence of P. falciparum. PMID:26456841

  2. Release of leukotriene C4 (LTC4) from human eosinophils following adherence to IgE- and IgG-coated schistosomula of Schistosoma mansoni.

    PubMed Central

    Moqbel, R; Macdonald, A J; Cromwell, O; Kay, A B

    1990-01-01

    The release of leukotriene C4 (LTC4) from human low-density eosinophils following adherence to live or formalin-fixed schistosomula of Schistosoma mansoni coated with parasite-specific IgE or IgG obtained from pooled human anti-S. mansoni serum has been studied. IgE-rich fractions were obtained after fractionation of pooled immune sera on fast-protein liquid chromatography (FPLC; polyanion SI-17 column) and were identified by parasite-specific RAST. Contaminating IgG was removed by adsorption on a Staphylococcus aureus-protein A affinity column. IgG-rich FPLC fractions were identified by a specific ELISA assay. IgG-dependent activities were confirmed by protein A adsorption. Low-density eosinophils adhered to live and formalin-fixed schistosomula coated with specific antisera and released 11.7 +/- 2.7 and 16.5 +/- 3.5 pmoles of LTC4/10(6) cells, respectively. LTC4 release induced by A23187 (5 x 10(-6) M) from the same cells was 80 +/- 24 pmoles/10(6) cells and 9.9 +/- 1 pmoles/10(6) cells in the presence of Sepharose particles (CNBr-activated 4B beads) covalently coated with normal human IgG. Fixed schistosomula coated with FPLC-purified IgE and IgG gave 7.6 +/- 0.4 and 6.0 +/- 0.1 pmoles of LTC4 per 10(6) low-density eosinophils, respectively. The same IgE- and IgG-rich fractions induced eosinophil-mediated cytotoxicity of live schistosomula in vitro. Removal of IgE by an anti-IgE affinity column abolished both the IgE-dependent release of LTC4 and the in vitro killing of larvae. Conversely, IgG-dependent activities were abolished by protein A, but not anti-IgE, adsorption. Normal density eosinophils generated undetectable amounts of LTC4 when incubated with IgE-coated schistosomula, whereas with IgG-coated larvae 4.6 pmoles/10(6) cells were obtained. Following preincubation with platelet-activating factor (PAF) (10(-7) M) and leukotriene B4 (LTB4) (10(-7) M), normal density eosinophils released LTC4 when in contact with larvae coated with antigen-specific Ig

  3. [Human intestinal parasites in Subsaharan Africa. II. Sao Tomé and Principe].

    PubMed

    Pampiglione, S; Visconti, S; Pezzino, G

    1987-04-01

    In 1983 the authors carried out a survey in the Democratic Republic of São Tomé and Principe, analysing 1050 specimens of stools collected among the population from apparently healthy subjects chosen at random and in a number proportional to the distribution of the population in the regions of the country (about 1% of the population was examined). The examined subjects were divided into 3 age groups (0-3, 4-12, more than 12 years old), to have homogeneous groups in relation principally to modalities of life and nutritional patterns. There were 488 male subjects and 562 females. The survey was preceded by a sensitization of the people to the problem of intestinal parasites and by two preliminary surveys about the number of existing latrines and about people's believes and attitudes in relation to helmintiasis. The tests were made according to the modified Ritchie technique on fecal specimens preserved with 10% formol solution. The following results were found: a) Protozoa: Entamoeba coli, 43.0%; Iodamoeba buetschlii, 9.0%; Giardia intestinalis, 8.8%; Endolimax nana, 7.0%; E. histolytica, 5.5%; E. hartmanni, 2.5%; Chilomastix mesnili, 2.3%; Trichomonas intestinalis, 0.2%; Balantidium coli, 0.1%. b) Helminths: Trichuris trichiura, 87.7%; Ascaris lumbricoides, 64.3%; Ancylostomatidae, 40.5%; Strongyloides stercoralis, 6.8%; Hymenolepis diminuta, 0.3%; H. nana, 0.2%; Schistosoma haematobium, 0.2%. In 28.2% of the specimens (with more than 50% of subjects in some villages) eggs of Heterophyidae were found, very similar to Metagonimus yokogawai, but not yet identified by us, with the following characteristics: elliptical shape, average size 25 mu (22.2-27.7) X 18.5 mu (17-21), thick wall, operculum difficult to see, not sticking out from the outline but visible by focusing being in a different refractiveness, presence of a small polar knob, colour slightly brownish, asymmetric miracidium. Further investigations are necessary to identify the species of this trematode and

  4. Mitochondrial gene order change in Schistosoma (Platyhelminthes: Digenea: Schistosomatidae).

    PubMed

    Webster, Bonnie L; Littlewood, D Timothy J

    2012-01-01

    In the flatworm genus Schistosoma, species of which include parasites of biomedical and veterinary importance, mitochondrial gene order is radically different in some species. A PCR-based survey of 19 schistosomatid spp. established which of 14 Schistosoma spp. have the ancestral (plesiomorphic) or derived gene order condition. A phylogeny for Schistosoma was estimated and used to infer the origin of the gene order change which is present in all members of a clade containing Schistosoma incognitum and members of the traditionally recognised Schistosoma indicum, Schistosoma mansoni and Schistosomahaematobium spp. groups. Schistosoma turkestanicum, with the plesiomorphic gene order state, is sister to this clade. Common interval analysis suggests change in gene order, from ancestral to derived, consisted of two sequential transposition events: (a) nad1_nad3 to nad3_nad1 and (b) [atp6,nad2]_[nad3,-nad1,cox1,rrnL,rrnS,cox2,nad6] to [nad3,nad1,cox1,rrnL,rrnS,cox2,nad6]_[atp6,nad2], where gene order offragments within square brackets remain unchanged. Gene order change is rare in parasitic flatworms and is a robust synapomorphy for schistosome spp. that exhibit it. The schistosomatid phylogeny casts some doubt on the origin of Schistosoma (Asian or African), highlights the propensity for species to hosts witch amongst mammalian (definitive) hosts, and indicates the likely importance of snail (intermediate)hosts in determining and defining patterns of schistosome radiation and continental invasion. Mitogenomic sampling of Schistosoma dattai and Schistosoma harinasutai to determine gene order, and within key species, especially S. turkestanicum and S. incognitum, to determine ancestral ranges, may help discover the geographic origins of gene order change in the genus. Samples of S. incognitum from India and Thailand suggest this taxon may include cryptic species. PMID:23362512

  5. Proteomic Analysis of the Schistosoma mansoni Miracidium.

    PubMed

    Wang, Tianfang; Zhao, Min; Rotgans, Bronwyn A; Strong, April; Liang, Di; Ni, Guoying; Limpanont, Yanin; Ramasoota, Pongrama; McManus, Donald P; Cummins, Scott F

    2016-01-01

    Despite extensive control efforts, schistosomiasis continues to be a major public health problem in developing nations in the tropics and sub-tropics. The miracidium, along with the cercaria, both of which are water-borne and free-living, are the only two stages in the life-cycle of Schistosoma mansoni which are involved in host invasion. Miracidia penetrate intermediate host snails and develop into sporocysts, which lead to cercariae that can infect humans. Infection of the snail host by the miracidium represents an ideal point at which to interrupt the parasite's life-cycle. This research focuses on an analysis of the miracidium proteome, including those proteins that are secreted. We have identified a repertoire of proteins in the S. mansoni miracidium at 2 hours post-hatch, including proteases, venom allergen-like proteins, receptors and HSP70, which might play roles in snail-parasite interplay. Proteins involved in energy production and conservation were prevalent, as were proteins predicted to be associated with defence. This study also provides a strong foundation for further understanding the roles that neurohormones play in host-seeking by schistosomes, with the potential for development of novel anthelmintics that interfere with its various life-cycle stages. PMID:26799066

  6. Genome sequence of the stramenopile Blastocystis, a human anaerobic parasite

    PubMed Central

    2011-01-01

    Background Blastocystis is a highly prevalent anaerobic eukaryotic parasite of humans and animals that is associated with various gastrointestinal and extraintestinal disorders. Epidemiological studies have identified different subtypes but no one subtype has been definitively correlated with disease. Results Here we report the 18.8 Mb genome sequence of a Blastocystis subtype 7 isolate, which is the smallest stramenopile genome sequenced to date. The genome is highly compact and contains intriguing rearrangements. Comparisons with other available stramenopile genomes (plant pathogenic oomycete and diatom genomes) revealed effector proteins potentially involved in the adaptation to the intestinal environment, which were likely acquired via horizontal gene transfer. Moreover, Blastocystis living in anaerobic conditions harbors mitochondria-like organelles. An incomplete oxidative phosphorylation chain, a partial Krebs cycle, amino acid and fatty acid metabolisms and an iron-sulfur cluster assembly are all predicted to occur in these organelles. Predicted secretory proteins possess putative activities that may alter host physiology, such as proteases, protease-inhibitors, immunophilins and glycosyltransferases. This parasite also possesses the enzymatic machinery to tolerate oxidative bursts resulting from its own metabolism or induced by the host immune system. Conclusions This study provides insights into the genome architecture of this unusual stramenopile. It also proposes candidate genes with which to study the physiopathology of this parasite and thus may lead to further investigations into Blastocystis-host interactions. PMID:21439036

  7. Dogs as Sources and Sentinels of Parasites in Humans and Wildlife, Northern Canada

    PubMed Central

    Salb, Amanda L.; Barkema, Herman W.; Elkin, Brett T.; Thompson, R.C. Andrew; Whiteside, Douglas P.; Black, Sandra R.; Dubey, J.P.

    2008-01-01

    A minimum of 11 genera of parasites, including 7 known or suspected to cause zoonoses, were detected in dogs in 2 northern Canadian communities. Dogs in remote settlements receive minimal veterinary care and may serve as sources and sentinels for parasites in persons and wildlife, and as parasite bridges between wildlife and humans. PMID:18258078

  8. Normocyte-binding protein required for human erythrocyte invasion by the zoonotic malaria parasite Plasmodium knowlesi.

    PubMed

    Moon, Robert W; Sharaf, Hazem; Hastings, Claire H; Ho, Yung Shwen; Nair, Mridul B; Rchiad, Zineb; Knuepfer, Ellen; Ramaprasad, Abhinay; Mohring, Franziska; Amir, Amirah; Yusuf, Noor A; Hall, Joanna; Almond, Neil; Lau, Yee Ling; Pain, Arnab; Blackman, Michael J; Holder, Anthony A

    2016-06-28

    The dominant cause of malaria in Malaysia is now Plasmodium knowlesi, a zoonotic parasite of cynomolgus macaque monkeys found throughout South East Asia. Comparative genomic analysis of parasites adapted to in vitro growth in either cynomolgus or human RBCs identified a genomic deletion that includes the gene encoding normocyte-binding protein Xa (NBPXa) in parasites growing in cynomolgus RBCs but not in human RBCs. Experimental deletion of the NBPXa gene in parasites adapted to growth in human RBCs (which retain the ability to grow in cynomolgus RBCs) restricted them to cynomolgus RBCs, demonstrating that this gene is selectively required for parasite multiplication and growth in human RBCs. NBPXa-null parasites could bind to human RBCs, but invasion of these cells was severely impaired. Therefore, NBPXa is identified as a key mediator of P. knowlesi human infection and may be a target for vaccine development against this emerging pathogen. PMID:27303038

  9. Mosquitoes as Potential Bridge Vectors of Malaria Parasites from Non-Human Primates to Humans

    PubMed Central

    Verhulst, Niels O.; Smallegange, Renate C.; Takken, Willem

    2012-01-01

    Malaria is caused by Plasmodium parasites which are transmitted by mosquitoes. Until recently, human malaria was considered to be caused by human-specific Plasmodium species. Studies on Plasmodium parasites in non-human primates (NHPs), however, have identified parasite species in gorillas and chimpanzees that are closely related to human Plasmodium species. Moreover, P. knowlesi, long known as a parasite of monkeys, frequently infects humans. The requirements for such a cross-species exchange and especially the role of mosquitoes in this process are discussed, as the latter may act as bridge vectors of Plasmodium species between different primates. Little is known about the mosquito species that would bite both humans and NHPs and if so, whether humans and NHPs share the same Plasmodium vectors. To understand the vector-host interactions that can lead to an increased Plasmodium transmission between species, studies are required that reveal the nature of these interactions. Studying the potential role of NHPs as a Plasmodium reservoir for humans will contribute to the ongoing efforts of human malaria elimination, and will help to focus on critical areas that should be considered in achieving this goal. PMID:22701434

  10. Degradation of extracellular matrix by larvae of Schistosoma mansoni. I. Degradation by cercariae as a model for initial parasite invasion of host

    SciTech Connect

    McKerrow, J.H.; Keene, W.E.; Jeong, K.H.; Werb, Z.

    1983-01-01

    The ability of cercariae of Schistosoma mansoni to degrade a model extracellular connective tissue matrix produced by rat vascular smooth muscle cells in culture was investigated. In this model, connective tissue macromolecules are present in the interactive framework that characterizes their structure in vivo. Cercariae were stimulated to degrade the matrix by skin lipid or linoleic acid. At the maximally stimulating concentration of linoleic acid (25 ..mu..g/cm/sup 2/), 68% of the total matrix was degraded, including 57% of the glycoprotein, 79% of the elastin, and 8% of the collagen. Degradation of matrix was inhibited by ..cap alpha../sub 1/-proteinase inhibitor and soybean trypsin inhibitor. Ethylenediaminetetraacetic acid inhibited degradation by unstimulated but not linoleic acid-stimulated cercariae. Preacetabular gland secretions collected from cercariae also degraded the matrix with an activity 86% of that of live cercariae. Preacetabular gland proteolytic activity was also inhibited by ..cap alpha../sub 1/-proteinase inhibitor, soybean trypsin inhibitor, and ethylenediaminetetraacetic acid. The similar characteristics of matrix degradation by both live cercariae and cercarial preacetabular gland secretions support the idea that a proteinase secreted from cercarial preacetabular glands facilitates invasion of skin and connective tissue by these larvae. Degradation of elastin and glycoprotein constituentes of extracellular matrix is probably essential for skin penetration.

  11. Migration and survival of gamma-irradiated Schistosoma mansoni larvae and the duration of host-parasite contact in relation to the induction of resistance in mice

    SciTech Connect

    Mangold, B.L.; Dean, D.A.

    1984-01-01

    The migration in mice of 20-, 50-, and 90-krad /sup 60/Co-irradiated Schistosoma mansoni larvae, biosynthetically radioisotope labeled with /sup 75/Se-selenomethionine, was evaluated by autoradiography of compressed tissues and compared to the migration of non-irradiated 75 Se-labeled larvae. By day 8 over 90% of both non-irradiated and 20 krad-irradiated organisms were located in the lungs. In contrast to non-irradiated organisms, however, only a small proportion of 20-krad organisms migrated to the liver. The delay in migration between skin and lungs was more pronounced with 50-krad-irradiated schistosomula. No more than an occasional 50-krad-irradiated organism was ever detected in the liver. In three experiments, over 85% of the 90-krad-irradiated organisms were retained in the skin; in a fourth experiment about half of the 90-krad-irradiated organisms migrated as far as the lungs. Only an occasional 90-krad organism was ever detected in the liver. In three experiments, over 85% of the 90 Krad.-irradiated organisms were retained in the skin, in a fourth experiment about half of the 90 Krad.-irradiated organisms migrated as far as the lungs. Only an occasional 90 Krad. organism was ever detected in the liver. Removal of the skin exposure site within the first 4 days of immunization with either 50- or 90-krad-irradiated cercariae completely blocked the induction of resistance. Removal between the 4th and the 6th days gave variable results.

  12. Targeting Purine and Pyrimidine Metabolism in Human Apicomplexan Parasites

    PubMed Central

    Hyde, John E.

    2009-01-01

    Synthesis de novo, acquisition by salvage and interconversion of purines and pyrimidines represent the fundamental requirements for their eventual assembly into nucleic acids as nucleotides and the deployment of their derivatives in other biochemical pathways. A small number of drugs targeted to nucleotide metabolism, by virtue of their effect on folate biosynthesis and recycling, have been successfully used against apicomplexan parasites such as Plasmodium and Toxoplasma for many years, although resistance is now a major problem in the prevention and treatment of malaria. Many targets not involving folate metabolism have also been explored at the experimental level. However, the unravelling of the genome sequences of these eukaryotic unicellular organisms, together with increasingly sophisticated molecular analyses, opens up possibilities of introducing new drugs that could interfere with these processes. This review examines the status of established drugs of this type and the potential for further exploiting the vulnerability of apicomplexan human pathogens to inhibition of this key area of metabolism. PMID:17266529

  13. A novel coagulation inhibitor from Schistosoma japonicum.

    PubMed

    Ranasinghe, Shiwanthi L; Fischer, Katja; Gobert, Geoffrey N; McManus, Donald P

    2015-12-01

    Little is known about the molecular mechanisms whereby the human blood fluke Schistosoma japonicum is able to survive in the host venous blood system. Protease inhibitors are likely released by the parasite enabling it to avoid attack by host proteolytic enzymes and coagulation factors. Interrogation of the S. japonicum genomic sequence identified a gene, SjKI-1, homologous to that encoding a single domain Kunitz protein (Sjp_0020270) which we expressed in recombinant form in Escherichia coli and purified. SjKI-1 is highly transcribed in adult worms and eggs but its expression was very low in cercariae and schistosomula. In situ immunolocalization with anti-SjKI-1 rabbit antibodies showed the protein was present in eggs trapped in the infected mouse intestinal wall. In functional assays, SjKI-1 inhibited trypsin in the picomolar range and chymotrypsin, neutrophil elastase, FXa and plasma kallikrein in the nanomolar range. Furthermore, SjKI-1, at a concentration of 7·5 µ m, prolonged 2-fold activated partial thromboplastin time of human blood coagulation. We also demonstrate that SjKI-1 has the ability to bind Ca(++). We present, therefore, characterization of the first Kunitz protein from S. japonicum which we show has an anti-coagulant properties. In addition, its inhibition of neutrophil elastase indicates SjKI-1 have an anti-inflammatory role. Having anti-thrombotic properties, SjKI-1 may point the way towards novel treatment for hemostatic disorders. PMID:26463744

  14. Anthropogenics: Human influence on global and genetic homogenization of parasite populations

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The distribution, abundance, and diversity of life on Earth have been greatly shaped by human activities. This is no truer than in the geographic expansion of parasites; however, measuring the extent to which humans have influenced the dissemination and population structure of parasites has been cha...

  15. [New drugs for the treatment of human parasitic protozoa].

    PubMed

    Dupouy-Camet, J

    2004-06-01

    Whereas parasitic diseases are always a heavy burden for humanity, few are the new antiparasitic molecules marketed during the last 25 years. Thus on the 1393 new molecules marketed between 1975 and 1999, only 7 have antiprotozoan properties. This talk will detail the progress made in the treatment of the intestinal protozoa, malaria, visceral leishmaniasis and toxoplasmosis, problems with which are especially confronted the European parasitologists. The treatment of Giardia and intestinal amoebas is based on 5-nitro-imidazoles derivatives. Single-dose treatments can be used with tinidazole or secnidazole. Resistance to these compounds of Giardia were described and in these cases, treatment by quinacrine or nitazoxanide are possible alternatives. Nitazoxanide is marketed in the United States and in Australia. It seems to be a well tolerated antiparasitic agent with a broad spectrum because it is active on a lot of intestinal protozoa and helminths. It acts on the same metabolic way as the 5-nitro-imidazoles (inhibition of the ferredoxine reductase) but without synthesis of free radicals and DNA deterioration of the target cell. It is thus neither teratogenic nor mutagenic. Artemisinin derivatives allowed considerable progress in the treatment of malaria. They have short half-lifes, allowing a fast parasitic clearance and these derivatives do no provoke resistance. They are first line drugs for the treatment of malaria in areas of drug resistance. The arthemeter-lumefantrine association (Riamet, Coartem) ensures a rapid disappearance of the circulating parasites and is well tolerated. Atovaquone-proguanil (Malarone) is usable in the treatment of acute malaria but also in disease prevention with the advantage of continuing drug intake for only 7 days after having left the infected area. The treatment of leishmaniasis is always delicate and is characterized by the worrying development of antimony resistances, probably related in the European zones to the treatment of

  16. A furoxan–amodiaquine hybrid as a potential therapeutic for three parasitic diseases†

    PubMed Central

    Mott, Bryan T.; Cheng, Ken Chih-Chien; Guha, Rajarshi; Kommer, Valerie P.; Williams, David L.; Vermeire, Jon J.; Cappello, Michael; Maloney, David J.; Rai, Ganesha; Jadhav, Ajit; Simeonov, Anton; Inglese, James; Posner, Gary H.

    2012-01-01

    Parasitic diseases continue to have a devastating impact on human populations worldwide. Lack of effective treatments, the high cost of existing ones, and frequent emergence of resistance to these agents provide a strong argument for the development of novel therapies. Here we report the results of a hybrid approach designed to obtain a dual acting molecule that would demonstrate activity against a variety of parasitic targets. The antimalarial drug amodiaquine has been covalently joined with a nitric oxide-releasing furoxan to achieve multiple mechanisms of action. Using in vitro and ex vivo assays, the hybrid molecule shows activity against three parasites – Plasmodium falciparum, Schistosoma mansoni, and Ancylostoma ceylanicum. PMID:23205265

  17. High Genetic Variability of Schistosoma haematobium in Mali and Nigeria

    PubMed Central

    Ezeh, Charles; Yin, Mingbo; Li, Hongyan; Zhang, Ting; Xu, Bin; Sacko, Moussa; Feng, Zheng; Hu, Wei

    2015-01-01

    Schistosoma haematobium is one of the most prevalent parasitic flatworms, infecting over 112 million people in Africa. However, little is known about the genetic diversity of natural S. haematobium populations from the human host because of the inaccessible location of adult worms in the host. We used 4 microsatellite loci to genotype individually pooled S. haematobium eggs directly from each patient sampled at 4 endemic locations in Africa. We found that the average allele number of individuals from Mali was significantly higher than that from Nigeria. In addition, no significant difference in allelic composition was detected among the populations within Nigeria; however, the allelic composition was significantly different between Mali and Nigeria populations. This study demonstrated a high level of genetic variability of S. haematobium in the populations from Mali and Nigeria, the 2 major African endemic countries, suggesting that geographical population differentiation may occur in the regions. PMID:25748721

  18. Epidemiology and control of human gastrointestinal parasites in children

    PubMed Central

    Harhay, Michael O; Horton, John; Olliaro, Piero L

    2010-01-01

    Parasites found in the human gastrointestinal tract can be largely categorized into two groups, protozoa and helminths. The soil-transmitted helminths (Ascaris lumbricoides, hookworm and Trichuris trichiura) are the most prevalent, infecting an estimated one-sixth of the global population. Infection rates are highest in children living in sub-Saharan Africa, followed by Asia and then Latin America and the Caribbean. The current momentum towards global drug delivery for their control is at a historical high through the efforts of numerous initiatives increasingly acting in coordination with donors, governments and local communities. Together, they have delivered enormous quantities of drugs, especially anthelmintics to children through nationwide annual or biannual mass drug administration largely coordinated through schools. However, a much larger and rapidly growing childhood population in these regions remains untreated and suffering from more than one parasite. Mass drug administration has profound potential for control but is not without considerable challenges and concerns. A principal barrier is funding. Stimulating a research and development pipeline, supporting the necessary clinical trials to refine treatment, in addition to procuring and deploying drugs (and sustaining these supply chains), requires substantial funding and resources that do not presently exist. Limited options for chemotherapy raise concerns about drug resistance developing through overuse, however, satisfactory pharmacoepidemiology and monitoring for drug resistance requires more developed health infrastructures than are generally available. Further, the limited pharmacopeia does not include any effective second-line options if resistance emerges, and the research and development pipeline is severely depressed. Herein, we discuss the major gastrointestinal protozoa and helminths reviewing their impact on child health, changing epidemiology and how this relates to their control. PMID

  19. Cross-species protection: Schistosoma mansoni Sm-p80 vaccine confers protection against Schistosoma haematobium in hamsters and baboons.

    PubMed

    Karmakar, Souvik; Zhang, Weidong; Ahmad, Gul; Torben, Workineh; Alam, Mayeen U; Le, Loc; Damian, Raymond T; Wolf, Roman F; White, Gary L; Carey, David W; Carter, Darrick; Reed, Steven G; Siddiqui, Afzal A

    2014-03-01

    The ability of the Schistosoma mansoni antigen, Sm-p80, to provide cross-species protection against Schistosoma haematobium challenge was evaluated in hamster and baboon models. Pronounced reduction in worm burden (48%) and in tissue egg load (64%) was observed in hamsters vaccinated with recombinant Sm-p80 admixed with glucopyranosyl lipid adjuvant-stable emulsion (GLA-SE). Similarly, in baboons, the Sm-p80/GLA-SE vaccine produced a 25% reduction in S. haematobium adult worms and decreased the egg load in the urinary bladder by 64%. A 40% and 53% reduction in fecal and urine egg output, respectively, was observed in vaccinated baboons. A balanced pro-inflammatory (Th17 and Th1) and Th2 type of response was generated after vaccination and appears indicative of augmented prophylactic efficacy. These data on cross-species protection coupled with the prophylactic, therapeutic and antifecundity efficacy against the homologous parasite, S. mansoni, reinforces Sm-p80 as a promising vaccine candidate. It is currently being prepared for GMP-compliant manufacture and for further pre-clinical development leading to human clinical trials. These results solidify the expectation that the Sm-p80 vaccine will provide relief for both the intestinal and the urinary schistosomiasis and thus will be greatly beneficial in reducing the overall burden of schistosomiasis. PMID:24397898

  20. Parasites of wild animals as a potential source of hazard to humans.

    PubMed

    Gałęcki, Remigiusz; Sokół, Rajmund; Koziatek, Sylwia

    2015-01-01

    The decline in wild animal habitats and the uncontrolled growth of their population make these animals come closer to human settlements. The aim of the study was to identify parasitic infections in wild animals in the selected area, and to specify the hazards they create for humans. In more than 66% of the analysed faecal samples from wild boar, hares, roe deer, deer and fallow deer various developmental forms of parasites were found. These included parasites dangerous for humans: Toxocara canis, Capillaria hepatica, Capillaria bovis, Trichuris suis, Trichuris ovis, Trichuris globulosus, Eimeria spp., and Trichostongylus spp. It is necessary to monitor parasitic diseases in wild animals as they can lead to the spread of parasites creating a hazard to humans, pets and livestock. PMID:26342506

  1. Proteomic Analysis of the Schistosoma mansoni Miracidium

    PubMed Central

    Wang, Tianfang; Zhao, Min; Rotgans, Bronwyn A.; Strong, April; Liang, Di; Ni, Guoying; Limpanont, Yanin; Ramasoota, Pongrama; McManus, Donald P.; Cummins, Scott F.

    2016-01-01

    Despite extensive control efforts, schistosomiasis continues to be a major public health problem in developing nations in the tropics and sub-tropics. The miracidium, along with the cercaria, both of which are water-borne and free-living, are the only two stages in the life-cycle of Schistosoma mansoni which are involved in host invasion. Miracidia penetrate intermediate host snails and develop into sporocysts, which lead to cercariae that can infect humans. Infection of the snail host by the miracidium represents an ideal point at which to interrupt the parasite’s life-cycle. This research focuses on an analysis of the miracidium proteome, including those proteins that are secreted. We have identified a repertoire of proteins in the S. mansoni miracidium at 2 hours post-hatch, including proteases, venom allergen-like proteins, receptors and HSP70, which might play roles in snail-parasite interplay. Proteins involved in energy production and conservation were prevalent, as were proteins predicted to be associated with defence. This study also provides a strong foundation for further understanding the roles that neurohormones play in host-seeking by schistosomes, with the potential for development of novel anthelmintics that interfere with its various life-cycle stages. PMID:26799066

  2. Human C1-Inhibitor Suppresses Malaria Parasite Invasion and Cytoadhesion via Binding to Parasite Glycosylphosphatidylinositol and Host Cell Receptors.

    PubMed

    Mejia, Pedro; Diez-Silva, Monica; Kamena, Faustin; Lu, Fengxin; Fernandes, Stacey M; Seeberger, Peter H; Davis, Alvin E; Mitchell, James R

    2016-01-01

    Plasmodium falciparum-induced severe malaria remains a continuing problem in areas of endemicity, with elevated morbidity and mortality. Drugs targeting mechanisms involved in severe malaria pathology, including cytoadhesion of infected red blood cells (RBCs) to host receptors and production of proinflammatory cytokines, are still necessary. Human C1-inhibitor (C1INH) is a multifunctional protease inhibitor that regulates coagulation, vascular permeability, and inflammation, with beneficial effects in inflammatory disease models, including septic shock. We found that human C1INH, at therapeutically relevant doses, blocks severe malaria pathogenic processes by 2 distinct mechanisms. First, C1INH bound to glycan moieties within P. falciparum glycosylphosphatidylinositol (PfGPI) molecules on the parasite surface, inhibiting parasite RBC invasion and proinflammatory cytokine production by parasite-stimulated monocytes in vitro and reducing parasitemia in a rodent model of experimental cerebral malaria (ECM) in vivo. Second, C1INH bound to host CD36 and chondroitin sulfate A molecules, interfering with cytoadhesion of infected RBCs by competitive binding to these receptors in vitro and reducing sequestration in specific tissues and protecting against ECM in vivo. This study reveals that C1INH is a potential therapeutic antimalarial molecule able to interfere with severe-disease etiology at multiple levels through specific interactions with both parasite PfGPIs and host cell receptors. PMID:26347576

  3. Epidemiology of human Schistosoma haematobium infection around Volta Lake, Ghana, 1973-75

    PubMed Central

    Scott, D.; Senker, K.; England, E. C.

    1982-01-01

    There was a dramatic rise in the prevalence of urinary schistosomiasis around Volta Lake within a year of its full impoundment in 1968. Research was undertaken to investigate the epidemiology of the disease in preparation for a control programme. The interplay of three factors—age, sex, and ethnic affiliation—largely defined the demographic patterns of the prevalence and the intensity of infection. Both of these increased in young children up to a peak at age 10-14 years, and then declined, the intensity of infection more rapidly than the prevalence. The prevalence and intensity of infection were both greater in males than females (above ages 15-24 years and 5-9 years, respectively), and differences between the two main ethnic groups were related to differences in their lake-related activities. Differences between the patterns of prevalence and intensity of infection are attributed to the greater sensitivity of the latter measurement in indicating changes in the level of transmission. Practical difficulties were encountered in obtaining a precise measurement of incidence, the most important being the considerable degree of population movement. A field cohort study showed a seasonality of transmission, greatest between January and April, during the period of high level of the lake and in the early part of the draw-down. Research on the intermediate snail host (Bulinus truncatus rohlfsi) and lakeside ecology established the focality of transmission at human water-contact sites serving the shore-line communities and, in conjunction with parasitological surveys, its seasonality: variations in ecology that accompanied the annual rise and fall of the lake led to high levels of transmission when the water level was high and lower levels during the draw-down. The geographical distribution of the infection was also affected by differences in ecology, specifically by variations in the distribution and abundance of the aquatic weed Ceratophyllum demersum. A non

  4. The Genome of Haemoproteus tartakovskyi and Its Relationship to Human Malaria Parasites

    PubMed Central

    Bensch, Staffan; Canbäck, Björn; DeBarry, Jeremy D.; Johansson, Tomas; Hellgren, Olof; Kissinger, Jessica C.; Palinauskas, Vaidas; Videvall, Elin; Valkiūnas, Gediminas

    2016-01-01

    The phylogenetic relationships among hemosporidian parasites, including the origin of Plasmodium falciparum, the most virulent malaria parasite of humans, have been heavily debated for decades. Studies based on multiple-gene sequences have helped settle many of these controversial phylogenetic issues. However, denser taxon sampling and genome-wide analyses are needed to confidently resolve the evolutionay relationships among hemosporidian parasites. Genome sequences of several Plasmodium parasites are available but only for species infecting primates and rodents. To root the phylogenetic tree of Plasmodium, genomic data from related parasites of birds or reptiles are required. Here, we use a novel approach to isolate parasite DNA from microgametes and describe the first genome of a bird parasite in the sister genus to Plasmodium, Haemoproteus tartakovskyi. Similar to Plasmodium parasites, H. tartakovskyi has a small genome (23.2 Mb, 5,990 genes) and a GC content (25.4%) closer to P. falciparum (19.3%) than to Plasmodium vivax (42.3%). Combined with novel transcriptome sequences of the bird parasite Plasmodium ashfordi, our phylogenomic analyses of 1,302 orthologous genes demonstrate that mammalian-infecting malaria parasites are monophyletic, thus rejecting the repeatedly proposed hypothesis that the ancestor of Laverania parasites originated from a secondary host shift from birds to humans. Genes and genomic features previously found to be shared between P. falciparum and bird malaria parasites, but absent in other mammal malaria parasites, are therefore signatures of maintained ancestral states. We foresee that the genome of H. tartakovskyi will open new directions for comparative evolutionary analyses of malarial adaptive traits. PMID:27190205

  5. The Genome of Haemoproteus tartakovskyi and Its Relationship to Human Malaria Parasites.

    PubMed

    Bensch, Staffan; Canbäck, Björn; DeBarry, Jeremy D; Johansson, Tomas; Hellgren, Olof; Kissinger, Jessica C; Palinauskas, Vaidas; Videvall, Elin; Valkiūnas, Gediminas

    2016-01-01

    The phylogenetic relationships among hemosporidian parasites, including the origin of Plasmodium falciparum, the most virulent malaria parasite of humans, have been heavily debated for decades. Studies based on multiple-gene sequences have helped settle many of these controversial phylogenetic issues. However, denser taxon sampling and genome-wide analyses are needed to confidently resolve the evolutionay relationships among hemosporidian parasites. Genome sequences of several Plasmodium parasites are available but only for species infecting primates and rodents. To root the phylogenetic tree of Plasmodium, genomic data from related parasites of birds or reptiles are required. Here, we use a novel approach to isolate parasite DNA from microgametes and describe the first genome of a bird parasite in the sister genus to Plasmodium, Haemoproteus tartakovskyi Similar to Plasmodium parasites, H. tartakovskyi has a small genome (23.2 Mb, 5,990 genes) and a GC content (25.4%) closer to P. falciparum (19.3%) than to Plasmodium vivax (42.3%). Combined with novel transcriptome sequences of the bird parasite Plasmodium ashfordi, our phylogenomic analyses of 1,302 orthologous genes demonstrate that mammalian-infecting malaria parasites are monophyletic, thus rejecting the repeatedly proposed hypothesis that the ancestor of Laverania parasites originated from a secondary host shift from birds to humans. Genes and genomic features previously found to be shared between P. falciparum and bird malaria parasites, but absent in other mammal malaria parasites, are therefore signatures of maintained ancestral states. We foresee that the genome of H. tartakovskyi will open new directions for comparative evolutionary analyses of malarial adaptive traits. PMID:27190205

  6. Schistosoma mansoni Infection Impairs Antimalaria Treatment and Immune Responses of Rhesus Macaques Infected with Mosquito-Borne Plasmodium coatneyi

    PubMed Central

    Semenya, Amma A.; Sullivan, JoAnn S.; Barnwell, John W.

    2012-01-01

    Malaria and schistosomiasis are the world's two most important parasitic infections in terms of distribution, morbidity, and mortality. In areas where Plasmodium and Schistosoma species are both endemic, coinfections are commonplace. Mouse models demonstrate that schistosomiasis worsens a malaria infection; however, just as mice and humans differ greatly, the murine-infecting Plasmodium species differ as much from those that infect humans. Research into human coinfections (Schistosoma haematobium-Plasmodium falciparum versus Schistosoma mansoni-P. falciparum) has produced conflicting results. The rhesus macaque model provides a helpful tool for understanding the role of S. mansoni on malaria parasitemia and antimalarial immune responses using Plasmodium coatneyi, a malaria species that closely resembles P. falciparum infection in humans. Eight rhesus macaques were exposed to S. mansoni cercariae. Eight weeks later, these animals plus 8 additional macaques were exposed to malaria either through bites of infected mosquitos or intravenous inoculation. When malaria infection was initiated from mosquito bites, coinfected animals displayed increased malaria parasitemia, decreased hematocrit levels, and suppressed malaria-specific antibody responses compared to those of malaria infection alone. However, macaques infected by intravenous inoculation with erythrocytic-stage parasites did not display these same differences in parasitemia, hematocrit, or antibody responses between the two groups. Use of the macaque model provides information that begins to unravel differences in pathological and immunological outcomes observed between humans with P. falciparum that are coinfected with S. mansoni or S. haematobium. Our results suggest that migration of malaria parasites through livers harboring schistosome eggs may alter host immune responses and infection outcomes. PMID:22907811

  7. HOW HUMAN HISTORY HAS INFLUENCED GEOGRAPHY AND GENETICS OF PARASITE POPULATIONS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Human beings have radically altered agricultural landscapes, establishing a limited repertoire of plants and animals over vast expanses. Here, I consider what impact such a history may have had on the distribution and diversity of animal parasite, hypothesizing that certain parasites may have been '...

  8. Trace elements in the human scalp hair and finger nails as affected by infection with Schistosoma mansoni

    NASA Astrophysics Data System (ADS)

    El-Khatib, Ahmed M.; Bahnassy, Ahmed A.; Denton, M.

    1995-01-01

    The concentration of 13 elements has been determined in finger nail and scalp hair of 4 groups representing normal and infected Schistosoma mansoni subjects. Samples were irradiated by thermal neutrons from a Triga Mark III Reactor, for 10 min. Measurements were made using a HPGe detector coupled with ADC and PDP {11}/{34} data processing equipment. The results showed significant increases of Al, Cl, I and Br in both finger nails and scalp hair of bilharzial patients above those of normal subjects while Mg, Ca, V, Mn, Cu, Sr, K, S and Na showed significant decreases. Most of the elements showed a higher concentration in finger nails than in hair.

  9. Quantitative Time-course Profiling of Parasite and Host Cell Proteins in the Human Malaria Parasite Plasmodium falciparum*

    PubMed Central

    Foth, Bernardo Javier; Zhang, Neng; Chaal, Balbir Kaur; Sze, Siu Kwan; Preiser, Peter Rainer; Bozdech, Zbynek

    2011-01-01

    Studies of the Plasmodium falciparum transcriptome have shown that the tightly controlled progression of the parasite through the intra-erythrocytic developmental cycle (IDC) is accompanied by a continuous gene expression cascade in which most expressed genes exhibit a single transcriptional peak. Because the biochemical and cellular functions of most genes are mediated by the encoded proteins, understanding the relationship between mRNA and protein levels is crucial for inferring biological activity from transcriptional gene expression data. Although studies on other organisms show that <50% of protein abundance variation may be attributable to corresponding mRNA levels, the situation in Plasmodium is further complicated by the dynamic nature of the cyclic gene expression cascade. In this study, we simultaneously determined mRNA and protein abundance profiles for P. falciparum parasites during the IDC at 2-hour resolution based on oligonucleotide microarrays and two-dimensional differential gel electrophoresis protein gels. We find that most proteins are represented by more than one isoform, presumably because of post-translational modifications. Like transcripts, most proteins exhibit cyclic abundance profiles with one peak during the IDC, whereas the presence of functionally related proteins is highly correlated. In contrast, the abundance of most parasite proteins peaks significantly later (median 11 h) than the corresponding transcripts and often decreases slowly in the second half of the IDC. Computational modeling indicates that the considerable and varied incongruence between transcript and protein abundance may largely be caused by the dynamics of translation and protein degradation. Furthermore, we present cyclic abundance profiles also for parasite-associated human proteins and confirm the presence of five human proteins with a potential role in antioxidant defense within the parasites. Together, our data provide fundamental insights into transcript

  10. Expression at a 20L scale and purification of the extracellular domain of the Schistosoma mansoni TSP-2 recombinant protein: a vaccine candidate for human intestinal schistosomiasis.

    PubMed

    Curti, Elena; Kwityn, Clifford; Zhan, Bin; Gillespie, Portia; Brelsford, Jill; Deumic, Vehid; Plieskatt, Jordan; Rezende, Wanderson C; Tsao, Eric; Kalampanayil, Bose; Hotez, Peter J; Bottazzi, Maria Elena

    2013-11-01

    A novel recombinant protein vaccine for human schistosomiasis caused by Schistosoma mansoni is under development. The Sm-TSP-2 schistosomiasis vaccine is comprised of a 9 kDa recombinant protein corresponding to the extracellular domain of a unique S. mansoni tetraspanin. Here, we describe the cloning and the expression of the external loop of Sm-TSP-2 recombinant protein secreted by Pichia Pink the process development at 20L scale fermentation, and the two-steps purification, which resulted in a protein recovery yield of 31% and a protein purity of 97%. The developed processes are suitable for the production of purified protein for subsequent formulation and Phase 1 clinical studies. PMID:23899507

  11. Anthropogenics: human influence on global and genetic homogenization of parasite populations.

    PubMed

    Zarlenga, Dante S; Hoberg, Eric; Rosenthal, Benjamin; Mattiucci, Simonetta; Nascetti, Giuseppe

    2014-12-01

    The distribution, abundance, and diversity of life on Earth have been greatly shaped by human activities. This includes the geographic expansion of parasites; however, measuring the extent to which humans have influenced the dissemination and population structure of parasites has been challenging. In-depth comparisons among parasite populations extending to landscape-level processes affecting disease emergence have remained elusive. New research methods have enhanced our capacity to discern human impact, where the tools of population genetics and molecular epidemiology have begun to shed light on our historical and ongoing influence. Only since the 1990s have parasitologists coupled morphological diagnosis, long considered the basis of surveillance and biodiversity studies, with state-of-the-art tools enabling variation to be examined among, and within, parasite populations. Prior to this time, populations were characterized only by phenotypic attributes such as virulence, infectivity, host range, and geographical location. The advent of genetic/molecular methodologies (multilocus allozyme electrophoresis, polymerase chain reaction-DNA [PCR-DNA] fragments analysis, DNA sequencing, DNA microsatellites, single nucleotide polymorphisms, etc.) have transformed our abilities to reveal variation among, and within, populations at local, regional, landscape, and global scales, and thereby enhanced our understanding of the biosphere. Numerous factors can affect population structure among parasites, e.g., evolutionary and ecological history, mode of reproduction and transmission, host dispersal, and life-cycle complexity. Although such influences can vary considerably among parasite taxa, anthropogenic factors are demonstrably perturbing parasite fauna. Minimal genetic structure among many geographically distinct (isolated) populations is a hallmark of human activity, hastened by geographic introductions, environmental perturbation, and global warming. Accelerating

  12. Co-dispersal of the blood fluke Schistosoma japonicum and Homo sapiens in the Neolithic Age.

    PubMed

    Yin, Mingbo; Zheng, Hong-Xiang; Su, Jing; Feng, Zheng; McManus, Donald P; Zhou, Xiao-Nong; Jin, Li; Hu, Wei

    2015-01-01

    The global spread of human infectious diseases is of considerable public health and biomedical interest. Little is known about the relationship between the distribution of ancient parasites and that of their human hosts. Schistosoma japonicum is one of the three major species of schistosome blood flukes causing the disease of schistosomiasis in humans. The parasite is prevalent in East and Southeast Asia, including the People's Republic of China, the Philippines and Indonesia. We studied the co-expansion of S. japonicum and its human definitive host. Phylogenetic reconstruction based on complete mitochondrial genome sequences showed that S. japonicum radiated from the middle and lower reaches of the Yangtze River to the mountainous areas of China, Japan and Southeast Asia. In addition, the parasite experienced two population expansions during the Neolithic agriculture era, coinciding with human migration and population growth. The data indicate that the advent of rice planting likely played a key role in the spread of schistosomiasis in Asia. Moreover, the presence of different subspecies of Oncomelania hupensis intermediate host snails in different localities in Asia allowed S. japonicum to survive in new rice-planting areas, and concurrently drove the intraspecies divergence of the parasite. PMID:26686813

  13. Co-dispersal of the blood fluke Schistosoma japonicum and Homo sapiens in the Neolithic Age

    PubMed Central

    Yin, Mingbo; Zheng, Hong-Xiang; Su, Jing; Feng, Zheng; McManus, Donald P.; Zhou, Xiao-Nong; Jin, Li; Hu, Wei

    2015-01-01

    The global spread of human infectious diseases is of considerable public health and biomedical interest. Little is known about the relationship between the distribution of ancient parasites and that of their human hosts. Schistosoma japonicum is one of the three major species of schistosome blood flukes causing the disease of schistosomiasis in humans. The parasite is prevalent in East and Southeast Asia, including the People’s Republic of China, the Philippines and Indonesia. We studied the co-expansion of S. japonicum and its human definitive host. Phylogenetic reconstruction based on complete mitochondrial genome sequences showed that S. japonicum radiated from the middle and lower reaches of the Yangtze River to the mountainous areas of China, Japan and Southeast Asia. In addition, the parasite experienced two population expansions during the Neolithic agriculture era, coinciding with human migration and population growth. The data indicate that the advent of rice planting likely played a key role in the spread of schistosomiasis in Asia. Moreover, the presence of different subspecies of Oncomelania hupensis intermediate host snails in different localities in Asia allowed S. japonicum to survive in new rice-planting areas, and concurrently drove the intraspecies divergence of the parasite. PMID:26686813

  14. Worm development in hamsters infected with unisex and cross-mated Schistosoma mansoni and Schistosoma haematobium.

    PubMed

    Khalil, S B; Mansour, N S

    1995-02-01

    Schistosoma mansoni and Schistosoma haematobium coexist in Egypt and in other areas in Africa, and people frequently are infected with parasites of both species. The effects of the interactions between worms of both sexes of the 2 species on development and egg laying were evaluated in vivo by infecting hamsters with cercariae from Biomphalaria alexandrina and Bulinus truncatus snails infected with single miracidia. In hamsters with unisex infections, male worms of both species were small. Schistosoma mansoni females were stunted and partially mature but did not contain eggs. Schistosoma haematobium females, though stunted, sometimes contained and laid small eggs, which were deposited in the liver, but few of which contained motile embryos. This suggests that unisexual infection with S. haematobium female worms produces a risk for liver damage due to egg deposition in tissues. Both S. mansoni and S. haematobium females that mated with males of the heterologous species were significantly larger than females from unisexual infections; they were sexually mature and possessed eggs in the uterus. The eggs in the liver homogenates of cross-specific infected hamsters contained fully developed miracidia that hatched in filtered pond water. PMID:7876983

  15. Structure–function analysis of apical membrane–associated molecules of the tegument of schistosome parasites of humans: prospects for identification of novel targets for parasite control

    PubMed Central

    Leow, Chiuan Yee; Willis, Charlene; Hofmann, Andreas; Jones, Malcolm K

    2015-01-01

    Neglected tropical diseases are a group of some 17 diseases that afflict poor and predominantly rural people in developing nations. One significant disease that contributes to substantial morbidity in endemic areas is schistosomiasis, caused by infection with one of five species of blood fluke belonging to the trematode genus Schistosoma. Although there is one drug available for treatment of affected individuals in clinics, or for mass administration in endemic regions, there is a need for new therapies. A prominent target organ of schistosomes, either for drug or vaccine development, is the peculiar epithelial syncytium that forms the body wall (tegument) of this parasite. This dynamic layer is maintained and organized by concerted activity of a range of proteins, among which are the abundant tegumentary annexins. In this review, we will outline advances in structure–function analyses of these annexins, as a means to understanding tegument cell biology in host–parasite interaction and their potential exploitation as targets for anti-schistosomiasis therapies. PMID:25176442

  16. In vitro parasite-monocyte interactions in human leishmaniasis: effect of enzyme treatments on attachment.

    PubMed Central

    Wyler, D J; Suzuki, K

    1983-01-01

    Essential to the pathogenesis of leishmaniasis is the ability of Leishmania spp. to attach to mononuclear phagocyte surfaces before entering this host cell which they parasitize. We have investigated the attachment phase of infection in vitro by quantitating the percent of human peripheral blood monocytes pretreated with cytochalasin (to prevent parasite entry) to which tissue-derived L. tropica amastigotes will attach during coincubation at 37 degrees C in serum-free medium. We determined that pretreatment of parasites with trypsin, chymotrypsin, Pronase, and neuraminidase reduced attachment. In contrast, parasites treated with beta-galactosidase had an enhanced ability to attach to host cells. Treatment of monocytes with chymotrypsin and Pronase, but not with trypsin or neuraminidase, reduced attachment of untreated amastigotes. We propose that in vitro amastigote attachment under serum-free conditions depends on the interaction of protein determinants on the surface of both parasite and host cell. Images PMID:6413414

  17. [Africa or Asia, which is the evolutionary origin of human schistosomes?].

    PubMed

    Zhang, G; Verneau, O; Qiu, C; Jourdane, J; Xia, M

    2001-11-01

    The origin and the evolution of Schistosomatidae species, due to their medical importance (responsible of the second most important human parasitosis after malaria), arouse a great interest. A combination of phylogenetic studies using several molecular markers has provided support for the traditional grouping and evolutionary inferences derived from morphological and biological data. The genus Schistosoma, which comprises all species parasitizing Man, is generally split into four evolutionary lineages (mansoni, haematobium, indicum and japonicum lineages). The group of African schistosomes (including mansoni and haematobium lineages) appears very divergent from the japonicum lineage. Recent phylogenetic studies using partial 28S rDNA sequencing and including Orientobilharzia turkestanicum from Iran, an Asian parasite of livestock, found, unexpectedly, that this species nested among Schistosoma species, thus rendering the latter paraphyletic, and suggested an Asian origin for the Schistosoma genus. The present work re-examines the question of the geographical origin of human schistosomes by analysing a new genomic marker (ITS2) as well as by including the use of O. turkestanicum originating from northeastern China. Our results are in agreement with previous work using 28S, in demonstrating that Schistosoma is not monophyletic. However, O. turkestanicum, whatever the method of analysis used (distance or parsimony), was grouped with members of the japonicum group to the exclusion of African Schistosoma species. Then, our data argue strongly for the need for further phylogenetic study including new taxa and new genomic sequences before definitely concluding either an Asian or African origin for the genus Schistosoma. PMID:11725698

  18. Human, vector and parasite Hsp90 proteins: A comparative bioinformatics analysis

    PubMed Central

    Faya, Ngonidzashe; Penkler, David L.; Tastan Bishop, Özlem

    2015-01-01

    The treatment of protozoan parasitic diseases is challenging, and thus identification and analysis of new drug targets is important. Parasites survive within host organisms, and some need intermediate hosts to complete their life cycle. Changing host environment puts stress on parasites, and often adaptation is accompanied by the expression of large amounts of heat shock proteins (Hsps). Among Hsps, Hsp90 proteins play an important role in stress environments. Yet, there has been little computational research on Hsp90 proteins to analyze them comparatively as potential parasitic drug targets. Here, an attempt was made to gain detailed insights into the differences between host, vector and parasitic Hsp90 proteins by large-scale bioinformatics analysis. A total of 104 Hsp90 sequences were divided into three groups based on their cellular localizations; namely cytosolic, mitochondrial and endoplasmic reticulum (ER). Further, the parasitic proteins were divided according to the type of parasite (protozoa, helminth and ectoparasite). Primary sequence analysis, phylogenetic tree calculations, motif analysis and physicochemical properties of Hsp90 proteins suggested that despite the overall structural conservation of these proteins, parasitic Hsp90 proteins have unique features which differentiate them from human ones, thus encouraging the idea that protozoan Hsp90 proteins should be further analyzed as potential drug targets. PMID:26793431

  19. Human red blood cell-adapted Plasmodium knowlesi parasites: a new model system for malaria research

    PubMed Central

    Grüring, Christof; Moon, Robert W.; Lim, Caeul; Holder, Anthony A.; Blackman, Michael J.; Duraisingh, Manoj T.

    2014-01-01

    Summary Plasmodium knowlesi is a simian malaria parasite primarily infecting macaque species in Southeast Asia. Although its capacity to infect humans has been recognized since the early part of the last century, it has recently become evident that human infections are widespread and potentially life threatening. Historically, P. knowlesi has proven to be a powerful tool in early studies of malaria parasites, providing key breakthroughs in understanding many aspects of Plasmodium biology. However, the necessity to grow the parasite either in macaques or in vitro using macaque blood restricted research to laboratories with access to these resources. The recent adaptation of P. knowlesi to grow and proliferate in vitro in human red blood cells (RBCs) is therefore a substantial step towards revitalizing and expanding research on P. knowlesi. Furthermore, the development of a highly efficient transfection system to genetically modify the parasite makes P. knowlesi an ideal model to study parasite biology. In this review we elaborate on the importance of P. knowlesi in earlier phases of malaria research and highlight the future potential of the newly available human adapted P. knowlesi parasite lines. PMID:24506567

  20. Human red blood cell-adapted Plasmodium knowlesi parasites: a new model system for malaria research.

    PubMed

    Grüring, Christof; Moon, Robert W; Lim, Caeul; Holder, Anthony A; Blackman, Michael J; Duraisingh, Manoj T

    2014-05-01

    Plasmodium knowlesi is a simian malaria parasite primarily infecting macaque species in Southeast Asia. Although its capacity to infect humans has been recognized since the early part of the last century, it has recently become evident that human infections are widespread and potentially life threatening. Historically, P.  knowlesi has proven to be a powerful tool in early studies of malaria parasites, providing key breakthroughs in understanding many aspects of Plasmodium biology. However, the necessity to grow the parasite either in macaques or in vitro using macaque blood restricted research to laboratories with access to these resources. The recent adaptation of P.  knowlesi to grow and proliferate in vitro in human red blood cells (RBCs) is therefore a substantial step towards revitalizing and expanding research on P.  knowlesi. Furthermore, the development of a highly efficient transfection system to genetically modify the parasite makes P.  knowlesi an ideal model to study parasite biology. In this review, we elaborate on the importance of P.  knowlesi in earlier phases of malaria research and highlight the future potential of the newly available human adapted P.  knowlesi parasite lines. PMID:24506567

  1. Morphological and Molecular Descriptors of the Developmental Cycle of Babesia divergens Parasites in Human Erythrocytes

    PubMed Central

    Rossouw, Ingrid; Maritz-Olivier, Christine; Niemand, Jandeli; van Biljon, Riette; Smit, Annel; Olivier, Nicholas A.; Birkholtz, Lyn-Marie

    2015-01-01

    Human babesiosis, especially caused by the cattle derived Babesia divergens parasite, is on the increase, resulting in renewed attentiveness to this potentially life threatening emerging zoonotic disease. The molecular mechanisms underlying the pathophysiology and intra-erythrocytic development of these parasites are poorly understood. This impedes concerted efforts aimed at the discovery of novel anti-babesiacidal agents. By applying sensitive cell biological and molecular functional genomics tools, we describe the intra-erythrocytic development cycle of B. divergens parasites from immature, mono-nucleated ring forms to bi-nucleated paired piriforms and ultimately multi-nucleated tetrads that characterizes zoonotic Babesia spp. This is further correlated for the first time to nuclear content increases during intra-erythrocytic development progression, providing insight into the part of the life cycle that occurs during human infection. High-content temporal evaluation elucidated the contribution of the different stages to life cycle progression. Moreover, molecular descriptors indicate that B. divergens parasites employ physiological adaptation to in vitro cultivation. Additionally, differential expression is observed as the parasite equilibrates its developmental stages during its life cycle. Together, this information provides the first temporal evaluation of the functional transcriptome of B. divergens parasites, information that could be useful in identifying biological processes essential to parasite survival for future anti-babesiacidal discoveries. PMID:25955414

  2. Morphological and Molecular Descriptors of the Developmental Cycle of Babesia divergens Parasites in Human Erythrocytes.

    PubMed

    Rossouw, Ingrid; Maritz-Olivier, Christine; Niemand, Jandeli; van Biljon, Riette; Smit, Annel; Olivier, Nicholas A; Birkholtz, Lyn-Marie

    2015-05-01

    Human babesiosis, especially caused by the cattle derived Babesia divergens parasite, is on the increase, resulting in renewed attentiveness to this potentially life threatening emerging zoonotic disease. The molecular mechanisms underlying the pathophysiology and intra-erythrocytic development of these parasites are poorly understood. This impedes concerted efforts aimed at the discovery of novel anti-babesiacidal agents. By applying sensitive cell biological and molecular functional genomics tools, we describe the intra-erythrocytic development cycle of B. divergens parasites from immature, mono-nucleated ring forms to bi-nucleated paired piriforms and ultimately multi-nucleated tetrads that characterizes zoonotic Babesia spp. This is further correlated for the first time to nuclear content increases during intra-erythrocytic development progression, providing insight into the part of the life cycle that occurs during human infection. High-content temporal evaluation elucidated the contribution of the different stages to life cycle progression. Moreover, molecular descriptors indicate that B. divergens parasites employ physiological adaptation to in vitro cultivation. Additionally, differential expression is observed as the parasite equilibrates its developmental stages during its life cycle. Together, this information provides the first temporal evaluation of the functional transcriptome of B. divergens parasites, information that could be useful in identifying biological processes essential to parasite survival for future anti-babesiacidal discoveries. PMID:25955414

  3. Praziquantel inhibits Schistosoma mansoni attachment in vitro.

    PubMed

    da-Silva, S P; Noel, F

    1990-01-01

    Male adult Schistosoma mansoni worms were placed in a glass dish containing Tyrode solution and observed for 15 min after addition of praziquantel (0.01 to 1 microM). Praziquantel promoted a concentration- and time-dependent inhibition of sucker-mediated attachment of the worm. Attachment inhibition was correlated with shortening of the parasite. We propose that the rapid and total inhibition of worm attachment observed in vitro with 1 microM praziquantel indicates that therapeutic concentrations of this drug should promote a rapid hepatic shift, in vivo, which may facilitate host tissue reaction. PMID:2101049

  4. Cell-Free DNA as a Diagnostic Tool for Human Parasitic Infections.

    PubMed

    Weerakoon, Kosala G; McManus, Donald P

    2016-05-01

    Parasites often cause devastating diseases and represent a significant public health and economic burden. More accurate and convenient diagnostic tools are needed in support of parasite control programmes in endemic regions, and for rapid point-of-care diagnosis in nonendemic areas. The detection of cell-free DNA (cfDNA) is a relatively new concept that is being applied in the current armamentarium of diagnostics. Here, we review the application of cfDNA detection with nucleic acid amplification tests for the diagnosis and evaluation of different human parasitic infections and highlight the significant benefits of the approach using non-invasive clinical samples. PMID:26847654

  5. Interacting parasites

    USGS Publications Warehouse

    Lafferty, Kevin D.

    2010-01-01

    Parasitism is the most popular life-style on Earth, and many vertebrates host more than one kind of parasite at a time. A common assumption is that parasite species rarely interact, because they often exploit different tissues in a host, and this use of discrete resources limits competition (1). On page 243 of this issue, however, Telfer et al. (2) provide a convincing case of a highly interactive parasite community in voles, and show how infection with one parasite can affect susceptibility to others. If some human parasites are equally interactive, our current, disease-by-disease approach to modeling and treating infectious diseases is inadequate (3).

