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Sample records for pre-erythrocytic stage infection

  1. Pre-erythrocytic antibody profiles induced by controlled human malaria infections in healthy volunteers under chloroquine prophylaxis

    PubMed Central

    Felgner, Philip L.; Roestenberg, Meta; Liang, Li; Hung, Christopher; Jain, Aarti; Pablo, Jozelyn; Nakajima-Sasaki, Rie; Molina, Douglas; Teelen, Karina; Hermsen, Cornelus C.; Sauerwein, Robert

    2013-01-01

    Complete sterile protection to Plasmodium falciparum (Pf) infection mediated by pre-erythrocytic immunity can be experimentally induced under chloroquine prophylaxis, through immunization with sporozoites from infected mosquitoes' bites (CPS protocol). To characterize the profile of CPS induced antibody (Ab) responses, we developed a proteome microarray containing 809 Pf antigens showing a distinct Ab profile with recognition of antigens expressed in pre-erythrocytic life-cycle stages. In contrast, plasma from naturally exposed semi-immune individuals from Kenya was skewed toward antibody reactivity against asexual blood stage antigens. CPS-immunized and semi-immune individuals generated antibodies against 192 and 202 Pf antigens, respectively, but only 60 antigens overlapped between the two groups. Although the number of reactive antigens varied between the CPS-immunized individuals, all volunteers reacted strongly against the pre-erythrocytic antigens circumsporozoite protein (CSP) and liver stage antigen 1 (LSA1). Well classified merozoite and erythrocytic antigens were strongly reactive in semi-immune individuals but lacking in the CPS immunized group. These data show that the antibody profile of CPS-immunized and semi-immune groups have quite distinct profiles reflecting their protective immunity; antibodies from CPS immunized individuals react strongly against pre-erythrocytic while semi-immune individuals mainly react against erythrocytic antigens. PMID:24351974

  2. DNA from pre-erythrocytic stage malaria parasites is detectable by PCR in the faeces and blood of hosts.

    PubMed

    Abkallo, Hussein M; Liu, Weimin; Hokama, Sarina; Ferreira, Pedro E; Nakazawa, Shusuke; Maeno, Yoshimasa; Quang, Nguyen T; Kobayashi, Nobuyuki; Kaneko, Osamu; Huffman, Michael A; Kawai, Satoru; Marchand, Ron P; Carter, Richard; Hahn, Beatrice H; Culleton, Richard

    2014-06-01

    Following the bite of an infective mosquito, malaria parasites first invade the liver where they develop and replicate for a number of days before being released into the bloodstream where they invade red blood cells and cause disease. The biology of the liver stages of malaria parasites is relatively poorly understood due to the inaccessibility of the parasites to sampling during this phase of their life cycle. Here we report the detection in blood and faecal samples of malaria parasite DNA throughout their development in the livers of mice and before the parasites begin their growth in the blood circulation. It is shown that parasite DNA derived from pre-erythrocytic stage parasites reaches the faeces via the bile. We then show that different primate malaria species can be detected by PCR in blood and faecal samples from naturally infected captive macaque monkeys. These results demonstrate that pre-erythrocytic parasites can be detected and quantified in experimentally infected animals. Furthermore, these results have important implications for both molecular epidemiology and phylogenetics of malaria parasites. In the former case, individuals who are malaria parasite negative by microscopy, but PCR positive for parasite DNA in their blood, are considered to be "sub-microscopic" blood stage parasite carriers. We now propose that PCR positivity is not necessarily an indicator of the presence of blood stage parasites, as the DNA could derive from pre-erythrocytic parasites. Similarly, in the case of molecular phylogenetics based on DNA sequences alone, we argue that DNA amplified from blood or faeces does not necessarily come from a parasite species that infects the red blood cells of that particular host.

  3. Interferon-γ, a valuable surrogate marker of Plasmodium falciparum pre-erythrocytic stages protective immunity

    PubMed Central

    2011-01-01

    Immunity against the pre-erythrocytic stages of malaria is the most promising, as it is strong and fully sterilizing. Yet, the underlying immune effectors against the human Plasmodium falciparum pre-erythrocytic stages remain surprisingly poorly known and have been little explored, which in turn prevents any rational vaccine progress. Evidence that has been gathered in vitro and in vivo, in higher primates and in humans, is reviewed here, emphasizing the significant role of IFN-γ, either as a critical immune mediator or at least as a valuable surrogate marker of protection. One may hope that these results will trigger investigations in volunteers immunized either by optimally irradiated or over-irradiated sporozoites, to quickly delineate better surrogates of protection, which are essential for the development of a successful malaria vaccine. PMID:21303495

  4. Determining liver stage parasite burden by real time quantitative PCR as a method for evaluating pre-erythrocytic malaria vaccine efficacy.

    PubMed

    Witney, A A; Doolan, D L; Anthony, R M; Weiss, W R; Hoffman, S L; Carucci, D J

    2001-12-01

    The detection and quantitation of blood stage parasitaemia is typically used as a surrogate endpoint for estimating the efficacy of vaccines targeted against the hepatic stage, as well as the erythrocytic stage, of the parasite. However, this does not provide an adequate means of evaluating the efficacy of vaccines, which may be only partially effective at the liver-stage. This is a particular concern for effective evaluation of immune enhancement strategies for candidate pre-erythrocytic stage vaccines. Here, we have developed and validated a method for detecting and quantitating liver stage parasites, using the TaqMan fluorescent real-time quantitative PCR system (PE Applied Biosystems). This method uses TaqMan primers designed to the Plasmodium yoelii 18S rRNA gene and rodent GAPDH to amplify products from infected mouse liver cDNA. The technique is highly reproducible as demonstrated with plasmid controls and capable of efficiently quantitating liver-stage parasite burden following a range of sporozoite challenge doses in strains of mice, which differ in their susceptibility to sporozoite infection. We have further demonstrated the capacity of this technique to evaluate the efficacy of a range of pre-erythrocytic stage vaccines. Our data establish this quantitative real-time PCR assay to be a fast and reproducible way of accurately assessing liver stage parasite burden and vaccine efficacy in rodent malaria models.

  5. Malaria vaccine candidate antigen targeting the pre-erythrocytic stage of Plasmodium falciparum produced at high level in plants.

    PubMed

    Voepel, Nadja; Boes, Alexander; Edgue, Güven; Beiss, Veronique; Kapelski, Stephanie; Reimann, Andreas; Schillberg, Stefan; Pradel, Gabriele; Fendel, Rolf; Scheuermayer, Matthias; Spiegel, Holger; Fischer, Rainer

    2014-11-01

    Plants have emerged as low-cost production platforms suitable for vaccines targeting poverty-related diseases. Besides functional efficacy, the stability, yield, and purification process determine the production costs of a vaccine and thereby the feasibility of plant-based production. We describe high-level plant production and functional characterization of a malaria vaccine candidate targeting the pre-erythrocytic stage of Plasmodium falciparum. CCT, a fusion protein composed of three sporozoite antigens (P. falciparum cell traversal protein for ookinetes and sporozoites [PfCelTOS], P. falciparum circumsporozoite protein [PfCSP], and P. falciparum thrombospondin-related adhesive protein [PfTRAP]), was transiently expressed by agroinfiltration in Nicotiana benthamiana leaves, accumulated to levels up to 2 mg/g fresh leaf weight (FLW), was thermostable up to 80°C and could be purified to >95% using a simple two-step procedure. Reactivity of sera from malaria semi-immune donors indicated the immunogenic conformation of the purified fusion protein consisting of PfCelTOS, PfCSP_TSR, PfTRAP_TSR domains (CCT) protein. Total IgG from the CCT-specific mouse immune sera specifically recognized P. falciparum sporozoites in immunofluorescence assays and induced up to 35% inhibition in hepatocyte invasion assays. Featuring domains from three promising sporozoite antigens with different roles (attachment and cell traversal) in the hepatocyte invasion process, CCT has the potential to elicit broader immune responses against the pre-erythrocytic stage of P. falciparum and represents an interesting new candidate, also as a component of multi-stage, multi-subunit malaria vaccine cocktails.

  6. Pre-erythrocytic malaria vaccines: identifying the targets

    PubMed Central

    Duffy, Patrick E; Sahu, Tejram; Akue, Adovi; Milman, Neta; Anderson, Charles

    2013-01-01

    Pre-erythrocytic malaria vaccines target Plasmodium during its sporozoite and liver stages, and can prevent progression to blood-stage disease, which causes a million deaths each year. Whole organism sporozoite vaccines induce sterile immunity in animals and humans and guide subunit vaccine development. A recombinant protein-in-adjuvant pre-erythrocytic vaccine called RTS,S reduces clinical malaria without preventing infection in field studies and additional antigens may be required to achieve sterile immunity. Although few vaccine antigens have progressed to human testing, new insights into parasite biology, expression profiles and immunobiology have offered new targets for intervention. Future advances require human trials of additional antigens, as well as platforms to induce the durable antibody and cellular responses including CD8+ T cells that contribute to sterile protection. PMID:23176657

  7. Identification of Novel Pre-Erythrocytic Malaria Antigen Candidates for Combination Vaccines with Circumsporozoite Protein

    PubMed Central

    Sahu, Tejram; Malkov, Vlad; Morrison, Robert; Pei, Ying; Juompan, Laure; Milman, Neta; Zarling, Stasya; Anderson, Charles; Wong-Madden, Sharon; Wendler, Jason; Ishizuka, Andrew; MacMillen, Zachary W.; Garcia, Valentino; Kappe, Stefan H. I.; Krzych, Urszula; Duffy, Patrick E.

    2016-01-01

    Malaria vaccine development has been hampered by the limited availability of antigens identified through conventional discovery approaches, and improvements are needed to enhance the efficacy of the leading vaccine candidate RTS,S that targets the circumsporozoite protein (CSP) of the infective sporozoite. Here we report a transcriptome-based approach to identify novel pre-erythrocytic vaccine antigens that could potentially be used in combination with CSP. We hypothesized that stage-specific upregulated genes would enrich for protective vaccine targets, and used tiling microarray to identify P. falciparum genes transcribed at higher levels during liver stage versus sporozoite or blood stages of development. We prepared DNA vaccines for 21 genes using the predicted orthologues in P. yoelii and P. berghei and tested their efficacy using different delivery methods against pre-erythrocytic malaria in rodent models. In our primary screen using P. yoelii in BALB/c mice, we found that 16 antigens significantly reduced liver stage parasite burden. In our confirmatory screen using P. berghei in C57Bl/6 mice, we confirmed 6 antigens that were protective in both models. Two antigens, when combined with CSP, provided significantly greater protection than CSP alone in both models. Based on the observations reported here, transcriptional patterns of Plasmodium genes can be useful in identifying novel pre-erythrocytic antigens that induce protective immunity alone or in combination with CSP. PMID:27434123

  8. An expanding toolkit for preclinical pre-erythrocytic malaria vaccine development: bridging traditional mouse malaria models and human trials.

    PubMed

    Steel, Ryan Wj; Kappe, Stefan Hi; Sack, Brandon K

    2016-12-01

    Malaria remains a significant public health burden with 214 million new infections and over 400,000 deaths in 2015. Elucidating relevant Plasmodium parasite biology can lead to the identification of novel ways to control and ultimately eliminate the parasite within geographic areas. Particularly, the development of an effective vaccine that targets the clinically silent pre-erythrocytic stages of infection would significantly augment existing malaria elimination tools by preventing both the onset of blood-stage infection/disease as well as spread of the parasite through mosquito transmission. In this Perspective, we discuss the role of small animal models in pre-erythrocytic stage vaccine development, highlighting how human liver-chimeric and human immune system mice are emerging as valuable components of these efforts.

  9. Cross-stage immunity for malaria vaccine development.

    PubMed

    Nahrendorf, Wiebke; Scholzen, Anja; Sauerwein, Robert W; Langhorne, Jean

    2015-12-22

    A vaccine against malaria is urgently needed for control and eventual eradication. Different approaches are pursued to induce either sterile immunity directed against pre-erythrocytic parasites or to mimic naturally acquired immunity by controlling blood-stage parasite densities and disease severity. Pre-erythrocytic and blood-stage malaria vaccines are often seen as opposing tactics, but it is likely that they have to be combined into a multi-stage malaria vaccine to be optimally safe and effective. Since many antigenic targets are shared between liver- and blood-stage parasites, malaria vaccines have the potential to elicit cross-stage protection with immune mechanisms against both stages complementing and enhancing each other. Here we discuss evidence from pre-erythrocytic and blood-stage subunit and whole parasite vaccination approaches that show that protection against malaria is not necessarily stage-specific. Parasites arresting at late liver-stages especially, can induce powerful blood-stage immunity, and similarly exposure to blood-stage parasites can afford pre-erythrocytic immunity. The incorporation of a blood-stage component into a multi-stage malaria vaccine would hence not only combat breakthrough infections in the blood should the pre-erythrocytic component fail to induce sterile protection, but would also actively enhance the pre-erythrocytic potency of this vaccine. We therefore advocate that future studies should concentrate on the identification of cross-stage protective malaria antigens, which can empower multi-stage malaria vaccine development.

  10. Protective Immunity to Pre-Erythrocytic Stage Malaria

    DTIC Science & Technology

    2011-01-01

    adjuvants including ASO2A, an oil- in-water emulsion containing QS-21 (a derivative of the saponin Quil A) and mono-phosphoryl lipid A, and ASO1B, which is a...long-lived T cell memory. Other adjuvants such as Iscoma- trix (cage-like structures consisting of saponin , phospho- lipid and cholesterol) could also

  11. Plasmodium vivax Pre-Erythrocytic–Stage Antigen Discovery: Exploiting Naturally Acquired Humoral Responses

    PubMed Central

    Molina, Douglas M.; Finney, Olivia C.; Arevalo-Herrera, Myriam; Herrera, Socrates; Felgner, Philip L.; Gardner, Malcolm J.; Liang, Xiaowu; Wang, Ruobing

    2012-01-01

    The development of pre-erythrocytic Plasmodium vivax vaccines is hindered by the lack of in vitro culture systems or experimental rodent models. To help bypass these roadblocks, we exploited the fact that naturally exposed Fy− individuals who lack the Duffy blood antigen (Fy) receptor are less likely to develop blood-stage infections; therefore, they preferentially develop immune responses to pre-erythrocytic–stage parasites, whereas Fy+ individuals experience both liver- and blood-stage infections and develop immune responses to both pre-erythrocytic and erythrocytic parasites. We screened 60 endemic sera from P. vivax-exposed Fy+ or Fy− donors against a protein microarray containing 91 P. vivax proteins with P. falciparum orthologs that were up-regulated in sporozoites. Antibodies against 10 P. vivax antigens were identified in sera from P. vivax-exposed individuals but not unexposed controls. This technology has promising implications in the discovery of potential vaccine candidates against P. vivax malaria. PMID:22826492

  12. Analysis of a Multi-component Multi-stage Malaria Vaccine Candidate--Tackling the Cocktail Challenge.

    PubMed

    Boes, Alexander; Spiegel, Holger; Voepel, Nadja; Edgue, Gueven; Beiss, Veronique; Kapelski, Stephanie; Fendel, Rolf; Scheuermayer, Matthias; Pradel, Gabriele; Bolscher, Judith M; Behet, Marije C; Dechering, Koen J; Hermsen, Cornelus C; Sauerwein, Robert W; Schillberg, Stefan; Reimann, Andreas; Fischer, Rainer

    2015-01-01

    Combining key antigens from the different stages of the P. falciparum life cycle in the context of a multi-stage-specific cocktail offers a promising approach towards the development of a malaria vaccine ideally capable of preventing initial infection, the clinical manifestation as well as the transmission of the disease. To investigate the potential of such an approach we combined proteins and domains (11 in total) from the pre-erythrocytic, blood and sexual stages of P. falciparum into a cocktail of four different components recombinantly produced in plants. After immunization of rabbits we determined the domain-specific antibody titers as well as component-specific antibody concentrations and correlated them with stage specific in vitro efficacy. Using purified rabbit immune IgG we observed strong inhibition in functional in vitro assays addressing the pre-erythrocytic (up to 80%), blood (up to 90%) and sexual parasite stages (100%). Based on the component-specific antibody concentrations we calculated the IC50 values for the pre-erythrocytic stage (17-25 μg/ml), the blood stage (40-60 μg/ml) and the sexual stage (1.75 μg/ml). While the results underline the feasibility of a multi-stage vaccine cocktail, the analysis of component-specific efficacy indicates significant differences in IC50 requirements for stage-specific antibody concentrations providing valuable insights into this complex scenario and will thereby improve future approaches towards malaria vaccine cocktail development regarding the selection of suitable antigens and the ratios of components, to fine tune overall and stage-specific efficacy.

  13. Analysis of a Multi-component Multi-stage Malaria Vaccine Candidate—Tackling the Cocktail Challenge

    PubMed Central

    Voepel, Nadja; Edgue, Gueven; Beiss, Veronique; Kapelski, Stephanie; Fendel, Rolf; Scheuermayer, Matthias; Pradel, Gabriele; Bolscher, Judith M.; Behet, Marije C.; Dechering, Koen J.; Hermsen, Cornelus C.; Sauerwein, Robert W.; Schillberg, Stefan; Reimann, Andreas; Fischer, Rainer

    2015-01-01

    Combining key antigens from the different stages of the P. falciparum life cycle in the context of a multi-stage-specific cocktail offers a promising approach towards the development of a malaria vaccine ideally capable of preventing initial infection, the clinical manifestation as well as the transmission of the disease. To investigate the potential of such an approach we combined proteins and domains (11 in total) from the pre-erythrocytic, blood and sexual stages of P. falciparum into a cocktail of four different components recombinantly produced in plants. After immunization of rabbits we determined the domain-specific antibody titers as well as component-specific antibody concentrations and correlated them with stage specific in vitro efficacy. Using purified rabbit immune IgG we observed strong inhibition in functional in vitro assays addressing the pre-erythrocytic (up to 80%), blood (up to 90%) and sexual parasite stages (100%). Based on the component-specific antibody concentrations we calculated the IC50 values for the pre-erythrocytic stage (17–25 μg/ml), the blood stage (40–60 μg/ml) and the sexual stage (1.75 μg/ml). While the results underline the feasibility of a multi-stage vaccine cocktail, the analysis of component-specific efficacy indicates significant differences in IC50 requirements for stage-specific antibody concentrations providing valuable insights into this complex scenario and will thereby improve future approaches towards malaria vaccine cocktail development regarding the selection of suitable antigens and the ratios of components, to fine tune overall and stage-specific efficacy. PMID:26147206

  14. Late Stage Infection in Sleeping Sickness

    PubMed Central

    Acker, Sven; Frey, Claudia; Meinert, Monika; Schönfeld, Caroline; Lazarus, Michael; Urade, Yoshihiro; Kubata, Bruno Kilunga; Duszenko, Michael

    2012-01-01

    At the turn of the 19th century, trypanosomes were identified as the causative agent of sleeping sickness and their presence within the cerebrospinal fluid of late stage sleeping sickness patients was described. However, no definitive proof of how the parasites reach the brain has been presented so far. Analyzing electron micrographs prepared from rodent brains more than 20 days after infection, we present here conclusive evidence that the parasites first enter the brain via the choroid plexus from where they penetrate the epithelial cell layer to reach the ventricular system. Adversely, no trypanosomes were observed within the parenchyma outside blood vessels. We also show that brain infection depends on the formation of long slender trypanosomes and that the cerebrospinal fluid as well as the stroma of the choroid plexus is a hostile environment for the survival of trypanosomes, which enter the pial space including the Virchow-Robin space via the subarachnoid space to escape degradation. Our data suggest that trypanosomes do not intend to colonize the brain but reside near or within the glia limitans, from where they can re-populate blood vessels and disrupt the sleep wake cycles. PMID:22496723

  15. Late stage infection in sleeping sickness.

    PubMed

    Wolburg, Hartwig; Mogk, Stefan; Acker, Sven; Frey, Claudia; Meinert, Monika; Schönfeld, Caroline; Lazarus, Michael; Urade, Yoshihiro; Kubata, Bruno Kilunga; Duszenko, Michael

    2012-01-01

    At the turn of the 19(th) century, trypanosomes were identified as the causative agent of sleeping sickness and their presence within the cerebrospinal fluid of late stage sleeping sickness patients was described. However, no definitive proof of how the parasites reach the brain has been presented so far. Analyzing electron micrographs prepared from rodent brains more than 20 days after infection, we present here conclusive evidence that the parasites first enter the brain via the choroid plexus from where they penetrate the epithelial cell layer to reach the ventricular system. Adversely, no trypanosomes were observed within the parenchyma outside blood vessels. We also show that brain infection depends on the formation of long slender trypanosomes and that the cerebrospinal fluid as well as the stroma of the choroid plexus is a hostile environment for the survival of trypanosomes, which enter the pial space including the Virchow-Robin space via the subarachnoid space to escape degradation. Our data suggest that trypanosomes do not intend to colonize the brain but reside near or within the glia limitans, from where they can re-populate blood vessels and disrupt the sleep wake cycles.

  16. Progress and prospects for blood-stage malaria vaccines.

    PubMed

    Miura, Kazutoyo

    2016-06-01

    There have been significant decreases in malaria mortality and morbidity in the last 10-15 years, and the most advanced pre-erythrocytic malaria vaccine, RTS,S, received a positive opinion from European regulators in July 2015. However, no blood-stage vaccine has reached a phase III trial. The first part of this review summarizes the pros and cons of various assays and models that have been and will be used to predict the efficacy of blood-stage vaccines. In the second part, blood-stage vaccine candidates that showed some efficacy in human clinical trials or controlled human malaria infection models are discussed. Then, candidates under clinical investigation are described in the third part, and other novel candidates and strategies are reviewed in the last part.

  17. Progress and prospects for blood-stage malaria vaccines

    PubMed Central

    Miura, Kazutoyo

    2016-01-01

    ABSTRACT There have been significant decreases in malaria mortality and morbidity in the last 10-15 years, and the most advanced pre-erythrocytic malaria vaccine, RTS,S, received a positive opinion from European regulators in July 2015. However, no blood-stage vaccine has reached a phase III trial. The first part of this review summarizes the pros and cons of various assays and models that have been and will be used to predict the efficacy of blood-stage vaccines. In the second part, blood-stage vaccine candidates that showed some efficacy in human clinical trials or controlled human malaria infection models are discussed. Then, candidates under clinical investigation are described in the third part, and other novel candidates and strategies are reviewed in the last part. PMID:26760062

  18. ChAd63-MVA–vectored Blood-stage Malaria Vaccines Targeting MSP1 and AMA1: Assessment of Efficacy Against Mosquito Bite Challenge in Humans

    PubMed Central

    Sheehy, Susanne H; Duncan, Christopher JA; Elias, Sean C; Choudhary, Prateek; Biswas, Sumi; Halstead, Fenella D; Collins, Katharine A; Edwards, Nick J; Douglas, Alexander D; Anagnostou, Nicholas A; Ewer, Katie J; Havelock, Tom; Mahungu, Tabitha; Bliss, Carly M; Miura, Kazutoyo; Poulton, Ian D; Lillie, Patrick J; Antrobus, Richard D; Berrie, Eleanor; Moyle, Sarah; Gantlett, Katherine; Colloca, Stefano; Cortese, Riccardo; Long, Carole A; Sinden, Robert E; Gilbert, Sarah C; Lawrie, Alison M; Doherty, Tom; Faust, Saul N; Nicosia, Alfredo; Hill, Adrian VS; Draper, Simon J

    2012-01-01

    The induction of cellular immunity, in conjunction with antibodies, may be essential for vaccines to protect against blood-stage infection with the human malaria parasite Plasmodium falciparum. We have shown that prime-boost delivery of P. falciparum blood-stage antigens by chimpanzee adenovirus 63 (ChAd63) followed by the attenuated orthopoxvirus MVA is safe and immunogenic in healthy adults. Here, we report on vaccine efficacy against controlled human malaria infection delivered by mosquito bites. The blood-stage malaria vaccines were administered alone, or together (MSP1+AMA1), or with a pre-erythrocytic malaria vaccine candidate (MSP1+ME-TRAP). In this first human use of coadministered ChAd63-MVA regimes, we demonstrate immune interference whereby responses against merozoite surface protein 1 (MSP1) are dominant over apical membrane antigen 1 (AMA1) and ME-TRAP. We also show that induction of strong cellular immunity against MSP1 and AMA1 is safe, but does not impact on parasite growth rates in the blood. In a subset of vaccinated volunteers, a delay in time to diagnosis was observed and sterilizing protection was observed in one volunteer coimmunized with MSP1+AMA1—results consistent with vaccine-induced pre-erythrocytic, rather than blood-stage, immunity. These data call into question the utility of T cell-inducing blood-stage malaria vaccines and suggest that the focus should remain on high-titer antibody induction against susceptible antigen targets. PMID:23089736

  19. Broadly distributed T cell reactivity, with no immunodominant loci, to the pre-erythrocytic antigen thrombospondin-related adhesive protein of Plasmodium falciparum in West Africans.

    PubMed

    Flanagan, K L; Plebanski, M; Akinwunmi, P; Lee, E A; Reece, W H; Robson, K J; Hill, A V; Pinder, M

    1999-06-01

    Protective immunity to malaria has been achieved in human volunteers utilizing the pre-erythrocytic Plasmodium falciparum antigen, the circumsporozoite protein (CS). However, T cell reactivity to CS is focused on several highly polymorphic T cell epitope regions, potentially limiting the efficacy of any vaccine to specific malaria strains. Another important pre-erythrocytic malaria antigen, the thrombospondin-related adhesive protein (TRAP), can induce protection in animal models of malaria, but knowledge of human T cell responses is limited to the identification of CD8 T cell epitopes, with no CD4 epitopes identified to date. This comprehensive study assessed reactivity to overlapping peptides spanning almost the whole of P. falciparum TRAP (PfTRAP), as well as peptides selected on the basis of HLA class II-binding motifs. A total of 50 naturally exposed Gambian adults were assessed to define 26 T cell epitopes in PfTRAP capable of inducing rapid IFN-gamma or IL-4 production, as assessed by enzyme-linked immunospot assays. In contrast to the CS protein, this reactivity was broadly distributed along the length of TRAP. Moreover, of the 26 epitopes identified, 10 were found to be conserved in West Africa.

  20. Disruption of the Plasmodium falciparum liver-stage antigen-1 locus causes a differentiation defect in late liver-stage parasites.

    PubMed

    Mikolajczak, Sebastian A; Sacci, John B; De La Vega, Patricia; Camargo, Nelly; VanBuskirk, Kelly; Krzych, Urszula; Cao, Jun; Jacobs-Lorena, Marcelo; Cowman, Alan F; Kappe, Stefan H I

    2011-08-01

    The malaria parasite Plasmodium falciparum infects humans and first targets the liver where liver-stage parasites undergo pre-erythrocytic replication. Liver-stage antigen-1 (LSA-1) is currently the only identified P. falciparum protein for which expression is restricted to liver stages. Yet, the importance of LSA-1 for liver-stage parasite development remains unknown. Here we deleted LSA-1 in the NF54 strain of P. falciparum and analysed the lsa-1(-) parasites throughout their life cycle. lsa-1(-) sporozoites had normal gliding motility and invasion into hepatocytes. Six days after infection of a hepatocytic cell line, lsa-1(-) parasites exhibited a moderate phenotype with an ~50% reduction of late liver-stage forms when compared with wild type. Strikingly, lsa-1(-) parasites growing in SCID/Alb-uPA mice with humanized livers showed a severe defect in late liver-stage differentiation and exo-erythrocytic merozoite formation 7 days after infection, a time point when wild-type parasites develop into mature merozoites. The lsa-1(-) parasites also showed aberrant liver-stage expression of key parasite proteins apical membrane antigen-1 and circumsporozoite protein. Our data show that LSA-1 plays a critical role during late liver-stage schizogony and is thus important in the parasite transition from the liver to blood. LSA-1 is the first P. falciparum protein identified to be required for this transitional stage of the parasite life cycle.

  1. Proteomic profiling of the infective trophozoite stage of Acanthamoeba polyphaga.

    PubMed

    Caumo, Karin Silva; Monteiro, Karina Mariante; Ott, Thiely Rodrigues; Maschio, Vinicius José; Wagner, Glauber; Ferreira, Henrique Bunselmeyer; Rott, Marilise Brittes

    2014-12-01

    Acanthamoeba polyphaga is a free-living protozoan pathogen, whose infective trophozoite form is capable of causing a blinding keratitis and fatal granulomatous encephalitis in humans. The damage caused by A. polyphaga trophozoites in human corneal or brain infections is the result of several different pathogenic mechanisms that have not yet been elucidated at the molecular level. We performed a comprehensive analysis of the proteins expressed by A. polyphaga trophozoites, based on complementary 2-DE MS/MS and gel-free LC-MS/MS approaches. Overall, 202 non-redundant proteins were identified. An A. polyphaga proteomic map in the pH range 3-10 was produced, with protein identification for 184 of 370 resolved spots, corresponding to 142 proteins. Additionally, 94 proteins were identified by gel-free LC-MS/MS. Functional classification revealed several proteins with potential importance for pathogen survival and infection of mammalian hosts, including surface proteins and proteins related to defense mechanisms. Our study provided the first comprehensive proteomic survey of the trophozoite infective stage of an Acanthamoeba species, and established foundations for prospective, comparative and functional studies of proteins involved in mechanisms of survival, development, and pathogenicity in A. polyphaga and other pathogenic amoebae.