  6. Genome sequencing of chimpanzee malaria parasites reveals possible pathways of adaptation to human hosts.

    PubMed

    Otto, Thomas D; Rayner, Julian C; Böhme, Ulrike; Pain, Arnab; Spottiswoode, Natasha; Sanders, Mandy; Quail, Michael; Ollomo, Benjamin; Renaud, François; Thomas, Alan W; Prugnolle, Franck; Conway, David J; Newbold, Chris; Berriman, Matthew

    2014-01-01

    Plasmodium falciparum causes most human malaria deaths, having prehistorically evolved from parasites of African Great Apes. Here we explore the genomic basis of P. falciparum adaptation to human hosts by fully sequencing the genome of the closely related chimpanzee parasite species P. reichenowi, and obtaining partial sequence data from a more distantly related chimpanzee parasite (P. gaboni). The close relationship between P. reichenowi and P. falciparum is emphasized by almost complete conservation of genomic synteny, but against this strikingly conserved background we observe major differences at loci involved in erythrocyte invasion. The organization of most virulence-associated multigene families, including the hypervariable var genes, is broadly conserved, but P. falciparum has a smaller subset of rif and stevor genes whose products are expressed on the infected erythrocyte surface. Genome-wide analysis identifies other loci under recent positive selection, but a limited number of changes at the host-parasite interface may have mediated host switching. PMID:25203297

  7. Genome sequencing of chimpanzee malaria parasites reveals possible pathways of adaptation to human hosts

    PubMed Central

    Otto, Thomas D.; Rayner, Julian C.; Böhme, Ulrike; Pain, Arnab; Spottiswoode, Natasha; Sanders, Mandy; Quail, Michael; Ollomo, Benjamin; Renaud, François; Thomas, Alan W.; Prugnolle, Franck; Conway, David J.; Newbold, Chris; Berriman, Matthew

    2014-01-01

    Plasmodium falciparum causes most human malaria deaths, having prehistorically evolved from parasites of African Great Apes. Here we explore the genomic basis of P. falciparum adaptation to human hosts by fully sequencing the genome of the closely related chimpanzee parasite species P. reichenowi, and obtaining partial sequence data from a more distantly related chimpanzee parasite (P. gaboni). The close relationship between P. reichenowi and P. falciparum is emphasized by almost complete conservation of genomic synteny, but against this strikingly conserved background we observe major differences at loci involved in erythrocyte invasion. The organization of most virulence-associated multigene families, including the hypervariable var genes, is broadly conserved, but P. falciparum has a smaller subset of rif and stevor genes whose products are expressed on the infected erythrocyte surface. Genome-wide analysis identifies other loci under recent positive selection, but a limited number of changes at the host–parasite interface may have mediated host switching. PMID:25203297

  8. Excretion/secretion products from Schistosoma mansoni adults, eggs and schistosomula have unique peptidase specificity profiles.

    PubMed

    Dvořák, Jan; Fajtová, Pavla; Ulrychová, Lenka; Leontovyč, Adrian; Rojo-Arreola, Liliana; Suzuki, Brian M; Horn, Martin; Mareš, Michael; Craik, Charles S; Caffrey, Conor R; O'Donoghue, Anthony J

    2016-03-01

    Schistosomiasis is one of a number of chronic helminth diseases of poverty that severely impact personal and societal well-being and productivity. Peptidases (proteases) are vital to successful parasitism, and can modulate host physiology and immunology. Interference of peptidase action by specific drugs or vaccines can be therapeutically beneficial. To date, research on peptidases in the schistosome parasite has focused on either the functional characterization of individual peptidases or their annotation as part of global genome or transcriptome studies. We were interested in functionally characterizing the complexity of peptidase activity operating at the host-parasite interface, therefore the excretory-secretory products of key developmental stages of Schistosoma mansoni that parasitize the human were examined. Using class specific peptidase inhibitors in combination with a multiplex substrate profiling assay, a number of unique activities derived from endo- and exo-peptidases were revealed in the excretory-secretory products of schistosomula (larval migratory worms), adults and eggs. The data highlight the complexity of the functional degradome for each developmental stage of this parasite and facilitate further enquiry to establish peptidase identity, physiological and immunological function, and utility as drug or vaccine candidates. PMID:26409899

  9. Human intestinal parasites in non-biting synanthropic flies in Ogun State, Nigeria.

    PubMed

    Adenusi, Adedotun Adesegun; Adewoga, Thomas O Sunday

    2013-01-01

    Filth-feeding and breeding, non-biting synanthropic flies have been incriminated in the dissemination of human enteropathogens in the environment. This study determined the species of non-biting synanthropic flies associated with four filthy sites in Ilishan, Ogun State, southwest Nigeria, and assessed their potentials for mechanical transmission of human intestinal parasites. 7190 flies identified as Musca domestica (33.94%), Chrysomya megacephala (26.01%), Musca sorbens (23.23%), Lucilia cuprina (8.76%), Calliphora vicina (4.59%), Sarcophaga sp. (2.78%) and Fannia scalaris (0.70%) were examined for human intestinal parasites by the formol-ether concentration and modified Ziehl-Neelsen techniques. Eggs of the following parasites: Ascaris lumbricoides (34.08%), Trichuris trichiura (25.87%), hookworms (20.45%), Taenia sp. (2.36%), Hymenolepis nana (1.11%), Enterobius vermicularis (0.56%), Strongyloides stercoralis (larvae; 3.89%) and cysts of Entamoeba histolytica/dispar (27.26%), Entamoeba coli (22.67%), Giardia lamblia (3.34%) and Cryptosporidium sp. (1.81%) were isolated from the body surfaces and or gut contents of 75.24% of 719 pooled fly batches. The helminths A. lumbricoides and T. trichiura and the protozoans, E. histolytica/dispar and E. coli were the dominant parasites detected, both on body surfaces and in the gut contents of flies. C. megacephala was the highest carrier of parasites (diversity and number). More parasites were isolated from the gut than from body surfaces (P < 0.05). Flies from soiled ground often carried more parasites than those from abattoir, garbage or open-air market. Synanthropic fly species identified in this study can be of potential epidemiological importance as mechanical transmitters of human intestinal parasites acquired naturally from filth and carried on their body surfaces and or in the gut, because of their vagility and feeding mechanisms. PMID:23290716

  10. Comparative Phylogenetic Studies on Schistosoma japonicum and Its Snail Intermediate Host Oncomelania hupensis: Origins, Dispersal and Coevolution

    PubMed Central

    Attwood, Stephen W.; Ibaraki, Motomu; Saitoh, Yasuhide; Nihei, Naoko; Janies, Daniel A.

    2015-01-01

    Background Schistosoma japonicum causes major public health problems in China and the Philippines; this parasite, which is transmitted by freshwater snails of the species Oncomelania hupensis, causes the disease intestinal schistosomiasis in humans and cattle. Researchers working on Schistosoma in Africa have described the relationship between the parasites and their snail intermediate hosts as coevolved or even as an evolutionary arms race. In the present study this hypothesis of coevolution is evaluated for S. japonicum and O. hupensis. The origins and radiation of the snails and the parasite across China, and the taxonomic validity of the sub-species of O. hupensis, are also assessed. Methodology/Principal Findings The findings provide no evidence for coevolution between S. japonicum and O. hupensis, and the phylogeographical analysis suggests a heterochronous radiation of the parasites and snails in response to different palaeogeographical and climatic triggers. The results are consistent with a hypothesis of East to West colonisation of China by Oncomelania with a re-invasion of Japan by O. hupensis from China. The Taiwan population of S. japonicum appears to be recently established in comparison with mainland Chinese populations. Conclusions/Significance The snail and parasite populations of the western mountain region of China (Yunnan and Sichuan) appear to have been isolated from Southeast Asian populations since the Pleistocene; this has implications for road and rail links being constructed in the region, which will breach biogeographical barriers between China and Southeast Asia. The results also have implications for the spread of S. japonicum. In the absence of coevolution, the parasite may more readily colonise new snail populations to which it is not locally adapted, or even new intermediate host species; this can facilitate its dispersal into new areas. Additional work is required to assess further the risk of spread of S. japonicum. PMID:26230619

  11. Genome sequence of the human malaria parasite Plasmodium falciparum

    PubMed Central

    Gardner, Malcolm J.; Hall, Neil; Fung, Eula; White, Owen; Berriman, Matthew; Hyman, Richard W.; Carlton, Jane M.; Pain, Arnab; Nelson, Karen E.; Bowman, Sharen; Paulsen, Ian T.; James, Keith; Eisen, Jonathan A.; Rutherford, Kim; Salzberg, Steven L.; Craig, Alister; Kyes, Sue; Chan, Man-Suen; Nene, Vishvanath; Shallom, Shamira J.; Suh, Bernard; Peterson, Jeremy; Angiuoli, Sam; Pertea, Mihaela; Allen, Jonathan; Selengut, Jeremy; Haft, Daniel; Mather, Michael W.; Vaidya, Akhil B.; Martin, David M. A.; Fairlamb, Alan H.; Fraunholz, Martin J.; Roos, David S.; Ralph, Stuart A.; McFadden, Geoffrey I.; Cummings, Leda M.; Subramanian, G. Mani; Mungall, Chris; Venter, J. Craig; Carucci, Daniel J.; Hoffman, Stephen L.; Newbold, Chris; Davis, Ronald W.; Fraser, Claire M.; Barrell, Bart

    2013-01-01

    The parasite Plasmodium falciparum is responsible for hundreds of millions of cases of malaria, and kills more than one million African children annually. Here we report an analysis of the genome sequence of P. falciparum clone 3D7. The 23-megabase nuclear genome consists of 14 chromosomes, encodes about 5,300 genes, and is the most (A + T)-rich genome sequenced to date. Genes involved in antigenic variation are concentrated in the subtelomeric regions of the chromosomes. Compared to the genomes of free-living eukaryotic microbes, the genome of this intracellular parasite encodes fewer enzymes and transporters, but a large proportion of genes are devoted to immune evasion and host–parasite interactions. Many nuclear-encoded proteins are targeted to the apicoplast, an organelle involved in fatty-acid and isoprenoid metabolism. The genome sequence provides the foundation for future studies of this organism, and is being exploited in the search for new drugs and vaccines to fight malaria. PMID:12368864

  12. Evolutionary immune response to conserved domains in parasites and aeroallergens.

    PubMed

    Bielory, Brett Phillip; Mainardi, Timothy; Rottem, Menachem

    2013-01-01

    The immune response based on immunoglobulin E (IgE) evolved as a defense against specific parasitic infections. In the absence of active helminthic infections, the immune system has redirected its IgE epitopes toward innocuous environmental antigens. Helminths and aeroallergens have a similar stereotypical IgE response to unique antigens that can not be explained by chance alone. This study was designed to evaluate potential homology between conserved protein domains embedded in parasitic organisms and aeroallergens. Search and retrieval systems for nucleotide and protein sequences (Entrez, BLAST, and National Center for Biotechnology Information) were searched to identify conserved domains between allergens and certain parasites. A total score was developed that correlated positively with homology between compared sequences. Over 2000 domains were examined. We found matches with a high total score (>100) that signified a strong positive correlation between sequences in allergens (n = 30) and parasites (n = 13). Multiple shared conserved domains were identified between parasites and allergens. Parasite-allergen combinations with the most significant homology (greatest total score) were Plasmodium falciparum enolase and Hev b9 (total score, 612), Schistosoma mansoni albumin and Fel d 2 (total score, 991), Ascaris lumbricoides tropomyosin and Ani s3 (total score, 531), and Wuchereria bancrofti trypsin and Blo t3 (138). Homologous conserved domains exist in specific parasites and allergens, consistent with the theory that the human IgE-eosinophil immune response to common allergens is a direct consequence of stimulation by parasitic organisms. PMID:23406942

  13. Analysis of Antibodies Directed against Merozoite Surface Protein 1 of the Human Malaria Parasite Plasmodium falciparum

    PubMed Central

    Woehlbier, Ute; Epp, Christian; Kauth, Christian W.; Lutz, Rolf; Long, Carole A.; Coulibaly, Boubacar; Kouyaté, Bocar; Arevalo-Herrera, Myriam; Herrera, Sócrates; Bujard, Hermann

    2006-01-01

    The 190-kDa merozoite surface protein 1 (MSP-1) of Plasmodium falciparum, an essential component in the parasite's life cycle, is a primary candidate for a malaria vaccine. Rabbit antibodies elicited by the heterologously produced MSP-1 processing products p83, p30, p38, and p42, derived from strain 3D7, were analyzed for the potential to inhibit in vitro erythrocyte invasion by the parasite and parasite growth. Our data show that (i) epitopes recognized by antibodies, which inhibit parasite replication, are distributed throughout the entire MSP-1 molecule; (ii) when combined, antibodies specific for different regions of MSP-1 inhibit in a strictly additive manner; (iii) anti-MSP-1 antibodies interfere with erythrocyte invasion as well as with the intraerythrocytic growth of the parasite; and (iv) antibodies raised against MSP-1 of strain 3D7 strongly cross-inhibit replication of the heterologous strain FCB-1. Accordingly, anti-MSP-1 antibodies appear to be capable of interfering with parasite multiplication at more than one level. Since the overall immunogenicity profile of MSP-1 in rabbits closely resembles that found in sera of Aotus monkeys immunized with parasite-derived MSP-1 and of humans semi-immune to malaria from whom highly inhibiting antigen-specific antibodies were recovered, we consider the findings reported here to be relevant for the development of MSP-1-based vaccines against malaria. PMID:16428781

  14. Molecular diagnosis of infections and resistance in veterinary and human parasites.

    PubMed

    Hunt, Peter W

    2011-08-01

    demonstrated, then qualities such as drug resistance, strain divergence, virulence, and origin of isolates could be inferred by DNA-based tests. No such tests are in clinical or commercial use in parasitology and few tests are available for other organisms. Why have DNA-based tests not had a bigger impact in veterinary and human medicine? To explore this question, technological, biological, economic and sociological factors must be considered. Additionally, a realistic expectation of research progress is needed. DNA-based tests could enhance parasite management in many ways, but patience, persistence and dedication will be needed to achieve this goal. PMID:21700392

  15. Dogs, cats, parasites, and humans in Brazil: opening the black box

    PubMed Central

    2014-01-01

    Dogs and cats in Brazil serve as primary hosts for a considerable number of parasites, which may affect their health and wellbeing. These may include endoparasites (e.g., protozoa, cestodes, trematodes, and nematodes) and ectoparasites (i.e., fleas, lice, mites, and ticks). While some dog and cat parasites are highly host-specific (e.g., Aelurostrongylus abstrusus and Felicola subrostratus for cats, and Angiostrongylus vasorum and Trichodectes canis for dogs), others may easily switch to other hosts, including humans. In fact, several dog and cat parasites (e.g., Toxoplasma gondii, Dipylidium caninum, Ancylostoma caninum, Strongyloides stercoralis, and Toxocara canis) are important not only from a veterinary perspective but also from a medical standpoint. In addition, some of them (e.g., Lynxacarus radovskyi on cats and Rangelia vitalii in dogs) are little known to most veterinary practitioners working in Brazil. This article is a compendium on dog and cat parasites in Brazil and a call for a One Health approach towards a better management of some of these parasites, which may potentially affect humans. Practical aspects related to the diagnosis, treatment, and control of parasitic diseases of dogs and cats in Brazil are discussed. PMID:24423244

  16. Intracellular protozoan parasites of humans: the role of molecular chaperones in development and pathogenesis.

    PubMed

    Shonhai, Addmore; Maier, Alexander G; Przyborski, Jude M; Blatch, Gregory L

    2011-02-01

    Certain kinetoplastid (Leishmania spp. and Tryapnosoma cruzi) and apicomplexan parasites (Plasmodium falciparum and Toxoplasma gondii) are capable of invading human cells as part of their pathology. These parasites appear to have evolved a relatively expanded or diverse complement of genes encoding molecular chaperones. The gene families encoding heat shock protein 90 (Hsp90) and heat shock protein 70 (Hsp70) chaperones show significant expansion and diversity (especially for Leishmania spp. and T. cruzi), and in particular the Hsp40 family appears to be an extreme example of phylogenetic radiation. In general, Hsp40 proteins act as co-chaperones of Hsp70 chaperones, forming protein folding pathways that integrate with Hsp90 to ensure proteostasis in the cell. It is tempting to speculate that the diverse environmental insults that these parasites endure have resulted in the evolutionary selection of a diverse and expanded chaperone network. Hsp90 is involved in development and growth of all of these intracellular parasites, and so far represents the strongest candidate as a target for chemotherapeutic interventions. While there have been some excellent studies on the molecular and cell biology of Hsp70 proteins, relatively little is known about the biological function of Hsp70-Hsp40 interactions in these intracellular parasites. This review focuses on intracellular protozoan parasites of humans, and provides a critique of the role of heat shock proteins in development and pathogenesis, especially the molecular chaperones Hsp90, Hsp70 and Hsp40. PMID:20955165

  17. Genetic determinism of parasitic circadian periodicity and subperiodicity in human lymphatic filariasis.

    PubMed

    Pichon, Gaston; Treuil, Jean-Pierre

    2004-12-01

    The larval parasites of the pantropical lymphatic filariasis exhibit two types of circadian behaviour. Typically, they only appear in the human bloodstream at nighttime, synchronised with their mosquito vectors. In Polynesia and parts of Southeast Asia, free of nocturnal vectors, they are found at all hours, and each population biorhythm differs. Through a geometrical approach, we explain this circadian diversity by a single, dominant mutation: the clocks of individual parasites are set at midnight (ubiquitous) or at 2 p.m. Compared to other circadian genes, this mutation must be very old, as it is shared by four biologically remote genera of parasites. This seniority sheds new light on several theoretical and practical aspects of vector-parasite temporal relations. PMID:15656351

  18. The Human Malaria Parasite Plasmodium falciparum Is Not Dependent on Host Coenzyme A Biosynthesis*

    PubMed Central

    Spry, Christina; Saliba, Kevin J.

    2009-01-01

    Pantothenate, a precursor of the fundamental enzyme cofactor coenzyme A (CoA), is essential for growth of the intraerythrocytic stage of human and avian malaria parasites. Avian malaria parasites have been reported to be incapable of de novo CoA synthesis and instead salvage CoA from the host erythrocyte; hence, pantothenate is required for CoA biosynthesis within the host cell and not the parasite itself. Whether the same is true of the intraerythrocytic stage of the human malaria parasite, Plasmodium falciparum, remained to be established. In this study we investigated the metabolic fate of [14C]pantothenate within uninfected and P. falciparum-infected human erythrocytes. We provide evidence consistent with normal human erythrocytes, unlike rat erythrocytes (which have been reported to possess an incomplete CoA biosynthesis pathway), being capable of CoA biosynthesis from pantothenate. We also show that CoA biosynthesis is substantially higher in P. falciparum-infected erythrocytes and that P. falciparum, unlike its avian counterpart, generates most of the CoA synthesized in the infected erythrocyte, presumably necessitated by insufficient CoA biosynthesis in the host erythrocyte. Our data raise the possibility that malaria parasites rationalize their biosynthetic activity depending on the capacity of their host cell to synthesize the metabolites they require. PMID:19584050

  19. Schistosoma mansoni PIII antigen modulates in vitro granuloma formation by regulating CD28, CTLA-4, and CD86 expression in humans.

    PubMed

    Zouain, C S; Falcão, P L; Goes, T S; Leite, M F; Goes, A M

    2004-02-15

    We investigated the in vitro responses of peripheral blood mononuclear cells (PBMC) from intestinal chronic schistosomiasis patients to PIII, a multivalent antigen prepared from Schistosoma mansoni adult worm. PIII decreased cellular proliferation and granulomatous reaction. Moreover, induced the reduction of IFN-gamma levels and increased IL-10 production. To better understand the mechanism through which the observed suppression occurs, the present study focused on the phenotypic pattern displayed by PBMC treated with PIII in an in vitro granuloma assay. Expression of the surface markers CD28, CTLA-4 and CD86 by lymphocytes and monocytes were analyzed by flow cytometry. Our results demonstrated a significant decrease of CD28+CD4+ and CD28+CD8+ T-cell percentage stimulated by PIII compared to its non-infected counterparts. This suppressive effect was related to a significant increase in the percentage of T-cells expressing CTLA-4. PIII also promoted a significant increase in the percentage of cells expressing CD86. Indeed, our results demonstrated that PIII was capable of modulating in vitro granuloma reaction, and this event was related to the balance of IL-10, IFN-gamma and CD28, CTLA-4, CD86 bringing new insight to the immunoregulation of granulomatous hypersensitivity in human schistosomiasis. PMID:15019278

  20. Atopy Is Inversely Related to Schistosome Infection Intensity: A Comparative Study in Zimbabwean Villages with Distinct Levels of Schistosoma haematobium Infection

    PubMed Central

    Rujeni, Nadine; Nausch, Norman; Bourke, Claire D.; Midzi, Nicholas; Mduluza, Takafira; Taylor, David W.; Mutapi, Francisca

    2012-01-01

    Background The hygiene hypothesis suggests that parasitic infections protect against allergic diseases by modulating the host's immune responses. Experimental studies indicate that this protection depends on the intensity of parasitic infection, but this observation has not been tested in human populations. The aim of this study is to investigate whether the intensity of Schistosoma haematobium infection is related to atopic responses and whether this relationship differs between populations with distinct parasite transmission dynamics. Methods The study was conducted in two villages with different Schistosoma haematobium transmission dynamics, i.e. high (n = 365) and low (n = 307) transmission. Allergic reactivity to the common house dust mite (Dermatophagoides pteronyssinus) was measured by skin prick tests and allergen-specific IgE and IgG4 quantified by enzyme-linked immunosorbent assay. Atopic responses were related to current infection intensity and schistosome transmission levels. Results Schistosome infection intensity was negatively associated with the skin prick reactivity, mite-specific IgE and the ratio IgE/IgG4 in the high-transmission village. However, when only low levels of infection were analyzed in the 2 villages, there was no correlation between mite-specific responses and infection intensity. Conclusion The relationship between schistosome infection and atopic responses is dependent on the intensity of current schistosome infection. Thus, consistent with results from animal models, with an increasing parasite burden, the immunoregulation of immune responses to allergens appears to become more pronounced. PMID:22398631

  1. Genetic recombination between human and animal parasites creates novel strains of human pathogen.

    PubMed

    Gibson, Wendy; Peacock, Lori; Ferris, Vanessa; Fischer, Katrin; Livingstone, Jennifer; Thomas, James; Bailey, Mick

    2015-03-01

    Genetic recombination between pathogens derived from humans and livestock has the potential to create novel pathogen strains, highlighted by the influenza pandemic H1N1/09, which was derived from a re-assortment of swine, avian and human influenza A viruses. Here we investigated whether genetic recombination between subspecies of the protozoan parasite, Trypanosoma brucei, from humans and animals can generate new strains of human pathogen, T. b. rhodesiense (Tbr) responsible for sleeping sickness (Human African Trypanosomiasis, HAT) in East Africa. The trait of human infectivity in Tbr is conferred by a single gene, SRA, which is potentially transferable to the animal pathogen Tbb by sexual reproduction. We tracked the inheritance of SRA in crosses of Tbr and Tbb set up by co-transmitting genetically-engineered fluorescent parental trypanosome lines through tsetse flies. SRA was readily transferred into new genetic backgrounds by sexual reproduction between Tbr and Tbb, thus creating new strains of the human pathogen, Tbr. There was no evidence of diminished growth or transmissibility of hybrid trypanosomes carrying SRA. Although expression of SRA is critical to survival of Tbr in the human host, we show that the gene exists as a single copy in a representative collection of Tbr strains. SRA was found on one homologue of chromosome IV in the majority of Tbr isolates examined, but some Ugandan Tbr had SRA on both homologues. The mobility of SRA by genetic recombination readily explains the observed genetic variability of Tbr in East Africa. We conclude that new strains of the human pathogen Tbr are being generated continuously by recombination with the much larger pool of animal-infective trypanosomes. Such novel recombinants present a risk for future outbreaks of HAT. PMID:25816228

  2. Genetic Recombination between Human and Animal Parasites Creates Novel Strains of Human Pathogen

    PubMed Central

    Gibson, Wendy; Peacock, Lori; Ferris, Vanessa; Fischer, Katrin; Livingstone, Jennifer; Thomas, James; Bailey, Mick

    2015-01-01

    Genetic recombination between pathogens derived from humans and livestock has the potential to create novel pathogen strains, highlighted by the influenza pandemic H1N1/09, which was derived from a re-assortment of swine, avian and human influenza A viruses. Here we investigated whether genetic recombination between subspecies of the protozoan parasite, Trypanosoma brucei, from humans and animals can generate new strains of human pathogen, T. b. rhodesiense (Tbr) responsible for sleeping sickness (Human African Trypanosomiasis, HAT) in East Africa. The trait of human infectivity in Tbr is conferred by a single gene, SRA, which is potentially transferable to the animal pathogen Tbb by sexual reproduction. We tracked the inheritance of SRA in crosses of Tbr and Tbb set up by co-transmitting genetically-engineered fluorescent parental trypanosome lines through tsetse flies. SRA was readily transferred into new genetic backgrounds by sexual reproduction between Tbr and Tbb, thus creating new strains of the human pathogen, Tbr. There was no evidence of diminished growth or transmissibility of hybrid trypanosomes carrying SRA. Although expression of SRA is critical to survival of Tbr in the human host, we show that the gene exists as a single copy in a representative collection of Tbr strains. SRA was found on one homologue of chromosome IV in the majority of Tbr isolates examined, but some Ugandan Tbr had SRA on both homologues. The mobility of SRA by genetic recombination readily explains the observed genetic variability of Tbr in East Africa. We conclude that new strains of the human pathogen Tbr are being generated continuously by recombination with the much larger pool of animal-infective trypanosomes. Such novel recombinants present a risk for future outbreaks of HAT. PMID:25816228

  3. Proteomic Analysis of Schistosoma mansoni Egg Secretions

    PubMed Central

    Cass, Cynthia L.; Johnson, Jeffrey R.; Califf, Lindsay L.; Xu, Tao; Hernandez, Hector J.; Stadecker, Miguel J.; Yates, John R.; Williams, David L.

    2007-01-01

    Schistosomiasis remains a largely neglected, global health problem. The morbid pathology of the disease stems from the host's inflammatory response to parasite eggs trapped in host tissues. Long term host/parasite survival is dependent upon the successful modulation of the acute pathological response, which is induced by egg antigens. In this study, using Multidimensional Protein Identification Technology, we identified the Schistosoma mansoni egg secretome consisting of 188 proteins. Notably we identified proteins involved in redox balance, molecular chaperoning and protein folding, development and signaling, scavenging and metabolic pathways, immune response modulation, and 32 novel, previously uncharacterized schistosome proteins. We localized a subset of previously-characterized schistosome proteins identified in egg secretions in this study, to the surface of live S. mansoni eggs using the circumoval precipitin reaction. The identification of proteins actively secreted by live schistosome eggs provides important new information for understanding immune modulation and the pathology of schistosomiasis. PMID:17644200

  4. Genomics of Loa loa, a Wolbachia-free filarial parasite of humans.

    PubMed

    Desjardins, Christopher A; Cerqueira, Gustavo C; Goldberg, Jonathan M; Dunning Hotopp, Julie C; Haas, Brian J; Zucker, Jeremy; Ribeiro, José M C; Saif, Sakina; Levin, Joshua Z; Fan, Lin; Zeng, Qiandong; Russ, Carsten; Wortman, Jennifer R; Fink, Doran L; Birren, Bruce W; Nutman, Thomas B

    2013-05-01

    Loa loa, the African eyeworm, is a major filarial pathogen of humans. Unlike most filariae, L. loa does not contain the obligate intracellular Wolbachia endosymbiont. We describe the 91.4-Mb genome of L. loa and that of the related filarial parasite Wuchereria bancrofti and predict 14,907 L. loa genes on the basis of microfilarial RNA sequencing. By comparing these genomes to that of another filarial parasite, Brugia malayi, and to those of several other nematodes, we demonstrate synteny among filariae but not with nonparasitic nematodes. The L. loa genome encodes many immunologically relevant genes, as well as protein kinases targeted by drugs currently approved for use in humans. Despite lacking Wolbachia, L. loa shows no new metabolic synthesis or transport capabilities compared to other filariae. These results suggest that the role of Wolbachia in filarial biology is more subtle than previously thought and reveal marked differences between parasitic and nonparasitic nematodes. PMID:23525074

  5. The Human Malaria Parasite Pfs47 Gene Mediates Evasion of the Mosquito Immune System

    PubMed Central

    Molina-Cruz, Alvaro; Garver, Lindsey S.; Alabaster, Amy; Bangiolo, Lois; Haile, Ashley; Winikor, Jared; Ortega, Corrie; van Schaijk, Ben C. L.; Sauerwein, Robert W.; Taylor-Salmon, Emma; Barillas-Mury, Carolina

    2013-01-01

    Summary The surface protein Pfs47 mediates Plasmodium falciparum evasion of the Anopheles gambiae complement-like immune system. Plasmodium falciparum transmission by Anopheles gambiae mosquitoes is remarkably efficient, resulting in a very high prevalence of human malaria infection in sub-Saharan Africa. A combination of genetic mapping, linkage group selection, and functional genomics was used to identify Pfs47 as a P. falciparum gene that allows the parasite to infect A. gambiae without activating the mosquito immune system. Disruption of Pfs47 greatly reduced parasite survival in the mosquito and this phenotype could be reverted by genetic complementation of the parasite or by disruption of the mosquito complement-like system. Pfs47 suppresses midgut nitration responses that are critical to activate the complement-like system. We provide direct experimental evidence that immune evasion mediated by Pfs47 is critical for efficient human malaria transmission by A. gambiae. PMID:23661646

  6. The human malaria parasite Pfs47 gene mediates evasion of the mosquito immune system.

    PubMed

    Molina-Cruz, Alvaro; Garver, Lindsey S; Alabaster, Amy; Bangiolo, Lois; Haile, Ashley; Winikor, Jared; Ortega, Corrie; van Schaijk, Ben C L; Sauerwein, Robert W; Taylor-Salmon, Emma; Barillas-Mury, Carolina

    2013-05-24

    Plasmodium falciparum transmission by Anopheles gambiae mosquitoes is remarkably efficient, resulting in a very high prevalence of human malaria infection in sub-Saharan Africa. A combination of genetic mapping, linkage group selection, and functional genomics was used to identify Pfs47 as a P. falciparum gene that allows the parasite to infect A. gambiae without activating the mosquito immune system. Disruption of Pfs47 greatly reduced parasite survival in the mosquito, and this phenotype could be reverted by genetic complementation of the parasite or by disruption of the mosquito complement-like system. Pfs47 suppresses midgut nitration responses that are critical to activate the complement-like system. We provide direct experimental evidence that immune evasion mediated by Pfs47 is critical for efficient human malaria transmission by A. gambiae. PMID:23661646

  7. Protein kinase A signalling in Schistosoma mansoni cercariae and schistosomules.

    PubMed

    Hirst, Natasha L; Lawton, Scott P; Walker, Anthony J

    2016-06-01

    Cyclic AMP (cAMP)-dependent protein kinase/protein kinase A regulates multiple processes in eukaryotes by phosphorylating diverse cellular substrates, including metabolic and signalling enzymes, ion channels and transcription factors. Here we provide insight into protein kinase A signalling in cercariae and 24h in vitro cultured somules of the blood parasite, Schistosoma mansoni, which causes human intestinal schistosomiasis. Functional mapping of activated protein kinase A using anti-phospho protein kinase A antibodies and confocal laser scanning microscopy revealed activated protein kinase A in the central and peripheral nervous system, oral-tip sensory papillae, oesophagus and excretory system of intact cercariae. Cultured 24h somules, which biologically represent the skin-resident stage of the parasite, exhibited similar activation patterns in oesophageal and nerve tissues but also displayed striking activation at the tegument and activation in a region resembling the germinal 'stem' cell cluster. The adenylyl cyclase activator, forskolin, stimulated somule protein kinase A activation and produced a hyperkinesia phenotype. The biogenic amines, serotonin and dopamine known to be present in skin also induced protein kinase A activation in somules, whereas neuropeptide Y or [Leu(31),Pro(34)]-neuropeptide Y attenuated protein kinase A activation. However, neuropeptide Y did not block the forskolin-induced somule hyperkinesia. Bioinformatic investigation of potential protein associations revealed 193 medium confidence and 59 high confidence protein kinase A interacting partners in S. mansoni, many of which possess putative protein kinase A phosphorylation sites. These data provide valuable insight into the intricacies of protein kinase A signalling in S. mansoni and a framework for further physiological investigations into the roles of protein kinase A in schistosomes, particularly in the context of interactions between the parasite and the host. PMID:26777870

  8. Genetic structure of Schistosoma mansoni in western Kenya: the effects of geography and host sharing

    PubMed Central

    Steinauer, M. L.; Hanelt, B.; Agola, L. E.; Mkoji, G. M.; Loker, E. S.

    2010-01-01

    We examined the spatial structure of Schistosoma mansoni, a parasite of humans, from natural infections at two levels: across the Lake Victoria basin of Kenya and among snail hosts. Using 20 microsatellite markers we examined geographic patterns of relatedness and population structure of cercariae and found weak, but significant structure detected by some, but not all analyses. We hypothesize structure created by aggregations of clonal individuals or adherence of hosts to local transmission sites is eroded by high amounts of gene flow in the region. This finding also supports previous hypotheses concerning the evolution of drug resistance in the region. Intrasnail dynamics were investigated in the context of aggregation and kin selection theory to determine how relatedness and also sex influence host sharing and host exploitation. Cercarial production did not differ significantly between snails with one or two genotypes suggesting that mixed infections resulted in decreased individual fitness and provides a framework for reproductive competition. Coinfection patterns in snails were independent of parasite relatedness indicating that schistosomes were not aggregated according to their relatedness and that kin selection was not influencing host sharing. Additionally, host exploitation in coinfections (measured by cercarial production) was not negatively correlated with relatedness, as predicted by classical models due to increased competition and thus exploitation when parasites are unrelated. Because of the low levels of relatedness within the population, schistosomes may rarely encounter close relatives and kin selection mechanisms that influence the distribution of individuals within snails or the virulence mode of the parasites may simply have not evolved. PMID:19464296

  9. Development and Application of a Simple Plaque Assay for the Human Malaria Parasite Plasmodium falciparum

    PubMed Central

    Thomas, James A.; Collins, Christine R.; Das, Sujaan; Hackett, Fiona; Graindorge, Arnault; Bell, Donald; Deu, Edgar; Blackman, Michael J.

    2016-01-01

    Malaria is caused by an obligate intracellular protozoan parasite that replicates within and destroys erythrocytes. Asexual blood stages of the causative agent of the most virulent form of human malaria, Plasmodium falciparum, can be cultivated indefinitely in vitro in human erythrocytes, facilitating experimental analysis of parasite cell biology, biochemistry and genetics. However, efforts to improve understanding of the basic biology of this important pathogen and to develop urgently required new antimalarial drugs and vaccines, suffer from a paucity of basic research tools. This includes a simple means of quantifying the effects of drugs, antibodies and gene modifications on parasite fitness and replication rates. Here we describe the development and validation of an extremely simple, robust plaque assay that can be used to visualise parasite replication and resulting host erythrocyte destruction at the level of clonal parasite populations. We demonstrate applications of the plaque assay by using it for the phenotypic characterisation of two P. falciparum conditional mutants displaying reduced fitness in vitro. PMID:27332706

  10. 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. PMID:24991919

  11. Host mitochondrial association evolved in the human parasite Toxoplasma gondii via neofunctionalization of a gene duplicate

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In Toxoplasma gondii, an intracellular parasite of humans and other warm-blooded animals, the ability to associate with host mitochondria (HMA) is driven by a locally expanded gene family that encodes multiple mitochondrial association factor 1 (MAF1) proteins. The importance of copy number in the e...

  12. Centrality in primate–parasite networks reveals the potential for the transmission of emerging infectious diseases to humans

    PubMed Central

    Gómez, José María; Nunn, Charles L.; Verdú, Miguel

    2013-01-01

    Most emerging infectious diseases (EIDs) in humans have arisen from animals. Identifying high-risk hosts is therefore vital for the control and surveillance of these diseases. Viewing hosts as connected through the parasites they share, we use network tools to investigate predictors of parasitism and sources of future EIDs. We generated host–parasite networks that link hosts when they share a parasite, using nonhuman primates as a model system because—owing to their phylogenetic proximity and ecological overlap with humans—they are an important source of EIDs to humans. We then tested whether centrality in the network of host species—a measurement of the importance of a given node (i.e., host species) in the network—is associated with that host serving as a potential EID source. We found that centrality covaries with key predictors of parasitism, such as population density and geographic range size. Importantly, we also found that primate species having higher values of centrality in the primate–parasite network harbored more parasites identified as EIDs in humans and had parasite communities more similar to those found in humans. These relationships were robust to the use of different centrality metrics and to multiple ways of controlling for variation in how well each species has been studied (i.e., sampling effort). Centrality may therefore estimate the role of a host as a source of EIDs to humans in other multispecific host–parasite networks. PMID:23610389

  13. Tapeworm Diphyllobothrium dendriticum (Cestoda)—Neglected or Emerging Human Parasite?

    PubMed Central

    Kuchta, Roman; Brabec, Jan; Kubáčková, Petra; Scholz, Tomáš

    2013-01-01

    Background A total number of 14 valid species of Diphyllobothrium tapeworms have been described in literature to be capable of causing diphyllobothriosis, with D. latum being the major causative agent of all human infections. However, recent data indicate that some of these infections, especially when diagnosed solely on the basis of morphology, have been identified with this causative agent incorrectly, confusing other Diphyllobothrium species with D. latum. Another widely distributed species, D. dendriticum, has never been considered as a frequent parasite of man, even though it is found commonly throughout arctic and subarctic regions parasitizing piscivorous birds and mammals. Recent cases of Europeans infected with this cestode called into question the actual geographic distribution of this tapeworm, largely ignored by medical parasitologists. Methodology and Results On the basis of revision of more than 900 available references and a description and revision of recent European human cases using morphological and molecular (cox1) data supplemented by newly characterized D. dendriticum sequences, we updated the current knowledge of the life-cycle, geographic distribution, epidemiological status, and molecular diagnostics of this emerging causal agent of zoonotic disease of man. Conclusions The tapeworm D. dendriticum represents an example of a previously neglected, probably underdiagnosed parasite of man with a potential to spread globally. Recent cases of diphyllobothriosis caused by D. dendriticum in Europe (Netherlands, Switzerland and Czech Republic), where the parasite has not been reported previously, point out that causative agents of diphyllobothriosis and other zoonoses can be imported throughout the world. Molecular tools should be used for specific and reliable parasite diagnostics, and also rare or non-native species should be considered. This will considerably help improve our knowledge of the distribution and epidemiology of these human parasites

  14. Ancient human sialic acid variant restricts an emerging zoonotic malaria parasite

    PubMed Central

    Dankwa, Selasi; Lim, Caeul; Bei, Amy K.; Jiang, Rays H. Y.; Abshire, James R.; Patel, Saurabh D.; Goldberg, Jonathan M.; Moreno, Yovany; Kono, Maya; Niles, Jacquin C.; Duraisingh, Manoj T.

    2016-01-01

    Plasmodium knowlesi is a zoonotic parasite transmitted from macaques causing malaria in humans in Southeast Asia. Plasmodium parasites bind to red blood cell (RBC) surface receptors, many of which are sialylated. While macaques synthesize the sialic acid variant N-glycolylneuraminic acid (Neu5Gc), humans cannot because of a mutation in the enzyme CMAH that converts N-acetylneuraminic acid (Neu5Ac) to Neu5Gc. Here we reconstitute CMAH in human RBCs for the reintroduction of Neu5Gc, which results in enhancement of P. knowlesi invasion. We show that two P. knowlesi invasion ligands, PkDBPβ and PkDBPγ, bind specifically to Neu5Gc-containing receptors. A human-adapted P. knowlesi line invades human RBCs independently of Neu5Gc, with duplication of the sialic acid-independent invasion ligand, PkDBPα and loss of PkDBPγ. Our results suggest that absence of Neu5Gc on human RBCs limits P. knowlesi invasion, but that parasites may evolve to invade human RBCs through the use of sialic acid-independent pathways. PMID:27041489

  15. Ancient human sialic acid variant restricts an emerging zoonotic malaria parasite.

    PubMed

    Dankwa, Selasi; Lim, Caeul; Bei, Amy K; Jiang, Rays H Y; Abshire, James R; Patel, Saurabh D; Goldberg, Jonathan M; Moreno, Yovany; Kono, Maya; Niles, Jacquin C; Duraisingh, Manoj T

    2016-01-01

    Plasmodium knowlesi is a zoonotic parasite transmitted from macaques causing malaria in humans in Southeast Asia. Plasmodium parasites bind to red blood cell (RBC) surface receptors, many of which are sialylated. While macaques synthesize the sialic acid variant N-glycolylneuraminic acid (Neu5Gc), humans cannot because of a mutation in the enzyme CMAH that converts N-acetylneuraminic acid (Neu5Ac) to Neu5Gc. Here we reconstitute CMAH in human RBCs for the reintroduction of Neu5Gc, which results in enhancement of P. knowlesi invasion. We show that two P. knowlesi invasion ligands, PkDBPβ and PkDBPγ, bind specifically to Neu5Gc-containing receptors. A human-adapted P. knowlesi line invades human RBCs independently of Neu5Gc, with duplication of the sialic acid-independent invasion ligand, PkDBPα and loss of PkDBPγ. Our results suggest that absence of Neu5Gc on human RBCs limits P. knowlesi invasion, but that parasites may evolve to invade human RBCs through the use of sialic acid-independent pathways. PMID:27041489

  16. [SWOT Analysis of the National Survey on Current Status of Major Human Parasitic Diseases in China].

    PubMed

    ZHU, Hui-hui; ZHOU, Chang-hai; CHEN, Ying-dan; ZANG, Wei; XIAO, Ning; ZHOU, Xiao-nong

    2015-10-01

    The National Survey on Current Status of Major Human Parasitic Diseases in China has been carried out since 2014 under the organization of the National Health and Family Planning Commission of the People's Republic of China. The National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (NIPD, China CDC) provided technical support and was responsible for quality control in this survey. This study used SWOT method to analyze the strengths, weaknesses, opportunities and threats that were encountered by he NIPD, China CDC during the completion of the survey. Accordingly, working strategies were proposed to facilitate the future field work. PMID:26931045

  17. A transcriptional switch underlies commitment to sexual development in human malaria parasites

    PubMed Central

    Kafsack, Björn F.C.; Rovira-Graells, Núria; Clark, Taane G.; Bancells, Cristina; Crowley, Valerie M.; Campino, Susana G.; Williams, April E.; Drought, Laura G.; Kwiatkowski, Dominic P.; Baker, David A.; Cortés, Alfred; Llinás, Manuel

    2014-01-01

    The life cycles of many parasites involve transitions between disparate host species, requiring these parasites to go through multiple developmental stages adapted to each of these specialized niches. Transmission of malaria parasites (Plasmodium spp.) from humans to the mosquito vector requires differentiation from asexual stages replicating within red blood cells into non-dividing male and female gametocytes. Although gametocytes were first described in 1880, our understanding of the molecular mechanisms involved in commitment to gametocyte formation is extremely limited and disrupting this critical developmental transition remains a long-standing goal1. We show here that expression levels of the DNA-binding protein PfAP2-G correlate strongly with levels of gametocyte formation. Using independent forward and reverse genetics approaches, we demonstrate that PfAP2-G function is essential for parasite sexual differentiation. By combining genome-wide PfAP2-G cognate motif occurrence with global transcriptional changes resulting from PfAP2-G ablation, we identify early gametocyte genes as likely targets of PfAP2-G and show that their regulation by PfAP2-G is critical for their wild-type level expression. In the asexual blood-stage parasites pfap2-g appears to be among a set of epigenetically silenced loci2,3 prone to spontaneous activation4. Stochastic activation presents a simple mechanism for a low baseline of gametocyte production. Overall, these findings identify PfAP2-G as a master regulator of sexual-stage development in malaria parasites and mark the first identification of a transcriptional switch controlling a differentiation decision in protozoan parasites. PMID:24572369

  18. The landscape of human genes involved in the immune response to parasitic worms

    PubMed Central

    2010-01-01

    Background More than 2 billion individuals worldwide suffer from helminth infections. The highest parasite burdens occur in children and helminth infection during pregnancy is a risk factor for preterm delivery and reduced birth weight. Therefore, helminth infections can be regarded as a strong selective pressure. Results Here we propose that candidate susceptibility genes for parasitic worm infections can be identified by searching for SNPs that display a strong correlation with the diversity of helminth species/genera transmitted in different geographic areas. By a genome-wide search we identified 3478 variants that correlate with helminth diversity. These SNPs map to 810 distinct human genes including loci involved in regulatory T cell function and in macrophage activation, as well as leukocyte integrins and co-inhibitory molecules. Analysis of functional relationships among these genes identified complex interaction networks centred around Th2 cytokines. Finally, several genes carrying candidate targets for helminth-driven selective pressure also harbour susceptibility alleles for asthma/allergy or are involved in airway hyper-responsiveness, therefore expanding the known parallelism between these conditions and parasitic infections. Conclusions Our data provide a landscape of human genes that modulate susceptibility to helminths and indicate parasitic worms as one of the major selective forces in humans. PMID:20807397

  19. Targeting of a Transporter to the Outer Apicoplast Membrane in the Human Malaria Parasite Plasmodium falciparum

    PubMed Central

    Goodman, Christopher D.; McFadden, Geoffrey I.

    2016-01-01

    Apicoplasts are vestigial plastids in apicomplexan parasites like Plasmodium, the causative agent of malaria. Apicomplexan parasites are dependant on their apicoplasts for synthesis of various molecules that they are unable to scavenge in sufficient quantity from their host, which makes apicoplasts attractive drug targets. Proteins known as plastid phosphate translocators (pPTs) are embedded in the outer apicoplast membrane and are responsible for the import of carbon, energy and reducing power to drive anabolic synthesis in the organelle. We investigated how a pPT is targeted into the outer apicoplast membrane of the human malaria parasite P. falciparum. We showed that a transmembrane domain is likely to act as a recessed signal anchor to direct the protein into the endomembrane system, and that a tyrosine in the cytosolic N-terminus of the protein is essential for targeting, but one or more, as yet unidentified, factors are also essential to direct the protein into the outer apicoplast membrane. PMID:27442138

  20. Current laboratory diagnosis of opportunistic enteric parasites in human immunodeficiency virus-infected patients

    PubMed Central

    De, Anuradha

    2013-01-01

    Diarrhea is a major cause of morbidity and mortality in human immunodeficiency virus (HIV)-infected individuals. Opportunistic enteric parasitic infections are encountered in 30-60% of HIV seropositive patients in developed countries and in 90% of patients in developing countries. Once the CD4+ cell count drops below 200 cells/μl, patients are considered to have developed acquired immunodeficiency syndrome (AIDS), with the risk of an AIDS-defining illness or opportunistic infection significantly increasing. Opportunistic enteric parasites encountered in these patients are Cryptosporidium, Isospora, Cyclospora, and microsporidia; as well as those more commonly associated with gastrointestinal disease, for example, Giardia intestinalis, Entamoeba histolytica, Strongyloides stercoralis, and also rarely Balantidium coli. In view of AIDS explosion in India, opportunistic enteric parasites are becoming increasingly important and it has to be identified properly. Apart from wet mounts, concentration methods for stool samples and special staining techniques for identification of these parasites, commercially available fecal immunoassays are widely available for the majority of enteric protozoa. Molecular methods such as polymerase chain reaction (PCR), PCR-restriction fragment length polymorphism, flow cytometry, and sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), have also come in the pipeline for early diagnosis of these infections. Proper disposal of the feces to prevent contamination of the soil and water, boiling/filtering drinking water along with improved personal hygiene might go a long way in preventing these enteric parasitic infections. PMID:23961436

  1. Multiple Simultaneous Gastrointestinal Parasitic Infections in a Patient with Human Immunodeficiency Virus.

    PubMed

    Del Pilar-Morales, Esteban A; Cardona-Rodríguez, Zaydalee; Bertrán-Pasarell, Jorge; Soto-Malave, Ruth; De León-Borras, Rafeal

    2016-06-01

    Patients with the human immunodeficiency virus (HIV) infection are at high risk for gastrointestinal infections causing diarrhea, particularly when those infections are parasitic in nature. This propensity is more pronounced in AIDS, where opportunistic parasitic infections may cause severe diarrhea, marked absorptive dysfunction, and significant risk of mortality. There are scant data regarding parasitic infections among HIV patients in the developed world; most studies and research come from povertystricken areas of South Africa, India, Iran, and the South Pacific. Although multiple infections with the same or different parasites have been reported, simultaneous infections are rare. We present the case of a 35-year-old man who developed a co-infection with Giardia, Cryptosporidium, and Strongyloides, simultaneously, the diagnosis being made after the judicious evaluation of a stool sample. Given the associated morbidity, prompt diagnosis and treatment are needed to avoid further complications in patients with HIV. To our knowledge this is the first reported case of triple parasitic infection in a patient with HIV. PMID:27232872

  2. Identification of new markers for the Schistosoma mansoni vitelline lineage.

    PubMed

    Wang, Jipeng; Collins, James J

    2016-06-01

    Schistosomes cause significant morbidity and mortality in millions of the world's poorest people. While parasite egg-induced inflammation is the primary driver of host pathology, relatively little is known at the molecular level about the organ systems that participate in schistosome egg production (i.e., testes, ovaries and vitellaria). Here we use transcriptional profiling and in situ hybridization to characterise the vitellarium of Schistosoma mansoni. We uncovered several previously uncharacterised vitellaria-specific factors and defined molecular markers for various stages in the vitellocyte differentiation process. These data provide the framework for future in-depth molecular studies exploring the biology of this important parasite organ. PMID:27056273

  3. Molecular Paleoparasitological Hybridization Approach as Effective Tool for Diagnosing Human Intestinal Parasites from Scarce Archaeological Remains

    PubMed Central

    Jaeger, Lauren Hubert; Iñiguez, Alena Mayo

    2014-01-01

    Paleoparasitology is the science that uses parasitological techniques for diagnosing parasitic diseases in the past. Advances in molecular biology brought new insights into this field allowing the study of archaeological material. However, due to technical limitations a proper diagnosis and confirmation of the presence of parasites is not always possible, especially in scarce and degraded archaeological remains. In this study, we developed a Molecular Paleoparasitological Hybridization (MPH) approach using ancient DNA (aDNA) hybridization to confirm and complement paleoparasitological diagnosis. Eight molecular targets from four helminth parasites were included: Ascaris sp., Trichuris trichiura, Enterobius vermicularis, and Strongyloides stercoralis. The MPH analysis using 18th century human remains from Praça XV cemetery (CPXV), Rio de Janeiro, Brazil, revealed for the first time the presence E. vermicularis aDNA (50%) in archaeological sites of Brazil. Besides, the results confirmed T. trichiura and Ascaris sp. infections. The prevalence of infection by Ascaris sp. and E. vermicularis increased considerably when MPH was applied. However, a lower aDNA detection of T. trichiura (40%) was observed when compared to the diagnosis by paleoparasitological analysis (70%). Therefore, based on these data, we suggest a combination of Paleoparasitological and MPH approaches to verify the real panorama of intestinal parasite infection in human archeological samples. PMID:25162694

  4. IMMUNODIAGNOSIS OF HUMAN STRONGYLOIDIASIS: USE OF SIX DIFFERENT ANTIGENIC FRACTIONS FROM Strongyloides venezuelensis PARASITIC FEMALES

    PubMed Central

    CORRAL, Marcelo Andreetta; de PAULA, Fabiana Martins; GOTTARDI, Maiara; MEISEL, Dirce Mary Correia Lima; CASTILHO, Vera Lucia Pagliusi; GONÇALVES, Elenice Messias do Nascimento; CHIEFFI, Pedro Paulo; GRYSCHEK, Ronaldo Cesar Borges

    2015-01-01

    SUMMARY The aim of this study was to evaluate six different antigenic fractions from Strongyloides venezuelensis parasitic females for the immunodiagnosis of human strongyloidiasis. Soluble and membrane fractions from S. venezuelensis parasitic females were prepared in phosphate-buffered saline (SSF and SMF, respectively), Tris-HCl (TSF and TMF, respectively), and an alkaline buffer (ASF and AMF, respectively). Serum samples obtained from patients with strongyloidiasis or, other parasitic diseases, and healthy individuals were analyzed by enzyme-linked immunosorbent assay (ELISA). Soluble fractions SSF, TSF, and ASF showed 85.0%, 75.0%, and 80.0% sensitivity and 93.1%, 93.1%, and 87.5% specificity, respectively. Membrane fractions SMF, TMF, and AMF showed 80.0%, 75.0%, and 85.0% sensitivity, and 95.8%, 90.3%, and 91.7% specificity, respectively. In conclusion, the present results suggest that the fractions obtained from parasitic females, especially the SSF and SMF, could be used as alternative antigen sources in the serodiagnosis of human strongyloidiasis. PMID:26603231

  5. [Algorithm for the coproscopic diagnosis of human intestinal parasites].

    PubMed

    Dolbin, D A; Tiurin, Iu A; Khaĭrullin, R M

    2012-01-01

    The purpose of the study was to elaborate a detection algorithm for human intestinal helminth eggs. There is a broad spectrum ofcoproscopic methods recommended for the detection of Opisthorchis eggs in man and animals; these include Fulleborn's method, formalin-ether method, Goryachev's, Katoh's, Kalantaryan's, Shcherbovich's, and Kotelnikov-Varenichev methods. Combined coproscopic methods are significantly more effective in detecting the causative agents of enteric parasitoses than is Katoh's method. Among the considered coproscopic techniques for the diagnosis of human ascariasis, it is most rational to use a combined method for fecal examination, the basis for which is a multicomponent flotation system (such as the author's one). The Kotelnikov-Varenichev method is optimal for diagnosing opisthorchiasis. It is optimal to use 2-3 methods of different groups simultaneously for the screening diagnosis of intestinal parasitoses. PMID:22774504

  6. Two allelic isoforms of the serotonin transporter from Schistosoma mansoni display electrogenic transport and high selectivity for serotonin

    PubMed Central

    Fontana, Andréia C. K.; Sonders, Mark S.; Pereira-Junior, Olavo S.; Knight, Matty; Javitch, Jonathan A.; Rodrigues, Vanderlei; Amara, Susan G.; Mortensen, Ole V.

    2009-01-01

    The human blood fluke Schistosoma mansoni is the primary cause of schistosomiasis, a debilitating disease that affects 200 million individuals in over 70 countries. The biogenic amine serotonin is essential for the survival of the parasite and serotonergic proteins are potential novel drug targets for treating schistosomiasis. Here we characterize two novel serotonin transporter gene transcripts, SmSERT-A and SmSERT-B, from Schistosoma mansoni. Southern blot analysis shows that the two mRNAs are the products of different alleles of a single SmSERT gene locus. The two SmSERT forms differ in three amino acid positions near the N-terminus of the protein. Both SmSERTs are expressed in the adult form and in the sporocyst form (infected snails) of the parasite, but are absent from all other stages of the parasite’s complex life cycle. Heterologous expression of the two cDNAs in mammalian cells resulted in saturable, sodium-dependent serotonin transport activity with an apparent affinity for serotonin comparable to that of the human serotonin transporter. Although the two SmSERTs are pharmacologically indistinguishable from each other, efflux experiments reveal notably higher substrate selectivity for serotonin compared with their mammalian counterparts. Several well-established substrates for human SERT including (±)MDMA, S-(+)amphetamine, RU 24969, and m-CPP are not transported by SmSERTs, underscoring the higher selectivity of the schistosomal isoforms. Voltage clamp recordings of SmSERT substrate-elicited currents confirm the substrate selectivity observed in efflux experiments and suggest that it may be possible to exploit the electrogenic nature of SmSERT to screen for compounds that target the parasite in vivo. PMID:19549517

  7. Activity of epiisopiloturine against Schistosoma mansoni.

    PubMed

    Veras, L M; Guimaraes, M A; Campelo, Y D; Vieira, M M; Nascimento, C; Lima, D F; Vasconcelos, L; Nakano, E; Kuckelhaus, S S; Batista, M C; Leite, J R; Moraes, J

    2012-01-01

    Schistosomiasis, caused by blood flukes of the genus Schistosoma, still imposes a considerable public health burden on large parts of the world. The control of this disease depends almost exclusively on the drug praziquantel, and there are no alternative drugs in sight. Natural compounds have recently attracted significant attention due to their relevance to parasitic infection and potential development into new therapeutic agents. Epiisopiloturine is an imidazole alkaloid isolated from the leaves of Pilocarpus microphyllus (Rutaceae), a native plant from Brazil. Here, we report the in vitro effect of this drug on the survival time of Schistosoma mansoni of different ages, such as 3 h old and 1, 3, 5, and 7 days old schistosomula, 49-day-old adults, and on egg output by adult worms. Epiisopiloturine at a concentration of 300 μg/mL caused the death of all schistosomula within 120 h. Extensive tegumental alterations and death were observed when adult schistosomes had been exposed to 150 μg/mL of the epiisopiloturine. At the highest sub-lethal dose of alkaloid (100 μg/mL), a 100% reduction in egg laying of paired adult worms was observed. Additionally, epiisopiloturine showed selective antischistosomal activity and exhibited no cytotoxicity to mammalian cells. This report provides the first evidence that epiisopiloturine is able to kill S. mansoni of different ages and inhibit worm egg laying. PMID:22420337

  8. Recognition of Human Erythrocyte Receptors by the Tryptophan-Rich Antigens of Monkey Malaria Parasite Plasmodium knowlesi

    PubMed Central

    Tyagi, Kriti; Gupta, Deepali; Saini, Ekta; Choudhary, Shilpa; Jamwal, Abhishek; Alam, Mohd. Shoeb; Zeeshan, Mohammad; Tyagi, Rupesh K.; Sharma, Yagya D.

    2015-01-01

    Background The monkey malaria parasite Plasmodium knowlesi also infect humans. There is a lack of information on the molecular mechanisms that take place between this simian parasite and its heterologous human host erythrocytes leading to this zoonotic disease. Therefore, we investigated here the binding ability of P. knowlesi tryptophan-rich antigens (PkTRAgs) to the human erythrocytes and sharing of the erythrocyte receptors between them as well as with other commonly occurring human malaria parasites. Methods Six PkTRAgs were cloned and expressed in E.coli as well as in mammalian CHO-K1 cell to determine their human erythrocyte binding activity by cell-ELISA, and in-vitro rosetting assay, respectively. Results Three of six PkTRAgs (PkTRAg38.3, PkTRAg40.1, and PkTRAg67.1) showed binding to human erythrocytes. Two of them (PkTRAg40.1 and PkTRAg38.3) showed cross-competition with each other as well as with the previously described P.vivax tryptophan-rich antigens (PvTRAgs) for human erythrocyte receptors. However, the third protein (PkTRAg67.1) utilized the additional but different human erythrocyte receptor(s) as it did not cross-compete for erythrocyte binding with either of these two PkTRAgs as well as with any of the PvTRAgs. These three PkTRAgs also inhibited the P.falciparum parasite growth in in-vitro culture, further indicating the sharing of human erythrocyte receptors by these parasite species and the biological significance of this receptor-ligand interaction between heterologous host and simian parasite. Conclusions Recognition and sharing of human erythrocyte receptor(s) by PkTRAgs with human parasite ligands could be part of the strategy adopted by the monkey malaria parasite to establish inside the heterologous human host. PMID:26393350

  9. Rationale for the Coadministration of Albendazole and Ivermectin to Humans for Malaria Parasite Transmission Control

    PubMed Central

    Kobylinski, Kevin C.; Alout, Haoues; Foy, Brian D.; Clements, Archie; Adisakwattana, Poom; Swierczewski, Brett E.; Richardson, Jason H.

    2014-01-01

    Recently there have been calls for the eradication of malaria and the elimination of soil-transmitted helminths (STHs). Malaria and STHs overlap in distribution, and STH infections are associated with increased risk for malaria. Indeed, there is evidence that suggests that STH infection may facilitate malaria transmission. Malaria and STH coinfection may exacerbate anemia, especially in pregnant women, leading to worsened child development and more adverse pregnancy outcomes than these diseases would cause on their own. Ivermectin mass drug administration (MDA) to humans for malaria parasite transmission suppression is being investigated as a potential malaria elimination tool. Adding albendazole to ivermectin MDAs would maximize effects against STHs. A proactive, integrated control platform that targets malaria and STHs would be extremely cost-effective and simultaneously reduce human suffering caused by multiple diseases. This paper outlines the benefits of adding albendazole to ivermectin MDAs for malaria parasite transmission suppression. PMID:25070998

  10. Rationale for the coadministration of albendazole and ivermectin to humans for malaria parasite transmission control.

    PubMed

    Kobylinski, Kevin C; Alout, Haoues; Foy, Brian D; Clements, Archie; Adisakwattana, Poom; Swierczewski, Brett E; Richardson, Jason H

    2014-10-01

    Recently there have been calls for the eradication of malaria and the elimination of soil-transmitted helminths (STHs). Malaria and STHs overlap in distribution, and STH infections are associated with increased risk for malaria. Indeed, there is evidence that suggests that STH infection may facilitate malaria transmission. Malaria and STH coinfection may exacerbate anemia, especially in pregnant women, leading to worsened child development and more adverse pregnancy outcomes than these diseases would cause on their own. Ivermectin mass drug administration (MDA) to humans for malaria parasite transmission suppression is being investigated as a potential malaria elimination tool. Adding albendazole to ivermectin MDAs would maximize effects against STHs. A proactive, integrated control platform that targets malaria and STHs would be extremely cost-effective and simultaneously reduce human suffering caused by multiple diseases. This paper outlines the benefits of adding albendazole to ivermectin MDAs for malaria parasite transmission suppression. PMID:25070998

  11. Effect of repeated targeted mass treatment with praziquantel on the prevalence, intensity of infection and morbidity due to Schistosoma intercalatum in an urban community in equatorial Guinea.

    PubMed

    Simarro, P P; Sima, F O; Mir, M; Ndong, P

    1991-09-01

    A longitudinal community-based study was carried out in order to evaluate the impact of repeated selective population chemotherapy with praziquantel on the epidemiology of an urban focus of Schistosoma intercalatum in the city of Bata, capital of the Continental Region of Equatorial Guinea. Three surveys were undertaken in January of 1988, 1989 and 1990, determining parasitological prevalence, intensity of infection and morbidity and applying repeated targeted mass treatment. One dose of praziquantel (40 mg/kg body weight) was given one week after treatment with mebendazole (100 mg every 12 hours for 3 days). A reduction of the overall prevalence by S. intercalatum of 69.9% and 79.3% in the first and second year respectively was found. Persons showing high parasite burden suffered a reduction of 95.7%. The cure rate (no more eggs in stool) was between 90% and 98.9%. A significant decrease of signs and symptoms was observed. No important side effects were detected. This study shows the positive action of praziquantel in reducing prevalence, intensity of infection and morbidity due to S. intercalatum, above all in the case of a high human population participation response. Cure rates obtained being similar to the ones observed using the same drug in Schistosoma mansoni and Schistosoma haematobium. PMID:1801138

  12. Proteomic profiling of the planarian Schmidtea mediterranea and its mucous reveals similarities with human secretions and those predicted for parasitic flatworms.

    PubMed

    Bocchinfuso, Donald G; Taylor, Paul; Ross, Eric; Ignatchenko, Alex; Ignatchenko, Vladimir; Kislinger, Thomas; Pearson, Bret J; Moran, Michael F

    2012-09-01

    The freshwater planarian Schmidtea mediterranea has been used in research for over 100 years, and is an emerging stem cell model because of its capability of regenerating large portions of missing body parts. Exteriorly, planarians are covered in mucous secretions of unknown composition, implicated in locomotion, predation, innate immunity, and substrate adhesion. Although the planarian genome has been sequenced, it remains mostly unannotated, challenging both genomic and proteomic analyses. The goal of the current study was to annotate the proteome of the whole planarian and its mucous fraction. The S. mediterranea proteome was analyzed via mass spectrometry by using multidimensional protein identification technology with whole-worm tryptic digests. By using a proteogenomics approach, MS data were searched against an in silico translated planarian transcript database, and by using the Swiss-Prot BLAST algorithm to identify proteins similar to planarian queries. A total of 1604 proteins were identified. The mucous subproteome was defined through analysis of a mucous trail fraction and an extract obtained by treating whole worms with the mucolytic agent N-acetylcysteine. Gene Ontology analysis confirmed that the mucous fractions were enriched with secreted proteins. The S. mediterranea proteome is highly similar to that predicted for the trematode Schistosoma mansoni associated with intestinal schistosomiasis, with the mucous subproteome particularly highly conserved. Remarkably, orthologs of 119 planarian mucous proteins are present in human mucosal secretions and tear fluid. We suggest planarians have potential to be a model system for the characterization of mucous protein function and relevant to parasitic flatworm infections and diseases underlined by mucous aberrancies, such as cystic fibrosis, asthma, and other lung diseases. PMID:22653920

  13. Proteomic Profiling of the Planarian Schmidtea mediterranea and Its Mucous Reveals Similarities with Human Secretions and Those Predicted for Parasitic Flatworms*

    PubMed Central

    Bocchinfuso, Donald G.; Taylor, Paul; Ross, Eric; Ignatchenko, Alex; Ignatchenko, Vladimir; Kislinger, Thomas; Pearson, Bret J.; Moran, Michael F.

    2012-01-01

    The freshwater planarian Schmidtea mediterranea has been used in research for over 100 years, and is an emerging stem cell model because of its capability of regenerating large portions of missing body parts. Exteriorly, planarians are covered in mucous secretions of unknown composition, implicated in locomotion, predation, innate immunity, and substrate adhesion. Although the planarian genome has been sequenced, it remains mostly unannotated, challenging both genomic and proteomic analyses. The goal of the current study was to annotate the proteome of the whole planarian and its mucous fraction. The S. mediterranea proteome was analyzed via mass spectrometry by using multidimensional protein identification technology with whole-worm tryptic digests. By using a proteogenomics approach, MS data were searched against an in silico translated planarian transcript database, and by using the Swiss-Prot BLAST algorithm to identify proteins similar to planarian queries. A total of 1604 proteins were identified. The mucous subproteome was defined through analysis of a mucous trail fraction and an extract obtained by treating whole worms with the mucolytic agent N-acetylcysteine. Gene Ontology analysis confirmed that the mucous fractions were enriched with secreted proteins. The S. mediterranea proteome is highly similar to that predicted for the trematode Schistosoma mansoni associated with intestinal schistosomiasis, with the mucous subproteome particularly highly conserved. Remarkably, orthologs of 119 planarian mucous proteins are present in human mucosal secretions and tear fluid. We suggest planarians have potential to be a model system for the characterization of mucous protein function and relevant to parasitic flatworm infections and diseases underlined by mucous aberrancies, such as cystic fibrosis, asthma, and other lung diseases. PMID:22653920

  14. Mitochondrial oxygen consumption in asexual and sexual blood stages of the human malarial parasite, Plasmodium falciparum.

    PubMed

    Krungkrai, J; Burat, D; Kudan, S; Krungkrai, S; Prapunwattana, P

    1999-12-01

    The two developmental stages of human malarial parasite Plasmodium falciparum, asexual and sexual blood stages, were continuously cultivated in vitro. Both asexual and sexual stages of the parasites were assayed for mitochondrial oxygen consumption by using a polarographic assay. The rate of oxygen consumption by both stages was found to be relatively low, and was not much different. Furthermore, the mitochondrial oxygen consumption by both stages was inhibited to various degrees by mammalian mitochondrial inhibitors that targeted each component of complexes I- IV of the respiratory system. The oxygen consumption by both stages was also affected by 5-fluoroorotate, a known inhibitor of enzyme dihydroorotate dehydrogenase of the pyrimidine pathway and by an antimalarial drug atovaquone that acted specifically on mitochondrial complex III of the parasite. Moreover, antimalarials primaquine and artemisinin had inhibitory effects on the oxygen consumption by both stages of the parasites. Our results suggest that P. falciparum in both developmental stages have functional mitochondria that operate a classical electron transport system, containing complexes I-IV, and linked to the pyrimidine biosynthetic pathway. PMID:10928353

  15. Purification and biochemical characterization of a heme containing peroxidase from the human parasite P. falciparum.

    PubMed

    Trivedi, Vishal; Srivastava, Kumkum; Puri, Sunil K; Maulik, Prakas R; Bandyopadhyay, Uday

    2005-05-01

    A peroxidase (30 kDa) has been purified from the human malaria parasite Plasmodium falciparum to its homogeneity. The protein is a dimer of 15 kDa subunit as evident from SDS-PAGE and MALDI-TOF mass analysis. The antibodies developed against the purified protein cross-react selectively with this protein present in parasite lysate. It is a heme containing peroxidase [R/Z value (A408/A278)=2.33] showing characteristic heme spectra with Soret peak at 408 nm and visible peaks at 536 and 572 nm. Analysis of Soret spectra in presence or absence of cyanide or azide reveals that iron of heme is in Fe-III state. Circular dichroism spectral analysis establishes that this protein contains mainly alpha-helix (60-70%). H2O2 interacts with the heme moiety of the enzyme as evidenced by optical difference spectroscopy and spectral studies indicate the formation of catalytically active peroxidase-H2O2 complex (Soret peak at 413 nm) to exhibit peroxidase activity. During the erythrocytic stages of its life cycle, the parasite is exposed to oxidative stress. As the parasite is susceptible to oxidative stress, this peroxidase may offer antioxidant role by scavenging endogenous H2O2. PMID:15802233

  16. Characterization of the phytochelatin synthase of Schistosoma mansoni.

    PubMed

    Ray, Debalina; Williams, David L

    2011-05-01

    Treatment for schistosomiasis, which is responsible for more than 280,000 deaths annually, depends exclusively on the use of praziquantel. Millions of people are treated annually with praziquantel and drug resistant parasites are likely to evolve. In order to identify novel drug targets the Schistosoma mansoni sequence databases were queried for proteins involved in glutathione metabolism. One potential target identified was phytochelatin synthase (PCS). Phytochelatins are oligopeptides synthesized enzymatically from glutathione by PCS that sequester toxic heavy metals in many organisms. However, humans do not have a PCS gene and do not synthesize phytochelatins. In this study we have characterized the PCS of S. mansoni (SmPCS). The conserved catalytic triad of cysteine-histidine-aspartate found in PCS proteins and cysteine proteases is also found in SmPCS, as are several cysteine residues thought to be involved in heavy metal binding and enzyme activation. The SmPCS open reading frame is considerably extended at both the N- and C-termini compared to PCS from other organisms. Multiple PCS transcripts are produced from the single encoded gene by alternative splicing, resulting in both mitochondrial and cytoplasmic protein variants. Expression of SmPCS in yeast increased cadmium tolerance from less than 50 µM to more than 1,000 µM. We confirmed the function of SmPCS by identifying PCs in yeast cell extracts using HPLC-mass spectrometry. SmPCS was found to be expressed in all mammalian stages of worm development investigated. Increases in SmPCS expression were seen in ex vivo worms cultured in the presence of iron, copper, cadmium, or zinc. Collectively, these results indicate that SmPCS plays an important role in schistosome response to heavy metals and that PCS is a potential drug target for schistosomiasis treatment. This is the first characterization of a PCS from a parasitic organism. PMID:21629724

  17. Characterization of the Phytochelatin Synthase of Schistosoma mansoni

    PubMed Central

    Ray, Debalina; Williams, David L.

    2011-01-01

    Treatment for schistosomiasis, which is responsible for more than 280,000 deaths annually, depends exclusively on the use of praziquantel. Millions of people are treated annually with praziquantel and drug resistant parasites are likely to evolve. In order to identify novel drug targets the Schistosoma mansoni sequence databases were queried for proteins involved in glutathione metabolism. One potential target identified was phytochelatin synthase (PCS). Phytochelatins are oligopeptides synthesized enzymatically from glutathione by PCS that sequester toxic heavy metals in many organisms. However, humans do not have a PCS gene and do not synthesize phytochelatins. In this study we have characterized the PCS of S. mansoni (SmPCS). The conserved catalytic triad of cysteine-histidine-aspartate found in PCS proteins and cysteine proteases is also found in SmPCS, as are several cysteine residues thought to be involved in heavy metal binding and enzyme activation. The SmPCS open reading frame is considerably extended at both the N- and C-termini compared to PCS from other organisms. Multiple PCS transcripts are produced from the single encoded gene by alternative splicing, resulting in both mitochondrial and cytoplasmic protein variants. Expression of SmPCS in yeast increased cadmium tolerance from less than 50 µM to more than 1,000 µM. We confirmed the function of SmPCS by identifying PCs in yeast cell extracts using HPLC-mass spectrometry. SmPCS was found to be expressed in all mammalian stages of worm development investigated. Increases in SmPCS expression were seen in ex vivo worms cultured in the presence of iron, copper, cadmium, or zinc. Collectively, these results indicate that SmPCS plays an important role in schistosome response to heavy metals and that PCS is a potential drug target for schistosomiasis treatment. This is the first characterization of a PCS from a parasitic organism. PMID:21629724

  18. Monoclonal antibodies produced against sporozoites of the human parasite Plasmodium malariae abolish infectivity of sporozoites of the simian parasite Plasmodium brasilianum.

    PubMed Central

    Cochrane, A H; Barnwell, J W; Collins, W E; Nussenzweig, R S

    1985-01-01

    We have used a sporozoite neutralization assay to define the biological relevance of the cross-reactivity of two monoclonal antibodies, raised against sporozoites of the human parasite Plasmodium malariae (Uganda 1/CDC), with sporozoites of the simian parasite Plasmodium brasilianum (Colombian). In vitro incubation of each of these two monoclonal antibodies with sporozoites of P. brasilianum totally abolished the infectivity of these parasites for Saimiri sciureus. Using Western blot analysis and one of the P. malariae monoclonal antibodies, we identified two sporozoite proteins characteristic of the Colombian isolate of P. brasilianum with apparent molecular weights of 56,000 and 66,000. The same monoclonal antibody identified two proteins in an extract of the Peruvian isolate of P. brasilianum with apparent molecular weights of 59,000 and 69,000. Images PMID:3899939

  19. Identification of Candidate Serum Biomarkers for Schistosoma mansoni Infected Mice Using Multiple Proteomic Platforms

    PubMed Central

    Kardoush, Manal I.

    2016-01-01

    Background Schistosomiasis is an important helminth infection of humans. There are few reliable diagnostic biomarkers for early infection, for recurrent infection or to document successful treatment. In this study, we compared serum protein profiles in uninfected and infected mice to identify disease stage-specific biomarkers. Methods Serum collected from CD1 mice infected with 50–200 Schistosoma mansoni cercariae were analyzed before infection and at 3, 6 and 12 weeks post-infection using three mass spectrometric (MS) platforms. Results Using SELDI-TOF MS, 66 discriminating m/z peaks were detected between S. mansoni infected mice and healthy controls. Used in various combinations, these peaks could 1) reliably diagnose early-stage disease, 2) distinguish between acute and chronic infection and 3) diagnose S. mansoni infection regardless the parasite burden. The most important contributors to these diagnostic algorithms were peaks at 3.7, 13 and 46 kDa. Employing sample fractionation and differential gel electrophoresis, we analyzed gel slices either by MALDI-TOF MS or Velos Orbitrap MS. The former yielded eight differentially-expressed host proteins in the serum at different disease stages including transferrin and alpha 1- antitrypsin. The latter suggested the presence of a surprising number of parasite-origin proteins in the serum during both the acute (n = 200) and chronic (n = 105) stages. The Orbitrap platform also identified many differentially-expressed host-origin serum proteins during the acute and chronic stages (296 and 220 respectively). The presence of one of the schistosome proteins, glutathione S transferase (GST: 25 KDa), was confirmed by Western Blot. This study provides proof-of-principle for an approach that can yield a large number of novel candidate biomarkers for Schistosoma infection. PMID:27138990

  20. Host cell deformability is linked to transmission in the human malaria parasite Plasmodium falciparum

    PubMed Central

    Aingaran, Mythili; Zhang, Rou; Law, Sue KaYee; Peng, Zhangli; Undisz, Andreas; Meyer, Evan; Diez-Silva, Monica; Burke, Thomas A.; Spielmann, Tobias; Lim, Chwee Teck; Suresh, Subra; Dao, Ming; Marti, Matthias

    2012-01-01

    SUMMARY Gametocyte maturation in Plasmodium falciparum is a critical step in the transmission of malaria. While the majority of parasites proliferate asexually in red blood cells, a small fraction of parasites undergo sexual conversion and mature over two weeks to become competent for transmission to a mosquito vector. Immature gametocytes sequester in deep tissues while mature stages must be able to circulate, pass the spleen and present themselves to the mosquito vector in order to complete transmission. Sequestration of asexual red blood cell stage parasites has been investigated in great detail. These studies have demonstrated that induction of cytoadherence properties through specific receptor-ligand interactions coincides with a significant increase in host cell stiffness. In contrast, the adherence and biophysical properties of gametocyte-infected red blood cells have not been studied systematically. Utilizing a transgenic line for 3D live imaging, in vitro capillary assays and 3D finite element whole cell modeling, we studied the role of cellular deformability in determining the circulatory characteristics of gametocytes. Our analysis shows that the red blood cell deformability of immature gametocytes displays an overall decrease followed by rapid restoration in mature gametocytes. Intriguingly, simulations suggest that along with deformability variations, the morphological changes of the parasite may play an important role in tissue distribution in vivo. Taken together we present a model, which suggests that mature but not immature gametocytes circulate in the peripheral blood for uptake in the mosquito blood meal and transmission to another human host thus ensuring long term survival of the parasite. PMID:22417683

  1. DNA Detection of Schistosoma japonicum: Diagnostic Validity of a LAMP Assay for Low-Intensity Infection and Effects of Chemotherapy in Humans

    PubMed Central

    Zhao, Bo; Wang, Yan-Yan; Cao, Yun; Zhang, Hui-Qin; Zhu, Xing-Quan; He, Yong-Kang; Xia, Chao-Ming

    2015-01-01

    Background Schistosomiasis has decreased significantly in prevalence and intensity of infection in China, thus more accurate and sensitive methods are desperately needed for the further control of schistosomiasis. The present work aimed to assess the utility of the loop-mediated isothermal amplification (LAMP) for detection of light intensity infection or false-negative patients and patients post-treatment, targeting the highly repetitive retrotransposon SjR2 of Schistosoma japonicum. Methodology/ Principal Findings LAMP was first assessed in rabbits with low intensity infection (EPG<10). Then 110 patient sera from Hunan Province, China, and 47 sera after treatment by praziquantel were used to evaluate the diagnostic validity of LAMP. Meanwhile, 42 sera from healthy individuals in a non-endemic area, and 60 sera from "healthy” residents who were identified as being negative for feces examination and immuno-methods in an endemic area were also examined. The results showed that LAMP could detect S. japonicum DNA in sera from rabbits at 3rd day post-infection. Following administration of praziquantel, the S. japonicum DNA in rabbit sera became negative at 10 weeks post-treatment. Of 110 sera from patients, LAMP showed 95.5% sensitivity, and even for 41 patients with less than 10 EPG, the sensitivity of LAMP still reached to 95.1%. For 47 patients after treatment, the negative conversion rate of S. japonicum DNA in patient sera increased from 23.4%, 61.7% to 83.0% at 3 months, 6 months and 9 months post-treatment, respectively. No false-positive result was obtained for 42 human sera from non-endemic area, while for the 60 “healthy” individuals from endemic area, 10 (16.7%) individuals were positive by LAMP, which suggested that these individuals might be false-negative patients. Conclusions/ Significance The present study demonstrated that the LAMP assay is sensitive, specific, and affordable, which would help reduce schistosomiasis transmission through targeted

  2. Crystal Structure of Schistosoma mansoni Arginase, a Potential Drug Target for the Treatment of Schistosomiasis

    PubMed Central

    2015-01-01

    The X-ray crystal structure of arginase from Schistosoma mansoni (SmARG) and the structures of its complexes with several amino acid inhibitors have been determined at atomic resolution. SmARG is a binuclear manganese metalloenzyme that catalyzes the hydrolysis of l-arginine to form l-ornithine and urea, and this enzyme is upregulated in all forms of the parasite that interact with the human host. Current hypotheses suggest that parasitic arginases could play a role in host immune evasion by depleting pools of substrate l-arginine that would otherwise be utilized for NO biosynthesis and NO-dependent processes in the immune response. Although the amino acid sequence of SmARG is only 42% identical with that of human arginase I, residues important for substrate binding and catalysis are strictly conserved. In general, classical amino acid inhibitors such as 2(S)-amino-6-boronohexanoic acid (ABH) tend to bind more weakly to SmARG than to human arginase I despite identical inhibitor binding modes in each enzyme active site. The identification of a patch on the enzyme surface capable of accommodating the additional Cα substitutent of an α,α-disubstituted amino acid inhibitor suggests that such inhibitors could exhibit higher affinity and biological activity. The structures of SmARG complexed with two different α,α-disubstituted derivatives of ABH are presented and provide a proof of concept for this approach in the enhancement of enzyme–inhibitor affinity. PMID:25007099

  3. Successful Feeding of Amblyomma coelebs (Acari: Ixodidae) Nymphs on Humans in Brazil: Skin Reactions to Parasitism.

    PubMed

    Garcia, Marcos V; Matias, Jaqueline; Aguirre, AndrÉ De A R; Csordas, Barbara G; SzabÓ, Matias P J; Andreotti, Renato

    2015-03-01

    Identifying the tick species that successfully feed on humans would increase knowledge of the epidemiology of several tick-borne diseases. These species salivate into the host, increasing the risk of pathogen transmission. However, there is a lack of data in the literature regarding the ticks that prefer to feed on humans. Herein, we describe the successful feeding of Amblyomma coelebs Neumann nymphs on two of the authors after accidental tick bites occurred during field surveys in two preserved areas of Mato Grosso do Sul, Brazil. One of the host-parasite interactions was closely monitored, and the tick development, gross host skin alterations, and related sensations are presented. PMID:26336294

  4. Successful Feeding of Amblyomma coelebs (Acari: Ixodidae) Nymphs on Humans in Brazil: Skin Reactions to Parasitism

    PubMed Central

    Garcia, Marcos V.; Matias, Jaqueline; Aguirre, André De A. R.; Csordas, Barbara G.; Szabó, Matias P. J.

    2015-01-01

    Identifying the tick species that successfully feed on humans would increase knowledge of the epidemiology of several tick-borne diseases. These species salivate into the host, increasing the risk of pathogen transmission. However, there is a lack of data in the literature regarding the ticks that prefer to feed on humans. Herein, we describe the successful feeding of Amblyomma coelebs Neumann nymphs on two of the authors after accidental tick bites occurred during field surveys in two preserved areas of Mato Grosso do Sul, Brazil. One of the host–parasite interactions was closely monitored, and the tick development, gross host skin alterations, and related sensations are presented. PMID:26336294

  5. Parasite Mitogen-Activated Protein Kinases as Drug Discovery Targets to Treat Human Protozoan Pathogens

    PubMed Central

    Brumlik, Michael J.; Pandeswara, Srilakshmi; Ludwig, Sara M.; Murthy, Kruthi; Curiel, Tyler J.

    2011-01-01

    Protozoan pathogens are a highly diverse group of unicellular organisms, several of which are significant human pathogens. One group of protozoan pathogens includes obligate intracellular parasites such as agents of malaria, leishmaniasis, babesiosis, and toxoplasmosis. The other group includes extracellular pathogens such as agents of giardiasis and amebiasis. An unfortunate unifying theme for most human protozoan pathogens is that highly effective treatments for them are generally lacking. We will review targeting protozoan mitogen-activated protein kinases (MAPKs) as a novel drug discovery approach towards developing better therapies, focusing on Plasmodia, Leishmania, and Toxoplasma, about which the most is known. PMID:21637385

  6. Parasitic Zoonoses in Humans and Their Dogs from a Rural Community of Tropical Mexico.

    PubMed

    Ortega-Pacheco, Antonio; Torres-Acosta, Juan F J; Alzina-López, Alejandro; Gutiérrez-Blanco, Eduardo; Bolio-González, Manuel E; Aguilar-Caballero, Armando J; Rodríguez-Vivas, Roger I; Gutiérrez-Ruiz, Edwin; Acosta-Viana, Karla Y; Guzmán-Marín, Eugenia; Rosado-Aguilar, Alberto; Jiménez-Coello, Matilde

    2015-01-01

    A cross-sectional study was made on 89 inhabitants and their dogs from a rural community of Yucatan, Mexico, to determine the serological prevalence of some zoonotic parasitic agents. Samples were taken to monitor the presence and intensity of infection with gastrointestinal parasites in dogs. In humans, the serological prevalence of T. canis, T. gondii, and T. spiralis was 29.2%, 91.0%, and 6.7%, respectively. No associations were found between positive cases and studied variables. From the total of blood samples taken from dogs, 87 (97.6%) were seropositive to T. gondii; only 52 viable fecal samples were collected from dogs of which 46.2% had the presence of gastrointestinal parasites with low to moderate intensity; from those, 12% had the presence of T. canis. This study demonstrates the presence of the studied zoonotic agents in the area particularly T. gondii which suggest a common source of infection in dogs and humans and a high number of oocyts present in the environment. Preventive measures must be designed towards good prophylactic practices in domestic and backyard animals (T. canis and T. spiralis). Contaminated sources with T. gondii (food and water) should be further investigated in order to design effective control measures. PMID:26770216

  7. Parasitic Zoonoses in Humans and Their Dogs from a Rural Community of Tropical Mexico

    PubMed Central

    Ortega-Pacheco, Antonio; Torres-Acosta, Juan F. J.; Alzina-López, Alejandro; Gutiérrez-Blanco, Eduardo; Bolio-González, Manuel E.; Aguilar-Caballero, Armando J.; Rodríguez-Vivas, Roger I.; Gutiérrez-Ruiz, Edwin; Guzmán-Marín, Eugenia; Rosado-Aguilar, Alberto; Jiménez-Coello, Matilde

    2015-01-01

    A cross-sectional study was made on 89 inhabitants and their dogs from a rural community of Yucatan, Mexico, to determine the serological prevalence of some zoonotic parasitic agents. Samples were taken to monitor the presence and intensity of infection with gastrointestinal parasites in dogs. In humans, the serological prevalence of T. canis, T. gondii, and T. spiralis was 29.2%, 91.0%, and 6.7%, respectively. No associations were found between positive cases and studied variables. From the total of blood samples taken from dogs, 87 (97.6%) were seropositive to T. gondii; only 52 viable fecal samples were collected from dogs of which 46.2% had the presence of gastrointestinal parasites with low to moderate intensity; from those, 12% had the presence of T. canis. This study demonstrates the presence of the studied zoonotic agents in the area particularly T. gondii which suggest a common source of infection in dogs and humans and a high number of oocyts present in the environment. Preventive measures must be designed towards good prophylactic practices in domestic and backyard animals (T. canis and T. spiralis). Contaminated sources with T. gondii (food and water) should be further investigated in order to design effective control measures. PMID:26770216

  8. The interaction between filarial parasites and human monocyte/macrophage populations.

    PubMed

    Semnani, Roshanak Tolouei

    2013-01-01

    Lymphatic filariasis is a mafor tropical disease affecting approximately 120 million people worldwide. Patent infection, by and large, is clinically asymptomatic but is associated with the inability of T cells to proliferate or produce IFN-γ in response to parasite antigen. Monocyte dysfunction is one hypothesis felt to explain the lack of an antigen-specific T cell response. In fact, monocytes from filaria-infected individuals have been shown to be studded with internalized filarial antigens. Understanding how the phenotype and the function of these monocytes are altered through the internalization of these parasite antigens is one of the areas our laboratory has focused on. In fact, the existence and/or function of alternatively activated macrophages in murine models of filarial infections have been extensively studied. Whether this population of macrophages can be induced in human filarial infections is the main focus of this review. PMID:23456837

  9. Transcriptionally Driven DNA Replication Program of the Human Parasite Leishmania major.

    PubMed

    Lombraña, Rodrigo; Álvarez, Alba; Fernández-Justel, José Miguel; Almeida, Ricardo; Poza-Carrión, César; Gomes, Fábia; Calzada, Arturo; Requena, José María; Gómez, María

    2016-08-01

    Faithful inheritance of eukaryotic genomes requires the orchestrated activation of multiple DNA replication origins (ORIs). Although origin firing is mechanistically conserved, how origins are specified and selected for activation varies across different model systems. Here, we provide a complete analysis of the nucleosomal landscape and replication program of the human parasite Leishmania major, building on a better evolutionary understanding of replication organization in Eukarya. We found that active transcription is a driving force for the nucleosomal organization of the L. major genome and that both the spatial and the temporal program of DNA replication can be explained as associated to RNA polymerase kinetics. This simple scenario likely provides flexibility and robustness to deal with the environmental changes that impose alterations in the genetic programs during parasitic life cycle stages. Our findings also suggest that coupling replication initiation to transcription elongation could be an ancient solution used by eukaryotic cells for origin maintenance. PMID:27477279

  10. Frequency and mitotic heritability of epimutations in Schistosoma mansoni.

    PubMed

    Roquis, David; Rognon, Anne; Chaparro, Cristian; Boissier, Jerome; Arancibia, Nathalie; Cosseau, Celine; Parrinello, Hugues; Grunau, Christoph

    2016-04-01

    Schistosoma mansoni is a parasitic platyhelminth responsible for intestinal bilharzia. It has a complex life cycle, infecting a freshwater snail of the Biomphalaria genus, and then a mammalian host. Schistosoma mansoni adapts rapidly to new (allopatric) strains of its intermediate host. To study the importance of epimutations in this process, we infected sympatric and allopatric mollusc strains with parasite clones. ChIP-Seq was carried out on four histone modifications (H3K4me3, H3K27me3, H3K27ac and H4K20me1) in parallel with genomewide DNA resequencing (i) on parasite larvae shed by the infected snails and (ii) on adult worms that had developed from the larvae. No change in single nucleotide polymorphisms and no mobilization of transposable elements were observed, but 58-105 copy number variations (CNVs) within the parasite clones in different molluscs were detected. We also observed that the allopatric environment induces three types of chromatin structure changes: (i) host-induced changes on larvae epigenomes in 51 regions of the genome that are independent of the parasites' genetic background, (ii) spontaneous changes (not related to experimental condition or genotype of the parasite) at 64 locations and (iii) 64 chromatin structure differences dependent on the parasite genotype. Up to 45% of the spontaneous, but none of the host-induced chromatin structure changes were transmitted to adults. In our model, the environment induces epigenetic changes at specific loci but only spontaneous epimutations are mitotically heritable and have therefore the potential to contribute to transgenerational inheritance. We also show that CNVs are the only source of genetic variation and occur at the same order of magnitude as epimutations. PMID:26826554

  11. Behavioural defences in animals against pathogens and parasites: parallels with the pillars of medicine in humans

    PubMed Central

    Hart, Benjamin L.

    2011-01-01

    No other theme in animal biology seems to be more central than the concept of employing strategies to survive and successfully reproduce. In nature, controlling or avoiding pathogens and parasites is an essential fitness strategy because of the ever-present disease-causing organisms. The disease-control strategies discussed here are: physical avoidance and removal of pathogens and parasites; quarantine or peripheralization of conspecifics that could be carrying potential pathogens; herbal medicine, animal style, to prevent or treat an infection; potentiation of the immune system; and care of sick or injured group members. These strategies are seen as also encompassing the pillars of human medicine: (i) quarantine; (ii) immune-boosting vaccinations; (iii) use of medicinal products; and (iv) caring or nursing. In contrast to animals, in humans, the disease-control strategies have been consolidated into a consistent and extensive medical system. A hypothesis that explains some of this difference between animals and humans is that humans are sick more often than animals. This increase in sickness in humans leading to an extensive, cognitively driven medical system is attributed to an evolutionary dietary transition from mostly natural vegetation to a meat-based diet, with an increase in health-eroding free radicals and a dietary reduction of free-radical-scavenging antioxidants. PMID:22042917

  12. Anopheles gambiae immune responses to human and rodent Plasmodium parasite species.

    PubMed

    Dong, Yuemei; Aguilar, Ruth; Xi, Zhiyong; Warr, Emma; Mongin, Emmanuel; Dimopoulos, George

    2006-06-01

    Transmission of malaria is dependent on the successful completion of the Plasmodium lifecycle in the Anopheles vector. Major obstacles are encountered in the midgut tissue, where most parasites are killed by the mosquito's immune system. In the present study, DNA microarray analyses have been used to compare Anopheles gambiae responses to invasion of the midgut epithelium by the ookinete stage of the human pathogen Plasmodium falciparum and the rodent experimental model pathogen P. berghei. Invasion by P. berghei had a more profound impact on the mosquito transcriptome, including a variety of functional gene classes, while P. falciparum elicited a broader immune response at the gene transcript level. Ingestion of human malaria-infected blood lacking invasive ookinetes also induced a variety of immune genes, including several anti-Plasmodium factors. Twelve selected genes were assessed for effect on infection with both parasite species and bacteria using RNAi gene silencing assays, and seven of these genes were found to influence mosquito resistance to both parasite species. An MD2-like receptor, AgMDL1, and an immunolectin, FBN39, showed specificity in regulating only resistance to P. falciparum, while the antimicrobial peptide gambicin and a novel putative short secreted peptide, IRSP5, were more specific for defense against the rodent parasite P. berghei. While all the genes that affected Plasmodium development also influenced mosquito resistance to bacterial infection, four of the antimicrobial genes had no effect on Plasmodium development. Our study shows that the impact of P. falciparum and P. berghei infection on A. gambiae biology at the gene transcript level is quite diverse, and the defense against the two Plasmodium species is mediated by antimicrobial factors with both universal and Plasmodium-species specific activities. Furthermore, our data indicate that the mosquito is capable of sensing infected blood constituents in the absence of invading

  13. Anopheles gambiae Immune Responses to Human and Rodent Plasmodium Parasite Species

    PubMed Central

    Dong, Yuemei; Aguilar, Ruth; Xi, Zhiyong; Warr, Emma; Mongin, Emmanuel; Dimopoulos, George

    2006-01-01

    Transmission of malaria is dependent on the successful completion of the Plasmodium lifecycle in the Anopheles vector. Major obstacles are encountered in the midgut tissue, where most parasites are killed by the mosquito's immune system. In the present study, DNA microarray analyses have been used to compare Anopheles gambiae responses to invasion of the midgut epithelium by the ookinete stage of the human pathogen Plasmodium falciparum and the rodent experimental model pathogen P. berghei. Invasion by P. berghei had a more profound impact on the mosquito transcriptome, including a variety of functional gene classes, while P. falciparum elicited a broader immune response at the gene transcript level. Ingestion of human malaria-infected blood lacking invasive ookinetes also induced a variety of immune genes, including several anti-Plasmodium factors. Twelve selected genes were assessed for effect on infection with both parasite species and bacteria using RNAi gene silencing assays, and seven of these genes were found to influence mosquito resistance to both parasite species. An MD2-like receptor, AgMDL1, and an immunolectin, FBN39, showed specificity in regulating only resistance to P. falciparum, while the antimicrobial peptide gambicin and a novel putative short secreted peptide, IRSP5, were more specific for defense against the rodent parasite P. berghei. While all the genes that affected Plasmodium development also influenced mosquito resistance to bacterial infection, four of the antimicrobial genes had no effect on Plasmodium development. Our study shows that the impact of P. falciparum and P. berghei infection on A. gambiae biology at the gene transcript level is quite diverse, and the defense against the two Plasmodium species is mediated by antimicrobial factors with both universal and Plasmodium-species specific activities. Furthermore, our data indicate that the mosquito is capable of sensing infected blood constituents in the absence of invading

  14. The prevalence and diversity of intestinal parasitic infections in humans and domestic animals in a rural Cambodian village.

    PubMed

    Schär, Fabian; Inpankaew, Tawin; Traub, Rebecca J; Khieu, Virak; Dalsgaard, Anders; Chimnoi, Wissanuwat; Chhoun, Chamnan; Sok, Daream; Marti, Hanspeter; Muth, Sinuon; Odermatt, Peter

    2014-08-01

    In Cambodia, intestinal parasitic infections are prevalent in humans and particularly in children. Yet, information on potentially zoonotic parasites in animal reservoir hosts is lacking. In May 2012, faecal samples from 218 humans, 94 dogs and 76 pigs were collected from 67 households in Dong village, Preah Vihear province, Cambodia. Faecal samples were examined microscopically using sodium nitrate and zinc sulphate flotation methods, the Baermann method, Koga Agar plate culture, formalin-ether concentration technique and Kato Katz technique. PCR was used to confirm hookworm, Ascaris spp., Giardia spp. and Blastocystis spp. Major gastrointestinal parasitic infections found in humans included hookworms (63.3%), Entamoeba spp. (27.1%) and Strongyloides stercoralis (24.3%). In dogs, hookworm (80.8%), Spirometra spp. (21.3%) and Strongyloides spp. (14.9%) were most commonly detected and in pigs Isospora suis (75.0%), Oesophagostomum spp. (73.7%) and Entamoeba spp. (31.6%) were found. Eleven parasite species were detected in dogs (eight helminths and three protozoa), seven of which have zoonotic potential, including hookworm, Strongyloides spp., Trichuris spp., Toxocara canis, Echinostoma spp., Giardia duodenalis and Entamoeba spp. Five of the parasite species detected in pigs also have zoonotic potential, including Ascaris spp., Trichuris spp., Capillaria spp., Balantidium coli and Entamoeba spp. Further molecular epidemiological studies will aid characterisation of parasite species and genotypes and allow further insight into the potential for zoonotic cross transmission of parasites in this community. PMID:24704609

  15. Release of Small RNA-containing Exosome-like Vesicles from the Human Filarial Parasite Brugia malayi

    PubMed Central

    Agbedanu, Prince N; Harischandra, Hiruni; Moorhead, Andrew R; Day, Tim A; Bartholomay, Lyric C; Kimber, Michael J

    2015-01-01

    Lymphatic filariasis (LF) is a socio-economically devastating mosquito-borne Neglected Tropical Disease caused by parasitic filarial nematodes. The interaction between the parasite and host, both mosquito and human, during infection, development and persistence is dynamic and delicately balanced. Manipulation of this interface to the detriment of the parasite is a promising potential avenue to develop disease therapies but is prevented by our very limited understanding of the host-parasite relationship. Exosomes are bioactive small vesicles (30–120 nm) secreted by a wide range of cell types and involved in a wide range of physiological processes. Here, we report the identification and partial characterization of exosome-like vesicles (ELVs) released from the infective L3 stage of the human filarial parasite Brugia malayi. Exosome-like vesicles were isolated from parasites in culture media and electron microscopy and nanoparticle tracking analysis were used to confirm that vesicles produced by juvenile B. malayi are exosome-like based on size and morphology. We show that loss of parasite viability correlates with a time-dependent decay in vesicle size specificity and rate of release. The protein cargo of these vesicles is shown to include common exosomal protein markers and putative effector proteins. These Brugia-derived vesicles contain small RNA species that include microRNAs with host homology, suggesting a potential role in host manipulation. Confocal microscopy shows J774A.1, a murine macrophage cell line, internalize purified ELVs, and we demonstrate that these ELVs effectively stimulate a classically activated macrophage phenotype in J774A.1. To our knowledge, this is the first report of exosome-like vesicle release by a human parasitic nematode and our data suggest a novel mechanism by which human parasitic nematodes may actively direct the host responses to infection. Further interrogation of the makeup and function of these bioactive vesicles could seed

  16. Human Monoclonal Antibodies to Pf 155, a Major Antigen of Malaria Parasite Plasmodium falciparum

    NASA Astrophysics Data System (ADS)

    Udomsangpetch, Rachanee; Lundgren, Katarina; Berzins, Klavs; Wahlin, Birgitta; Perlmann, Hedvig; Troye-Blomberg, Marita; Carlsson, Jan; Wahlgren, Mats; Perlmann, Peter; Bjorkman, Anders

    1986-01-01

    Pf 155, a protein of the human malaria parasite Plasmodium falciparum, is strongly immunogenic in humans and is believed to be a prime candidate for the preparation of a vaccine. Human monoclonal antibodies to Pf 155 were obtained by cloning B cells that had been prepared from an immune donor and transformed with Epstein-Barr virus. When examined by indirect immunofluorescence, these antibodies stained the surface of infected erythrocytes, free merozoites, segmented schizonts, and gametocytes. They bound to a major polypeptide with a relative molecular weight of 155K and to two minor ones (135K and 120K), all having high affinity for human glycophorin. The antibodies strongly inhibited merozoite reinvasion in vitro, suggesting that they might be appropriate reagents for therapeutic administration in vivo.

  17. Parasitism of prehistoric humans and companion animals from Antelope Cave, Mojave County, northwest Arizona.

    PubMed

    Fugassa, Martín H; Reinhard, Karl J; Johnson, Keith L; Gardner, Scott L; Vieira, Mônica; Araújo, Adauto

    2011-10-01

    Previously, we reported a tick recovered from Antelope Cave in extreme northwest Arizona. Further analyses of coprolites from Antelope Cave revealed additional parasitological data from coprolites of both human and canid origin. A second tick was found. This site is the only archaeological locality where ticks have been recovered. We also discovered an acanthocephalan in association with Enterobius vermicularis eggs in the same coprolite. This association shows that the coprolite was deposited by a human. This discovery expands our knowledge of the range of prehistoric acanthocephalan infection. In addition, findings from canid coprolites of Trichuris vulpis are reported. This is the first published discovery of T. vulpis from a North American archaeological context. The close association of dogs with humans at Ancestral Puebloan (Anasazi) sites raises the potential that zoonotic parasites were transferred to the human population. The archaeological occupation is associated with the Ancestral Pueblo culture 1,100 yr ago. PMID:21506807

  18. Insights into the pyrimidine biosynthetic pathway of human malaria parasite Plasmodium falciparum as chemotherapeutic target.

    PubMed

    Krungkrai, Sudaratana R; Krungkrai, Jerapan

    2016-06-01

    Malaria is a major cause of morbidity and mortality in humans. Artemisinins remain as the first-line treatment for Plasmodium falciparum (P. falciparum) malaria although drug resistance has already emerged and spread in Southeast Asia. Thus, to fight this disease, there is an urgent need to develop new antimalarial drugs for malaria chemotherapy. Unlike human host cells, P. falciparum cannot salvage preformed pyrimidine bases or nucleosides from the extracellular environment and relies solely on nucleotides synthesized through the de novo biosynthetic pathway. This review presents significant progress on understanding the de novo pyrimidine pathway and the functional enzymes in the human parasite P. falciparum. Current knowledge in genomics and metabolomics are described, particularly focusing on the parasite purine and pyrimidine nucleotide metabolism. These include gene annotation, characterization and molecular mechanism of the enzymes that are different from the human host pathway. Recent elucidation of the three-dimensional crystal structures and the catalytic reactions of three enzymes: dihydroorotate dehydrogenase, orotate phosphoribosyltransferase, and orotidine 5'-monophosphate decarboxylase, as well as their inhibitors are reviewed in the context of their therapeutic potential against malaria. PMID:27262062

  19. An interesting finding in the uterine cervix: Schistosoma hematobium calcified eggs

    PubMed Central

    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. PMID:26484333

  20. Assessment and Molecular Characterization of Human Intestinal Parasites in Bivalves from Orchard Beach, NY, USA

    PubMed Central

    Tei, Freda F.; Kowalyk, Steven; Reid, Jhenelle A.; Presta, Matthew A.; Yesudas, Rekha; Mayer, D.C. Ghislaine

    2016-01-01

    Bivalves have been shown to be carriers of the human intestinal parasites Cryptosporidium parvum and Toxoplasma gondii. The goal of this study is to determine the prevalence of protozoan parasites in mollusks of New York City using a polymerase chain reaction (PCR)-based assay. Four species of mollusks, Mya arenaria, Geukensia demissa, Crassostrea virginica, and Mytilis edulis, were collected from Orchard Beach, NY in the fall of 2014, totaling 159 specimens. Each individual mollusk was dissected to harvest the digestive gland, the mantle, the gills, the foot and the siphon. The tissues were assayed for the presence of Cryptosporidium parvum, Giardia lamblia, and Toxoplasma gondii DNA by using primers that target parasite-specific genes. C. parvum was found at a prevalence of 50%, 11.3%, and 1%, respectively, in Mya arenaria, G. demissa, and Mytilis edulis. C. parvum DNA was detected in all the tissues of these bivalve species, except the gills. Furthermore, G. lamblia was detected in Mya arenaria, G. demissa, Crassostrea virginica and Mytilis edulis at a prevalence of 37.5%, 4.5%, 60%, and 20.6%, respectively, while T. gondii DNA was not detected. PMID:27043590

  1. The Clp Chaperones and Proteases of the Human Malaria Parasite Plasmodium falciparum

    SciTech Connect

    Bakkouri, Majida El; Pow, Andre; Mulichak, Anne; Cheung, Kevin L.Y.; Artz, Jennifer D.; Amani, Mehrnaz; Fell, Stuart; de Koning-Ward, Tania F.; Goodman, C. Dean; McFadden, Geoffrey I.; Ortega, Joaquin; Hui, Raymond; Houry, Walid A.

    2015-02-09

    The Clp chaperones and proteases play an important role in protein homeostasis in the cell. They are highly conserved across prokaryotes and found also in the mitochondria of eukaryotes and the chloroplasts of plants. They function mainly in the disaggregation, unfolding and degradation of native as well as misfolded proteins. Here, we provide a comprehensive analysis of the Clp chaperones and proteases in the human malaria parasite Plasmodium falciparum. The parasite contains four Clp ATPases, which we term PfClpB1, PfClpB2, PfClpC and PfClpM. One PfClpP, the proteolytic subunit, and one PfClpR, which is an inactive version of the protease, were also identified. Expression of all Clp chaperones and proteases was confirmed in blood-stage parasites. The proteins were localized to the apicoplast, a non-photosynthetic organelle that accommodates several important metabolic pathways in P. falciparum, with the exception of PfClpB2 (also known as Hsp101), which was found in the parasitophorous vacuole. Both PfClpP and PfClpR form mostly homoheptameric rings as observed by size-exclusion chromatography, analytical ultracentrifugation and electron microscopy. The X-ray structure of PfClpP showed the protein as a compacted tetradecamer similar to that observed for Streptococcus pneumoniae and Mycobacterium tuberculosis ClpPs. Our data suggest the presence of a ClpCRP complex in the apicoplast of P. falciparum.

  2. Assessment and Molecular Characterization of Human Intestinal Parasites in Bivalves from Orchard Beach, NY, USA.

    PubMed

    Tei, Freda F; Kowalyk, Steven; Reid, Jhenelle A; Presta, Matthew A; Yesudas, Rekha; Mayer, D C Ghislaine

    2016-01-01

    Bivalves have been shown to be carriers of the human intestinal parasites Cryptosporidium parvum and Toxoplasma gondii. The goal of this study is to determine the prevalence of protozoan parasites in mollusks of New York City using a polymerase chain reaction (PCR)-based assay. Four species of mollusks, Mya arenaria, Geukensia demissa, Crassostrea virginica, and Mytilis edulis, were collected from Orchard Beach, NY in the fall of 2014, totaling 159 specimens. Each individual mollusk was dissected to harvest the digestive gland, the mantle, the gills, the foot and the siphon. The tissues were assayed for the presence of Cryptosporidium parvum, Giardia lamblia, and Toxoplasma gondii DNA by using primers that target parasite-specific genes. C. parvum was found at a prevalence of 50%, 11.3%, and 1%, respectively, in Mya arenaria, G. demissa, and Mytilis edulis. C. parvum DNA was detected in all the tissues of these bivalve species, except the gills. Furthermore, G. lamblia was detected in Mya arenaria, G. demissa, Crassostrea virginica and Mytilis edulis at a prevalence of 37.5%, 4.5%, 60%, and 20.6%, respectively, while T. gondii DNA was not detected. PMID:27043590

  3. Variation in infection length and superinfection enhance selection efficiency in the human malaria parasite.

    PubMed

    Chang, Hsiao-Han; Childs, Lauren M; Buckee, Caroline O

    2016-01-01

    The capacity for adaptation is central to the evolutionary success of the human malaria parasite Plasmodium falciparum. Malaria epidemiology is characterized by the circulation of multiple, genetically diverse parasite clones, frequent superinfection, and highly variable infection lengths, a large number of which are chronic and asymptomatic. The impact of these characteristics on the evolution of the parasite is largely unknown, however, hampering our understanding of the impact of interventions and the emergence of drug resistance. In particular, standard population genetic frameworks do not accommodate variation in infection length or superinfection. Here, we develop a population genetic model of malaria including these variations, and show that these aspects of malaria infection dynamics enhance both the probability and speed of fixation for beneficial alleles in complex and non-intuitive ways. We find that populations containing a mixture of short- and long-lived infections promote selection efficiency. Interestingly, this increase in selection efficiency occurs even when only a small fraction of the infections are chronic, suggesting that selection can occur efficiently in areas of low transmission intensity, providing a hypothesis for the repeated emergence of drug resistance in the low transmission setting of Southeast Asia. PMID:27193195

  4. Variation in infection length and superinfection enhance selection efficiency in the human malaria parasite

    PubMed Central

    Chang, Hsiao-Han; Childs, Lauren M.; Buckee, Caroline O.

    2016-01-01

    The capacity for adaptation is central to the evolutionary success of the human malaria parasite Plasmodium falciparum. Malaria epidemiology is characterized by the circulation of multiple, genetically diverse parasite clones, frequent superinfection, and highly variable infection lengths, a large number of which are chronic and asymptomatic. The impact of these characteristics on the evolution of the parasite is largely unknown, however, hampering our understanding of the impact of interventions and the emergence of drug resistance. In particular, standard population genetic frameworks do not accommodate variation in infection length or superinfection. Here, we develop a population genetic model of malaria including these variations, and show that these aspects of malaria infection dynamics enhance both the probability and speed of fixation for beneficial alleles in complex and non-intuitive ways. We find that populations containing a mixture of short- and long-lived infections promote selection efficiency. Interestingly, this increase in selection efficiency occurs even when only a small fraction of the infections are chronic, suggesting that selection can occur efficiently in areas of low transmission intensity, providing a hypothesis for the repeated emergence of drug resistance in the low transmission setting of Southeast Asia. PMID:27193195

  5. Molecular interaction of ferredoxin and ferredoxin-NADP+ reductase from human malaria parasite.

    PubMed

    Kimata-Ariga, Yoko; Saitoh, Takashi; Ikegami, Takahisa; Horii, Toshihiro; Hase, Toshiharu

    2007-12-01

    The malaria parasite possesses plant-type ferredoxin (Fd) and ferredoxin-NADP(+) reductase (FNR) in a plastid-derived organelle called the apicoplast. This Fd/FNR redox system, which potentially provides reducing power for essential biosynthetic pathways in the apicoplast, has been proposed as a target for the development of specific new anti-malarial agents. We studied the molecular interaction of Fd and FNR of human malaria parasite (Plasmodium falciparum), which were produced as recombinant proteins in Escherichia coli. NMR chemical shift perturbation analysis mapped the location of the possible FNR interaction sites on the surface of P. falciparum Fd. Site-specific mutation of acidic Fd residues in these regions and the resulting analyses of electron transfer activity and affinity chromatography of those mutants revealed that two acidic regions (a region including Asp26, Glu29 and Glu34, and the other including Asp65 and Glu66) dominantly contribute to the electrostatic interaction with P. falciparum FNR. The combination of Asp26/Glu29/Glu34 conferred a larger contribution than that of Asp65/Glu66, and among Asp26, Glu29 and Glu34, Glu29 was shown to be the most important residue for the interaction with P. falciparum FNR. These findings provide the basis for understanding molecular recognition between Fd and FNR of the malaria parasite. PMID:17938142

  6. Toxic effects of chromium on Schistosoma haematobium miracidia

    SciTech Connect

    Wolmarans, C.T.; Yssel, E.; Hamilton-Attwell, V.L.

    1988-12-01

    Various heavy metals have recently been evaluated as molluscicides for freshwater snails, which act as intermediate hosts of trematode parasites of medical or veterinary importance. Very little information, however, is available on heavy metals that may be suitable to eliminate the parasites as such. Suitable compounds should also inhibit the penetration ability of parasites as well as stunt the development of those who do not penetrate their hosts. In the light of these requirements, the present study evaluated the effect of chromium on the miracidia of Schistosoma haematobium, which causes urinary bilharzia. Attention was mainly focused on (1) the chromium concentration which resulted in 100% mortality (2) the effect of chromium on the external and internal morphology of the miracidia, and (3) the ability of the miracidia to form sporocytes in vitro and in vivo and to penetrate their intermediate host snail, Bulinus africanus.

  7. Natural infection of Plasmodium brasilianum in humans: Man and monkey share quartan malaria parasites in the Venezuelan Amazon

    PubMed Central

    Lalremruata, Albert; Magris, Magda; Vivas-Martínez, Sarai; Koehler, Maike; Esen, Meral; Kempaiah, Prakasha; Jeyaraj, Sankarganesh; Perkins, Douglas Jay; Mordmüller, Benjamin; Metzger, Wolfram G.

    2015-01-01

    Background The quartan malaria parasite Plasmodium malariae is the widest spread and best adapted human malaria parasite. The simian Plasmodium brasilianum causes quartan fever in New World monkeys and resembles P. malariae morphologically. Since the genetics of the two parasites are nearly identical, differing only in a range of mutations expected within a species, it has long been speculated that the two are the same. However, no naturally acquired infection with parasites termed as P. brasilianum has been found in humans until now. Methods We investigated malaria cases from remote Yanomami indigenous communities of the Venezuelan Amazon and analyzed the genes coding for the circumsporozoite protein (CSP) and the small subunit of ribosomes (18S) by species-specific PCR and capillary based-DNA sequencing. Findings Based on 18S rRNA gene sequencing, we identified 12 patients harboring malaria parasites which were 100% identical with P. brasilianum isolated from the monkey, Alouatta seniculus. Translated amino acid sequences of the CS protein gene showed identical immunodominant repeat units between quartan malaria parasites isolated from both humans and monkeys. Interpretation This study reports, for the first time, naturally acquired infections in humans with parasites termed as P. brasilianum. We conclude that quartan malaria parasites are easily exchanged between humans and monkeys in Latin America. We hypothesize a lack of host specificity in mammalian hosts and consider quartan malaria to be a true anthropozoonosis. Since the name P. brasilianum suggests a malaria species distinct from P. malariae, we propose that P. brasilianum should have a nomenclatorial revision in case further research confirms our findings. The expansive reservoir of mammalian hosts discriminates quartan malaria from other Plasmodium spp. and requires particular research efforts. PMID:26501116

  8. Serine proteases of parasitic helminths.

    PubMed

    Yang, Yong; Wen, Yun jun; Cai, Ya Nan; Vallée, Isabelle; Boireau, Pascal; Liu, Ming Yuan; Cheng, Shi Peng

    2015-02-01

    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

  9. 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

  10. Associations between common intestinal parasites and bacteria in humans as revealed by qPCR.

    PubMed

    O'Brien Andersen, L; Karim, A B; Roager, H M; Vigsnæs, L K; Krogfelt, K A; Licht, T R; Stensvold, C R

    2016-09-01

    Several studies have shown associations between groups of intestinal bacterial or specific ratios between bacterial groups and various disease traits. Meanwhile, little is known about interactions and associations between eukaryotic and prokaryotic microorganisms in the human gut. In this work, we set out to investigate potential associations between common single-celled parasites such as Blastocystis spp. and Dientamoeba fragilis and intestinal bacteria. Stool DNA from patients with intestinal symptoms were selected based on being Blastocystis spp.-positive (B+)/negative (B-) and D. fragilis-positive (D+)/negative (D-), and split into four groups of 21 samples (B+ D+, B+ D-, B- D+, and B- D-). Quantitative PCR targeting the six bacterial taxa Bacteroides, Prevotella, the butyrate-producing clostridial clusters IV and XIVa, the mucin-degrading Akkermansia muciniphila, and the indigenous group of Bifidobacterium was subsequently performed, and the relative abundance of these bacteria across the four groups was compared. The relative abundance of Bacteroides in B- D- samples was significantly higher compared with B+ D- and B+ D+ samples (P < 0.05 and P < 0.01, respectively), and this association was even more significant when comparing all parasite-positive samples with parasite-negative samples (P < 0.001). Additionally, our data revealed that a low abundance of Prevotella and a higher abundance of Clostridial cluster XIVa was associated with parasite-negative samples (P < 0.05 and P < 0.01, respectively). Our data support the theory that Blastocystis alone or combined with D. fragilis is associated with gut microbiota characterized by low relative abundances of Bacteroides and Clostridial cluster XIVa and high levels of Prevotella. PMID:27230509

  11. RNA Interference in Schistosoma mansoni Schistosomula: Selectivity, Sensitivity and Operation for Larger-Scale Screening

    PubMed Central

    Horn, Martin; Braschi, Simon; Sojka, Daniel; Ruelas, Debbie S.; Suzuki, Brian; Lim, Kee-Chong; Hopkins, Stephanie D.; McKerrow, James H.; Caffrey, Conor R.

    2010-01-01

    Background The possible emergence of resistance to the only available drug for schistosomiasis spurs drug discovery that has been recently incentivized by the availability of improved transcriptome and genome sequence information. Transient RNAi has emerged as a straightforward and important technique to interrogate that information through decreased or loss of gene function and identify potential drug targets. To date, RNAi studies in schistosome stages infecting humans have focused on single (or up to 3) genes of interest. Therefore, in the context of standardizing larger RNAi screens, data are limited on the extent of possible off-targeting effects, gene-to-gene variability in RNAi efficiency and the operational capabilities and limits of RNAi. Methodology/Principal Findings We investigated in vitro the sensitivity and selectivity of RNAi using double-stranded (ds)RNA (approximately 500 bp) designed to target 11 Schistosoma mansoni genes that are expressed in different tissues; the gut, tegument and otherwise. Among the genes investigated were 5 that had been previously predicted to be essential for parasite survival. We employed mechanically transformed schistosomula that are relevant to parasitism in humans, amenable to screen automation and easier to obtain in greater numbers than adult parasites. The operational parameters investigated included defined culture media for optimal parasite maintenance, transfection strategy, time- and dose- dependency of RNAi, and dosing limits. Of 7 defined culture media tested, Basch Medium 169 was optimal for parasite maintenance. RNAi was best achieved by co-incubating parasites and dsRNA (standardized to 30 µg/ml for 6 days); electroporation provided no added benefit. RNAi, including interference of more than one transcript, was selective to the gene target(s) within the pools of transcripts representative of each tissue. Concentrations of dsRNA above 90 µg/ml were directly toxic. RNAi efficiency was transcript

  12. Leukocyte Lysis and Cytokine Induction by the Human Sexually Transmitted Parasite Trichomonas vaginalis

    PubMed Central

    Mercer, Frances; Diala, Fitz Gerald I.; Chen, Yi-Pei; Molgora, Brenda M.; Ng, Shek Hang; Johnson, Patricia J.