  2. Parasitic infection in various stages life of cultured Acipenser persicus

    PubMed Central

    Adel, Milad; Safari, Reza; Yaghoubzadeh, Zahra; Fazli, Hassan; Khalili, Elham

    2016-01-01

    The present study was conducted to evaluate the status of the parasite fauna in Acipenser persicus at different development stages, in order to find prevention protocols for parasitic diseases in this valuable species. For this purpose, sampling from each sex breeder, 10 egg samples, 5-day-old larvae (n = 20), 20-day-old larvae (n = 80) and fingerling of A. persicus (n = 60) released in earthen ponds were done. After the bioassay and preparing wet mount from the internal and external organs, identification was done according to the keys. According to the results, no fauna parasites were isolated from egg samples and 5-day-old larvae; but Trichodina spp. was isolated from 20-day-old larvae. Also, the same protozoan was isolated from fingerling released in earthen ponds, the mean intensity, prevalence and range of contamination by fingerling were higher with compared to 20-day-old larvae. Trichodina sp. and Diplostomum spathaceum were isolated from skin and eyes of females, respectively. However, Trichodina sp. and Ichthyophthirius multifiliis were isolated from skin of male breeders. In this study, no parasites were isolated from internal organs of larves and fingerling but four intestinal parasites included: Cucullanus sphaerocephlaus, Anisakis sp., Skyrjabinopsilus semiarmatus, and Lepto-rhynchoides plagicephalu were isolated from internal organs of breeder. Based on a wide range of parasitic infection observed in various life stages of A. persicus, it seems necessary to consider hygienic and management measures. PMID:27226891

  3. Parasitic infection in various stages life of cultured Acipenser persicus.

    PubMed

    Adel, Milad; Safari, Reza; Yaghoubzadeh, Zahra; Fazli, Hassan; Khalili, Elham

    2016-01-01

    The present study was conducted to evaluate the status of the parasite fauna in Acipenser persicus at different development stages, in order to find prevention protocols for parasitic diseases in this valuable species. For this purpose, sampling from each sex breeder, 10 egg samples, 5-day-old larvae (n = 20), 20-day-old larvae (n = 80) and fingerling of A. persicus (n = 60) released in earthen ponds were done. After the bioassay and preparing wet mount from the internal and external organs, identification was done according to the keys. According to the results, no fauna parasites were isolated from egg samples and 5-day-old larvae; but Trichodina spp. was isolated from 20-day-old larvae. Also, the same protozoan was isolated from fingerling released in earthen ponds, the mean intensity, prevalence and range of contamination by fingerling were higher with compared to 20-day-old larvae. Trichodina sp. and Diplostomum spathaceum were isolated from skin and eyes of females, respectively. However, Trichodina sp. and Ichthyophthirius multifiliis were isolated from skin of male breeders. In this study, no parasites were isolated from internal organs of larves and fingerling but four intestinal parasites included: Cucullanus sphaerocephlaus, Anisakis sp., Skyrjabinopsilus semiarmatus, and Lepto-rhynchoides plagicephalu were isolated from internal organs of breeder. Based on a wide range of parasitic infection observed in various life stages of A. persicus, it seems necessary to consider hygienic and management measures.

  4. World Conference on Pre-Erythrocytic Stage Malaria Vaccine Development: Current Status and Future Prospects Held in Bethesda, Maryland on April 12-15, 1989

    DTIC Science & Technology

    1989-12-01

    Myron Levine2, James Murphy 2, Jonathan DavIs 2, Ian Bathurst 3 Philip Barr, Pedro Romero ’, and Fiedl Zavala’. ’Department of Medical and Molecular...Eileen D. Franke and Carmen Lucas. U. S. Naval Medical Research Institite Detachment, Uma, Peru. The presence of a humoral Immune response to central

  5. Toxoplasma gondii: the effects of infection at different stages of pregnancy on the offspring of mice.

    PubMed

    Wang, Tao; Liu, Min; Gao, Xiao-Jie; Zhao, Zhi-Jun; Chen, Xiao-Guang; Lun, Zhao-Rong

    2011-01-01

    Congenital toxoplasmosis can cause fetal damage in humans and domestic animals. This study was focused on the effects of Toxoplasma gondii (Prugniaud strain) infection at different stages of pregnancy on the offspring of mice. Results showed that newborn mice from all infected groups were significantly lower in weight than those from the control group but significant difference was not found among these groups at day 60 after birth. The survival rate of the offspring from the group of mice infected at the earlier stage of pregnancy was significantly lower than those of infected and control groups. The positive offspring (with cysts found in their brain tissues) born from the mice infected at the earlier and intermediate stages of pregnancy showed a shorter latency and greater number of errors in the step-through passive avoidance test than those born from the mice infected at the late stage of pregnancy, the control group and the negative offspring from the infected groups. The number of cysts in the brain tissue was significantly higher in the offspring born from the groups of mice infected at the earlier and intermediate stages of pregnancy than those from the group of mice infected at the late stage of pregnancy. In addition, our results indicated that a high congenital transmission rate (90%) occurred in this NIH mouse model. In conclusion, the earlier and intermediate maternal infection of T. gondii can result in severe congenital toxoplasmosis, exhibiting conditions such as stillbirth or non-viability, and learning or memory capability damage in this mouse model. These results not only provide useful data for better understanding the effects of T. gondii infection on the offspring of mice infected at different stages of pregnancy but also for better consideration of the effect of this infection on other mammalian hosts including humans.

  6. Progress with viral vectored malaria vaccines: A multi-stage approach involving "unnatural immunity".

    PubMed

    Ewer, Katie J; Sierra-Davidson, Kailan; Salman, Ahmed M; Illingworth, Joseph J; Draper, Simon J; Biswas, Sumi; Hill, Adrian V S

    2015-12-22

    Viral vectors used in heterologous prime-boost regimens are one of very few vaccination approaches that have yielded significant protection against controlled human malaria infections. Recently, protection induced by chimpanzee adenovirus priming and modified vaccinia Ankara boosting using the ME-TRAP insert has been correlated with the induction of potent CD8(+) T cell responses. This regimen has progressed to field studies where efficacy against infection has now been reported. The same vectors have been used pre-clinically to identify preferred protective antigens for use in vaccines against the pre-erythrocytic, blood-stage and mosquito stages of malaria and this work is reviewed here for the first time. Such antigen screening has led to the prioritization of the PfRH5 blood-stage antigen, which showed efficacy against heterologous strain challenge in non-human primates, and vectors encoding this antigen are in clinical trials. This, along with the high transmission-blocking activity of some sexual-stage antigens, illustrates well the capacity of such vectors to induce high titre protective antibodies in addition to potent T cell responses. All of the protective responses induced by these vectors exceed the levels of the same immune responses induced by natural exposure supporting the view that, for subunit vaccines to achieve even partial efficacy in humans, "unnatural immunity" comprising immune responses of very high magnitude will need to be induced.

  7. 1-stage primary arthroplasty of mechanically failed internally fixated of hip fractures with deep wound infection

    PubMed Central

    Klatte, Till O; O’Loughlin, Padraigh F; Citak, Mustafa; Rueger, Johannes M; Gehrke, Thorsten; Kendoff, Daniel

    2013-01-01

    Background and purpose Mechanically failed internal fixation following hip fracture is often treated by salvage arthroplasty. If deep wound infection is present, a 2-stage procedure is often used. We have used a 1-stage procedure in infected cases, and we now report the outcome. Patients and methods We reviewed 16 cases of deep wound infection after mechanically failed hip fracture fixation, treated between 1994 and 2010. In all patients, a joint prosthesis was implanted in a 1-stage procedure. Results After an average follow-up period of 12 (2–18) years, no reinfection was detected. In 4 cases, a hip dislocation occurred and 3 of these needed further surgery. Interpretation A 1-stage procedure for arthroplasty of an infected, mechanically failed hip fracture fixation is feasible and carries a low risk of infection. PMID:23799345

  8. Nitroheterocyclic drugs cure experimental Trypanosoma cruzi infections more effectively in the chronic stage than in the acute stage

    PubMed Central

    Francisco, Amanda Fortes; Jayawardhana, Shiromani; Lewis, Michael D.; White, Karen L.; Shackleford, David M.; Chen, Gong; Saunders, Jessica; Osuna-Cabello, Maria; Read, Kevin D.; Charman, Susan A.; Chatelain, Eric; Kelly, John M.

    2016-01-01

    The insect-transmitted protozoan parasite Trypanosoma cruzi is the causative agent of Chagas disease, and infects 5–8 million people in Latin America. Chagas disease is characterised by an acute phase, which is partially resolved by the immune system, but then develops as a chronic life-long infection. There is a consensus that the front-line drugs benznidazole and nifurtimox are more effective against the acute stage in both clinical and experimental settings. However, confirmative studies have been restricted by difficulties in demonstrating sterile parasitological cure. Here, we describe a systematic study of nitroheterocyclic drug efficacy using highly sensitive bioluminescence imaging of murine infections. Unexpectedly, we find both drugs are more effective at curing chronic infections, judged by treatment duration and therapeutic dose. This was not associated with factors that differentially influence plasma drug concentrations in the two disease stages. We also observed that fexinidazole and fexinidazole sulfone are more effective than benznidazole and nifurtimox as curative treatments, particularly for acute stage infections, most likely as a result of the higher and more prolonged exposure of the sulfone derivative. If these findings are translatable to human patients, they will have important implications for treatment strategies. PMID:27748443

  9. Two-stage Revision for Periprosthetic Hip and Knee Joint Infections

    PubMed Central

    Kini, Sunil Gurpur; Gabr, Ayman; Das, Rishi; Sukeik, Mohamed; Haddad, Fares Sami

    2016-01-01

    Background: Periprosthetic joint infection (PJI) continues to be one of the leading causes of failure following hip and knee surgery. The diagnostic workflow of PJI includes detailed clinical examination, serum markers, imaging and aspiration/biopsy of the affected joint. The goals of treatment are eradication of the infection, alleviation of pain, and restoration of joint function. Surgical management of PJI consists of debridement, antibiotics and implant retention (DAIR) and single or two-stage revision procedures. Two-stage revision remains the gold standard for treatment of PJIs. We aim to discuss the two stage procedure in this article and report the outcomes. Methods: The first stage of the two stages consists of removal of all components and associated cement with aggressive debridement and placement of an antibiotic-loaded cement spacer. Patients are then treated with variable periods of parenteral antibiotics, followed by an antibiotic free period to help ensure the infection has been eradicated. If the clinical evaluation and serum inflammatory markers suggest infection control, then the second stage can be undertaken and this involves removal of the cement spacer, repeat debridement, and placement of a new prosthesis. Results: Common themes around the two-stage revision procedure include timing of the second stage, antibiotics used in the interim period, length of the interim period before consideration of reimplantation and close liaising with microbiologists. Conclusion: Successful eradication of infection and good functional outcome using the two stage procedure is dependent on a multidisciplinary approach and having a standard reproducible startegy. PMID:28144371

  10. Procalcitonin role in differential diagnosis of infection stages and non infection inflammation.

    PubMed

    Ghorbani, Gholamali

    2009-02-15

    The aim of this study is evaluation of procalcitonin role in the diagnosis of infectious and non infectious inflammation. This cross-sectional study was conducted in one hundred patients in Baqiyatallah Hospital of Iran in 2008. Patients suspected to infection were recruited to study. They were divided to four groups as: systemic inflammatory response syndrome, sepsis, sepsis syndrome and septic shock. Procalcitonin quantitative was assayed by immunoluminometric kit manufactured in Germany. Procalcitonin level was divided to four groups in < 0.5 ng mL(-1) compatible for SIRS, 0.5-2 ng mL(-1) for sepsis and 2-10 ng mL(-1) for sepsis syndrome and > 10 ng mL(-1) for septic shock. Data was analyzed by SPSS 13 for window software; T student test, ANOVA and Chi-square were used. In this study 53(53%) of subjects were men with mean age of 56.16 +/- 19.5 years old. The diagnosis was SIRS in 36%, sepsis in 38%, sepsis syndrome in 14% and septic shock in 12% of cases. Procalcitonin level was less than 0.5 ng mL(-1) in 61% and more than 10 ng mL(-1) in 10% of patients. Procalcitonin level showed significant association with septic shock, positive blood culture and mental dysfunction. Ultimately this study showed that high level of procalcitonin can differentiate septic shock from SIRS and other stages of infection. Dysfunction of mental status and high level of procalcitonin can determine septic shock.

  11. Prospective Double-Blind Study of Zidovudine (AZT) in Early Stage HIV infection

    DTIC Science & Technology

    1988-05-01

    FRONT COVER FUNDING NO. 87PP7875 S L. TITLE: Prospective Double-Blind Study of Zidovudine (AZT) in Early Stage HIV Infection PRINCIPAL INVESTIGATOR...Prospective Double-Blind Study of Zidovudine (AZT) in Early State HIV Infection 12. PERSONAL AUTHOR(S) Shannon M. Harrison 13a. TYPE OF REPORT 113b...COSATI CODES 18. SUBJECT TERMS (Continue on reverse if necessary and identify by block number) FIELD GROUP SUBGROUP HIV , Zidovudine, Early, Infection 06

  12. One-stage Exchange Arthroplasty for Periprosthetic Hip and Knee Joint Infections

    PubMed Central

    Nguyen, Manny; Sukeik, Mohamed; Zahar, Akos; Nizam, Ikram; Haddad, Fares Sami

    2016-01-01

    Background: Periprosthetic joint infection (PJI) is a devastating complication of joint replacement surgery. In an aging population of the developed world, the increasing numbers of hip and knee replacements will inevitably lead to increasing incidence of PJI, carrying with (it) significant patient morbidity and cost to the health care system. Two-stage exchange arthroplasty is currently the gold standard but it is associated with multiple operations, prolonged hospitalization and impaired functionality. One-stage exchange arthroplasty is similar to the two-stage procedure but the interval between removal of the prosthesis and reimplantation of a new one is only a few minutes. It has the theoretical benefits of a single anesthetic, shorter hospitalization, less cost and improved function. Methods: We reviewed the current literature regarding the outcomes of one-stage exchange arthroplasties focusing on re-infection rates and functional outcomes. Results: Current themes around the one-stage exchange procedure include the indications for the procedure, definition of re-infection, surgical techniques used to provide fixation and differences in approach for hip and knee replacements. Conclusion: The current literature on one-stage exchange procedure is promising, with comparable results to two-stage revisions for hips and knees in selected patients. However, there is a great need for a large multi-centred randomized control trial, focusing on re-infection rates and functional scores postoperatively, to provide concrete guidelines in managing this complex condition. PMID:28144374

  13. Cancer Stage at Diagnosis in HIV-infected People and Transplant Recipients

    PubMed Central

    Shiels, Meredith S.; Copeland, Glenn; Goodman, Marc T.; Harrell, Janna; Lynch, Charles F.; Pawlish, Karen; Pfeiffer, Ruth M.; Engels, Eric A.

    2015-01-01

    Background It is unknown whether immunosuppression results in more aggressive, advanced stage cancers. As cancer stage is influenced both by tumor biology and medical surveillance, we assessed cancer stage in HIV-infected individuals and solid organ transplant recipients, two immunosuppressed groups with differences in healthcare utilization. Methods We used data on all cases of 15 cancer types, diagnosed during 1996–2010 in two studies that linked U.S. cancer registries to HIV and transplant registries. Odds ratios (ORs) for advanced (vs. local) disease were estimated comparing HIV and transplant populations to immunocompetent people in polytomous logistic regression models, adjusted for age, sex, race, registry and year. Results A total of 8,411 of 4.5 million cancer cases occurred in HIV-infected people, and 7,322 of 6.4 million cancer cases occurred in transplant recipients. Compared to immunocompetent people with cancer, HIV-infected people were more likely to be diagnosed with distant stage lung (OR=1.13), female breast (OR=1.99), and prostate cancers (OR=1.57), while transplant recipients had fewer distant stage lung (OR=0.54), female breast (OR=0.75) and prostate cancers (OR=0.72). Both immunosuppressed populations had a shift toward advanced stage melanoma (ORs: HIV=1.97; transplant=1.82) and bladder cancer (ORs: HIV=1.42; transplant=1.54). Conclusions Bladder cancer and melanoma were more likely to be diagnosed at non-local stage in both HIV-infected people and transplant recipients, suggesting a role of immunosuppression in their progression. Additionally, we observed a shift for some common cancers toward later stages in HIV-infected individuals and toward earlier stages in transplant recipients, consistent with differential access to medical care or surveillance. PMID:25739496

  14. The stability analysis of a general viral infection model with distributed delays and multi-staged infected progression

    NASA Astrophysics Data System (ADS)

    Wang, Jinliang; Liu, Shengqiang

    2015-01-01

    We investigate an in-host model with general incidence and removal rate, as well as distributed delays in virus infections and in productions. By employing Lyapunov functionals and LaSalle's invariance principle, we define and prove the basic reproductive number R0 as a threshold quantity for stability of equilibria. It is shown that if R0 > 1 , then the infected equilibrium is globally asymptotically stable, while if R0 ⩽ 1 , then the infection free equilibrium is globally asymptotically stable under some reasonable assumptions. Moreover, n + 1 distributed delays describe (i) the time between viral entry and the transcription of viral RNA, (ii) the n - 1 -stage time needed for activated infected cells between viral RNA transcription and viral release, and (iii) the time necessary for the newly produced viruses to be infectious (maturation), respectively. The model can describe the viral infection dynamics of many viruses such as HIV-1, HCV and HBV.

  15. Hepcidin is regulated during blood-stage malaria and plays a protective role in malaria infection.

    PubMed

    Wang, Hai-Zhen; He, Ying-Xin; Yang, Chun-Ju; Zhou, Wei; Zou, Cheng-Gang

    2011-12-15

    Hepcidin is one of the regulators of iron metabolism. The expression of hepcidin is induced in spleens and livers of mice infected with pathogenic bacteria. Recent studies have indicated that serum hepcidin level is also increased in human subjects infected with Plasmodium falciparum. The mechanism of the regulation of hepcidin expression and its role in the infection of malaria remains unknown. In this study, we determined the expression of hepcidin in livers of mice infected with Plasmodium berghei. The expression of hepcidin in the liver was upregulated and downregulated during the early and late stages of malaria infection, respectively. Inflammation and erythropoietin, rather than the iron-sensing pathway, are involved in the regulation of hepcidin expression in livers of infected mice. Meanwhile, we investigated the effect of hepcidin on the survival of mice infected with P. berghei. Treatment of malaria-infected mice with anti-hepcidin neutralizing Abs promoted the rates of parasitemia and mortality. In contrast, lentiviral vector-mediated overexpression of hepcidin improved the outcome of P. berghei infection in mice. Our data demonstrate an important role of hepcidin in modulating the course and outcome of blood-stage malaria.

  16. Susceptibility of some vertebrate hosts to infection with early third-stage larvae of Gnathostoma hispidum.

    PubMed

    Sohn, W M; Lee, S H

    1997-09-01

    Susceptibility of some vertebrates was examined to the early third-stage larvae (EL3) of Gnathostoma hispidum. The larvae collected from the Chinese loaches were infected to 4 silk carps, 3 snake heads, 3 bullfrogs, 5 mice and 9 albino rats. No worms were detected in fish, silk carps and snake heads. In 3 bullfrogs fed 30 larvae, a total of 9 EL3 was recovered in the gastrointestinal tract (8 larvae) and liver (one). In 5 mice infected with 50 larvae, a total of 37 (74.0%) advanced third-stage larvae (AdL3) was recovered from the muscle (31 larvae), liver (5 larvae) and kidney at 4 weeks after infection. In 9 albino rats infected with 115 larvae, a total of 40 (34.8%) AdL3 was found in the muscle. The mammalian hosts were found susceptible to the EL3 of G. hispidum from Chinese loaches.

  17. Tools for the diagnosis of hepatitis C virus infection and hepatic fibrosis staging

    PubMed Central

    Saludes, Verónica; González, Victoria; Planas, Ramon; Matas, Lurdes; Ausina, Vicente; Martró, Elisa

    2014-01-01

    Hepatitis C virus (HCV) infection represents a major public health issue. Hepatitis C can be cured by therapy, but many infected individuals are unaware of their status. Effective HCV screening, fast diagnosis and characterization, and hepatic fibrosis staging are highly relevant for controlling transmission, treating infected patients and, consequently, avoiding end-stage liver disease. Exposure to HCV can be determined with high sensitivity and specificity with currently available third generation serology assays. Additionally, the use of point-of-care tests can increase HCV screening opportunities. However, active HCV infection must be confirmed by direct diagnosis methods. Additionally, HCV genotyping is required prior to starting any treatment. Increasingly, high-volume clinical laboratories use different types of automated platforms, which have simplified sample processing, reduced hands-on-time, minimized contamination risks and human error and ensured full traceability of results. Significant advances have also been made in the field of fibrosis stage assessment with the development of non-invasive methods, such as imaging techniques and serum-based tests. However, no single test is currently available that is able to completely replace liver biopsy. This review focuses on approved commercial tools used to diagnose HCV infection and the recommended hepatic fibrosis staging tests. PMID:24707126

  18. 2-stage revision of 120 deep infected hip and knee prostheses using gentamicin-PMMA beads.

    PubMed

    Janssen, Daniël M C; Geurts, Jan A P; Jütten, Liesbeth M C; Walenkamp, Geert H I M

    2016-08-01

    Background and purpose - A 2-stage revision is the most common treatment for late deep prosthesis-related infections and in all cases of septic loosening. However, there is no consensus about the optimal interval between the 2 stages. Patients and methods - We retrospectively studied 120 deep infections of total hip (n = 95) and knee (n = 25) prostheses that had occurred over a period of 25 years. The mean follow-up time was 5 (2-20) years. All infections had been treated with extraction, 1 or more debridements with systemic antibiotics, and implantation of gentamicin-PMMA beads. There had been different time intervals between extraction and reimplantation: median 14 (11-47) days for short-term treatment with uninterrupted hospital stay, and 7 (3-22) months for long-term treatment with temporary discharge. We analyzed the outcome regarding resolution of the infection and clinical results. Results - 88% (105/120) of the infections healed, with no difference in healing rate between short- and long-term treatment. 82 prostheses were reimplanted. In the most recent decade, we treated patients more often with a long-term treatment but reduced the length of time between the extraction and the reimplantation. More reimplantations were performed in long-term treatments than in short-term treatments, despite more having difficult-to-treat infections with worse soft-tissue condition. Interpretation - Patient, wound, and infection considerations resulted in an individualized treatment with different intervals between stages. The 2-stage revision treatment in combination with local gentamicin-PMMA beads gave good results even with difficult prosthesis infections and gentamicin-resistant bacteria.

  19. Susceptibility to Plasmodium liver stage infection is altered by hepatocyte polyploidy

    PubMed Central

    Austin, Laura S.; Kaushansky, Alexis; Kappe, Stefan H.I.

    2014-01-01

    Summary Plasmodium parasites infect hepatocytes of their mammalian hosts and within undergo obligate liver stage development. The specific host cell attributes that are important for liver infection remain largely unknown. Several host signaling pathways are perturbed in infected hepatocytes, some of which are important in the generation of hepatocyte polyploidy. To test the functional consequence of polyploidy in liver infection, we infected hepatocytes with the rodent malaria parasite Plasmodium yoelii both in vitro and in vivo and examined the ploidy of infected and uninfected hepatocytes by flow cytometry. In both hepatoma cell lines and in the mouse liver, the fraction of polyploid cells was higher in the infected cell population than in the uninfected cell population. When the data were reanalyzed by comparing the extent of Plasmodium infection within each ploidy subset, we found that infection rates were elevated in more highly polyploid cells and lower in diploid cells. Furthermore, we found that the parasite’s preference for host cells with high ploidy is conserved among rodent malaria species and the human malaria parasite Plasmodium falciparum. This parasite preference for host cells of high ploidy cannot be explained by differences in hepatocyte size or DNA replication. We conclude that Plasmodium preferentially infects and develops in polyploid hepatocytes. PMID:24612025

  20. Interrogation of infected hepatocyte signaling reveals that suppression of host p53 is critical for Plasmodium liver stage infection

    PubMed Central

    Kaushansky, Alexis; Ye, Albert S.; Austin, Laura S.; Mikolajczak, Sebastian A.; Vaughan, Ashley M.; Camargo, Nelly; Metzger, Peter G.; Douglass, Alyse N.; MacBeath, Gavin; Kappe, Stefan H.I.

    2013-01-01

    Summary Plasmodium parasites infect the liver and replicate inside hepatocytes before they invade erythrocytes and trigger clinical malaria. Analysis of host signaling pathways affected by liver stage infection could provide critical insights into host-pathogen interactions and reveal targets for intervention. Using protein lysate microarrays we found that Plasmodium yoelii rodent malaria parasites perturb hepatocyte regulatory pathways involved in cell survival, proliferation and autophagy. Notably, the pro-death protein p53 was substantially decreased in infected hepatocytes, suggesting it could be targeted by the parasite to foster survival. Indeed, mice that express increased levels of p53 showed reduced liver stage parasite burden whereas p53 knockout mice suffered increased liver stage burden. Furthermore, boosting p53 levels using the small molecule Nutlin-3 dramatically reduced liver stage burden in vitro and in vivo. We conclude that perturbation of the hepatocyte p53 pathway critically impacts parasite survival. Thus, host pathways might constitute potential targets for host-based antimalarial prophylaxis. PMID:23478020

  1. Viral RNA at Two Stages of Reovirus Infection Is Required for the Induction of Necroptosis.

    PubMed

    Berger, Angela K; Hiller, Bradley E; Thete, Deepti; Snyder, Anthony J; Perez, Encarnacion; Upton, Jason W; Danthi, Pranav

    2017-03-15

    Necroptosis, a regulated form of necrotic cell death, requires the activation of the RIP3 kinase. Here, we identify that infection of host cells with reovirus can result in necroptosis. We find that necroptosis requires sensing of the genomic RNA within incoming virus particles via cytoplasmic RNA sensors to produce type I interferon (IFN). While these events that occur prior to the de novo synthesis of viral RNA are required for the induction of necroptosis, they are not sufficient. The induction of necroptosis also requires late stages of reovirus infection. Specifically, efficient synthesis of double-stranded RNA (dsRNA) within infected cells is required for necroptosis. These data indicate that viral RNA interfaces with host components at two different stages of infection to induce necroptosis. This work provides new molecular details about events in the viral replication cycle that contribute to the induction of necroptosis following infection with an RNA virus.IMPORTANCE An appreciation of how cell death pathways are regulated following viral infection may reveal strategies to limit tissue destruction and prevent the onset of disease. Cell death following virus infection can occur by apoptosis or a regulated form of necrosis known as necroptosis. Apoptotic cells are typically disposed of without activating the immune system. In contrast, necroptotic cells alert the immune system, resulting in inflammation and tissue damage. While apoptosis following virus infection has been extensively investigated, how necroptosis is unleashed following virus infection is understood for only a small group of viruses. Here, using mammalian reovirus, we highlight the molecular mechanism by which infection with a dsRNA virus results in necroptosis.

  2. Two-Stage Cementless Revision Total Hip Arthroplasty for Infected Primary Hip Arthroplasties.

    PubMed

    Camurcu, Yalkin; Sofu, Hakan; Buyuk, Abdul Fettah; Gursu, Sarper; Kaygusuz, Mehmet Akif; Sahin, Vedat

    2015-09-01

    The main purpose of the present study was to analyze the clinical features, the most common infective agents, and the results of two-stage total hip revision using a teicoplanin-impregnated spacer. Between January 2005 and July 2011, 41 patients were included. At the clinical status analysis, physical examination was performed, Harris hip score was noted, isolated microorganisms were recorded, and the radiographic evaluation was performed. The mean Harris hip score was improved from 38.9 ± 9.6 points to 81.8 ± 5.8 points (P<0.05). Infection was eradicated in 39 hips. Radiographic evidence of stability was noted in 37 acetabular revision components, and all femoral stems. Two-stage revision of the infected primary hip arthroplasty is a time-consuming but a reliable procedure with high rates of success.

  3. Dynamics of a Class of HIV Infection Models with Cure of Infected Cells in Eclipse Stage.

    PubMed

    Maziane, Mehdi; Lotfi, El Mehdi; Hattaf, Khalid; Yousfi, Noura

    2015-12-01

    In this paper, we propose two HIV infection models with specific nonlinear incidence rate by including a class of infected cells in the eclipse phase. The first model is described by ordinary differential equations (ODEs) and generalizes a set of previously existing models and their results. The second model extends our ODE model by taking into account the diffusion of virus. Furthermore, the global stability of both models is investigated by constructing suitable Lyapunov functionals. Finally, we check our theoretical results with numerical simulations.

  4. Fasciola hepatica induces eosinophil apoptosis in the migratory and biliary stages of infection in sheep.

    PubMed

    Escamilla, A; Bautista, M J; Zafra, R; Pacheco, I L; Ruiz, M T; Martínez-Cruz, S; Méndez, A; Martínez-Moreno, A; Molina-Hernández, V; Pérez, J

    2016-01-30

    The aim of the present work was to evaluate the number of apoptotic eosinophils in the livers of sheep experimentally infected with Fasciola hepatica during the migratory and biliary stages of infection. Four groups (n=5) of sheep were used; groups 1-3 were orally infected with 200 metacercariae (mc) and sacrificed at 8 and 28 days post-infection (dpi), and 17 weeks post-infection (wpi), respectively. Group 4 was used as an uninfected control. Apoptosis was detected using immunohistochemistry with a polyclonal antibody against anti-active caspase-3, and transmission electron microscopy (TEM). Eosinophils were identified using the Hansel stain in serial sections for caspase-3, and by ultrastructural features using TEM. At 8 and 28 dpi, numerous caspase-3(+) eosinophils were mainly found at the periphery of acute hepatic necrotic foci. The percentage of caspase -3(+) apoptotic eosinophils in the periphery of necrotic foci was high (46.1-53.9) at 8 and 28 dpi, respectively, and decreased in granulomas found at 28 dpi (6%). Transmission electron microscopy confirmed the presence of apoptotic eosinophils in hepatic lesions at 8 and 28 dpi. At 17 wpi, apoptotic eosinophils were detected in the infiltrate surrounding some enlarged bile ducts containing adult flukes. This is the first report of apoptosis induced by F. hepatica in sheep and the first study reporting apoptosis in eosinophils in hepatic inflammatory infiltrates in vivo. The high number of apoptotic eosinophils in acute necrotic tracts during the migratory and biliary stages of infection suggests that eosinophil apoptosis may play a role in F. hepatica survival during different stages of infection.

  5. Divergent evolution of arrested development in the dauer stage of Caenorhabditis elegans and the infective stage of Heterodera glycines

    PubMed Central

    Elling, Axel A; Mitreva, Makedonka; Recknor, Justin; Gai, Xiaowu; Martin, John; Maier, Thomas R; McDermott, Jeffrey P; Hewezi, Tarek; McK Bird, David; Davis, Eric L; Hussey, Richard S; Nettleton, Dan; McCarter, James P; Baum, Thomas J

    2007-01-01

    Background The soybean cyst nematode Heterodera glycines is the most important parasite in soybean production worldwide. A comprehensive analysis of large-scale gene expression changes throughout the development of plant-parasitic nematodes has been lacking to date. Results We report an extensive genomic analysis of H. glycines, beginning with the generation of 20,100 expressed sequence tags (ESTs). In-depth analysis of these ESTs plus approximately 1,900 previously published sequences predicted 6,860 unique H. glycines genes and allowed a classification by function using InterProScan. Expression profiling of all 6,860 genes throughout the H. glycines life cycle was undertaken using the Affymetrix Soybean Genome Array GeneChip. Our data sets and results represent a comprehensive resource for molecular studies of H. glycines. Demonstrating the power of this resource, we were able to address whether arrested development in the Caenorhabditis elegans dauer larva and the H. glycines infective second-stage juvenile (J2) exhibits shared gene expression profiles. We determined that the gene expression profiles associated with the C. elegans dauer pathway are not uniformly conserved in H. glycines and that the expression profiles of genes for metabolic enzymes of C. elegans dauer larvae and H. glycines infective J2 are dissimilar. Conclusion Our results indicate that hallmark gene expression patterns and metabolism features are not shared in the developmentally arrested life stages of C. elegans and H. glycines, suggesting that developmental arrest in these two nematode species has undergone more divergent evolution than previously thought and pointing to the need for detailed genomic analyses of individual parasite species. PMID:17919324

  6. Blastomycosis infection of the knee treated with staged total knee arthroplasty.

    PubMed

    MacLean, Ian S; Day, Shandra R; Moore, Christopher C; Browne, James A

    2015-12-01

    Blastomycosis is a rare fungal disease that can cause intraarticular infection and joint destruction requiring surgical reconstruction. We describe a patient who presented with destruction of the knee joint of unknown etiology. The patient was initially treated with debridement and spacer placement followed by antifungal therapy after cultures grew blastomycosis. Following adequate treatment of the infection, the patient was taken back to the operating room for reconstruction with a total knee arthroplasty. The patient had a successful outcome with no evidence of infection at two years following surgery. To our knowledge, this case report represents the first documented case in which a blastomycotic infection of a native knee was successfully treated with a two-stage total knee arthroplasty.