    2016-01-01

    Trichomonas vaginalis (Tv) is an extracellular protozoan parasite that causes the most common non-viral sexually transmitted infection: trichomoniasis. While acute symptoms in women may include vaginitis, infections are often asymptomatic, but can persist and are associated with medical complications including increased HIV susceptibility, infertility, pre-term labor, and higher incidence of cervical cancer. Heightened inflammation resulting from Tv infection could account for these complications. Effective cellular immune responses to Tv have not been characterized, and re-infection is common, suggesting a dysfunctional adaptive immune response. Using primary human leukocyte components, we have established an in vitro co-culture system to assess the interaction between Tv and the cells of the human immune system. We determined that in vitro, Tv is able to lyse T-cells and B-cells, showing a preference for B-cells. We also found that Tv lysis of lymphocytes was mediated by contact-dependent and soluble factors. Tv lysis of monocytes is far less efficient, and almost entirely contact-dependent. Interestingly, a common symbiont of Tv, Mycoplasma hominis, did not affect cytolytic activity of the parasite, but had a major impact on cytokine responses. M. hominis enabled more diverse inflammatory cytokine secretion in response to Tv and, of the cytokines tested, Tv strains cleared of M. hominis induced only IL-8 secretion from monocytes. The quality of the adaptive immune response to Tv is therefore likely influenced by Tv symbionts, commensals, and concomitant infections, and may be further complicated by direct parasite lysis of effector immune cells. PMID:27529696

  13. Moxidectin causes adult worm mortality of human lymphatic filarial parasite Brugia malayi in rodent models.

    PubMed

    Verma, Meenakshi; Pathak, Manisha; Shahab, Mohd; Singh, Kavita; Mitra, Kalyan; Misra-Bhattacharya, Shailja

    2014-12-01

    Moxidectin is a macrocyclic lactone belonging to milbemycin family closely related to ivermectin and is currently progressing towards Phase III clinical trial against human infection with the filaria Onchocerca volvulus (Leuckart, 1894). There is a single report on the microfilaricidal and embryostatic activity of moxidectin in case of the human lymphatic filarial parasite Brugia malayi (Brug, 1927) in Mastomys coucha (Smith) but without any adulticidal action. In the present study, the in vitro and in vivo antifilarial efficacy of moxidectin was evaluated on, B. malayi. In vitro moxidectin showed 100% reduction in adult female worm motility at 0.6 μM concentration within 7 days with 68% inhibition in the reduction of MTT (3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide dye) (which is used to detect viability of worms). A 50% inhibitory concentration (IC50) of moxidectin for adult female parasite was 0.242 μM, for male worm 0.186 μM and for microfilaria IC50 was 0.813 μM. In adult B. malayi-transplanted primary screening model (Meriones unguiculatus Milne-Edwards), moxidectin at a single optimal dose of 20 mg/kg by oral and subcutaneous route was found effective on both adult parasites and microfilariae. In secondary screening (M coucha, subcutaneously inoculated with infective larvae), moxidectin at the same dose by subcutaneous route brought about death of 49% of adult worms besides causing sterilisation in 54% of the recovered live female worms. The treated animals exhibited a continuous and sustained reduction in peripheral blood microfilaraemia throughout the observation period of 90 days. The mechanism of action of moxidectin is suggested to be similar to avermectins. The in silico studies were also designed to explore the interaction of moxidectin with glutamate-gated chloride channels of B. malayi. The docking results revealed a close interaction of moxidectin with various GluCl ligand sites of B. malayi. PMID:25651699

  14. Leukocyte Lysis and Cytokine Induction by the Human Sexually Transmitted Parasite Trichomonas vaginalis.

    PubMed

    Mercer, Frances; Diala, Fitz Gerald I; Chen, Yi-Pei; Molgora, Brenda M; Ng, Shek Hang; Johnson, Patricia J

    2016-08-01

    Trichomonas vaginalis (Tv) is an extracellular protozoan parasite that causes the most common non-viral sexually transmitted infection: trichomoniasis. While acute symptoms in women may include vaginitis, infections are often asymptomatic, but can persist and are associated with medical complications including increased HIV susceptibility, infertility, pre-term labor, and higher incidence of cervical cancer. Heightened inflammation resulting from Tv infection could account for these complications. Effective cellular immune responses to Tv have not been characterized, and re-infection is common, suggesting a dysfunctional adaptive immune response. Using primary human leukocyte components, we have established an in vitro co-culture system to assess the interaction between Tv and the cells of the human immune system. We determined that in vitro, Tv is able to lyse T-cells and B-cells, showing a preference for B-cells. We also found that Tv lysis of lymphocytes was mediated by contact-dependent and soluble factors. Tv lysis of monocytes is far less efficient, and almost entirely contact-dependent. Interestingly, a common symbiont of Tv, Mycoplasma hominis, did not affect cytolytic activity of the parasite, but had a major impact on cytokine responses. M. hominis enabled more diverse inflammatory cytokine secretion in response to Tv and, of the cytokines tested, Tv strains cleared of M. hominis induced only IL-8 secretion from monocytes. The quality of the adaptive immune response to Tv is therefore likely influenced by Tv symbionts, commensals, and concomitant infections, and may be further complicated by direct parasite lysis of effector immune cells. PMID:27529696

  15. Study of the gastrointestinal parasitic fauna of captive non-human primates (Macaca fascicularis).

    PubMed

    Zanzani, Sergio Aurelio; Gazzonis, Alessia Libera; Epis, Sara; Manfredi, Maria Teresa

    2016-01-01

    The aim of this study was to examine helminths and protozoans in cynomolgus macaques (Macaca fascicularis) imported from registered breeding facilities in China and their relation to health risks for non-human primate handlers in biomedical research centers and in breeding facilities. Fresh fecal samples were collected from a total of 443 M. fascicularis and analyzed by copromicroscopical analysis, immunoenzymatic, or molecular assays. As to helminths, whose eggs were shed in 2.03% of the samples, Trichuris and Oesophagostomum were the only two taxa found, with low prevalence and low eggs per gram (EPG) values. Protozoans were more frequently detected (87.40%), with Entamoeba coli (85.19%) and Endolimax nana (79.26%) as the most prevalent species shed. Other parasites found by fecal smear examination were uninucleated-cyst-producing Entamoebas (78.52%), Iodamoeba bütschlii (42.96%), and Chilomastix mesnili (24.44%), while cysts of Balantidium coli (22.2%) were only observed by sedimentation. No coproantigens of Giardia duodenalis, Cryptosporidium spp., and Entamoeba histolytica complex were detected. Blastocystis sp. infection was noticed in 87.63% of macaques by PCR. These cynomolgus monkeys were infected with many subtypes (ST1, ST2, ST3, ST5, and ST7), where the predominant Blastocystis sp. subtypes were ST2 (77.5%), followed by ST1 (63.5%). Data collected confirmed the presence of potentially zoonotic parasites and a high parasite diversity, suggesting the need for appropriate and sensitive techniques to adequately control them and related health risks for handlers of non-human primates in biomedical research centers and in breeding facilities. PMID:26374536

  16. In silico multiple-targets identification for heme detoxification in the human malaria parasite Plasmodium falciparum.

    PubMed

    Phaiphinit, Suthat; Pattaradilokrat, Sittiporn; Lursinsap, Chidchanok; Plaimas, Kitiporn

    2016-01-01

    Detoxification of hemoglobin byproducts or free heme is an essential step and considered potential targets for anti-malaria drug development. However, most of anti-malaria drugs are no longer effective due to the emergence and spread of the drug resistant malaria parasites. Therefore, it is an urgent need to identify potential new targets and even for target combinations for effective malaria drug design. In this work, we reconstructed the metabolic networks of Plasmodium falciparum and human red blood cells for the simulation of steady mass and flux flows of the parasite's metabolites under the blood environment by flux balance analysis (FBA). The integrated model, namely iPF-RBC-713, was then adjusted into two stage-specific metabolic models, which first was for the pathological stage metabolic model of the parasite when invaded the red blood cell without any treatment and second was for the treatment stage of the parasite when a drug acted by inhibiting the hemozoin formation and caused high production rate of heme toxicity. The process of identifying target combinations consisted of two main steps. Firstly, the optimal fluxes of reactions in both the pathological and treatment stages were computed and compared to determine the change of fluxes. Corresponding enzymes of the reactions with zero fluxes in the treatment stage but non-zero fluxes in the pathological stage were predicted as a preliminary list of potential targets in inhibiting heme detoxification. Secondly, the combinations of all possible targets listed in the first step were examined to search for the best promising target combinations resulting in more effective inhibition of the detoxification to kill the malaria parasites. Finally, twenty-three enzymes were identified as a preliminary list of candidate targets which mostly were in pyruvate metabolism and citrate cycle. The optimal set of multiple targets for blocking the detoxification was a set of heme ligase, adenosine transporter, myo

  17. Schistosoma mekongi cathepsin B and its use in the development of an immunodiagnosis.

    PubMed

    Sangfuang, Manaw; Chusongsang, Yupa; Limpanont, Yanin; Vanichviriyakit, Rapeepun; Chotwiwatthanakun, Charoonroj; Sobhon, Prasert; Preyavichyapugdee, Narin

    2016-03-01

    Schistosomiasis mekongi is one of the most important human parasitic diseases caused by Schistosoma mekongi in South-east Asia. The endemic area is the Mekong River sub-region from Laos to Cambodia. This parasite also infects dogs and pigs which are its alternative host species. Currently, the lack of reliable rapid diagnosis makes it difficult to monitor the infection and spreading of the disease. In this study, we screened the antigens of the parasite with sera of infected mice using Western blotting and identified proteins of interest with LC-MS/MS to obtain potential candidate proteins for diagnostic development. This assay yielded 2 immunoreactive bands at molecular masses of 31 and 22kDa. The 31kDa protein was the major band identified as cathepsin B, and its gene was cloned to obtain a full cDNA sequence (SmekCatB). The cDNA consisted of 1123bp and its longest reading frame encoded for 342 amino acids with some putative post translation modifications. The recombinant SmekCatB (rSmekCatB) with hexahistidine tag at the C-terminus was expressed in Escherichia coli and purified by Ni-NTA resin under denaturing conditions. The rSmekCatB reacted with sera of S. mekongi-infected mice. Indirect ELISA using rSmekCatB as the antigen to detect mouse antibodies, revealed a sensitivity of 91.67% for schistosomiasis mekongi and the specificity of 100%. Our data suggested that SmekCatB is one of the most promising parasitic antigens that could be used for the diagnosis of S. mekongi infection. PMID:26655041

  18. Urban epidemiology of Schistosoma intercalatum in the city of Bata, Equatorial Guinea.

    PubMed

    Simarro, P P; Sima, F O; Mir, M

    1990-09-01

    In a cross sectional study, 1221 individuals were enrolled to determine the urban epidemiology of Schistosoma intercalatum in the city of Bata, Equatorial Guinea. Bulinus forskalii was the only intermediate host for schistosomes found in the study areas. The only Schistosoma species detected in faeces was S. intercalatum. However, no Schistosoma eggs were found in urine. The overall prevalence of S. intercalatum infection was 21.2%. Although infected subjects were found in all age groups, peak prevalence and highest parasite load occurred in 5-14 years old children. But only 38 individuals (3.1%) had infection with more than 400 eggs per gram faeces. Thirty out of these (78.9%), were children between 5 and 14 years of age. In the heavily infected subjects (greater than 400 eggs/g. faeces) highly significantly more diarrhoea with microscopic and macroscopic blood in stool was present (p less than 0.0001). PMID:2255841

  19. 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. PMID:26883596

  20. Discovery and Characterization of Novel Anti-schistosomal Properties of the Anti-anginal Drug, Perhexiline and Its Impact on Schistosoma mansoni Male and Female Reproductive Systems

    PubMed Central

    Perlas, Emerald; Bolasco, Giulia; Nibbio, Martina; Monteagudo, Edith; Bresciani, Alberto; Ruberti, Giovina

    2016-01-01

    Background Schistosomiasis, one of the world’s greatest human neglected tropical diseases, is caused by parasitic trematodes of the genus Schistosoma. A unique feature of schistosome biology is that the induction of sexual maturation as well as the maintenance of the differentiation status of female reproductive organs and egg production, necessary for both disease transmission and pathogenesis, are strictly dependent on the male. The treatment and most control initiatives of schistosomiasis rely today on the long-term application of a single drug, praziquantel (PZQ), mostly by campaigns of mass drug administration. PZQ, while very active on adult parasites, has much lower activity against juvenile worms. Monotherapy also favors the selection of drug resistance and, therefore, new drugs are urgently needed. Methods and Findings Following the screening of a small compound library with an ATP-based luminescent assay on Schistosoma mansoni schistosomula, we here report the identification and characterization of novel antischistosomal properties of the anti-anginal drug perhexiline maleate (PHX). By phenotypic worm survival assays and confocal microscopy studies we show that PHX, in vitro, has a marked lethal effect on all S. mansoni parasite life stages (newly transformed schistosomula, juvenile and adult worms) of the definitive host. We further demonstrate that sub-lethal doses of PHX significantly impair egg production and lipid depletion within the vitellarium of adult female worms. Moreover, we highlighted tegumental damage in adult male worms and remarkable reproductive system alterations in both female and male adult parasites. The in vivo study in S. mansoni-patent mice showed a notable variability of worm burdens in the individual experiments, with an overall minimal schistosomicidal effect upon PHX treatment. The short PHX half-life in mice, together with its very high rodent plasma proteins binding could be the cause of the modest efficacy of PHX in the

  1. Intestinal Parasite Co-infection among Pulmonary Tuberculosis Cases without Human Immunodeficiency Virus Infection in a Rural County in China

    PubMed Central

    Li, Xin-Xu; Chen, Jia-Xu; Wang, Li-Xia; Tian, Li-Guang; Zhang, Yu-Ping; Dong, Shuang-Pin; Hu, Xue-Guang; Liu, Jian; Wang, Feng-Feng; Wang, Yue; Yin, Xiao-Mei; He, Li-Jun; Yan, Qiu-Ye; Zhang, Hong-Wei; Xu, Bian-Li; Zhou, Xiao-Nong

    2014-01-01

    Epidemiologic studies of co-infection with tuberculosis (TB) and intestinal parasites in humans have not been extensively investigated in China. A cross-section study was conducted in a rural county of Henan Province, China. Pulmonary TB (PTB) case-patients receiving treatment for infection with Mycobacterium tuberculosis and healthy controls matched for geographic area, age, and sex were surveyed by using questionnaires. Fecal and blood specimens were collected for detection of intestinal parasites, routine blood examination, and infection with human immunodeficiency virus. The chi-square test was used for univariate analysis and multivariate logistic regression models were used to adjust for potential confounding factors. A total of 369 persons with PTB and 366 healthy controls were included; all participants were negative for human immunodeficiency virus. The overall prevalence of intestinal parasites in persons with PTB was 14.9%, including intestinal protozoa (7.9%) and helminthes (7.6%). The infection spectrum of intestinal parasites was Entamoeba spp. (1.4%), Blastocystis hominis (6.2%), Trichomonas hominis (0.3%), Clonorchis sinensis (0.3%), Ascaris lumbricoides (0.5%), Trichuris trichiura (2.2%), and hookworm (4.6%). The prevalence of intestinal parasites showed no significant difference between persons with PTB and healthy controls after adjusting for potential confounding factors. There was no factor that affected infection rates for intestinal parasites between the two groups. Infection with intestinal parasites of persons with PTB was associated with female sex (adjusted odds ratio [AOR] = 2.05, 95% confidence interval [CI] = 1.01–4.17), body mass index ≤ 19 (AOR = 3.02, 95% CI = 1.47–6.20), and anemia (AOR = 2.43, 95% CI = 1.17–5.03). Infection of healthy controls was only associated with an annual labor time in farmlands > 2 months (AOR = 4.50, 95% CI = 2.03–10.00). In addition, there was no significant trend between rates of infection with

  2. Parasites and fungi as risk factors for human and animal health.

    PubMed

    Góralska, Katarzyna; Błaszkowska, Joanna

    2015-01-01

    Recent literature data suggests that parasitic and fungal diseases, which pose a threat to both human and animal health, remain a clinical, diagnostic and therapeutic problem. Attention is increasingly paid to the role played by natural microbiota in maintaining homeostasis in humans. A particular emphasis is placed on the possibility of manipulating the human microbiota (permanent, transient, pathogenic) and macrobiota (e.g., Trichuris suis) to support the treatment of selected diseases such as Crohn's disease, obesity, diabetes and cancer. Emphasis is placed on important medical species whose infections not only impair health but can also be life threatening, such as Plasmodium falciparum, Echinococcus multilocularis and Baylisascaris procyonis, which expand into areas which have so far been uninhabited. This article also presents the epidemiology, diagnosis and treatment of opportunistic parasitoses imported from the tropics, which spread across large groups of people through human-to-human transmission (Enterobius vermicularis, Sarcoptes scabiei). It also discusses the problem of environmentally-conditioned parasitoses, particularly their etiological factors associated with food contaminated with invasive forms (Trichinella sp., Toxoplasma gondii). The analysis also concerns the presence of developmental forms of geohelminths (Toxocara sp.) and ectoparasites (ticks), which are vectors of serious human diseases (Lyme borreliosis, anaplasmosis, babesiosis), in the environment. Mycological topics contains rare cases of mycoses environmentally conditioned (CNS aspergillosis) and transmissions of these pathogens in a population of hospitalized individuals, as well as seeking new methods used to treat mycoses. PMID:26878617

  3. Evidence that leishmania donovani utilizes a mannose receptor on human mononuclear phagocytes to establish intracellular parasitism

    SciTech Connect

    Wilson, M.E.; Pearson, R.D.

    1986-01-01

    The pathogenic protozoan Leishmania donovani must gain entrance into mononuclear phagocytes to successfully parasitize man. The parasite's extracellular promastigote stage is ingested by human peripheral blood monocytes or monocyte-derived macrophages in the absence of serum, in a manner characteristic of receptor-mediated endocytosis. Remarkable similarities have been found between the macrophage receptor(s) for promastigotes and a previously characterized eucaryotic receptor system, the mannose/fucose receptor (MFR), that mediates the binding of zymosan particles and mannose- or fucose-terminal glycoconjugates to macrophages. Ingestion of promastigotes by monocyte-derived macrophages was inhibited by several MFR ligands; that is mannan, mannose-BSA and fucose-BSA. In contrast, promastigote ingestion by monocytes was unaffected by MFR ligands. Furthermore, attachment of promastigotes to macrophages, assessed by using cytochalasin D to prevent phagocytosis, was reduced 49.8% by mannan. Reorientation of the MFR to the ventral surface of the cell was achieved by plating macrophages onto mannan-coated coverslips, reducing MFR activity on the exposed cell surface by 94% as assessed by binding of /sup 125/I-mannose-BSA. Under these conditions, ingestion of promastigotes was inhibited by 71.4%. Internalization of the MFR by exposure of macrophages to zymosan before infection with promastigotes resulted in a 62.3% decrease in parasite ingestion. Additionally, NH/sub 4/Cl decreased macrophage ingestion of promastigotes by 38.2%. Subinhibitory concentration of NH/sub 4/Cl (10 mM) and of mannan (0.25 mg/ml) together inhibited parsite ingestion by 76.4%.

  4. Host Mitochondrial Association Evolved in the Human Parasite Toxoplasma gondii via Neofunctionalization of a Gene Duplicate.

    PubMed

    Adomako-Ankomah, Yaw; English, Elizabeth D; Danielson, Jeffrey J; Pernas, Lena F; Parker, Michelle L; Boulanger, Martin J; Dubey, Jitender P; Boyle, Jon P

    2016-05-01

    In Toxoplasma gondii, an intracellular parasite of humans and other animals, host mitochondrial association (HMA) is driven by a gene family that encodes multiple mitochondrial association factor 1 (MAF1) proteins. However, the importance of MAF1 gene duplication in the evolution of HMA is not understood, nor is the impact of HMA on parasite biology. Here we used within- and between-species comparative analysis to determine that the MAF1 locus is duplicated in T. gondii and its nearest extant relative Hammondia hammondi, but not another close relative, Neospora caninum Using cross-species complementation, we determined that the MAF1 locus harbors multiple distinct paralogs that differ in their ability to mediate HMA, and that only T. gondii and H. hammondi harbor HMA(+) paralogs. Additionally, we found that exogenous expression of an HMA(+) paralog in T. gondii strains that do not normally exhibit HMA provides a competitive advantage over their wild-type counterparts during a mouse infection. These data indicate that HMA likely evolved by neofunctionalization of a duplicate MAF1 copy in the common ancestor of T. gondii and H. hammondi, and that the neofunctionalized gene duplicate is selectively advantageous. PMID:26920761

  5. A New High-Throughput Approach to Genotype Ancient Human Gastrointestinal Parasites.

    PubMed

    Côté, Nathalie M L; Daligault, Julien; Pruvost, Mélanie; Bennett, E Andrew; Gorgé, Olivier; Guimaraes, Silvia; Capelli, Nicolas; Le Bailly, Matthieu; Geigl, Eva-Maria; Grange, Thierry

    2016-01-01

    Human gastrointestinal parasites are good indicators for hygienic conditions and health status of past and present individuals and communities. While microscopic analysis of eggs in sediments of archeological sites often allows their taxonomic identification, this method is rarely effective at the species level, and requires both the survival of intact eggs and their proper identification. Genotyping via PCR-based approaches has the potential to achieve a precise species-level taxonomic determination. However, so far it has mostly been applied to individual eggs isolated from archeological samples. To increase the throughput and taxonomic accuracy, as well as reduce costs of genotyping methods, we adapted a PCR-based approach coupled with next-generation sequencing to perform precise taxonomic identification of parasitic helminths directly from archeological sediments. Our study of twenty-five 100 to 7,200 year-old archeological samples proved this to be a powerful, reliable and efficient approach for species determination even in the absence of preserved eggs, either as a stand-alone method or as a complement to microscopic studies. PMID:26752051

  6. Host Mitochondrial Association Evolved in the Human Parasite Toxoplasma gondii via Neofunctionalization of a Gene Duplicate

    PubMed Central

    Adomako-Ankomah, Yaw; English, Elizabeth D.; Danielson, Jeffrey J.; Pernas, Lena F.; Parker, Michelle L.; Boulanger, Martin J.; Dubey, Jitender P.; Boyle, Jon P.

    2016-01-01

    In Toxoplasma gondii, an intracellular parasite of humans and other animals, host mitochondrial association (HMA) is driven by a gene family that encodes multiple mitochondrial association factor 1 (MAF1) proteins. However, the importance of MAF1 gene duplication in the evolution of HMA is not understood, nor is the impact of HMA on parasite biology. Here we used within- and between-species comparative analysis to determine that the MAF1 locus is duplicated in T. gondii and its nearest extant relative Hammondia hammondi, but not another close relative, Neospora caninum. Using cross-species complementation, we determined that the MAF1 locus harbors multiple distinct paralogs that differ in their ability to mediate HMA, and that only T. gondii and H. hammondi harbor HMA+ paralogs. Additionally, we found that exogenous expression of an HMA+ paralog in T. gondii strains that do not normally exhibit HMA provides a competitive advantage over their wild-type counterparts during a mouse infection. These data indicate that HMA likely evolved by neofunctionalization of a duplicate MAF1 copy in the common ancestor of T. gondii and H. hammondi, and that the neofunctionalized gene duplicate is selectively advantageous. PMID:26920761

  7. A New High-Throughput Approach to Genotype Ancient Human Gastrointestinal Parasites

    PubMed Central

    Côté, Nathalie M. L.; Daligault, Julien; Pruvost, Mélanie; Bennett, E. Andrew; Gorgé, Olivier; Guimaraes, Silvia; Capelli, Nicolas; Le Bailly, Matthieu; Geigl, Eva-Maria; Grange, Thierry

    2016-01-01

    Human gastrointestinal parasites are good indicators for hygienic conditions and health status of past and present individuals and communities. While microscopic analysis of eggs in sediments of archeological sites often allows their taxonomic identification, this method is rarely effective at the species level, and requires both the survival of intact eggs and their proper identification. Genotyping via PCR-based approaches has the potential to achieve a precise species-level taxonomic determination. However, so far it has mostly been applied to individual eggs isolated from archeological samples. To increase the throughput and taxonomic accuracy, as well as reduce costs of genotyping methods, we adapted a PCR-based approach coupled with next-generation sequencing to perform precise taxonomic identification of parasitic helminths directly from archeological sediments. Our study of twenty-five 100 to 7,200 year-old archeological samples proved this to be a powerful, reliable and efficient approach for species determination even in the absence of preserved eggs, either as a stand-alone method or as a complement to microscopic studies. PMID:26752051

  8. Some secrets are revealed: parasitic keratitis amoebae as vectors of the scarcely described pandoraviruses to humans.

    PubMed

    Scheid, Patrick; Balczun, Carsten; Schaub, Günter A

    2014-10-01

    In this article, the results of a long effort to derive valuable phylogenetic data about an extraordinary spore-like infectious particle (endocytobiont) within host amoebae (Acanthamoeba sp.) recently isolated from the contact lens and the inflamed eye of a patient with keratitis are presented. The development of these endocytobionts has already been demonstrated with electron microscopic photo sequences, leading to a relevant model of its development presented here. The molecular biological investigation following the discovery of two other Pandoravirus species within aquatic sediments in 2013 led to the taxonomic affiliation of our endocytobiont with the genus Pandoravirus. A range of endocytobionts (intracellular biofilms) have been found in recent years, among which are several viruses which obligatorily proliferate within free-living amoebae. In human medicine, foreign objects which are placed in or on humans cause problems with microorganisms in biofilms. Contact lenses are especially important, because they are known as a source of a rapid formation of biofilm. These were the first Pandoraviruses described, and because this is additionally the first documented association with humans, we have clearly demonstrated how easily such (viral) endocytobionts can be transferred to humans. This case counts as an example of parasites acting as vectors of phylogenetically different microorganisms especially when living sympatric within their biocoenosis of biofilms. As the third part of the "Pandoravirus trilogy", it finally reveals the phylogenetic nature of these "extraordinary endocytobionts" within Acanthamoebae. PMID:25033816

  9. Genome-wide mapping of DNA methylation in the human malaria parasite Plasmodium falciparum

    PubMed Central

    Ponts, Nadia; Fu, Lijuan; Harris, Elena Y.; Zhang, Jing; Chung, Duk-Won D.; Cervantes, Michael C.; Prudhomme, Jacques; Atanasova-Penichon, Vessela; Zehraoui, Enric; Bunnik, Evelien; Rodrigues, Elisandra M.; Lonardi, Stefano; Hicks, Glenn R.; Wang, Yinsheng; Le Roch, Karine G.

    2014-01-01

    SUMMARY Cytosine DNA methylation is an epigenetic mark in most eukaryotic cells that regulates numerous processes, including gene expression and stress responses. We performed a genome-wide analysis of DNA methylation in the human malaria parasite Plasmodium falciparum. We mapped the positions of methylated cytosines and identified a single functional DNA methyltransferase, PfDNMT, that may mediate these genomic modifications. These analyses revealed that the malaria genome is asymmetrically methylated, in which only one DNA strand is methylated, and shares common features with undifferentiated plant and mammalian cells. Notably, core promoters are hypomethylated and transcript levels correlate with intra-exonic methylation. Additionally, there are sharp methylation transitions at nucleosome and exon-intron boundaries. These data suggest that DNA methylation could regulate virulence gene expression and transcription elongation. Furthermore, the broad range of action of DNA methylation and uniqueness of PfDNMT suggest that the methylation pathway is a potential target for anti-malarial strategies. PMID:24331467

  10. An ensemble of specifically targeted proteins stabilizes cortical microtubules in the human parasite Toxoplasma gondii

    PubMed Central

    Liu, Jun; He, Yudou; Benmerzouga, Imaan; Sullivan, William J.; Morrissette, Naomi S.; Murray, John M.; Hu, Ke

    2016-01-01

    Although all microtubules within a single cell are polymerized from virtually identical subunits, different microtubule populations carry out specialized and diverse functions, including directional transport, force generation, and cellular morphogenesis. Functional differentiation requires specific targeting of associated proteins to subsets or even subregions of these polymers. The cytoskeleton of Toxoplasma gondii, an important human parasite, contains at least five distinct tubulin-based structures. In this work, we define the differential localization of proteins along the cortical microtubules of T. gondii, established during daughter biogenesis and regulated by protein expression and exchange. These proteins distinguish cortical from mitotic spindle microtubules, even though the assembly of these subsets is contemporaneous during cell division. Finally, proteins associated with cortical microtubules collectively protect the stability of the polymers with a remarkable degree of functional redundancy. PMID:26680740

  11. Structure of a two-CAP-domain protein from the human hookworm parasite Necator americanus

    SciTech Connect

    Asojo, Oluwatoyin A.

    2011-05-01

    The first structure of a two-CAP-domain protein, Na-ASP-1, from the major human hookworm parasite N. americanus refined to a resolution limit of 2.2 Å is presented. Major proteins secreted by the infective larval stage hookworms upon host entry include Ancylostoma secreted proteins (ASPs), which are characterized by one or two CAP (cysteine-rich secretory protein/antigen 5/pathogenesis related-1) domains. The CAP domain has been reported in diverse phylogenetically unrelated proteins, but has no confirmed function. The first structure of a two-CAP-domain protein, Na-ASP-1, from the major human hookworm parasite Necator americanus was refined to a resolution limit of 2.2 Å. The structure was solved by molecular replacement (MR) using Na-ASP-2, a one-CAP-domain ASP, as the search model. The correct MR solution could only be obtained by truncating the polyalanine model of Na-ASP-2 and removing several loops. The structure reveals two CAP domains linked by an extended loop. Overall, the carboxyl-terminal CAP domain is more similar to Na-ASP-2 than to the amino-terminal CAP domain. A large central cavity extends from the amino-terminal CAP domain to the carboxyl-terminal CAP domain, encompassing the putative CAP-binding cavity. The putative CAP-binding cavity is a characteristic cavity in the carboxyl-terminal CAP domain that contains a His and Glu pair. These residues are conserved in all single-CAP-domain proteins, but are absent in the amino-terminal CAP domain. The conserved His residues are oriented such that they appear to be capable of directly coordinating a zinc ion as observed for CAP proteins from reptile venoms. This first structure of a two-CAP-domain ASP can serve as a template for homology modeling of other two-CAP-domain proteins.

  12. Effect of glycolipids of Leishmania parasites on human monocyte activity. Inhibition by lipophosphoglycan.

    PubMed

    Frankenburg, S; Leibovici, V; Mansbach, N; Turco, S J; Rosen, G

    1990-12-15

    Lipophosphoglycan (LPG) and glycosyl phosphatidylinositol Ag (GPI), are glycolipids present on the membrane of Leishmania parasites. Both glycolipids have been chemically characterized. LPG is a polysaccharide of repeating phosphorylated units linked to a phosphocarbohydrate core that is anchored to the membrane by lysoalkyl phosphatidylinositol (PI). The GPI are smaller glycolipids with a structure resembling the phosphocarbohydrate core of the LPG. They are anchored to the membrane by alkyl acyl PI. Their relative abundance, uniqueness of structure, and cellular location suggest a role in interactions of the parasites with host cells. In the present study we examined the effect of LPG and GPI on the activation of human peripheral blood monocytes. Three parameters were studied: the production of IL-1, chemotactic locomotion, and oxidative burst. We found that whereas neither GPI nor LPG directly affected monocyte activity, preincubation of the monocytes with LPG strongly inhibited further activation: The production of IL-1, after stimulation with LPS, was decreased in a dose-dependent manner. Previous incubation with LPG also inhibited chemotactic locomotion of monocytes and neutrophils in response to diacylglycerol, zymosan-activated serum, FMLP and LTB4. Luminol-dependent chemiluminiscence caused by stimulation of the monocytes with streptococci and histone was also inhibited. After fragmentation of the LPG into phosphoglycan and 1-O-alkylglycerol by phosphatidylinositol-phospholipase C, only the phosphoglycan retained inhibitory activity. No difference in inhibitory activity was found between LPG prepared from Leishmania major or Leishmania donovani promastigotes. These results show that the phosphoglycan of LPG inhibits the immunologic response of normal human monocytes and neutrophils, and suggest that LPG may influence the nature of the inflammatory response surrounding infected cells. PMID:2147940

  13. An Isochore-Like Structure in the Genome of the Flatworm Schistosoma mansoni

    PubMed Central

    Lamolle, Guillermo; Protasio, Anna V.; Iriarte, Andrés; Jara, Eugenio; Simón, Diego; Musto, Héctor

    2016-01-01

    Eukaryotic genomes are compositionally heterogeneous, that is, composed by regions that differ in guanine–cytosine (GC) content (isochores). The most well documented case is that of vertebrates (mainly mammals) although it has been also noted among unicellular eukaryotes and invertebrates. In the human genome, regarded as a typical mammal, this heterogeneity is associated with several features. Specifically, genes located in GC-richest regions are the GC3-richest, display CpG islands and have shorter introns. Furthermore, these genes are more heavily expressed and tend to be located at the extremes of the chromosomes. Although the compositional heterogeneity seems to be widespread among eukaryotes, the associated properties noted in the human genome and other mammals have not been investigated in depth in other taxa. Here we provide evidence that the genome of the parasitic flatworm Schistosoma mansoni is compositionally heterogeneous and exhibits an isochore-like structure, displaying some features associated, until now, only with the human and other vertebrate genomes, with the exception of gene concentration. PMID:27435793

  14. An Isochore-Like Structure in the Genome of the Flatworm Schistosoma mansoni.

    PubMed

    Lamolle, Guillermo; Protasio, Anna V; Iriarte, Andrés; Jara, Eugenio; Simón, Diego; Musto, Héctor

    2016-01-01

    Eukaryotic genomes are compositionally heterogeneous, that is, composed by regions that differ in guanine-cytosine (GC) content (isochores). The most well documented case is that of vertebrates (mainly mammals) although it has been also noted among unicellular eukaryotes and invertebrates. In the human genome, regarded as a typical mammal, this heterogeneity is associated with several features. Specifically, genes located in GC-richest regions are the GC3-richest, display CpG islands and have shorter introns. Furthermore, these genes are more heavily expressed and tend to be located at the extremes of the chromosomes. Although the compositional heterogeneity seems to be widespread among eukaryotes, the associated properties noted in the human genome and other mammals have not been investigated in depth in other taxa Here we provide evidence that the genome of the parasitic flatworm Schistosoma mansoni is compositionally heterogeneous and exhibits an isochore-like structure, displaying some features associated, until now, only with the human and other vertebrate genomes, with the exception of gene concentration. PMID:27435793

  15. FMRFamide-like peptides (FLPs) enhance voltage-gated calcium currents to elicit muscle contraction in the human parasite Schistosoma mansoni.

    PubMed

    Novozhilova, Ekaterina; Kimber, Michael J; Qian, Hai; McVeigh, Paul; Robertson, Alan P; Zamanian, Mostafa; Maule, Aaron G; Day, Tim A

    2010-01-01

    Schistosomes are amongst the most important and neglected pathogens in the world, and schistosomiasis control relies almost exclusively on a single drug. The neuromuscular system of schistosomes is fertile ground for therapeutic intervention, yet the details of physiological events involved in neuromuscular function remain largely unknown. Short amidated neuropeptides, FMRFamide-like peptides (FLPs), are distributed abundantly throughout the nervous system of every flatworm examined and they produce potent myoexcitation. Our goal here was to determine the mechanism by which FLPs elicit contractions of schistosome muscle fibers. Contraction studies showed that the FLP Tyr-Ile-Arg-Phe-amide (YIRFamide) contracts the muscle fibers through a mechanism that requires Ca(2+) influx through sarcolemmal voltage operated Ca(2+) channels (VOCCs), as the contractions are inhibited by classical VOCC blockers nicardipine, verapamil and methoxyverapamil. Whole-cell patch-clamp experiments revealed that inward currents through VOCCs are significantly and reversibly enhanced by the application of 1 microM YIRFamide; the sustained inward currents were increased to 190% of controls and the peak currents were increased to 180%. In order to examine the biochemical link between the FLP receptor and the VOCCs, PKC inhibitors calphostin C, RO 31-8220 and chelerythrine were tested and all produced concentration dependent block of the contractions elicited by 1 microM YIRFamide. Taken together, the data show that FLPs elicit contractions by enhancing Ca(2+) influx through VOCC currents using a PKC-dependent pathway. PMID:20706630

  16. 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. PMID:21232174

  17. Parasites, Plants, and People.

    PubMed

    Johnson, Marion; Moore, Tony

    2016-06-01

    Anthelminthic resistance is acknowledged worldwide and is a major problem in Aotearoa New Zealand, thus alternative parasite management strategies are imperative. One Health is an initiative linking animal, human, and environmental health. Parasites, plants, and people illustrate the possibilities of providing diverse diets for stock thereby lowering parasite burdens, improving the cultural wellbeing of a local community, and protecting the environment. PMID:27105933

  18. Macrophage-derived human resistin is induced in multiple helminth infections and promotes inflammatory monocytes and increased parasite burden.

    PubMed

    Jang, Jessica C; Chen, Gang; Wang, Spencer H; Barnes, Mark A; Chung, Josiah I; Camberis, Mali; Le Gros, Graham; Cooper, Philip J; Steel, Cathy; Nutman, Thomas B; Lazar, Mitchell A; Nair, Meera G

    2015-01-01

    Parasitic helminth infections can be associated with lifelong morbidity such as immune-mediated organ failure. A better understanding of the host immune response to helminths could provide new avenues to promote parasite clearance and/or alleviate infection-associated morbidity. Murine resistin-like molecules (RELM) exhibit pleiotropic functions following helminth infection including modulating the host immune response; however, the relevance of human RELM proteins in helminth infection is unknown. To examine the function of human resistin (hResistin), we utilized transgenic mice expressing the human resistin gene (hRetnTg+). Following infection with the helminth Nippostrongylus brasiliensis (Nb), hResistin expression was significantly upregulated in infected tissue. Compared to control hRetnTg- mice, hRetnTg+ mice suffered from exacerbated Nb-induced inflammation characterized by weight loss and increased infiltration of inflammatory monocytes in the lung, along with elevated Nb egg burdens and delayed parasite expulsion. Genome-wide transcriptional profiling of the infected tissue revealed that hResistin promoted expression of proinflammatory cytokines and genes downstream of toll-like receptor signaling. Moreover, hResistin preferentially bound lung monocytes, and exogenous treatment of mice with recombinant hResistin promoted monocyte recruitment and proinflammatory cytokine expression. In human studies, increased serum resistin was associated with higher parasite load in individuals infected with soil-transmitted helminths or filarial nematode Wuchereria bancrofti, and was positively correlated with proinflammatory cytokines. Together, these studies identify human resistin as a detrimental factor induced by multiple helminth infections, where it promotes proinflammatory cytokines and impedes parasite clearance. Targeting the resistin/proinflammatory cytokine immune axis may provide new diagnostic or treatment strategies for helminth infection and associated

  19. Macrophage-Derived Human Resistin Is Induced in Multiple Helminth Infections and Promotes Inflammatory Monocytes and Increased Parasite Burden

    PubMed Central

    Jang, Jessica C.; Chen, Gang; Wang, Spencer H.; Barnes, Mark A.; Chung, Josiah I.; Camberis, Mali; Le Gros, Graham; Cooper, Philip J.; Steel, Cathy; Nutman, Thomas B.; Lazar, Mitchell A.; Nair, Meera G.

    2015-01-01

    Parasitic helminth infections can be associated with lifelong morbidity such as immune-mediated organ failure. A better understanding of the host immune response to helminths could provide new avenues to promote parasite clearance and/or alleviate infection-associated morbidity. Murine resistin-like molecules (RELM) exhibit pleiotropic functions following helminth infection including modulating the host immune response; however, the relevance of human RELM proteins in helminth infection is unknown. To examine the function of human resistin (hResistin), we utilized transgenic mice expressing the human resistin gene (hRetnTg+). Following infection with the helminth Nippostrongylus brasiliensis (Nb), hResistin expression was significantly upregulated in infected tissue. Compared to control hRetnTg− mice, hRetnTg+ mice suffered from exacerbated Nb-induced inflammation characterized by weight loss and increased infiltration of inflammatory monocytes in the lung, along with elevated Nb egg burdens and delayed parasite expulsion. Genome-wide transcriptional profiling of the infected tissue revealed that hResistin promoted expression of proinflammatory cytokines and genes downstream of toll-like receptor signaling. Moreover, hResistin preferentially bound lung monocytes, and exogenous treatment of mice with recombinant hResistin promoted monocyte recruitment and proinflammatory cytokine expression. In human studies, increased serum resistin was associated with higher parasite load in individuals infected with soil-transmitted helminths or filarial nematode Wuchereria bancrofti, and was positively correlated with proinflammatory cytokines. Together, these studies identify human resistin as a detrimental factor induced by multiple helminth infections, where it promotes proinflammatory cytokines and impedes parasite clearance. Targeting the resistin/proinflammatory cytokine immune axis may provide new diagnostic or treatment strategies for helminth infection and associated

  20. Draft genome of neurotropic nematode parasite Angiostrongylus cantonensis, causative agent of human eosinophilic meningitis.

    PubMed

    Yong, Hoi-Sen; Eamsobhana, Praphathip; Lim, Phaik-Eem; Razali, Rozaimi; Aziz, Farhanah Abdul; Rosli, Nurul Shielawati Mohamed; Poole-Johnson, Johan; Anwar, Arif

    2015-08-01

    Angiostrongylus cantonensis is a bursate nematode parasite that causes eosinophilic meningitis (or meningoencephalitis) in humans in many parts of the world. The genomic data from A. cantonensis will form a useful resource for comparative genomic and chemogenomic studies to aid the development of diagnostics and therapeutics. We have sequenced, assembled and annotated the genome of A. cantonensis. The genome size is estimated to be ∼260 Mb, with 17,280 genomic scaffolds, 91X coverage, 81.45% for complete and 93.95% for partial score based on CEGMA analysis of genome completeness. The number of predicted genes of ≥300 bp was 17,482. A total of 7737 predicted protein-coding genes of ≥50 amino acids were identified in the assembled genome. Among the proteins of known function, kinases are the most abundant followed by transferases. The draft genome contains 34 excretory-secretory proteins (ES), a minimum of 44 Nematode Astacin (NAS) metalloproteases, 12 Homeobox (HOX) genes, and 30 neurotransmitters. The assembled genome size (260 Mb) is larger than those of Pristionchus pacificus, Caenorhabditis elegans, Necator americanus, Caenorhabditis briggsae, Trichinella spiralis, Brugia malayi and Loa loa, but smaller than Haemonchus contortus and Ascaris suum. The repeat content (25%) is similar to H. contortus. The GC content (41.17%) is lower compared to P. pacificus (42.7%) and H. contortus (43.1%) but higher compared to C. briggsae (37.69%), A. suum (37.9%) and N. americanus (40.2%) while the scaffold N50 is 42,191. This draft genome will facilitate the understanding of many unresolved issues on the parasite and the disorder it causes. PMID:25910624

  1. DNA typing of ancient parasite eggs from environmental samples identifies human and animal worm infections in Viking-age settlement.

    PubMed

    Søe, Martin Jensen; Nejsum, Peter; Fredensborg, Brian Lund; Kapel, Christian Moliin Outzen

    2015-02-01

    Ancient parasite eggs were recovered from environmental samples collected at a Viking-age settlement in Viborg, Denmark, dated 1018-1030 A.D. Morphological examination identified Ascaris sp., Trichuris sp., and Fasciola sp. eggs, but size and shape did not allow species identification. By carefully selecting genetic markers, PCR amplification and sequencing of ancient DNA (aDNA) isolates resulted in identification of: the human whipworm, Trichuris trichiura , using SSUrRNA sequence homology; Ascaris sp. with 100% homology to cox1 haplotype 07; and Fasciola hepatica using ITS1 sequence homology. The identification of T. trichiura eggs indicates that human fecal material is present and, hence, that the Ascaris sp. haplotype 07 was most likely a human variant in Viking-age Denmark. The location of the F. hepatica finding suggests that sheep or cattle are the most likely hosts. Further, we sequenced the Ascaris sp. 18S rRNA gene in recent isolates from humans and pigs of global distribution and show that this is not a suited marker for species-specific identification. Finally, we discuss ancient parasitism in Denmark and the implementation of aDNA analysis methods in paleoparasitological studies. We argue that when employing species-specific identification, soil samples offer excellent opportunities for studies of human parasite infections and of human and animal interactions of the past. PMID:25357228

  2. Schistosoma mansoni and Biomphalaria: past history and future trends.

    PubMed

    Morgan, J A; Dejong, R J; Snyder, S D; Mkoji, G M; Loker, E S

    2001-01-01

    Schistosoma mansoni is one of the most abundant infectious agents of humankind. Its widespread distribution is permitted by the broad geographic range of susceptible species of the freshwater snail genus Biomphalaria that serve as obligatory hosts for its larval stages. Molecular phylogenetic studies suggest that Schistosoma originated in Asia, and that a pulmonate-transmitted progenitor colonized Africa and gave rise to both terminal-spined and lateral-spined egg species groups, the latter containing S. mansoni. Schistosoma mansoni likely appeared only after the trans-Atlantic dispersal of Biomphalaria from the Neotropics to Africa, an event that, based on the present African fossil record, occurred only 2-5 million years ago. This parasite became abundant in tropical Africa and then entered the New World with the slave trade. It prospered in the Neotropics because a remarkably susceptible and productive host, B. glabrata, was widely distributed there. Indeed, a snail similar to B. glabrata may have given rise to the African species of Biomphalaria. Schistosoma mansoni has since spread into other Neotropical Biomphalaria species and mammalian hosts. The distribution of S. mansoni is in a state of flux. In Egypt, S. mansoni has nearly completely replaced S. haematobium in the Nile Delta, and has spread to other regions of the country. A susceptible host snail, B. straminea, has been introduced into Asia and there is evidence of S. mansoni transmission in Nepal. Dam and barrage construction has lead to an epidemic of S. mansoni in Senegal, and the parasite continues its spread in Brazil. Because of competition with introduced aquatic species and environmental changes, B. glabrata and consequently S. mansoni have become less abundant on the Caribbean islands. Control of S. mansoni using praziquantel and oxamniquine has reduced global prevalence but control is difficult to sustain, and S. mansoni can develop tolerance/resistance to praziquantel, raising concerns about

  3. Molecular and functional characterization of macrophage migration inhibitory factor (MIF) homolog of human from lymphatic filarial parasite Wuchereria bancrofti.

    PubMed

    Sharma, Rohit; Hoti, S L; Meena, R L; Vasuki, V; Sankari, T; Kaliraj, P

    2012-11-01

    The ability of nematode parasites to survive in a highly complex immune system involves diverse strategies including production of a variety of host immune modulators. Various parasite-associated surface antigens or excretory and secretory products may possibly play a role in the host-parasite interactions and successful survival of parasite in their respective host. One among these molecules is a human cytokine homolog, macrophage migration inhibitory factor-1 (MIF-1) in various parasites. We identified a homolog of this cytokine from human lymphatic filarial parasite, Wuchereria bancrofti, expression cloned and investigated its molecular characteristics and catalytic properties. We also assessed the humoral reactivity of the recombinant MIF-1 of W. bancrofti (rWb-MIF-1) against sera belonging to different categories of individuals viz. microfilaremic, chronic patients, endemic normal, and non-endemic normal. Our results showed that the complete coding sequence of W. bancrofti is 1,078 bp, comprising two introns and three exons: first and second introns being 577 and 153 bp long, while the three exons I, II, and III being 108, 173, and 67 bp long, respectively. The rWb-MIF-1 was overexpressed in a salt-inducible host, Escherichia coli GJ 1158, and its functional activity was determined by dopachrome tautomerase and insulin reduction assays. The results of both the assays showed that the purified protein is functionally active and hence folded appropriately. The rWb-MIF-1 protein did not show elevation of specific IgG4 antibodies in microfilaremic cases, a hallmark in case of lymphatic filariasis, while it showed IgE reactivity in some of these cases (five out of ten). PMID:22875393

  4. The Interaction of Classical Complement Component C1 with Parasite and Host Calreticulin Mediates Trypanosoma cruzi Infection of Human Placenta

    PubMed Central

    Castillo, Christian; Ramírez, Galia; Valck, Carolina; Aguilar, Lorena; Maldonado, Ismael; Rosas, Carlos; Galanti, Norbel; Kemmerling, Ulrike; Ferreira, Arturo

    2013-01-01

    Background 9 million people are infected with Trypanosoma cruzi in Latin America, plus more than 300,000 in the United States, Canada, Europe, Australia, and Japan. Approximately 30% of infected individuals develop circulatory or digestive pathology. While in underdeveloped countries transmission is mainly through hematophagous arthropods, transplacental infection prevails in developed ones. Methodology/Principal Findings During infection, T. cruzi calreticulin (TcCRT) translocates from the endoplasmic reticulum to the area of flagellum emergence. There, TcCRT acts as virulence factor since it binds maternal classical complement component C1q that recognizes human calreticulin (HuCRT) in placenta, with increased parasite infectivity. As measured ex vivo by quantitative PCR in human placenta chorionic villi explants (HPCVE) (the closest available correlate of human congenital T. cruzi infection), C1q mediated up to a 3–5-fold increase in parasite load. Because anti-TcCRT and anti-HuCRT F(ab′)2 antibody fragments are devoid of their Fc-dependent capacity to recruit C1q, they reverted the C1q-mediated increase in parasite load by respectively preventing its interaction with cell-bound CRTs from both parasite and HPCVE origins. The use of competing fluid-phase recombinant HuCRT and F(ab′)2 antibody fragments anti-TcCRT corroborated this. These results are consistent with a high expression of fetal CRT on placental free chorionic villi. Increased C1q-mediated infection is paralleled by placental tissue damage, as evidenced by histopathology, a damage that is ameliorated by anti-TcCRT F(ab′)2 antibody fragments or fluid-phase HuCRT. Conclusions/Significance T. cruzi infection of HPCVE is importantly mediated by human and parasite CRTs and C1q. Most likely, C1q bridges CRT on the parasite surface with its receptor orthologue on human placental cells, thus facilitating the first encounter between the parasite and the fetal derived placental tissue. The results

  5. DETC Induces Leishmania Parasite Killing in Human In Vitro and Murine In Vivo Models: A Promising Therapeutic Alternative in Leishmaniasis

    PubMed Central

    Khouri, Ricardo; Novais, Fernanda; Santana, Gisélia; de Oliveira, Camila Indiani; Vannier dos Santos, Marcos André; Barral, Aldina; Barral-Netto, Manoel; Van Weyenbergh, Johan

    2010-01-01

    Background Chemotherapy remains the primary tool for treatment and control of human leishmaniasis. However, currently available drugs present serious problems regarding side-effects, variable efficacy, and cost. Affordable and less toxic drugs are urgently needed for leishmaniasis. Methodology/Principal Findings We demonstrate, by microscopy and viability assays, that superoxide dismutase inhibitor diethyldithiocarbamate (DETC) dose-dependently induces parasite killing (p<0.001) and is able to “sterilize” Leishmania amazonensis infection at 2 mM in human macrophages in vitro. We also show that DETC-induced superoxide production (p<0.001) and parasite destruction (p<0.05) were reverted by the addition of the antioxidant N-acetylcysteine, indicating that DETC-induced killing occurs through oxidative damage. Furthermore, ultrastructural analysis by electron microscopy demonstrates a rapid and highly selective destruction of amastigotes in the phagosome upon DETC treatment, without any apparent damage to the host cell, including its mitochondria. In addition, DETC significantly induced parasite killing in Leishmania promastigotes in axenic culture. In murine macrophages infected with Leishmania braziliensis, DETC significantly induced in vitro superoxide production (p = 0.0049) and parasite killing (p = 0.0043). In vivo treatment with DETC in BALB/C mice infected with Leishmania braziliensis caused a significant decrease in lesion size (p<0.0001), paralleled by a 100-fold decrease (p = 0.0087) in parasite burden. Conclusions/Significance Due to its strong leishmanicidal effect in human macrophages in vitro, its in vivo effectiveness in a murine model, and its previously demonstrated in vivo safety profile in HIV treatment, DETC treatment might be considered as a valuable therapeutic option in human leishmaniasis, including HIV/Leishmania co-infection. PMID:21200432

  6. Use of Geospatial Modeling to Predict Schistosoma mansoni Prevalence in Nyanza Province, Kenya

    PubMed Central

    Woodhall, Dana M.; Wiegand, Ryan E.; Wellman, Michael; Matey, Elizabeth; Abudho, Bernard; Karanja, Diana M. S.; Mwinzi, Pauline M. N.; Montgomery, Susan P.; Secor, W. Evan

    2013-01-01

    Background Schistosomiasis, a parasitic disease that affects over 200 million people, can lead to significant morbidity and mortality; distribution of single dose preventative chemotherapy significantly reduces disease burden. Implementation of control programs is dictated by disease prevalence rates, which are determined by costly and labor intensive screening of stool samples. Because ecological and human factors are known to contribute to the focal distribution of schistosomiasis, we sought to determine if specific environmental and geographic factors could be used to accurately predict Schistosoma mansoni prevalence in Nyanza Province, Kenya. Methodology/Principal Findings A spatial mixed model was fit to assess associations with S. mansoni prevalence in schools. Data on S. mansoni prevalence and GPS location of the school were obtained from 457 primary schools. Environmental and geographic data layers were obtained from publicly available sources. Spatial models were constructed using ArcGIS 10 and R 2.13.0. Lower S.mansoni prevalence was associated with further distance (km) to Lake Victoria, higher day land surface temperature (LST), and higher monthly rainfall totals. Altitude, night LST, human influence index, normalized difference vegetation index, soil pH, soil texture, soil bulk density, soil water capacity, population, and land use variables were not significantly associated with S. mansoni prevalence. Conclusions Our model suggests that there are specific environmental and geographic factors that influence S. mansoni prevalence rates in Nyanza Province, Kenya. Validation and use of schistosomiasis prevalence maps will allow control programs to plan and prioritize efficient control campaigns to decrease schistosomiasis burden. PMID:23977096

  7. Parasites of importance for human health in Nigerian dogs: high prevalence and limited knowledge of pet owners

    PubMed Central

    Ugbomoiko, Uade Samuel; Ariza, Liana; Heukelbach, Jorg

    2008-01-01

    Background Dogs are the most common pet animals worldwide. They may harbour a wide range of parasites with zoonotic potential, thus causing a health risk to humans. In Nigeria, epidemiological knowledge on these parasites is limited. Methods In a community-based study, we examined 396 dogs in urban and rural areas of Ilorin (Kwara State, Central Nigeria) for ectoparasites and intestinal helminths. In addition, a questionnaire regarding knowledge and practices was applied to pet owners. Results Nine ectoparasite species belonging to four taxa and six intestinal helminth species were identified: fleas (Ctenocephalides canis, Pulex irritans, Tunga penetrans), mites (Demodex canis, Otodectes sp., Sarcoptes scabiei var. canis), ticks (Rhipicephalus sanguineus, Ixodes sp.), and lice (Trichodectes canis); and Toxocara canis, Ancylostoma sp., Trichuris vulpis, Dipylidium caninum, Taenidae and Strongyloides sp. Overall prevalence of ectoparasites was 60.4% and of intestinal helminths 68.4%. The occurrence of C. canis, R. sanguineus, T. canis, Ancylostoma sp. and T. vulpis was most common (prevalence 14.4% to 41.7%). Prevalence patterns in helminths were age-dependent, with T. canis showing a decreasing prevalence with age of host, and a reverse trend in other parasite species. Knowledge regarding zoonoses was very limited and the diseases not considered a major health problem. Treatment with antiparasitic drugs was more frequent in urban areas. Conclusion Parasites of importance for human health were highly prevalent in Nigerian dogs. Interventions should include health education provided to dog owners and the establishment of a program focusing on zoonotic diseases. PMID:19068110

  8. Structure, Function and Inhibition of the Phosphoethanolamine Methyltransferases of the Human Malaria Parasites Plasmodium vivax and Plasmodium knowlesi

    PubMed Central

    Garg, Aprajita; Lukk, Tiit; Kumar, Vidya; Choi, Jae-Yeon; Augagneur, Yoann; Voelker, Dennis R.; Nair, Satish; Mamoun, Choukri Ben

    2015-01-01

    Phosphoethanolamine methyltransferases (PMTs) catalyze the three-step methylation of phosphoethanolamine to form phosphocholine, a critical step in the synthesis of phosphatidylcholine in a select number of eukaryotes including human malaria parasites, nematodes and plants. Genetic studies in the malaria parasite Plasmodium falciparum have shown that the methyltransferase PfPMT plays a critical function in parasite development and differentiation. The presence of PMT orthologs in other malaria parasites that infect humans and their absence in mammals make them ideal targets for the development of selective antimalarials with broad specificity against different Plasmodium species. Here we describe the X-ray structures and biochemical properties of PMT orthologs from Plasmodium vivax and Plasmodium knowlesi and show that both enzymes are inhibited by amodiaquine and NSC158011, two drugs with potent antimalarial activity. Metabolic studies in a yeast mutant that relies on PkPMT or PvPMT for survival demonstrated that these compounds inhibit phosphatidylcholine biosynthesis from ethanolamine. Our structural and functional data provide insights into the mechanism of catalysis and inhibition of PMT enzymes and set the stage for a better design of more specific and selective antimalarial drugs. PMID:25761669

  9. Structure, Function and Inhibition of the Phosphoethanolamine Methyltransferases of the Human Malaria Parasites Plasmodium vivax and Plasmodium knowlesi

    SciTech Connect

    Garg, Aprajita; Lukk, Tiit; Kumar, Vidya; Choi, Jae-Yeon; Augagneur, Yoann; Voelker, Dennis R.; Nair, Satish; Mamoun, Choukri Ben

    2015-03-12

    Phosphoethanolamine methyltransferases (PMTs) catalyze the three-step methylation of phosphoethanolamine to form phosphocholine, a critical step in the synthesis of phosphatidylcholine in a select number of eukaryotes including human malaria parasites, nematodes and plants. Genetic studies in the malaria parasite Plasmodium falciparum have shown that the methyltransferase PfPMT plays a critical function in parasite development and differentiation. The presence of PMT orthologs in other malaria parasites that infect humans and their absence in mammals make them ideal targets for the development of selective antimalarials with broad specificity against different Plasmodium species. Here we describe the X-ray structures and biochemical properties of PMT orthologs from Plasmodium vivax and Plasmodium knowlesi and show that both enzymes are inhibited by amodiaquine and NSC158011, two drugs with potent antimalarial activity. Metabolic studies in a yeast mutant that relies on PkPMT or PvPMT for survival demonstrated that these compounds inhibit phosphatidylcholine biosynthesis from ethanolamine. Our structural and functional data provide insights into the mechanism of catalysis and inhibition of PMT enzymes and set the stage for a better design of more specific and selective antimalarial drugs.

  10. Structure, Function and Inhibition of the Phosphoethanolamine Methyltransferases of the Human Malaria Parasites Plasmodium vivax and Plasmodium knowlesi

    DOE PAGESBeta

    Garg, Aprajita; Lukk, Tiit; Kumar, Vidya; Choi, Jae-Yeon; Augagneur, Yoann; Voelker, Dennis R.; Nair, Satish; Mamoun, Choukri Ben

    2015-03-12

    Phosphoethanolamine methyltransferases (PMTs) catalyze the three-step methylation of phosphoethanolamine to form phosphocholine, a critical step in the synthesis of phosphatidylcholine in a select number of eukaryotes including human malaria parasites, nematodes and plants. Genetic studies in the malaria parasite Plasmodium falciparum have shown that the methyltransferase PfPMT plays a critical function in parasite development and differentiation. The presence of PMT orthologs in other malaria parasites that infect humans and their absence in mammals make them ideal targets for the development of selective antimalarials with broad specificity against different Plasmodium species. Here we describe the X-ray structures and biochemical properties ofmore » PMT orthologs from Plasmodium vivax and Plasmodium knowlesi and show that both enzymes are inhibited by amodiaquine and NSC158011, two drugs with potent antimalarial activity. Metabolic studies in a yeast mutant that relies on PkPMT or PvPMT for survival demonstrated that these compounds inhibit phosphatidylcholine biosynthesis from ethanolamine. Our structural and functional data provide insights into the mechanism of catalysis and inhibition of PMT enzymes and set the stage for a better design of more specific and selective antimalarial drugs.« less

  11. Structure of a Protozoan Virus from the Human Genitourinary Parasite Trichomonas vaginalis

    PubMed Central

    Parent, Kristin N.; Takagi, Yuko; Cardone, Giovanni; Olson, Norman H.; Ericsson, Maria; Yang, May; Lee, Yujin; Asara, John M.; Fichorova, Raina N.; Baker, Timothy S.; Nibert, Max L.

    2013-01-01

    ABSTRACT The flagellated protozoan Trichomonas vaginalis is an obligate human genitourinary parasite and the most frequent cause of sexually transmitted disease worldwide. Most clinical isolates of T. vaginalis are persistently infected with one or more double-stranded RNA (dsRNA) viruses from the genus Trichomonasvirus, family Totiviridae, which appear to influence not only protozoan biology but also human disease. Here we describe the three-dimensional structure of Trichomonas vaginalis virus 1 (TVV1) virions, as determined by electron cryomicroscopy and icosahedral image reconstruction. The structure reveals a T = 1 capsid comprising 120 subunits, 60 in each of two nonequivalent positions, designated A and B, as previously observed for fungal Totiviridae family members. The putative protomer is identified as an asymmetric AB dimer consistent with either decamer or tetramer assembly intermediates. The capsid surface is notable for raised plateaus around the icosahedral 5-fold axes, with canyons connecting the 2- and 3-fold axes. Capsid-spanning channels at the 5-fold axes are unusually wide and may facilitate release of the viral genome, promoting dsRNA-dependent immunoinflammatory responses, as recently shown upon the exposure of human cervicovaginal epithelial cells to either TVV-infected T. vaginalis or purified TVV1 virions. Despite extensive sequence divergence, conservative features of the capsid reveal a helix-rich fold probably derived from an ancestor shared with fungal Totiviridae family members. Also notable are mass spectrometry results assessing the virion proteins as a complement to structure determination, which suggest that translation of the TVV1 RNA-dependent RNA polymerase in fusion with its capsid protein involves −2, and not +1, ribosomal frameshifting, an uncommonly found mechanism to date. PMID:23549915

  12. Functional Analysis of Protein Kinase CK2 of the Human Malaria Parasite Plasmodium falciparum▿ †

    PubMed Central

    Holland, Zoë; Prudent, Renaud; Reiser, Jean-Baptiste; Cochet, Claude; Doerig, Christian

    2009-01-01

    Protein kinase CK2 (casein kinase 2) is a eukaryotic serine/threonine protein kinase with multiple substrates and roles in diverse cellular processes, including differentiation, proliferation, and translation. The mammalian holoenzyme consists of two catalytic alpha or alpha′ subunits and two regulatory beta subunits. We report the identification and characterization of a Plasmodium falciparum CK2α orthologue, PfCK2α, and two PfCK2β orthologues, PfCK2β1 and PfCK2β2. Recombinant PfCK2α possesses protein kinase activity, exhibits similar substrate and cosubstrate preferences to those of CK2α subunits from other organisms, and interacts with both of the PfCK2β subunits in vitro. Gene disruption experiments show that the presence of PfCK2α is crucial to asexual blood stage parasites and thereby validate the enzyme as a possible drug target. PfCK2α is amenable to inhibitor screening, and we report differential susceptibility between the human and P. falciparum CK2α enzymes to a small molecule inhibitor. Taken together, our data identify PfCK2α as a potential target for antimalarial chemotherapeutic intervention. PMID:19114502

  13. Polysome profiling reveals translational control of gene expression in the human malaria parasite Plasmodium falciparum

    PubMed Central

    2013-01-01

    Background In eukaryotic organisms, gene expression is regulated at multiple levels during the processes of transcription and translation. The absence of a tight regulatory network for transcription in the human malaria parasite suggests that gene expression may largely be controlled at post-transcriptional and translational levels. Results In this study, we compare steady-state mRNA and polysome-associated mRNA levels of Plasmodium falciparum at different time points during its asexual cell cycle. For more than 30% of its genes, we observe a delay in peak transcript abundance in the polysomal fraction as compared to the steady-state mRNA fraction, suggestive of strong translational control. Our data show that key regulatory mechanisms could include inhibitory activity of upstream open reading frames and translational repression of the major virulence gene family by intronic transcripts. In addition, we observe polysomal mRNA-specific alternative splicing events and widespread transcription of non-coding transcripts. Conclusions These different layers of translational regulation are likely to contribute to a complex network that controls gene expression in this eukaryotic pathogen. Disrupting the mechanisms involved in such translational control could provide novel anti-malarial strategies. PMID:24267660

  14. The pattern of parasitic infection in human gut at the Specialist Hospital, Benin City, Nigeria.

    PubMed

    Obiamiwe, B A

    1977-03-01

    In a survey of 6213 persons conducted between January 1973 to December 1974, at the Specialist Hospital, Benin City, the most common helminths were Necator americanus (16.8%), Ascaris lumbricoides (19l5%) and Trichuris trichiur (5-9%). Dicrocoelium hospes (0-06%) was also recorded and this may become an important liver parasite of man in Nigeria. Its snail vectors are believed to be species of Limicolaria and Achatina which are widely dispersed in Nigeria. Entamoeba coli and E. histolytica showed peaks during the "fly seasons", indicating that the housefly, as well as water, may be an important source of contamination. Trichomonas hominis showed peaks in the rainy seasons, and this suggests that in Benin City transmission is chiefly via contaminated domestic water-supply. The incidence of A. lumbricoides and N. americanus was high throughout the rainy and dry seasons, indicating poor disposal of human excreta and a continuous pattern of infection. The type of food and method of cooking prevented or reduced the incidence of Taenia solium, T. saginata, Diphyllobothrium latum and Fasciola gigantica. PMID:849017

  15. Role of adult worm antigen-specific immunoglobulin E in acquired immunity to Schistosoma mansoni infection in baboons.

    PubMed

    Nyindo, M; Kariuki, T M; Mola, P W; Farah, I O; Elson, L; Blanton, R E; King, C L

    1999-02-01

    Allergic-type immune responses, particularly immunoglobulin E (IgE), correlate with protective immunity in human schistosomiasis. To better understand the mechanisms of parasite elimination we examined the immune correlates of protection in baboons (Papio cynocephalus anubis), which are natural hosts for Schistosoma mansoni and also develop allergic-type immunity with infection. In one experiment, animals were exposed to a single infection (1,000 cercariae) or were exposed multiple times (100 cercariae per week for 10 weeks) and subsequently were cured with praziquantel prior to challenge with 1, 000 cercariae. Singly and multiply infected animals mounted 59 and 80% reductions in worm burden, respectively (P < 0.01). In a second experiment, animals were inoculated with S. mansoni ova and recombinant human interleukin 12 (IL-12). This produced a 37 to 39% reduction in adult worm burden after challenge (P < 0.05). Parasite-specific IgG, IgE, IgM, and peripheral blood cytokine production were evaluated. The only immune correlate of protection in both experiments was levels of soluble adult worm antigen (SWAP)-specific IgE in serum at the time of challenge infection and/or 6 weeks later. Baboons repeatedly infected with cercariae or immunized with ova and IL-12 developed two- to sixfold-greater levels of SWAP-specific IgE in serum than did controls, and this correlated with reductions in worm burden (r2, -0.40 to -0.64; P, <0. 01). Thus, in baboons and unlike mice, adult worm-specific IgE is uniquely associated with acquired immunity to S. mansoni infection. This similar association of parasite-specific IgE and protection among primates infected with schistosomiasis, along with similar pathology, anatomy, and genetic make-up, indicates that baboons provide an excellent permissive experimental model for better understanding the mechanisms of innate and acquired immunity to schistosomiasis in humans. PMID:9916070

  16. Trickle or clumped infection process? A stochastic model for the infection process of the parasitic roundworm of humans, Ascaris lumbricoides.

    PubMed

    Walker, Martin; Hall, Andrew; Basáñez, María-Gloria

    2010-10-01

    The importance of the mode of acquisition of infectious stages of directly-transmitted parasitic helminths has been acknowledged in population dynamics models; hosts may acquire eggs/larvae singly in a "trickle" type manner or in "clumps". Such models have shown that the mode of acquisition influences the distribution and dynamics of parasite loads, the stability of host-parasite systems and the rate of emergence of anthelmintic resistance, yet very few field studies have allowed these questions to be explored with empirical data. We have analysed individual worm weight data for the parasitic roundworm of humans, Ascaris lumbricoides, collected from a three-round chemo-expulsion study in Dhaka, Bangladesh, with the aim of discerning whether a trickle or a clumped infection process predominates. We found that hosts tend to harbour female worms of a similar weight, indicative of a clumped infection process, but acknowledged that unmeasured host heterogeneities (random effects) could not be completely excluded as a cause. Here, we complement our previous statistical analyses using a stochastic infection model to simulate sizes of individual A. lumbricoides infecting a population of humans. We use the intraclass correlation coefficient (ICC) as a quantitative measure of similarity among simulated worm sizes and explore the behaviour of this statistic under assumptions corresponding to trickle or clumped infections and unmeasured host heterogeneities. We confirm that both mechanisms are capable of generating aggregates of similar-sized worms, but that the particular pattern of ICCs described pre- and post-anthelmintic treatment in the data is more consistent with aggregation generated by clumped infections than by host heterogeneities alone. This provides support to the notion that worms may be acquired in clumps. We discuss our results in terms of the population biology of A. lumbricoides and highlight the significance of our modelling approach for the study of the

  17. [A national survey on current status of the important parasitic diseases in human population].

    PubMed

    2005-10-30

    In order to understand the current status and trends of the important parasitic diseases in human population, to evaluate the effect of control activities in the past decade and provide scientific base for further developing control strategies, a national survey was carried out in the country (Taiwan, Hongkong and Macau not included) from June, 2001 to 2004 under the sponsorship of the Ministry of Health. The sample sizes of the nationwide survey and of the survey in each province (autonomous region and municipality, P/A/M) were determined following a calculating formula based on an estimation of the sample size of random sampling to the rate of population. A procedure of stratified cluster random sampling was conducted in each province based on geographical location and economical condition with three strata: county/city, township/town, and spot, each spot covered a sample of 500 people. Parasitological examinations were conducted for the infections of soil-transmitted nematodes, Taenia spp, and Clonorchis sinensis, including Kato-Katz thick smear method, scotch cellulose adhesive tape technique and test tube-filter paper culture (for larvae). At the same time, another sampled investigation for Clonorchis sinensis infection was carried out in the known endemic areas in 27 provinces. Serological tests combined with questionnaire and/or clinical diagnosis were applied for hydatid disease, cysticercosis, paragonimiasis, trichinosis, and toxoplasmosis. A total sampled population of 356 629 from the 31 P/A/M was examined by parasitological methods and 26 species of helminth were recorded. Among these helminth, human infections of Metorchis orientalis and Echinostoma aegypti were detected in Fujian Province which seemed to be the first report in the world, and Haplorchis taichui infection in Guangxi Region was the first human infection record in the country. The overall prevalence of helminth infections was 21.74%. The prevalence of soil-transmitted nematodes was 19

  18. SURVEY OF HOUSE RAT INTESTINAL PARASITES FROM SURABAYA DISTRICT, EAST JAVA, INDONESIA THAT CAN CAUSE OPPORTUNISTIC INFECTIONS IN HUMANS.

    PubMed

    Prasetyo, R H

    2016-03-01

    The purpose of this study was to investigate the prevalence of house rat zoonotic intestinal parasites from Surabaya District, East Java, Indonesia that have the potential to cause opportunistic infection in humans. House rat fecal samples were collected from an area of Surabaya District with a dense rat population during May 2015. Intestinal parasites were detected microscopically using direct smear of feces stained with Lugol's iodine and modified Ziehl-Neelsen stains. The fecal samples were also cultured for Strongyloides stercoralis. Ninety-eight house rat fecal samples were examined. The potential opportunistic infection parasite densities found in those samples were Strongyloides stercoralis in 53%, Hymenolepis nana in 42%, Cryptosporidium spp in 33%, and Blastocystis spp in 6%. This is the first report of this kind in Surabaya District. Measures need to be taken to control the house rat population in the study area to reduce the risk of the public health problem. Keywords: zoonotic intestinal parasites, opportunistic infection, house rat, densely populated area, Indonesia PMID:27244955

  19. Infection with schistosome parasites in snails leads to increased predation by prawns: implications for human schistosomiasis control.

    PubMed

    Swartz, Scott J; De Leo, Giulio A; Wood, Chelsea L; Sokolow, Susanne H

    2015-12-01

    Schistosomiasis - a parasitic disease that affects over 200 million people across the globe - is primarily transmitted between human definitive hosts and snail intermediate hosts. To reduce schistosomiasis transmission, some have advocated disrupting the schistosome life cycle through biological control of snails, achieved by boosting the abundance of snails' natural predators. But little is known about the effect of parasitic infection on predator-prey interactions, especially in the case of schistosomiasis. Here, we present the results of laboratory experiments performed on Bulinus truncatus and Biomphalaria glabrata snails to investigate: (i) rates of predation on schistosome-infected versus uninfected snails by a sympatric native river prawn, Macrobrachium vollenhovenii, and (ii) differences in snail behavior (including movement, refuge-seeking and anti-predator behavior) between infected and uninfected snails. In predation trials, prawns showed a preference for consuming snails infected with schistosome larvae. In behavioral trials, infected snails moved less quickly and less often than uninfected snails, and were less likely to avoid predation by exiting the water or hiding under substrate. Although the mechanism by which the parasite alters snail behavior remains unknown, these results provide insight into the effects of parasitic infection on predator-prey dynamics and suggest that boosting natural rates of predation on snails may be a useful strategy for reducing transmission in schistosomiasis hotspots. PMID:26677260

  20. Human schistosomiasis

    PubMed Central

    Colley, Daniel G; Bustinduy, Amaya L; Secor, W Evan; King, Charles H

    2015-01-01

    Human schistosomiasis—or bilharzia—is a parasitic disease caused by trematode flukes of the genus Schistosoma. By conservative estimates, at least 230 million people worldwide are infected with Schistosoma spp. Adult schistosome worms colonise human blood vessels for years, successfully evading the immune system while excreting hundreds to thousands of eggs daily, which must either leave the body in excreta or become trapped in nearby tissues. Trapped eggs induce a distinct immune-mediated granulomatous response that causes local and systemic pathological effects ranging from anaemia, growth stunting, impaired cognition, and decreased physical fitness, to organ-specific effects such as severe hepatosplenism, periportal fibrosis with portal hypertension, and urogenital inflammation and scarring. At present, preventive public health measures in endemic regions consist of treatment once every 1 or 2 years with the isoquinolinone drug, praziquantel, to suppress morbidity. In some locations, elimination of transmission is now the goal; however, more sensitive diagnostics are needed in both the field and clinics, and integrated environmental and health-care management will be needed to ensure elimination. PMID:24698483

  1. Parasitic helminth infections and the control of human allergic and autoimmune disorders.

    PubMed

    Maizels, R M

    2016-06-01

    The profile of global health today presents a striking reciprocal distribution between parasitic diseases in many of the world's lower-income countries, and ever-increasing levels of inflammatory disorders such as allergy, autoimmunity and inflammatory bowel diseases in the more affluent societies. Attention is particularly focused on helminth worm parasites, which are associated with protection from allergy and inflammation in both epidemiologic and laboratory settings. One mechanistic explanation of this is that helminths drive the regulatory arm of the immune system, abrogating the ability of the host to expel the parasites, while also dampening reactivity to many bystander specificities. Interest has therefore heightened into whether helminth parasites, or their products, hold therapeutic potential for immunologic disorders of the developed world. In this narrative review, progress across a range of trials is discussed, together with prospects for isolating individual molecular mediators from helminths that may offer defined new therapies for inflammatory conditions. PMID:27172808

  2. Sex Steroids Effects on the Molting Process of the Helminth Human Parasite Trichinella spiralis

    PubMed Central

    Hernández-Bello, Romel; Ramirez-Nieto, Ricardo; Muñiz-Hernández, Saé; Nava-Castro, Karen; Pavón, Lenin; Sánchez-Acosta, Ana Gabriela; Morales-Montor, Jorge

    2011-01-01

    We evaluated the in vitro effects of estradiol, progesterone, and testosterone on the molting process, which is the initial and crucial step in the development of the muscular larvae (ML or L1) to adult worm. Testosterone had no significative effect on the molting rate of the parasite, however, progesterone decreased the molting rate about a 50% in a concentration- and time-independent pattern, while estradiol had a slight effect (10%). The gene expression of caveolin-1, a specific gene used as a marker of parasite development, showed that progesterone and estradiol downregulated its expression, while protein expression was unaffected. By using flow citometry, a possible protein that is recognized by a commercial antiprogesterone receptor antibody was detected. These findings may have strong implications in the host-parasite coevolution, in the sex-associated susceptibility to this infection and could point out to possibilities to use antihormones to inhibit parasite development. PMID:22162638

  3. 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

  4. Increase of malaria attacks among children presenting concomitant infection by Schistosoma mansoni in Senegal

    PubMed Central

    Sokhna, Cheikh; Le Hesran, Jean-Yves; Mbaye, Pape A; Akiana, Jean; Camara, Pape; Diop, Mamadou; Ly, Abdoulaye; Druilhe, Pierre

    2004-01-01

    Helminthic infections concomitant with malaria are common in inter-tropical areas. A recent study showed that mice co-infected with Schistosoma mansoni and Plasmodium chabaudi develop higher P. chabaudi parasitaemia and had a higher mortality rate. This important observation deserved to be further investigated among human populations. Malaria attacks were recorded in 512 children aged 6–15 years living in Richard Toll (Northern Senegal) among whom 336 were infected by S. mansoni, and 175 were not. The incidence rate of malaria attacks was significantly higher among S. mansoni-infected individuals, particularly those carrying the highest worm loads, as compared to uninfected subjects (26.6% versus 16,4 %). In contrast, the rate of malaria attacks was lower, without reaching significance, in medium grade S. mansoni infections. Thus, infection by S. mansoni affects susceptibility to malaria, but this can vary according to the intensity of parasite load. The immunological mechanisms underlying this dual effect need to be further explored. PMID:15544703

  5. Immunological characterization of a chimeric form of Schistosoma mansoni aquaporin in the murine model.

    PubMed

    Figueiredo, Barbara Castro Pimentel; De Assis, Natan Raimundo Gonçalves; De Morais, Suellen Batistoni; Martins, Vicente Paulo; Ricci, Natasha Delaqua; Bicalho, Rodrigo Marques; Pinheiro, Carina Da Silva; Oliveira, Sergio Costa

    2014-09-01

    Aquaporin (SmAQP) is the most abundant transmembrane protein in the tegument of Schistosoma mansoni. This protein is expressed in all developmental stages and seems to be essential in parasite survival since it plays a crucial role in osmoregulation, nutrient transport and drug uptake. In this study, we utilized the murine model to evaluate whether this protein was able to induce protection against challenge infection with S. mansoni cercariae. A chimeric (c) SmAQP was formulated with Freund's adjuvant for vaccination trial and evaluation of the host's immune response was performed. Our results demonstrated that immunization with cSmAQP induced the production of high levels of specific anti-cSmAQP IgG antibodies and a Th1/Th17 type of immune response characterized by IFN-γ, TNF-α and IL-17 cytokines. However, vaccination of mice with cSmAQP failed to reduce S. mansoni worm burden and liver pathology. Finally, we were unable to detect humoral immune response anti-cSmAQP in the sera of S. mansoni-infected human patients. Our results lead us to believe that SmAQP, as formulated in this study, may not be a good target in the search for an anti-schistosomiasis vaccine. PMID:24786243

  6. Purine nucleoside phosphorylase from Schistosoma mansoni in complex with ribose-1-phosphate

    PubMed Central

    D’Muniz Pereira, Humberto; Oliva, Glaucius; Garratt, Richard Charles

    2011-01-01

    Schistosomes are blood flukes which cause schistosomiasis, a disease affecting approximately 200 million people worldwide. Along with several other important human parasites including trypanosomes and Plasmodium, schistosomes lack the de novo pathway for purine synthesis and depend exclusively on the salvage pathway for their purine requirements, making the latter an attractive target for drug development. Part of the pathway involves the conversion of inosine (or guanosine) into hypoxanthine (or guanine) together with ribose-1-phosphate (R1P) or vice versa. This inter-conversion is undertaken by the enzyme purine nucleoside phosphorylase (PNP) which has been used as the basis for the development of novel anti-malarials, conceptually validating this approach. It has been suggested that, during the reverse reaction, R1P binding to the enzyme would occur only as a consequence of conformational changes induced by hypoxanthine, thus making a binary PNP–R1P complex unlikely. Contradictory to this statement, a crystal structure of just such a binary complex involving the Schistosoma mansoni enzyme has been successfully obtained. The ligand shows an intricate hydrogen-bonding network in the phosphate and ribose binding sites and adds a further chapter to our knowledge which could be of value in the future development of selective inhibitors. PMID:21169694

  7. Discovery of new inhibitors of Schistosoma mansoni PNP by pharmacophore-based virtual screening.

    PubMed

    Postigo, Matheus P; Guido, Rafael V C; Oliva, Glaucius; Castilho, Marcelo S; da R Pitta, Ivan; de Albuquerque, Julianna F C; Andricopulo, Adriano D

    2010-09-27

    Schistosomiasis is considered the second most important tropical parasitic disease, with severe socioeconomic consequences for millions of people worldwide. Schistosoma mansoni , one of the causative agents of human schistosomiasis, is unable to synthesize purine nucleotides de novo, which makes the enzymes of the purine salvage pathway important targets for antischistosomal drug development. In the present work, we describe the development of a pharmacophore model for ligands of S. mansoni purine nucleoside phosphorylase (SmPNP) as well as a pharmacophore-based virtual screening approach, which resulted in the identification of three thioxothiazolidinones (1-3) with substantial in vitro inhibitory activity against SmPNP. Synthesis, biochemical evaluation, and structure-activity relationship investigations led to the successful development of a small set of thioxothiazolidinone derivatives harboring a novel chemical scaffold as new competitive inhibitors of SmPNP at the low-micromolar range. Seven compounds were identified with IC(50) values below 100 μM. The most potent inhibitors 7, 10, and 17 with IC(50) of 2, 18, and 38 μM, respectively, could represent new potential lead compounds for further development of the therapy of schistosomiasis. PMID:20695479

  8. Human behavior and opportunities for parasite transmission in communities surrounding long-tailed macaque populations in Bali, Indonesia.

    PubMed

    Lane-DeGraaf, Kelly E; Putra, I G A Arta; Wandia, I Nengah; Rompis, Aida; Hollocher, Hope; Fuentes, Agustin

    2014-02-01

    Spatial overlap and shared resources between humans and wildlife can exacerbate parasite transmission dynamics. In Bali, Indonesia, an agricultural-religious temple system provides sanctuaries for long-tailed macaques (Macaca fascicularis), concentrating them in areas in close proximity to humans. In this study, we interviewed individuals in communities surrounding 13 macaque populations about their willingness to participate in behaviors that would put them at risk of exposure to gastrointestinal parasites to understand if age, education level, or occupation are significant determinants of exposure behaviors. These exposure risk behaviors and attitudes include fear of macaques, direct contact with macaques, owning pet macaques, hunting and eating macaques, and overlapping water uses. We find that willingness to participate in exposure risk behaviors are correlated with an individual's occupation, age, and/or education level. We also found that because the actual risk of infection varies across populations, activities such as direct macaque contact and pet ownership, could be putting individuals at real risk in certain contexts. Thus, we show that human demographics and social structure can influence willingness to participate in behaviors putting them at increased risk for exposure to parasites. PMID:24123083

  9. The apicomplexan parasite Babesia divergens internalizes band 3, glycophorin A and spectrin during invasion of human red blood cells.

    PubMed

    Repnik, Urska; Gangopadhyay, Preetish; Bietz, Sven; Przyborski, Jude M; Griffiths, Gareth; Lingelbach, Klaus

    2015-07-01

    Plasmodium falciparum invades human red blood cells (RBC), while Babesia divergens infects bovine and, occasionally, human RBC. The mammalian RBC is normally unable to endocytose or phagocytose and the events leading to invasion are incompletely understood. Initially, both parasites are surrounded by the RBC plasma membrane-derived parasitophorous vacuolar membrane (PVM) that is formed during invasion. In P. falciparum-infected RBC, the PVM persists at least until parasite replication is completed whereas it has been proposed that the B. divergens PVM is disintegrated soon upon invasion. Here, we have used a B. divergens strain adapted to human RBC to investigate the formation and fate of the PVM. Using ultrastructural analysis and whole-mount or on-section immunofluorescence and immunogold labelling, we demonstrate that the initial vacuolar membrane is formed from protein and lipid components of the RBC plasma membrane. Integral membrane proteins band 3 and glycophorin A and the cytoskeletal protein spectrin are associated with the PVM of the B. divergens, but are absent from the PVM of P. falciparum at the ring or the trophozoite stage. Our results provide evidence that the biophysical properties of the RBC cytoskeleton per se do not preclude the internalization of cytoskeletal proteins by invading parasites. PMID:25628009

  10. Development and Evaluation of a Sensitive PCR-ELISA System for Detection of Schistosoma Infection in Feces

    PubMed Central

    Gomes, Luciana Inácia; dos Santos Marques, Letícia Helena; Enk, Martin Johannes; de Oliveira, Maria Cláudia; Coelho, Paulo Marcos Zech; Rabello, Ana

    2010-01-01

    Background A PCR-enzyme-linked immunosorbent assay (PCR-ELISA) was developed to overcome the need for sensitive techniques for the efficient diagnosis of Schistosoma infection in endemic settings with low parasitic burden. Methodology/Principal Findings This system amplifies a 121-base pair tandem repeat DNA sequence, immobilizes the resultant 5′ biotinylated product on streptavidin-coated strip-well microplates and uses anti-fluorescein antibodies conjugated to horseradish peroxidase to detect the hybridized fluorescein-labeled oligonucleotide probe. The detection limit of the Schistosoma PCR-ELISA system was determined to be 1.3 fg of S. mansoni genomic DNA (less than the amount found in a single cell) and estimated to be 0.15 S. mansoni eggs per gram of feces (fractions of an egg). The system showed good precision and genus specificity since the DNA target was found in seven Schistosoma DNA samples: S. mansoni, S. haematobium, S. bovis, S. intercalatum, S. japonicum, S. magrebowiei and S. rhodaini. By evaluating 206 patients living in an endemic area in Brazil, the prevalence of S. mansoni infection was determined to be 18% by examining 12 Kato-Katz slides (41.7 mg/smear, 500 mg total) of a single fecal sample from each person, while the Schistosoma PCR-ELISA identified a 30% rate of infection using 500-mg of the same fecal sample. When considering the Kato-Katz method as the reference test, artificial sensitivity and specificity rates of the PCR-ELISA system were 97.4% and 85.1%, respectively. The potential for estimating parasitic load by DNA detection in feces was assessed by comparing absorbance values and eggs per gram of feces, with a Spearman correlation coefficient of 0.700 (P<0.0001). Conclusions/Significance This study reports the development and field evaluation of a sensitive Schistosoma PCR-ELISA, a system that may serve as an alternative for diagnosing Schistosoma infection. PMID:20421918

  11. Origin and evolution of Schistosoma japonicum.

    PubMed

    Agatsuma, Takeshi

    2003-12-01

    In his hypothesis on the coevolution of Asian schistosomes and snails, Davis implies that the ancestors of the Schistosoma japonicum and S. indicum species group were African and arrived in Asia via the Indian plate. This paper briefly reviews molecular phylogenetic relationships among species of the genus Schistosoma to test Davis' theory about the origin and evolution of S. japonicum. All analyses using DNA base sequences, mitochondrial genome gene order and C-banding patterns suggest that Schistosoma originated in Asia and not Africa. PMID:14665391

  12. Parasite sources and sinks in a patched Ross-Macdonald malaria model with human and mosquito movement: Implications for control.

    PubMed

    Ruktanonchai, Nick W; Smith, David L; De Leenheer, Patrick

    2016-09-01

    We consider the dynamics of a mosquito-transmitted pathogen in a multi-patch Ross-Macdonald malaria model with mobile human hosts, mobile vectors, and a heterogeneous environment. We show the existence of a globally stable steady state, and a threshold that determines whether a pathogen is either absent from all patches, or endemic and present at some level in all patches. Each patch is characterized by a local basic reproduction number, whose value predicts whether the disease is cleared or not when the patch is isolated: patches are known as "demographic sinks" if they have a local basic reproduction number less than one, and hence would clear the disease if isolated; patches with a basic reproduction number above one would sustain endemic infection in isolation, and become "demographic sources" of parasites when connected to other patches. Sources are also considered focal areas of transmission for the larger landscape, as they export excess parasites to other areas and can sustain parasite populations. We show how to determine the various basic reproduction numbers from steady state estimates in the patched network and knowledge of additional model parameters, hereby identifying parasite sources in the process. This is useful in the context of control of the infection on natural landscapes, because a commonly suggested strategy is to target focal areas, in order to make their corresponding basic reproduction numbers less than one, effectively turning them into sinks. We show that this is indeed a successful control strategy-albeit a conservative and possibly expensive one-in case either the human host, or the vector does not move. However, we also show that when both humans and vectors move, this strategy may fail, depending on the specific movement patterns exhibited by hosts and vectors. PMID:27436636

  13. The relationships between the burden of adult parasites, host age and the microfilarial density in human onchocerciasis.

    PubMed

    Duerr, H P; Dietz, K; Schulz-Key, H; Büttner, D W; Eichner, M

    2004-03-29

    We investigate the relationship between the microfilarial density in the skin and the burden of adult female Onchocerca volvulus by analysing pre-control nodulectomy data which allow for a direct approach, independent of exposure. The data of 169 patients in Burkina Faso and 182 patients in Liberia represent savannah and forest onchocerciasis in West Africa, respectively. Whereas in Burkina Faso, a saturating relationship between microfilarial density and worm burden suggests the operation of density-dependent processes within human hosts, the Liberian data show a linear relationship implying no density dependence. The differences may derive from differences between both parasite strains, i.e. the savannah or the forest strain of O. volvulus. Consistently for both parasite strains and independent of the worm burden, the microfilarial density increases with host age emphasising the concept of the acquisition of immunological tolerance. In male hosts in Liberia, the microfilarial density increases stronger with the worm burden than in female hosts, whereas such sex-specific differences cannot be found in Burkina Faso. In the methodological part of this investigation, we suggest the beta-distribution to be most appropriate for describing variability in microfilarial densities and we present an approach to consider the uncertainty in the adult parasite burden which cannot be determined precisely in helminth infections. Implications of density dependence are discussed with respect to immunological processes in the human host and with respect to the success of control programs. The relationships described show that regulatory processes between the parasite and the human host are multi-dimensional, operating within a high degree of biological variability. PMID:15013736

  14. Schistosoma mansoni Annexin 2: molecular characterization and immunolocalization.

    PubMed

    Tararam, Cibele Aparecida; Farias, Leonardo Paiva; Wilson, R Alan; Leite, Luciana Cezar de Cerqueira

    2010-10-01

    We here describe the cloning and characterization of the Schistosoma mansoni Annexin 2, previously identified in the tegument by proteomic studies, and as an up-regulated gene in schistosomulum stage by microarray data. In silico analysis predicts a conserved core containing four repeat domains of Annexin (ANX) and a variable N-terminal region similar to that described for mammalian isoforms. Real-time RT-PCR and Western blot analysis determined that S. mansoni Annexin 2 is significantly up-regulated in the transition from free-living cercaria to schistosomulum and adult worm parasitic stages. Immunolocalization experiments and tegument membrane preparations confirmed Annexin 2 as a protein mainly localized in the tegument of schistosomula and adult worms. Furthermore, it binds to the tegument surface membranes in a calcium-dependent manner. These results suggest that S. mansoni Annexin 2 is closely associated to the tegument arrangement, being a potential target for immune intervention. PMID:20417203

  15. Cercarial emergence pattern of Schistosoma haematobium from Libreville, Gabon.

    PubMed

    Mintsa-Nguéma, Rodrigue; Moné, Hélène; Ibikounlé, Moudachirou; Mengué-Ngou-Milama, Krystina; Kombila, Maryvonne; Mouahid, Gabriel

    2014-01-01

    Although schistosomiasis has been a public health issue in Gabon for nearly a century, little is known about its current transmission dynamics. We analyzed the chronobiology of 137 cercarial emission profiles of Schistosoma haematobium from Libreville, the capital of Gabon, located in an open area for schistosomiasis. We found that 88% of the cercariae were shed between 11 a.m. and 3 p.m. and that the average pattern was of circadian type, with the average peak at 1 p.m., and representing 27% of the total number of cercariae of the day. The rhythms of emergence may be associated with environmental pressures on the parasite, especially those related to their definitive hosts. PMID:24502943

  16. Protective Effect of Chronic Schistosomiasis in Baboons Coinfected with Schistosoma mansoni and Plasmodium knowlesi.

    PubMed

    Nyakundi, Ruth K; Nyamongo, Onkoba; Maamun, Jeneby; Akinyi, Mercy; Mulei, Isaac; Farah, Idle O; Blankenship, D'Arbra; Grimberg, Brian; Hau, Jann; Malhotra, Indu; Ozwara, Hastings; King, Christopher L; Kariuki, Thomas M

    2016-05-01

    Malaria and schistosomiasis coinfections are common, and chronic schistosomiasis has been implicated in affecting the severity of acute malaria. However, whether it enhances or attenuates malaria has been controversial due the lack of appropriately controlled human studies and relevant animal models. To examine this interaction, we conducted a randomized controlled study using the baboon (Papio anubis) to analyze the effect of chronic schistosomiasis on severe malaria. Two groups of baboons (n = 8 each) and a schistosomiasis control group (n = 3) were infected with 500 Schistosoma mansoni cercariae. At 14 and 15 weeks postinfection, one group was given praziquantel to treat schistosomiasis infection. Four weeks later, the two groups plus a new malaria control group (n = 8) were intravenously inoculated with 10(5) Plasmodium knowlesi parasites and monitored daily for development of severe malaria. A total of 81% of baboons exposed to chronic S. mansoni infection with or without praziquantel treatment survived malaria, compared to only 25% of animals infected with P. knowlesi only (P = 0.01). Schistosome-infected animals also had significantly lower parasite burdens (P = 0.004) than the baboons in the P. knowlesi-only group and were protected from severe anemia. Coinfection was associated with increased spontaneous production of interleukin-6 (IL-6), suggesting an enhanced innate immune response, whereas animals infected with P. knowlesi alone failed to develop mitogen-driven tumor necrosis factor alpha and IL-10, indicating the inability to generate adequate protective and balancing immunoregulatory responses. These results indicate that chronic S. mansoni attenuates the severity of P. knowlesi coinfection in baboons by mechanisms that may enhance innate immunity to malaria. PMID:26883586

  17. Modelling the time course of antimalarial parasite killing: a tour of animal and human models, translation and challenges

    PubMed Central

    Patel, Kashyap; Simpson, Julie A; Batty, Kevin T; Zaloumis, Sophie; Kirkpatrick, Carl M

    2015-01-01

    Malaria remains a global public health concern and current treatment options are suboptimal in some clinical settings. For effective chemotherapy, antimalarial drug concentrations must be sufficient to remove completely all of the parasites in the infected host. Optimized dosing therefore requires a detailed understanding of the time course of antimalarial response, whilst simultaneously considering the parasite life cycle and host immune elimination. Recently, the World Health Organization (WHO) has recommended the development of mathematical models for understanding better antimalarial drug resistance and management. Other international groups have also suggested that mechanistic pharmacokinetic (PK) and pharmacodynamic (PD) models can support the rationalization of antimalarial dosing strategies. At present, artemisinin-based combination therapy (ACT) is recommended as first line treatment of falciparum malaria for all patient groups. This review summarizes the PK–PD characterization of artemisinin derivatives and other partner drugs from both preclinical studies and human clinical trials. We outline the continuous and discrete time models that have been proposed to describe antimalarial activity on specific stages of the parasite life cycle. The translation of PK–PD predictions from animals to humans is considered, because preclinical studies can provide rich data for detailed mechanism-based modelling. While similar sampling techniques are limited in clinical studies, PK–PD models can be used to optimize the design of experiments to improve estimation of the parameters of interest. Ultimately, we propose that fully developed mechanistic models can simulate and rationalize ACT or other treatment strategies in antimalarial chemotherapy. PMID:24251882

  18. Host choice and penetration by Schistosoma haematobium miracidia.

    PubMed

    Allan, F; Rollinson, D; Smith, J E; Dunn, A M

    2009-03-01

    Schistosome parasites commonly show specificity to their intermediate mollusc hosts and the degree of specificity can vary between parasite strains and geographical location. Here the role of miracidial behaviour in host specificity of Schistosoma haematobium on the islands of Zanzibar is investigated. In choice-chamber experiments, S. haematobium miracidia moved towards Bulinus globosus snail hosts in preference to empty chambers. In addition, miracidia preferred uninfected over patent B. globosus. This preference should benefit the parasite as patent snails are likely to have mounted an immune response to S. haematobium as well as providing poorer resources than uninfected snails. Miracidia also discriminated between the host B. globosus and the sympatric, non-host species Cleopatra ferruginea. In contrast, S. haematobium did not discriminate against the allopatric Bulinus nasutus. Penetration of the host by miracidia was investigated by screening snails 24 h after exposure using polymerase chain reaction (PCR) with S. haematobium specific DraI repeat primers. There was no difference in the frequency of penetration of B. globosus versus B. nasutus. These responses to different snail species may reflect selection pressure to avoid sympatric non-hosts which represent a transmission dead end. The distribution of B. nasutus on Unguja is outside the endemic zone and so there is less chance of exposure to S. haematobium, hence there will be little selection pressure to avoid this non-host snail. PMID:18922204

  19. A Loop-Mediated Isothermal Amplification (LAMP) Assay for Early Detection of Schistosoma mansoni in Stool Samples: A Diagnostic Approach in a Murine Model

    PubMed Central

    Fernández-Soto, Pedro; Gandasegui Arahuetes, Javier; Sánchez Hernández, Alicia; López Abán, Julio; Vicente Santiago, Belén; Muro, Antonio

    2014-01-01

    Background Human schistosomiasis, mainly due to Schistosoma mansoni species, is one of the most prevalent parasitic diseases worldwide. To overcome the drawbacks of classical parasitological and serological methods in detecting S. mansoni infections, especially in acute stage of the disease, development of cost-effective, simple and rapid molecular methods is still needed for the diagnosis of schistosomiasis. A promising approach is the loop-mediated isothermal amplification (LAMP) technology. Compared to PCR-based assays, LAMP has the advantages of reaction simplicity, rapidity, specificity, cost-effectiveness and higher amplification efficiency. Additionally, as results can be inspected by the naked eye, the technique has great potential for use in low-income countries. Methodology/Principal findings A sequence corresponding to a mitochondrial S. mansoni minisatellite DNA region was selected as a target for designing a LAMP-based method to detect S. mansoni DNA in stool samples. We used a S. mansoni murine model to obtain well defined stool and sera samples from infected mice with S. mansoni cercariae. Samples were taken weekly from week 0 to 8 post-infection and the Kato-Katz and ELISA techniques were used for monitoring the infection. Primer set designed were tested using a commercial reaction mixture for LAMP assay and an in house mixture to compare results. Specificity of LAMP was tested using 16 DNA samples from different parasites, including several Schistosoma species, and no cross-reactions were found. The detection limit of our LAMP assay (SmMIT-LAMP) was 1 fg of S. mansoni DNA. When testing stool samples from infected mice the SmMIT-LAMP detected S. mansoni DNA as soon as 1 week post-infection. Conclusions/Significance We have developed, for the first time, a cost-effective, easy to perform, specific and sensitive LAMP assay for early detection of S. mansoni in stool samples. The method is potentially and readily adaptable for field diagnosis and

  20. Parasitic Diseases

    MedlinePlus

    ... a bug bite, or sexual contact. Some parasitic diseases are easily treated and some are not. Parasites ... be seen with the naked eye. Some parasitic diseases occur in the United States. Contaminated water supplies ...

  1. Parasitic Diseases

    MedlinePlus

    ... water, a bug bite, or sexual contact. Some parasitic diseases are easily treated and some are not. Parasites ... can be seen with the naked eye. Some parasitic diseases occur in the United States. Contaminated water supplies ...

  2. Drug resistance. Population transcriptomics of human malaria parasites reveals the mechanism of artemisinin resistance.

    PubMed

    Mok, Sachel; Ashley, Elizabeth A; Ferreira, Pedro E; Zhu, Lei; Lin, Zhaoting; Yeo, Tomas; Chotivanich, Kesinee; Imwong, Mallika; Pukrittayakamee, Sasithon; Dhorda, Mehul; Nguon, Chea; Lim, Pharath; Amaratunga, Chanaki; Suon, Seila; Hien, Tran Tinh; Htut, Ye; Faiz, M Abul; Onyamboko, Marie A; Mayxay, Mayfong; Newton, Paul N; Tripura, Rupam; Woodrow, Charles J; Miotto, Olivo; Kwiatkowski, Dominic P; Nosten, François; Day, Nicholas P J; Preiser, Peter R; White, Nicholas J; Dondorp, Arjen M; Fairhurst, Rick M; Bozdech, Zbynek

    2015-01-23

    Artemisinin resistance in Plasmodium falciparum threatens global efforts to control and eliminate malaria. Polymorphisms in the kelch domain-carrying protein K13 are associated with artemisinin resistance, but the underlying molecular mechanisms are unknown. We analyzed the in vivo transcriptomes of 1043 P. falciparum isolates from patients with acute malaria and found that artemisinin resistance is associated with increased expression of unfolded protein response (UPR) pathways involving the major PROSC and TRiC chaperone complexes. Artemisinin-resistant parasites also exhibit decelerated progression through the first part of the asexual intraerythrocytic development cycle. These findings suggest that artemisinin-resistant parasites remain in a state of decelerated development at the young ring stage, whereas their up-regulated UPR pathways mitigate protein damage caused by artemisinin. The expression profiles of UPR-related genes also associate with the geographical origin of parasite isolates, further suggesting their role in emerging artemisinin resistance in the Greater Mekong Subregion. PMID:25502316

  3. Selective Killing of the Human Malaria Parasite Plasmodium falciparum by a Benzylthiazolium dye

    PubMed Central

    Kelly, Jane X.; Winter, Rolf W.; Braun, Theodore P.; Osei-Agyemang, Myralyn; Hinrichs, David J.; Riscoe, Michael K.

    2007-01-01

    Malaria is an infectious disease caused by protozoan parasites of the genus Plasmodium. The most virulent form of the disease is caused by P. falciparum which infects hundreds of millions of people and is responsible for the deaths of 1 to 2 million individuals each year. An essential part of the parasitic process is the remodeling of the red blood cell membrane and its protein constituents to permit a higher flux of nutrients and waste products into or away from the intracellular parasite. Much of this increased permeability is due to a single type of broad specificity channel variously called the new permeation pathway (NPP), the nutrient channel, and the Plasmodial surface anion channel (PSAC). This channel is permeable to a range of low molecular weight solutes both charged and uncharged, with a strong preference for anions. Drugs such as furosemide that are known to block anion-selective channels inhibit PSAC. In this study we have investigated a dye known as benzothiocarboxypurine, BCP, which had been studied as a possible diagnostic aid given its selective uptake by P. falciparum infected red cells. We found that the dye enters parasitized red cells via the furosemide-inhibitable PSAC, forms a brightly fluorescent complex with parasite nucleic acids, and is selectively toxic to infected cells. Our study describes an antimalarial agent that exploits the altered permeability of Plasmodium-infected red cells as a means to killing the parasite and highlights a chemical reagent that may prove useful in high throughput screening of compounds for inhibitors of the channel. PMID:17266952

  4. [Human intestinal parasites in Subsaharan Africa. III. Pemba Island (Zanzibar-Tanzania)].

    PubMed

    Pampiglione, S; Visconti, S; Stefanini, A

    1987-04-01

    The authors carried out a coprological survey in Pemba Island, analysing, by modified Ritchie technique, 413 stools samples. The specimens were collected among the population from apparently healthy subjects chosen at random in a number equal to 2% of the whole population. The examined subjects were divided in 3 age groups, 211 were males, 202 females. The following results were obtained (in order of prevalence): a) Protozoa: Entamoeba coli 35.6%, Giardia intestinalis 5.6%, Endolimax nana 4.3%, E. histolytica 3.1%, Chilomastix mesnili 2.9%, Iodamoeba buetschlii 4.3%, E. hartmanni 0.7%; b) Helminths: Trichuris trichiura 87.9%, Ancylostomatidae 67.5%, Ascaris lumbricoides 39.7%, Strongyloides stercoralis 18.9%, Schistosoma haematobium 1.9%, S. mansoni 0.2%, S. fuelleborni 0.2%, Enterobius vermicularis 0.2%. The high moisture of soil and the rain distribution during the year could be favouring the high prevalence of T. trichiura and Ancylostomatidae. The case of schistosomiasis due to S. mansoni reported, seems to be imported from the Mainland, while the case of S. fuelleborni could be autochtonous. Totally, 392 subjects (94.4%) were found positive for pathogenic species (Helminths and Protozoa). PMID:3508507

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

    PubMed

    Mansour, Nuha R; Paveley, Ross; Gardner, J Mark F; Bell, Andrew S; Parkinson, Tanya; Bickle, Quentin

    2016-04-01

    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

  6. 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

  7. O2-Dependent Efficacy of Novel Piperidine- and Piperazine-Based Chalcones against the Human Parasite Giardia intestinalis

    PubMed Central

    Bahadur, Vijay; Mastronicola, Daniela; Tiwari, Hemandra Kumar; Kumar, Yogesh; Falabella, Micol; Pucillo, Leopoldo Paolo; Sarti, Paolo

    2014-01-01

    Giardia intestinalis is the most frequent protozoan agent of intestinal diseases worldwide. Though commonly regarded as an anaerobic pathogen, it preferentially colonizes the fairly oxygen-rich mucosa of the proximal small intestine. Therefore, when testing new potential antigiardial drugs, O2 should be taken into account, since it also reduces the efficacy of metronidazole, the gold standard drug against giardiasis. In this study, 46 novel chalcones were synthesized by microwave-assisted Claisen-Schmidt condensation, purified, characterized by high-resolution mass spectrometry, 1H and 13C nuclear magnetic resonance, and infrared spectroscopy, and tested for their toxicity against G. intestinalis under standard anaerobic conditions. As a novel approach, compounds showing antigiardial activity under anaerobiosis were also assayed under microaerobic conditions, and their selectivity against parasitic cells was assessed in a counterscreen on human epithelial colorectal adenocarcinoma cells. Among the tested compounds, three [30(a), 31(e), and 33] were more effective in the presence of O2 than under anaerobic conditions and killed the parasite 2 to 4 times more efficiently than metronidazole under anaerobiosis. Two of them [30(a) and 31(e)] proved to be selective against parasitic cells, thus representing potential candidates for the design of novel antigiardial drugs. This study highlights the importance of testing new potential antigiardial agents not only under anaerobic conditions but also at low, more physiological O2 concentrations. PMID:24217695

  8. Expression of senescent antigen on erythrocytes infected with a knobby variant of the human malaria parasite Plasmodium falciparum

    SciTech Connect

    Winograd, E.; Greenan, J.R.T.; Sherman, I.W.

    1987-04-01

    Erythrocytes infected with a knobby variant of Plasmodium falciparum selectively bind IgG autoantibodies in normal human serum. Quantification of membrane-bound IgG, by use of /sup 125/I-labeled protein A, revealed that erythrocytes infected with the knobby variant bound 30 times more protein A than did noninfected erythrocytes; infection with a knobless variant resulted in less than a 2-fold difference compared with noninfected erythrocytes. IgG binding to knobby erythrocytes appeared to be related to parasite development, since binding of /sup 125/I-labeled protein A to cells bearing young trophozoites (less than 20 hr after parasite invasion) was similar to binding to uninfected erythrocytes. By immunoelectron microscopy, the membrane-bound IgG on erythrocytes infected with the knobby variant was found to be preferentially associated with the protuberances (knobs) of the plasma membrane. The removal of aged or senescent erythrocytes from the peripheral circulation is reported to involve the binding of specific antibodies to an antigen (senescent antigen) related to the major erythrocyte membrane protein band 3. Since affinity-purified autoantibodies against band 3 specifically bound to the plasma membrane of erythrocytes infected with the knobby variant of P. falciparum, it is clear that the malaria parasite induces expression of senescent antigen.

  9. A Global Comparison of the Human and T. brucei Degradomes Gives Insights about Possible Parasite Drug Targets

    PubMed Central

    Mashiyama, Susan T.; Koupparis, Kyriacos; Caffrey, Conor R.; McKerrow, James H.; Babbitt, Patricia C.

    2012-01-01

    We performed a genome-level computational study of sequence and structure similarity, the latter using crystal structures and models, of the proteases of Homo sapiens and the human parasite Trypanosoma brucei. Using sequence and structure similarity networks to summarize the results, we constructed global views that show visually the relative abundance and variety of proteases in the degradome landscapes of these two species, and provide insights into evolutionary relationships between proteases. The results also indicate how broadly these sequence sets are covered by three-dimensional structures. These views facilitate cross-species comparisons and offer clues for drug design from knowledge about the sequences and structures of potential drug targets and their homologs. Two protease groups (“M32” and “C51”) that are very different in sequence from human proteases are examined in structural detail, illustrating the application of this global approach in mining new pathogen genomes for potential drug targets. Based on our analyses, a human ACE2 inhibitor was selected for experimental testing on one of these parasite proteases, TbM32, and was shown to inhibit it. These sequence and structure data, along with interactive versions of the protein similarity networks generated in this study, are available at http://babbittlab.ucsf.edu/resources.html. PMID:23236535

  10. Coinfection with Plasmodium falciparum and Schistosoma haematobium: additional evidence of the protective effect of Schistosomiasis on malaria in Senegalese children.

    PubMed

    Lemaitre, Magali; Watier, Laurence; Briand, Valérie; Garcia, André; Le Hesran, Jean Yves; Cot, Michel

    2014-02-01

    Parasitic infections are associated with high morbidity and mortality in developing countries. Several studies focused on the influence of helminth infections on malaria but the nature of the biological interaction is under debate. Our objective was to undertake a study to explore the influence of the measure of excreted egg load caused by Schistosoma haematobium on Plasmodium falciparum parasite densities. Ten measures of malaria parasite density and two measures of schistosomiasis egg urinary excretion over a 2-year follow-up period on 178 Senegalese children were considered. A linear mixed-effect model was developed to take data dependence into account. This work showed that children with a light S. haematobium infection (1-9 eggs/mL of urine) presented lower P. falciparum parasite densities than children not infected by S. haematobium (P < 0.04). Possible changes caused by parasite coinfections should be considered in the anti-helminth treatment of children and in malaria vaccination development. PMID:24323515

  11. Helminth Allergens, Parasite-Specific IgE, and Its Protective Role in Human Immunity

    PubMed Central

    Fitzsimmons, Colin Matthew; Falcone, Franco Harald; Dunne, David William

    2014-01-01

    The Th2 immune response, culminating in eosinophilia and IgE production, is not only characteristic of allergy but also of infection by parasitic worms (helminths). Anti-parasite IgE has been associated with immunity against a range of helminth infections and many believe that IgE and its receptors evolved to help counter metazoan parasites. Allergens (IgE-antigens) are present in only a small minority of protein families and known IgE targets in helminths belong to these same families (e.g., EF-hand proteins, tropomyosin, and PR-1 proteins). During some helminth infection, especially with the well adapted hookworm, the Th2 response is moderated by parasite-expressed molecules. This has been associated with reduced allergy in helminth endemic areas and worm infection or products have been proposed as treatments for allergic conditions. However, some infections (especially Ascaris) are associated with increased allergy and this has been linked to cross-reactivity between worm proteins (e.g., tropomyosins) and highly similar molecules in dust-mites and insects. The overlap between allergy and helminth infection is best illustrated in Anisakis simplex, a nematode that when consumed in under-cooked fish can be both an infective helminth and a food allergen. Nearly 20 molecular allergens have been isolated from this species, including tropomyosin (Ani s 3) and the EF-hand protein, Ani s troponin. In this review, we highlight aspects of the biology and biochemistry of helminths that may have influenced the evolution of the IgE response. We compare dominant IgE-antigens in worms with clinically important environmental allergens and suggest that arrays of such molecules will provide important information on anti-worm immunity as well as allergy. PMID:24592267

  12. Helminth Allergens, Parasite-Specific IgE, and Its Protective Role in Human Immunity.

    PubMed

    Fitzsimmons, Colin Matthew; Falcone, Franco Harald; Dunne, David William

    2014-01-01

    The Th2 immune response, culminating in eosinophilia and IgE production, is not only characteristic of allergy but also of infection by parasitic worms (helminths). Anti-parasite IgE has been associated with immunity against a range of helminth infections and many believe that IgE and its receptors evolved to help counter metazoan parasites. Allergens (IgE-antigens) are present in only a small minority of protein families and known IgE targets in helminths belong to these same families (e.g., EF-hand proteins, tropomyosin, and PR-1 proteins). During some helminth infection, especially with the well adapted hookworm, the Th2 response is moderated by parasite-expressed molecules. This has been associated with reduced allergy in helminth endemic areas and worm infection or products have been proposed as treatments for allergic conditions. However, some infections (especially Ascaris) are associated with increased allergy and this has been linked to cross-reactivity between worm proteins (e.g., tropomyosins) and highly similar molecules in dust-mites and insects. The overlap between allergy and helminth infection is best illustrated in Anisakis simplex, a nematode that when consumed in under-cooked fish can be both an infective helminth and a food allergen. Nearly 20 molecular allergens have been isolated from this species, including tropomyosin (Ani s 3) and the EF-hand protein, Ani s troponin. In this review, we highlight aspects of the biology and biochemistry of helminths that may have influenced the evolution of the IgE response. We compare dominant IgE-antigens in worms with clinically important environmental allergens and suggest that arrays of such molecules will provide important information on anti-worm immunity as well as allergy. PMID:24592267

  13. Structure-Based Design and Synthesis of Novel Inhibitors Targeting HDAC8 from Schistosoma mansoni for the Treatment of Schistosomiasis.

    PubMed

    Heimburg, Tino; Chakrabarti, Alokta; Lancelot, Julien; Marek, Martin; Melesina, Jelena; Hauser, Alexander-Thomas; Shaik, Tajith B; Duclaud, Sylvie; Robaa, Dina; Erdmann, Frank; Schmidt, Matthias; Romier, Christophe; Pierce, Raymond J; Jung, Manfred; Sippl, Wolfgang

    2016-03-24

    Schistosomiasis is a major neglected parasitic disease that affects more than 265 million people worldwide and for which the control strategy consists of mass treatment with the only available drug, praziquantel. In this study, a series of new benzohydroxamates were prepared as potent inhibitors of Schistosoma mansoni histone deacetylase 8 (smHDAC8). Crystallographic analysis provided insights into the inhibition mode of smHDAC8 activity by these 3-amidobenzohydroxamates. The newly designed inhibitors were evaluated in screens for enzyme inhibitory activity against schistosome and human HDACs. Twenty-seven compounds were found to be active in the nanomolar range, and some of them showed selectivity toward smHDAC8 over the major human HDACs (1 and 6). The active benzohydroxamates were additionally screened for lethality against the schistosome larval stage using a fluorescence-based assay. Four of these showed significant dose-dependent killing of the schistosome larvae and markedly impaired egg laying of adult worm pairs maintained in culture. PMID:26937828

  14. Molluscicidal activity of the plant Eupatorium adenophorum against Oncomelania hupensis, the intermediate host snail of Schistosoma japonicum.

    PubMed

    Zou, F C; Duan, G; Xie, Y J; Zhou, Y; Dong, G D; Lin, R Q; Zhu, X Q

    2009-09-01

    The potential molluscicidal activities of aqueous extracts of Eupatorium adenophorum have recently been evaluated against Oncomelania hupensis, the intermediate host snail of Schistosoma japonicum. The snails were continuously exposed to extracts of the leaves, roots or stems [each at concentrations of 0.27%, 0.50% and 0.86% (w/v)], with survival recorded 6, 12, 24, 30, 36, 48, 52, 58, 70, 76, 82 and 96 h after the start of the exposure. Even at the lowest concentration tested (0.27%), the leaf extract caused mortality in excess of 50% after 58 h and 100% mortality after 82 h. This extract was significantly more effective against O. hupensis than the stem or root extract (P<0.05) but there was no statistically significant difference between the root and stem extracts in their molluscicidal effects (P>0.05). These preliminary results indicate that E. adenophorum may potentially provide a new molluscicide that could give effective and environmentally-friendly control of schistosomiasis in humans and livestock. The toxicity of E. adenophorum extracts, or molluscicidal compounds isolated from such extracts, to other snail hosts of human parasites and to non-target species of aquatic life will be investigated. PMID:19695160

  15. Does Magnetic Field Affect Malaria Parasite Replication in Human Red Blood Cells?

    NASA Technical Reports Server (NTRS)

    Chanturiya, Alexandr N.; Glushakova, Svetlana; Yin, Dan; Zimmerberg, Joshua

    2004-01-01

    Digestion of red blood cell (RBC) hemoglobin by the malaria parasite results in the formation of paramagnetic hemazoin crystals inside the parasite body. A number of reports suggest that magnetic field interaction with hamazoin crystals significantly reduces the number of infected cells in culture, and thus magnetic field can be used to combat malaria. We studies the effects of magnetic filed on the Plasmodium falciparum asexual life cycle inside RBCs under various experimental conditions. No effect was found during prolonged exposure of infected RBCs to constant magnetic fields up to 6000 Gauss. Infected RBCs were also exposed, under temperature-controlled conditions, to oscillating magnetic fields with frequencies in the range of 500-20000 kHz, and field strength 30-600 Gauss. This exposure often changed the proportion of different parasite stages in treated culture compared to controls. However, no significant effect on parasitemia was observed in treated cultures. This result indicates that the magnetic field effect on Plasmodium falciparum is negligible, or that hypothetical negative and positive effects on different stages within one 48-hour compensate each other.

  16. Microsatellite polymorphism in the sexually transmitted human pathogen Trichomonas vaginalis indicates a genetically diverse parasite.

    PubMed

    Conrad, Melissa; Zubacova, Zuzana; Dunn, Linda A; Upcroft, Jacqui; Sullivan, Steven A; Tachezy, Jan; Carlton, Jane M

    2011-01-01

    Given the growing appreciation of serious health sequelae from widespread Trichomonas vaginalis infection, new tools are needed to study the parasite's genetic diversity. To this end we have identified and characterized a panel of 21 microsatellites and six single-copy genes from the T. vaginalis genome, using seven laboratory strains of diverse origin. We have (1) adapted our microsatellite typing method to incorporate affordable fluorescent labeling, (2) determined that the microsatellite loci remain stable in parasites continuously cultured for up to 17 months, and (3) evaluated microsatellite marker coverage of the six chromosomes that comprise the T. vaginalis genome, using fluorescent in situ hybridization (FISH). We have used the markers to show that T. vaginalis is a genetically diverse parasite in a population of commonly used laboratory strains. In addition, we have used phylogenetic methods to infer evolutionary relationships from our markers in order to validate their utility in future population analyses. Our panel is the first series of robust polymorphic genetic markers for T. vaginalis that can be used to classify and monitor lab strains, as well as provide a means to measure the genetic diversity and population structure of extant and future T. vaginalis isolates. PMID:20813140

  17. Efficient in vitro RNA interference and immunofluorescence-based phenotype analysis in a human parasitic nematode, Brugia malayi

    PubMed Central

    2012-01-01

    Background RNA interference (RNAi) is an efficient reverse genetics technique for investigating gene function in eukaryotes. The method has been widely used in model organisms, such as the free-living nematode Caenorhabditis elegans, where it has been deployed in genome-wide high throughput screens to identify genes involved in many cellular and developmental processes. However, RNAi techniques have not translated efficiently to animal parasitic nematodes that afflict humans, livestock and companion animals across the globe, creating a dependency on data tentatively inferred from C. elegans. Results We report improved and effective in vitro RNAi procedures we have developed using heterogeneous short interfering RNA (hsiRNA) mixtures that when coupled with optimized immunostaining techniques yield detailed analysis of cytological defects in the human parasitic nematode, Brugia malayi. The cellular disorganization observed in B. malayi embryos following RNAi targeting the genes encoding γ-tubulin, and the polarity determinant protein, PAR-1, faithfully phenocopy the known defects associated with gene silencing of their C. elegans orthologs. Targeting the B. malayi cell junction protein, AJM-1 gave a similar but more severe phenotype than that observed in C. elegans. Cellular phenotypes induced by our in vitro RNAi procedure can be observed by immunofluorescence in as little as one week. Conclusions We observed cytological defects following RNAi targeting all seven B. malayi transcripts tested and the phenotypes mirror those documented for orthologous genes in the model organism C. elegans. This highlights the reliability, effectiveness and specificity of our RNAi and immunostaining procedures. We anticipate that these techniques will be widely applicable to other important animal parasitic nematodes, which have hitherto been mostly refractory to such genetic analysis. PMID:22243803

  18. Exploring molecular variation in Schistosoma japonicum in China

    PubMed Central

    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.

    2015-01-01

    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. PMID:26621075

  19. Interaction of Plasmodium vivax Tryptophan-rich Antigen PvTRAg38 with Band 3 on Human Erythrocyte Surface Facilitates Parasite Growth*

    PubMed Central

    Alam, Mohd. Shoeb; Choudhary, Vandana; Zeeshan, Mohammad; Tyagi, Rupesh K.; Rathore, Sumit; Sharma, Yagya D.

    2015-01-01

    Plasmodium tryptophan-rich proteins are involved in host-parasite interaction and thus potential drug/vaccine targets. Recently, we have described several P. vivax tryptophan-rich antigens (PvTRAgs), including merozoite expressed PvTRAg38, from this noncultivable human malaria parasite. PvTRAg38 is highly immunogenic in humans and binds to host erythrocytes, and this binding is inhibited by the patient sera. This binding is also affected if host erythrocytes were pretreated with chymotrypsin. Here, Band 3 has been identified as the chymotrypsin-sensitive erythrocyte receptor for this parasite protein. Interaction of PvTRAg38 with Band 3 has been mapped to its three different ectodomains (loops 1, 3, and 6) exposed at the surface of the erythrocyte. The binding region of PvTRAg38 to Band3 has been mapped to its sequence, KWVQWKNDKIRSWLSSEW, present at amino acid positions 197–214. The recombinant PvTRAg38 was able to inhibit the parasite growth in in vitro Plasmodium falciparum culture probably by competing with the ligand(s) of this heterologous parasite for the erythrocyte Band 3 receptor. In conclusion, the host-parasite interaction at the molecular level is much more complicated than known so far and should be considered during the development of anti-malarial therapeutics. PMID:26149684

  20. Asexual Populations of the Human Malaria Parasite, Plasmodium falciparum, Use a Two-Step Genomic Strategy to Acquire Accurate, Beneficial DNA Amplifications

    PubMed Central

    Ahyong, Vida; Patrapuvich, Rapatbhorn; White, John; Gujjar, Ramesh; Phillips, Margaret A.; DeRisi, Joseph; Rathod, Pradipsinh K.