  7. Dynamics of an HIV Model with Multiple Infection Stages and Treatment with Different Drug Classes.

    PubMed

    Wang, Xia; Song, Xinyu; Tang, Sanyi; Rong, Libin

    2016-02-01

    Highly active antiretroviral therapy can effectively control HIV replication in infected individuals. Some clinical and modeling studies suggested that viral decay dynamics may depend on the inhibited stages of the viral replication cycle. In this paper, we develop a general mathematical model incorporating multiple infection stages and various drug classes that can interfere with specific stages of the viral life cycle. We derive the basic reproductive number and obtain the global stability results of steady states. Using several simple cases of the general model, we study the effect of various drug classes on the dynamics of HIV decay. When drugs are assumed to be 100% effective, drugs acting later in the viral life cycle lead to a faster or more rapid decay in viremia. This is consistent with some patient and experimental data, and also agrees with previous modeling results. When drugs are not 100% effective, the viral decay dynamics are more complicated. Without a second population of long-lived infected cells, the viral load decline can have two phases if drugs act at an intermediate stage of the viral replication cycle. The slopes of viral load decline depend on the drug effectiveness, the death rate of infected cells at different stages, and the transition rate of infected cells from one to the next stage. With a second population of long-lived infected cells, the viral load decline can have three distinct phases, consistent with the observation in patients receiving antiretroviral therapy containing the integrase inhibitor raltegravir. We also fit modeling prediction to patient data under efavirenz (a nonnucleoside reverse-transcriptase inhibitor) and raltegravir treatment. The first-phase viral load decline under raltegravir therapy is longer than that under efavirenz, resulting in a lower viral load at initiation of the second-phase decline in patients taking raltegravir. This explains why patients taking a raltegravir-based therapy were faster to achieve

  8. Immunization with Pre-Erythrocytic Antigen CelTOS from Plasmodium falciparum Elicits Cross-Species Protection against Heterologous Challenge with Plasmodium berghei

    DTIC Science & Technology

    2010-08-01

    and the insect host, warranted an evaluation of whether targeted immune responses against this antigen could prevent the infection of the liver in...stimulate the PBMC’s isolated from volunteers immunized with irradiated sporozoites, a highly effective vaccine inducing sterile protection, to produce...1969) Specificity of protective immunity produced by X- irradiated Plasmodium berghei sporozoites. Nature 222: 488–489. 5. Sina BJ, Do Rosario VE

  9. Hepatitis C virus infection in end-stage renal disease and kidney transplantation.

    PubMed

    Burra, Patrizia; Rodríguez-Castro, Kryssia I; Marchini, Francesco; Bonfante, Luciana; Furian, Lucrezia; Ferrarese, Alberto; Zanetto, Alberto; Germani, Giacomo; Russo, Francesco Paolo; Senzolo, Marco

    2014-09-01

    Liver disease secondary to chronic hepatitis C virus (HCV) infection is an important cause of morbidity and mortality in patients with end-stage renal disease (ESRD) on renal replacement therapy and after kidney transplantation (KT). Hemodialytic treatment (HD) for ESRD constitutes a risk factor for bloodborne infections because of prolonged vascular access and the potential for exposure to infected patients and contaminated equipment. Evaluation of HCV-positive/ESRD and HCV-positive/KT patients is warranted to determine the stage of disease and the appropriateness of antiviral therapy, despite such treatment is challenging especially due to tolerability issues. Antiviral treatment with interferon (IFN) is contraindicated after transplantation due to the risk of rejection, and therefore, treatment is recommended before KT. Newer treatment strategies of direct-acting antiviral agents in combination are revolutionizing HCV therapy, as a result of encouraging outcomes streaming from recent studies which report increased sustained viral response, low or no resistance, and good safety profiles, including preservation of renal function. KT has been demonstrated to yield better outcomes with respect to remaining on HD although survival after KT is penalized by the presence of HCV infection with respect to HCV-negative transplant recipients. Therefore, an appropriate, comprehensive, easily applicable set of clinical practice management guidelines is necessary in both ESRD and KT patients with HCV infection and HCV-related liver disease.

  10. The relationship between cognitive reserve and the clinical stage of HIV infection.

    PubMed

    Alvarez-Tostado, Pablo; Inozemtseva, Olga; Aguiñiga, Miguel A; López, Enrique; Matute, Esmeralda

    2016-01-01

    The objective of this study was to determine whether the effect of cognitive reserve (CR) on neuropsychological functioning differs according to the clinical stage of HIV infection. A sample of 34 HIV-positive individuals aged 23-49, with a minimum of 9 years of formal education, was assessed. Participants were grouped according to the Centers for Disease Control and Prevention's (CDC) clinical stages (A = 10, B = 16, C = 8). CR was calculated for each clinical stage group in accordance with estimates of premorbid IQ, years of education, and occupational attainment. The sum of these three variables was then transformed into z-scores. Individuals above the median were classified as having "High" CR (HCR), those below the median were classified as "Low" CR (LCR). Participants completed an evaluation of cognitive and executive functions based on selected, modified tasks from the HIV University of Miami Annotated Neuropsychological test in Spanish (HUMANS). Assessment included the following domains: attention, memory (visual, verbal, and working memory), executive functions (cognitive flexibility, switching), language (naming), and visual constructive skills (block design). HCR outperformed LCR in all cognitive domains. Comparison of HCR and LCR in each clinical stage revealed that the effect of CR was stronger in stage B than in stages A and C, suggesting that this effect does indeed vary among stages.

  11. Expression of a hydrophilic surface protein in infective stages of Leishmania major.

    PubMed

    Flinn, H M; Rangarajan, D; Smith, D F

    1994-06-01

    A family of differentially expressed genes from Leishmania major contains one sequence (Gene B) that encodes a novel, hydrophilic protein found on the surface of infective parasite stages. The 177-residue, acidic Gene B protein is characterised by an amino acid repetitive element, comprising 45% of the total molecule, that is related to the cell-wall binding domain of protein A from Staphylococcus aureus. No identifiable signal peptide, membrane-spanning domain or consensus for glycosylphosphatidylinositol anchor attachment to the cell surface is found elsewhere in the deduced protein sequence. In vitro, the Gene B protein fractionates with the parasite cell surface glycoconjugates, lipophosphoglycan and the glycoinositolphospholipids. This protein is the first characterised surface peptide marker for infective stages of the Leishmania life cycle.

  12. Two-stage hierarchical group testing for multiple infections with application to the Infertility Prevention Project

    PubMed Central

    Tebbs, Joshua M.; McMahan, Christopher S.; Bilder, Christopher R.

    2015-01-01

    Summary Screening for sexually transmitted diseases has benefited greatly from the use of group testing (pooled testing) to lower costs. With the development of assays that detect multiple infections, screening practices now involve testing pools of individuals for multiple infections simultaneously. Building on the research for single infection group testing procedures, we examine the performance of group testing for multiple infections. Our work is motivated by chlamydia and gonorrhea testing for the Infertility Prevention Project (IPP), a national program in the United States. We consider a two-stage pooling algorithm currently used to perform testing for the IPP. We first derive the operating characteristics of this algorithm for classification purposes (e.g., expected number of tests, misclassification probabilities, etc.) and identify pool sizes that minimize the expected number of tests. We then develop an expectation-maximization algorithm to estimate probabilities of infection using both group and individual retest responses. Our research shows that group testing can offer large cost savings when classifying individuals for multiple infections and can provide prevalence estimates that are actually more efficient than those from individual testing. PMID:24117173

  13. Cucumber Necrosis Virus Recruits Cellular Heat Shock Protein 70 Homologs at Several Stages of Infection

    PubMed Central

    Alam, Syed Benazir

    2015-01-01

    ABSTRACT RNA viruses often depend on host factors for multiplication inside cells due to the constraints of their small genome size and limited coding capacity. One such factor that has been exploited by several plant and animal viruses is heat shock protein 70 (HSP70) family homologs which have been shown to play roles for different viruses in viral RNA replication, viral assembly, disassembly, and cell-to-cell movement. Using next generation sequence analysis, we reveal that several isoforms of Hsp70 and Hsc70 transcripts are induced to very high levels during cucumber necrosis virus (CNV) infection of Nicotiana benthamiana and that HSP70 proteins are also induced by at least 10-fold. We show that HSP70 family protein homologs are co-opted by CNV at several stages of infection. We have found that overexpression of Hsp70 or Hsc70 leads to enhanced CNV genomic RNA, coat protein (CP), and virion accumulation, whereas downregulation leads to a corresponding decrease. Hsc70-2 was found to increase solubility of CNV CP in vitro and to increase accumulation of CNV CP independently of viral RNA replication during coagroinfiltration in N. benthamiana. In addition, virus particle assembly into virus-like particles in CP agroinfiltrated plants was increased in the presence of Hsc70-2. HSP70 was found to increase the targeting of CNV CP to chloroplasts during infection, reinforcing the role of HSP70 in chloroplast targeting of host proteins. Hence, our findings have led to the discovery of a highly induced host factor that has been co-opted to play multiple roles during several stages of the CNV infection cycle. IMPORTANCE Because of the small size of its RNA genome, CNV is dependent on interaction with host cellular components to successfully complete its multiplication cycle. We have found that CNV induces HSP70 family homologs to a high level during infection, possibly as a result of the host response to the high levels of CNV proteins that accumulate during infection

  14. Effects of High Ambient Temperature on Various Stages of Rabies Virus Infection in Mice

    PubMed Central

    Bell, J. F.; Moore, G. J.

    1974-01-01

    Effects of high ambient temperatures on various stages of rabies virus infection have been studied. Ambient temperature increased within the tolerated range was found to have little effect upon body temperature of normal mice, but caused marked elevation of temperature during illness. Temperatures at onset of patent illness in mice were lower than normal. Increased body temperature in the higher thermic ambience during the incubation period was associated with decreased mortality and frequent abortive infections. Exposure to high ambient temperature late in the incubation period delayed onset of illness, decreased mortality, and increased frequency of abortive infections, but exposure to high ambient temperature after onset of patent illness did not affect the course of the disease. PMID:4426698

  15. Transcriptomic Analysis of Calonectria pseudoreteaudii during Various Stages of Eucalyptus Infection

    PubMed Central

    Ye, Xiaozhen; Liu, Hongyi; Jin, Yajie; Guo, Mengmeng; Huang, Aizhen; Chen, Quanzhu; Guo, Wenshuo; Zhang, Feiping; Feng, Lizhen

    2017-01-01

    Eucalyptus leaf blight caused by Calonectria spp. is a serious disease in Eucalyptus seedling and plantations. However, the molecular mechanisms of the infection process and pathogenesis of Calonectria to Eucalyptus is not well-studied. In this study, we analyzed the transcriptomes of C. pseudoreteaudii at three stages of Eucalyptus leaf infection, and in mycelium grown in potato dextrose broth using Illumina RNA-Seq technology. We identified 161 differentially expressed genes between C. pseudoreteaudii from leaf and mycelium grown in potato dextrose broth. GO and KEGG enrichment analyses of these genes suggested that they were mainly involved in oxidoreductase activity, hydrolase activity, and transmembrane transporter activity. Most of the differentially expressed genes at the early infection stage were upregulated. These upregulated genes were mainly involved in cell wall hydrolysis and toxin synthesis, suggesting a role for toxin and cell wall hydrolases in the establishment of Calonectria leaf blight. Genes related to detoxification of phytoalexins were continually upregulated during infection. The candidate effectors and putative pathogenicity determinants identified in this study will help in the functional analysis of C. pseudoreteaudii virulence and pathogenicity. PMID:28072879

  16. Two-stage revision of hip prosthesis infection using a hip spacer with stabilising proximal cementation.

    PubMed

    Gil Gonzalez, Sergi; Marqués López, Fernando; Rigol Ramon, Pau; Mestre Cortadellas, Carlos; Cáceres Palou, Enric; León García, Alfonso

    2010-01-01

    Two-stage revision hip arthroplasty for infection using an antibiotic-loaded cement spacer has been used frequently with good results. However, spacer instability is also frequent. Proximal cementation of the spacer could avoid spacer dislocation. We retrospectively assessed 35 patients in whom a 2-stage revision hip arthroplasty for infection was carried out using an antibiotic-loaded cement spacer with gentamicin (Spacer-G) in which the spacer was proximally cemented in 16 patients. The mean follow-up was 32 months. We assessed spacer stability and infection elimination. There were 8 spacer dislocations (22.9%), 5 in hips without proximal cementation and 2 in hips with proximal cementation (p>0.05). There was no fracture in any hip. Reinfection occurred in 5 hips (14.3%), in 3 with the same microorganism, while 2 had a different microorganism. Our results indicate that the proximal cementation of the spacer prevents its dislocation. Infection was eliminated in 86% of the hips.

  17. Antibiotic-Loaded Spacer for Two-Stage Revision of Infected Total Knee Arthroplasty.

    PubMed

    Vecchini, Eugenio; Micheloni, Gian Mario; Perusi, Francesco; Scaglia, Marco; Maluta, Tommaso; Lavini, Franco; Bondi, Manuel; Dall'Oca, Carlo; Magnan, Bruno

    2017-03-01

    Infection of total knee arthroplasty (TKA) is a challenge in orthopedic surgery. In literature TKA infection is classified according to the time after surgery: acute postoperative; late chronic; acute hematogenous; positive intraoperative microbiological growth. The purpose of this study is to present the results of the use of a preformed antibiotic-loaded spacer in TKA infections, treated by a two-stage revision procedure. A series of 19 consecutive patients (20 knees) with a diagnosis of infected TKA were treated from January 2003 to February 2012. Two-stage reimplantation protocols were completed only in 16 patients and these data were included in the study. We lost three patients at follow-up. An antibiotic-loaded preformed articulating polymethylmethacrylate spacer was applied. Patients were observed 1, 3, and 6 months postoperatively and then yearly for clinical and radiographic examination. The mean American Knee Society Score improved from 68.4 preoperatively (range, from 34 to 108) to 112.7 at final follow-up (range, from 49 to 180). The pain was evaluated as part of clinical score. It improved from an average of 19.3 preoperatively (range, from 10 to 30) to 34.3 at final follow-up (range, from 10 to 50). The average range of motion improved from 40.1 degrees (range, from 6 to 90 degrees) to 79.3 degrees (range, from 45 to 125 degrees). The use of the spacer allows obtaining a reduction of pain, an improvement of quality of life in the period of time between the two surgical stages and an easier reimplantation of TKA.

  18. Separation of Plasmodium falciparum Late Stage-infected Erythrocytes by Magnetic Means

    PubMed Central

    Coronado, Lorena Michelle; Tayler, Nicole Michelle; Correa, Ricardo; Giovani, Rita Marissa; Spadafora, Carmenza

    2013-01-01

    Unlike other Plasmodium species, P. falciparum can be cultured in the lab, which facilitates its study 1. While the parasitemia achieved can reach the ≈40% limit, the investigator usually keeps the percentage at around 10%. In many cases it is necessary to isolate the parasite-containing red blood cells (RBCs) from the uninfected ones, to enrich the culture and proceed with a given experiment. When P. falciparum infects the erythrocyte, the parasite degrades and feeds from haemoglobin 2, 3. However, the parasite must deal with a very toxic iron-containing haem moiety 4, 5. The parasite eludes its toxicity by transforming the haem into an inert crystal polymer called haemozoin 6, 7. This iron-containing molecule is stored in its food vacuole and the metal in it has an oxidative state which differs from the one in haem 8. The ferric state of iron in the haemozoin confers on it a paramagnetic property absent in uninfected erythrocytes. As the invading parasite reaches maturity, the content of haemozoin also increases 9, which bestows even more paramagnetism on the latest stages of P. falciparum inside the erythrocyte. Based on this paramagnetic property, the latest stages of P. falciparum infected-red blood cells can be separated by passing the culture through a column containing magnetic beads. These beads become magnetic when the columns containing them are placed on a magnet holder. Infected RBCs, due to their paramagnetism, will then be trapped inside the column, while the flow-through will contain, for the most part, uninfected erythrocytes and those containing early stages of the parasite. Here, we describe the methodology to enrich the population of late stage parasites with magnetic columns, which maintains good parasite viability 10. After performing this procedure, the unattached culture can be returned to an incubator to allow the remaining parasites to continue growing. PMID:23486405

  19. Use of staged molecular analysis to determine causes of unexplained central nervous system infections.

    PubMed

    Hsu, Chien-Chin; Tokarz, Rafal; Briese, Thomas; Tsai, Hung-Chin; Quan, Phenix-Lan; Lipkin, W Ian

    2013-01-01

    No agent is implicated in most central nervous system (CNS) infections. To investigate cerebrospinal fluid samples from patients with CNS infections of unknown cause in 1 hospital in Taiwan, we used a staged molecular approach, incorporating techniques including multiplex MassTag PCR, 16S rRNA PCR, DNA microarray, and high-throughput pyrosequencing. We determined the infectious agent for 31 (24%) of 131 previously negative samples. Candidate pathogens were identified for 25 (27%) of 94 unexplained meningitis cases and 6 (16%) of 37 unexplained encephalitis cases. Epstein-Barr virus (18 infections) accounted for most of the identified agents in unexplained meningitis cases, followed by Escherichia coli (5), enterovirus (2), human herpesvirus 2 (1), and Mycobacterium tuberculosis. Herpesviruses were identified in samples from patients with unexplained encephalitis cases, including varicella-zoster virus (3 infections), human herpesvirus 1 (2), and cytomegalovirus (1). Our study confirms the power of multiplex MassTag PCR as a rapid diagnostic tool for identifying pathogens causing unexplained CNS infections.

  20. Characterization of a 14,000 dalton antigen of Dirofilaria immitis infective third stage larvae

    SciTech Connect

    Fuller, S.A.; Cachia, P.J.; Wong, M.M.; Hurrell, J.G.R.

    1986-05-01

    Immunogenic proteins of Dirofilaria immitis (canine heartworm) were identified by probing extracts of adult worms or their excretory-secretory proteins (ESP) blotted to nitrocellulose following SDS-PAGE with control or infected dog sera. A 14,000 dalton antigen (a prominent component of ESP by protein staining) was consistently recognized both in extracts and ESP by dog sera as early as three months post infection. This indicates a larval origin for the antigen since no adult worms are present until approximately five months post infection. Monoclonal antibodies (MAbs) prepared against the 14,000 dalton antigen confirmed by immunoblotting that this antigen is expressed by infective third stage larvae, adults and microfilariae and is present intact in the sera of infected dogs. Surface-labelling of whole adult D. immitis with Na/sup 125/I produced radiolabelled antigens closely corresponding to those of ESP. An anti-14,000 dalton MAb was able to immunoprecipitate radiolabelled antigen which strongly suggest a surface or membrane location in the intact organism. Gel filtration data suggests that the protein is a native monomer. A MAb-affinity column has been used to purify the 14,000 dalton antigen to at least 98% homogeneity in one step from crude worm extracts. Further fractionation by HPLC yields a homogeneous preparation. Amino acid analysis and the N-terminal amino acid sequence data will be presented.

  1. The Brain NO Levels and NOS Activities Ascended in the Early and Middle Stages and Descended in the Terminal Stage in Scrapie-Infected Animal Models.

    PubMed

    Chen, Li-Na; Sun, Jing; Yang, Xiao-Dong; Xiao, Kang; Lv, Yan; Zhang, Bao-Yun; Zhou, Wei; Chen, Cao; Gao, Chen; Shi, Qi; Dong, Xiao-Ping

    2017-04-01

    The infections of prion agents may cause progressive and fatal neurodegenerative diseases in humans and a serial of animal species. Previous studies have proposed that the levels of nitric oxide (NO) and nitric oxide synthase (NOS) in the brains of some neurodegeneration diseases changed, while S-nitrosylation (SNO) of many brain proteins altered in prion diseases. To elucidate the potential changes of brain NO levels during prion infection, the NO levels and NOS activities in the brain tissues of three scrapie experimental rodents were measured, including scrapie agent 263 K-infected hamsters and 139A- and ME7-infected mice. Both NO levels and NOS activities, including total NOS (TNOS) and inducible NOS (iNOS), were increased at the terminal stages of scrapie-infected animals. Assays of the brain samples collected at different time points during scrapie infection showed that the NO levels and NOS activities started to increase at early stage, reached to the peak in the middle stage, and dropped down at late stage. Western blots for brain iNOS revealed increased firstly and decreased late, especially in the brains of 139A- and ME7-infected mice. In line with those alterations, the levels of the SNO forms of several selected brain proteins such as aquaporin-1 (AQP1), calcium/calmodulin-dependent protein kinase II (CaMKII), neurogranin, and opalin, underwent similar changing trends, while their total protein levels did not change obviously during scrapie infection. Our data here for the first time illustrate the changing profile of brain NO and NOS during prion infection. Time-dependent alterations of brain NO level and the associated protein S-nitrosylation process may contribute greatly to the neuropathological damage in prion diseases.

  2. Raman spectroscopy based investigation of molecular changes associated with an early stage of dengue virus infection

    NASA Astrophysics Data System (ADS)

    Bilal, Maria; Bilal, Muhammad; Saleem, Muhammad; Khurram, Muhammad; Khan, Saranjam; Ullah, Rahat; Ali, Hina; Ahmed, Mushtaq; Shahzada, Shaista; Ullah Khan, Ehsan

    2017-04-01

    Raman spectroscopy based investigations of the molecular changes associated with an early stage of dengue virus infection (DENV) using a partial least squares (PLS) regression model is presented. This study is based on non-structural protein 1 (NS1) which appears after three days of DENV infection. In total, 39 blood sera samples were collected and divided into two groups. The control group contained samples which were the negative for NS1 and antibodies and the positive group contained those samples in which NS1 is positive and antibodies were negative. Out of 39 samples, 29 Raman spectra were used for the model development while the remaining 10 were kept hidden for blind testing of the model. PLS regression yielded a vector of regression coefficients as a function of Raman shift, which were analyzed. Cytokines in the region 775–875 cm‑1, lectins at 1003, 1238, 1340, 1449 and 1672 cm‑1, DNA in the region 1040–1140 cm‑1 and alpha and beta structures of proteins in the region 933–967 cm‑1 have been identified in the regression vector for their role in an early stage of DENV infection. Validity of the model was established by its R-square value of 0.891. Sensitivity, specificity and accuracy were 100% each and the area under the receiver operator characteristic curve was found to be 1.

  3. End-Stage Renal Disease Among HIV-Infected Adults in North America

    PubMed Central

    Abraham, Alison G.; Althoff, Keri N.; Jing, Yuezhou; Estrella, Michelle M.; Kitahata, Mari M.; Wester, C. William; Bosch, Ronald J.; Crane, Heidi; Eron, Joseph; Gill, M. John; Horberg, Michael A.; Justice, Amy C.; Klein, Marina; Mayor, Angel M.; Moore, Richard D.; Palella, Frank J.; Parikh, Chirag R.; Silverberg, Michael J.; Golub, Elizabeth T.; Jacobson, Lisa P.; Napravnik, Sonia; Lucas, Gregory M.; Kirk, Gregory D.; Benson, Constance A.; Bosch, Ronald J.; Collier, Ann C.; Boswell, Stephen; Grasso, Chris; Mayer, Ken; Hogg, Robert S.; Harrigan, Richard; Montaner, Julio; Cescon, Angela; Brooks, John T.; Buchacz, Kate; Gebo, Kelly A.; Moore, Richard D.; Moore, Richard D.; Carey, John T.; Rodriguez, Benigno; Horberg, Michael A.; Silverberg, Michael J.; Thorne, Jennifer E.; Goedert, James J.; Jacobson, Lisa P.; Klein, Marina B.; Rourke, Sean B.; Burchell, Ann; Rachlis, Anita R.; Hunter-Mellado, Robert F.; Mayor, Angel M.; Gill, M. John; Deeks, Steven G.; Martin, Jeffrey N.; Saag, Michael S.; Mugavero, Michael J.; Willig, James; Eron, Joseph J.; Napravnik, Sonia; Kitahata, Mari M.; Crane, Heidi M.; Justice, Amy C.; Dubrow, Robert; Fiellin, David; Sterling, Timothy R.; Haas, David; Bebawy, Sally; Turner, Megan; Gange, Stephen J.; Anastos, Kathryn; Moore, Richard D.; Saag, Michael S.; Gange, Stephen J.; Althoff, Keri N.; Kitahata, Mari M.; McKaig, Rosemary G.; Justice, Amy C.; Freeman, Aimee M.; Moore, Richard D.; Freeman, Aimee M.; Lent, Carol; Kitahata, Mari M.; Van Rompaey, Stephen E.; Crane, Heidi M.; Webster, Eric; Morton, Liz; Simon, Brenda; Gange, Stephen J.; Althoff, Keri N.; Abraham, Alison G.; Lau, Bryan; Zhang, Jinbing; Jing, Jerry; Golub, Elizabeth; Modur, Shari; Hanna, David B.; Rebeiro, Peter; Wong, Cherise; Mendes, Adell

    2015-01-01

    Background. Human immunodeficiency virus (HIV)-infected adults, particularly those of black race, are at high-risk for end-stage renal disease (ESRD), but contributing factors are evolving. We hypothesized that improvements in HIV treatment have led to declines in risk of ESRD, particularly among HIV-infected blacks. Methods. Using data from the North American AIDS Cohort Collaboration for Research and Design from January 2000 to December 2009, we validated 286 incident ESRD cases using abstracted medical evidence of dialysis (lasting >6 months) or renal transplant. A total of 38 354 HIV-infected adults aged 18–80 years contributed 159 825 person-years (PYs). Age- and sex-standardized incidence ratios (SIRs) were estimated by race. Poisson regression was used to identify predictors of ESRD. Results. HIV-infected ESRD cases were more likely to be of black race, have diabetes mellitus or hypertension, inject drugs, and/or have a prior AIDS-defining illness. The overall SIR was 3.2 (95% confidence interval [CI], 2.8–3.6) but was significantly higher among black patients (4.5 [95% CI, 3.9–5.2]). ESRD incidence declined from 532 to 303 per 100 000 PYs and 138 to 34 per 100 000 PYs over the time period for blacks and nonblacks, respectively, coincident with notable increases in both the prevalence of viral suppression and the prevalence of ESRD risk factors including diabetes mellitus, hypertension, and hepatitis C virus coinfection. Conclusions. The risk of ESRD remains high among HIV-infected individuals in care but is declining with improvements in virologic suppression. HIV-infected black persons continue to comprise the majority of cases, as a result of higher viral loads, comorbidities, and genetic susceptibility. PMID:25409471

  4. Exposure of the snail Potamopyrgus antipodarum to herbicide boosts output and survival of parasite infective stages.

    PubMed

    Hock, Sabrina D; Poulin, Robert

    2012-12-01

    Anthropogenic stressors such as pollutants can modulate levels of parasitic infections in aquatic animals by suppressing host immunity or through some other mechanisms. One such mechanism could involve increases in either the quantity or quality of infective stages produced by parasites. We investigated the effect of exposure of infected snails, Potamopyrgus antipodarum, to different concentrations of the widely-used herbicide glyphosate, on (i) the production of infective cercariae by three trematode species, Coitocaecum parvum, Apatemon sp. and an undescribed renicolid, and (ii) the survival of cercariae of the latter species. For all three trematode species, infected snails exposed over a month to low (0.36 mg a.i. L(-1)) or medium (3.6 mg a.i. L(-1)) formulated glyphosate concentrations released between 1.5 and 3 times more cercariae per day than snails under control conditions. The similar pattern seen in all trematodes suggests a general weakening of the host benefiting any of its parasites rather than some parasite species-specific mechanism. In addition, the survival of renicolid cercariae improved with increasing glyphosate concentrations, with cercariae living about 50% longer in the medium concentration (3.6 mg a.i. L(-1)) than in control conditions. Our results demonstrate a clear interaction between glyphosate pollution and parasitism by trematodes in freshwater systems, occurring at glyphosate concentrations recorded in aquatic habitats, and within the environmental exposure limit allowed in New Zealand freshwaters. Future risk assessments and toxicity tests need to consider indirect impacts resulting from infections to invertebrate and vertebrate species penetrated by cercariae and serving as second intermediate hosts of trematodes.

  5. Titanium-copper-nitride coated spacers for two-stage revision of infected total hip endoprostheses

    PubMed Central

    Ellenrieder, Martin; Haenle, Maximilian; Lenz, Robert; Bader, Rainer; Mittelmeier, Wolfram

    2011-01-01

    Within the first two years after total hip arthroplasty implant-associated infection has become the second most common reason for a revision surgery. Two-stage implant exchange is frequently conducted using temporary spacers made of antibiotic-loaded cement in order to prevent a bacterial colonization on the spacer. Avoiding several disadvantages of cement spacers, a conventional hemi-endoprosthesis was equipped with a copper-containing implant coating for inhibition of bacterial biofilms. In the present paper details of this novel treatment concept are presented including a case report. PMID:22242097

  6. Titanium-copper-nitride coated spacers for two-stage revision of infected total hip endoprostheses.

    PubMed

    Ellenrieder, Martin; Haenle, Maximilian; Lenz, Robert; Bader, Rainer; Mittelmeier, Wolfram

    2011-01-01

    Within the first two years after total hip arthroplasty implant-associated infection has become the second most common reason for a revision surgery. Two-stage implant exchange is frequently conducted using temporary spacers made of antibiotic-loaded cement in order to prevent a bacterial colonization on the spacer. Avoiding several disadvantages of cement spacers, a conventional hemi-endoprosthesis was equipped with a copper-containing implant coating for inhibition of bacterial biofilms. In the present paper details of this novel treatment concept are presented including a case report.