    2013-01-01

    Malaria drug resistance contributes to up to a million annual deaths. Judicious deployment of new antimalarials and vaccines could benefit from an understanding of early molecular events that promote the evolution of parasites. Continuous in vitro challenge of Plasmodium falciparum parasites with a novel dihydroorotate dehydrogenase (DHODH) inhibitor reproducibly selected for resistant parasites. Genome-wide analysis of independently-derived resistant clones revealed a two-step strategy to evolutionary success. Some haploid blood-stage parasites first survive antimalarial pressure through fortuitous DNA duplications that always included the DHODH gene. Independently-selected parasites had different sized amplification units but they were always flanked by distant A/T tracks. Higher level amplification and resistance was attained using a second, more efficient and more accurate, mechanism for head-to-tail expansion of the founder unit. This second homology-based process could faithfully tune DNA copy numbers in either direction, always retaining the unique DNA amplification sequence from the original A/T-mediated duplication for that parasite line. Pseudo-polyploidy at relevant genomic loci sets the stage for gaining additional mutations at the locus of interest. Overall, we reveal a population-based genomic strategy for mutagenesis that operates in human stages of P. falciparum to efficiently yield resistance-causing genetic changes at the correct locus in a successful parasite. Importantly, these founding events arise with precision; no other new amplifications are seen in the resistant haploid blood stage parasite. This minimizes the need for meiotic genetic cleansing that can only occur in sexual stage development of the parasite in mosquitoes. PMID:23717205

  1. Newly incriminated anopheline vectors of human malaria parasites in Junin Department, Peru.

    PubMed

    Hayes, J; Calderon, G; Falcon, R; Zambrano, V

    1987-09-01

    Sporozoite data from salivary gland dissections are presented that clearly incriminate Anopheles trinkae, An. pseudopunctipennis, An. sp. near fluminensis, An. oswaldoi, An. nuneztovari and An. rangeli as vectors of malaria parasites in the Rio Ene Valley, a hyperendemic malarious area in Junin Department, eastern Peru. Anopheles trinkae is considered the most important vector based on dissections, abundance and man-vector contact. Other notes are presented on the relative abundance, bionomics and previous records of these species in Peru and in the study sites. PMID:3333060

  2. Human infection by acanthocephalan parasites belonging to the genus Corynosoma found from small bowel endoscopy.

    PubMed

    Fujita, Tomoki; Waga, Eriko; Kitaoka, Keisuke; Imagawa, Takayuki; Komatsu, Yuuya; Takanashi, Kunihiro; Anbo, Fumie; Anbo, Tomonori; Katuki, Shinichi; Ichihara, Shin; Fujimori, Shunji; Yamasaki, Hiroshi; Morishima, Yasuyuki; Sugiyama, Hiromu; Katahira, Hirotaka

    2016-10-01

    A 73-year-old man with a suspected ileus in January 2013 and subsequently suffered melena in February 2014 was endoscopically examined. As a result of the examinations, unidentified species of Corynosoma sp. and Corynosoma villosum were recovered from the small intestine, further endoscopic diagnosis suggested relevance between abdominal pain and the present infections in the small intestine. The recovered worms were composed of gravid females with developed eggs, suggesting that these parasites can survive for a long time in the intestine after infection. In this case, the short interval between infections appears to be due to the individual's eating habits which consist of regularly consuming uncooked seafood. PMID:27396515

  3. Human cysticercosis and intestinal parasitism amongst the Ekari people of Irian Jaya.

    PubMed

    Muller, R; Lillywhite, J; Bending, J J; Catford, J C

    1987-12-01

    A random sample of 242 people showed that 42 had palpable cysts of Taenia solium. Faecal examination recovered eggs of T. solium in seven (3%), while Trichuris (83%), Ascaris (83%), hookworms (76%), Strongyloides stercoralis (10%) and Strongyloides sp. (29%), Entamoeba histolytica (14%), Entamoeba coli (22%), Entamoeba hartmanni (7%), Entamoeba polecki (7%), Balantidium coli (9%) and Dientamoeba fragilis (21%) were the most common other intestinal parasites encountered. ELISA tests, using antigens prepared from adults and eggs of T. solium and from cysticerci of T. saginata were not very sensitive, the last diagnosing less than half of known positives while still retaining good specificity. PMID:3430662

  4. 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

  5. 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

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

    PubMed

    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

  7. 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. PMID:27114544

  8. Crystallization and X-ray analysis of the Schistosoma mansoni guanidino kinase

    PubMed Central

    Awama, Ayman M.; Paracuellos, Patricia; Laurent, Sabine; Dissous, Colette; Marcillat, Olivier; Gouet, Patrice

    2008-01-01

    The 716-amino-acid guanidino kinase from the parasitic flatworm Schistosoma mansoni results from the fusion of two guanidino kinase subunits. Crystals of this 80 kDa protein have been obtained in the monoclinic space group P21, with unit-cell parameters a = 52.7, b = 122.1, c = 63.2 Å, β = 108.5°. Synchrotron data were collected to 2.8 Å resolution on ESRF beamline ID29. The structure was solved by the molecular-replacement method, using the 357-amino-acid structure of the arginine kinase from Trypanosoma cruzi as the search model. PMID:18765922

  9. DEAD/DExH-Box RNA Helicases in Selected Human Parasites

    PubMed Central

    Marchat, Laurence A.; Arzola-Rodríguez, Silvia I.; Hernandez-de la Cruz, Olga; Lopez-Rosas, Itzel; Lopez-Camarillo, Cesar

    2015-01-01

    DEAD/DExH-box RNA helicases catalyze the folding and remodeling of RNA molecules in prokaryotic and eukaryotic cells, as well as in many viruses. They are characterized by the presence of the helicase domain with conserved motifs that are essential for ATP binding and hydrolysis, RNA interaction, and unwinding activities. Large families of DEAD/DExH-box proteins have been described in different organisms, and their role in all molecular processes involving RNA, from transcriptional regulation to mRNA decay, have been described. This review aims to summarize the current knowledge about DEAD/DExH-box proteins in selected protozoan and nematode parasites of medical importance worldwide, such as Plasmodium falciparum, Leishmania spp., Trypanosoma spp., Giardia lamblia, Entamoeba histolytica, and Brugia malayi. We discuss the functional characterization of several proteins in an attempt to understand better the molecular mechanisms involving RNA in these pathogens. The current data also highlight that DEAD/DExH-box RNA helicases might represent feasible drug targets due to their vital role in parasite growth and development. PMID:26537038

  10. The Clp Chaperones and Proteases of the Human Malaria Parasite Plasmodium falciparum

    SciTech Connect

    M El Bakkouri; A Pow; A Mulichak; K Cheung; J Artz; M Amani; S Fell; T de Koning-Ward; C Goodman; et al.

    2011-12-31

    The Clpchaperones and proteases play an important role in protein homeostasis in the cell. They are highly conserved across prokaryotes and found also in the mitochondria of eukaryotes and the chloroplasts of plants. They function mainly in the disaggregation, unfolding and degradation of native as well as misfolded proteins. Here, we provide a comprehensive analysis of the Clpchaperones and proteases in the humanmalariaparasitePlasmodiumfalciparum. The parasite contains four Clp ATPases, which we term PfClpB1, PfClpB2, PfClpC and PfClpM. One PfClpP, the proteolytic subunit, and one PfClpR, which is an inactive version of the protease, were also identified. Expression of all Clpchaperones and proteases was confirmed in blood-stage parasites. The proteins were localized to the apicoplast, a non-photosynthetic organelle that accommodates several important metabolic pathways in P. falciparum, with the exception of PfClpB2 (also known as Hsp101), which was found in the parasitophorous vacuole. Both PfClpP and PfClpR form mostly homoheptameric rings as observed by size-exclusion chromatography, analytical ultracentrifugation and electron microscopy. The X-ray structure of PfClpP showed the protein as a compacted tetradecamer similar to that observed for Streptococcus pneumoniae and Mycobacterium tuberculosis ClpPs. Our data suggest the presence of a ClpCRP complex in the apicoplast of P. falciparum.

  11. The Plasmodium PHIST and RESA-Like Protein Families of Human and Rodent Malaria Parasites.

    PubMed

    Moreira, Cristina K; Naissant, Bernina; Coppi, Alida; Bennett, Brandy L; Aime, Elena; Franke-Fayard, Blandine; Janse, Chris J; Coppens, Isabelle; Sinnis, Photini; Templeton, Thomas J

    2016-01-01

    The phist gene family has members identified across the Plasmodium genus, defined by the presence of a domain of roughly 150 amino acids having conserved aromatic residues and an all alpha-helical structure. The family is highly amplified in P. falciparum, with 65 predicted genes in the genome of the 3D7 isolate. In contrast, in the rodent malaria parasite P. berghei 3 genes are identified, one of which is an apparent pseudogene. Transcripts of the P. berghei phist genes are predominant in schizonts, whereas in P. falciparum transcript profiles span different asexual blood stages and gametocytes. We pursued targeted disruption of P. berghei phist genes in order to characterize a simplistic model for the expanded phist gene repertoire in P. falciparum. Unsuccessful attempts to disrupt P. berghei PBANKA_114540 suggest that this phist gene is essential, while knockout of phist PBANKA_122900 shows an apparent normal progression and non-essential function throughout the life cycle. Epitope-tagging of P. falciparum and P. berghei phist genes confirmed protein export to the erythrocyte cytoplasm and localization with a punctate pattern. Three P. berghei PEXEL/HT-positive exported proteins exhibit at least partial co-localization, in support of a common vesicular compartment in the cytoplasm of erythrocytes infected with rodent malaria parasites. PMID:27022937

  12. The Plasmodium PHIST and RESA-Like Protein Families of Human and Rodent Malaria Parasites

    PubMed Central

    Moreira, Cristina K.; Naissant, Bernina; Coppi, Alida; Bennett, Brandy L.; Aime, Elena; Franke-Fayard, Blandine; Janse, Chris J.; Coppens, Isabelle; Sinnis, Photini; Templeton, Thomas J.

    2016-01-01

    The phist gene family has members identified across the Plasmodium genus, defined by the presence of a domain of roughly 150 amino acids having conserved aromatic residues and an all alpha-helical structure. The family is highly amplified in P. falciparum, with 65 predicted genes in the genome of the 3D7 isolate. In contrast, in the rodent malaria parasite P. berghei 3 genes are identified, one of which is an apparent pseudogene. Transcripts of the P. berghei phist genes are predominant in schizonts, whereas in P. falciparum transcript profiles span different asexual blood stages and gametocytes. We pursued targeted disruption of P. berghei phist genes in order to characterize a simplistic model for the expanded phist gene repertoire in P. falciparum. Unsuccessful attempts to disrupt P. berghei PBANKA_114540 suggest that this phist gene is essential, while knockout of phist PBANKA_122900 shows an apparent normal progression and non-essential function throughout the life cycle. Epitope-tagging of P. falciparum and P. berghei phist genes confirmed protein export to the erythrocyte cytoplasm and localization with a punctate pattern. Three P. berghei PEXEL/HT-positive exported proteins exhibit at least partial co-localization, in support of a common vesicular compartment in the cytoplasm of erythrocytes infected with rodent malaria parasites. PMID:27022937

  13. Within-host competition and drug resistance in the human malaria parasite Plasmodium falciparum.

    PubMed

    Bushman, Mary; Morton, Lindsay; Duah, Nancy; Quashie, Neils; Abuaku, Benjamin; Koram, Kwadwo A; Dimbu, Pedro Rafael; Plucinski, Mateusz; Gutman, Julie; Lyaruu, Peter; Kachur, S Patrick; de Roode, Jacobus C; Udhayakumar, Venkatachalam

    2016-03-16

    Infections with the malaria parasite Plasmodium falciparum typically comprise multiple strains, especially in high-transmission areas where infectious mosquito bites occur frequently. However, little is known about the dynamics of mixed-strain infections, particularly whether strains sharing a host compete or grow independently. Competition between drug-sensitive and drug-resistant strains, if it occurs, could be a crucial determinant of the spread of resistance. We analysed 1341 P. falciparum infections in children from Angola, Ghana and Tanzania and found compelling evidence for competition in mixed-strain infections: overall parasite density did not increase with additional strains, and densities of individual chloroquine-sensitive (CQS) and chloroquine-resistant (CQR) strains were reduced in the presence of competitors. We also found that CQR strains exhibited low densities compared with CQS strains (in the absence of chloroquine), which may underlie observed declines of chloroquine resistance in many countries following retirement of chloroquine as a first-line therapy. Our observations support a key role for within-host competition in the evolution of drug-resistant malaria. Malaria control and resistance-management efforts in high-transmission regions may be significantly aided or hindered by the effects of competition in mixed-strain infections. Consideration of within-host dynamics may spur development of novel strategies to minimize resistance while maximizing the benefits of control measures. PMID:26984625

  14. Identification of Host Insulin Binding Sites on Schistosoma japonicum Insulin Receptors

    PubMed Central

    Stephenson, Rachel J.; Toth, Istvan; Liang, Jiening; Mangat, Amanjot; McManus, Donald P.; You, Hong

    2016-01-01

    Schistosoma japonicum insulin receptors (SjIRs) have been identified as encouraging vaccine candidates. Interrupting or blocking the binding between host insulin and the schistosome insulin receptors (IRs) may result in reduced glucose uptake leading to starvation and stunting of worms with a reduction in egg output. To further understand how schistosomes are able to exploit host insulin for development and growth, and whether these parasites and their mammalian hosts compete for the same insulin source, we identified insulin binding sites on the SjIRs. Based on sequence analysis and the predicted antigenic structure of the primary sequences of the SjIRs, we designed nine and eleven peptide analogues from SjIR-1 and SjIR-2, respectively. Using the Octet RED system, we identified analogues derived from SjIR-1 (10) and SjIR-2 (20, 21 and 22) with insulin-binding sequences specific for S. japonicum. Nevertheless, the human insulin receptor (HIR) may compete with the SjIRs in binding human insulin in other positions which are important for HIR binding to insulin. However, no binding occurred between insulin and parasite analogues derived from SjIR-1 (2, 7 and 8) and SjIR-2 (14, 16 and 18) at the same locations as HIR sequences which have been shown to have strong insulin binding affinities. Importantly, we found two analogues (1 and 3), derived from SjIR-1, and two analogues (13 and 15) derived from SjIR-2, were responsible for the major insulin binding affinity in S. japonicum. These peptide analogues were shown to have more than 10 times (in KD value) stronger binding capacity for human insulin compared with peptides derived from the HIR in the same sequence positions. Paradoxically, analogues 1, 3, 13 and 15 do not appear to contain major antigenic determinants which resulted in poor antibody responses to native S. japonicum protein. This argues against their future development as peptide-vaccine candidates. PMID:27441998

  15. Parasites: Water

    MedlinePlus

    ... Tropical Diseases Laboratory Diagnostic Assistance [DPDx] Parasites Home Water Recommend on Facebook Tweet Share Compartir Parasites can live in natural water sources. When outdoors, treat your water before drinking ...

  16. Cultivation of a human-associated TM7 phylotype reveals a reduced genome and epibiotic parasitic lifestyle

    PubMed Central

    He, Xuesong; McLean, Jeffrey S.; Edlund, Anna; Yooseph, Shibu; Hall, Adam P.; Liu, Su-Yang; Dorrestein, Pieter C.; Esquenazi, Eduardo; Hunter, Ryan C.; Cheng, Genhong; Nelson, Karen E.; Lux, Renate; Shi, Wenyuan

    2015-01-01

    The candidate phylum TM7 is globally distributed and often associated with human inflammatory mucosal diseases. Despite its prevalence, the TM7 phylum remains recalcitrant to cultivation, making it one of the most enigmatic phyla known. In this study, we cultivated a TM7 phylotype (TM7x) from the human oral cavity. This extremely small coccus (200–300 nm) has a distinctive lifestyle not previously observed in human-associated microbes. It is an obligate epibiont of an Actinomyces odontolyticus strain (XH001) yet also has a parasitic phase, thereby killing its host. This first completed genome (705 kb) for a human-associated TM7 phylotype revealed a complete lack of amino acid biosynthetic capacity. Comparative genomics analyses with uncultivated environmental TM7 assemblies show remarkable conserved gene synteny and only minimal gene loss/gain that may have occurred as TM7x adapted to conditions within the human host. Transcriptomic and metabolomic profiles provided the first indications, to our knowledge, that there is signaling interaction between TM7x and XH001. Furthermore, the induction of TNF-α production in macrophages by XH001 was repressed in the presence of TM7x, suggesting its potential immune suppression ability. Overall, our data provide intriguing insights into the uncultivability, pathogenicity, and unique lifestyle of this previously uncharacterized oral TM7 phylotype. PMID:25535390

  17. Praziquantel: physiological evidence for its site(s) of action in magnesium-paralysed Schistosoma mansoni.

    PubMed

    Blair, K L; Bennett, J L; Pax, R A

    1992-02-01

    The mechanism whereby praziquantel produces a contraction and subsequent flaccid paralysis (a loss of sensitivity to subsequent stimuli) of Schistosoma mansoni in a medium containing an elevated Mg2+:Ca2+ ratio was investigated. In RPMI, praziquantel produced a concentration-dependent tonic contraction of the parasite with an EC50 of 200 nM. Magnesium inhibited the contraction in such a manner as to convert the tonic contraction to a phasic one without altering the peak force generated. The Mg(2+)-dependent block was non-competitive with praziquantel but was competitive with extracellular Ca2+, ratios of 7.5:1;Mg2+:Ca2+ being needed to inhibit the tonic contraction and to induce flaccid paralysis. Flaccid paralysis was associated with a reduced ability of the parasite to take up 45Ca2+ from the bath compared to parasites that had not entered into flaccid paralysis and flaccid paralysis was reversible. Recovery from flaccid paralysis was accelerated by treatments that are expected to increase Ca2+ uptake by the parasite. At a concentration of 500 nM, praziquantel produced 2 distinct phasic contractions in intact parasites incubated in an elevated [Mg2+] medium but only 1 phasic contraction in parasites lacking their surface tegumental membranes. In zero Ca2+ I-RPMI, 10 microM praziquantel produced a phasic contraction of intact parasites but did not stimulate contraction of detegumented parasites until Ca2+ was reintroduced into the bath. These results indicate that praziquantel interacts with specific Ca(2+)-permeable sites in the tegumental and sarcoplasmic membranes of the parasite and that under these conditions of elevated Mg2+:Ca2+ ratios, these sites become blocked by Mg2+, leading to flaccid paralysis of the parasite. PMID:1614741

  18. Genome sequences of the human body louse and its primary endosymbiont provide insights into the permanent parasitic lifestyle

    PubMed Central

    Kirkness, Ewen F.; Haas, Brian J.; Sun, Weilin; Braig, Henk R.; Perotti, M. Alejandra; Clark, John M.; Lee, Si Hyeock; Robertson, Hugh M.; Kennedy, Ryan C.; Elhaik, Eran; Gerlach, Daniel; Kriventseva, Evgenia V.; Elsik, Christine G.; Graur, Dan; Hill, Catherine A.; Veenstra, Jan A.; Walenz, Brian; Tubío, José Manuel C.; Ribeiro, José M. C.; Rozas, Julio; Johnston, J. Spencer; Reese, Justin T.; Popadic, Aleksandar; Tojo, Marta; Raoult, Didier; Reed, David L.; Tomoyasu, Yoshinori; Kraus, Emily; Mittapalli, Omprakash; Margam, Venu M.; Li, Hong-Mei; Meyer, Jason M.; Johnson, Reed M.; Romero-Severson, Jeanne; VanZee, Janice Pagel; Alvarez-Ponce, David; Vieira, Filipe G.; Aguadé, Montserrat; Guirao-Rico, Sara; Anzola, Juan M.; Yoon, Kyong S.; Strycharz, Joseph P.; Unger, Maria F.; Christley, Scott; Lobo, Neil F.; Seufferheld, Manfredo J.; Wang, NaiKuan; Dasch, Gregory A.; Struchiner, Claudio J.; Madey, Greg; Hannick, Linda I.; Bidwell, Shelby; Joardar, Vinita; Caler, Elisabet; Shao, Renfu; Barker, Stephen C.; Cameron, Stephen; Bruggner, Robert V.; Regier, Allison; Johnson, Justin; Viswanathan, Lakshmi; Utterback, Terry R.; Sutton, Granger G.; Lawson, Daniel; Waterhouse, Robert M.; Venter, J. Craig; Strausberg, Robert L.; Collins, Frank H.; Zdobnov, Evgeny M.; Pittendrigh, Barry R.

    2010-01-01

    As an obligatory parasite of humans, the body louse (Pediculus humanus humanus) is an important vector for human diseases, including epidemic typhus, relapsing fever, and trench fever. Here, we present genome sequences of the body louse and its primary bacterial endosymbiont Candidatus Riesia pediculicola. The body louse has the smallest known insect genome, spanning 108 Mb. Despite its status as an obligate parasite, it retains a remarkably complete basal insect repertoire of 10,773 protein-coding genes and 57 microRNAs. Representing hemimetabolous insects, the genome of the body louse thus provides a reference for studies of holometabolous insects. Compared with other insect genomes, the body louse genome contains significantly fewer genes associated with environmental sensing and response, including odorant and gustatory receptors and detoxifying enzymes. The unique architecture of the 18 minicircular mitochondrial chromosomes of the body louse may be linked to the loss of the gene encoding the mitochondrial single-stranded DNA binding protein. The genome of the obligatory louse endosymbiont Candidatus Riesia pediculicola encodes less than 600 genes on a short, linear chromosome and a circular plasmid. The plasmid harbors a unique arrangement of genes required for the synthesis of pantothenate, an essential vitamin deficient in the louse diet. The human body louse, its primary endosymbiont, and the bacterial pathogens that it vectors all possess genomes reduced in size compared with their free-living close relatives. Thus, the body louse genome project offers unique information and tools to use in advancing understanding of coevolution among vectors, symbionts, and pathogens. PMID:20566863

  19. The streamlined genome of Phytomonas spp. relative to human pathogenic kinetoplastids reveals a parasite tailored for plants.

    PubMed

    Porcel, Betina M; Denoeud, France; Opperdoes, Fred; Noel, Benjamin; Madoui, Mohammed-Amine; Hammarton, Tansy C; Field, Mark C; Da Silva, Corinne; Couloux, Arnaud; Poulain, Julie; Katinka, Michael; Jabbari, Kamel; Aury, Jean-Marc; Campbell, David A; Cintron, Roxana; Dickens, Nicholas J; Docampo, Roberto; Sturm, Nancy R; Koumandou, V Lila; Fabre, Sandrine; Flegontov, Pavel; Lukeš, Julius; Michaeli, Shulamit; Mottram, Jeremy C; Szöőr, Balázs; Zilberstein, Dan; Bringaud, Frédéric; Wincker, Patrick; Dollet, Michel

    2014-02-01

    Members of the family Trypanosomatidae infect many organisms, including animals, plants and humans. Plant-infecting trypanosomes are grouped under the single genus Phytomonas, failing to reflect the wide biological and pathological diversity of these protists. While some Phytomonas spp. multiply in the latex of plants, or in fruit or seeds without apparent pathogenicity, others colonize the phloem sap and afflict plants of substantial economic value, including the coffee tree, coconut and oil palms. Plant trypanosomes have not been studied extensively at the genome level, a major gap in understanding and controlling pathogenesis. We describe the genome sequences of two plant trypanosomatids, one pathogenic isolate from a Guianan coconut and one non-symptomatic isolate from Euphorbia collected in France. Although these parasites have extremely distinct pathogenic impacts, very few genes are unique to either, with the vast majority of genes shared by both isolates. Significantly, both Phytomonas spp. genomes consist essentially of single copy genes for the bulk of their metabolic enzymes, whereas other trypanosomatids e.g. Leishmania and Trypanosoma possess multiple paralogous genes or families. Indeed, comparison with other trypanosomatid genomes revealed a highly streamlined genome, encoding for a minimized metabolic system while conserving the major pathways, and with retention of a full complement of endomembrane organelles, but with no evidence for functional complexity. Identification of the metabolic genes of Phytomonas provides opportunities for establishing in vitro culturing of these fastidious parasites and new tools for the control of agricultural plant disease. PMID:24516393

  20. The Streamlined Genome of Phytomonas spp. Relative to Human Pathogenic Kinetoplastids Reveals a Parasite Tailored for Plants

    PubMed Central

    Porcel, Betina M.; Denoeud, France; Opperdoes, Fred; Noel, Benjamin; Madoui, Mohammed-Amine; Hammarton, Tansy C.; Field, Mark C.; Da Silva, Corinne; Couloux, Arnaud; Poulain, Julie; Katinka, Michael; Jabbari, Kamel; Aury, Jean-Marc; Campbell, David A.; Cintron, Roxana; Dickens, Nicholas J.; Docampo, Roberto; Sturm, Nancy R.; Koumandou, V. Lila; Fabre, Sandrine; Flegontov, Pavel; Lukeš, Julius; Michaeli, Shulamit; Mottram, Jeremy C.; Szöőr, Balázs; Zilberstein, Dan; Bringaud, Frédéric; Wincker, Patrick; Dollet, Michel

    2014-01-01

    Members of the family Trypanosomatidae infect many organisms, including animals, plants and humans. Plant-infecting trypanosomes are grouped under the single genus Phytomonas, failing to reflect the wide biological and pathological diversity of these protists. While some Phytomonas spp. multiply in the latex of plants, or in fruit or seeds without apparent pathogenicity, others colonize the phloem sap and afflict plants of substantial economic value, including the coffee tree, coconut and oil palms. Plant trypanosomes have not been studied extensively at the genome level, a major gap in understanding and controlling pathogenesis. We describe the genome sequences of two plant trypanosomatids, one pathogenic isolate from a Guianan coconut and one non-symptomatic isolate from Euphorbia collected in France. Although these parasites have extremely distinct pathogenic impacts, very few genes are unique to either, with the vast majority of genes shared by both isolates. Significantly, both Phytomonas spp. genomes consist essentially of single copy genes for the bulk of their metabolic enzymes, whereas other trypanosomatids e.g. Leishmania and Trypanosoma possess multiple paralogous genes or families. Indeed, comparison with other trypanosomatid genomes revealed a highly streamlined genome, encoding for a minimized metabolic system while conserving the major pathways, and with retention of a full complement of endomembrane organelles, but with no evidence for functional complexity. Identification of the metabolic genes of Phytomonas provides opportunities for establishing in vitro culturing of these fastidious parasites and new tools for the control of agricultural plant disease. PMID:24516393

  1. Crystallization and preliminary crystallographic analysis of orotidine 5′-monophosphate decarboxylase from the human malaria parasite Plasmodium falciparum

    SciTech Connect

    Krungkrai, Sudaratana R.; Tokuoka, Keiji; Kusakari, Yukiko; Inoue, Tsuyoshi; Adachi, Hiroaki; Matsumura, Hiroyoshi; Takano, Kazufumi; Murakami, Satoshi; Mori, Yusuke; Kai, Yasushi; Krungkrai, Jerapan; Horii, Toshihiro

    2006-06-01

    Orotidine 5′-monophosphate decarboxylase of human malaria parasite P. falciparum was crystallized by the seeding method in a hanging drop using PEG 3000 as a precipitant. A complete set of diffraction data from a native crystal was collected to 2.7 Å resolution at 100 K using synchrotron radiation. Orotidine 5′-monophosphate (OMP) decarboxylase (OMPDC; EC 4.1.1.23) catalyzes the final step in the de novo synthesis of uridine 5′-monophosphate (UMP) and defects in the enzyme are lethal in the malaria parasite Plasmodium falciparum. Active recombinant P. falciparum OMPDC (PfOMPDC) was crystallized by the seeding method in a hanging drop using PEG 3000 as a precipitant. A complete set of diffraction data from a native crystal was collected to 2.7 Å resolution at 100 K using synchrotron radiation at the Swiss Light Source. The crystal exhibits trigonal symmetry (space group R3), with hexagonal unit-cell parameters a = b = 201.81, c = 44.03 Å. With a dimer in the asymmetric unit, the solvent content is 46% (V{sub M} = 2.3 Å{sup 3} Da{sup −1})

  2. Serine protease inhibitors of parasitic helminths.

    PubMed

    Molehin, Adebayo J; Gobert, Geoffrey N; McManus, Donald P

    2012-05-01

    Serine protease inhibitors (serpins) are a superfamily of structurally conserved proteins that inhibit serine proteases and play key physiological roles in numerous biological systems such as blood coagulation, complement activation and inflammation. A number of serpins have now been identified in parasitic helminths with putative involvement in immune regulation and in parasite survival through interference with the host immune response. This review describes the serpins and smapins (small serine protease inhibitors) that have been identified in Ascaris spp., Brugia malayi, Ancylostoma caninum Onchocerca volvulus, Haemonchus contortus, Trichinella spiralis, Trichostrongylus vitrinus, Anisakis simplex, Trichuris suis, Schistosoma spp., Clonorchis sinensis, Paragonimus westermani and Echinococcus spp. and discusses their possible biological functions, including roles in host-parasite interplay and their evolutionary relationships. PMID:22310379

  3. Serum albumin and α-1 acid glycoprotein impede the killing of Schistosoma mansoni by the tyrosine kinase inhibitor Imatinib.

    PubMed

    Beckmann, Svenja; Long, Thavy; Scheld, Christina; Geyer, Rudolf; Caffrey, Conor R; Grevelding, Christoph G

    2014-12-01

    In the search for new drugs and drug targets to treat the flatworm disease schistosomiasis, protein kinases (PKs) have come under particular scrutiny because of their essential roles in developmental and physiological processes in schistosome parasites. In this context the application of the anti-cancer Abl tyrosine kinase (TK) inhibitor Imatinib (Gleevec/Glivec; STI-571) to adult Schistosoma mansoni in vitro has indicated negative effects on diverse physiological processes including survival. Motivated by these in vitro findings, we performed in vivo experiments in rodent models of S. mansoni infection. Unexpectedly, Imatinib had no effect on worm burden or egg-production. We found that the blood components serum albumin (SA) and alpha-1 acid glycoprotein (AGP or orosomucoid) negated Imatinib's deleterious effects on adult S. mansoni and schistosomula (post-infective larvae) in vitro. This negative effect was partially reversed by erythromycin. AGP synthesis can increase as a consequence of inflammatory processes or infection; in addition upon infection AGP levels are 6-8 times higher in mice compared to humans. Therefore, mice and probably other rodents are poor infection models for measuring the effects of Imatinib in vivo. Accordingly, we suggest the routine evaluation of the ability of AGP and SA to block in vitro anti-schistosomal effects of small molecules like Imatinib prior to laborious and expensive animal experiments. PMID:25516839

  4. 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. PMID:27253696

  5. Retrotransposon-microsatellite amplified polymorphism, an electrophoretic approach for studying genetic variability among Schistosoma japonicum geographical isolates.

    PubMed

    Li, Juan; Zhao, Guang-Hui; Zhou, Dong-Hui; Sugiyama, Hiromu; Nisbet, Alasdair J; Li, Xiao-Yan; Zou, Feng-Cai; Li, Hai-Long; Ai, Lin; Zhu, Xing-Quan

    2012-09-01

    In the present study, retrotransposon-microsatellite amplified polymorphism (REMAP) was used to examine genetic variability among Schistosoma japonicum isolates from different endemic provinces in mainland China, using S. japonicum from Japan and the Philippines for comparison. Of the 50 primer combinations screened, eight produced highly reproducible REMAP fragments. Using these primers, 190 distinct DNA fragments were generated in total, of which 147 (77.37%) were polymorphic, indicating considerable genetic variation among the 43 S. japonicum isolates examined. The percentage of polymorphic bands (PPB) among S. japonicum isolates from mainland China, Japan, and the Philippines was 77.37%; PPB values of 18.42% and 53.68% were found among isolates from southwestern (SW) China and the lower Yangtze/Zhejiang province in eastern (E) China, respectively. Based on REMAP profiles, unweighted pair-group method with arithmetic averages (UPGMA) dendrogram analysis revealed that all of the S. japonicum samples grouped into three distinct clusters: parasites from mainland China, Japan, and the Philippines were clustered in each individual clade. Within the mainland China cluster, SW China isolates (from Sichuan and Yunnan provinces) grouped together, whereas worms from E China (Zhejiang, Anhui, Jiangxi, Jiangsu, Hunan, and Hubei provinces) grouped together. These results demonstrated that the REMAP marker system provides a reliable electrophoretic technique for studying genetic diversity and population structures of S. japonicum isolates from mainland China, and could be applied to other pathogens of human and animal health significance. PMID:23019103

  6. Protein Kinase C and Extracellular Signal-Regulated Kinase Regulate Movement, Attachment, Pairing and Egg Release in Schistosoma mansoni

    PubMed Central

    Ressurreição, Margarida; De Saram, Paulu; Kirk, Ruth S.; Rollinson, David; Emery, Aidan M.; Page, Nigel M.; Davies, Angela J.; Walker, Anthony J.

    2014-01-01

    Protein kinases C (PKCs) and extracellular signal-regulated kinases (ERKs) are evolutionary conserved cell signalling enzymes that coordinate cell function. Here we have employed biochemical approaches using ‘smart’ antibodies and functional screening to unravel the importance of these enzymes to Schistosoma mansoni physiology. Various PKC and ERK isotypes were detected, and were differentially phosphorylated (activated) throughout the various S. mansoni life stages, suggesting isotype-specific roles and differences in signalling complexity during parasite development. Functional kinase mapping in adult worms revealed that activated PKC and ERK were particularly associated with the adult male tegument, musculature and oesophagus and occasionally with the oesophageal gland; other structures possessing detectable activated PKC and/or ERK included the Mehlis' gland, ootype, lumen of the vitellaria, seminal receptacle and excretory ducts. Pharmacological modulation of PKC and ERK activity in adult worms using GF109203X, U0126, or PMA, resulted in significant physiological disturbance commensurate with these proteins occupying a central position in signalling pathways associated with schistosome muscular activity, neuromuscular coordination, reproductive function, attachment and pairing. Increased activation of ERK and PKC was also detected in worms following praziquantel treatment, with increased signalling associated with the tegument and excretory system and activated ERK localizing to previously unseen structures, including the cephalic ganglia. These findings support roles for PKC and ERK in S. mansoni homeostasis, and identify these kinase groups as potential targets for chemotherapeutic treatments against human schistosomiasis, a neglected tropical disease of enormous public health significance. PMID:24921927

  7. Proteomic Analysis on Cercariae and Schistosomula in Reference to Potential Proteases Involved in Host Invasion of Schistosoma japonicum Larvae.

    PubMed

    Liu, Mu; Ju, Chuan; Du, Xiao-Feng; Shen, Hai-Mo; Wang, Ji-Peng; Li, Jian; Zhang, Xu-Min; Feng, Zheng; Hu, Wei

    2015-11-01

    Schistosomiasis is a parasitic zoonosis posing great threat to human health. The infection is acquired by larval cercariae penetrating host skin and transforming into juveniles, schistosomula. Proteolytic enzymes secreted from the cercarial acetabular glands are known to aid to the skin penetration, but molecular mechanisms remain largely unclear. To profile the protein composition and identify potential invasive proteases, we developed a new method for simulating cercarial transformation and collecting schistosomula, and for the first time, we compared the proteomes of Schistosoma japonicum cercariae and schistosomula by using in-gel shotgun proteomic analysis. Totally, 1972 proteins were identified in association with ten main biological processes based on Gene Ontology analysis; 46 proteases were detected in cercariae, and among them, 25 proteases disappeared after penetrated. Notably, leishmanolysins and serine and cysteine proteases were found abundant but differentially expressed. Recombinant serine protease SjCE2b and cysteine protease SjCB2 were produced and used for validation of native proteins. Immunofluorescence and Western blotting assays detected SjCE2b and SjCB2 in cercariae but not in schistosomula, suggesting the two enzymes might be consumed upon skin migration. Our data comprehensively chart the proteomic changes during cercarial invasion, revealing the potential proteases involved, providing a platform for the development of molecular anti-infection strategy. PMID:26370134

  8. 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

  9. 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

  10. Serum albumin and α-1 acid glycoprotein impede the killing of Schistosoma mansoni by the tyrosine kinase inhibitor Imatinib

    PubMed Central

    Beckmann, Svenja; Long, Thavy; Scheld, Christina; Geyer, Rudolf; Caffrey, Conor R.; Grevelding, Christoph G.

    2014-01-01

    In the search for new drugs and drug targets to treat the flatworm disease schistosomiasis, protein kinases (PKs) have come under particular scrutiny because of their essential roles in developmental and physiological processes in schistosome parasites. In this context the application of the anti-cancer Abl tyrosine kinase (TK) inhibitor Imatinib (Gleevec/Glivec; STI-571) to adult Schistosoma mansoni in vitro has indicated negative effects on diverse physiological processes including survival. Motivated by these in vitro findings, we performed in vivo experiments in rodent models of S. mansoni infection. Unexpectedly, Imatinib had no effect on worm burden or egg-production. We found that the blood components serum albumin (SA) and alpha-1 acid glycoprotein (AGP or orosomucoid) negated Imatinib’s deleterious effects on adult S. mansoni and schistosomula (post-infective larvae) in vitro. This negative effect was partially reversed by erythromycin. AGP synthesis can increase as a consequence of inflammatory processes or infection; in addition upon infection AGP levels are 6–8 times higher in mice compared to humans. Therefore, mice and probably other rodents are poor infection models for measuring the effects of Imatinib in vivo. Accordingly, we suggest the routine evaluation of the ability of AGP and SA to block in vitro anti-schistosomal effects of small molecules like Imatinib prior to laborious and expensive animal experiments. PMID:25516839

  11. The Redox Biology of Schistosome Parasites and Applications for Drug Development

    PubMed Central

    Huang, Hsin-Hung; Rigouin, Coraline; Williams, David L.

    2013-01-01

    Schistosomiasis caused by Schistosoma spp. is a serious public health concern, especially in sub-Saharan Africa. Praziquantel is the only drug currently administrated to treat this disease. However, praziquantel-resistant parasites have been identified in endemic areas and can be generated in the laboratory. Therefore, it is essential to find new therapeutics. Antioxidants are appealing drug targets. In order to survive in their hosts, schistosomes are challenged by reactive oxygen species from intrinsic and extrinsic sources. Schistosome antioxidant enzymes have been identified as essential proteins and novel drug targets and inhibition of the antioxidant response can lead to parasite death. Because the organization of the redox network in schistosomes is significantly different form that in humans, new drugs are being developed targeting schistosome antioxidants. In this paper the redox biology of schistosomes is discussed and their potential use as drug targets is reviewed. It is hoped that compounds targeting parasite antioxidant responses will become clinically relevant drugs in the near future. PMID:22607149

  12. 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

  13. Synergy of Omeprazole and Praziquantel In Vitro Treatment against Schistosoma mansoni Adult Worms

    PubMed Central

    Anderson, Leticia; Venancio, Thiago M.; Nakaya, Helder I.; Miyasato, Patrícia A.; Rofatto, Henrique K.; Zerlotini, Adhemar; Nakano, Eliana; Oliveira, Guilherme; Verjovski-Almeida, Sergio

    2015-01-01

    Background Treatment and morbidity control of schistosomiasis relies on a single drug, praziquantel (PZQ), and the selection of resistant worms under repeated treatment is a concern. Therefore, there is a pressing need to understand the molecular effects of PZQ on schistosomes and to investigate alternative or synergistic drugs against schistosomiasis. Methodology We used a custom-designed Schistosoma mansoni expression microarray to explore the effects of sublethal doses of PZQ on large-scale gene expression of adult paired males and females and unpaired mature females. We also assessed the efficacy of PZQ, omeprazole (OMP) or their combination against S. mansoni adult worms with a survival in vitro assay. Principal Findings We identified sets of genes that were affected by PZQ in paired and unpaired mature females, however with opposite gene expression patterns (up-regulated in paired and down-regulated in unpaired mature females), indicating that PZQ effects are heavily influenced by the mating status. We also identified genes that were similarly affected by PZQ in males and females. Functional analyses of gene interaction networks were performed with parasite genes that were differentially expressed upon PZQ treatment, searching for proteins encoded by these genes whose human homologs are targets of different drugs used for other diseases. Based on these results, OMP, a widely prescribed proton pump inhibitor known to target the ATP1A2 gene product, was chosen and tested. Sublethal doses of PZQ combined with OMP significantly increased worm mortality in vitro when compared with PZQ or OMP alone, thus evidencing a synergistic effect. Conclusions Functional analysis of gene interaction networks is an important approach that can point to possible novel synergistic drug candidates. We demonstrated the potential of this strategy by showing that PZQ in combination with OMP displayed increased efficiency against S. mansoni adult worms in vitro when compared with

  14. Identification and characterization of six novel tetraspanins from Schistosoma japonicum

    PubMed Central

    2011-01-01

    Background Tetraspanins (TSPs), also known as members of the trans-membrane 4 super-family (TM4SF), comprise an assemblage of surface antigens reported in eukaryotic organisms. In the work presented here, six novel TSP proteins from the human blood fluke Schistosoma japonicum (S. japonicum) were produced and analyzed through a combination of bioinformatics and experimental approaches. Results Six novel TSP proteins of Schistosoma japonicum (designated as Sj-TSP-#1~6) contained four trans-membrane regions and one large extracellular loop (LEL) with a conserved CCG motif. Size of the proteins varied from 227 to 291 amino acid residues. All the six proteins were produced in E.coli and immune sera to each protein were prepared. Analysis of transcription profiles of the proteins by RT-PCR showed that Sj-TSP-#4 was transcribed only in the egg stage while transcription of the Sj-TSP-#2 was detected in female worms but not in males. The similar results were obtained by Western blot. Immunolocalization of the TSP proteins by immunofluorescence assay showed that the Sj-TSP-#2, Sj-TSP-#5 and Sj-TSP-#6 were located in the tegument of worms. Conclusions This study provided six novel TSP members of S. japonicum including their sequences and recombinant proteins. Availability of the novel proteins and information on their expression profile and location provided a basis for further investigation of the TSP proteins for their biological functions and as vaccine candidates. PMID:21958506

  15. Identification and biochemical characterization of macrophage migration inhibitory factor-2 (MIF-2) homologue of human lymphatic filarial parasite, Wuchereria bancrofti.

    PubMed

    Chauhan, Nikhil; Sharma, Rohit; Hoti, S L

    2015-02-01

    Homologues of human macrophage migration inhibitory factor (hMIF) have been reported from vertebrates, invertebrates and prokaryotes, as well as plants. Filarial parasites produce two homologues of hMIF viz., MIF-1 and MIF-2, which play important role in the host immune modulation. Earlier, we have characterized MIF-1 (Wba-mif-1) from Wuchereria bancrofti, the major causal organism of human lymphatic filariasis. Here, we are reporting the molecular and biochemical characterization of MIF-2 from this parasite (Wba-mif-2). The complete Wba-mif-2 gene and its cDNA were amplified, cloned and sequenced. The size of Wba-mif-2 gene and cDNA were found to be 4.275 kb and 363 bp, respectively. The gene annotation revealed the presence of a large intron of 3.912 kb interspersed with two exons of 183 bp and 180 bp. The alignment of derived amino acid sequences of Wba-MIF-2 with Wba-MIF-1 showed 44% homology. The conserved CXXC oxido-reductase catalytic site present in Wba-mif-1 was found absent in Wba-mif-2 coding sequence. The amplified Wba-mif-2 cDNA was cloned into an expression vector pRSET-B and transformed into salt inducible Escherichia coli strain GJ1158. The expressed recombinant Wba-MIF-2 protein showed tautomerase activity against L-dopachrome methyl ester and the specific activity was determined to be 18.57±0.77 μmol/mg/min. Three known inhibitors of hMIF tautomerase activity significantly inhibited the tautomerase activity of recombinant Wba-MIF-2. Although the conserved CXXC oxido-reductase motif is absent in Wba-mif-2, the recombinant protein showed significant oxido-reductase activity in the insulin reduction assay, possibly because of the presence of vicinal cysteine residues. PMID:25446175

  16. Structure-Bioactivity Relationship for Benzimidazole Thiophene Inhibitors of Polo-Like Kinase 1 (PLK1), a Potential Drug Target in Schistosoma mansoni

    PubMed Central

    Long, Thavy; Neitz, R. Jeffrey; Beasley, Rachel; Kalyanaraman, Chakrapani; Suzuki, Brian M.; Jacobson, Matthew P.; Dissous, Colette; McKerrow, James H.; Drewry, David H.; Zuercher, William J.; Singh, Rahul; Caffrey, Conor R.

    2016-01-01

    Background Schistosoma flatworm parasites cause schistosomiasis, a chronic and debilitating disease of poverty in developing countries. Praziquantel is employed for treatment and disease control. However, its efficacy spectrum is incomplete (less active or inactive against immature stages of the parasite) and there is a concern of drug resistance. Thus, there is a need to identify new drugs and drug targets. Methodology/Principal Findings We show that RNA interference (RNAi) of the Schistosoma mansoni ortholog of human polo-like kinase (huPLK)1 elicits a deleterious phenotypic alteration in post-infective larvae (schistosomula or somules). Phenotypic screening and analysis of schistosomula and adult S. mansoni with small molecule inhibitors of huPLK1 identified a number of potent anti-schistosomals. Among these was a GlaxoSmithKline (GSK) benzimidazole thiophene inhibitor that has completed Phase I clinical trials for treatment of solid tumor malignancies. We then obtained GSKs Published Kinase Inhibitor Sets (PKIS) 1 and 2, and phenotypically screened an expanded series of 38 benzimidazole thiophene PLK1 inhibitors. Computational analysis of controls and PLK1 inhibitor-treated populations of somules demonstrated a distinctive phenotype distribution. Using principal component analysis (PCA), the phenotypes exhibited by these populations were mapped, visualized and analyzed through projection to a low-dimensional space. The phenotype distribution was found to have a distinct shape and topology, which could be elicited using cluster analysis. A structure-activity relationship (SAR) was identified for the benzimidazole thiophenes that held for both somules and adult parasites. The most potent inhibitors produced marked phenotypic alterations at 1–2 μM within 1 h. Among these were compounds previously characterized as potent inhibitors of huPLK1 in cell assays. Conclusions/Significance The reverse genetic and chemical SAR data support a continued investigation of Sm

  17. [Immunoenzyme assay of parasite-specific IgG4 antibodies in schistosomiasis using the monoclonal antibody BL-IgG4/1].

    PubMed

    Sauer, H; Ambrosius, H; Behn, I; Fiebig, H; Köllner, B; Leykun, J; Schubert, S; Spannemann, B

    1990-01-01

    Sera from 251 children living in endemic areas (Schistosoma mansoni or Schistosoma haematobium) and from 188 hospital outpatients in Ethiopia were evaluated for specific IgG4 antibodies reacting with Schistosoma mansoni adult worm antigen employing an enzyme-immunoassay. Patients with schistosomiasis (n = 140) possessed a significantly higher mean value of specific IgG4 antibodies than normal controls (n = 30) and individuals from different countries who had no schistosomiasis but are infected with other parasites (n = 114). Blood samples dried on filter paper were also acceptable in these test. The use of the test in diagnosis is compared and assessed with parasitological methods. PMID:2097901

  18. 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. PMID:24966869

  19. Immunopathology of Schistosoma mansoni infection.

    PubMed Central

    Boros, D L

    1989-01-01

    Schistosomiasis mansoni is a chronic helminthic disease that affects about 100 million people in the tropics. The worms have a life span of 5 to 10 years, and they live in the mesenteric veins of the host. Lightly infected individuals are asymptomatic or manifest mild intestinal symptoms. Heavily infected individuals often develop severe morbidity with hepatosplenomegaly, sometimes with a fatal outcome. Morbidity is attributed to the strong humoral and T-cell-mediated host immune responses developed to a variety of parasite antigens and expressed as tissue inflammations. The immunopathology includes dermatitis, immune complex-mediated kidney disease, and, chiefly, T-cell-mediated granuloma formation and fibrosis around disseminated parasite eggs. This review describes the mechanisms of induction and expression of immunopathology in infected persons and experimental animals. Immunoregulatory mechanisms that modulate the enhanced immune responses and may ameliorate excessive morbidity are discussed. PMID:2504481

  20. Differential Evolutionary Selection and Natural Evolvability Observed in ALT Proteins of Human Filarial Parasites

    PubMed Central

    Devoe, Neil C.; Corbett, Ian J.; Barker, Linsey; Chang, Robert; Gudis, Polyxeni; Mullen, Nathan; Perez, Kailey; Raposo, Hugo; Scholz, John; May, Meghan

    2016-01-01

    The abundant larval transcript (ALT-2) protein is present in all members of the Filarioidea, and has been reported as a potential candidate antigen for a subunit vaccine against lymphatic filariasis. To assess the potential for vaccine escape or heterologous protection, we examined the evolutionary selection acting on ALT-2. The ratios of nonsynonymous (K(a)) to synonymous (K(s)) mutation frequencies (ω) were calculated for the alt-2 genes of the lymphatic filariasis agents Brugia malayi and Wuchereria bancrofti and the agents of river blindness and African eyeworm disease Onchocerca volvulus and Loa loa. Two distinct Bayesian models of sequence evolution showed that ALT-2 of W. bancrofti and L. loa were under significant (P<0.05; P < 0.001) diversifying selection, while ALT-2 of B. malayi and O. volvulus were under neutral to stabilizing selection. Diversifying selection as measured by ω values was notably strongest on the region of ALT-2 encoding the signal peptide of L. loa and was elevated in the variable acidic domain of L. loa and W. bancrofti. Phylogenetic analysis indicated that the ALT-2 consensus sequences formed three clades: the first consisting of B. malayi, the second consisting of W. bancrofti, and the third containing both O. volvulus and L. loa. ALT-2 selection was therefore not predictable by phylogeny or pathology, as the two species parasitizing the eye were selected differently, as were the two species parasitizing the lymphatic system. The most immunogenic regions of L. loa and W. bancrofti ALT-2 sequence as modeled by antigenicity prediction analysis did not correspond with elevated levels of diversifying selection, and were not selected differently than predicted antigenic epitopes in B. malayi and O. volvulus. Measurements of ALT-2 evolvability made by χ2 analysis between alleles that were stable (O. volvulus and B. malayi) and those that were under diversifying selection (W. bancrofti and L. loa) indicated significant (P<0

  1. Differential Evolutionary Selection and Natural Evolvability Observed in ALT Proteins of Human Filarial Parasites.

    PubMed

    Devoe, Neil C; Corbett, Ian J; Barker, Linsey; Chang, Robert; Gudis, Polyxeni; Mullen, Nathan; Perez, Kailey; Raposo, Hugo; Scholz, John; May, Meghan

    2016-01-01

    The abundant larval transcript (ALT-2) protein is present in all members of the Filarioidea, and has been reported as a potential candidate antigen for a subunit vaccine against lymphatic filariasis. To assess the potential for vaccine escape or heterologous protection, we examined the evolutionary selection acting on ALT-2. The ratios of nonsynonymous (K(a)) to synonymous (K(s)) mutation frequencies (ω) were calculated for the alt-2 genes of the lymphatic filariasis agents Brugia malayi and Wuchereria bancrofti and the agents of river blindness and African eyeworm disease Onchocerca volvulus and Loa loa. Two distinct Bayesian models of sequence evolution showed that ALT-2 of W. bancrofti and L. loa were under significant (P<0.05; P < 0.001) diversifying selection, while ALT-2 of B. malayi and O. volvulus were under neutral to stabilizing selection. Diversifying selection as measured by ω values was notably strongest on the region of ALT-2 encoding the signal peptide of L. loa and was elevated in the variable acidic domain of L. loa and W. bancrofti. Phylogenetic analysis indicated that the ALT-2 consensus sequences formed three clades: the first consisting of B. malayi, the second consisting of W. bancrofti, and the third containing both O. volvulus and L. loa. ALT-2 selection was therefore not predictable by phylogeny or pathology, as the two species parasitizing the eye were selected differently, as were the two species parasitizing the lymphatic system. The most immunogenic regions of L. loa and W. bancrofti ALT-2 sequence as modeled by antigenicity prediction analysis did not correspond with elevated levels of diversifying selection, and were not selected differently than predicted antigenic epitopes in B. malayi and O. volvulus. Measurements of ALT-2 evolvability made by χ2 analysis between alleles that were stable (O. volvulus and B. malayi) and those that were under diversifying selection (W. bancrofti and L. loa) indicated significant (P<0

  2. Acute Small-Bowel Obstruction From Intestinal Anisakiasis After the Ingestion of Raw Clams; Documenting a New Method of Marine-to-Human Parasitic Transmission

    PubMed Central

    Shweiki, Ehyal; Rittenhouse, David W.; Ochoa, Joana E.; Punja, Viren P.; Zubair, Muhammad H.; Baliff, Jeffrey P.

    2014-01-01

    Enteric anisakiasis is a known parasitic infection. To date, human infection has been reported as resulting from the inadvertent ingestion of the anisakis larvae when eating raw/undercooked fish, squid, or eel. We present a first reported case of intestinal obstruction caused by anisakiasis, after the ingestion of raw clams. PMID:25734153

  3. Functional and phenotypic characteristics of alternative activation induced in human monocytes by interleukin-4 or the parasitic nematode Brugia malayi.

    PubMed

    Semnani, Roshanak Tolouei; Mahapatra, Lily; Moore, Vanessa; Sanprasert, Vivornpun; Nutman, Thomas B

    2011-10-01

    Human monocytes from patients with patent filarial infections are studded with filarial antigen and express markers associated with alternative activation of macrophages (MΦ). To explore the role of filaria-derived parasite antigen in differentiation of human monocytes, cells were exposed to microfilariae (mf) of Brugia malayi, and their phenotypic and functional characteristics were compared with those of monocytes exposed to factors known to generate either alternatively (interleukin-4 [IL-4]) or classically (macrophage colony-stimulating factor [MCSF]) activated MΦ. IL-4 upregulated mRNA expression of CCL13, CCL15, CCL17, CCL18, CCL22, CLEC10A, MRC1, CADH1, CD274, and CD273 associated with alternative activation of MΦ but not arginase 1. IL-4-cultured monocytes had a diminished ability to promote proliferation of both CD4(+) and CD8(+) T cells compared to that of unexposed monocytes. Similar to results with IL-4, exposure of monocytes to live mf induced upregulation of CCL15, CCL17, CCL18, CCL22, CD274, and CD273 and downregulation of Toll-like receptor 3 (TLR3), TLR5, and TLR7. In contrast to results with MCSF-cultured monocytes, exposure of monocytes to mf resulted in significant inhibition of the phagocytic ability of these cells to the same degree as that seen with IL-4. Our data suggest that short exposure of human monocytes to IL-4 induces a phenotypic characteristic of alternative activation and that secreted filarial products skew monocytes similarly. PMID:21788379

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

    SciTech Connect

    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 demonstrate 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.

  5. Parasitic colitis.

    PubMed

    Hechenbleikner, Elizabeth M; McQuade, Jennifer A

    2015-06-01

    Over one billion people worldwide harbor intestinal parasites. Parasitic intestinal infections have a predilection for developing countries due to overcrowding and poor sanitation but are also found in developed nations, such as the United States, particularly in immigrants or in the setting of sporadic outbreaks. Although the majority of people are asymptomatically colonized with parasites, the clinical presentation can range from mild abdominal discomfort or diarrhea to serious complications, such as perforation or bleeding. Protozoa and helminths (worms) are the two major classes of intestinal parasites. Protozoal intestinal infections include cryptosporidiosis, cystoisosporiasis, cyclosporiasis, balantidiasis, giardiasis, amebiasis, and Chagas disease, while helminth infections include ascariasis, trichuriasis, strongyloidiasis, enterobiasis, and schistosomiasis. Intestinal parasites are predominantly small intestine pathogens but the large intestine is also frequently involved. This article highlights important aspects of parasitic infections of the colon including epidemiology, transmission, symptoms, and diagnostic methods as well as appropriate medical and surgical treatment. PMID:26034403

  6. Parasitic Colitis

    PubMed Central

    Hechenbleikner, Elizabeth M.; McQuade, Jennifer A.

    2015-01-01

    Over one billion people worldwide harbor intestinal parasites. Parasitic intestinal infections have a predilection for developing countries due to overcrowding and poor sanitation but are also found in developed nations, such as the United States, particularly in immigrants or in the setting of sporadic outbreaks. Although the majority of people are asymptomatically colonized with parasites, the clinical presentation can range from mild abdominal discomfort or diarrhea to serious complications, such as perforation or bleeding. Protozoa and helminths (worms) are the two major classes of intestinal parasites. Protozoal intestinal infections include cryptosporidiosis, cystoisosporiasis, cyclosporiasis, balantidiasis, giardiasis, amebiasis, and Chagas disease, while helminth infections include ascariasis, trichuriasis, strongyloidiasis, enterobiasis, and schistosomiasis. Intestinal parasites are predominantly small intestine pathogens but the large intestine is also frequently involved. This article highlights important aspects of parasitic infections of the colon including epidemiology, transmission, symptoms, and diagnostic methods as well as appropriate medical and surgical treatment. PMID:26034403

  7. New Praziquantel Derivatives Containing NO-donor Furoxans and Related Furazans as Active Agents against Schistosoma mansoni

    PubMed Central

    Guglielmo, Stefano; Cortese, Daniela; Vottero, Francesca; Rolando, Barbara; Kommer, Valerie P.; Williams, David L.; Fruttero, Roberta; Gasco, Alberto

    2014-01-01

    A series of NO-donor praziquantel hybrid compounds was obtained by combining praziquantel (PZQ) and furoxan moieties in a single entity. NO-donor properties of the furoxan derivatives were evaluated by detecting nitrite after incubation of the products in 7.4 pH buffered solution in the presence of L-cysteine. Structurally-related furazans, devoid of NO release capacity, were also synthesized for control purposes. All products were studied for their ability to inhibit recombinant Schistosoma mansoni thioredoxin glutathione reductase (TGR). Mobility and death of adult Schistosoma mansoni worms cultured in the presence of the products were evaluated versus PZQ. Analysis of the results showed that some products were endowed with both PZQ and NO-dependent antiparasitic properties. Compounds 6, 7, 18, and 24 emerged as the most interesting balanced hybrids, worthy of additional study on PZQ-resistant parasites. PMID:25016371

  8. Partial purification and characterization of an inhibitor from newborn-rat epidermis with activity against the proteinase of Schistosoma mansoni cercariae.