  7. Exogenous and endogenous stages of Eimeria perforans naturally infected domestic rabbit (Oryctolagus cuniculus) in Saudi Arabia: Light microscopic study

    PubMed Central

    Al-Quraishy, Saleh

    2011-01-01

    Exogenous and endogenous stages of Eimeria perforans naturally infected rabbits in Saudi Arabia were described. The prevalence of infection was 75%. Oocysts were ovoid to elliptical and measured 16 × 10 μm. The four dizoic sporocysts were ovoid and measured 7 × 5 μm. Endogenous stages were restricted to the duodenum. Meronts, microgamonts, macrogamonts and young oocysts were recorded and described. PMID:23961159

  8. One-stage treatment of deep infection following repair of Achilles tendon rupture with flexor hallucis longus transfer.

    PubMed

    Lee, Kang; Moon, Jeong Seok; Seo, Jeong Gook; Lee, Woo Chun

    2009-03-01

    We present one-stage treatment of deep infection following repair of Achilles tendon rupture using flexor hallucis longus transfer. Flexor hallucis longus was used not only to connect the defect in Achillles tendon, but also to control the soft tissue infection with its abundant blood supply, simultaneously. The clinical results for the two patients in this report were excellent without major complication.

  9. Immunization of broiler chicks by in ovo injection of infective stages of Eimeria.

    PubMed

    Weber, F H; Genteman, K C; LeMay, M A; Lewis, D O; Evans, N A

    2004-03-01

    Immunization of chickens by in ovo injection of infective stages of 5 species of Eimeria was investigated. Fertile Hubbard x Petersen broiler chicken eggs were injected through the air cell on d 18 of incubation with oocysts of E. acervulina, E. maxima, E. mitis, E. praecox, or E. brunetti. Injected doses of all species ranged from 1 x 10(2) to 1 x 10(6) sporulated oocysts per egg. Chicks receiving oocysts in ovo shed oocysts posthatch. After 2 wk in wire-floored cages, birds were given a challenge infection with the homologous Eimeria species. Chicks immunized by in ovo injection of oocysts had significantly reduced lesion scores, improved weight gain, or reduced oocyst output compared with their nonimmunized counterparts. In additional studies, eggs were injected with 1 x 10(5) sporozoites of E. tenella, E. maxima, or E. acervulina per egg. Sporozoites of E. acervulina were not infective for chick embryos when administered in phosphate-buffered saline, but if sporozoites were suspended in tissue culture medium when injected in ovo, hatched chicks shed oocysts with peak output occurring 3 to 4 d posthatch. Sporozoites of E. maxima and E. tenella were infective for 18-d-old embryos regardless of the vehicle. The results demonstrate that immunization of broiler chickens against several species of coccidia by in ovo injection of oocysts is feasible. The infectivity of sporozoites for 18-d-old chick embryos varied depending on the species of Eimeria and the vehicle in which the sporozoites were suspended prior to injection.

  10. Lipid droplet dynamics at early stages of Mycobacterium marinum infection in Dictyostelium.

    PubMed

    Barisch, Caroline; Paschke, Peggy; Hagedorn, Monica; Maniak, Markus; Soldati, Thierry

    2015-09-01

    Lipid droplets exist in virtually every cell type, ranging not only from mammals to plants, but also to eukaryotic and prokaryotic unicellular organisms such as Dictyostelium and bacteria. They serve among other roles as energy reservoir that cells consume in times of starvation. Mycobacteria and some other intracellular pathogens hijack these organelles as a nutrient source and to build up their own lipid inclusions. The mechanisms by which host lipid droplets are captured by the pathogenic bacteria are extremely poorly understood. Using the powerful Dictyostelium discoideum/Mycobacterium marinum infection model, we observed that, immediately after their uptake, lipid droplets translocate to the vicinity of the vacuole containing live but not dead mycobacteria. Induction of lipid droplets in Dictyostelium prior to infection resulted in a vast accumulation of neutral lipids and sterols inside the bacterium-containing compartment. Subsequently, under these conditions, mycobacteria accumulated much larger lipid inclusions. Strikingly, the Dictyostelium homologue of perilipin and the murine perilipin 2 surrounded bacteria that had escaped to the cytosol of Dictyostelium or microglial BV-2 cells respectively. Moreover, bacterial growth was inhibited in Dictyostelium plnA knockout cells. In summary, our results provide evidence that mycobacteria actively manipulate the lipid metabolism of the host from very early infection stages.

  11. Tantalum acetabular augments in one-stage exchange of infected total hip arthroplasty: a case-control study.

    PubMed

    Klatte, Till Orla; Kendoff, Daniel; Sabihi, Reza; Kamath, Atul F; Rueger, Johannes M; Gehrke, Thorsten

    2014-07-01

    During the one-stage exchange procedure for periprosthetic joint infection (PJI) after total hip arthroplasty (THA), acetabular defects challenge reconstructive options. Porous tantalum augments are an established tool for addressing acetabular destruction in aseptic cases, but their utility in septic exchange is unknown. This retrospective case-control study presents the initial results of tantalum augmentation during one-stage exchange for PJI. Primary endpoints were rates of re-infection and short-term complications associated with this technique. Study patients had no higher risk of re-infection with equivalent durability at early follow-up with a re-infection rate in both groups of 4%. In conclusion, tantalum augments are a viable option for addressing acetabular defects in one-stage exchange for septic THA. Further study is necessary to assess long-term durability when compared to traditional techniques for acetabular reconstruction.

  12. 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.

  13. [Lymphocytic alveolitis in the early stages of HIV infection: correlation with biological and prognostic factors].

    PubMed

    Quint, L; Autran, B; Guillon, J M; Parrot, A; Denis, M; Debre, P; Mayaud, C M; Akoun, G M

    1992-01-01

    Broncho-alveolar lavage was performed to assess the degree of pulmonary lymphocytic alveolitis in 32 asymptomatic patients who were infected with the Human Immunodeficiency Virus (VIH). The patients were stages II and III of the CDC classification and the aim of the study was to determine the frequency, nature and prognostic role of the findings. 62.5% of the subjects (20/32) presented with a lymphocytic alveolitis which consisted predominantly of CD8 lymphocyte (64.3 +/- 3.5%), in the absence of an opportunistic infection or broncho-pulmonary tumours. Two sub-populations of alveolar CD8 were shown at comparable levels, a) sub-population CD8+D44+ (22.1 +/- 5%), in whom we showed the possession of cytotoxic activity in particular specific for VIH; b) sub-population CD8+CD57+ (19.6 +/- 3%) which we have shown to be capable in vitro of inhibiting the effector phase of cytotoxic activity of CD8+D44+ alveolar cells specific for VIH. In this group of 32 patients the occurrence of an alveolitis was not correlated with the usual prognostic factors of infection by VIH measured simultaneously with broncho-alveolar lavage (the level of CD4+ blood lymphocytes, and the beta 2-plasma microglobulins and the presence of p24 antigenaemia). In addition the level of CD4 lymphocytes supperior to 400/mm3 and of beta 2-microglobulins less then 3 mg/l whether a lymphocytic alveolitis was there or not confirmed the relatively poorly developed state of the VIH infection in these asymptomatic patients. Also the occurrence of a lymphocytic alveolitis did not seem to be linked to progression of the disease in the group of patients studied.(ABSTRACT TRUNCATED AT 250 WORDS)

  14. Transcriptional dynamics of Phytophthora infestans during sequential stages of hemibiotrophic infection of tomato.

    PubMed

    Zuluaga, Andrea P; Vega-Arreguín, Julio C; Fei, Zhangjun; Ponnala, Lalit; Lee, Sang Jik; Matas, Antonio J; Patev, Sean; Fry, William E; Rose, Jocelyn K C

    2016-01-01

    Hemibiotrophic plant pathogens, such as the oomycete Phytophthora infestans, employ a biphasic infection strategy, initially behaving as biotrophs, where minimal symptoms are exhibited by the plant, and subsequently as necrotrophs, feeding on dead plant tissue. The regulation of this transition and the breadth of molecular mechanisms that modulate plant defences are not well understood, although effector proteins secreted by the pathogen are thought to play a key role. We examined the transcriptional dynamics of P. infestans in a compatible interaction with its host tomato (Solanum lycopersicum) at three infection stages: biotrophy; the transition from biotrophy to necrotrophy; and necrotrophy. The expression data suggest a tight temporal regulation of many pathways associated with the suppression of plant defence mechanisms and pathogenicity, including the induction of putative cytoplasmic and apoplastic effectors. Twelve of these were experimentally evaluated to determine their ability to suppress necrosis caused by the P. infestans necrosis-inducing protein PiNPP1.1 in Nicotiana benthamiana. Four effectors suppressed necrosis, suggesting that they might prolong the biotrophic phase. This study suggests that a complex regulation of effector expression modulates the outcome of the interaction.

  15. Type I Interferons Regulate Immune Responses in Humans with Blood-Stage Plasmodium falciparum Infection

    PubMed Central

    Montes de Oca, Marcela; Kumar, Rajiv; de Labastida Rivera, Fabian; Amante, Fiona H.; Sheel, Meru; Faleiro, Rebecca J.; Bunn, Patrick T.; Best, Shannon E.; Beattie, Lynette; Ng, Susanna S.; Edwards, Chelsea L.; Boyle, Glen M.; Price, Ric N.; Anstey, Nicholas M.; Loughland, Jessica R.; Burel, Julie; Doolan, Denise L.; Haque, Ashraful; McCarthy, James S.; Engwerda, Christian R.

    2016-01-01

    Summary The development of immunoregulatory networks is important to prevent disease. However, these same networks allow pathogens to persist and reduce vaccine efficacy. Here, we identify type I interferons (IFNs) as important regulators in developing anti-parasitic immunity in healthy volunteers infected for the first time with Plasmodium falciparum. Type I IFNs suppressed innate immune cell function and parasitic-specific CD4+ T cell IFNγ production, and they promoted the development of parasitic-specific IL-10-producing Th1 (Tr1) cells. Type I IFN-dependent, parasite-specific IL-10 production was also observed in P. falciparum malaria patients in the field following chemoprophylaxis. Parasite-induced IL-10 suppressed inflammatory cytokine production, and IL-10 levels after drug treatment were positively associated with parasite burdens before anti-parasitic drug administration. These findings have important implications for understanding the development of host immune responses following blood-stage P. falciparum infection, and they identify type I IFNs and related signaling pathways as potential targets for therapies or vaccine efficacy improvement. PMID:27705789

  16. Host-cell sensors for Plasmodium activate innate immunity against liver-stage infection.

    PubMed

    Liehl, Peter; Zuzarte-Luís, Vanessa; Chan, Jennie; Zillinger, Thomas; Baptista, Fernanda; Carapau, Daniel; Konert, Madlen; Hanson, Kirsten K; Carret, Céline; Lassnig, Caroline; Müller, Mathias; Kalinke, Ulrich; Saeed, Mohsan; Chora, Angelo Ferreira; Golenbock, Douglas T; Strobl, Birgit; Prudêncio, Miguel; Coelho, Luis P; Kappe, Stefan H; Superti-Furga, Giulio; Pichlmair, Andreas; Vigário, Ana M; Rice, Charles M; Fitzgerald, Katherine A; Barchet, Winfried; Mota, Maria M

    2014-01-01

    Before they infect red blood cells and cause malaria, Plasmodium parasites undergo an obligate and clinically silent expansion phase in the liver that is supposedly undetected by the host. Here, we demonstrate the engagement of a type I interferon (IFN) response during Plasmodium replication in the liver. We identified Plasmodium RNA as a previously unrecognized pathogen-associated molecular pattern (PAMP) capable of activating a type I IFN response via the cytosolic pattern recognition receptor Mda5. This response, initiated by liver-resident cells through the adaptor molecule for cytosolic RNA sensors, Mavs, and the transcription factors Irf3 and Irf7, is propagated by hepatocytes in an interferon-α/β receptor-dependent manner. This signaling pathway is critical for immune cell-mediated host resistance to liver-stage Plasmodium infection, which we find can be primed with other PAMPs, including hepatitis C virus RNA. Together, our results show that the liver has sensor mechanisms for Plasmodium that mediate a functional antiparasite response driven by type I IFN.

  17. Neurocognitive Impairment Associated with Predominantly Early Stage HIV infection in Abuja, Nigeria

    PubMed Central

    Akolo, Christopher; Royal, Walter; Cherner, Mariana; Okwuasaba, Kanayo; Eyzaguirre, Lindsay; Adebiyi, Ruxton; Umlauf, Anya; Hendrix, Terence; Johnson, Joyce; Abimiku, Alashl’e; Blattner, William A.

    2014-01-01

    Detailed neuropsychological testing was performed on 134 HIV seropositive (SP) and 77 HIV seronegative (SN) individuals, 86% with early stage HIV infection in Nigeria, to determine the frequency of HIV-related neurocognitive impairment among the HIV-infected group. Twenty-two tests were administered to assess the following seven ability domains: speed of information processing (SIP); attention/working memory (AWM); executive functioning (EF); learning (LN); memory (MEM); verbal fluency (VF); and motor speed/dexterity (MSD). Demographically corrected individual test scores and scores for each domain or reflecting a global deficit (a global deficit score, or GDS) were compared for the SP and SN groups. SP participants were older, had fewer years of education, were more likely to be married, differed in ethnicity and had higher depression scores than SN individuals. On the testing, SP performed worse than SN on four tests that individually assessed LN, VF and MSD (the timed gait). SP subjects, however, performed better than SN on the finger-tapping test, also a motor task. Within the seven ability domains, SP performed worse than SN with respect to SIP, EF, LN, MEM and VF and also on the global measure. SP were also more frequently impaired on tests of SIP, and there was a borderline increase in the frequency of global impairment. Performance by SP subjects was not associated with CD4 counts. However, there were significant correlations between viral load measurements and individual tests of SIP, EF, LN and VF and with overall EF and a borderline correlation with the GDS. Depression scores for SP were associated with impairment on only a single test of EF. These results demonstrate that the ability of these assessments to identify areas of impairment that may be specifically linked to a history of HIV infection among individuals in Nigeria. Confirmation of these findings awaits analyses using data from a larger number of control subjects. PMID:24927825

  18. Screening of early antigen genes of adult-stage Trichinella spiralis using pig serum from different stages of early infection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The goal of this work was to identify novel, early antigens present in Trichinella spiralis. To this end, a cDNA library generated from 3-day old adult worms (Ad3) was immunologically screened using serum from a pig infected with 20,000 muscle larvae. The serum was obtained from multiple, time cours...

  19. Stage-specific activity in vitro on the Theileria infection process of serum from calves treated prophylactically with buparvaquone.

    PubMed

    Wilkie, G M; Kirvar, E; Thomas, E M; Sparagano, O; Brown, C G

    1998-12-31

    An in vitro method for testing activity of buparvaquone in serum on the infection and development of Theileria in its bovine host mononuclear cells is described and results compared with the effect exhibited in vivo. Serum samples were collected over a time course from calves in a clinical trial of 5 mg kg(-1) buparvaquone prophylaxis on Theileria annulata or T. parva experimental infection. To evaluate drug levels and persistence in each animal for a period of 14 days and its effect on the early infection stages, the sera were tested on established macroschizont infected cell lines and against the in vitro infection and development process of the sporozoite and trophozoite stages of the two Theileria species. Results from the in vitro assays show that buparvaquone in serum can completely prevent the establishment of Theileria infection during the first 48 h after administration at 5 mg kg(-1). After seven days, levels are sufficient to delay the establishment of infection. The drug is more effective in the prevention of the de novo development of the parasite in cells than against established macroschizont infected cell culture. At low concentrations, it is more effective against T. parva than against T. annulata. Drug effect peaks during the first 24 h but residual effect persists for 14 days, particularly against T. parva infection. These novel findings demonstrate how high doses of buparvaquone could over-protect calves if used in the 'infection-and-treatment' method of immunisation when drug is administered prophylactically at the same time as infection with live sporozoites. It is suggested that in certain high Theileria risk situations there may be potential for the immunoprophylactic use of buparvaquone without simultaneous infection. The in vitro assay itself has been shown to be of value as a model for Theileria establishment in cattle.

  20. The rodent malaria liver stage survives in the rapamycin-induced autophagosome of infected Hepa1–6 cells

    PubMed Central

    Zhao, Chenghao; Liu, Taiping; Zhou, Taoli; Fu, Yong; Zheng, Hong; Ding, Yan; Zhang, Kun; Xu, Wenyue

    2016-01-01

    It has been reported that non-selective autophagy of infected hepatocytes could facilitate the development of malaria in the liver stage, but the fate of parasites following selective autophagy of infected hepatocytes is still not very clear. Here, we confirmed that sporozoite infection can induce a selective autophagy-like process targeting EEFs (exo-erythrocytic forms) in Hepa1–6. Rapamycin treatment greatly enhanced this process in EEFs and non-selective autophagy of infected Hepa1-6 cells and enhanced the development of the malaria liver stage in vivo. Although rapamycin promoted the fusion of autophagosomes containing the malaria parasite with lysosomes, some parasites inside the autophagosome survived and replicated normally. Further study showed that the maturation of affected autolysosomes was greatly inhibited. Therefore, in addition to the previously described positive role of rapamycin-induced nonselective autophagy of hepatocytes, we provide evidence that the survival of EEFs in the autophagosome of the infected hepatocytes also contributes to rapamycin-enhanced development of the malaria liver stage, possibly due to the suppression of autolysosome maturation by EEFs. These data suggest that the inhibition of autolysosome maturation might be a novel escape strategy used by the malaria liver stage. PMID:27901110

  1. In vitro alterations do not reflect a requirement for host cell cycle progression during Plasmodium liver stage infection.

    PubMed

    Hanson, Kirsten K; March, Sandra; Ng, Shengyong; Bhatia, Sangeeta N; Mota, Maria M

    2015-01-01

    Prior to invading nonreplicative erythrocytes, Plasmodium parasites undergo their first obligate step in the mammalian host inside hepatocytes, where each sporozoite replicates to generate thousands of merozoites. While normally quiescent, hepatocytes retain proliferative capacity and can readily reenter the cell cycle in response to diverse stimuli. Many intracellular pathogens, including protozoan parasites, manipulate the cell cycle progression of their host cells for their own benefit, but it is not known whether the hepatocyte cell cycle plays a role during Plasmodium liver stage infection. Here, we show that Plasmodium parasites can be observed in mitotic hepatoma cells throughout liver stage development, where they initially reduce the likelihood of mitosis and ultimately lead to significant acquisition of a binucleate phenotype. However, hepatoma cells pharmacologically arrested in S phase still support robust and complete Plasmodium liver stage development, which thus does not require cell cycle progression in the infected cell in vitro. Furthermore, murine hepatocytes remain quiescent throughout in vivo infection with either Plasmodium berghei or Plasmodium yoelii, as do Plasmodium falciparum-infected primary human hepatocytes, demonstrating that the rapid and prodigious growth of liver stage parasites is accomplished independent of host hepatocyte cell cycle progression during natural infection.

  2. NK cells contribute to persistent airway inflammation and AHR during the later stage of RSV infection in mice.

    PubMed

    Long, Xiaoru; Xie, Jun; Zhao, Keting; Li, Wei; Tang, Wei; Chen, Sisi; Zang, Na; Ren, Luo; Deng, Yu; Xie, Xiaohong; Wang, Lijia; Fu, Zhou; Liu, Enmei

    2016-10-01

    RSV can lead to persistent airway inflammation and AHR and is intimately associated with childhood recurrent wheezing and asthma, but the underlying mechanisms remain unclear. There are high numbers of NK cells in the lung, which not only play important roles in the acute stage of RSV infection, but also are pivotal in regulating the pathogenesis of asthma. Therefore, in this study, we assumed that NK cells might contribute to persistent airway disease during the later stage of RSV infection. Mice were killed at serial time points after RSV infection to collect samples. Leukocytes in bronchoalveolar lavage fluid (BALF) were counted, lung histopathology was examined, and airway hyperresponsiveness (AHR) was measured by whole-body plethysmography. Cytokines were detected by ELISA, and NK cells were determined by flow cytometry. Rabbit anti-mouse asialo-GM-1 antibodies and resveratrol were used to deplete or suppress NK cells. Inflammatory cells in BALF, lung tissue damage and AHR were persistent for 60 days post-RSV infection. Type 2 cytokines and NK cells were significantly increased during the later stage of infection. When NK cells were decreased by the antibodies or resveratrol, type 2 cytokines, the persistent airway inflammation and AHR were all markedly reduced. NK cells can contribute to the RSV-associated persistent airway inflammation and AHR at least partially by promoting type 2 cytokines. Therefore, therapeutic targeting of NK cells may provide a novel approach to alleviating the recurrent wheezing subsequent to RSV infection.

  3. Association of Helicobacter pylori infection with chemotherapy-induced thrombocytopenia in patients with stage III colon cancer: a pilot study.

    PubMed

    Tanriverdi, Ozgur

    2014-01-01

    In this study, the effects of the pre-treatment presence of Helicobacter pylori (H. pylori) infection on chemotherapy-induced thrombocytopenia (CIT) were investigated in patients with stage III colon cancer (CC). A cohort of 74 patients with early stage CC was analysed through a review of clinical records and personal interviews. Helicobacter pylori infections were diagnosed in these patients prior to chemotherapy. The subjects were divided into two groups according to H. pylori infection status: Group 1, H. pylori-positive and Group 2, H. pylori-negative. In all patients, bone marrow toxicity and other study variables were compared. Helicobacter pylori infections were detected in 31 of the 74 CC patients. Helicobacter pylori-infected patients (Group 1) showed significantly higher incidences of CIT than did non-infected patients (Group 2; p = 0.029). Helicobacter pylori infection status correlated significantly with tumour location (r = 0.547; p = 0.043) and the most common location of CC in H. pylori-infected patients was the ascending colon (n = 13, 42%) in comparison to non-infected patients (n = 6, 14%; p= 0.042). The relationship between CIT and H. pylori infection status in CC was determined to be independent from the other study variables (p = 0.037; OR = 3.32, CI 95% = 1.16-9.70). In this study, the small number of patients resulted in an inadequate demonstration of the relationship between H. pylori infection and CIT. Therefore, clinical and molecular studies that include more patients are warranted.

  4. Neurocognitive impairment associated with predominantly early stage HIV infection in Abuja, Nigeria.

    PubMed

    Akolo, Christopher; Royal, Walter; Cherner, Mariana; Okwuasaba, Kanayo; Eyzaguirre, Lindsay; Adebiyi, Ruxton; Umlauf, Anya; Hendrix, Terence; Johnson, Joyce; Abimiku, Alashl'e; Blattner, William A

    2014-08-01

    Detailed neuropsychological testing was performed on 133 human immunodeficiency virus (HIV) seropositive (SP) and 77 HIV seronegative (SN) individuals, 86 % with early stage HIV infection in Nigeria, to determine the frequency of HIV-related neurocognitive impairment among the HIV-infected group. The tests were administered to assess the following seven ability domains: speed of information processing, attention/working memory, executive functioning, learning, memory, verbal fluency, and motor function motor. Demographically corrected individual test scores and scores for each domain or reflecting a global deficit (a global deficit score, or GDS) were compared for the SP and SN groups. SP participants were older, had fewer years of education, were more likely to be married, differed in ethnicity, and had higher depression scores than SN individuals. Within the seven ability domains, SP performed worse than SN with respect to speed of information processing, executive function, learning, memory, and verbal fluency and also on the global measure. SP were also more frequently impaired on tests of SIP, and there was a borderline increase in the frequency of global impairment. On the individual tests, SP performed worse than SN on four tests that assessed learning, verbal fluency, memory, and motor function (the Timed Gait). SP subjects, however, performed better than SN on the Finger-tapping test, also a motor task. Performance by SP subjects was not associated on the timed gait which showed a borderline statistically significant correlation with CD4 counts. However, there were significant correlations between viral load measurements and individual tests of speed of information processing, executive function, learning, and verbal fluency and with overall executive function and a borderline correlation with the GDS. Depression scores for SP were associated with impairment on only a single test of executive function. These results demonstrate the ability of these

  5. Comparative susceptibility of larval stages of Amblyomma aureolatum, Amblyomma cajennense, and Rhipicephalus sanguineus to infection by Rickettsia rickettsii.

    PubMed

    Labruna, Marcelo B; Ogrzewalska, Maria; Martins, Thiago F; Pinter, Adriano; Horta, Maurício C

    2008-11-01

    The current study compared the susceptibility of larval stages of Amblyomma cajennense (F.), Amblyomma aureolatum (Pallas), and Rhipicephalus sanguineus (Latreille) to infection by a Brazilian strain of Rickettsia rickettsii. Guinea pigs experimentally infected by R. rickettsii were simultaneously infested by larvae of the three tick species. Recovered engorged larvae were allowed to molt to nymphs and held in an incubator at 23 degrees C and 85-90% RH. Subsequent flat nymphs were tested for rickettsial infection by polymerase chain reaction (PCR). Concomitant infestations with sibling ticks on noninfected guinea pigs (control) were done. While 10-60% of the A. cajennense nymphs were shown to be infected by R. rickettsii, both A. aureolatum and R. sanguineus were highly susceptible to R. rickettsii, since 80-100% of their nymphs were shown to be infected in the corresponding trials. Most of the engorged larvae (approximately 70-95%), regardless of being infected or not, successfully molted to nymphs. Mortality rates for engorged larvae tended to be statistically similar (P > 0.05) for ticks recovered from R. rickettsii-infected and noninfected guinea pigs, within each tick species. The only exceptions were the significantly higher mortalities (P < 0.05) for engorged A. cajennense larvae recovered from two infected guinea pigs. Therefore, A. cajennense was less susceptible to R. rickettsii infection than A. aureolatum and R. sanguineus, while feeding on rickettsemic guinea pigs. These two later species were similarly highly susceptible.

  6. Revision of Infected Total Knee Arthroplasty: Two-Stage Reimplantation Using an Antibiotic-Impregnated Static Spacer

    PubMed Central

    Almeida, Fernando; Renovell, Pablo; Morante, Elena; López, Raúl

    2013-01-01

    Background A two-stage revision remains as the "gold standard" treatment for chronically infected total knee arthroplasties. Methods Forty-five septic knee prostheses were revised with a minimum follow-up of 5 years. Static antibiotic-impregnated cement spacers were used in all cases. Intravenous antibiotics according to sensitivity test of the culture were applied during patients' hospital stay. Oral antibiotics were given for another 5 weeks. Second-stage surgery was undertaken after control of infection with normal erythrocyte sedimentation rate and C-reactive protein values. Extensile techniques were used if needed and metallic augments were employed for bone loss in 32 femoral and 29 tibial revisions. Results The average interval between the first-stage resection and reimplantation was 4.4 months. Significant improvement was obtained with respect to visual analog scale pain and clinical and functional scores, and infection was eradicated in 95.6% of cases following a two-stage revision total knee arthroplasty. Radiographic evaluation showed suitable alignment without signs of mechanical loosening. Conclusions This technique is a reasonable procedure to eradicate chronic infection in knee arthroplasty and provides proper functional and clinical results. However, it sometimes requires extensile surgical approaches that could imply arduous surgeries. Metallic augments with cementless stems available in most of the knee revision systems are a suitable alternative to handle bone deficiencies, avoiding the use of bone allografts with its complications. PMID:24009903

  7. Gamma-delta T cell responses in subclinical and clinical stages of Bovine Mycobacterium Avium Paratuberculosis infection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The early immune response to Mycobacterium avium subsp. paratuberculosis (MAP) in cattle is characterized by a Th1-like immune response effective in controlling bacterial proliferation during the subclinical stage of infection. In young calves nearly 60% of circulating lymphocytes are gamma delta T ...

  8. Radiolabeling of infective third-stage larvae of Strongyloides stercoralis by feeding ( sup 75 Se)selenomethionine-labeled Escherichia coli to first- and second-stage larvae

    SciTech Connect

    Aikens, L.M.; Schad, G.A. )

    1989-10-01

    A technique is described for radiolabeling Strongyloides stercoralis larvae with ({sup 75}Se)selenomethionine. Cultures of an auxotrophic methionine-dependent stain of Escherichia coli were grown in a medium containing Dulbecco's modified Eagle's medium supplemented with 5% nutrient broth, amino acids, and ({sup 75}Se)selenomethionine. When the {sup 75}Se-labeled bacterial populations were in the stationary phase of growth, cultures were harvested and the bacteria dispersed on agar plates to serve as food for S. stercoralis larvae. Use of nondividing bacteria is important for successful labeling because the isotope is not diluted by cell division and death of larvae attributable to overgrowth by bacteria is prevented. First-stage S. stercoralis larvae were recovered from feces of infected dogs and reared in humid air at 30 C on agar plates seeded with bacteria. After 7 days, infective third-stage larvae were harvested. The mean specific activity of 6 different batches of larvae ranged from 75 to 330 counts per min/larva with 91.8 +/- 9.5% of the population labeled sufficiently to produce an autoradiographic focus during a practicable, 6-wk period of exposure. Labeled infective larvae penetrated the skin of 10-day-old puppies and migrated to the small intestine, where the developed to adulthood.

  9. Generating a detailed protein profile of Fasciola hepatica during the chronic stage of infection in cattle.

    PubMed

    Haçarız, Orçun; Baykal, Ahmet Tarık; Akgün, Mete; Kavak, Pınar; Sağıroğlu, Mahmut Şamil; Sayers, Gearóid Patrick

    2014-06-01

    Fasciola hepatica is a trematode helminth causing a damaging disease, fasciolosis, in ruminants and humans. Comprehensive proteomic studies broaden our knowledge of the parasite's protein profile, and provide new insights into the development of more effective strategies to deal with fasciolosis. The objective of this study was to generate a comprehensive profile of F. hepatica proteins expressed during the chronic stage of infection in cattle by building on previous efforts in this area. The approach included an improved sample preparation procedure for surface and internal layers of the parasite, the application of nano-UPLC-ESI-qTOF-MS (nano-ultra-performance LC and ESI quadrupole TOF MS) integrated with different acquisition methods and in silico database search against various protein databases and a transcript database including a new assembly of publically available EST. Of a total of 776 identified proteins, 206 and 332 were specific to the surface and internal layers of the parasite, respectively. Furthermore, 238 proteins were common to both layers, with comparative differences of 172 proteins detected. Specific proteins not previously identified in F. hepatica, but shown to be immunomodulatory or potential drug targets for other parasites, are discussed.