    PubMed Central

    Tzeng, S; McKerrow, J H; Jeong, K; Fukuyama, K; Epstein, W L

    1982-01-01

    The penetration of cercariae through the skin initiates infection of the host with the human trematode parasite Schistosoma mansoni. Many larvae fail to migrate into the living epidermal cell layer. In order to determine if chemical as well as mechanical barriers to cercarial skin penetration exist, inhibitory activity of epidermal cell extracts against the proteinase obtained from cercarial secretions was assayed. An inhibitor was purified 50-fold by gel filtration on Sephadex G 75 and cation exchange chromatography at pH 5.8 and 4.9. The inhibitor has a relative molecular mass (Mr) of approx. 40 000-53 000. Oxidation of the inhibitor with N-chlorosuccinimide eliminated its inhibitory activity and thus indicated a critical methionine residue. The inhibitor was active against a wide spectrum of serine proteinases: porcine pancreatic elastase, human granulocyte elastase, bovine trypsin, and bovine alpha-chymotrypsin. However, no inhibition was detected against papain or clostridial collagenase. The inhibitor did not cross react with antiserum to human or rat serum alpha 1-proteinase inhibitor. Images Fig. 3. PMID:7165704

  9. Bayesian Risk Mapping and Model-Based Estimation of Schistosoma haematobium–Schistosoma mansoni Co-distribution in Côte d′Ivoire

    PubMed Central

    Chammartin, Frédérique; Houngbedji, Clarisse A.; Hürlimann, Eveline; Yapi, Richard B.; Silué, Kigbafori D.; Soro, Gotianwa; Kouamé, Ferdinand N.; N′Goran, Eliézer K.; Utzinger, Jürg; Raso, Giovanna; Vounatsou, Penelope

    2014-01-01

    Background Schistosoma haematobium and Schistosoma mansoni are blood flukes that cause urogenital and intestinal schistosomiasis, respectively. In Côte d′Ivoire, both species are endemic and control efforts are being scaled up. Accurate knowledge of the geographical distribution, including delineation of high-risk areas, is a central feature for spatial targeting of interventions. Thus far, model-based predictive risk mapping of schistosomiasis has relied on historical data of separate parasite species. Methodology We analyzed data pertaining to Schistosoma infection among school-aged children obtained from a national, cross-sectional survey conducted between November 2011 and February 2012. More than 5,000 children in 92 schools across Côte d′Ivoire participated. Bayesian geostatistical multinomial models were developed to assess infection risk, including S. haematobium–S. mansoni co-infection. The predicted risk of schistosomiasis was utilized to estimate the number of children that need preventive chemotherapy with praziquantel according to World Health Organization guidelines. Principal Findings We estimated that 8.9% of school-aged children in Côte d′Ivoire are affected by schistosomiasis; 5.3% with S. haematobium and 3.8% with S. mansoni. Approximately 2 million annualized praziquantel treatments would be required for preventive chemotherapy at health districts level. The distinct spatial patterns of S. haematobium and S. mansoni imply that co-infection is of little importance across the country. Conclusions/Significance We provide a comprehensive analysis of the spatial distribution of schistosomiasis risk among school-aged children in Côte d′Ivoire and a strong empirical basis for a rational targeting of control interventions. PMID:25522007

  10. Transcriptome Bioinformatical Analysis of Vertebrate Stages of Schistosoma japonicum Reveals Alternative Splicing Events

    PubMed Central

    Wang, Xinye; Xu, Xindong; Lu, Xingyu; Zhang, Yuanbin; Pan, Weiqing

    2015-01-01

    Alternative splicing is a molecular process that contributes greatly to the diversification of proteome and to gene functions. Understanding the mechanisms of stage-specific alternative splicing can provide a better understanding of the development of eukaryotes and the functions of different genes. Schistosoma japonicum is an infectious blood-dwelling trematode with a complex lifecycle that causes the tropical disease schistosomiasis. In this study, we analyzed the transcriptome of Schistosoma japonicum to discover alternative splicing events in this parasite, by applying RNA-seq to cDNA library of adults and schistosomula. Results were validated by RT-PCR and sequencing. We found 11,623 alternative splicing events among 7,099 protein encoding genes and average proportion of alternative splicing events per gene was 42.14%. We showed that exon skip is the most common type of alternative splicing events as found in high eukaryotes, whereas intron retention is the least common alternative splicing type. According to intron boundary analysis, the parasite possesses same intron boundaries as other organisms, namely the classic “GT-AG” rule. And in alternative spliced introns or exons, this rule is less strict. And we have attempted to detect alternative splicing events in genes encoding proteins with signal peptides and transmembrane helices, suggesting that alternative splicing could change subcellular locations of specific gene products. Our results indicate that alternative splicing is prevalent in this parasitic worm, and that the worm is close to its hosts. The revealed secretome involved in alternative splicing implies new perspective into understanding interaction between the parasite and its host. PMID:26407301

  11. Transcriptome Bioinformatical Analysis of Vertebrate Stages of Schistosoma japonicum Reveals Alternative Splicing Events.

    PubMed

    Wang, Xinye; Xu, Xindong; Lu, Xingyu; Zhang, Yuanbin; Pan, Weiqing

    2015-01-01

    Alternative splicing is a molecular process that contributes greatly to the diversification of proteome and to gene functions. Understanding the mechanisms of stage-specific alternative splicing can provide a better understanding of the development of eukaryotes and the functions of different genes. Schistosoma japonicum is an infectious blood-dwelling trematode with a complex lifecycle that causes the tropical disease schistosomiasis. In this study, we analyzed the transcriptome of Schistosoma japonicum to discover alternative splicing events in this parasite, by applying RNA-seq to cDNA library of adults and schistosomula. Results were validated by RT-PCR and sequencing. We found 11,623 alternative splicing events among 7,099 protein encoding genes and average proportion of alternative splicing events per gene was 42.14%. We showed that exon skip is the most common type of alternative splicing events as found in high eukaryotes, whereas intron retention is the least common alternative splicing type. According to intron boundary analysis, the parasite possesses same intron boundaries as other organisms, namely the classic "GT-AG" rule. And in alternative spliced introns or exons, this rule is less strict. And we have attempted to detect alternative splicing events in genes encoding proteins with signal peptides and transmembrane helices, suggesting that alternative splicing could change subcellular locations of specific gene products. Our results indicate that alternative splicing is prevalent in this parasitic worm, and that the worm is close to its hosts. The revealed secretome involved in alternative splicing implies new perspective into understanding interaction between the parasite and its host. PMID:26407301

  12. Imatinib Treatment Causes Substantial Transcriptional Changes in Adult Schistosoma mansoni In Vitro Exhibiting Pleiotropic Effects

    PubMed Central

    Oliveira, Katia C.; Dissous, Colette; Cailliau, Katia; Marhöfer, Richard J.; Selzer, Paul M.; Verjovski-Almeida, Sergio; Grevelding, Christoph G.

    2014-01-01

    Background Schistosome parasites cause schistosomiasis, one of the most important infectious diseases worldwide. For decades Praziquantel (PZQ) is the only drug widely used for controlling schistosomiasis. The absence of a vaccine and fear of PZQ resistance have motivated the search for alternatives. Studies on protein kinases (PKs) demonstrated their importance for diverse physiological processes in schistosomes. Among others two Abl tyrosine kinases, SmAbl1 and SmAbl2, were identified in Schistosoma mansoni and shown to be transcribed in the gonads and the gastrodermis. SmAbl1 activity was blocked by Imatinib, a known Abl-TK inhibitor used in human cancer therapy (Gleevec/Glivec). Imatinib exhibited dramatic effects on the morphology and physiology of adult schistosomes in vitro causing the death of the parasites. Methodology/Principal Findings Here we show modeling data supporting the targeting of SmAbl1/2 by Imatinib. A biochemical assay confirmed that SmAbl2 activity is also inhibited by Imatinib. Microarray analyses and qRT-PCR experiments were done to unravel transcriptional processes influenced by Imatinib in adult schistosomes in vitro demonstrating a wide influence on worm physiology. Surface-, muscle-, gut and gonad-associated processes were affected as evidenced by the differential transcription of e.g. the gynecophoral canal protein gene GCP, paramyosin, titin, hemoglobinase, and cathepsins. Furthermore, transcript levels of VAL-7 and egg formation-associated genes such as tyrosinase 1, p14, and fs800-like were affected as well as those of signaling genes including a ribosomal protein S6 kinase and a glutamate receptor. Finally, a comparative in silico analysis of the obtained microarray data sets and previous data analyzing the effect of a TGFβR1 inhibitor on transcription provided first evidence for an association of TGFβ and Abl kinase signaling. Among others GCP and egg formation-associated genes were identified as common targets. Conclusions

  13. Evaluation of protective immune response in mice by vaccination the recombinant adenovirus for expressing Schistosoma japonicum inhibitor apoptosis protein.

    PubMed

    Hu, Chao; Zhu, Lihui; Luo, Rong; Dao, Jinwei; Zhao, Jiangping; Shi, Yaojun; Li, Hao; Lu, Ke; Feng, Xingang; Lin, Jiaojiao; Liu, Jinming; Cheng, Guofeng

    2014-11-01

    Schistosomiasis is a worldwide parasitic disease, and while it can be successfully treated with chemotherapy, this does not prevent reinfection with the parasite. Adenovirus vectors have been widely used for vaccine delivery, and a vaccination approach has the potential to prevent infection with Schistosoma. Here, we developed a recombinant adenoviral vector that expresses Schistosoma japonicum inhibitor apoptosis protein (Ad-SjIAP) and assessed its immunoprotective functions against schistosomiasis in mice. Murine immune responses following vaccination were investigated using enzyme-linked immunosorbent assays (ELISA), lymphocyte proliferation, and cytokine assays. The protective immunity in mice was evaluated by challenging with S. japonicum cercariae. Our results indicated that immunization with the Ad-SjIAP in mice induced a strong serum IgG response against IAP including IgG1, IgG2a, and IgG2b. In addition, lymphocyte proliferation experiments showed that mice treated with Ad-SjIAP significantly increased the lymphocyte response upon stimulation with recombinant Schistosoma japonicum inhibitor apoptosis protein (rSjIAP). Moreover, cytokine assays indicated that vaccination of Ad-SjIAP significantly increased the production of interferon (IFN)-γ and IL-2 as compared to the corresponding control group. Furthermore, following the challenge with S. japonicum cercariae, the vaccine conferred moderate protection, with an average rate of 37.95% for worm reduction and 31.7% for egg reduction. Taken together, our preliminarily results suggested that schistosoma IAP may be a potential vaccine against S. japonicum and that adenoviral vectors may serve as an alternative delivery vehicle for schistosome vaccine development. PMID:25185668

  14. Parasitic Roundworm Diseases

    MedlinePlus

    ... The eggs or larvae also can enter the human body directly through the skin. With the exception of the parasitic roundworm that causes trichinosis, mature adult roundworms eventually end up or live in human intestines and cause infection and disease. In trichinosis, ...

  15. Schistosoma mansoni Sirtuins: Characterization and Potential as Chemotherapeutic Targets

    PubMed Central

    Lancelot, Julien; Caby, Stéphanie; Dubois-Abdesselem, Florence; Vanderstraete, Mathieu; Trolet, Jacques; Oliveira, Guilherme; Bracher, Franz; Jung, Manfred; Pierce, Raymond J.

    2013-01-01

    Background The chemotherapy of schistosomiasis currently depends on the use of a single drug, praziquantel. In order to develop novel chemotherapeutic agents we are investigating enzymes involved in the epigenetic modification of chromatin. Sirtuins are NAD+ dependent lysine deacetylases that are involved in a wide variety of cellular processes including histone deacetylation, and have been demonstrated to be therapeutic targets in various pathologies, including cancer. Methodology, Principal Findings In order to determine whether Schistosoma mansoni sirtuins are potential therapeutic targets we first identified and characterized their protein sequences. Five sirtuins (SmSirt) are encoded in the S. mansoni genome and phylogenetic analysis showed that they are orthologues of mammalian Sirt1, Sirt2, Sirt5, Sirt6 and Sirt7. Both SmSirt1 and SmSirt7 have large insertion in the catalytic domain compared to their mammalian orthologues. SmSirt5 is the only mitochondrial sirtuin encoded in the parasite genome (orthologues of Sirt3 and Sirt4 are absent) and transcripts corresponding to at least five splicing isoforms were identified. All five sirtuins are expressed throughout the parasite life-cycle, but with distinct patterns of expression. Sirtuin inhibitors were used to treat both schistosomula and adult worms maintained in culture. Three inhibitors in particular, Sirtinol, Salermide and MS3 induced apoptosis and death of schistosomula, the separation of adult worm pairs, and a reduction in egg laying. Moreover, Salermide treatment led to a marked disruption of the morphology of ovaries and testes. Transcriptional knockdown of SmSirt1 by RNA interference in adult worms led to morphological changes in the ovaries characterized by a marked increase in mature oocytes, reiterating the effects of sirtuin inhibitors and suggesting that SmSirt1 is their principal target. Conclusion, Significance Our data demonstrate the potential of schistosome sirtuins as therapeutic targets

  16. A case report of an uncommon parasitic infection of human balantidiasis.

    PubMed

    Kumar, Manochitra; Rajkumari, Nonika; Mandal, Jharna; Parija, S C

    2016-01-01

    Balantidium coli, a large, ciliated pathogen, is known to cause balantidiasis in humans. We report a case of B. coli infection in a 37-year-old male with tuberculosis and presenting with fever, anorexia, mild abdominal pain, and episodes of loose stools for 1 week. PMID:26998438

  17. Gedunin and photogedunin of Xylocarpus granatum possess antifilarial activity against human lymphatic filarial parasite Brugia malayi in experimental rodent host.

    PubMed

    Misra, Sweta; Verma, Meenakshi; Mishra, Sunil Kumar; Srivastava, Shishir; Lakshmi, Vijai; Misra-Bhattacharya, Shailja

    2011-11-01

    The present study is aimed to evaluate antifilarial activity of Xylocarpus granatum (fruit from Andaman) against human lymphatic filarial parasite Brugia malayi in vivo. The in vitro antifilarial activity has already been reported earlier for this mangrove plant which has traditionally been used against several ailments. Aqueous ethanolic crude extract, four fractions (ethyl acetate fraction, n-butanol fraction, water-soluble fraction and water-insoluble fraction) and pure molecule/s of X. granatum (fruit) were tested in vitro on adult worms and microfilariae (mf) of B. malayi and the active samples were further evaluated in vivo in B. malayi (intraperitoneally) i.p. transplanted in the jird model (Meriones unguiculatus) and Mastomys coucha subcutaneously infected with infective larvae (L3). The crude aqueous ethanolic extract was active in vitro (IC50: adult = 15.46 μg/ml; mf = 13.17 μg/ml) and demonstrated 52.8% and 62.7% adulticidal and embryostatic effect on B. malayi, respectively, in Mastomys at a dose of 5 × 50 mg/kg by oral route. The antifilarial activity was primarily localized in the ethyl acetate-soluble fraction which revealed IC50 of 8.5 and 6.9 μg/ml in adult and mf, respectively. This fraction possessed moderate adulticidal and embryostatic action in vivo in Mastomys. Out of eight pure molecules isolated from the active fraction, two compounds gedunin (IC50 = 0.239 μg/ml, CC50 = 212.5 μg/ml, SI = 889.1) and photogedunin (IC50 = 0.213 μg/ml, CC50 = 262.3 μg/ml, SI = 1231.4) at 5 × 100 mg/kg by subcutaneous route revealed excellent adulticidal efficacy resulting in to the death of 80% and 70% transplanted adult B. malayi in the peritoneal cavity of jirds respectively in addition to noticeable microfilaricidalo action on the day of autopsy. The findings reveal that the extract from the fruit X. granatum contains promising in vitro and in vivo antifilarial activity against human lymphatic filarial parasite B. malayi which could be attributed to

  18. Radicicol-Mediated Inhibition of Topoisomerase VIB-VIA Activity of the Human Malaria Parasite Plasmodium falciparum

    PubMed Central

    Chalapareddy, Sureshkumar; Chakrabarty, Swati; Bhattacharyya, Mrinal Kanti

    2016-01-01

    ABSTRACT Plasmodium falciparum topoisomerase VIB (TopoVIB)-TopoVIA (TopoVIB-VIA) complex can be potentially exploited as a drug target against malaria due to its absence from the human genome. Previous work in our laboratory has suggested that P. falciparum TopoVIB (PfTopoVIB) might be a target of radicicol since treatment of parasite cultures with this antibiotic is associated with upregulation of Plasmodium TopoVIB at the transcript level as well as at the protein level. Further studies demonstrated that radicicol treatment impaired mitochondrial replication of human malaria parasite P. falciparum. However, the technical challenge associated with the expression of the above protein complex hampered its functional characterization. Using Saccharomyces cerevisiae as a heterologous system, we expressed PfTopoVIB (Myc-tagged) and PfTopoVIA (Flag-tagged) (PfTopoVIB-VIA) proteins. Yeast two-hybrid analysis showed the formation of PfTopoVIB homodimers and PfTopoVIB/PfTopoVIA heteromers. Our study demonstrated that PfTopoVIB and PfTopoVIA together can rescue the lethal phenotype of yeast ΔtopoII mutants, whereas Plasmodium topoisomerase VIB alone cannot. Using yeast cell-free extracts harboring the PfTopoVIB-VIA protein complex, we have performed a decatenation assay and observed that PfTopoVIB-VIA can decatenate DNA in an ATP- and Mg2+-dependent manner. The specificity of this enzyme is established by abrogation of its activity in the presence of PfTopoVIB-specific antibody. Our study results show that radicicol and etoposide can specifically inhibit PfTopoVIB-VIA decatenation activity whereas the gyrase inhibitor novobiocin cannot. Such a yeast-based assay system can be employed in screening specific inhibitors against Plasmodium VIB-VIA. IMPORTANCE In this study we characterize topoisomerase VI from Plasmodium falciparum using genetic and biochemical approaches. We use various inhibitors and identify radicicol as a specific inhibitor of its decatenation activity. We

  19. A Clinical and Epidemiological Investigation of the First Reported Human Infection With the Zoonotic Parasite Trypanosoma evansi in Southeast Asia

    PubMed Central

    Van Vinh Chau, Nguyen; Buu Chau, Le; Desquesnes, Marc; Herder, Stephane; Phu Huong Lan, Nguyen; Campbell, James I.; Van Cuong, Nguyen; Yimming, Benjarat; Chalermwong, Piangjai; Jittapalapong, Sathaporn; Ramon Franco, Jose; Tri Tue, Ngo; Rabaa, Maia A.; Carrique-Mas, Juan; Pham Thi Thanh, Tam; Tran Vu Thieu, Nga; Berto, Alessandra; Thi Hoa, Ngo; Van Minh Hoang, Nguyen; Canh Tu, Nguyen; Khac Chuyen, Nguyen; Wills, Bridget; Tinh Hien, Tran; Thwaites, Guy E.; Yacoub, Sophie; Baker, Stephen

    2016-01-01

    Background. Trypanosoma is a genus of unicellular parasitic flagellate protozoa. Trypanosoma brucei species and Trypanosoma cruzi are the major agents of human trypanosomiasis; other Trypanosoma species can cause human disease, but are rare. In March 2015, a 38-year-old woman presented to a healthcare facility in southern Vietnam with fever, headache, and arthralgia. Microscopic examination of blood revealed infection with Trypanosoma. Methods. Microscopic observation, polymerase chain reaction (PCR) amplification of blood samples, and serological testing were performed to identify the infecting species. The patient's blood was screened for the trypanocidal protein apolipoprotein L1 (APOL1), and a field investigation was performed to identify the zoonotic source. Results. PCR amplification and serological testing identified the infecting species as Trypanosoma evansi. Despite relapsing 6 weeks after completing amphotericin B therapy, the patient made a complete recovery after 5 weeks of suramin. The patient was found to have 2 wild-type APOL1 alleles and a normal serum APOL1 concentration. After responsive animal sampling in the presumed location of exposure, cattle and/or buffalo were determined to be the most likely source of the infection, with 14 of 30 (47%) animal blood samples testing PCR positive for T. evansi. Conclusions. We report the first laboratory-confirmed case of T. evansi in a previously healthy individual without APOL1 deficiency, potentially contracted via a wound while butchering raw beef, and successfully treated with suramin. A linked epidemiological investigation revealed widespread and previously unidentified burden of T. evansi in local cattle, highlighting the need for surveillance of this infection in animals and the possibility of further human cases. PMID:26908809

  20. The phylogeography of Asian Schistosoma (Trematoda: Schistosomatidae).

    PubMed

    Attwood, S W; Upatham, E S; Meng, X H; Qiu, D C; Southgate, V R

    2002-08-01

    Partial (DNA) sequences are presented for 2 nuclear (18S and 28S rRNA genes) and 2 mitochondrial (12S rRNA and ND1 genes) loci for 5 species belonging to the Schistosoma japonicum, S. sinensium and S. indicum groups of Asian Schistosoma. Fresh field isolates were collected and cultured for the following taxa: S. incognitum (S. indicum group, central Thailand), S. mekongi (S. japonicum group, southern Laos), S. ovuncatum (S. sinensium group, northern Thailand), S. spindale (S. indicum group, northeast Thailand and central Thailand isolates) and S. sinensium (S. sinensium group, Sichuan Province, China). This represents the first published DNA sequence data for S. ovuncatum and for S. sinensium s.s. from the type locality in China. The paper also presents the first sequence data at the above loci for S. incognitum (except for the 28S sequences) and S. sinensium. Congruence was observed between the phylogenies estimated for each locus, although the relationships of S. incognitum were not so well resolved. Fitch-Margoliash, maximum likelihood (M/L) and maximum parsimony methods were used to estimate the phylogenies and the agreement between them was similar to that observed between loci. The ML tree was considered to best represent the data and additional 28S sequences (taken from the GenBank), for S. haematobium, S. japonicum, S. mansoni and Orientobilharzia turkestanicum, were used to construct an overall phylogeny. The S. indicum group taxa showed considerable divergence from the other Asian species and closest affinity with the African group. S. ovuncatum and S. sinensium appeared as sister taxa but their status as sibling species remained supported. The findings are discussed in the context of phylogeographical hypotheses for the origin of Schistosoma. An Asian origin for Schistosoma is also considered. PMID:12211613

  1. Effect of Clinoptilolite and Sepiolite Nanoclays on Human and Parasitic Highly Phagocytic Cells

    PubMed Central

    Toledano-Magaña, Yanis; Flores-Santos, Leticia; Montes de Oca, Georgina; González-Montiel, Alfonso; Laclette, Juan-Pedro; Carrero, Julio-César

    2015-01-01

    Nanoclays have potential applications in biomedicine raising the need to evaluate their toxicity in in vitro models as a first approach to its biocompatibility. In this study, in vitro toxicity of clinoptilolite and sepiolite nanoclays (NC) was analyzed in highly phagocytic cultures of amoebas and human and mice macrophages. While amebic viability was significantly affected only by sepiolite NC at concentrations higher than 0.1 mg/mL, the effect on macrophage cultures was dependent on the origin of the cells. Macrophages derived from human peripheral blood monocytes were less affected in viability (25% decrease at 48 h), followed by the RAW 264.7 cell line (40%), and finally, macrophages derived from mice bone marrow monocytes (98%). Moreover, the cell line and mice macrophages die mainly by necrosis, whereas human macrophages exhibit increased apoptosis. Cytokine expression analysis in media of sepiolite NC treated cultures showed a proinflammatory profile (INFγ, IL-1α, IL-8, and IL-6), in contrast with clinoptilolite NC that induced lees cytokines with concomitant production of IL-10. The results show that sepiolite NC is more toxic to amoebas and macrophages than clinoptilolite NC, mostly in a time and dose-dependent manner. However, the effect of sepiolite NC was comparable with talc powder suggesting that both NC have low cytotoxicity in vitro. PMID:26090385

  2. Effect of Clinoptilolite and Sepiolite Nanoclays on Human and Parasitic Highly Phagocytic Cells.

    PubMed

    Toledano-Magaña, Yanis; Flores-Santos, Leticia; Montes de Oca, Georgina; González-Montiel, Alfonso; Laclette, Juan-Pedro; Carrero, Julio-César

    2015-01-01

    Nanoclays have potential applications in biomedicine raising the need to evaluate their toxicity in in vitro models as a first approach to its biocompatibility. In this study, in vitro toxicity of clinoptilolite and sepiolite nanoclays (NC) was analyzed in highly phagocytic cultures of amoebas and human and mice macrophages. While amebic viability was significantly affected only by sepiolite NC at concentrations higher than 0.1 mg/mL, the effect on macrophage cultures was dependent on the origin of the cells. Macrophages derived from human peripheral blood monocytes were less affected in viability (25% decrease at 48 h), followed by the RAW 264.7 cell line (40%), and finally, macrophages derived from mice bone marrow monocytes (98%). Moreover, the cell line and mice macrophages die mainly by necrosis, whereas human macrophages exhibit increased apoptosis. Cytokine expression analysis in media of sepiolite NC treated cultures showed a proinflammatory profile (INFγ, IL-1α, IL-8, and IL-6), in contrast with clinoptilolite NC that induced lees cytokines with concomitant production of IL-10. The results show that sepiolite NC is more toxic to amoebas and macrophages than clinoptilolite NC, mostly in a time and dose-dependent manner. However, the effect of sepiolite NC was comparable with talc powder suggesting that both NC have low cytotoxicity in vitro. PMID:26090385

  3. A New Human 3D-Liver Model Unravels the Role of Galectins in Liver Infection by the Parasite Entamoeba histolytica

    PubMed Central

    Petropolis, Debora B.; Faust, Daniela M.; Deep Jhingan, Gagan; Guillen, Nancy

    2014-01-01

    Investigations of human parasitic diseases depend on the availability of appropriate in vivo animal models and ex vivo experimental systems, and are particularly difficult for pathogens whose exclusive natural hosts are humans, such as Entamoeba histolytica, the protozoan parasite responsible for amoebiasis. This common infectious human disease affects the intestine and liver. In the liver sinusoids E. histolytica crosses the endothelium and penetrates into the parenchyma, with the concomitant initiation of inflammatory foci and subsequent abscess formation. Studying factors responsible for human liver infection is hampered by the complexity of the hepatic environment and by the restrictions inherent to the use of human samples. Therefore, we built a human 3D-liver in vitro model composed of cultured liver sinusoidal endothelial cells and hepatocytes in a 3D collagen-I matrix sandwich. We determined the presence of important hepatic markers and demonstrated that the cell layers function as a biological barrier. E. histolytica invasion was assessed using wild-type strains and amoebae with altered virulence or different adhesive properties. We showed for the first time the dependence of endothelium crossing upon amoebic Gal/GalNAc lectin. The 3D-liver model enabled the molecular analysis of human cell responses, suggesting for the first time a crucial role of human galectins in parasite adhesion to the endothelial cells, which was confirmed by siRNA knockdown of galectin-1. Levels of several pro-inflammatory cytokines, including galectin-1 and -3, were highly increased upon contact of E. histolytica with the 3D-liver model. The presence of galectin-1 and -3 in the extracellular medium stimulated pro-inflammatory cytokine release, suggesting a further role for human galectins in the onset of the hepatic inflammatory response. These new findings are relevant for a better understanding of human liver infection by E. histolytica. PMID:25211477

  4. P2X7 receptor-mediated killing of an intracellular parasite, Toxoplasma gondii, by human and murine macrophages1

    PubMed Central

    Lees, Michael P.; Fuller, Stephen J.; McLeod, Rima; Boulter, Nicola R.; Miller, Catherine M.; Zakrzewski, Alana M.; Mui, Ernest J.; Witola, William H.; Coyne, Jessica J.; Hargrave, Aubrey C.; Jamieson, Sarra E.; Blackwell, Jenefer M.; Wiley, James S.; Smith, Nicholas C.

    2010-01-01

    The P2X7 receptor (P2X7R)4 is highly expressed on the macrophage cell surface and activation of infected cells by extracellular ATP has been shown to kill intracellular bacteria and parasites. Furthermore, single nucleotide polymorphisms (SNPs) that decrease receptor function reduce the ability of human macrophages to kill Mycobacterium tuberculosis and are associated with extrapulmonary tuberculosis. In this paper we show that macrophages from people with the 1513C (rs3751143) loss-of-function P2X7R SNP are less effective in killing intracellular Toxoplasma gondii after exposure to ATP compared with macrophages from people with the 1513A wild-type allele. Supporting a P2X7R-specific effect on T. gondii, macrophages from P2X7R knock-out mice (P2X7R−/−) are unable to kill T. gondii as effectively as macrophages from wild-type mice. We show that P2X7R-mediated T. gondii killing occurs in parallel with host cell apoptosis and is independent of NO production. PMID:20488797

  5. Zoonotic and human parasites of inhabitants of Cueva de los Muertos Chiquitos, Rio Zape Valley, Durango, Mexico.

    PubMed

    Jiménez, F Agustín; Gardner, Scott L; Araújo, Adauto; Fugassa, Martín; Brooks, Richard H; Racz, Elizabeth; Reinhard, Karl J

    2012-04-01

    We present the first reconstruction of the parasitoses among the people of the Loma San Gabriel culture, as represented by 36 coprolites excavated from the Cueva de los Muertos Chiquitos in Durango, Mexico. The coprolites date to approximately 1,400-yr-ago. Species identified based on eggs recovered include the trematode Echinostoma sp., the tapeworms Hymenolepis sp. and Dipylidium caninum , and the nematodes Ancylostoma duodenale, Enterobius vermicularis, and Trichuris trichiura. After rehydration and screening, 2 methods were used to recover eggs from these samples including spontaneous sedimentation and flotation. Samples were analyzed by 3 different laboratories for independent verification and comparison of methods. Spontaneous sedimentation resulted in the discovery of hymenolepidid eggs that were not found with flotation. Sedimentation was a more-sensitive indicator of prevalence as well. The modified method of flotation permitted estimation of egg concentration and resulted in the detection of a few specimens not found by sedimentation. The results of both methods showed that 19 (of 36) coprolites contained helminth eggs. Our results detected the presence of pathogenic helminths including hookworms and whipworms. The cestodes found do not cause severe pathology in humans. The early dates of hookworm and whipworm, relative to other findings in the southwest United States, indicate that these parasites arrived relatively late in prehistory in Arizona and New Mexico, probably moving into the area with travelers from Mesoamerica. PMID:22014000

  6. New records and human parasitism by Ornithodoros mimon (Acari: Argasidae) in Brazil.

    PubMed

    Labruna, Marcelo B; Marcili, Arlei; Ogrzewalska, Maria; Barros-Battesti, Darci M; Dantas-Torres, Filipe; Fernandes, André A; Leite, Romario C; Venzal, Jose M

    2014-01-01

    The bat tick Ornithodoros mimon Kohls, Clifford & Jones is currently known by only few reports in Bolivia, Uruguay, Argentina, and the state of São Paulo in southeastern Brazil. Here, we expand the distribution of O. mimon in Brazil to the states of Minas Gerais (southeastern region), Goiás (central-western), Pernambuco, and Rio Grande do Norte (northeastern). Ticks were collected on human dwellings, where there had been repeated complains of tick bites on persons during the night. Tick bites were generally followed by intense inflammatory reactions that lasted for several weeks at the bite site. Bats and opossums were reported to inhabit the attic of the infested houses. In addition, a free-ranging opossum (Didelphis albiventris Lund) trapped in Rio Grande do Norte was found infested by argasid larvae. Based on morphological and/or molecular analysis, all ticks were identified as O. mimon. From one of the sites (Tiradentes, state of Minas Gerais), 20 field-collected nymphs were tested by a battery of polymerase chain reaction protocols targeting tick-borne microorganisms of the genera Babesia, Hepatozoon, Rickettsia, Borrelia, Anaplasma, Ehrlichia, and Coxiella; no tick specimen was found infected by any of these microorganism genera. The current study expands northwards the distribution of O. mimon, which has been shown to be very harmful to humans because of the intense inflammatory response that usually occurs after tick bites. PMID:24605480

  7. Protozoan Parasites.

    PubMed

    Custodio, Haidee

    2016-02-01

    • Stool antigen detection for Cryptosporidium sp, Giardia lamblia and Entamoeba histolytica are now commercially available, have better sensitivity and specificity than the traditional stool microscopy, and are less dependent on personnel skill. Tests employing newer techniques with faster turnaround time are also available for diagnosing trichomoniasis.• Nitazoxanide, the only U.S. Food and Drug Administration-approved medication for therapy of cryptosporidiosis, is effective among immunocompetent patients. However, on the basis of strong evidence from multiple clinical trials, nitazoxanide is considered ineffective among immunocompromised patients. (14) • Giardiasis can be asymptomatic or have a chronic course leading to malabsorption and failure to thrive. It can be treated with metronidazole, tinidazole, or nitazoxanide. On the basis of growing observational studies, postinfectious and extraintestinal manifestations of giardiasis occur, but the mechanisms are unclear. Given the high prevalence of giardiasis, public health implications need to be defined. (16) • Eradicating E histolytica from the gastrointestinal tract requires only intraluminal agent therapy. Therapy for invasive illnesses requires use of imidazole followed by intraluminal agents to eliminate persistent intraluminal parasites. • Malaria is considered the most lethal parasitic infection, with Plasmodium falciparum as the predominant cause of mortality. P vivax and P ovale can be dormant in the liver, and primaquine is necessary to resolve infection by P vivax and P ovale. • Among immunocompetent patients, infection with Toxoplasma gondii may be asymptomatic, involve localized lymphadenopathy, or cause ocular infection. In immunocompromised patients, reactivation or severe infection is not uncommon. On the basis of limited observational studies (there are no well-controlled randomized trials), therapy is recommended for acute infection during pregnancy to prevent transmission to the

  8. RNA interference targeting leucine aminopeptidase blocks hatching of Schistosoma mansoni eggs

    PubMed Central

    Rinaldi, Gabriel; Morales, Maria E.; Alrefaei, Yousef N.; Cancela, Martín; Castillo, Estela; Dalton, John P.; Tort, José F.; Brindley, Paul J.

    2009-01-01

    Schistosoma mansoni leucine aminopeptidase (LAP) is thought to play a central role in hatching of the miracidium from the schistosome egg. We identified two discrete LAPs genes in the Schistosoma mansoni genome, and their orthologs in S. japonicum. The similarities in sequence and exon/intron structure of the two genes, LAP1 and LAP2, suggest that they arose by gene duplication and that this occurred before separation of the mansoni and japonicum lineages. The SmLAP 1 and 2 genes have different expression patterns in diverse stages of the cycle; whereas both are equally expressed in the blood dwelling stages (schistosomules and adult), SmLAP 2 expression was higher in free living larval (miracidia) and in parasitic intra-snail (sporocysts) stages. We investigated the role of each enzyme in hatching of schistosome eggs and the early stages of schistosome development by RNA interference (RNAi). Using RNAi, we observed marked and specific reduction of mRNAs, along with a loss of exopeptidase activity in soluble parasite extracts against the diagnostic substrate L-leucine-7-amido-4-methylcoumarin hydroxide. Strikingly, knockdown of either SmLAP1 or SmLAP2, or both together, was accompanied by ≥ 80% inhibition of hatching of schistosome eggs showing that both enzymes are important to the escape of miracidia from the egg. The methods employed here refine the utility of RNAi for functional genomics studies in helminth parasites and confirm these can be used to identify potential drug targets, in this case schistosome aminopeptidases. PMID:19463860

  9. 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

  10. FASCIOLA HEPATICA AND SCHISTOSOMA MANSONI: IDENTIFICATION OF COMMON PROTEINS BY COMPARATIVE PROTEOMIC ANALYSIS

    PubMed Central

    Boukli, Nawal M.; Delgado, Bonnibel; Ricaurte, Martha; Espino, Ana M.

    2013-01-01

    It is not unusual to find common molecules among parasites of different species, genera, or phyla. When those molecules are antigenic, they may be used for developing drugs or vaccines that simultaneously target different species or genera of parasite. In the present study, we used a proteomic-based approach to identify proteins that are common to adult Fasciola hepatica and Schistosoma mansoni. Whole-worm extracts from each parasite were separated by 2-dimensional electrophoresis (2-DE), and digital images of both proteomes were superimposed using imaging software to identify proteins with identical isoelectric points and molecular weights. Protein identities were determined by mass spectrometry. Imaging and immunoblot analyses identified 28 immunoreactive proteins that are common to both parasites. Among these molecules are antioxidant proteins (thioredoxin and glutathione-S-transferase), glycolytic enzymes (glyceraldehyde 6-phosphate dehydrogenase and enolase), proteolytic enzymes (cathepsin-L and -D), inhibitors (Kunitz-type, Stefin-1), proteins with chaperone activity (heat shock protein 70 and fatty acid–binding protein), and structural proteins (calcium-binding protein, actin, and myosin). Some of the identified proteins could be used to develop drugs and vaccines against fascioliasis and schistosomiasis. PMID:21506812

  11. Changes in the transcriptome of the malaria parasite Plasmodium falciparum during the initial phase of transmission from the human to the mosquito

    PubMed Central

    2013-01-01

    Background The transmission of the malaria parasite Plasmodium falciparum from the human to the mosquito is mediated by dormant sexual precursor cells, the gametocytes, which become activated in the mosquito midgut. Because gametocytes are the only parasite stages able to establish an infection in the mosquito, they play a crucial role in spreading the tropical disease. The human-to-mosquito transmission triggers important molecular changes in the gametocytes, which initiate gametogenesis and prepare the parasite for life-cycle progression in the insect vector. Results To better understand gene regulations during the initial phase of malaria parasite transmission, we focused on the transcriptome changes that occur within the first half hour of parasite development in the mosquito. Comparison of mRNA levels of P. falciparum gametocytes before and 30 min following activation using suppression subtractive hybridization (SSH) identified 126 genes, which changed in expression during gametogenesis. Among these, 17.5% had putative functions in signaling, 14.3% were assigned to cell cycle and gene expression, 8.7% were linked to the cytoskeleton or inner membrane complex, 7.9% were involved in proteostasis and 6.4% in metabolism, 12.7% were cell surface-associated proteins, 11.9% were assigned to other functions, and 20.6% represented genes of unknown function. For 40% of the identified genes there has as yet not been any protein evidence. For a subset of 27 genes, transcript changes during gametogenesis were studied in detail by real-time RT-PCR. Of these, 22 genes were expressed in gametocytes, and for 15 genes transcript expression in gametocytes was increased compared to asexual blood stage parasites. Transcript levels of seven genes were particularly high in activated gametocytes, pointing at functions downstream of gametocyte transmission to the mosquito. For selected genes, a regulated expression during gametogenesis was confirmed on the protein level, using

  12. Characterization of the Phytochelatin Synthase from the Human Parasitic Nematode Ancylostoma ceylanicum

    PubMed Central

    Rigouin, Coraline; Vermeire, Jon J.; Nylin, Elyse; Williams, David L.

    2013-01-01

    Hookworm disease is a debilitating worm infection that affects hundreds of millions of people. Despite the existence of anthelmintic drugs, reports have testified of a decrease in efficacy of these drugs. Therefore, it is imperative to find new drugs and drug targets for hookworm disease treatment. In this study we identify the gene encoding the phytochelatin synthase in the human hookworm, Ancylostoma ceylanicum (AcePCS). Phytochelatin synthase 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. Phytochelatin synthase proteins also function in the elimination of xenobiotics by processing GSH S-conjugates. We found that in vitro AcePCS could both synthesize phytochelatins and hydrolyze a GSH S-conjugate. Interestingly, the enzyme works through a thiol-dependant and, notably, metal-independent mechanism for both transpeptidase (phytochelatin synthesis) and peptidase (hydrolysis of GSH S-conjugates) activities. AcePCS mRNAs are expressed in vivo throughout the life cycle of A. ceylanicum. Mature adult male hookworms isolated from the small intestines of their hosts displayed significantly enhanced expression of AcePCS with transcript levels 5-fold greater than other developmental forms. Although the role of AcePCS in A. ceylanicum biology has yet to be fully investigated the results reported here provide encouraging evidence of the potential that this enzyme holds as a target for new chemotherapeutic intervention. PMID:23916800

  13. Characterization of the phytochelatin synthase from the human parasitic nematode Ancylostoma ceylanicum.

    PubMed

    Rigouin, Coraline; Vermeire, Jon J; Nylin, Elyse; Williams, David L

    2013-09-01

    Hookworm disease is a debilitating worm infection that affects hundreds of millions of people. Despite the existence of anthelmintic drugs, reports have testified of a decrease in efficacy of these drugs. Therefore, it is imperative to find new drugs and drug targets for hookworm disease treatment. In this study we identify the gene encoding the phytochelatin synthase in the human hookworm, Ancylostoma ceylanicum (AcePCS). Phytochelatin synthase 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. Phytochelatin synthase proteins also function in the elimination of xenobiotics by processing GSH S-conjugates. We found that in vitro AcePCS could both synthesize phytochelatins and hydrolyze a GSH S-conjugate. Interestingly, the enzyme works through a thiol-dependent and, notably, metal-independent mechanism for both transpeptidase (phytochelatin synthesis) and peptidase (hydrolysis of GSH S-conjugates) activities. AcePCS mRNAs are expressed in vivo throughout the life cycle of A. ceylanicum. Mature adult male hookworms isolated from the small intestines of their hosts displayed significantly enhanced expression of AcePCS with transcript levels 5-fold greater than other developmental forms. Although the role of AcePCS in A. ceylanicum biology has yet to be fully investigated the results reported here provide encouraging evidence of the potential that this enzyme holds as a target for new chemotherapeutic intervention. PMID:23916800

  14. Eosinophilia in Patients Infected with Human Immunodeficiency Virus

    PubMed Central

    Chou, Andrew; Serpa, Jose A.

    2015-01-01

    Eosinophilia is not uncommonly encountered in patients infected with human immunodeficiency virus (HIV); particularly at initiation of care or among those with advanced disease. The clinical manifestation most commonly associated with eosinophilia in this patient population is skin rash. Management of these patients is challenging due to a paucity of data evaluating diagnostic testing and therapeutic strategies. Patients born in or with significant travel to parasite-endemic countries are more likely to have tissue-invasive helminthes, such as Strongyloides or Schistosoma. Patients without such risk factors are unlikely to have parasitic infections and frequently will have self-resolution of eosinophilia. When a detailed history, physical exam and diagnostic work-up is unrevealing, we sometimes consider empirical therapy with ivermectin. Praziquantel may also be considered for those at risk for schistosomiasis. PMID:26126686

  15. In Vitro Effect of the Synthetic cal14.1a Conotoxin, Derived from Conus californicus, on the Human Parasite Toxoplasma gondii.

    PubMed

    De León-Nava, Marco A; Romero-Núñez, Eunice; Luna-Nophal, Angélica; Bernáldez-Sarabia, Johanna; Sánchez-Campos, Liliana N; Licea-Navarro, Alexei F; Morales-Montor, Jorge; Muñiz-Hernández, Saé

    2016-04-01

    Toxins that are secreted by cone snails are small peptides that are used to treat several diseases. However, their effects on parasites with human and veterinary significance are unknown. Toxoplasma gondii is an opportunistic parasite that affects approximately 30% of the world's population and can be lethal in immunologically compromised individuals. The conventional treatment for this parasitic infection has remained the same since the 1950s, and its efficacy is limited to the acute phase of infection. These findings have necessitated the search for new drugs that specifically target T. gondii. We examined the effects of the synthetic toxin cal14.1a (s-cal14.1a) from C. californicus on the tachyzoite form of T. gondii. Our results indicate that, at micromolar concentrations, s-cal14.1a lowers viability and inhibits host cell invasion (by 50% and 61%, respectively) on exposure to extracellular parasites. Further, intracellular replication decreased significantly while viability of the host cell was unaffected. Our study is the first report on the antiparasitic activity of a synthetic toxin of C. californicus. PMID:27070627

  16. In Vitro Effect of the Synthetic cal14.1a Conotoxin, Derived from Conus californicus, on the Human Parasite Toxoplasma gondii

    PubMed Central

    De León-Nava, Marco A.; Romero-Núñez, Eunice; Luna-Nophal, Angélica; Bernáldez-Sarabia, Johanna; Sánchez-Campos, Liliana N.; Licea-Navarro, Alexei F.; Morales-Montor, Jorge; Muñiz-Hernández, Saé

    2016-01-01

    Toxins that are secreted by cone snails are small peptides that are used to treat several diseases. However, their effects on parasites with human and veterinary significance are unknown. Toxoplasma gondii is an opportunistic parasite that affects approximately 30% of the world’s population and can be lethal in immunologically compromised individuals. The conventional treatment for this parasitic infection has remained the same since the 1950s, and its efficacy is limited to the acute phase of infection. These findings have necessitated the search for new drugs that specifically target T. gondii. We examined the effects of the synthetic toxin cal14.1a (s-cal14.1a) from C. californicus on the tachyzoite form of T. gondii. Our results indicate that, at micromolar concentrations, s-cal14.1a lowers viability and inhibits host cell invasion (by 50% and 61%, respectively) on exposure to extracellular parasites. Further, intracellular replication decreased significantly while viability of the host cell was unaffected. Our study is the first report on the antiparasitic activity of a synthetic toxin of C. californicus. PMID:27070627

  17. Detection of Giardia lamblia, Entamoeba histolytica/Entamoeba dispar, and Cryptosporidium parvum Antigens in Human Fecal Specimens Using the Triage Parasite Panel Enzyme Immunoassay

    PubMed Central

    Garcia, Lynne S.; Shimizu, Robyn Y.; Bernard, Caroline N.

    2000-01-01

    The Triage parasite panel (BIOSITE Diagnostics, San Diego, Calif.) is a new qualitative enzyme immunoassay (EIA) panel for the detection of Giardia lamblia, Entamoeba histolytica/E. dispar, and Cryptosporidium parvum in fresh or fresh, frozen, unfixed human fecal specimens. By using specific antibodies, antigens specific for these organisms are captured and immobilized on a membrane. Panel performance was evaluated with known positive and negative stool specimens (a total of 444 specimens) that were tested by the standard ova and parasite (O&P) examination as the “gold standard,” including staining with both trichrome and modified acid-fast stains. Specimens with discrepant results between the reference and Triage methods were retested by a different method, either EIA or immunofluorescence. A number of samples with discrepant results with the Triage device were confirmed to be true positives. After resolution of discrepant results, the number of positive specimens and the sensitivity and specificity results were as follows: for G. lamblia, 170, 95.9%, and 97.4%, respectively; for E. histolytica/E. dispar, 99, 96.0%, and 99.1%, respectively; and for C. parvum, 60, 98.3%, and 99.7%, respectively. There was no cross-reactivity with other parasites found in stool specimens, including eight different protozoa (128 challenges) and three different helminths (83 challenges). The ability to perform the complete O&P examination should remain an option for those patients with negative parasite panel results but who are still symptomatic. PMID:10970380

  18. Epidemiology of Ornithodoros brasiliensis (mouro tick) in the southern Brazilian highlands and the description of human and animal retrospective cases of tick parasitism.

    PubMed

    Reck, José; Marks, Fernanda S; Guimarães, Jorge A; Termignoni, Carlos; Martins, João Ricardo

    2013-02-01

    Ornithodoros brasiliensis, also known as the "mouro" tick, is an argasid tick found exclusively in the southern Brazilian highlands. O. brasiliensis parasitism is frequently associated with severe symptoms directly induced by the tick bite, a condition compatible with the definition of tick toxicosis. The objectives of this work include (i) the determination of the distribution of O. brasiliensis in farms located in the tick-endemic region, (ii) the description of the characteristics of O. brasiliensis habitats, (iii) the analysis of risk factors associated with O. brasiliensis, and (iv) the retrospective description of cases of human and animal parasitism by O. brasiliensis. Of the 30 farms included in this study, O. brasiliensis was identified on 5 farms (frequency 16.7%), in which several ticks found in high density buried in soil were collected. Information regarding the tick habitats and the local population was recorded. The data indicated that O. brasiliensis feeds on humans, dogs, armadillos (Dasypus hybridus), and possibly skunks (Conepatus chinga). The analysis of risk factors indicated that the presence of house basements with an unpaved (natural soil) floor on farms and insufficient sanitary conditions significantly enhanced the probability of identifying O. brasiliensis. Additionally, we describe retrospectively cases of tick parasitism in 28 humans and 11 dogs including the most common symptoms associated with tick toxicosis. This is the first study concerning O. brasiliensis epidemiology, distribution, and habitat, and the report represents the most comprehensive characterization of Ornithodoros bite-associated toxicosis syndrome. PMID:23238249

  19. Optimising Controlled Human Malaria Infection Studies Using Cryopreserved P. falciparum Parasites Administered by Needle and Syringe

    PubMed Central

    Sheehy, Susanne H.; Spencer, Alexandra J.; Douglas, Alexander D.; Sim, B. Kim Lee; Longley, Rhea J.; Edwards, Nick J.; Poulton, Ian D.; Kimani, Domtila; Williams, Andrew R.; Anagnostou, Nicholas A.; Roberts, Rachel; Kerridge, Simon; Voysey, Merryn; James, Eric R.; Billingsley, Peter F.; Gunasekera, Anusha; Lawrie, Alison M.; Hoffman, Stephen L.; Hill, Adrian V. S.

    2013-01-01

    Background Controlled human malaria infection (CHMI) studies have become a routine tool to evaluate efficacy of candidate anti-malarial drugs and vaccines. To date, CHMI trials have mostly been conducted using the bite of infected mosquitoes, restricting the number of trial sites that can perform CHMI studies. Aseptic, cryopreserved P. falciparum sporozoites (PfSPZ Challenge) provide a potentially more accurate, reproducible and practical alternative, allowing a known number of sporozoites to be administered simply by injection. Methodology We sought to assess the infectivity of PfSPZ Challenge administered in different dosing regimens to malaria-naive healthy adults (n = 18). Six participants received 2,500 sporozoites intradermally (ID), six received 2,500 sporozoites intramuscularly (IM) and six received 25,000 sporozoites IM. Findings Five out of six participants receiving 2,500 sporozoites ID, 3/6 participants receiving 2,500 sporozoites IM and 6/6 participants receiving 25,000 sporozoites IM were successfully infected. The median time to diagnosis was 13.2, 17.8 and 12.7 days for 2,500 sporozoites ID, 2,500 sporozoites IM and 25,000 sporozoites IM respectively (Kaplan Meier method; p = 0.024 log rank test). Conclusions 2,500 sporozoites ID and 25,000 sporozoites IM have similar infectivities. Given the dose response in infectivity seen with IM administration, further work should evaluate increasing doses of PfSPZ Challenge IM to identify a dosing regimen that reliably infects 100% of participants. Trial Registration ClinicalTrials.gov NCT01465048 PMID:23823332

  20. Some strains of Plasmodium falciparum, a human malaria parasite, evade the complement-like system of Anopheles gambiae mosquitoes.

    PubMed

    Molina-Cruz, Alvaro; DeJong, Randall J; Ortega, Corrie; Haile, Ashley; Abban, Ekua; Rodrigues, Janneth; Jaramillo-Gutierrez, Giovanna; Barillas-Mury, Carolina

    2012-07-10

    Plasmodium falciparum lines differ in their ability to infect mosquitoes. The Anopheles gambiae L3-5 refractory (R) line melanizes most Plasmodium species, including the Brazilian P. falciparum 7G8 line, but it is highly susceptible to some African P. falciparum strains such as 3D7, NF54, and GB4. We investigated whether these lines differ in their ability to evade the mosquito immune system. Silencing key components of the mosquito complement-like system [thioester-containing protein 1 (TEP1), leucine-rich repeat protein 1, and Anopheles Plasmodium-responsive leucine-rich repeat protein 1] prevented melanization of 7G8 parasites, reverting the refractory phenotype. In contrast, it had no effect on the intensity of infection with NF54, suggesting that this line is able to evade TEP1-mediated lysis. When R females were coinfected with a line that is melanized (7G8) and a line that survives (3D7), the coinfection resulted in mixed infections with both live and encapsulated parasites on individual midguts. This finding shows that survival of individual parasites is parasite-specific and not systemic in nature, because parasites can evade TEP1-mediated lysis even when other parasites are melanized in the same midgut. When females from an extensive genetic cross between R and susceptible A. gambiae (G3) mosquitoes were infected with P. berghei, encapsulation was strongly correlated with the TEP1-R1 allele. However, P. falciparum 7G8 parasites were no longer encapsulated by females from this cross, indicating that the TEP1-R1 allele is not sufficient to melanize this line. Evasion of the A. gambiae immune system by P. falciparum may be the result of parasite adaptation to sympatric mosquito vectors and may be an important factor driving malaria transmission. PMID:22623529

  1. Molecular characterization of serine protease inhibitor isoform 3, SmSPI, from Schistosoma mansoni.

    PubMed

    Pakchotanon, Pattarakul; Molee, Patamaporn; Nuamtanong, Supaporn; Limpanont, Yanin; Chusongsang, Phiraphol; Limsomboon, Jareemate; Chusongsang, Yupa; Maneewatchararangsri, Santi; Chaisri, Urai; Adisakwattana, Poom

    2016-08-01

    Serine protease inhibitors, known as serpins, are pleiotropic regulators of endogenous and exogenous proteases, and molecule transporters. They have been documented in animals, plants, fungi, bacteria, and viruses; here, we characterize a serpin from the trematode platyhelminth Schistosoma mansoni. At least eight serpins have been found in the genome of S. mansoni, but only two have characterized molecular properties and functions. Here, the function of S. mansoni serpin isoform 3 (SmSPI) was analyzed, using both computational and molecular biological approaches. Phylogenetic analysis showed that SmSPI was closely related to Schistosoma haematobium serpin and Schistosoma japonicum serpin B10. Structure determined in silico confirmed that SmSPI belonged to the serpin superfamily, containing nine α-helices, three β-sheets, and a reactive central loop. SmSPI was highly expressed in schistosomules, predominantly in the head gland, and in adult male and female with intensive accumulation on the spines, which suggests that it may have a role in facilitating intradermal and intravenous survival. Recombinant SmSPI was overexpressed in Escherichia coli; the recombinant protein was of the same size (46 kDa) as the native protein. Immunological analysis suggested that mice infected with S. mansoni responded to rSmSPI at 8 weeks postinfection (wpi) but not earlier. The inhibitory activity of rSmSPI was specific to chymotrypsin but not trypsin, neutrophil elastase, and porcine pancreatic elastase. Elucidating the biological and physiological functions of SmSPI as well as other serpins will lead to further understanding of host-parasite interaction machinery that may provide novel strategies to prevent and control schistosomiasis in the future. PMID:27083187

  2. Spatially explicit Schistosoma infection risk in eastern Africa using Bayesian geostatistical modelling.

    PubMed

    Schur, Nadine; Hürlimann, Eveline; Stensgaard, Anna-Sofie; Chimfwembe, Kingford; Mushinge, Gabriel; Simoonga, Christopher; Kabatereine, Narcis B; Kristensen, Thomas K; Utzinger, Jürg; Vounatsou, Penelope

    2013-11-01

    Schistosomiasis remains one of the most prevalent parasitic diseases in the tropics and subtropics, but current statistics are outdated due to demographic and ecological transformations and ongoing control efforts. Reliable risk estimates are important to plan and evaluate interventions in a spatially explicit and cost-effective manner. We analysed a large ensemble of georeferenced survey data derived from an open-access neglected tropical diseases database to create smooth empirical prevalence maps for Schistosoma mansoni and Schistosoma haematobium for a total of 13 countries of eastern Africa. Bayesian geostatistical models based on climatic and other environmental data were used to account for potential spatial clustering in spatially structured exposures. Geostatistical variable selection was employed to reduce the set of covariates. Alignment factors were implemented to combine surveys on different age-groups and to acquire separate estimates for individuals aged ≤20 years and entire communities. Prevalence estimates were combined with population statistics to obtain country-specific numbers of Schistosoma infections. We estimate that 122 million individuals in eastern Africa are currently infected with either S. mansoni, or S. haematobium, or both species concurrently. Country-specific population-adjusted prevalence estimates range between 12.9% (Uganda) and 34.5% (Mozambique) for S. mansoni and between 11.9% (Djibouti) and 40.9% (Mozambique) for S. haematobium. Our models revealed that infection risk in Burundi, Eritrea, Ethiopia, Kenya, Rwanda, Somalia and Sudan might be considerably higher than previously reported, while in Mozambique and Tanzania, the risk might be lower than current estimates suggest. Our empirical, large-scale, high-resolution infection risk estimates for S. mansoni and S. haematobium in eastern Africa can guide future control interventions and provide a benchmark for subsequent monitoring and evaluation activities. PMID:22019933

  3. Effects of Treatment on IgE Responses against Parasite Allergen-Like Proteins and Immunity to Reinfection in Childhood Schistosome and Hookworm Coinfections

    PubMed Central

    Jones, Frances M.; Wilson, Shona; Tukahebwa, Edridah; Fitzsimmons, Colin M.; Mwatha, Joseph K.; Bethony, Jeffrey M.; Kabatereine, Narcis B.; Dunne, David W.

    2013-01-01

    Naturally occurring human immunity to both schistosomiasis and hookworm infection has been associated with IgE responses against parasite allergen-like proteins. Since the two helminths frequently coinfect the same individuals, there is growing advocacy for their concurrent treatment. However, both helminths are known to exert strong immunomodulatory effects; therefore, coinfected individuals could have immune responses different from those characteristically seen in monoinfected individuals. In this study, we measured changes in IgE, IgG1, and IgG4 responses to schistosome and hookworm antigens, including the allergen-like proteins Schistosoma mansoni tegumental-allergen-like 1 protein (SmTAL1), SmTAL2, and Necator americanus Ancylostoma-secreted protein-2 (Na-ASP-2), following concurrent treatment of schoolchildren coinfected with Schistosoma mansoni and hookworm. Antibody responses to schistosome egg (soluble egg antigen and SmTAL2) or somatic adult hookworm (AHW) antigens either decreased after treatment or were unchanged, whereas those to schistosome worm antigens (soluble worm antigen and SmTAL1) increased. The observed different effects of treatment likely reflect the different modes of drug action and sites of infection for these two helminths. Importantly, there was no evidence that the simultaneous treatment of coinfected children with praziquantel and albendazole affected schistosome- and hookworm-specific humoral responses differently from those characteristic of populations in which only one organism is endemic; schistosome- and hookworm-specific responses were not associated, and there was no evidence for cross-regulation. Posttreatment increases in the levels of IgE to schistosome worm antigens were associated with lower Schistosoma mansoni reinfection intensity, while no associations between humoral responses to AHW antigen and protection from hookworm reinfection were observed in this sample of school-aged children. PMID:23071136

  4. Multiple Zoonotic Parasites Identified in Dog Feces Collected in Ponte de Lima, Portugal — A Potential Threat to Human Health

    PubMed Central

    Letra Mateus, Teresa; Castro, António; Niza Ribeiro, João; Vieira-Pinto, Madalena

    2014-01-01

    Dogs play many roles and their presence within people’s houses has increased. In rural settings dog faeces are not removed from the streets, representing an environmental pollution factor. Our aim was to evaluate the occurrence of environmental contamination with zoonotic intestinal parasites of three groups of dogs in Ponte de Lima, Portugal, with a particular emphasis on Echinococcus granulosus. We collected 592 dog faecal samples from the environment, farm and hunting dogs. Qualitative flotation coprological analysis was performed and the frequency in the positive samples ranged between 57.44% and 81.19% in different groups. We isolated up to four different parasites in one sample and detected seven intestinal parasitic species, genera or families overall. Ancylostomatidae was the most prevalent parasite, followed by Trichuris spp., Toxocara spp., Isospora spp., Dipylidium caninum, Taeniidae and Toxascaris leonina. Taeniidae eggs were analyzed with the PCR technique and revealed not to be from Echinococcus. The parasite prevalence and the diversity of zoonotic parasites found were high, which calls for a greater awareness of the problem among the population, especially hunters. Promoting research at the local level is important to plan control strategies. Health education should be developed with regard to farmers and hunters, and a closer collaboration between researchers, practitioners and public health authorities is needed. PMID:25257358

  5. Foodborne and waterborne parasites.

    PubMed

    Pozio, Edoardo

    2003-01-01

    More than 72 species of protozoan and helminth parasites can reach humans by food and water, and most of these infections are zoonoses. Some parasites show a cosmopolitan distribution, others a more restricted distribution due to their complex life cycles, which need the presence of one or more intermediate hosts. Of this large number of pathogens, only Toxoplasma gondii can be transmitted to humans by two different ways, i.e., by cysts present in infected meat and by oocysts contaminating food and water. Eleven helminthic species (Taenia saginata, Taenia solium, Taenia asiatica, Trichinella spiralis, Tr. nativa, Tr. britovi, Tr. pseudospiralis, Tr. murrelli, Tr nelsoni, Tr. papuae and Tr. zimbabwensis) can grow in meat of different animal species and can be transmitted to humans by the consumption of raw meat or meat products. Twenty trematode species, four cestode species and seven nematode species can infect humans through the consumption of raw sea- and/or fresh-water food (fishes, molluscs, frogs, tadpoles, camarons, crayfishes). Six species of Cryptosporidium, Isospora belli, Cyclospora cayetanensis, Giardia duodenalis and Entamoeba histolytica/E. dispar can contaminate food and water. Among the helminths, seven trematode species, seven cestode species and five species of nematodes can reach humans by contaminated food and water. Diagnostic and detection methods that can be carried out routinely on food and water samples are available only for few parasites (Cryptosporidium sp., Giardia sp., Anisakidae, Trichinella sp., Taenia sp.), i.e., for parasites which represent a risk to human populations living in industrialised countries. The majority of food and waterborne infections of parasitic origin are related to poverty, low sanitation, and old food habits. PMID:15058817

  6. Navigating parasite webs and parasite flow: emerging and re-emerging parasitic zoonoses of wildlife origin.

    PubMed

    Polley, Lydden

    2005-10-01

    Wildlife are now recognised as an important source of emerging human pathogens, including parasites. This paper discusses the linkages between wildlife, people, zoonotic parasites and the ecosystems in which they co-exist, revisits definitions for 'emerging' and 're-emerging', and lists zoonotic parasites that can be acquired from wildlife including, for some, estimates of the associated global human health burdens. The paper also introduces the concepts of 'parasite webs' and 'parasite flow', provides a context for parasites, relative to other infectious agents, as causes of emerging human disease, and discusses drivers of disease emergence and re-emergence, especially changes in biodiversity and climate. Angiostrongylus cantonensis in the Caribbean and the southern United States, Baylisascaris procyonis in California and Georgia, Plasmodium knowlesi in Sarawak, Malaysia, Human African Trypanosomiasis, Sarcoptes scabiei in carnivores, and Cryptosporidium, Giardia and Toxoplasma in marine ecosystems are presented as examples of wildlife-derived zoonotic parasites of particular recent interest. An ecological approach to disease is promoted, as is a need for an increased profile for this approach in undergraduate and graduate education in the health sciences. Synergy among scientists and disciplines is identified as critical for the study of parasites and parasitic disease in wildlife populations. Recent advances in techniques for the investigation of parasite fauna of wildlife are presented and monitoring and surveillance systems for wildlife disease are discussed. Some of the limitations inherent in predictions for the emergence and re-emergence of infection and disease associated with zoonotic parasites of wildlife are identified. The importance of public awareness and public education in the prevention and control of emerging and re-emerging zoonotic infection and disease are emphasised. Finally, some thoughts for the future are presented. PMID:16168994

  7. Schistosoma mansoni in a low-prevalence area in Brazil: the importance of additional methods for the diagnosis of hard-to-detect individual carriers by low-cost immunological assays

    PubMed Central

    Grenfell, Rafaella Fortini Queiroz; Martins, Watson; Enk, Martin; Almeida, Áureo; Siqueira, Liliane; Silva-Moraes, Vanessa; Oliveira, Edward; Carneiro, Nídia Francisca de Figueiredo; Coelho, Paulo Marcos Zech

    2013-01-01

    Schistosomiasis diagnosis is based on the detection of eggs in the faeces, which is laborious and lacks sensitivity, especially for patients with a low parasite burden. Immunological assays for specific antibody detection are available, but they usually demonstrate low sensitivity and/or specificity. In this study, two simple immunological assays were evaluated for the detection of soluble Schistosoma mansoni adult worm preparation (SWAP) and egg-specific IgGs. These studies have not yet been evaluated for patients with low parasite burdens. Residents of an endemic area in Brazil donated sera and faecal samples for our study. The patients were initially diagnosed by a rigorous Kato-Katz analysis of 18 thick smears from four different stool samples. The ELISA-SWAP was successful for human diagnosis with 90% sensitivity and specificity, confirming the Kato-Katz diagnosis with nearly perfect agreement, as seen by the Kappa index (0.85). Although the ELISA-soluble S. mansoni egg antigen was 85% sensitive, it exhibited low specificity (80%; Kappa index: 0.75) and was more susceptible to cross-reactivity. We believe that immunological assays should be used in conjunction with Kato-Katz analysis as a supplementary tool for the diagnosis of schistosomiasis for patients with low infection burdens, which are usually hard to detect. PMID:23778663

  8. The Use of Reverse Vaccinology and Molecular Modeling Associated with Cell Proliferation Stimulation Approach to Select Promiscuous Epitopes from Schistosoma mansoni.

    PubMed

    Oliveira, Flávio M; Coelho, Ivan E V; Lopes, Marcelo D; Taranto, Alex G; Junior, Moacyr C; Santos, Luciana L D; Villar, José A P F; Fonseca, Cristina T; Lopes, Débora D O

    2016-07-01

    Schistosomiasis remains an important parasitic disease that affects millions of individuals worldwide. Despite the availability of chemotherapy, the occurrence of constant reinfection demonstrates the need for additional forms of intervention and the development of a vaccine represents a relevant strategy to control this disease. With the advent of genomics and bioinformatics, new strategies to search for vaccine targets have been proposed, as the reverse vaccinology. In this work, computational analyses of Schistosoma mansoni membrane proteins were performed to predict epitopes with high affinity for different human leukocyte antigen (HLA)-DRB1. Ten epitopes were selected and along with murine major histocompatibility complex (MHC) class II molecule had their three-dimensional structures optimized. Epitope interactions were evaluated against murine MHC class II molecule through molecular docking, electrostatic potential, and molecular volume. The epitope Sm141290 and Sm050890 stood out in most of the molecular modeling analyses. Cellular proliferation assay was performed to evaluate the ability of these epitopes to bind to murine MHC II molecules and stimulate CD4+ T cells showing that the same epitopes were able to significantly stimulate cell proliferation. This work showed an important strategy of peptide selection for epitope-based vaccine design, achieved by in silico analyses that can precede in vivo and in vitro experiments, avoiding excessive experimentation. PMID:26979443

  9. Expression of a 28-kilodalton glutathione S-transferase antigen of Schistosoma mansoni on the surface of filamentous phages and evaluation of its vaccine potential.

    PubMed

    Rao, Kakuturu V N; He, Yi-Xun; Kalyanasundaram, Ramaswamy

    2003-07-01

    A cloning and expression system that allows display of proteins on the surface of filamentous phages was exploited to display a 28-kDa glutathione S-transferase (Sm28GST) antigen of the human parasite Schistosoma mansoni. The phage-displayed Sm28GST (pdGST) was immunoreactive and was recognized by immune sera, suggesting that the Sm28GST protein displayed on the surface of phages potentially maintains native conformation. Subsequent immunization studies showed that mice can develop high titers of antibodies against pdGST and do not require any additional adjuvant for immunization. Isotype analysis suggested that the pdGST immunization predominantly induced immunoglobulin G2b (IgG2b), IgG3, and IgM anti-GST antibodies in mice. Furthermore, the pdGST immunization was found to confer about 30% protection after a challenge infection with 100 cercariae of S. mansoni in BALB/c mice. These findings suggest that phage display is a simple, efficient, and promising tool to express candidate vaccine antigens for immunization against infectious agents. PMID:12853382

  10. Evaluation of the immune response and protective efficacy of Schistosoma mansoni Cathepsin B in mice using CpG dinucleotides as adjuvant.

    PubMed

    Ricciardi, Alessandra; Dalton, John P; Ndao, Momar

    2015-01-01

    Schistosomiasis is the most important human helminth infection due to its impact on public health. Worldwide, schistosomiasis is estimated to infect at least 200 million individuals while 700 million are at risk. The clinical manifestations are chronic and significantly decrease an individual's quality of life. Infected individuals suffer from long-term organ pathologies including fibrosis which eventually leads to organ failure. The development of a vaccine against this parasitic disease would contribute to a long-lasting decrease in disease spectrum and transmission. Our group has chosen to target Schistosoma mansoni Cathepsin B as a prospective vaccine candidate. The recombinant protein was tested in the presence of synthetic oligodeoxynucleotides containing unmethylated CpG dinucleotides, which are Toll-like receptor 9 agonists known to stimulate a Th1 response. This formulation conferred a 59% decrease in worm burden as well as a reduction in egg burden. Hepatic egg burden and intestinal egg burden were decreased by 56% and 54% respectively. Immunizations with the formulation elicited robust production of Sm-Cathepsin B specific antibodies, both IgG1 and IgG2c but with the latter predominating. Furthermore, splenocytes isolated from the immunized animals, compared to control animals, had increased secretion levels of key Th1 cytokines, IFN-γ and TNF-α, as well as the chemokine CCL5 when stimulated with recombinant Sm-Cathepsin B. These results highlight the potential of Sm-Cathepsin B/CpG as a vaccine candidate against schistosomiasis. PMID:25448114

  11. Evidence that cytokine-mediated immune interactions induced by Schistosoma mansoni alter disease outcome in mice concurrently infected with Trichuris muris

    PubMed Central

    1995-01-01

    In murine models of Schistosoma mansoni infection, egg production is associated with a switch from T helper cell (Th)1- to Th2-type responses to both schistosome-specific and unrelated antigens. Polyparasitism is common in human populations within S. mansoni endemic areas. We have, therefore, examined whether coinfection with S. mansoni could affect the outcome of a second parasitic infection, through Th2 cytokine-dependent modifications to the host immune response. We find that when mice susceptible to infection with the gut nematode Trichuris muris are coinfected with S. mansoni, they acquire the capacity to resolve T. muris infection, thus demonstrating a resistant phenotype. This ability to expel T. muris is associated with the production of Th2- associated cytokines, and corresponding antibody isotypes, in response to S. mansoni egg antigens. The Th2 response shows that there is no compartmentalization between spleen and mesenteric lymph nodes, and that the expulsion of T. muris is not caused by any changes in the host intestine associated with excretion of schistosome eggs. This influence of schistosome infections may be important, not only for the outcome of infections with unrelated pathogens in endemic areas, but also for the efficacy of vaccines in such areas. PMID:7836929

  12. Molecular evidence supports an african affinity of the neotropical freshwater gastropod, Biomphalaria glabrata, say 1818, an intermediate host for Schistosoma mansoni.

    PubMed

    Campbell, G; Jones, C S; Lockyer, A E; Hughes, S; Brown, D; Noble, L R; Rollinson, D

    2000-12-01

    Freshwater snails of the genus Biomphalaria, Preston 1910, are the most important and widely distributed intermediate hosts of Schistosoma mansoni, the blood fluke responsible for human intestinal schistosomiasis, in Africa and the Neotropics. S. mansoni is thought to have been imported repeatedly into the Americas during the last 500 years with the African slave trade. Surprisingly considering that the New and Old World separated 95-106 million years (Myr) ago, the disease rapidly became established due to the presence of endemic susceptible hosts. Reconstructing the phylogenetic relationships within Biomphalaria may provide insights into the successful intercontinental spread of S. mansoni. Parsimony and distance analyses of mitochondrial and nuclear sequences show African taxa to be monophyletic and Neotropical species paraphyletic, with Biomphalaria glabrata forming a separate clade from other Neotropical Biomphalaria, and ancestral to the African taxa. A west to east trans-Atlantic dispersal of a B. glabrata-like taxon, possibly as recently as the Plio-Pleistocene (1.8-3.6 Myr ago) according to a general mitochondrial clock, would fit these observations. Vicariance or an African origin for B. glabrata followed by multiple introductions to South America over the past 500 years with the African slave trade seem unlikely explanations. Knowledge of the phylogenetic relationships among important intermediate host species may prove useful in furthering control measures which exploit genetic differences in susceptibility to parasites, and in elucidating the evolution of schistosome resistance. PMID:11133023

  13. Genomes and geography: genomic insights into the evolution and phylogeography of the genus Schistosoma

    PubMed Central

    2011-01-01

    Blood flukes within the genus Schistosoma still remain a major cause of disease in the tropics and subtropics and the study of their evolution has been an area of major debate and research. With the advent of modern molecular and genomic approaches deeper insights have been attained not only into the divergence and speciation of these worms, but also into the historic movement of these parasites from Asia into Africa, via migration and dispersal of definitive and snail intermediate hosts. This movement was subsequently followed by a radiation of Schistosoma species giving rise to the S. mansoni and S. haematobium groups, as well as the S. indicum group that reinvaded Asia. Each of these major evolutionary events has been marked by distinct changes in genomic structure evident in differences in mitochondrial gene order and nuclear chromosomal architecture between the species associated with Asia and Africa. Data from DNA sequencing, comparative molecular genomics and karyotyping are indicative of major constitutional genomic events which would have become fixed in the ancestral populations of these worms. Here we examine how modern genomic techniques may give a more in depth understanding of the evolution of schistosomes and highlight the complexity of speciation and divergence in this group. PMID:21736723

  14. Genomes and geography: genomic insights into the evolution and phylogeography of the genus Schistosoma.

    PubMed

    Lawton, Scott P; Hirai, Hirohisa; Ironside, Joe E; Johnston, David A; Rollinson, David

    2011-01-01

    Blood flukes within the genus Schistosoma still remain a major cause of disease in the tropics and subtropics and the study of their evolution has been an area of major debate and research. With the advent of modern molecular and genomic approaches deeper insights have been attained not only into the divergence and speciation of these worms, but also into the historic movement of these parasites from Asia into Africa, via migration and dispersal of definitive and snail intermediate hosts. This movement was subsequently followed by a radiation of Schistosoma species giving rise to the S. mansoni and S. haematobium groups, as well as the S. indicum group that reinvaded Asia. Each of these major evolutionary events has been marked by distinct changes in genomic structure evident in differences in mitochondrial gene order and nuclear chromosomal architecture between the species associated with Asia and Africa. Data from DNA sequencing, comparative molecular genomics and karyotyping are indicative of major constitutional genomic events which would have become fixed in the ancestral populations of these worms. Here we examine how modern genomic techniques may give a more in depth understanding of the evolution of schistosomes and highlight the complexity of speciation and divergence in this group. PMID:21736723

  15. Schistosoma mansoni: cercarial responses to irradiance changes

    SciTech Connect

    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.

  16. Intraspecific variation in Schistosoma haematobium from Algeria.

    PubMed

    Kechemir, N; Théron, A

    1997-03-01

    A comparative analysis has been carried out between two populations of Schistosoma haematobium using the same intermediate snail host, Bulinus truncatus, but originating from two distinct ecological areas of Algeria: Khemis-El-Khechna in a sub-humid mediterranean zone and Djanet in a saharan bioclimatic zone. Four parameters have been studied: the growth rate of adult worms, size and shape of the eggs, chronobiology of cercarial emergence and the compatibility with the intermediate host. Results showing divergences for all the characters studied are discussed for the origin of this intraspecific polymorphism of S. haematobium in Algeria. PMID:9166441

  17. Comparative Analysis of Transcriptional Profiles of Adult Schistosoma japonicum from Different Laboratory Animals and the Natural Host, Water Buffalo

    PubMed Central

    Wu, Chuang; Hou, Nan; Chen, Qijun

    2015-01-01

    Background Schistosomiasis is one of the most widely distributed parasitic diseases in the world. Schistosoma japonicum, a zoonotic parasite with a wide range of mammalian hosts, is one of the major pathogens of this disease. Although numerous studies on schistosomiasis japonica have been performed using laboratory animal models, systematic comparative analysis of whole-genome expression profiles in parasites from different laboratory animals and nature mammalian hosts is lacking to date. Methodology/Principal Findings Adult schistosomes were obtained from laboratory animals BALB/c mice, C57BL/6 mice, New Zealand white rabbits and the natural host, water buffaloes. The gene expression profiles of schistosomes from these animals were obtained and compared by genome-wide oligonucleotide microarray analysis. The results revealed that the gene expression profiles of schistosomes from different laboratory animals and buffaloes were highly consistent (r>0.98) genome-wide. Meanwhile, a total of 450 genes were identified to be differentially expressed in schistosomes which can be clustered into six groups. Pathway analysis revealed that these genes were mainly involved in multiple signal transduction pathways, amino acid, energy, nucleotide and lipid metabolism. We also identified a group of 1,540 abundantly and stably expressed gene products in adult worms, including a panel of 179 Schistosoma- or Platyhelminthes-specific genes that may be essential for parasitism and may be regarded as novel potential anti-parasite intervention targets for future research. Conclusions/Significance This study provides a comprehensive database of gene expression profiles of schistosomes derived from different laboratory animals and water buffaloes. An expanded number of genes potentially affecting the development of schistosomes in different animals were identified. These findings lay the foundation for schistosomiasis research in different laboratory animals and natural hosts at the

  18. Differential Anti-Glycan Antibody Responses in Schistosoma mansoni-Infected Children and Adults Studied by Shotgun Glycan Microarray

    PubMed Central

    van Diepen, Angela; Smit, Cornelis H.; van Egmond, Loes; Kabatereine, Narcis B.; Pinot de Moira, Angela; Dunne, David W.; Hokke, Cornelis H.

    2012-01-01

    Background Schistosomiasis (bilharzia) is a chronic and potentially deadly parasitic disease that affects millions of people in (sub)tropical areas. An important partial immunity to Schistosoma infections does develop in disease endemic areas, but this takes many years of exposure and maturation of the immune system. Therefore, children are far more susceptible to re-infection after treatment than older children and adults. This age-dependent immunity or susceptibility to re-infection has been shown to be associated with specific antibody and T cell responses. Many antibodies generated during Schistosoma infection are directed against the numerous glycans expressed by Schistosoma. The nature of glycan epitopes recognized by antibodies in natural schistosomiasis infection serum is largely unknown. Methodology/Principal Findings The binding of serum antibodies to glycans can be analyzed efficiently and quantitatively using glycan microarray approaches. Very small amounts of a large number of glycans are presented on a solid surface allowing binding properties of various glycan binding proteins to be tested. We have generated a so-called shotgun glycan microarray containing natural N-glycan and lipid-glycan fractions derived from 4 different life stages of S. mansoni and applied this array to the analysis of IgG and IgM antibodies in sera from children and adults living in an endemic area. This resulted in the identification of differential glycan recognition profiles characteristic for the two different age groups, possibly reflecting differences in age or differences in length of exposure or infection. Conclusions/Significance Using the shotgun glycan microarray approach to study antibody response profiles against schistosome-derived glycan elements, we have defined groups of infected individuals as well as glycan element clusters to which antibody responses are directed in S. mansoni infections. These findings are significant for further exploration of Schistosoma

  19. Gastrointestinal Parasitic Infections

    PubMed Central

    Embil, Juan A.; Embil, John M.

    1988-01-01

    This article surveys the most important gastrointestinal parasites that affect humans. The modes of acquisition, pathology, epidemiology, diagnosis, and treatment are all briefly examined. Gastrointestinal parasites have become increasingly important in the differential diagnosis of gastrointestinal disease, as a result of a number of circumstances. These circumstances include: increasing travel to developing countries; increased numbers, for one reason or another, of immunocompromised individuals; increased consumption of raw or partially cooked ethnic delicacies; more crowding in day-care centres; increased immigration from developing countries; and an endemic pocket of individuals with certain unhygienic or unsanitary practices. PMID:21253148

  20. The mechanics of malaria parasite invasion of the human erythrocyte - towards a reassessment of the host cell contribution.

    PubMed

    Koch, Marion; Baum, Jake

    2016-03-01

    Despite decades of research, we still know little about the mechanics of Plasmodium host cell invasion. Fundamentally, while the essential or non-essential nature of different parasite proteins is becoming clearer, their actual function and how each comes together to govern invasion are poorly understood. Furthermore, in recent years an emerging world view is shifting focus away from the parasite actin-myosin motor being the sole force responsible for entry to an appreciation of host cell dynamics and forces and their contribution to the process. In this review, we discuss merozoite invasion of the erythrocyte, focusing on the complex set of pre-invasion events and how these might prime the red cell to facilitate invasion. While traditionally parasite interactions at this stage have been viewed simplistically as mediating adhesion only, recent work makes it apparent that by interacting with a number of host receptors and signalling pathways, combined with secretion of parasite-derived lipid material, that the merozoite may initiate cytoskeletal re-arrangements and biophysical changes in the erythrocyte that greatly reduce energy barriers for entry. Seen in this light Plasmodium invasion may well turn out to be a balance between host and parasite forces, much like that of other pathogen infection mechanisms. PMID:26663815

  1. A potential screening factor for accumulation of cholesteyl ester transfer protein deficiency in East Asia: Schistosoma japonicum.

    PubMed

    Yokoyama, Shinji

    2014-04-01

    Cholesteryl ester transfer protein (CETP)-deficiency manifests a unique plasma lipoprotein profile without other apparent symptoms. It is highly common in East Asia while rather rare anywhere else. A potential environmental screening factor(s) may therefore contribute to this eccentric distribution, such as its selective advantage against a regional illness, most likely an infectious disease, in relation to plasma lipoproteins. Blood flukes use the host plasma lipoproteins as nutrient sources through the lipoprotein receptor-like systems. Its Asian-specific species, Schistosoma (S) japonicum, which has been endemic in East Asia, takes up cholesteryl ester (CE) from high-density lipoprotein (HDL) for the embryonation of their eggs to miracidia, a critical step of the hepatic pathogenesis of this parasite, but poorly from HDL of CETP-deficiency. CD36-related protein (CD36RP) was cloned from the adults and the eggs of S. japonicum, with 1880-bp encoding 506 amino-acid residues exhibiting the CD36 domains and two transmembrane regions. Its extracellular domain selectively bound human HDL but neither LDL nor CETP-deficiency HDL, and the antibody against the extracellular domain suppressed the selective HDL-CE uptake and embryonation of the eggs. When infected with S. japonicum, wild-type mice developed less hepatic granulomatosis than CETP-transgenic mice by the ectopic egg embryonation. CD36RP is thus a candidate receptor of S. japonicum to facilitate uptake of HDL-CE necessary for egg embryonation. Abnormal HDL caused by CETP-deficiency retards this process and thereby protects the patients from development of hepatic lesions. S. japonicum infection is a potential screening factor for high prevalence of CETP deficiency in East Asia. PMID:24388961

  2. Environmental epidemiology of intestinal schistosomiasis and genetic diversity of Schistosoma mansoni infections in snails at Bugoigo village, Lake Albert.

    PubMed

    Levitz, Sarah; Standley, Claire J; Adriko, Moses; Kabatereine, Narcis B; Stothard, J Russell

    2013-11-01

    Intestinal schistosomiasis continues to be hyper-endemic in the fishing community of Bugoigo located on the eastern shore of Lake Albert, Uganda. Our study aimed to identify the factors that determine the local distribution and abundance of Biomphalaria, as well as infection(s) with Schistosoma mansoni inclusive of their genetic diversity. In addition, a DNA barcoding approach was taken to genotype schistosome cercariae, exploring the micro-epidemiology of infections. Over a 3-week period in June-July 2010, several hundred Biomphalaria spp. were collected, together with environmental information, from 10 selected sites, representative of both putative wave-exposed (n=5) and wave-sheltered shorelines (n=5). A Mann-Whitney U-test and a generalized linear model were used to assess associations with snail abundance and parasite infections across the shoreline. Levels of local wave action were recorded over the 19-day period using digital accelerometers. The general absence of wave action on the sheltered shoreline likely helped to raise and focalize other environmental parameters, such as water conductivity by lack of mixing, that foster transmission of intestinal schistosomiasis. Over the study period, a total of 10 infected snails were encountered and a selection of schistosome cercariae from each infected snail was harvested for analysis by DNA barcoding. In total, 91 DNA barcodes were generated with 15 unique barcode types identified. Of these, 4 barcodes had been found previously in Lake Albert and (or) Victoria, the remaining 11 were newly encountered here and described. The distribution of DNA barcodes across infected snails and sampled locations revealed a complicated spatial sub-structuring. By shedding new light on the fine-scale patterning of infections, DNA barcoding has revealed a rather heterogeneous landscape of cercariae, likely inclusive of multi-miracidial infections within the snail, which will in turn interplay with human water contact activities to

  3. Vaccination against helminth parasite infections.

    PubMed

    Hewitson, James P; Maizels, Rick M

    2014-04-01

    Helminth parasites infect over one fourth of the human population and are highly prevalent in livestock worldwide. In model systems, parasites are strongly immunomodulatory, but the immune system can be driven to expel them by prior vaccination. However, no vaccines are currently available for human use. Recent advances in vaccination with recombinant helminth antigens have been successful against cestode infections of livestock and new vaccines are being tested against nematode parasites of animals. Numerous vaccine antigens are being defined for a wide range of helminth parasite species, but greater understanding is needed to define the mechanisms of vaccine-induced immunity, to lay a rational platform for new vaccines and their optimal design. With human trials underway for hookworm and schistosomiasis vaccines, a greater integration between veterinary and human studies will highlight the common molecular and mechanistic pathways, and accelerate progress towards reducing the global health burden of helminth infection. PMID:24606541

  4. Human intestinal parasites in Karakuak, West Flores, Indonesia and the effect of treatment with mebendazole and pyrantel pamoate.

    PubMed

    Purnomo; Partono, F; Soewarta, A

    1980-09-01

    A survey for intestinal parasites and mass-treatment with a combination of mebendazole and pyrantel pamoate were conducted in Karakuak, West Flores in 1977. A total of 198 stool specimens from 104 males and 94 females ranging in age from less than 1 to 70 years were examined and 72% harbored one or more intestinal parasites. Ascaris lumbricoides (43%) and Entamoeba histolytica (21%) were the most common, followed by Entamoeba coli (19%), hookworm (18%), Iodamoeba bütschlii (8%), Giardia lamblia (5%) and Trichuris trichiura (4%). Other intestinal parasites infrequently found were: Entamoeba hartmanni (2%), Chilomastix mesnili (2%), Endolimax nana (1%), Enterobius vermicularis (1%) and a heterophyid sp. (1%). A combination of mebendazole base at 200 mg/day and pyrantel pamoate salt at 60 mg/day for three consecutive days was 100% effective. PMID:7444573

  5. Internal parasites of reptiles.

    PubMed

    Raś-Noryńska, Małgorzata; Sokół, Rajmund

    2015-01-01

    Nowadays a growing number of exotic reptiles are kept as pets. The aim of this study was to determine the species of parasites found in reptile patients of veterinary practices in Poland. Fecal samples obtained from 76 lizards, 15 turtles and 10 snakes were examined by flotation method and direct smear stained with Lugol's iodine. In 63 samples (62.4%) the presence of parasite eggs and oocysts was revealed. Oocysts of Isospora spp. (from 33% to 100% of the samples, depending on the reptilian species) and Oxyurids eggs (10% to 75%) were predominant. In addition, isolated Eimeria spp. oocysts and Giardia intestinalis cysts were found, as well as Strongylus spp. and Hymenolepis spp. eggs. Pet reptiles are often infected with parasites, some of which are potentially dangerous to humans. A routine parasitological examination should be done in such animals. PMID:26342508

  6. Pharmacokinetics and risk evaluation of DNA vaccine against Schistosoma japonicum.

    PubMed

    Liu, Hai-Feng; Li, Wei; Lu, Ming-Bo; Yu, Long-Jiang

    2013-01-01

    DNA plasmid immunization is a novel approach of preventive and therapeutic vaccine. More than 100 DNA vaccines have been on preclinical or clinical phase trials, and four kinds of DNA vaccines for livestock have been approved by USDA, CFIA, and APVMA. Schistosomiasis is a worldwide parasitic disease, and vaccine immunization is supposed to be a promising approach to control the health crisis. On the basis of former preclinical studies, we further focused on the pharmacokinetics and risk evaluation of DNA vaccine in vivo. In the present study, enhanced green fluorescent protein (EGFP) report gene was fused with Schistosoma japonicum 23 kDa transmembrane protein antigen gene (Sj23) and constructed into DNA vaccine pVIVO2-Sj23.EGFP. After intramuscularly injecting 100 μg of purified DNA vaccine plasmid to immunizate BALB/c mice, we studied the tissue distribution of DNA plasmid and expressed Sj23.EGFP antigen, the persistence time of elicited antibodies, and the risk of DNA vaccine transferred into intestinal microorganisms. The results showed that DNA vaccine plasmid could be distributed into all tissues of the body after injection; however, only few organs including the injected muscle were detected DNA vaccine at postimmunization until the 100 days by PCR technology; the detection of green fluorescence protein displayed that DNA vaccine could be expressed in almost every tissue and organs; the ELISA assay indicated the immune antibody against Sj23 could persist over 70 days; and the DNA vaccine transferring intestinal flora results was negative. The results indicated that the DNA vaccine has systemic protection and long-lasting effectivity and is safe to intestinal flora. PMID:22990210

  7. Characterization of the Ras homologue of Schistosoma mansoni.

    PubMed

    Osman, A; Niles, E G; LoVerde, P T

    1999-05-15

    Ras is a member of a super-family of guanine-binding or G-proteins. Ras functions as a molecular switch in the transduction of signals generated by the activation of a variety of cell surface receptors and relays the signals to downstream effectors. Little is known about signal transduction in schistosomes. In order for Schistosoma mansoni to survive different immune responses triggered by the host as well as to migrate from the site of penetration at the skin to the final destination in portal circulation, they must receive signals from the host environment and respond to them in a way that allows their survival. We have isolated the schistosome Ras cDNA by using sequence information of the schistosome Ras homologue submitted to the Genbank database. Analysis of the encoded peptide revealed 81% identity and 92% similarity with K-Ras from various species. Ras is a single copy gene as determined by quantitative hybridization experiments. The cDNA was cloned into pGEX-4T and the expressed peptide was used to generate specific antibody reagents. Affinity purified antibodies identified a 23 kDa native protein that localizes to the subtegument. Ras is not associated with the tegument. Ras is expressed in all the developmental stages of the parasite. However, Ras is over-expressed in female worms compared to males. Schistosome Ras was also shown to be post-translationally modified by addition of farnesyl isoprenoid moiety to the cysteine residue in the C-terminal box. Using a schistosome extract in vitro SmRas farnesylation was inhibited by the farnesyl transferase inhibitor, FTI-277, at concentrations comparable to those required to inhibit K-Ras processing. These initial studies on signal transduction in schistosomes should provide a solid basis for improving our understanding of schistosome-host interactions. PMID:10376991

  8. Laboratory and field evaluation of Schistosoma japonicum DNA vaccines in sheep and water buffalo in China.

    PubMed

    Shi, F; Zhang, Y; Ye, P; Lin, J; Cai, Y; Shen, W; Bickle, Q D; Taylor, M G

    2001-11-12

    Vaccines are needed to control zoonotic Schistosoma japonicum infection and several vaccine candidates have now been identified. Two of these (Sj28GST and Sj23) have shown particular promise in sheep when injected with Freund's adjuvants. The objective of the present work was to find a vaccine formulation which may have potential for widespread use in the field. DNA vaccine formulations of these antigens were produced and tested first in sheep under laboratory conditions and then in both the laboratory and the field in water buffalo. In both host species partial protection as evidenced by a reduction in parasite counts in vaccinated compared with control animals was induced by both vaccines, and in water buffalo the vaccines were shown to be partially protective in the field as well as in the laboratory. These results suggest that the two DNA vaccines tested here may have potential for large-scale field use. PMID:11672910

  9. Differences in the Gene Expression Profiles of Haemocytes from Schistosome-Susceptible and -Resistant Biomphalaria glabrata Exposed to Schistosoma mansoni Excretory-Secretory Products

    PubMed Central

    Davies, Angela J.; Kirk, Ruth S.; Emery, Aidan M.; Rollinson, David; Jones, Catherine S.; Noble, Leslie R.; Walker, Anthony J.

    2014-01-01

    During its life cycle, the helminth parasite Schistosoma mansoni uses the freshwater snail Biomphalaria glabrata as an intermediate host to reproduce asexually generating cercariae for infection of the human definitive host. Following invasion of the snail, the parasite develops from a miracidium to a mother sporocyst and releases excretory-secretory products (ESPs) that likely influence the outcome of host infection. To better understand molecular interactions between these ESPs and the host snail defence system, we determined gene expression profiles of haemocytes from S. mansoni-resistant or -susceptible strains of B. glabrata exposed in vitro to S. mansoni ESPs (20 μg/ml) for 1 h, using a 5K B. glabrata cDNA microarray. Ninety-eight genes were found differentially expressed between haemocytes from the two snail strains, 57 resistant specific and 41 susceptible specific, 60 of which had no known homologue in GenBank. Known differentially expressed resistant-snail genes included the nuclear factor kappa B subunit Relish, elongation factor 1α, 40S ribosomal protein S9, and matrilin; known susceptible-snail specific genes included cathepsins D and L, and theromacin. Comparative analysis with other gene expression studies revealed 38 of the 98 identified genes to be uniquely differentially expressed in haemocytes in the presence of ESPs, thus identifying for the first time schistosome ESPs as important molecules that influence global snail host-defence cell gene expression profiles. Such immunomodulation may benefit the schistosome, enabling its survival and successful development in the snail host. PMID:24663063

  10. Extracellular vesicles in parasitic diseases

    PubMed Central

    Marcilla, Antonio; Martin-Jaular, Lorena; Trelis, Maria; de Menezes-Neto, Armando; Osuna, Antonio; Bernal, Dolores; Fernandez-Becerra, Carmen; Almeida, Igor C.; del Portillo, Hernando A.

    2014-01-01

    Parasitic diseases affect billions of people and are considered a major public health issue. Close to 400 species are estimated to parasitize humans, of which around 90 are responsible for great clinical burden and mortality rates. Unfortunately, they are largely neglected as they are mainly endemic to poor regions. Of relevance to this review, there is accumulating evidence of the release of extracellular vesicles (EVs) in parasitic diseases, acting both in parasite–parasite inter-communication as well as in parasite–host interactions. EVs participate in the dissemination of the pathogen and play a role in the regulation of the host immune systems. Production of EVs from parasites or parasitized cells has been described for a number of parasitic infections. In this review, we provide the most relevant findings of the involvement of EVs in intercellular communication, modulation of immune responses, involvement in pathology, and their potential as new diagnostic tools and therapeutic agents in some of the major human parasitic pathogens. PMID:25536932

  11. Crystallization and preliminary X-ray analysis of Na-ASP-1, a multi-domain pathogenesis-related-1 protein from the human hookworm parasite Necator americanus

    SciTech Connect

    Asojo, Oluwatoyin A.; Loukas, Alex; Inan, Mehmet; Barent, Rick; Huang, Jicai; Plantz, Brad; Swanson, Amber; Gouthro, Mark; Meagher, Michael M.; Hotez, Peter J.

    2005-04-01

    In order to clarify the structural basis of the pathogenesis-related-1 domain, Na-ASP-1, the first multi-domain ASP from the human hookworm parasite N. americanus, has been crystallized. 2.2 Å resolution data have been collected from a crystal belonging to the monoclinic space group P2{sub 1}. Human hookworm infection is a major cause of anemia and malnutrition in the developing world. In an effort to control hookworm infection, the Human Hookworm Vaccine Initiative has identified candidate vaccine antigens from the infective larval stage (L3) of the parasite, including a family of pathogenesis-related-1 (PR-1) proteins known as the ancylostoma-secreted proteins (ASPs). The functions of the ASPs are unknown. In addition, it is unclear why some ASPs have one while others have multiple PR-1 domains. There are no known structures of a multi-domain ASP and in an effort to remedy this situation, recombinant Na-ASP-1 has been expressed, purified and crystallized. Na-ASP-1 is a 406-amino-acid multi-domain ASP from the prevalent human hookworm parasite Necator americanus. Useful X-ray data to 2.2 Å have been collected from a crystal that belongs to the monoclinic space group P2{sub 1} with unit-cell parameters a = 67.7, b = 74.27, c = 84.60 Å, β = 112.12°. An initial molecular-replacement solution has been obtained with one monomer in the asymmetric unit.

  12. Parasitic Apologies

    ERIC Educational Resources Information Center

    Galatolo, Renata; Ursi, Biagio; Bongelli, Ramona

    2016-01-01

    The action of apologizing can be accomplished as the main business of the interaction or incidentally while participants are doing something else. We refer to these apologies as "parasitic apologies," because they are produced "en passant" (Schegloff, 2007), and focus our analysis on this type of apology occurring at the…

  13. Foodborne Parasites

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Foodborne infections are a significant cause of morbidity and mortality worldwide, and foodborne parasitic diseases, though not as widespread as bacterial and viral infections, are common on all continents and in most ecosystems, including arctic, temperate, and tropical regions. Certain foodborne ...

  14. The Role of Efflux Pumps in Schistosoma mansoni Praziquantel Resistant Phenotype

    PubMed Central

    Armada, Ana; Belo, Silvana; Carrilho, Emanuel; Viveiros, Miguel; Afonso, Ana

    2015-01-01

    Background Schistosomiasis is a neglected disease caused by a trematode of the genus Schistosoma that is second only to malaria in public health significance in Africa, South America, and Asia. Praziquantel (PZQ) is the drug of choice to treat this disease due to its high cure rates and no significant side effects. However, in the last years increasingly cases of tolerance to PZQ have been reported, which has caused growing concerns regarding the emergency of resistance to this drug. Methodology/Principal Findings Here we describe the selection of a parasitic strain that has a stable resistance phenotype to PZQ. It has been reported that drug resistance in helminths might involve efflux pumps such as members of ATP-binding cassette transport proteins, including P-glycoprotein and multidrug resistance-associated protein families. Here we evaluate the role of efflux pumps in Schistosoma mansoni resistance to PZQ, by comparing the efflux pumps activity in susceptible and resistant strains. The evaluation of the efflux activity was performed by an ethidium bromide accumulation assay in presence and absence of Verapamil. The role of efflux pumps in resistance to PZQ was further investigated comparing the response of susceptible and resistant parasites in the absence and presence of different doses of Verapamil, in an ex vivo assay, and these results were further reinforced through the comparison of the expression levels of SmMDR2 RNA by RT-PCR. Conclusions/Significance This work strongly suggests the involvement of Pgp-like transporters SMDR2 in Praziquantel drug resistance in S. mansoni. Low doses of Verapamil successfully reverted drug resistance. Our results might give an indication that a combination therapy with PZQ and natural or synthetic Pgp modulators can be an effective strategy for the treatment of confirmed cases of resistance to PZQ in S. mansoni. PMID:26445012

  15. Local Antiglycan Antibody Responses to Skin Stage and Migratory Schistosomula of Schistosoma japonicum.

    PubMed

    Smit, Cornelis H; Kies, Christiaan L; McWilliam, Hamish E G; Meeusen, Els N T; Hokke, Cornelis H; van Diepen, Angela

    2016-01-01

    Schistosomiasis is a tropical disease affecting over 230 million people worldwide. Although effective drug treatment is available, reinfections are common, and development of immunity is slow. Most antibodies raised during schistosome infection are directed against glycans, some of which are thought to be protective. Developing schistosomula are considered most vulnerable to immune attack, and better understanding of local antibody responses raised against glycans expressed by this life stage might reveal possible glycan vaccine candidates for future vaccine research. We used antibody-secreting cell (ASC) probes to characterize local antiglycan antibody responses against migrating Schistosoma japonicum schistosomula in different tissues of rats. Analysis by shotgun Schistosoma glycan microarray resulted in the identification of antiglycan antibody response patterns that reflected the migratory pathway of schistosomula. Antibodies raised by skin lymph node (LN) ASC probes mainly targeted N-glycans with terminal mannose residues, Galβ1-4GlcNAc (LacNAc) and Galβ1-4(Fucα1-3)GlcNAc (LeX). Also, responses to antigenic and schistosome-specific glycosphingolipid (GSL) glycans containing highly fucosylated GalNAcβ1-4(GlcNAcβ1)n stretches that are believed to be present at the parasite's surface constitutively upon transformation were found. Antibody targets recognized by lung LN ASC probes were mainly N-glycans presenting GalNAcβ1-4GlcNAc (LDN) and GlcNAc motifs. Surprisingly, antibodies against highly antigenic multifucosylated motifs of GSL glycans were not observed in lung LN ASC probes, indicating that these antigens are not expressed in lung stage schistosomula or are not appropriately exposed to induce immune responses locally. The local antiglycan responses observed in this study highlight the stage- and tissue-specific expression of antigenic parasite glycans and provide insights into glycan targets possibly involved in resistance to S. japonicum infection

  16. Local Antiglycan Antibody Responses to Skin Stage and Migratory Schistosomula of Schistosoma japonicum

    PubMed Central

    Smit, Cornelis H.; Kies, Christiaan L.; McWilliam, Hamish E. G.; Meeusen, Els N. T.; Hokke, Cornelis H.

    2015-01-01

    Schistosomiasis is a tropical disease affecting over 230 million people worldwide. Although effective drug treatment is available, reinfections are common, and development of immunity is slow. Most antibodies raised during schistosome infection are directed against glycans, some of which are thought to be protective. Developing schistosomula are considered most vulnerable to immune attack, and better understanding of local antibody responses raised against glycans expressed by this life stage might reveal possible glycan vaccine candidates for future vaccine research. We used antibody-secreting cell (ASC) probes to characterize local antiglycan antibody responses against migrating Schistosoma japonicum schistosomula in different tissues of rats. Analysis by shotgun Schistosoma glycan microarray resulted in the identification of antiglycan antibody response patterns that reflected the migratory pathway of schistosomula. Antibodies raised by skin lymph node (LN) ASC probes mainly targeted N-glycans with terminal mannose residues, Galβ1-4GlcNAc (LacNAc) and Galβ1-4(Fucα1-3)GlcNAc (LeX). Also, responses to antigenic and schistosome-specific glycosphingolipid (GSL) glycans containing highly fucosylated GalNAcβ1-4(GlcNAcβ1)n stretches that are believed to be present at the parasite's surface constitutively upon transformation were found. Antibody targets recognized by lung LN ASC probes were mainly N-glycans presenting GalNAcβ1-4GlcNAc (LDN) and GlcNAc motifs. Surprisingly, antibodies against highly antigenic multifucosylated motifs of GSL glycans were not observed in lung LN ASC probes, indicating that these antigens are not expressed in lung stage schistosomula or are not appropriately exposed to induce immune responses locally. The local antiglycan responses observed in this study highlight the stage- and tissue-specific expression of antigenic parasite glycans and provide insights into glycan targets possibly involved in resistance to S. japonicum infection

  17. Challenges in predicting the effects of climate change on Schistosoma mansoni and Schistosoma haematobium transmission potential.

    PubMed

    McCreesh, Nicky; Booth, Mark

    2013-11-01

    Climate change will inevitably influence both the distribution of Schistosoma mansoni and Schistosoma haematobium and the incidence of schistosomiasis in areas where it is currently endemic, and impact on the feasibility of schistosomiasis control and elimination goals. There are several limitations of current models of climate and schistosome transmission, and substantial gaps in empirical data that impair model development. In this review we consider how temperature, precipitation, heat waves, drought, and flooding could impact on snail and schistosome population dynamics. We discuss how widely used degree day models of schistosome development may not be accurate at lower temperatures, and highlight the need for further research to improve our understanding of the relationship between air and water temperature and schistosome and snail development. PMID:24064438

  18. The mechanics of malaria parasite invasion of the human erythrocyte – towards a reassessment of the host cell contribution

    PubMed Central

    Koch, Marion

    2016-01-01

    Summary Despite decades of research, we still know little about the mechanics of Plasmodium host cell invasion. Fundamentally, while the essential or non‐essential nature of different parasite proteins is becoming clearer, their actual function and how each comes together to govern invasion are poorly understood. Furthermore, in recent years an emerging world view is shifting focus away from the parasite actin–myosin motor being the sole force responsible for entry to an appreciation of host cell dynamics and forces and their contribution to the process. In this review, we discuss merozoite invasion of the erythrocyte, focusing on the complex set of pre‐invasion events and how these might prime the red cell to facilitate invasion. While traditionally parasite interactions at this stage have been viewed simplistically as mediating adhesion only, recent work makes it apparent that by interacting with a number of host receptors and signalling pathways, combined with secretion of parasite‐derived lipid material, that the merozoite may initiate cytoskeletal re‐arrangements and biophysical changes in the erythrocyte that greatly reduce energy barriers for entry. Seen in this light Plasmodium invasion may well turn out to be a balance between host and parasite forces, much like that of other pathogen infection mechanisms. PMID:26663815

  19. Lundep, a Sand Fly Salivary Endonuclease Increases Leishmania Parasite Survival in Neutrophils and Inhibits XIIa Contact Activation in Human Plasma

    PubMed Central

    Chagas, Andrezza C.; Oliveira, Fabiano; Debrabant, Alain; Valenzuela, Jesus G.; Ribeiro, José M. C.; Calvo, Eric

    2014-01-01

    Neutrophils are the host's first line of defense against infections, and their extracellular traps (NET) were recently shown to kill Leishmania parasites. Here we report a NET-destroying molecule (Lundep) from the salivary glands of Lutzomyia longipalpis. Previous analysis of the sialotranscriptome of Lu. longipalpis showed the potential presence of an endonuclease. Indeed, not only was the cloned cDNA (Lundep) shown to encode a highly active ss- and dsDNAse, but also the same activity was demonstrated to be secreted by salivary glands of female Lu. longipalpis. Lundep hydrolyzes both ss- and dsDNA with little sequence specificity with a calculated DNase activity of 300000 Kunitz units per mg of protein. Disruption of PMA (phorbol 12 myristate 13 acetate)- or parasite-induced NETs by treatment with recombinant Lundep or salivary gland homogenates increases parasite survival in neutrophils. Furthermore, co-injection of recombinant Lundep with metacyclic promastigotes significantly exacerbates Leishmania infection in mice when compared with PBS alone or inactive (mutagenized) Lundep. We hypothesize that Lundep helps the parasite to establish an infection by allowing it to escape from the leishmanicidal activity of NETs early after inoculation. Lundep may also assist blood meal intake by lowering the local viscosity caused by the release of host DNA and as an anticoagulant by inhibiting the intrinsic pathway of coagulation. PMID:24516388

  20. Ultrastructural studies of the killing of schistosomula of Schistosoma mansoni by activated macrophages in vitro.

    PubMed

    McLaren, D J; James, S L

    1985-05-01

    Immunologically activated murine macrophages have been shown elsewhere to kill skin stage schistosomula of Schistosoma mansoni in vitro, in a manner analogous to the extracellular killing of tumour cell targets. In this study, the kinetics of the interaction between activated macrophages and larval targets and the resultant ultrastructural changes in parasite morphology that culminated in death have been analysed in detail. Unlike granulocyte-mediated schistosomular killing, macrophage-mediated cytotoxicity did not appear to be directed against the surface tissues of the parasite. Macrophages adhered only transiently following initiation of the cultures, yet changes in the subtegumental mitochondria and muscle cells of the larva were detected within the first hour of incubation. Progressive internal disorganisation followed rapidly, but the tegument and tegumental outer membrane remained intact, to form a 'shell' that maintained the general shape of the parasite. Such changes were recognised irrespective of whether the effector cell population comprised peritoneal macrophages activated by lymphokine treatment in vitro, or by infection with Mycobacterium bovis (strain BCG), or S. mansoni in vivo. That macrophages rather than contaminating granulocytes or lymphocytes, had mediated the observed damage was demonstrated by the use of a lymphokine treated macrophage cell line, IC-21. The observation that macrophage cytotoxicity is directed against internal organelles rather than the tegumental outer membrane of this multicellular target, may help to elucidate the general mechanism of extracellular killing by these cells. PMID:3892433

  1. Robust inducible Cre recombinase activity in the human malaria parasite Plasmodium falciparum enables efficient gene deletion within a single asexual erythrocytic growth cycle.

    PubMed

    Collins, Christine R; Das, Sujaan; Wong, Eleanor H; Andenmatten, Nicole; Stallmach, Robert; Hackett, Fiona; Herman, Jean-Paul; Müller, Sylke; Meissner, Markus; Blackman, Michael J

    2013-05-01

    Asexual blood stages of the malaria parasite, which cause all the pathology associated with malaria, can readily be genetically modified by homologous recombination, enabling the functional study of parasite genes that are not essential in this part of the life cycle. However, no widely applicable method for conditional mutagenesis of essential asexual blood-stage malarial genes is available, hindering their functional analysis. We report the application of the DiCre conditional recombinase system to Plasmodium falciparum, the causative agent of the most dangerous form of malaria. We show that DiCre can be used to obtain rapid, highly regulated site-specific recombination in P. falciparum, capable of excising loxP-flanked sequences from a genomic locus with close to 100% efficiency within the time-span of a single erythrocytic growth cycle. DiCre-mediated deletion of the SERA5 3' UTR failed to reduce expression of the gene due to the existence of alternative cryptic polyadenylation sites within the modified locus. However, we successfully used the system to recycle the most widely used drug resistance marker for P. falciparum, human dihydrofolate reductase, in the process producing constitutively DiCre-expressing P. falciparum clones that have broad utility for the functional analysis of essential asexual blood-stage parasite genes. PMID:23489321

  2. Tumor necrosis factor alpha neutralization has no direct effect on parasite burden, but causes impaired IFN-γ production by spleen cells from human visceral leishmaniasis patients.

    PubMed

    Singh, Neetu; Kumar, Rajiv; Engwerda, Christian; Sacks, David; Nylen, Susanne; Sundar, Shyam

    2016-09-01

    The pro-inflammatory cytokine tumor necrosis factor (TNF)-α has an important role in control of experimental Leishmania donovani infection. Less is known about the role of TNF-α in human visceral leishmaniasis (VL). Evidence for a protective role is primarily based on case reports of VL development in individuals treated with TNF-α neutralizing antibody. In this study, we have evaluated how TNF-α neutralization affects parasite replication and cytokine production in ex vivo splenic aspirates (SA) from active VL patients. The effect of TNF-α neutralization on cell mediated antigen specific responses were also evaluated using whole blood cultures. Neutralization of TNF-α did not affect parasite numbers in SA cultures. Interferon (IFN)-γ levels were significantly reduced, but interleukin (IL)-10 levels were unchanged in these cultures. Leishmania antigen stimulated SA produced significant TNF-α which suggests that TNF-α is actively produced in VL spleen. Further it stimulates IFN-γ production, but no direct effect on parasite replication. PMID:27372917

  3. Pulmonary leukocytic responses are linked to the acquired immunity of mice vaccinated with irradiated cercariae of Schistosoma mansoni

    SciTech Connect

    Aitken, R.; Coulson, P.S.; Wilson, R.A.

    1988-05-15

    Pulmonary cellular responses in C57BL/6 mice exposed to Schistosoma mansoni have been investigated by sampling cells from the respiratory airways with bronchoalveolar lavage. Mice exposed to cercariae attenuated with 20 krad gamma-radiation developed stronger and more persistent pulmonary leukocytic responses than animals exposed to equal numbers of normal parasites. Although vaccination with irradiated cercariae also stimulated T cell responses of greater magnitude and duration than normal infection, the lymphocytic infiltrate elicited by each regimen did not differ substantially in its composition, 5 wk after exposure. Studies with cercariae attenuated by different treatments established that a link exists between the recruitment of leukocytes to the lungs of vaccinated mice and resistance to reinfection. There was a strong association between pulmonary leukocytic responses and the elimination of challenge infections by vaccinated mice. Animals exposed to irradiated cercariae of S. mansoni were resistant to homologous challenge infection but were not protected against Schistosoma margrebowiei. Homologous challenge of vaccinated mice stimulated anamnestic leukocytic and T lymphocytic responses in the lungs, 2 wk postinfection, but exposure of immunized animals to the heterologous species failed to trigger an expansion in these populations of cells. Our studies indicate that pulmonary leukocytes and T lymphocytes are intimately involved in the mechanism of vaccine-induced resistance to S. mansoni. It remains unclear whether these populations of cells initiate protective inflammatory reactions against challenge parasites in the lungs, or accumulate in response to the activation of the protective mechanism by other means.

  4. Crystallization and preliminary X-ray analysis of Na-ASP-1, a multi-domain pathogenesis-related-1 protein from the human hookworm parasite Necator americanus

    PubMed Central

    Asojo, Oluwatoyin A.; Loukas, Alex; Inan, Mehmet; Barent, Rick; Huang, Jicai; Plantz, Brad; Swanson, Amber; Gouthro, Mark; Meagher, Michael M.; Hotez, Peter J.

    2005-01-01

    Human hookworm infection is a major cause of anemia and malnutrition in the developing world. In an effort to control hookworm infection, the Human Hookworm Vaccine Initiative has identified candidate vaccine antigens from the infective larval stage (L3) of the parasite, including a family of pathogenesis-related-1 (PR-1) proteins known as the ancylostoma-secreted proteins (ASPs). The functions of the ASPs are unknown. In addition, it is unclear why some ASPs have one while others have multiple PR-1 domains. There are no known structures of a multi-domain ASP and in an effort to remedy this situation, recombinant Na-ASP-1 has been expressed, purified and crystallized. Na-ASP-1 is a 406-amino-acid multi-domain ASP from the prevalent human hookworm parasite Necator americanus. Useful X-ray data to 2.2 Å have been collected from a crystal that belongs to the monoclinic space group P21 with unit-cell parameters a = 67.7, b = 74.27, c = 84.60 Å, β = 112.12°. An initial molecular-replacement solution has been obtained with one monomer in the asymmetric unit. PMID:16511050

  5. A whole-genome RNAi screen uncovers a novel role for human potassium channels in cell killing by the parasite Entamoeba histolytica

    PubMed Central

    Marie, Chelsea; Verkerke, Hans P.; Theodorescu, Dan; Petri, William A.

    2015-01-01

    The parasite Entamoeba histolytica kills human cells resulting in ulceration, inflammation and invasion of the colonic epithelium. We used the cytotoxic properties of ameba to select a genome-wide RNAi library to reveal novel host factors that control susceptibility to amebic killing. We identified 281 candidate susceptibility genes and bioinformatics analyses revealed that ion transporters were significantly enriched among susceptibility genes. Potassium (K+) channels were the most common transporter identified. Their importance was further supported by colon biopsy of humans with amebiasis that demonstrated suppressed K+ channel expression. Inhibition of human K+ channels by genetic silencing, pharmacologic inhibitors and with excess K+ protected diverse cell types from E. histolytica-induced death. Contact with E. histolytica parasites triggered K+ channel activation and K+ efflux by intestinal epithelial cells, which preceded cell killing. Specific inhibition of Ca2+-dependent K+ channels was highly effective in preventing amebic cytotoxicity in intestinal epithelial cells and macrophages. Blockade of K+ efflux also inhibited caspase-1 activation, IL-1β secretion and pyroptotic death in THP-1 macrophages. We concluded that K+ channels are host mediators of amebic cytotoxicity in multiple cells types and of inflammasome activation in macrophages. PMID:26346926

  6. 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

  7. NLR proteins and parasitic disease.

    PubMed

    Clay, Gwendolyn M; Sutterwala, Fayyaz S; Wilson, Mary E

    2014-08-01

    Parasitic diseases are a serious global health concern. Many of the most common and most severe parasitic diseases, including Chagas' disease, leishmaniasis, and schistosomiasis, are also classified as neglected tropical diseases and are comparatively less studied than infectious diseases prevalent in high income nations. The NLRs (nucleotide-binding domain leucine-rich-repeat-containing proteins) are cytosolic proteins known to be involved in pathogen detection and host response. The role of NLRs in the host response to parasitic infection is just beginning to be understood. The NLR proteins NOD1 and NOD2 have been shown to contribute to immune responses during Trypanosoma cruzi infection, Toxoplasma gondii infection, and murine cerebral malaria. The NLRP3 inflammasome is activated by T. cruzi and Leishmania amazonensis but also induces pathology during infection with schistosomes or malaria. Both the NLRP1 and NLRP3 inflammasomes respond to T. gondii infection. The NLRs may play crucial roles in human immune responses during parasitic infection, usually acting as innate immune sensors and driving the inflammatory response against invading parasites. However, this inflammatory response can either kill the invading parasite or be responsible for destructive pathology. Therefore, understanding the role of the NLR proteins will be critical to understanding the host defense against parasites as well as the fine balance between homeostasis and parasitic disease. PMID:24989828

  8. Parasite-Derived MicroRNAs in Host Serum As Novel Biomarkers of Helminth Infection

    PubMed Central

    Hoy, Anna M.; Lundie, Rachel J.; Ivens, Alasdair; Quintana, Juan F.; Nausch, Norman; Forster, Thorsten; Jones, Frances; Kabatereine, Narcis B.; Dunne, David W.; Mutapi, Francisca; MacDonald, Andrew S.; Buck, Amy H.

    2014-01-01

    Background MicroRNAs (miRNAs) are a class of short non-coding RNA that play important roles in disease processes in animals and are present in a highly stable cell-free form in body fluids. Here, we examine the capacity of host and parasite miRNAs to serve as tissue or serum biomarkers of Schistosoma mansoni infection. Methods/Principal Findings We used Exiqon miRNA microarrays to profile miRNA expression in the livers of mice infected with S. mansoni at 7 weeks post-infection. Thirty-three mouse miRNAs were differentially expressed in infected compared to naïve mice (>2 fold change, p<0.05) including miR-199a-3p, miR-199a-5p, miR-214 and miR-21, which have previously been associated with liver fibrosis in other settings. Five of the mouse miRNAs were also significantly elevated in serum by twelve weeks post-infection. Sequencing of small RNAs from serum confirmed the presence of these miRNAs and further revealed eleven parasite-derived miRNAs that were detectable by eight weeks post infection. Analysis of host and parasite miRNA abundance by qRT-PCR was extended to serum of patients from low and high infection sites in Zimbabwe and Uganda. The host-derived miRNAs failed to distinguish uninfected from infected individuals. However, analysis of three of the parasite-derived miRNAs (miR-277, miR-3479-3p and bantam) could detect infected individuals from low and high infection intensity sites with specificity/sensitivity values of 89%/80% and 80%/90%, respectively. Conclusions This work identifies parasite-derived miRNAs as novel markers of S. mansoni infection in both mice and humans, with the potential to be used with existing techniques to improve S. mansoni diagnosis. In contrast, although host miRNAs are differentially expressed in the liver during infection their abundance levels in serum are variable in human patients and may be useful in cases of extreme pathology but likely hold limited value for detecting prevalence of infection. PMID:24587461

  9. Stage-specific proteomic expression patterns of the human filarial parasite Brugia malayi and its endosymbiont Wolbachia

    PubMed Central

    Bennuru, Sasisekhar; Meng, Zhaojing; Ribeiro, José M. C.; Semnani, Roshanak Tolouei; Ghedin, Elodie; Chan, King; Lucas, David A.; Veenstra, Timothy D.; Nutman, Thomas B.

    2011-01-01

    Global proteomic analyses of pathogens have thus far been limited to unicellular organisms (e.g., protozoa and bacteria). Proteomic analyses of most eukaryotic pathogens (e.g., helminths) have been restricted to specific organs, specific stages, or secretomes. We report here a large-scale proteomic characterization of almost all the major mammalian stages of Brugia malayi, a causative agent of lymphatic filariasis, resulting in the identification of more than 62% of the products predicted from the Bm draft genome. The analysis also yielded much of the proteome of Wolbachia, the obligate endosymbiont of Bm that also expressed proteins in a stage-specific manner. Of the 11,610 predicted Bm gene products, 7,103 were definitively identified from adult male, adult female, blood-borne and uterine microfilariae, and infective L3 larvae. Among the 4,956 gene products (42.5%) inferred from the genome as “hypothetical,” the present study was able to confirm 2,336 (47.1%) as bona fide proteins. Analysis of protein families and domains coupled with stage-specific expression highlight the important pathways that benefit the parasite during its development in the host. Gene set enrichment analysis identified extracellular matrix proteins and those with immunologic effects as enriched in the microfilarial and L3 stages. Parasite sex- and stage-specific protein expression identified those pathways related to parasite differentiation and demonstrates stage-specific expression by the Bm endosymbiont Wolbachia as well. PMID:21606368

  10. Stage-specific proteomic expression patterns of the human filarial parasite Brugia malayi and its endosymbiont Wolbachia.

    PubMed

    Bennuru, Sasisekhar; Meng, Zhaojing; Ribeiro, José M C; Semnani, Roshanak Tolouei; Ghedin, Elodie; Chan, King; Lucas, David A; Veenstra, Timothy D; Nutman, Thomas B

    2011-06-01

    Global proteomic analyses of pathogens have thus far been limited to unicellular organisms (e.g., protozoa and bacteria). Proteomic analyses of most eukaryotic pathogens (e.g., helminths) have been restricted to specific organs, specific stages, or secretomes. We report here a large-scale proteomic characterization of almost all the major mammalian stages of Brugia malayi, a causative agent of lymphatic filariasis, resulting in the identification of more than 62% of the products predicted from the Bm draft genome. The analysis also yielded much of the proteome of Wolbachia, the obligate endosymbiont of Bm that also expressed proteins in a stage-specific manner. Of the 11,610 predicted Bm gene products, 7,103 were definitively identified from adult male, adult female, blood-borne and uterine microfilariae, and infective L3 larvae. Among the 4,956 gene products (42.5%) inferred from the genome as "hypothetical," the present study was able to confirm 2,336 (47.1%) as bona fide proteins. Analysis of protein families and domains coupled with stage-specific expression highlight the important pathways that benefit the parasite during its development in the host. Gene set enrichment analysis identified extracellular matrix pr