  10. Inhibition of human coronavirus NL63 infection at early stages of the replication cycle.

    PubMed

    Pyrc, Krzysztof; Bosch, Berend Jan; Berkhout, Ben; Jebbink, Maarten F; Dijkman, Ronald; Rottier, Peter; van der Hoek, Lia

    2006-06-01

    Human coronavirus NL63 (HCoV-NL63), a recently discovered member of the Coronaviridae family, has spread worldwide and is associated with acute respiratory illness in young children and elderly and immunocompromised persons. Further analysis of HCoV-NL63 pathogenicity seems warranted, in particular because the virus uses the same cellular receptor as severe acute respiratory syndrome-associated coronavirus. As there is currently no HCoV-NL63-specific and effective vaccine or drug therapy available, we evaluated several existing antiviral drugs and new synthetic compounds as inhibitors of HCoV-NL63, targeting multiple stages of the replication cycle. Of the 28 compounds that we tested, 6 potently inhibited HCoV-NL63 at early steps of the replication cycle. Intravenous immunoglobulins, heptad repeat 2 peptide, small interfering RNA1 (siRNA1), siRNA2, beta-D-N(4)-hydroxycytidine, and 6-azauridine showed 50% inhibitory concentrations of 125 microg/ml, 2 microM, 5 nM, 3 nM, 400 nM, and 32 nM, respectively, and low 50% cytotoxicity concentrations (>10 mg/ml, >40 microM, >200 nM, >200 nM, >100 microM, and 80 microM, respectively). These agents may be investigated further for the treatment of coronavirus infections.

  11. Variation in infection prevention practices in dialysis facilities: results from the national opportunity to improve infection control in ESRD (End-Stage Renal Disease) project.

    PubMed

    Chenoweth, Carol E; Hines, Stephen C; Hall, Kendall K; Saran, Rajiv; Kalbfleisch, John D; Spencer, Teri; Frank, Kelly M; Carlson, Diane; Deane, Jan; Roys, Erik; Scholz, Natalie; Parrotte, Casey; Messana, Joseph M

    2015-07-01

    OBJECTIVE To observe patient care across hemodialysis facilities enrolled in the National Opportunity to Improve Infection Control in ESRD (end-stage renal disease) (NOTICE) project in order to evaluate adherence to evidence-based practices aimed at prevention of infection. SETTING AND PARTICIPANTS Thirty-four hemodialysis facilities were randomly selected from among 772 facilities in 4 end-stage renal disease participating networks. Facility selection was stratified on dialysis organization affiliation, size, socioeconomic status, and urban/rural status. MEASUREMENTS Trained infection control evaluators used an infection control worksheet to observe 73 distinct infection control practices at the hemodialysis facilities, from October 1, 2011, through January 31, 2012. RESULTS There was considerable variation in infection control practices across enrolled facilities. Overall adherence to recommended practices was 68% (range, 45%-92%) across all facilities. Overall adherence to expected hand hygiene practice was 72% (range, 10%-100%). Compliance to hand hygiene before and after procedures was high; however, during procedures hand hygiene compliance averaged 58%. Use of chlorhexidine as the specific agent for exit site care was 19% overall but varied from 0% to 35% by facility type. The 8 checklists varied in the frequency of perfect performance from 0% for meeting every item on the checklist for disinfection practices to 22% on the arteriovenous access practices at initiation. CONCLUSIONS Our findings suggest that there are many areas for improvement in hand hygiene and other infection prevention practices in end-stage renal disease. These NOTICE project findings will help inform the development of a larger quality improvement initiative at dialysis facilities.

  12. Therapeutic PD-L1 and LAG-3 blockade rapidly clears established blood-stage Plasmodium infection

    PubMed Central

    Butler, Noah S.; Moebius, Jacqueline; Pewe, Lecia L.; Traore, Boubacar; Doumbo, Ogobara K.; Tygrett, Lorraine T.; Waldschmidt, Thomas J.; Crompton, Peter D.; Harty, John T.

    2011-01-01

    Plasmodium infection of erythrocytes induces clinical malaria. Parasite-specific CD4+ T cells correlate with reduced parasite burdens and severity of human malaria, and are required to control blood-stage infection in mice. However, the characteristics of CD4+ T cells that determine protection or parasite persistence remain unknown. Here we show that P. falciparum infection of humans increased expression of an inhibitory receptor (PD-1) associated with T cell dysfunction. In vivo blockade of PD-L1 and LAG-3 restored CD4+ T cell function, amplified T follicular helper cell and germinal center B cell and plasmablast numbers, enhanced protective antibodies and rapidly cleared blood-stage malaria in mice. Thus, chronic malaria drives specific T cell dysfunction, which can be rescued to enhance parasite control using inhibitory therapies. PMID:22157630

  13. Therapeutic blockade of PD-L1 and LAG-3 rapidly clears established blood-stage Plasmodium infection.

    PubMed

    Butler, Noah S; Moebius, Jacqueline; Pewe, Lecia L; Traore, Boubacar; Doumbo, Ogobara K; Tygrett, Lorraine T; Waldschmidt, Thomas J; Crompton, Peter D; Harty, John T

    2011-12-11

    Infection of erythrocytes with Plasmodium species induces clinical malaria. Parasite-specific CD4(+) T cells correlate with lower parasite burdens and severity of human malaria and are needed to control blood-stage infection in mice. However, the characteristics of CD4(+) T cells that determine protection or parasite persistence remain unknown. Here we show that infection of humans with Plasmodium falciparum resulted in higher expression of the inhibitory receptor PD-1 associated with T cell dysfunction. In vivo blockade of the PD-1 ligand PD-L1 and the inhibitory receptor LAG-3 restored CD4(+) T cell function, amplified the number of follicular helper T cells and germinal-center B cells and plasmablasts, enhanced protective antibodies and rapidly cleared blood-stage malaria in mice. Thus, chronic malaria drives specific T cell dysfunction, and proper function can be restored by inhibitory therapies to enhance parasite control.

  14. Bilateral One-Stage Revision of Infected Total Hip Arthroplasties: Report of Two Cases and Management of Antibiotic Therapy

    PubMed Central

    Pommepuy, Thomas; Lons, Adrien; Benad, Kevin; Beltrand, Eric; Senneville, Eric; Migaud, Henri

    2016-01-01

    Recommendations for the management of chronic and bilateral total hip arthroplasty (THA) infection are lacking. However, this type of infection involves medical problems concerning the management of the antibiotic therapy. We report two cases of such infections operated as one-stage revision. For each case, both hips were infected with the same bacteria (Staphylococcus caprae for one patient and methicillin-sensitive Staphylococcus aureus for the other). The probabilistic antibiotic treatment started during the first side (after harvesting intraoperative samples) did not prevent the culture of the bacteriologic harvested during the intervention of the second side. Cultures were positive for the same bacteria for both sides in the two cases presented herein. After results of intraoperative cultures, patients received culture-guided antibiotic therapy for three months and were considered cured at the end of a two-year follow-up. Our results suggest one-stage bilateral change of infected THA is a viable option and that early intraoperative antibiotic, started during the first-side exchange, does not jeopardize microbiological documentation of the second side. This work brings indirect arguments, in favor of the use of prophylactic antibiotics during revision of infected THA. PMID:26904335

  15. Influence of Ribeiroia ondatrae (Trematoda: Digenea) infection on limb development and survival of northern leopard frogs (Rana pipiens): effects of host stage and parasite-exposure level

    USGS Publications Warehouse

    Schotthoefer, Anna M.; Koehler, Anson V.; Meteyer, Carol U.; Cole, Rebecca A.

    2003-01-01

    Recent evidence suggests that infection by larvae of the trematode Ribeiroia ondatrae accounts for a significant proportion of limb malformations currently observed in amphibian populations of North America. However, the effects of R. ondatrae infection on northern leopard frogs (Rana pipiens), one of the species most frequently reported with malformations, have not been adequately explored. Moreover, the risk factors associated with R. ondatrae-induced malformations have not been clearly identified. We examined the effects of timing of infection on tadpole survival and limb development. Rana pipiens tadpoles were individually exposed to R. ondatrae cercariae at the pre-limb-bud (Gosner stages 24 and 25), limb-bud (Gosner stages 27 and 28), or paddle (Gosner stages 31–33) stages of development and monitored through metamorphosis. The effects of infection were stage-specific. Infections acquired at the pre-limb-bud stage resulted in a high mortality rate (47.5–97.5%), whereas tadpoles infected at the limb-bud stage displayed a high malformation rate (16% overall), and the magnitude of effects increased with the level of exposure to cercariae. In contrast, infections acquired at the paddle stage had no effect on limb development or tadpole survival, which suggests that the timing of R. ondatrae infection in relation to the stage structure of tadpole populations in the wild is an important determinant of the degree to which populations are affected by R. ondatrae.

  16. Aggregation of Infective Stages of Parasites as an Adaptation and Its Implications for the Study of Parasite-Host Interactions.

    PubMed

    Morrill, André; Forbes, Mark R

    2016-02-01

    The causes and consequences of aggregation among conspecifics have received much attention. For infecting macroparasites, causes include variation among hosts in susceptibility and whether infective stages are aggregated in the environment. Here, we link these two phenomena and explore whether aggregation of infective stages in the environment is adaptive to parasites encountering host condition-linked defenses and what effect such aggregations have for parasite-host interactions. Using simulation models, we show that parasite fitness is increased by aggregates attacking a host, particularly when investment into defenses is high. The fitness benefit of aggregation remains despite inclusion of factors that should curb the benefits of aggregation, namely, mortality of low-condition hosts (those hosts expected to be most susceptible to parasitism) and costs of high coinfection. For sample sizes common in studies, aggregation of infective stages reduces the likelihood of detecting host condition-parasitism relations, even when host condition is the only other factor in models affecting parasitism. Thus, it is not surprising that the expected inverse relations between host condition and parasitism, commonly a premise in studies of parasite-host interactions, are inconsistently found. An understanding of how parasites encounter hosts is thus needed for developing theory for parasite-host ecological and evolutionary interactions.

  17. Transcriptomic analysis of the host response to early stage salmonid alphavirus (SAV-1) infection in Atlantic salmon Salmo salar L.

    PubMed

    Herath, Tharangani K; Bron, James E; Thompson, Kim D; Taggart, John B; Adams, Alexandra; Ireland, Jacqueline H; Richards, Randolph H

    2012-05-01

    Salmon pancreas disease, caused by salmonid alphavirus (SAV) of the family Togaviridae, is an economically important disease affecting farmed Atlantic salmon (Salmo salar L.) in Scotland, Norway, and Ireland. The virus causes characteristic lesions in the pancreas, heart, kidney and skeletal muscle of infected fish. The mechanisms responsible for the pathology and the immune responses elicited in infected Atlantic salmon are not fully understood. A microarray-based study was therefore performed to evaluate the host transcriptomic response during the early stages of an experimentally-induced SAV-1 infection. Atlantic salmon parr were injected intra-peritoneally with viral cell culture supernatant or cell culture supernatant without virus. RNA, extracted from head kidney sampled from infected and control fish at 1, 3 and 5 days post-injection (d.p.i.), was interrogated with the 17 k TRAITS/SGP cDNA microarray. The greatest number of significantly differentially expressed genes was recorded at 3 d.p.i., mainly associated with immune and defence mechanisms, including genes involved in interferon I pathways and Major Histocompatibility Complex Class I and II responses. Genes associated with apoptosis and cellular stress were also found to be differentially expressed between infected and uninfected individuals, as were genes involved in inhibiting viral attachment and replication. The microarray results were validated by follow-on analysis of eight genes by real-time PCR. The findings of the study reflect mechanisms used by the host to protect itself during the early stages of SAV-1 infection. In particular, there was evidence of rapid induction of interferon-mediated responses similar to those seen during mammalian alphavirus infections, and also early involvement of an adaptive immune response. This study provides essential knowledge to assist in the development of effective control and management strategies for SAV-1 infection.

  18. Quantitative and qualitative profiles of circulating monocytes may help identifying tuberculosis infection and disease stages

    PubMed Central

    La Manna, Marco Pio; Orlando, Valentina; Dieli, Francesco; Di Carlo, Paola; Cascio, Antonio; Cuzzi, Gilda; Palmieri, Fabrizio; Goletti, Delia

    2017-01-01

    Tuberculosis (TB) is one of the most important cause of morbidity and death among infectious diseases, and continuous efforts are needed to improve diagnostic tools and therapy. Previous published studies showed that the absolute cells number of monocytes or lymphocytes in peripheral blood or yet the ratio of monocytes to lymphocytes displayed the ability to predict the risk of active TB. In the present study we evaluated the ratio of monocytes to lymphocytes variation and we also analyzed the ex-vivo expression of CD64 on monocytes as tools to identify biomarkers for discriminating TB stages. Significant differences were found when the average ratio of monocytes to lymphocytes of active TB patients was compared with latent TB infection (LTBI) subjects, cured TB and healthy donors (HD). By the receiver operator characteristics (ROC) curve analysis the cut-off value of 0.285, allowed the discrimination of active TB from HD, with a sensitivity of 91.04% and a specificity of 93.55% (95% of confidence interval: 0.92–0.99). The ROC curve analysis comparing TB patients and LTBI groups, led to a sensitivity and the specificity of the assay of 85.07% and 85.71%, respectively (95% of confidence interval: 0.85 to 0.96). The upregulation of CD64 expression on circulating monocytes in active TB patients could represent an additional biomarker for diagnosis of active TB. In conclusion, we found that the ML ratio or monocyte absolute count or phenotypic measures show predictive value for active TB. PMID:28208160

  19. Contrasting expression of immune genes in scaled and scaleless skin of Atlantic salmon infected with young stages of Lepeophtheirus salmonis.

    PubMed

    Holm, H Jodaa; Skugor, S; Bjelland, A K; Radunovic, S; Wadsworth, S; Koppang, E O; Evensen, Ø

    2017-02-01

    Atlantic salmon skin tissues with and without scales were taken from two preferred sites of salmon louse (Lepeophtheirus salmonis) attachment, behind the dorsal fin (scaled) and from the top of the head (scaleless), respectively. Tissues were profiled by qPCR of 32 genes to study responses to copepodids, 4 days post infection (dpi), and during the moult of copepodids to the chalimus stage, at 8 dpi. Basal/constitutive differences were found for many immune-related genes between the two skin sites; e.g., mannose binding protein C was over 100 fold higher expressed in the scaled skin from the back in comparison to the skin without scales from the head. With lice-infection, at 4 dpi most genes in both tissues showed lower values than in the non-infected control. By 8 dpi, the majority of responses increased towards the control levels, including cytokines of Th1, Th17 and Th2 pathways. Immunohistochemistry of three immune factors revealed an even distribution of MHC class II positive cells throughout epidermis, including the top layer of keratinocytes, marked compartmentalization of Mx(+) and CD8α(+) cells close to stratum basale, and an increase in numbers of CD8α(+) cells in response to infection. In conclusion, suppression of immune genes during the copepodid stage likely sets off a beneficial situation for the parasite. At the moult to chalimus stage 8 dpi, only few genes surpassed the non-infected control levels, including CD8α. The gene expression pattern was reflected in the increased number of CD8α expressing cells, thus revealing a relatively minor activation of skin T-cell defenses in Atlantic salmon in response to L. salmonis infection.

  20. Single-virus tracking approach to reveal the interaction of Dengue virus with autophagy during the early stage of infection

    NASA Astrophysics Data System (ADS)

    Chu, Li-Wei; Huang, Yi-Lung; Lee, Jin-Hui; Huang, Long-Ying; Chen, Wei-Jun; Lin, Ya-Hsuan; Chen, Jyun-Yu; Xiang, Rui; Lee, Chau-Hwang; Ping, Yueh-Hsin

    2014-01-01

    Dengue virus (DENV) is one of the major infectious pathogens worldwide. DENV infection is a highly dynamic process. Currently, no antiviral drug is available for treating DENV-induced diseases since little is known regarding how the virus interacts with host cells during infection. Advanced molecular imaging technologies are powerful tools to understand the dynamics of intracellular interactions and molecular trafficking. This study exploited a single-virus particle tracking technology to address whether DENV interacts with autophagy machinery during the early stage of infection. Using confocal microscopy and three-dimensional image analysis, we showed that DENV triggered the formation of green fluorescence protein-fused microtubule-associated protein 1A/1B-light chain 3 (GFP-LC3) puncta, and DENV-induced autophagosomes engulfed DENV particles within 15-min postinfection. Moreover, single-virus particle tracking revealed that both DENV particles and autophagosomes traveled together during the viral infection. Finally, in the presence of autophagy suppressor 3-methyladenine, the replication of DENV was inhibited and the location of DENV particles spread in cytoplasma. In contrast, the numbers of newly synthesized DENV were elevated and the co-localization of DENV particles and autophagosomes was detected while the cells were treated with autophagy inducer rapamycin. Taken together, we propose that DENV particles interact with autophagosomes at the early stage of viral infection, which promotes the replication of DENV.

  1. Can Taenia solium latent post-oncospheral stages be found in muscle tissue of cysticercosis-infected pigs (Sus scrofa)?

    PubMed

    Rodrìguez, Mary L; Rodriguez, Silvia; Gonzalez, Armando E; Verastegui, Manuela; Bernal, Teresa; Jimenez, Juan A; Garcia, Hector H

    2006-02-01

    The existence of latent Taenia solium post-oncospheral stages in the tissues of infected pigs has been postulated. To assess whether such structures exist and can be detected, we examined muscle samples from cysticercosis-infected and uninfected pigs. Pork samples were homogenized, centrifuged, and resuspended in saline solution. Round microscopic structures of approximately 10 microm with variable refringence were found in the pellets of all samples from both infected and uninfected pigs. These became homogeneously red after staining with Sudan IV and disappeared after ether extraction. The only difference between samples from infected and uninfected pigs was the presence of inflammatory cells and tissue necrosis debris in the former group. Taenia solium oncospheres were stained and observed for comparative purposes, before and after inoculation into pork. Control oncospheres were ellipsoidal, had nucleated basophile cells in their interior, and showed red aggregates on their surfaces when stained with 3% Sudan IV. While rounded microscopical structures similar to those previously reported were found, these differed morphologically from oncospheres, were of a lipid nature, and occurred in both infected and uninfected animals. No evidence supporting the presence of latent post-oncospheral stages of Taenia solium was generated in this series of experiments.

  2. Stage-specific immunity to Taenia taeniaeformis infection in mice. A histological study of the course of infection in mice vaccinated with either oncosphere or metacestode antigens.

    PubMed

    Bøgh, H O; Lightowlers, M W; Sullivan, N D; Mitchell, G F; Rickard, M D

    1990-03-01

    The course of Taenia taeniaeformis infection in mice previously vaccinated with antigens prepared from either oncosphere (TtO) or metacestode (TtM) was followed by histological examination of livers from mice killed at various times post-infection (p.i.). Distinctly different immune responses occurred in the two groups. Very few cysts were seen at any stage of infection in TtO-vaccinated mice and most of those which were present appeared histologically similar to cysts in control mice. In TtM-vaccinated mice many cysts were present from early in infection but histologically it was apparent that most were dying from 15 days p.i. because the tegument had lost its integrity, and degranulated polymorphonuclear leucocytes were present inside the parasites. These findings support earlier suggestions that stage-specific antigens are expressed in oncospheres and metacestodes. Parasites developing normally were surrounded by a halo of alcian blue staining amorphous acellular material. This material appeared to act as a barrier to attack by host inflammatory cells, and disappearance of this layer signalled death of the parasite. The possibility that the gut acted as a barrier to delay migration of oncospheres to the liver in vaccinated mice was investigated, but no evidence for this could be found.

  3. Role of Suppressive Oral Antibiotics in Orthopedic Hardware Infections for Those Not Undergoing Two-Stage Replacement Surgery

    PubMed Central

    Keller, Sara C.; Cosgrove, Sara E.; Higgins, Yvonne; Piggott, Damani A.; Osgood, Greg; Auwaerter, Paul G.

    2016-01-01

    Background. The use of suppressive antibiotics in treatment of orthopedic hardware infections (OHIs), including spinal hardware infections, prosthetic joint infections, and infections of internal fixation devices, is controversial. Methods. Over a 4-year period at 2 academic medical centers, patients with OHI who were treated with debridement and retention of hardware components, with single-stage exchange, or without surgery were studied to determine whether use of oral antibiotics for at least 6 months after diagnosis impacts successful treatment of the infection at 1 year after diagnosis. Results. Of 89 patients in the study, 42 (47.2%) were free of clinical infection 1 year after initial diagnosis. Suppressive antibiotics used for at least 6 months after diagnosis was not associated with being free of clinical infection (adjusted odds ratio [aOR], 5.29; 95% confidence interval [CI], .74–37.80), but being on suppressive antibiotics at least 3 months after diagnosis was associated with being free of clinical infection (OR, 3.50; 95% CI, 1.30–9.43). Causative organisms impacted the likelihood of success; patients with methicillin-resistant Staphylococcus aureus as well as with Gram-negative rods were both less likely to have achieved clinical success at 1 year after surgery (aOR = 0.018, 95% CI = .0017–.19 and aOR = 0.20, 95% CI = .039–.99, respectively). Conclusions. Oral suppressive antibiotic therapy in treatment of OHI with retention of hardware for 3 months, but not 6 months, postdiagnosis increases the likelihood of treatment success. The organisms implicated in the infection directly impact the likelihood of treatment success. PMID:27747252

  4. MAPK phosphotase 5 deficiency contributes to protection against blood-stage Plasmodium yoelii 17XL infection in mice.

    PubMed

    Cheng, Qianqian; Zhang, Qingfeng; Xu, Xindong; Yin, Lan; Sun, Lin; Lin, Xin; Dong, Chen; Pan, Weiqing

    2014-04-15

    Cell-mediated immunity plays a crucial role in the development of host resistance to asexual blood-stage malaria infection. However, little is known of the regulatory factors involved in this process. In this study, we investigated the impact of MAPK phosphotase 5 (MKP5) on protective immunity against a lethal Plasmodium yoelii 17XL blood-stage infection using MKP5 knockout C57BL/6 mice. Compared with wild-type control mice, MKP5 knockout mice developed significantly lower parasite burdens with prolonged survival times. We found that this phenomenon correlated with a rapid and strong IFN-γ-dependent cellular immune response during the acute phase of infection. Inactivation of IFN-γ by the administration of a neutralizing Ab significantly reduced the protective effects in MKP5 knockout mice. By analyzing IFN-γ production in innate and adaptive lymphocyte subsets, we observed that MKP5 deficiency specifically enhanced the IFN-γ response mediated by CD4+ T cells, which was attributable to the increased stimulatory capacity of splenic CD11c+ dendritic cells. Furthermore, following vaccination with whole blood-stage soluble plasmodial Ag, MKP5 knockout mice acquired strongly enhanced Ag-specific immune responses and a higher level of protection against subsequent P. yoelii 17XL challenge. Finally, we found the enhanced response mediated by MKP5 deficiency resulted in a lethal consequence in mice when infected with nonlethal P. yoelii 17XNL. Thus, our data indicate that MKP5 is a potential regulator of immune resistance against Plasmodium infection in mice, and that an understanding of the role of MKP5 in manipulating anti-malaria immunity may provide valuable information on the development of better control strategies for human malaria.

  5. Lipocalin 2 bolsters innate and adaptive immune responses to blood-stage malaria infection by reinforcing host iron metabolism.

    PubMed

    Zhao, Hong; Konishi, Aki; Fujita, Yukiko; Yagi, Masanori; Ohata, Keiichi; Aoshi, Taiki; Itagaki, Sawako; Sato, Shintaro; Narita, Hirotaka; Abdelgelil, Noha H; Inoue, Megumi; Culleton, Richard; Kaneko, Osamu; Nakagawa, Atsushi; Horii, Toshihiro; Akira, Shizuo; Ishii, Ken J; Coban, Cevayir

    2012-11-15

    Plasmodium parasites multiply within host erythrocytes, which contain high levels of iron, and parasite egress from these cells results in iron release and host anemia. Although Plasmodium requires host iron for replication, how host iron homeostasis and responses to these fluxes affect Plasmodium infection are incompletely understood. We determined that Lipocalin 2 (Lcn2), a host protein that sequesters iron, is abundantly secreted during human (P. vivax) and mouse (P. yoeliiNL) blood-stage malaria infections and is essential to control P. yoeliiNL parasitemia, anemia, and host survival. During infection, Lcn2 bolsters both host macrophage function and granulocyte recruitment and limits reticulocytosis, or the expansion of immature erythrocytes, which are the preferred target cell of P. yoeliiNL. Additionally, a chronic iron imbalance due to Lcn2 deficiency results in impaired adaptive immune responses against Plasmodium parasites. Thus, Lcn2 exerts antiparasitic effects by maintaining iron homeostasis and promoting innate and adaptive immune responses.

  6. Rationale for one stage exchange of infected hip replacement using uncemented implants and antibiotic impregnated bone graft.

    PubMed

    Winkler, Heinz

    2009-09-04

    Infection of a total hip replacement (THR) is considered a devastating complication, necessitating its complete removal and thorough debridement of the site. It is undoubted that one stage exchange, if successful, would provide the best benefit both for the patient and the society. Still the fear of re-infection dominates the surgeons decisions and in the majority of cases directs them to multiple stage protocols. However, there is no scientifically based argument for that practice. Successful eradication of infection with two stage procedures is reported to average 80% to 98%. On the other hand a literature review of Jackson and Schmalzried (CORR 2000) summarizing the results of 1,299 infected hip replacements treated with direct exchange (almost exclusively using antibiotic loaded cement), reports of 1,077 (83%) having been successful. The comparable results suggest, that the major factor for a successful outcome with traditional approaches may be found in the quality of surgical debridement and dead space management. Failures in all protocols seem to be caused by small fragments of bacterial colonies remaining after debridement, whereas neither systemic antibiotics nor antibiotic loaded bone cement (PMMA) have been able to improve the situation significantly. Reasons for failure may be found in the limited sensitivity of traditional bacterial culturing and reduced antibiotic susceptibility of involved pathogens, especially considering biofilm formation. Whenever a new prosthesis is implanted into a previously infected site the surgeon must be aware of increased risk of failure, both in single or two stage revisions. Eventual removal therefore should be easy with low risk of additional damage to the bony substance. On the other hand it should also have potential of a good long term result in case of success. Cemented revisions generally show inferior long term results compared to uncemented techniques; the addition of antibiotics to cement reduces its

  7. Contribution of mammary epithelial cells to the immune response during early stages of a bacterial infection to Staphylococcus aureus

    PubMed Central

    2014-01-01

    To differentiate between the contribution of mammary epithelial cells (MEC) and infiltrating immune cells to gene expression profiles of mammary tissue during early stage mastitis, we investigated in goats the in vivo transcriptional response of MEC to an experimental intra mammary infection (IMI) with Staphylococcus aureus, using a non-invasive RNA sampling method from milk fat globules (MFG). Microarrays were used to record gene expression patterns during the first 24 hours post-infection (hpi). This approach was combined with laser capture microdissection of MEC from frozen slides of mammary tissue to analyze some relevant genes at 30 hpi. During the early stages post-inoculation, MEC play an important role in the recruitment and activation of inflammatory cells through the IL-8 signalling pathway and initiate a sharp induction of innate immune genes predominantly associated with the pro-inflammatory response. At 30 hpi, MEC express genes encoding different acute phase proteins, including SAA3, SERPINA1 and PTX3 and factors, such as S100A12, that contribute directly to fighting the infection. No significant change in the expression of genes encoding caseins was observed until 24 hpi, thus validating our experimental model to study early stages of infection before the occurrence of tissue damage, since the milk synthesis function is still operative. This is to our knowledge the first report showing in vivo, in goats, how MEC orchestrate the innate immune response to an IMI challenge with S. aureus. Moreover, the non-invasive sampling method of mammary representative RNA from MFG provides a valuable tool to easily follow the dynamics of gene expression in MEC to search for sensitive biomarkers in milk for early detection of mastitis and therefore, to successfully improve the treatment and thus animal welfare. PMID:24521038

  8. CD8+ T cells from a novel T cell receptor transgenic mouse induce liver-stage immunity that can be boosted by blood-stage infection in rodent malaria.

    PubMed

    Lau, Lei Shong; Fernandez-Ruiz, Daniel; Mollard, Vanessa; Sturm, Angelika; Neller, Michelle A; Cozijnsen, Anton; Gregory, Julia L; Davey, Gayle M; Jones, Claerwen M; Lin, Yi-Hsuan; Haque, Ashraful; Engwerda, Christian R; Nie, Catherine Q; Hansen, Diana S; Murphy, Kenneth M; Papenfuss, Anthony T; Miles, John J; Burrows, Scott R; de Koning-Ward, Tania; McFadden, Geoffrey I; Carbone, Francis R; Crabb, Brendan S; Heath, William R

    2014-05-01

    To follow the fate of CD8+ T cells responsive to Plasmodium berghei ANKA (PbA) infection, we generated an MHC I-restricted TCR transgenic mouse line against this pathogen. T cells from this line, termed PbT-I T cells, were able to respond to blood-stage infection by PbA and two other rodent malaria species, P. yoelii XNL and P. chabaudi AS. These PbT-I T cells were also able to respond to sporozoites and to protect mice from liver-stage infection. Examination of the requirements for priming after intravenous administration of irradiated sporozoites, an effective vaccination approach, showed that the spleen rather than the liver was the main site of priming and that responses depended on CD8α+ dendritic cells. Importantly, sequential exposure to irradiated sporozoites followed two days later by blood-stage infection led to augmented PbT-I T cell expansion. These findings indicate that PbT-I T cells are a highly versatile tool for studying multiple stages and species of rodent malaria and suggest that cross-stage reactive CD8+ T cells may be utilized in liver-stage vaccine design to enable boosting by blood-stage infections.

  9. Induction of immune response in macaque monkeys infected with simian-human immunodeficiency virus having the TNF-{alpha} gene at an early stage of infection

    SciTech Connect

    Shimizu, Yuya; Miyazaki, Yasuyuki; Ibuki, Kentaro; Suzuki, Hajime; Kaneyasu, Kentaro; Goto, Yoshitaka; Hayami, Masanori; Miura, Tomoyuki; Haga, Takeshi . E-mail: a0d518u@cc.miyazaki-u.ac.jp

    2005-12-20

    TNF-{alpha} has been implicated in the pathogenesis of, and the immune response against, HIV-1 infection. To clarify the roles of TNF-{alpha} against HIV-1-related virus infection in an SHIV-macaque model, we genetically engineered an SHIV to express the TNF-{alpha} gene (SHIV-TNF) and characterized the virus's properties in vivo. After the acute viremic stage, the plasma viral loads declined earlier in the SHIV-TNF-inoculated monkeys than in the parental SHIV (SHIV-NI)-inoculated monkeys. SHIV-TNF induced cell death in the lymph nodes without depletion of circulating CD4{sup +} T cells. SHIV-TNF provided some immunity in monkeys by increasing the production of the chemokine RANTES and by inducing an antigen-specific proliferation of lymphocytes. The monkeys immunized with SHIV-TNF were partly protected against a pathogenic SHIV (SHIV-C2/1) challenge. These findings suggest that TNF-{alpha} contributes to the induction of an effective immune response against HIV-1 rather than to the progression of disease at the early stage of infection.

  10. The Biting Midge Culicoides sonorensis (Diptera: Ceratopogonidae) Is Capable of Developing Late Stage Infections of Leishmania enriettii

    PubMed Central

    Seblova, Veronika; Sadlova, Jovana; Vojtkova, Barbora; Votypka, Jan; Carpenter, Simon; Bates, Paul Andrew; Volf, Petr

    2015-01-01

    Background Despite their importance in animal and human health, the epidemiology of species of the Leishmania enriettii complex remains poorly understood, including the identity of their biological vectors. Biting midges of the genus Forcipomyia (Lasiohelea) have been implicated in the transmission of a member of the L. enriettii complex in Australia, but the far larger and more widespread genus Culicoides has not been investigated for the potential to include vectors to date. Methodology/Principal Findings Females from colonies of the midges Culicoides nubeculosus Meigen and C. sonorensis Wirth & Jones and the sand fly Lutzomyia longipalpis Lutz & Nevia (Diptera: Psychodidae) were experimentally infected with two different species of Leishmania, originating from Australia (Leishmania sp. AM-2004) and Brazil (Leishmania enriettii). In addition, the infectivity of L. enriettii infections generated in guinea pigs and golden hamsters for Lu. longipalpis and C. sonorensis was tested by xenodiagnosis. Development of L. enriettii in Lu. longipalpis was relatively poor compared to other Leishmania species in this permissive vector. Culicoides nubeculosus was not susceptible to infection by parasites from the L. enriettii complex. In contrast, C. sonorensis developed late stage infections with colonization of the thoracic midgut and the stomodeal valve. In hamsters, experimental infection with L. enriettii led only to mild symptoms, while in guinea pigs L. enriettii grew aggressively, producing large, ulcerated, tumour-like lesions. A high proportion of C. sonorensis (up to 80%) feeding on the ears and nose of these guinea pigs became infected. Conclusions/Significance We demonstrate that L. enriettii can develop late stage infections in the biting midge Culicoides sonorensis. This midge was found to be susceptible to L. enriettii to a similar degree as Lutzomyia longipalpis, the vector of Leishmania infantum in South America. Our results support the hypothesis that some

  11. The stage-specific in vitro efficacy of a malaria antigen cocktail provides valuable insights into the development of effective multi-stage vaccines.

    PubMed

    Spiegel, Holger; Boes, Alexander; Kastilan, Robin; Kapelski, Stephanie; Edgue, Güven; Beiss, Veronique; Chubodova, Ivana; Scheuermayer, Matthias; Pradel, Gabriele; Schillberg, Stefan; Reimann, Andreas; Fischer, Rainer

    2015-10-01

    Multicomponent vaccines targeting different stages of Plasmodium falciparum represent a promising, holistic concept towards better malaria vaccines. Additionally, an effective vaccine candidate should demonstrate cross-strain specificity because many antigens are polymorphic, which can reduce vaccine efficacy. A cocktail of recombinant fusion proteins (VAMAX-Mix) featuring three diversity-covering variants of the blood-stage antigen PfAMA1, each combined with the conserved sexual-stage antigen Pfs25 and one of the pre-erythrocytic-stage antigens PfCSP_TSR or PfCelTOS, or the additional blood-stage antigen PfMSP1_19, was produced in Pichia pastoris and used to immunize rabbits. The immune sera and purified IgG were used to perform various assays determining antigen specific titers and in vitro efficacy against different parasite stages and strains. In functional in vitro assays we observed robust inhibition of blood-stage (up to 90%), and sexual-stage parasites (up to 100%) and biased inhibition of pre-erythrocytic parasites (0-40%). Cross-strain blood-stage efficacy was observed in erythrocyte invasion assays using four different P. falciparum strains. The quantification of antigen-specific IgGs allowed the determination of specific IC50 values. The significant difference in antigen-specific IC50 requirements, the direct correlation between antigen-specific IgG and the relative quantitative representation of antigens within the cocktail, provide valuable implementations for future multi-stage, multi-component vaccine designs.

  12. Transcriptional changes of cytokines in rooster testis and epididymis during sexual maturation stages and Salmonella infection.

    PubMed

    Anastasiadou, M; Michailidis, G

    2016-08-01

    Infection of rooster testis and epididymis by pathogens can lead to impaired fertility, resulting in economic losses in the poultry industry. Antimicrobial protection of rooster reproductive organs is, therefore, an important aspect of reproductive physiology. Salmonellosis is one of the most important zoonotic diseases, caused by Salmonella bacteria including Salmonella Enteritidis (SE) and is usually the result of infection of the reproductive organs. Thus, knowledge of the endogenous innate immune mechanisms of the rooster testis and epididymis is an emerging aspect of reproductive physiology. Cytokines are key factors for stimulating the immune response and inflammation in chickens to Salmonella infection. In the present study the expression profile of 11 pro-inflammatory cytokine genes in the rooster testis and epididymis in vivo and transcriptional changes in these organs during sexual maturation and SE infection were investigated. Gene expression analysis data revealed that in both testis and epididymis nine cytokines namely the IL-1β, IL-6, IL-8, IL-10, IL-12, IL-15, IL-16, IL-17 and IL-18 genes were expressed, while no mRNA transcripts were detected in both organs for IL-2 and IL-4. Furthermore, the expression of various cytokine genes during sexual maturation appeared to be developmentally regulated, while SE infection resulted in a significant up-regulation of IL-1β, -6, -12 and -18 genes in the testis and an increase in the mRNA relative abundance of IL-1β, -6, -12, -16 and -18 in the epididymis of SE-infected sexually mature 28-week-old roosters. These results suggest a cytokine-mediated immune response mechanism against Salmonella infection in the rooster reproductive tract.

  13. The effects of benzimidazoles on the larval stage of Toxocara cati in experimentally infected chickens.

    PubMed

    Oryan, A; Sadjjani, S M; Azizi, S

    2009-04-01

    Toxocara cati (T. cati) and Toxocara canis (T. canis), roundworms of cats and dogs, are zoonotic parasites that cause visceral and ocular larval migrans in human beings. Humans and other paratenic hosts are infected by ingesting the infective Toxocara eggs from contaminated soil, unwashed hands, contaminated raw vegetables or ingestion of under-cooked organs and muscle tissues of infected paratenic hosts such as chickens, cattle and sheep. It has been shown that the seroprevalence of toxocariasis in the rural and urban children of southern Iran is high and more than 50% of cats of this area are also infected with T. cati. It is stated that consumption of raw chicken meat resulted in visceral toxocariasis. It is possible that poultry reared outdoors and feeding in open range system, gain Toxocara eggs from soil and or by eating infected earthworms as paratenic host. The aim of the present study was to investigate the effects of albendazole and febendazole in experimentally infected chickens with eggs of T. cati by histopathological and digestive methods. Pathologic lesions were observed only in the untreated group and larvae were detected in brain of 3 chickens of this group by squash method. No larva was observed at histopathological level in liver, lungs, brain, cardiac and skeletal muscles and other examined organs of either treated or untreated animals. No lesion was seen in other tissues of the infected untreated chickens. Treatment resulted in disappearance of the larvae and disappearance of the gross and histopathologic abnormalities from their organs. No detectable difference was observed in chemosusceptibility of the two drugs.

  14. Multi-Agent Simulations of the Immune Response to Hiv during the Acute Stage of Infection

    NASA Astrophysics Data System (ADS)

    Walshe, R.; Ruskin, H. J.; Callaghan, A.

    Results of multi-agent based simulations of the immune response to HIV during the acute phase of infection are presented here. The model successfully recreates the viral dynamics associated with the acute phase of infection, i.e., a rapid rise in viral load followed by a sharp decline to what is often referred to as a "set point", a result of T-cell response and emergence of HIV neutralizing antibodies. The results indicate that sufficient T Killer cell response is the key factor in controlling viral growth during this phase with antibody levels of critical importance only in the absence of a sufficient T Killer response.

  15. Supplement of L-Arg improves protective immunity during early-stage Plasmodium yoelii 17XL infection.

    PubMed

    Zhu, X; Pan, Y; Li, Y; Cui, L; Cao, Y

    2012-01-01

    L-arginine (L-Arg), the precursor of nitric oxide (NO), plays multiple important roles in nutrient metabolism and immune regulation. L-Arg supplement serves as a potential adjunctive therapy for severe malaria, because it improves NO bioavailability and reverses endothelial dysfunction in severe malaria patients. In this study, we investigated the effect of dietary L-Arg supplement on host immune responses during subsequent malaria infection using the Plasmodium yoelii 17XL - BALB/c mouse model. We have shown that pretreatment of mice with L-Arg significantly decreased parasitemia and prolonged the survival time of mice after infection. L-Arg supplement led to significant increases in activated CD4(+)T-bet(+)IFN-γ(+) T cells and F4/80(+)CD36(+) macrophages during early-stage infection, which were accompanied by enhanced synthesis of IFN-γ, TNF-α and NO by spleen cells. Moreover, L-Arg-pretreated mice developed more splenic myeloid and plasmacytoid dendritic cells with up-regulated expression of MHC II, CD86 and TLR9. In comparison, L-Arg treatment did not change the number of regulatory T cells and the level of anti-inflammatory cytokine IL-10. Taken together, our results showed that L-Arg pretreatment could improve the protective immune response in experimental malaria infection in mice, which underlines potential importance of L-Arg supplement in malaria-endemic human populations.

  16. Metabolic profiles of soybean roots during early stages of Fusarium tucumaniae infection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Soybean germplasm exhibits various levels of resistance to Fusarium tucumaniae, the main causal agent of sudden death syndrome (SDS) of soybean in Argentina. In this study, two soybean genotypes, one susceptible (NA 4613) and one partially resistant (DM 4670) to SDS infection, were inoculated with F...

  17. Functional Impairment of Myeloid Dendritic Cells during Advanced Stage of HIV-1 Infection: Role of Factors Regulating Cytokine Signaling

    PubMed Central

    Sachdeva, Meenakshi; Sharma, Aman; Arora, Sunil K.

    2015-01-01

    Introduction Severely immunocompromised state during advanced stage of HIV-1 infection has been linked to functionally defective antigen presentation by dendritic cells (DCs). The molecular mechanisms behind DC impairment are still obscure. We investigated changes in DC function and association of key regulators of cytokine signaling during different stages of HIV-1 infection and following antiretroviral therapy (ART). Methods Phenotypic and functional characteristics of circulating myeloid DCs (mDCs) in 56 ART-naive patients (23 in early and 33 in advanced stage of disease), 36 on ART and 24 healthy controls were evaluated. Sixteen patients were studied longitudinally prior-to and 6 months after the start of ART. For functional studies, monocyte-derived DCs (Mo-DCs) were evaluated for endocytosis, allo-stimulation and cytokine secretion. The expression of suppressor of cytokine signaling (SOCS)-1 and other regulators of cytokine signaling was evaluated by real-time RT-PCR. Results The ability to respond to an antigenic stimulation was severely impaired in patients in advanced HIV-1 disease which showed partial recovery in the treated group. Mo-DCs from patients with advanced HIV-disease remained immature with low allo-stimulation and reduced cytokine secretion even after TLR-4 mediated stimulation ex-vivo. The cells had an increased expression of negative regulatory factors like SOCS-1, SOCS-3, SH2-containing phosphatase(SHP)-1 and a reduced expression of positive regulators like Janus kinase(JAK)2 and Nuclear factor kappa-light-chain-enhancer of activated B cells(NF-κB)1. A functional recovery after siRNA mediated silencing of SOCS-1 in these mo-DCs confirms the role of negative regulatory factors in functional impairment of these cells. Conclusions Functionally defective DCs in advanced stage of HIV-1 infection seems to be due to imbalanced state of negative and positive regulatory gene expression. Whether this is a cause or effect of increased viral

  18. Molecular basis of early stages of Clostridium difficile infection: germination and colonization.

    PubMed

    Sarker, Mahfuzur R; Paredes-Sabja, Daniel

    2012-08-01

    Clostridium difficile infections (CDIs) occur when antibiotic therapy disrupts the gastrointestinal flora, favoring infected C. difficile spores to germinate, outgrow, colonize and produce toxins. During CDI, C. difficile vegetative cells initiate the process of sporulation allowing a fraction of the spores to remain adhered to the intestinal surfaces. These spores, which are unaffected by antibiotic therapy commonly used for CDIs, then germinate, outgrow and recolonize the host's GI tract causing relapse of CDI. Consequently, the germination and colonization processes can be considered as the earliest and most essential steps for the development as well as relapse of CDI. The aim of this review is to provide an overview on the molecular basis involved in C. difficile spore germination and colonization.

  19. Iridovirus Bcl-2 protein inhibits apoptosis in the early stage of viral infection.

    PubMed

    Lin, Pei-Wen; Huang, Yi-Jen; John, Joseph Abraham Christopher; Chang, Ya-Nan; Yuan, Chung-Hsiang; Chen, Wen-Ya; Yeh, Chiao-Hwa; Shen, San-Tai; Lin, Fu-Pang; Tsui, Wen-Huei; Chang, Chi-Yao

    2008-01-01

    The grouper iridovirus (GIV) belongs to the family Iridoviridae, whose genome contains an antiapoptotic B-cell lymphoma (Bcl)-2-like gene. This study was carried-out to understand whether GIV blocks apoptosis in its host. UV-irradiated grouper kidney (GK) cells underwent apoptosis. However, a DNA fragmentation assay of UV-exposed GK cells after GIV infection revealed an inhibition of apoptosis. The UV- or heat-inactivated GIV failed to inhibit apoptosis, implying that a gene or protein of the viral particle might contribute to an apoptosis inhibitory function. The DNA ladder assay for GIV-infected GK cells after UV irradiation confirmed that apoptosis inhibition was an early process which occurred as early as 5 min post-infection. A GIV-Bcl sequence comparison showed distant sequence similarities to that of human and four viruses; however, all possessed the putative Bcl-2 homology (BH) domains of BH1, BH2, BH3, and BH4, as well as a transmembrane domain. Northern blot hybridization showed that GIV-Bcl transcription began at 2 h post-infection, and the mRNA level significantly increased in the presence of cycloheximide or aphidicolin, indicating that this GIV-Bcl is an immediate-early gene. This was consistent with the Western blot results, which also revealed that the virion carries the Bcl protein. We observed the localization of GIV-Bcl on the mitochondrial membrane and other defined intracellular areas. By immunostaining, it was proven that GIV-Bcl-expressing cells effectively inhibited apoptosis. Taken together, these results demonstrate that GIV inhibits the promotion of apoptosis by GK cells, which is mediated by the immediate early expressed viral Bcl gene.

  20. Surface Proteome of “Mycobacterium avium subsp. hominissuis” during the Early Stages of Macrophage Infection

    PubMed Central

    McNamara, Michael; Tzeng, Shin-Cheng; Maier, Claudia; Zhang, Li

    2012-01-01

    “Mycobacterium avium subsp. hominissuis” is a robust and pervasive environmental bacterium that can cause opportunistic infections in humans. The bacterium overcomes the host immune response and is capable of surviving and replicating within host macrophages. Little is known about the bacterial mechanisms that facilitate these processes, but it can be expected that surface-exposed proteins play an important role. In this study, the selective biotinylation of surface-exposed proteins, streptavidin affinity purification, and shotgun mass spectrometry were used to characterize the surface-exposed proteome of M. avium subsp. hominissuis. This analysis detected more than 100 proteins exposed at the bacterial surface of M. avium subsp. hominissuis. Comparisons of surface-exposed proteins between conditions simulating early infection identified several groups of proteins whose presence on the bacterial surface was either constitutive or appeared to be unique to specific culture conditions. This proteomic profile facilitates an improved understanding of M. avium subsp. hominissuis and how it establishes infection. Additionally, surface-exposed proteins are excellent targets for the host adaptive immune system, and their identification can inform the development of novel treatments, diagnostic tools, and vaccines for mycobacterial disease. PMID:22392927

  1. IFNAR1-Signalling Obstructs ICOS-mediated Humoral Immunity during Non-lethal Blood-Stage Plasmodium Infection

    PubMed Central

    Sebina, Ismail; James, Kylie R.; Soon, Megan S. F.; Best, Shannon E.; Montes de Oca, Marcela; Amante, Fiona H.; Thomas, Bryce S.; Beattie, Lynette; Souza-Fonseca-Guimaraes, Fernando; Smyth, Mark J.; Hertzog, Paul J.; Hill, Geoffrey R.; Engwerda, Christian R.

    2016-01-01

    Parasite-specific antibodies protect against blood-stage Plasmodium infection. However, in malaria-endemic regions, it takes many months for naturally-exposed individuals to develop robust humoral immunity. Explanations for this have focused on antigenic variation by Plasmodium, but have considered less whether host production of parasite-specific antibody is sub-optimal. In particular, it is unclear whether host immune factors might limit antibody responses. Here, we explored the effect of Type I Interferon signalling via IFNAR1 on CD4+ T-cell and B-cell responses in two non-lethal murine models of malaria, P. chabaudi chabaudi AS (PcAS) and P. yoelii 17XNL (Py17XNL) infection. Firstly, we demonstrated that CD4+ T-cells and ICOS-signalling were crucial for generating germinal centre (GC) B-cells, plasmablasts and parasite-specific antibodies, and likewise that T follicular helper (Tfh) cell responses relied on B cells. Next, we found that IFNAR1-signalling impeded the resolution of non-lethal blood-stage infection, which was associated with impaired production of parasite-specific IgM and several IgG sub-classes. Consistent with this, GC B-cell formation, Ig-class switching, plasmablast and Tfh differentiation were all impaired by IFNAR1-signalling. IFNAR1-signalling proceeded via conventional dendritic cells, and acted early by limiting activation, proliferation and ICOS expression by CD4+ T-cells, by restricting the localization of activated CD4+ T-cells adjacent to and within B-cell areas of the spleen, and by simultaneously suppressing Th1 and Tfh responses. Finally, IFNAR1-deficiency accelerated humoral immune responses and parasite control by boosting ICOS-signalling. Thus, we provide evidence of a host innate cytokine response that impedes the onset of humoral immunity during experimental malaria. PMID:27812214

  2. Fighting while Parasitized: Can Nematode Infections Affect the Outcome of Staged Combat in Beetles?

    PubMed Central

    Vasquez, David; Willoughby, Anna; Davis, Andrew K.

    2015-01-01

    The effects of non-lethal parasites may be felt most strongly when hosts engage in intense, energy-demanding behaviors. One such behavior is fighting with conspecifics, which is common among territorial animals, including many beetle species. We examined the effects of parasites on the fighting ability of a saproxylic beetle, the horned passalus (Odontotaenius disjunctus, Family: Passalidae), which is host to a non-lethal nematode, Chondronema passali. We pitted pairs of randomly-chosen (but equally-weighted) beetles against each other in a small arena and determined the winner and aggression level of fights. Then we examined beetles for the presence, and severity of nematode infections. There was a non-significant tendency (p = 0.065) for the frequency of wins, losses and draws to differ between beetles with and without C. passali; non-parasitized individuals (n = 104) won 47% of their fights while those with the parasite (n = 88) won 34%, a 13% difference in wins. The number of nematodes in a beetle affected the outcome of fights between infected and uninfected individuals in an unexpected fashion: fighting ability was lowest in beetles with the lowest (p = 0.033), not highest (p = 0.266), nematode burdens. Within-fight aggression was highest when both beetles were uninfected and lowest when both were infected (p = 0.034). Collectively, these results suggest the nematode parasite, C. passali, is associated with a modest reduction in fighting ability in horned passalus beetles, consistent with the idea that parasitized beetles have lower energy available for fighting. This study adds to a small but growing body of evidence showing how parasites negatively influence fighting behavior in animals. PMID:25830367

  3. Experimental caprine neosporosis: the influence of gestational stage on the outcome of infection.

    PubMed

    Porto, Wagnner José Nascimento; Regidor-Cerrillo, Javier; Kim, Pomy de Cássia Peixoto; Benavides, Julio; Silva, Ana Clécia dos Santos; Horcajo, Pilar; Oliveira, Andrea Alice da Fonseca; Ferre, Ignacio; Mota, Rinaldo Aparecido; Ortega-Mora, Luis Miguel

    2016-02-11

    Here, we assessed outcome of experimental infection by Neospora caninum in goats intravenously inoculated with 10(6) tachyzoites of the Nc-Spain7 isolate at 40 (G1), 90 (G2) and 120 (G3) days of gestation. Infected goats had fever between 5 and 9 days post inoculation (dpi); all were seropositive at the time of abortion/birth. Foetal death occurred in G1 from 10 to 21 dpi (n = 7) and in G2 from 27 to 35 dpi (n = 4). Goats in G2 also had seropositive stillbirth (n = 1) and healthy kids (n = 2). G3 goats (n = 7) had 3 seropositive and 3 seronegative weak kids, and 2 seronegative healthy kids. Parasite DNA detection in placentomes was 100% in G2, 85.7% in G3 and in G1 was detected only in placentomes from the goats with foetal losses from 17 dpi (100%). Parasites were detected in foetal/kid brain (>85.7%) and liver (≥ 50%) of G2 and G3, and in G1 after 17 dpi (100%). The highest parasite loads were detected in the placentomes of G1 from 17 dpi and G2, and in foetal tissues of G1 from 17 dpi and G3. Multifocal necrotic lesions were observed in the placentas of the three groups, but they were larger and more frequent in G1 and G2. Similar lesions were observed in foetal tissues, but they were more frequent in G3. These findings suggest that, as observed in cattle and sheep, the clinical consequences of N. caninum in pregnant goats are dependent in part on the time of gestation when animals were infected.

  4. Depressed Hypoxic and Hypercapnic Ventilatory Responses at Early Stage of Lethal Avian Influenza A Virus Infection in Mice

    PubMed Central

    Pollock, Zemmie; Harrod, Kevin S.; Xu, Fadi

    2016-01-01

    H5N1 virus infection results in ~60% mortality in patients primarily due to respiratory failure, but the underlying causes of mortality are unclear. The goal of this study is to reveal respiratory disorders occurring at the early stage of infection that may be responsible for subsequent respiratory failure and death. BALB/c mice were intranasally infected with one of two H5N1 virus strains: HK483 (lethal) or HK486 (non-lethal) virus. Pulmonary ventilation and the responses to hypoxia (HVR; 7% O2 for 3 min) and hypercapnia (HCVR; 7% CO2 for 5 min) were measured daily at 2 days prior and 1, 2, and 3 days postinfection (dpi) and compared to mortality typically by 8 dpi. At 1, 2, and 3 dpi, immunoreactivities (IR) of substance P (SP-IR) in the nodose ganglion or tyrosine hydroxylase (TH-IR) in the carotid body coupled with the nucleoprotein of influenza A (NP-IR) was examined in some mice, while arterial blood was collected in others. Our results showed that at 2 and 3 dpi: 1) both viral infections failed to alter body temperature and weight, V˙CO2, or induce viremia while producing similarly high lung viral titers; 2) HK483, but not HK486, virus induced tachypnea and depressed HVR and HCVR without changes in arterial blood pH and gases; and 3) only HK483 virus led to NP-IR in vagal SP-IR neurons, but not in the carotid body, and increased density of vagal SP-IR neurons. In addition, all HK483, rather than HK486, mice died at 6 to 8 dpi and the earlier death was correlated with more severe depression of HVR and HCVR. Our data suggest that tachypnea and depressed HVR/HCVR occur at the early stage of lethal H5N1 viral infection associated with viral replication and increased SP-IR density in vagal neurons, which may contribute to the respiratory failure and death. PMID:26808681

  5. A lethal case of Plasmodium falciparum infection in a young patient with end-stage renal failure who underwent regular hemodialysis.

    PubMed

    Hartopo, Anggoro Budi; Wijisaksono, Doni Priambodo

    2010-01-01

    Acute renal failure associated with Plasmodium falciparum infection is already well recognized. Nevertheless, end-stage chronic renal failure and falciparum malaria comorbidity is a rare condition. We report a case of Plasmodium falciparum infection in a young male Javanese patient with end-stage chronic renal failure who underwent regular hemodialysis. This rare comorbidity led to rapid deterioration of consciousness and metabolic disturbances which had already existed in end-stage renal failure. Because of the immunosuppressive condition due to organ failure, the patient did not survive despite anti-malarial chemotherapy.

  6. Pf155/RESA protein influences the dynamic microcirculatory behavior of ring-stage Plasmodium falciparum infected red blood cells

    PubMed Central

    Diez-Silva, Monica; Park, YongKeun; Huang, Sha; Bow, Hansen; Mercereau-Puijalon, Odile; Deplaine, Guillaume; Lavazec, Catherine; Perrot, Sylvie; Bonnefoy, Serge; Feld, Michael S.; Han, Jongyoon; Dao, Ming; Suresh, Subra

    2012-01-01

    Proteins exported by Plasmodium falciparum to the red blood cell (RBC) membrane modify the structural properties of the parasitized RBC (Pf-RBC). Although quasi-static single cell assays show reduced ring-stage Pf-RBCs deformability, the parameters influencing their microcirculatory behavior remain unexplored. Here, we study the dynamic properties of ring-stage Pf-RBCs and the role of the parasite protein Pf155/Ring-Infected Erythrocyte Surface Antigen (RESA). Diffraction phase microscopy revealed RESA-driven decreased Pf-RBCs membrane fluctuations. Microfluidic experiments showed a RESA-dependent reduction in the Pf-RBCs transit velocity, which was potentiated at febrile temperature. In a microspheres filtration system, incubation at febrile temperature impaired traversal of RESA-expressing Pf-RBCs. These results show that RESA influences ring-stage Pf-RBCs microcirculation, an effect that is fever-enhanced. This is the first identification of a parasite factor influencing the dynamic circulation of young asexual Pf-RBCs in physiologically relevant conditions, offering novel possibilities for interventions to reduce parasite survival and pathogenesis in its human host. PMID:22937223

  7. Infections of Larval Stages of Dicrocoelium dendriticum and Brachylaima sp. in Brown Garden Snail, Helix aspersa, in Turkey

    PubMed Central

    Köse, Mustafa; Eser, Mustafa; Kartal, Kürşat; Bozkurt, Mehmet Fatih

    2015-01-01

    The aim of this study was to determine the presence and prevalence of larval stages of Dicrocoelium dendriticum and Brachylaima sp. in the first intermediate host, a species of land snail, Helix aspersa, in Turkey. A total of 211 snails were collected in April-May 2014 from pastures in Mersin District. Larval stages of D. dendriticum were identified under a light microscope. Hepatopancreas from naturally infected H. aspersa snails were examined histologically. The prevalence of larval stages of D. dendriticum and Brachylaima sp. in H. aspersa snails was found to be 2.4% and 1.9%, respectively, in Mersin, Turkey. Cercariae were not matured in sporocysts at the beginning of April; however, it was observed that cercariae matured and started to leave sporocysts by early-May. Thus, it was concluded that H. aspersa acts as an intermediate host to D. dendriticumin and Brachylaima sp. in Mersin, Turkey. A digenean trematode Brachylaima sp. was seen for the first time in Turkey. PMID:26537045

  8. Infections of Larval Stages of Dicrocoelium dendriticum and Brachylaima sp. in Brown Garden Snail, Helix aspersa, in Turkey.

    PubMed

    Köse, Mustafa; Eser, Mustafa; Kartal, Kürşat; Bozkurt, Mehmet Fatih

    2015-10-01

    The aim of this study was to determine the presence and prevalence of larval stages of Dicrocoelium dendriticum and Brachylaima sp. in the first intermediate host, a species of land snail, Helix aspersa, in Turkey. A total of 211 snails were collected in April-May 2014 from pastures in Mersin District. Larval stages of D. dendriticum were identified under a light microscope. Hepatopancreas from naturally infected H. aspersa snails were examined histologically. The prevalence of larval stages of D. dendriticum and Brachylaima sp. in H. aspersa snails was found to be 2.4% and 1.9%, respectively, in Mersin, Turkey. Cercariae were not matured in sporocysts at the beginning of April; however, it was observed that cercariae matured and started to leave sporocysts by early-May. Thus, it was concluded that H. aspersa acts as an intermediate host to D. dendriticumin and Brachylaima sp. in Mersin, Turkey. A digenean trematode Brachylaima sp. was seen for the first time in Turkey.

  9. Pf155/RESA protein influences the dynamic microcirculatory behavior of ring-stage Plasmodium falciparum infected red blood cells

    NASA Astrophysics Data System (ADS)

    Diez-Silva, Monica; Park, Yongkeun; Huang, Sha; Bow, Hansen; Mercereau-Puijalon, Odile; Deplaine, Guillaume; Lavazec, Catherine; Perrot, Sylvie; Bonnefoy, Serge; Feld, Michael S.; Han, Jongyoon; Dao, Ming; Suresh, Subra

    2012-08-01

    Proteins exported by Plasmodium falciparum to the red blood cell (RBC) membrane modify the structural properties of the parasitized RBC (Pf-RBC). Although quasi-static single cell assays show reduced ring-stage Pf-RBCs deformability, the parameters influencing their microcirculatory behavior remain unexplored. Here, we study the dynamic properties of ring-stage Pf-RBCs and the role of the parasite protein Pf155/Ring-Infected Erythrocyte Surface Antigen (RESA). Diffraction phase microscopy revealed RESA-driven decreased Pf-RBCs membrane fluctuations. Microfluidic experiments showed a RESA-dependent reduction in the Pf-RBCs transit velocity, which was potentiated at febrile temperature. In a microspheres filtration system, incubation at febrile temperature impaired traversal of RESA-expressing Pf-RBCs. These results show that RESA influences ring-stage Pf-RBCs microcirculation, an effect that is fever-enhanced. This is the first identification of a parasite factor influencing the dynamic circulation of young asexual Pf-RBCs in physiologically relevant conditions, offering novel possibilities for interventions to reduce parasite survival and pathogenesis in its human host.

  10. Experimental infections of rabbits with proliferative and latent stages of Besnoitia besnoiti.

    PubMed

    Liénard, Emmanuel; Pop, Loredana; Prevot, Françoise; Grisez, Christelle; Mallet, Virginie; Raymond-Letron, Isabelle; Bouhsira, Émilie; Franc, Michel; Jacquiet, Philippe

    2015-10-01

    Cattle besnoitiosis due to Besnoitia besnoiti is spreading across Europe and is responsible for severe economic losses in newly infected herds. Experimentally speaking, rabbits have been found to be susceptible to this parasite. The adaptation of B. besnoiti to rabbits may offer a new, easier and cheaper model of investigation for this disease. This study compared the virulence between tachyzoites and bradyzoites of B. besnoiti in rabbits. Eighteen New Zealand rabbits were allocated into three groups of six animals each. The rabbits from the control (group C), "tachyzoite" (group T) and "bradyzoite" (group B) groups were subcutaneously injected in the right flank with 66 μg of ovalbumin, 6.10(6) tachyzoites (125th passage on Vero cells) and 6.10(6) bradyzoites (collected from a natural infected cow) of B. besnoiti, respectively. Clinical follow-up and blood sampling for serological survey and qPCR were performed during 10 weeks until euthanasia. Molecular and immunohistochemistry examination was achieved on 25 samples of tissue per rabbit. Seroconversion occurred in group T without any clinical signs. Rabbits of group B exhibited a febrile condition (temperature above 40 °C from day 8 to day 11 following injection) with positive qPCR in blood. Cysts of B. besnoiti were found on skin samples and organs of rabbits from group B in tissue explored with threshold cycle (Ct) values below 30. These results suggest a higher virulence of bradyzoites in rabbits than Vero cell-cultivated tachyzoites. The proposed model could be used to assess the in vivo effectiveness of vaccine or drugs against cattle besnoitiosis.

  11. Signaling Strategies of Malaria Parasite for Its Survival, Proliferation, and Infection during Erythrocytic Stage.

    PubMed

    Soni, Rani; Sharma, Drista; Rai, Praveen; Sharma, Bhaskar; Bhatt, Tarun K

    2017-01-01

    Irrespective of various efforts, malaria persist the most debilitating effect in terms of morbidity and mortality. Moreover, the existing drugs are also vulnerable to the emergence of drug resistance. To explore the potential targets for designing the most effective antimalarial therapies, it is required to focus on the facts of biochemical mechanism underlying the process of parasite survival and disease pathogenesis. This review is intended to bring out the existing knowledge about the functions and components of the major signaling pathways such as kinase signaling, calcium signaling, and cyclic nucleotide-based signaling, serving the various aspects of the parasitic asexual stage and highlighted the Toll-like receptors, glycosylphosphatidylinositol-mediated signaling, and molecular events in cytoadhesion, which elicit the host immune response. This discussion will facilitate a look over essential components for parasite survival and disease progression to be implemented in discovery of novel antimalarial drugs and vaccines.

  12. Signaling Strategies of Malaria Parasite for Its Survival, Proliferation, and Infection during Erythrocytic Stage

    PubMed Central

    Soni, Rani; Sharma, Drista; Rai, Praveen; Sharma, Bhaskar; Bhatt, Tarun K.

    2017-01-01

    Irrespective of various efforts, malaria persist the most debilitating effect in terms of morbidity and mortality. Moreover, the existing drugs are also vulnerable to the emergence of drug resistance. To explore the potential targets for designing the most effective antimalarial therapies, it is required to focus on the facts of biochemical mechanism underlying the process of parasite survival and disease pathogenesis. This review is intended to bring out the existing knowledge about the functions and components of the major signaling pathways such as kinase signaling, calcium signaling, and cyclic nucleotide-based signaling, serving the various aspects of the parasitic asexual stage and highlighted the Toll-like receptors, glycosylphosphatidylinositol-mediated signaling, and molecular events in cytoadhesion, which elicit the host immune response. This discussion will facilitate a look over essential components for parasite survival and disease progression to be implemented in discovery of novel antimalarial drugs and vaccines.

  13. Analysis of the Transcriptome of the Infective Stage of the Beet Cyst Nematode, H. schachtii

    PubMed Central

    Fosu-Nyarko, John; Nicol, Paul; Naz, Fareeha; Gill, Reetinder; Jones, Michael G. K.

    2016-01-01

    The beet cyst nematode, Heterodera schachtii, is a major root pest that significantly impacts the yield of sugar beet, brassicas and related species. There has been limited molecular characterisation of this important plant pathogen: to identify target genes for its control the transcriptome of the pre-parasitic J2 stage of H. schachtii was sequenced using Roche GS FLX. Ninety seven percent of reads (i.e., 387,668) with an average PHRED score > 22 were assembled with CAP3 and CLC Genomics Workbench into 37,345 and 47,263 contigs, respectively. The transcripts were annotated by comparing with gene and genomic sequences of other nematodes and annotated proteins on public databases. The annotated transcripts were much more similar to sequences of Heterodera glycines than to those of Globodera pallida and root knot nematodes (Meloidogyne spp.). Analysis of these transcripts showed that a subset of 2,918 transcripts was common to free-living and plant parasitic nematodes suggesting that this subset is involved in general nematode metabolism and development. A set of 148 contigs and 183 singletons encoding putative homologues of effectors previously characterised for plant parasitic nematodes were also identified: these are known to be important for parasitism of host plants during migration through tissues or feeding from cells or are thought to be involved in evasion or modulation of host defences. In addition, the presence of sequences from a nematode virus is suggested. The sequencing and annotation of this transcriptome significantly adds to the genetic data available for H. schachtii, and identifies genes primed to undertake required roles in the critical pre-parasitic and early post-parasitic J2 stages. These data provide new information for identifying potential gene targets for future protection of susceptible crops against H. schachtii. PMID:26824923

  14. Sensitivity of two in vitro assays for evaluating plant activity against the infective stage of Haemonchus contortus strains.

    PubMed

    Al-Rofaai, A; Rahman, W A; Abdulghani, Mahfoudh

    2013-02-01

    The sensitivity of larval paralysis assay (LPA) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide-formazan (MTT-formazan) assay was compared to evaluate the anthelmintic activity of plant extracts. In this study, the methanolic extract of Azadirachta indica (neem) was evaluated for its activity against the infective-stage larvae (L(3)) of susceptible and resistant Haemonchus contortus strains using the two aforementioned assays. In both in vitro assays, the same serial concentrations of the extract were used, and the median lethal concentrations were determined to compare the sensitivity of both assays. The results revealed a significant difference (P < 0.05) in the sensitivity of the LPA and the MTT-formazan assay. The MTT-formazan assay is more feasible for practical applications because it measured the L(3) mortality more accurately than LPA. This study may help find a suitable assay for investigating the anthelmintic activity of plant extracts against trichostrongylid nematodes.

  15. Simultaneous versus sequential one-stage combined anterior and posterior spinal surgery for spinal infections (outcomes and complications)

    PubMed Central

    Ozturk, Cagatay; Vural, Recep; Sehirlioglu, Ali; Mutlu, Muren

    2006-01-01

    To compare simultaneous with sequential one-stage (same anaesthesia) combined anterior and posterior spinal surgery in the treatment of spinal infections in terms of the operation time, blood loss and complication rate. Fifty-six patients who underwent one-stage (same anaesthesia) simultaneous or sequential anterior decompression and posterior stabilisation of the involved vertebrae for spinal infection from January 1994 to December 2002 were reviewed. In group I (n=29), sequential anterior and posterior surgery was performed. In group II (n=27), simultaneous anterior and posterior spinal surgery was performed. With regard to age and gender, there was no statistical difference between both groups (P=0.05). The analysed and compared data between the two groups included the age, gender, blood loss, operation time and postoperative complications. There was a statistically significant difference between the two groups in terms of the duration of surgery, amount of blood transfusion needed and occurrence of major postoperative complications (P<0.05). The mean correction of the kyphotic deformity was similar in both groups (P>0.05) without a subsequent loss of correction on follow-up radiographic films at a mean follow-up of 6.5 years (range, 3 to 11 years). Simultaneous anterior and posterior surgery is a good alternative procedure. It provides the ability to manipulate both anterior and posterior aspects of the spine at the same time and appears to result in less blood loss, a shorter operative time and fewer complications. However, gaining experience and the availability of two surgical teams are important factors in the success of the procedure. PMID:16736143

  16. Lack of flagella disadvantages Salmonella enterica serovar Enteritidis during the early stages of infection in the rat.

    PubMed

    Robertson, Jeanette M C; McKenzie, Norma H; Duncan, Michelle; Allen-Vercoe, Emma; Woodward, Martin J; Flint, Harry J; Grant, George

    2003-01-01

    The roles of flagella and five fimbriae (SEF14, SEF17, SEF21, pef, lpf) in the early stages (up to 3 days) of Salmonella enterica serovar Enteritidis (S. Enteritidis) infection have been investigated in the rat. Wild-type strains LA5 and S1400 (fim+/fla+) and insertionally inactivated mutants unable to express the five fimbriae (fim-/fla+), flagella (fim+/fla-) or fimbriae and flagella (fim-/fla-) were used. All wild-type and mutant strains were able to colonize the gut and spread to the mesenteric lymph nodes, liver and spleen. There appeared to be little or no difference between the fim-/fla+ and wild-type (fim+/fla+) strains. In contrast, the numbers of aflagellate (fim+/fla- or fim-/fla-) salmonella in the liver and spleen were transiently reduced. In addition, fim+/fla- or fim-/fla- strains were less able to persist in the upper gastrointestinal tract and the inflammatory responses they elicited in the gut were less severe. Thus, expression of SEF14, SEF17, SEF21, pef and lpf did not appear to be a prerequisite for induction of S. Enteritidis infection in the rat. Deletion of flagella did, however, disadvantage the bacterium. This may be due to the inability to produce or release the potent immunomodulating protein flagellin.

  17. Host PI(3,5)P2 activity is required for Plasmodium berghei growth during liver stage infection

    PubMed Central

    Thieleke-Matos, Carolina; da Silva, Mafalda Lopes; Cabrita-Santos, Laura; Pires, Cristiana F.; Ramalho, José S.; Ikonomov, Ognian; Seixas, Elsa; Shisheva, Assia; Seabra, Miguel C.; Barral, Duarte C.

    2014-01-01

    Malaria parasites go through an obligatory liver stage before they infect erythrocytes and cause disease symptoms. In the host hepatocytes, the parasite is enclosed by a parasitophorous vacuole membrane (PVM). Here, we dissected the interaction between the Plasmodium parasite and the host cell late endocytic pathway and show that parasite growth is dependent on the phosphoinositide 5-kinase (PIKfyve), which converts phosphatidylinositol 3-phosphate [PI(3)P] into phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2] in the endosomal system. We found that inhibition of PIKfyve either by pharmacological or non-pharmacological means causes a delay in parasite growth. Moreover, we show that the PI(3,5)P2 effector protein TRPML1 that is involved in late endocytic membrane fusion, is present in vesicles closely contacting the PVM and is necessary for parasite growth. Thus, our studies suggest that the parasite PVM is able to fuse with host late endocytic vesicles in a PI(3,5)P2-dependent manner, allowing the exchange of material between the host and the parasite, which is essential for successful infection. PMID:24992508

  18. Association of caveolin with Chlamydia trachomatis inclusions at early and late stages of infection.

    PubMed

    Norkin, L C; Wolfrom, S A; Stuart, E S

    2001-06-10

    The mechanism by which the intracellular bacterial pathogen Chlamydia trachomatis enters eukaryotic cells is poorly understood. There are conflicting reports of entry occurring by clathrin-dependent and clathrin-independent processes. We report here that C. trachomatis serovar K enters HEp-2 and HeLa 229 epithelial cells and J-774A.1 mouse macrophage/monocyte cells via caveolin-containing sphingolipid and cholesterol-enriched raft microdomains in the host cell plasma membranes. First, filipin and nystatin, drugs that specifically disrupt raft function by cholesterol chelation, each impaired entry of C. trachomatis serovar K. In control experiments, filipin did not impair entry of the same organism by an antibody-mediated opsonic process, nor did it impair entry of BSA-coated microspheres. Second, the chlamydia-containing endocytic vesicles specifically reacted with antisera against the caveolae marker protein caveolin. These vesicles are known to become the inclusions in which parasite replication occurs. They avoid fusion with lysosomes and instead traffic to the Golgi region, where they intercept Golgi-derived vesicles that recycle sphingolipids and cholesterol to the plasma membrane. We also report that late-stage C. trachomatis inclusions continue to display high levels of caveolin, which they likely acquire from the exocytic Golgi vesicles. We suggest that the atypical raft-mediated entry process may have important consequences for the host-pathogen interaction well after entry has occurred. These consequences include enabling the chlamydial vesicle to avoid acidification and fusion with lysosomes, to traffic to the Golgi region, and to intercept sphingolipid-containing vesicles from the Golgi.

  19. Infection of Goose with Genotype VIId Newcastle Disease Virus of Goose Origin Elicits Strong Immune Responses at Early Stage

    PubMed Central

    Xu, Qianqian; Chen, Yuqiu; Zhao, Wenjun; Zhang, Tingting; Liu, Chenggang; Qi, Tianming; Han, Zongxi; Shao, Yuhao; Ma, Deying; Liu, Shengwang

    2016-01-01

    Newcastle disease (ND), caused by virulent strains of Newcastle disease virus (NDV), is a highly contagious disease of birds that is responsible for heavy economic losses for the poultry industry worldwide. However, little is known about host-virus interactions in waterfowl, goose. In this study, we aim to characterize the host immune response in goose, based on the previous reports on the host response to NDV in chickens. Here, we evaluated viral replication and mRNA expression of 27 immune-related genes in 10 tissues of geese challenged with a genotype VIId NDV strain of goose origin (go/CH/LHLJ/1/06). The virus showed early replication, especially in digestive and immune tissues. The expression profiles showed up-regulation of Toll-like receptor (TLR)1–3, 5, 7, and 15, avian β-defensin (AvBD) 5–7, 10, 12, and 16, cytokines [interleukin (IL)-8, IL-18, IL-1β, and interferon-γ], inducible NO synthase (iNOS), and MHC class I in some tissues of geese in response to NDV. In contrast, NDV infection suppressed expression of AvBD1 in cecal tonsil of geese. Moreover, we observed a highly positive correlation between viral replication and host mRNA expressions of TLR1-5 and 7, AvBD4-6, 10, and 12, all the cytokines measured, MHC class I, FAS ligand, and iNOS, mainly at 72 h post-infection. Taken together, these results demonstrated that NDV infection induces strong innate immune responses and intense inflammatory responses at early stage in goose which may associate with the viral pathogenesis. PMID:27757109

  20. Circulation of HIV antigen in blood according to stage of infection, risk group, age and geographic origin.

    PubMed

    Goudsmit, J; Paul, D A

    1987-12-01

    Human immunodeficiency virus antigen (HIV-ag) was determined by enzyme immunoassay (EIA) in HIV-antibody (anti-HIV) positive as well as pre-anti-HIV seroconversion sera and the results analysed according to stage of infection, risk group, age and geographic origin. Eleven (19%) of 58 homosexual men tested showed HIV-ag in a serum taken 3-4 months before or one at the time of anti-HIV seroconversion. In another eight (14%) HIV-ag persisted after seroconversion and half of them developed AIDS or AIDS-related complex (ARC) in contrast to none of the other 50 anti-HIV seroconversions. Two (13%) of 16 haemophiliacs tested had HIV-ag only in the first anti-HIV seropositive sample. HIV-ag was present in 86% (30/35) of Dutch homosexual men with AIDS, in 32% (7/22) of men with ARC and in 17% (24/145) of men with persistent generalized lymphadenopathy (PGL) or without symptoms. Three percent (2/60) of sera of asymptomatic i.v. drug users from Amsterdam were HIV-ag positive. Ten percent (1 of 10) of sera from Central Africans with 'Slim Disease' were HIV-ag positive. Among infected children from the USA or Europe 89-100% (8/9 and 2/2) of AIDS cases, 67-100% (6/9 and 3/3) of children with ARC and 75% (3/4) of asymptomatic children were HIV-ag positive. The HIV-ag EIA appears to be able to identify HIV infection earlier than the available anti-HIV assays in a significant number of cases. Since persistence of HIV-ag, except possibly in African cases, is strongly associated with clinical deterioration, HIV-ag appears to be a suitable marker for, independent of their clinical status, selecting individuals for antiviral therapy and also for monitoring the efficiency of such therapy.

  1. Infection of Goose with Genotype VIId Newcastle Disease Virus of Goose Origin Elicits Strong Immune Responses at Early Stage.

    PubMed

    Xu, Qianqian; Chen, Yuqiu; Zhao, Wenjun; Zhang, Tingting; Liu, Chenggang; Qi, Tianming; Han, Zongxi; Shao, Yuhao; Ma, Deying; Liu, Shengwang

    2016-01-01

    Newcastle disease (ND), caused by virulent strains of Newcastle disease virus (NDV), is a highly contagious disease of birds that is responsible for heavy economic losses for the poultry industry worldwide. However, little is known about host-virus interactions in waterfowl, goose. In this study, we aim to characterize the host immune response in goose, based on the previous reports on the host response to NDV in chickens. Here, we evaluated viral replication and mRNA expression of 27 immune-related genes in 10 tissues of geese challenged with a genotype VIId NDV strain of goose origin (go/CH/LHLJ/1/06). The virus showed early replication, especially in digestive and immune tissues. The expression profiles showed up-regulation of Toll-like receptor (TLR)1-3, 5, 7, and 15, avian β-defensin (AvBD) 5-7, 10, 12, and 16, cytokines [interleukin (IL)-8, IL-18, IL-1β, and interferon-γ], inducible NO synthase (iNOS), and MHC class I in some tissues of geese in response to NDV. In contrast, NDV infection suppressed expression of AvBD1 in cecal tonsil of geese. Moreover, we observed a highly positive correlation between viral replication and host mRNA expressions of TLR1-5 and 7, AvBD4-6, 10, and 12, all the cytokines measured, MHC class I, FAS ligand, and iNOS, mainly at 72 h post-infection. Taken together, these results demonstrated that NDV infection induces strong innate immune responses and intense inflammatory responses at early stage in goose which may associate with the viral pathogenesis.

  2. Point prevalence of infection with Mycoplasma bovoculi and Moraxella spp. in cattle at different stages of infectious bovine keratoconjunctivitis.

    PubMed

    Schnee, Christiane; Heller, Martin; Schubert, Evelyn; Sachse, Konrad

    2015-01-01

    Infectious bovine keratoconjunctivitis (IBK) has significant economic consequences and a detrimental impact on animal welfare. Although Moraxella (Mor.) bovis is the primary causative agent, the role of other bacteria, such as Mor. ovis, Mor. bovoculi and Mycoplasma (Myc.) bovoculi, is not well understood. To assess the prevalence of infection with these organisms, and to correlate this with outbreaks of IBK, conjunctival samples from four herds of cattle in Germany of differing IBK status were examined. Herds were selected to represent a hypothetical course of IBK ranging from the pre-outbreak stage (herd 1), to the acute disease stage (herd 2), to a stage where treatment had ceased (herd 3). Unaffected animals were also included (herd 4). To facilitate effective, sensitive sample analysis, a new real-time PCR for Myc. bovoculi was developed and used in concert with established real-time PCR protocols for Myc. bovis and Moraxella spp. Herds 1 and 2 showed similarly high rates of detection for Myc. bovoculi (92.5% and 84.0%, respectively), whereas herds 3 and 4 had a lower prevalence (35.5% and 26.2%, respectively). Mor. bovis and Mor. ovis were more prevalent in herd 1 (32.5% and 87.5%, respectively) and herd 2 (38% and 58%, respectively) than herd 3 (10.4% and 1.3%, respectively) and herd 4 (9.8% and 31.1%, respectively). Mor. bovoculi was the only pathogen that correlated with clinical signs of IBK; at 20% prevalence, it was almost exclusively detected in herd 2. The results indicate that herds with high Myc. bovoculi prevalence are more predisposed to outbreaks of IBK, possibly due to a synergistic interaction with Moraxella spp.

  3. Ultrastructure study of the excretory system and the genital primordium of the infective stage of Onchocerca volvulus (Nematoda:Filarioidea).

    PubMed

    Strote, G; Bonow, I

    1995-01-01

    The electron microscopic investigation of the anterior part of the infective third-stage juvenile of Onchocerca volvulus provides first insights into the structure of the excretory system of this developmental stage of the parasite. The most anterior part of this system consists of a cell process of the syncytial excretory cells. At this height the excretory cells enclose the cuticle-lined excretory channel. The channel is in the process of elongation in the anterior-posterior direction, indicated by cell division in this region. More posteriad an ampulla-like structure is forming in the cytoplasm of the excretory cells. The inner surface of this ampulla is lined with a small number of single microvilli. In this part of the system the cytoplasm of the excretory cells is rich in Golgi bodies and endocytic vesicles. The ampulla has direct access to the exterior by the excretory duct. The excretory duct is a cuticle-lined structure surrounded by supporting fibres of an additional cell. This duct cell connects the excretory duct to the body-wall cuticle at the excretory pore. Adjacent to the region of the excretory system a cell is found that resembles a gland cell. This cell is in close contact to the ventral nerve cord. The genital primordia of the third-stage juvenile consist of several dividing cells. The female genital primordium is seen at the junction of the muscular with the glandular oesophagus and the male primordium can be found at the junction of the glandular oesophagus with the gut.

  4. Cellular effector mechanisms against Plasmodium liver stages.

    PubMed

    Frevert, Ute; Nardin, Elizabeth

    2008-10-01

    Advances in our understanding of the molecular and cell biology of the malaria parasite have led to new vaccine development efforts resulting in a pipeline of over 40 candidates undergoing clinical phase I-III trials. Vaccine-induced CD4+ and CD8+ T cells specific for pre-erythrocytic stage antigens have been found to express cytolytic and multi-cytokine effector functions that support a key role for these T cells within the hepatic environment. However, little is known of the cellular interactions that occur during the effector phase in which the intracellular hepatic stage of the parasite is targeted and destroyed. This review focuses on cell biological aspects of the interaction between malaria-specific effector cells and the various antigen-presenting cells that are known to exist within the liver, including hepatocytes, dendritic cells, Kupffer cells, stellate cells and sinusoidal endothelia. Considering the unique immune properties of the liver, it is conceivable that these different hepatic antigen-presenting cells fulfil distinct but complementary roles during the effector phase against Plasmodium liver stages.

  5. EVALUATION OF THE THERAPEUTIC EFFICACY OF LEVAMISOLE HYDROCHLORIDE ON THIRD-STAGE LARVAE OF Lagochilascaris minor IN EXPERIMENTALLY INFECTED MICE

    PubMed Central

    CAMPOS, Dulcinéa Maria Barbosa; BARBOSA, Alverne Passos; OLIVEIRA, Jayrson Araújo; BARBOSA, Carlos Augusto Lopes; LOBO, Tamara Flavia Correa; SILVA, Luana Gabriella; THOMAZ, Douglas Vieira; PEIXOTO, Josana de Castro

    2016-01-01

    Lagochilascariosis, a disease caused by Lagochilascaris minor, affects the neck, sinuses, tonsils, lungs, the sacral region, dental alveoli, eyeballs and the central nervous system of humans. A cycle of autoinfection may occur in human host tissues characterized by the presence of eggs, larvae and adult worms. This peculiarity of the cycle hinders therapy, since there are no drugs that exhibit ovicidal, larvicidal and vermicidal activity. Given these facts, we studied the action of levamisole hydrochloride on third-stage larvae in the migration phase (G1) and on encysted larvae (G3) of L. minor. To this end, 87 inbred mice of the C57BL/6 strain were divided into test groups comprising 67 animals (G1-37; G3-30) and a control group (G2-10; G4-10) with 20 animals. Each animal was inoculated orally with 2,000 infective eggs of the parasite. The animals of the test groups were treated individually with a single oral dose of levamisole hydrochloride at a concentration of 0.075 mg. The drug was administered either 30 minutes prior to the parasite inoculation (G1 animals) or 120 days after the inoculation (G3 animals). The mice in the control groups were not treated with the drug. After the time required for the migration and the encysting of L. minor larvae, all the animals were euthanized and their tissues examined. The data were analyzed using the Student's unpaired t-test and the Levene test. The groups showed no statistically significant difference. Levamisole hydrochloride was ineffective on third-stage larvae of L. minor. These findings explain the massive expulsion of live adult worms, as well as the use of long treatment schemes, owing to the persistence of larvae and eggs in human parasitic lesions. PMID:27253745

  6. Development of life stages of Leptotrombidium imphalum and Leptotrombidium chiangraiensis (Acari: Trombiculidae) uninfected and infected with the scrub typhus rickettsia, Orientia tsustugamushi

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Leptotrombidium chiangraiensis Tanskul and Linthicum and Leptotrombidium imphalum Vercammen-Grandjean are important vectors of scrub typhus in ricefield habitats in northern Thailand. The developmental biology of all stages of the life cycle of two generations of mites infected with Orientia tsutsug...

  7. Morphological and morphometric differentiation of dorsal-spined first stage larvae of lungworms, (Nematoda: Protostrongylidae) infecting muskoxen (Ovibos moschatus) in the Central Canadian Arctic

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Umingmakstrongylus pallikuukensis and Varestrongylus eleguneniensis are the two most common protostrongylid nematodes infecting muskoxen in the North American Arctic and Subarctic. First stage larvae (L1) of both these lungworms have a characteristic dorsal spine originating at the level of proxima...

  8. Ultrastructure of endogenous stages of Eimeria ninakohlyakimovae Yakimoff & Rastegaieff, 1930 Emend. Levine, 1961 in experimentally infected goat.

    PubMed

    Vieira, L S; Lima, J D; Ribeiro, M F; Bozzi, I A; Camargos, E R

    1997-01-01

    The ultrastructure of endogenous stages of Eimeria ninakohlyakimovae was observed in epithelial cells of cecum and colon crypts from a goat experimentally infected with 2.0 x 10(5) oocysts/kg. The secondary meronts developed above the nucleus of the host cell. The nucleus first divides and merozoites then form on the surface of multinucleated meronts. Free merozoites in the parasitophorous vacuole present a conoid, double membrane, one pair of rhoptries, micronemes, micropore, anterior and posterior polar ring, a nucleus with a nucleolus and peripheral chromatin. The microgamonts are located below the nucleus of the host cell and contain several nuclei at the periphery of the parasite. The microgametes consist of a body, a nucleus, three flagella and mitochondria. The macrogamonts develop below the nucleus of the host cell and have a large nucleus with a prominent nucleolus. The macrogametes contain a nucleus, wall-forming bodies of type I and type II. The young oocysts present a wall containing two layers and a sporont.

  9. Multi-Stage Tuberculosis Subunit Vaccine Candidate LT69 Provides High Protection against Mycobacterium tuberculosis Infection in Mice.

    PubMed

    Niu, Hongxia; Peng, Jinxiu; Bai, Chunxiang; Liu, Xun; Hu, Lina; Luo, Yanping; Wang, Bingxiang; Zhang, Ying; Chen, Jianzhu; Yu, Hongjuan; Xian, Qiaoyang; Zhu, Bingdong

    2015-01-01

    Effective tuberculosis (TB) vaccine should target tubercle bacilli with various metabolic states and confer long-term protective immunity. In this study, we constructed a novel multi-stage TB subunit vaccine based on fusion protein ESAT6-Ag85B-MPT64(190-198)-Mtb8.4-HspX (LT69 for short) which combined early expressed antigens and latency-associated antigen. The fusion protein was mixed with an adjuvant being composed of N, N'-dimethyl-N, N'-dioctadecylammonium bromide (DDA) and polyriboinosinic polyribocytidylic acid (PolyI:C) to construct subunit vaccine, whose immunogenicity and protective ability were evaluated in C57BL/6 mice. The results showed that LT69 had strong immunogenicity and high protective effect against Mycobacterium tuberculosis (M. tuberculosis) H37Rv aerosol challenge. Low-dose (2 μg) of LT69 generated long-term immune memory responses and provided effective protection, which was even higher than traditional vaccine BCG did at 30 weeks post the last vaccination. In conclusion, multistage subunit vaccine LT69 showed high and long-term protection against M. tuberculosis infection in mice, whose effect could be enhanced by using a relative low dosage of antigen.

  10. Colletotrichum orbiculare WHI2, a Yeast Stress-Response Regulator Homolog, Controls the Biotrophic Stage of Hemibiotrophic Infection Through TOR Signaling.

    PubMed

    Harata, Ken; Nishiuchi, Takumi; Kubo, Yasuyuki

    2016-06-01

    The hemibiotrophic fungus Colletotrichum orbiculare first establishes a biotrophic infection stage in cucumber (Cucumber sativus) epidermal cells and subsequently transitions to a necrotrophic stage. Here, we found that C. orbiculare established hemibiotrophic infection via C. orbiculare WHI2, a yeast stress regulator homolog, and TOR (target of rapamycin) signaling. Plant defense responses such as callose deposition, H2O2, and antimicrobial proteins were strongly induced by the C. orbiculare whi2Δ mutant, resulting in defective pathogenesis. Expression analysis of biotrophy-specific genes evaluated by the promoter VENUS fusion gene indicated weaker VENUS signal intensity in the whi2Δ mutant, thereby suggesting that C. orbiculare WHI2 plays a key role in regulating biotrophic infection of C. orbiculare. The involvement of CoWHI2 in biotrophic infection was further explored with a DNA microarray. In the Cowhi2Δ mutant, TOR-dependent ribosomal protein-related genes were strikingly upregulated compared with the wild type. Moreover, callose deposition in the host plant after inoculation with the Cowhi2Δ mutant treated with rapamycin, which inhibits TOR activity, was reduced, and the mutant remained biotrophic in contrast to the untreated mutant. Thus, regulation of TOR by Whi2 is apparently crucial to the biotrophic stage of hemibiotrophic infection in C. orbiculare.

  11. Stages of HIV Infection

    MedlinePlus

    ... Hospitalization and Palliative Care Friends & Family Dating and Marriage Family Planning Mixed-Status Couples Discrimination Legal Issues ... National HIV/AIDS and Aging Awareness Day National Gay Men's HIV/AIDS Awareness Day National Latinx AIDS ...

  12. Rapid and Slow Progressors Show Increased IL-6 and IL-10 Levels in the Pre-AIDS Stage of HIV Infection

    PubMed Central

    de Medeiros, Rúbia M.; Valverde-Villegas, Jacqueline M.; Junqueira, Dennis M.; Gräf, Tiago; Lindenau, Juliana D.; de Mello, Marineide G.; Vianna, Priscila; Almeida, Sabrina E. M.; Chies, Jose Artur B.

    2016-01-01

    Cytokines are intrinsically related to disease progression in HIV infection. We evaluated the plasma levels of Th1/Th2/Th17 cytokines in extreme progressors, including slow (SPs) and rapid (RPs) progressors, who were thus classified based on clinical and laboratory follow-up covering a period of time before the initiation of HAART, ranging from 93–136.5 months for SPs and 7.5–16.5 months for RPs. Analyses were also performed based on the different stages of HIV infection (chronic, pre-HAART individuals—subjects sampled before initiating HAART but who initiated therapy from 12 to 24 months—and those receiving HAART). The plasma cytokine levels of 16 HIV-infected rapid progressors and 25 slow progressors were measured using a Human Th1/Th2/Th17 CBA kit. The IL-6 and IL-10 plasma levels differed significantly between the stages of HIV infection. The IL-6 levels were higher in slow progressors pre-HAART than in chronically infected SPs and HIV-seronegative individuals. The IL-10 levels were higher in slow progressors pre-HAART than in slow progressors receiving HAART and HIV-seronegative controls, and in rapid progressors, the IL-10 levels were higher in pre-HAART subjects than in HIV-seronegative controls. The results reflect the changes in the cytokine profile occurring during different clinical stages in HIV+ subjects. Our results suggest an association between increased IL-6 and IL-10 levels and pre-HAART stages independent of the slow or rapid progression status of the subjects. Thus, increased IL-6 and IL-10 levels could indicate a global inflammatory status and could be used as markers of the disease course in HIV-infected individuals. PMID:27214135

  13. Results of single stage exchange arthroplasty with retention of well fixed cement-less femoral component in management of infected total hip arthroplasty

    PubMed Central

    Rahman, Wael A; Kazi, Hussain A; Gollish, Jeffery D

    2017-01-01

    AIM To investigate success of one stage exchange with retention of fixed acetabular cup. METHODS Fifteen patients treated by single stage acetabular component exchange with retention of well-fixed femoral component in infected total hip arthroplasty (THA) were retrospectively reviewed. Inclusion criteria were patients with painful chronic infected total hip. The patient had radiologically well fixed femoral components, absence of major soft tissue or bone defect compromising, and infecting organism was not poly or virulent micro-organism. The organisms were identified preoperatively in 14 patients (93.3%), coagulase negative Staphylococcus was the infecting organism in 8 patients (53.3%). RESULTS Mean age of the patients at surgery was 58.93 (± 10.67) years. Mean follow-up was 102.8 mo (36-217 mo, SD 56.4). Fourteen patients had no recurrence of the infection; one hip (6.7%) was revised for management of infection. Statistical analysis using Kaplan Meier curve showed 93.3% survival rate. One failure in our series; the infection recurred after 14 mo, the patient was treated successfully with surgical intervention by irrigation, and debridement and liner exchange. Two complications: The first patient had recurrent hip dislocation 12 years following the definitive procedure, which was managed by revision THA with abductor reconstruction and constrained acetabular liner; the second complication was aseptic loosening of the acetabular component 2 years following the definitive procedure. CONCLUSION Successful in management of infected THA when following criteria are met; well-fixed stem, no draining sinuses, non-immune compromised patients, and infection with sensitive organisms. PMID:28361019

  14. The shiitake mushroom-derived immuno-stimulant lentinan protects against murine malaria blood-stage infection by evoking adaptive immune-responses.

    PubMed

    Zhou, Lian-di; Zhang, Qi-hui; Zhang, Ying; Liu, Jun; Cao, Ya-ming

    2009-04-01

    Lentinan, a (1-3)-beta glucan from Lentinus edodes, is an effective immunostimulatory drug. We tested the effects of lentinan during blood-stage infection by Plasmodium yoelii 17XL (P.y17XL). Pre-treatment of mice with lentinan significantly decreased the parasitemia and increased their survival after infection. Enhanced IL-12, IFN-gamma and NO production induced by lentinan in spleen cells of infected mice revealed that the Th1 immune response was stimulated against malaria infection. In vitro and in vivo, lentinan can result in enhanced expression of MHC II, CD80/CD86, and Toll-like receptors (TLR2/TLR4), and increased production of IL-12 in spleen dendritic cells (DCs) co-cultured with parasitized red blood cells (pRBCs). Moreover, both the number of CD4(+)CD25(+) regulatory T cells (Tregs) and the levels of IL-10 secreted by Tregs were reduced by pre-treatment with lentinan in the spleen of malaria-infected mice. Meanwhile, apoptosis of CD4(+) T cell in spleens of mice pretreated with lentinan was significantly reduced. In summary, lentinan can induce protective Th1 immune responses to control the proliferation of malaria parasites during the blood-stage of P.y17XL infection by stimulating maturation of DCs to inhibit negative regulation of the Th1 immune response by Tregs. Taken together, our findings suggest that lentinan has prophylactic potential for the treatment of malaria.

  15. Expression of late viral proteins is restricted in nasal mucosal leucocytes but not in epithelial cells during early-stage equine herpes virus-1 infection.

    PubMed

    Gryspeerdt, Annick C; Vandekerckhove, Annelies P; Baghi, Hossein Bannazadeh; Van de Walle, Gerlinde R; Nauwynck, Hans J

    2012-08-01

    Equine herpes virus (EHV)-1 replicates in the epithelial cells of the upper respiratory tract and reaches the lamina propria and bloodstream in infected mononuclear cells. This study evaluated expression of the late viral proteins gB, gC, gD and gM in respiratory epithelial and mononuclear cells using: (1) epithelial-like rabbit kidney cells and peripheral blood mononuclear cells infected with EHV-1 in vitro; (2) an equine ex vivo nasal explant system; and (3) nasal mucosa tissue of ponies infected in vivo. The viral proteins were expressed in all late-infected epithelial cells, whereas expression was not observed in infected leucocytes where proteins gB and gM were expressed in 60-90%, and proteins gC and gD in only 20% of infected cells, respectively. The results indicate that expression of these viral proteins during early-stage EHV-1 infection is highly dependent on the cell type infected.

  16. Amelioration of Citrobacter rodentium proliferation in early stage of infection in mice by pre-treatment with Lactobacillus brevis KB290 and verification using in vivo bioluminescence imaging.

    PubMed

    Waki, Naoko; Kuwabara, Yuki; Yoshikawa, Yuko; Suganuma, Hiroyuki; Koide, Hiroyuki; Oku, Naoto; Ohashi, Norio

    2016-11-10

    Bioluminescent imaging (BLI) has become a useful tool for monitoring bacterial infections in real time. Citrobacter rodentium and its BLI are widely used as a murine model of enteropathogenic and enterohaemorrhagic Escherichia coli infection. In this study, we evaluated the protective effects of the probiotic Lactobacillus brevis KB290 against C. rodentium infection by the BLI approach. First, we examined several solutions for making the suspension of bioluminescent C. rodentium for an oral inoculation to establish a stable intestinal infection. Three percent NaHCO 3 solution was found to be the best. Subsequently, mice were orally administered KB290 once daily for 7 days before inoculation with bioluminescent C. rodentium and for 8 days after infection. The bioluminescence intensity of mice fed with KB290 was significantly lower than that of unfed mice on days 1-3 post-infection . The mRNA levels of tumour necrosis factor-α and interferon-γ in the distal colon from KB290-fed mice were shown to be significantly higher than those from unfed mice on day 3 post-infection. The results suggested that KB290 intake partially inhibited the proliferation of C. rodentium , especially in the early stages of infection, via the moderate enhancement of tumour necrosis factor-α and interferon-γ production in the colon.

  17. Long-Term Relationships: the Complicated Interplay between the Host and the Developmental Stages of Toxoplasma gondii during Acute and Chronic Infections

    PubMed Central

    Pittman, Kelly J.

    2015-01-01

    SUMMARY Toxoplasma gondii represents one of the most common parasitic infections in the world. The asexual cycle can occur within any warm-blooded animal, but the sexual cycle is restricted to the feline intestinal epithelium. T. gondii is acquired through consumption of tissue cysts in undercooked meat as well as food and water contaminated with oocysts. Once ingested, it differentiates into a rapidly replicating asexual form and disseminates throughout the body during acute infection. After stimulation of the host immune response, T. gondii differentiates into a slow-growing, asexual cyst form that is the hallmark of chronic infection. One-third of the human population is chronically infected with T. gondii cysts, which can reactivate and are especially dangerous to individuals with reduced immune surveillance. Serious complications can also occur in healthy individuals if infected with certain T. gondii strains or if infection is acquired congenitally. No drugs are available to clear the cyst form during the chronic stages of infection. This therapeutic gap is due in part to an incomplete understanding of both host and pathogen responses during the progression of T. gondii infection. While many individual aspects of T. gondii infection are well understood, viewing the interconnections between host and parasite during acute and chronic infection may lead to better approaches for future treatment. The aim of this review is to provide an overview of what is known and unknown about the complex relationship between the host and parasite during the progression of T. gondii infection, with the ultimate goal of bridging these events. PMID:26335719

  18. A multidisciplinary team approach to two-stage revision for the infected hip replacement: a minimum five-year follow-up study.

    PubMed

    Ibrahim, M S; Raja, S; Khan, M A; Haddad, F S

    2014-10-01

    We report the five year outcomes of a two-stage approach for infected total hip replacement. This is a single-surgeon experience at a tertiary centre where the more straightforward cases are treated using single-stage exchange. This study highlights the vital role of the multidisciplinary team in managing these cases. A total of 125 patients (51 male, 74 female) with a mean age of 68 years (42 to 78) were reviewed prospectively. Functional status was assessed using the Harris hip score (HHS). The mean HHS improved from 38 (6 to 78.5) pre-operatively to 81.2 (33 to 98) post-operatively. Staphylococcus species were isolated in 85 patients (68%). The rate of control of infection was 96% at five years. In all, 19 patients died during the period of the study. This represented a one year mortality of 0.8% and an overall mortality of 15.2% at five years. No patients were lost to follow-up. We report excellent control of infection in a series of complex patients and infections using a two-stage revision protocol supported by a multidisciplinary approach. The reason for the high rate of mortality in these patients is not known.

  19. Is caprine arthritis encephalitis virus (CAEV) transmitted vertically to early embryo development stages (morulae or blastocyst) via in vitro infected frozen semen?

    PubMed

    Al Ahmad, M Z Ali; Chebloune, Y; Chatagnon, G; Pellerin, J L; Fieni, F

    2012-05-01

    The aim of this study was to determine, in vivo, whether in vitro infected cryopreserved caprine sperm is capable of transmitting caprine arthritis-encephalitis virus (CAEV) vertically to early embryo development stages via artificial insemination with in vitro infected semen. Sperm was collected from CAEV-free bucks by electroejaculation. Half of each ejaculate was inoculated with CAEV-pBSCA at a viral concentration of 10(4) TCID(50)/mL. The second half of each ejaculate was used as a negative control. The semen was then frozen. On Day 13 of superovulation treatment, 14 CAEV-free does were inseminated directly into the uterus under endoscopic control with thawed infected semen. Six CAEV-free does, used as a negative control, were inseminated intrauterine with thawed CAEV-free sperm, and eight CAEV-free does were mated with naturally infected bucks. Polymerase chain reaction (PCR) was used to detect CAEV proviral-DNA in the embryos at the D7 stage, in the embryo washing media, and in the uterine secretions of recipient does. At Day 7, all the harvested embryos were PCR-negative for CAEV proviral-DNA; however, CAEV proviral-DNA was detected in 8/14 uterine smears, and 9/14 flushing media taken from does inseminated with infected sperm, and in 1/8 uterine swabs taken from the does mated with infected bucks. The results of this study confirm that (i) artificial insemination with infected semen or mating with infected bucks may result in the transmission of CAEV to the does genital tack seven days after insemination, and (ii) irrespective of the medical status of the semen or the recipient doe, it is possible to obtain CAEV-free early embryos usable for embryo transfer.

  20. The usefulness of DNA derived from third stage larvae in the detection of Ashworthius sidemi infection in European bison, by a simple polymerase chain reaction

    PubMed Central

    2014-01-01

    Background Ashworthius sidemi, a blood-sucking nematode, is a primary parasite of Asiatic cervides, primarily sika deer (Cervus nippon). As A. sidemi infections are common in bison, red and roe deer, and gastrointestinal nematodes are often exchanged between animals, it is possible that other farm animals such as cows and sheep that may use the same pastures can be infected. Hence, histopathological changes observed in the walls of the abomasa and duodena of infected wildlife caused by a strong parasite presence may become an important health problem also for farm animals. Methods In the present study, a simple PCR test for the detection of A. sidemi infection in European bison based on DNA from third stage infective larvae (L3) has been optimized. Results The species-specific primers generated a 406 bp fragment, and A. sidemi DNA could be detected at concentrations of 0.1 pg/μl. The specificity of PCR was confirmed by the use of the genomic DNA of adult Ostertagia ostertagi, Haemonchus contortus, Cooperiaoncophora as negative controls. Conclusion It is possible to detect A. sidemi infection in European bison using DNA from L3. If this nematode infection is transmitted to cows this method may be effective to diagnose invasion in breeding animals in vivo. PMID:24886355

  1. Altered microRNA expression and pre-mRNA splicing events reveal new mechanisms associated with early stage Mycobacterium avium subspecies paratuberculosis infection.

    PubMed

    Liang, Guanxiang; Malmuthuge, Nilusha; Guan, Yongjuan; Ren, Yuwei; Griebel, Philip J; Guan, Le Luo

    2016-04-22

    The molecular regulatory mechanisms of host responses to Mycobacterium avium subsp. paratuberculosis (MAP) infection during the early subclinical stage are still not clear. In this study, surgically isolated ileal segments in newborn calves (n = 5) were used to establish in vivo MAP infection adjacent to an uninfected control intestinal compartment. RNA-Seq was used to profile the whole transcriptome (mRNAs) and the microRNAome (miRNAs) of ileal tissues collected at one-month post-infection. The most related function of the differentially expressed mRNAs between infected and uninfected tissues was "proliferation of endothelial cells", indicating that MAP infection may lead to the over-proliferation of endothelial cells. In addition, 46.2% of detected mRNAs displayed alternative splicing events. The pre-mRNA of two genes related to macrophage maturation (monocyte to macrophage differentiation-associated) and lysosome function (adenosine deaminase) showed differential alternative splicing events, suggesting that specific changes in the pre-mRNA splicing sites may be a mechanism by which MAP escapes host immune responses. Moreover, 9 miRNAs were differentially expressed after MAP infection. The integrated analysis of microRNAome and transcriptome revealed that these miRNAs might regulate host responses to MAP infection, such as "proliferation of endothelial cells" (bta-miR-196 b), "bacteria recognition" (bta-miR-146 b), and "regulation of the inflammatory response" (bta-miR-146 b).

  2. Disruption of the phagosomal membrane and egress of Legionella pneumophila into the cytoplasm during the last stages of intracellular infection of macrophages and Acanthamoeba polyphaga.

    PubMed

    Molmeret, Maëlle; Bitar, Dina M; Han, Lihui; Kwaik, Yousef Abu

    2004-07-01

    Although the early stages of intracellular infection by Legionella pneumophila are well established at the ultrastructural level, a detailed ultrastructural analysis of late stages of intracellular replication has never been done. Here we show that the membrane of the L. pneumophila-containing phagosome (LCP) is intact for up to 8 h postinfection of macrophages and Acanthamoeba polyphaga. At 12 h, 71 and 74% of the LCPs are disrupted within macrophages and A. polyphaga, respectively, while the plasma membrane remains intact. At 18 and 24 h postinfection, cytoplasmic elements such as mitochondria, lysosomes, vesicles, and amorphous material are dispersed among the bacteria and these bacteria are considered cytoplasmic. At 18 h, 77% of infected macrophages and 32% of infected A. polyphaga amoebae harbor cytoplasmic bacteria. At 24 h, 99 and 78% of infected macrophages and amoebae, respectively, contain cytoplasmic bacteria. On the basis of lysosomal acid phosphatase staining of infected macrophages and A. polyphaga, the lysosomal enzyme is present among the bacteria when host vesicles are dispersed among bacteria. Our data indicate that bacterial replication proceeds despite physical disruption of the phagosomal membrane. We also show that an lspG mutant that is defective in the type II secretion system and therefore does not secrete the hydrolytic enzymes metalloprotease, p-nitrophenol phosphorylcholine hydrolase, lipase, phospholipase A, and lysophospholipase A is as efficient as the wild-type strain in disruption of the LCP. Therefore, L. pneumophila disrupts the phagosomal membrane and becomes cytoplasmic at the last stages of infection in both macrophages and A. polyphaga. Lysosomal elements, mitochondria, cytoplasmic vesicles, and amorphous material are all dispersed among the bacteria, after phagosomal disruption, within both human macrophages and A. polyphaga. The disruption of the LCP is independent of the hydrolytic enzymes exported by the type II secretion

  3. Infection

    DTIC Science & Technology

    2010-09-01

    standing, diagnosis, and treatment of musculoskeletal infections. Key Words: musculoskeletal infection, biofilm , bacteria, biomaterial (J Orthop Trauma...form a biofilm , or slime layer.1 The recurrence of infections is often the result of microbial biofilm formation on the implant, enabling the persistence...Klebsiella pneumoniae). Staphylococcus species is by far the most studied pathogen in musculoskeletal infections and can produce a multilayered biofilm

  4. Life stage-related differences in density of questing ticks and infection with Borrelia burgdorferi sensu lato within a single cohort of Ixodes pacificus (Acari: Ixodidae).

    PubMed

    Eisen, Rebecca J; Mun, Jeomhee; Eisen, Lars; Lane, Robert S

    2004-07-01

    The primary aims of this study were to quantify the density of Ixodes pacificus Cooley and Kohls nymphs and adults of the same generational cohort collected within a single year in six oak or madrone leaf litter habitats and to compare the prevalence of infection with Borrelia burgdorferi sensu lato (s.l.) in adults originating from nymphal cohorts with a low (<1%) versus high (>10%) infection prevalence. Because adult densities were very low both in and adjacent to several sites, direct comparisons of infection prevalence between nymphs and adults were possible only for two sites. Mean density in these sites decreased from 11.95/100 m2 for nymphs to 0/100 m2 for adults in leaf litter, and infection prevalence with B. burgdorferi s.l. was four-fold higher in nymphs (7.4%) versus adults (1.6%) of the same generational cohort collected in ecotones bordering the leaf litter areas. Assuming a density of adults in leaf litter of 0.04/100 m2 (mean for all six examined sites) and an infection prevalence similar to that found in adults collected from litter ecotones, the risk of encountering infected ticks in leaf litter decreased >1,000-fold from the nymphal to adult stage. Regardless of site-specific infection prevalence in the nymphal stage (n = 2 sites; 0.7 versus 14%), the infection prevalence for the adults of the same generational cohort was similarly low (1.5-1.6%). Peak densities of adult I. pacificus were 0-0.1/100 m2 in leaf litter, 0-6.5/100 m2 in ecotonal grasslands, and 2.0-39.0/100 m2 in ecotonal chaparral. Despite more intensive sampling efforts in leaf litter, the vast majority of the 282 adults collected came from grass or chaparral ecotones (98.9%, n = 279) rather than leaf litter (1.1%, n = 3). The study yielded eight B. burgdorferi s.l.-infected adults; four of these carried B. burgdorferi sensu stricto Johnson, Schmidt, Hyde, Steigerwalt, and Brenner, and the remaining four were infected with currently undescribed B. burgdorferi s.l. spirochetes. This

  5. Kaposi’s Sarcoma-Associated Herpesvirus Genome Programming during the Early Stages of Primary Infection of Peripheral Blood Mononuclear Cells

    PubMed Central

    Jha, Hem C.; Lu, Jie; Verma, Subhash C.; Banerjee, Shuvomoy; Mehta, Devan

    2014-01-01

    ABSTRACT The early period of Kaposi’s sarcoma-associated herpesvirus (KSHV) infection involves the dynamic expression of viral genes, which are temporally and epigenetically regulated. KSHV can effectively infect and persist in endothelial as well as human B cells with different gene expression patterns. To understand the temporal epigenetic changes which occur when KSHV infects the lymphocytic compartment, we infected human peripheral blood mononuclear cells (PBMCs) and comprehensively analyzed the changes which occurred at the binding sites of virally encoded lytic as well as latent proteins along with epigenetic modifications across the KSHV genome during early primary infection. Using chromatin immunoprecipitation (ChIP) assays, we showed that the KSHV genome acquires a uniquely distinct histone modification pattern of methylation (H3K4me3, H3K9me3, and H3K27me3) and acetylation (H3Ac) during de novo infection of human PBMCs. This pattern showed that the epigenetic changes were temporally controlled. The binding profiles of KSHV latent protein LANA and the immediate early proteins RTA and K8 showed specific patterns at different times postinfection, which reflects the gene expression program. Further analysis demonstrated that KSHV can concurrently express lytic and latent genes which were associated with histone modifications at these specific regions on the viral genome. We identified three KSHV genes, K3, ORF49, and ORF64, which exhibited different profiles of histone modifications during the early stages of PBMC infection. These studies established a distinct pattern of epigenetic modification which correlates with viral gene expression temporally regulated during the first 7 days of PBMC infection and provides clues to the regulatory program required for successful infection by KSHV of human PBMCs. PMID:25516617

  6. The 11,600-MW protein encoded by region E3 of adenovirus is expressed early but is greatly amplified at late stages of infection.

    PubMed Central

    Tollefson, A E; Scaria, A; Saha, S K; Wold, W S

    1992-01-01

    We have reported that an 11,600-MW (11.6K) protein is coded by region E3 of adenovirus. We have now prepared two new antipeptide antisera that have allowed us to characterize this protein further. The 11.6K protein migrates as multiple diffuse bands having apparent Mws of about 14,000, 21,000, and 31,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Immunoblotting as well as virus mutants with deletions in the 11.6K gene were used to show that the various gel bands represent forms of 11.6K. The 11.6K protein was synthesized in very low amounts during early stages of infection, from the scarce E3 mRNAs d and e which initiate from the E3 promoter. However, 11.6K was synthesized very abundantly at late stages of infection, approximately 400 times the rate at early stages, from new mRNAs termed d' and e'. Reverse transcriptase-polymerase chain reaction and RNA blot experiments indicated that mRNAs d' and e' had the same body (the coding portion) and the same middle exon (the y leader) as early E3 mRNAs d and e, but mRNAs d' and e' were spliced at their 5' termini to the major late tripartite leader which is found in all mRNAs in the major late transcription unit. mRNAs d' and e' and the 11.6K protein were the only E3 mRNAs and protein that were scarce early and were greatly amplified at late stages of infection. This suggests that specific cis- or trans-acting sequences may function to enhance the splicing of mRNAs d' and e' at late stages of infection and perhaps to suppress the splicing of mRNAs d and e at early stages of infection. We propose that the 11.6K gene be considered not only a member of region E3 but also a member of the major late transcription unit. Images PMID:1316473

  7. Cyclooxygenase activity is important for efficient replication of mouse hepatitis virus at an early stage of infection.

    PubMed

    Raaben, Matthijs; Einerhand, Alexandra W C; Taminiau, Lucas J A; van Houdt, Michel; Bouma, Janneke; Raatgeep, Rolien H; Büller, Hans A; de Haan, Cornelis A M; Rossen, John W A

    2007-06-07

    Cyclooxygenases (COXs) play a significant role in many different viral infections with respect to replication and pathogenesis. Here we investigated the role of COXs in the mouse hepatitis coronavirus (MHV) infection cycle. Blocking COX activity by different inhibitors or by RNA interference affected MHV infection in different cells. The COX inhibitors reduced MHV infection at a post-binding step, but early in the replication cycle. Both viral RNA and viral protein synthesis were affected with subsequent loss of progeny virus production. Thus, COX activity appears to be required for efficient MHV replication, providing a potential target for anti-coronaviral therapy.

  8. Comparative Transcriptome Analysis between Broccoli (Brassica oleracea var. italica) and Wild Cabbage (Brassica macrocarpa Guss.) in Response to Plasmodiophora brassicae during Different Infection Stages

    PubMed Central

    Zhang, Xiaoli; Liu, Yumei; Fang, Zhiyuan; Li, Zhansheng; Yang, Limei; Zhuang, Mu; Zhang, Yangyong; Lv, Honghao

    2016-01-01

    Clubroot, one of the most devastating diseases to the Brassicaceae family, is caused by the obligate biotrophic pathogen Plasmodiophora brassicae. However, studies of the molecular basis of disease resistance are still poor especially in quantitative resistance. In the present paper, two previously identified genotypes, a clubroot-resistant genotype (wild cabbage, B2013) and a clubroot-susceptible genotype (broccoli, 90196) were inoculated by P. brassicae for 0 (T0), 7 (T7), and 14 (T14) day after inoculation (DAI). Gene expression pattern analysis suggested that response changes in transcript level of two genotypes under P. brassicae infection were mainly activated at the primary stage (T7). Based on the results of DEGs functional enrichments from two infection stages, genes associated with cell wall biosynthesis, glucosinolate biosynthesis, and plant hormone signal transduction showed down-regulated at T14 compared to T7, indicating that defense responses to P. brassicae were induced earlier, and related pathways were repressed at T14. In addition, the genes related to NBS-LRR proteins, SA signal transduction, cell wall and phytoalexins biosynthesis, chitinase, Ca2+ signals and RBOH proteins were mainly up-regulated in B2013 by comparing those of 90196, indicating the pathways of response defense to clubroot were activated in the resistant genotype. This is the first report about comparative transcriptome analysis for broccoli and its wild relative during the different stages of P. brassicae infection and the results should be useful for molecular assisted screening and breeding of clubroot-resistant genotypes. PMID:28066482

  9. Sustained high level of serum VEGF at convalescent stage contributes to the renal recovery after HTNV infection in patients with hemorrhagic fever with renal syndrome.

    PubMed

    Ma, Ying; Liu, Bei; Yuan, Bin; Wang, Jiuping; Yu, Haitao; Zhang, Yun; Xu, Zhuwei; Zhang, Yusi; Yi, Jing; Zhang, Chunmei; Zhou, Xingchun; Yang, Angang; Zhuang, Ran; Jin, Boquan

    2012-01-01

    To investigate the role of vascular endothelial growth factor (VEGF) in the increased permeability of vascular endothelial cells after Hantaan virus (HTNV) infection in humans, the concentration of VEGF in serum from HTNV infected patients was quantified with sandwich ELISA. Generally, the level of serum VEGF in patients was elevated to 607.0 (542.2-671.9) pg/mL, which was dramatically higher compared with healthy controls (P < 0.001). There was a rapid increase of the serum VEGF level in all patients from the fever onset to oliguric stage, at which the serum creatinine reached the peak level of the disease, indicating that VEGF may be involved in the pathogenesis of renal hyper-permeability. Moreover, the serum VEGF level at convalescent stage was positively correlated with the degree of the disease severity. The sustained high level of serum VEGF at convalescence was observed in critical HFRS patients, suggesting that VEGF would probably contribute to the renal recovery after the virus clearance. Taken together, our results suggested that the VEGF would be involved in the pathogenesis of renal dysfunction at the oliguric stage after HTNV infection, but may function as a recovery factor during the convalescence to help the body self-repair of the renal injury.

  10. Two-Stage Revision Total Hip Arthroplasty for Periprosthetic Infections Using Antibiotic-Impregnated Cement Spacers of Various Types and Materials

    PubMed Central

    Takahira, Naonobu; Moriya, Mitsutoshi; Yamamoto, Takeaki; Minegishi, Yojiro; Sakai, Rina; Itoman, Moritoshi; Takaso, Masashi

    2013-01-01

    Antibiotic-impregnated hip cement spacers of various types and materials have been used in the treatment of periprosthetic hip infections. We developed a handmade spacer by using polymethylmethacrylate (PMMA) and/or α-tricalcium phosphate (α-TCP). In this study, we retrospectively reviewed the surgical outcomes in 36 consecutive patients treated with 2-stage revision total hip arthroplasty by using our antibiotic-impregnated hip cement spacers. We aimed to analyze the infection control and reinfection rates after revision surgery. Moreover, we analyzed the possible predictors of postoperative reinfection. After exclusion of 1 patient who died immediately after the first-stage surgery, infection was controlled in 33 of the 36 hips (success rate, 91.7%). Two of these 33 hips underwent resection arthroplasty. Of the 36 hips that had been treated with the antibiotic-cement spacer, 31 hips (86.1%) were eligible for the second-stage prosthesis re-implantation. The 31 protocol hip joints of patients followed up for >6 months (mean, 48.6 months). Ten of these 31 hips (32.3%) became reinfected. No possible predictor examined differed significantly between the reinfection-positive and reinfection-negative groups. However, spacers consisting of PMMA cement alone were associated with the highest risk of reinfection. Therefore, α-TCP-containing antibiotic-impregnated hip cement spacers might decrease the reinfection rate in patients undergoing re-implantation. PMID:24381509

  11. Comparative Transcriptome Analysis between Broccoli (Brassica oleracea var. italica) and Wild Cabbage (Brassica macrocarpa Guss.) in Response to Plasmodiophora brassicae during Different Infection Stages.

    PubMed

    Zhang, Xiaoli; Liu, Yumei; Fang, Zhiyuan; Li, Zhansheng; Yang, Limei; Zhuang, Mu; Zhang, Yangyong; Lv, Honghao

    2016-01-01

    Clubroot, one of the most devastating diseases to the Brassicaceae family, is caused by the obligate biotrophic pathogen Plasmodiophora brassicae. However, studies of the molecular basis of disease resistance are still poor especially in quantitative resistance. In the present paper, two previously identified genotypes, a clubroot-resistant genotype (wild cabbage, B2013) and a clubroot-susceptible genotype (broccoli, 90196) were inoculated by P. brassicae for 0 (T0), 7 (T7), and 14 (T14) day after inoculation (DAI). Gene expression pattern analysis suggested that response changes in transcript level of two genotypes under P. brassicae infection were mainly activated at the primary stage (T7). Based on the results of DEGs functional enrichments from two infection stages, genes associated with cell wall biosynthesis, glucosinolate biosynthesis, and plant hormone signal transduction showed down-regulated at T14 compared to T7, indicating that defense responses to P. brassicae were induced earlier, and related pathways were repressed at T14. In addition, the genes related to NBS-LRR proteins, SA signal transduction, cell wall and phytoalexins biosynthesis, chitinase, Ca(2+) signals and RBOH proteins were mainly up-regulated in B2013 by comparing those of 90196, indicating the pathways of response defense to clubroot were activated in the resistant genotype. This is the first report about comparative transcriptome analysis for broccoli and its wild relative during the different stages of P. brassicae infection and the results should be useful for molecular assisted screening and breeding of clubroot-resistant genotypes.

  12. Debridement with prosthesis retention and antibiotherapy vs. two-stage revision for periprosthetic knee infection within 3 months after arthroplasty: a case-control study.

    PubMed

    Lizaur-Utrilla, A; Gonzalez-Parreño, S; Gil-Guillen, V; Lopez-Prats, F A

    2015-09-01

    Sixty-four patients with periprosthetic infection within 3 months of index arthroplasty, of whom 39 underwent debridement with prosthesis retention and antibiotherapy (DPRA), and 25 underwent two-stage revision (2SR), were compared regarding control of infection and functional outcomes by use of Knee Society scores. Failure was defined as the need for subsequent surgery to control infection. The failure rate after DPRA was 61.5%, and that after 2SR was 12.0% (p 0.001). The failure risk was not significantly associated with the duration of symptoms (≤4 weeks). The only predictor of failure was isolation of Staphylococcus aureus or Staphylococcus epidermidis. Treatment with 2SR required fewer surgical operations, a shorter duration of hospitalization, and a shorter duration of treatment. All patients who required a second debridement ultimately underwent prosthesis removal. The functional outcome was significantly better for 2SR at the last follow-up.

  13. C-reactive protein, procalcitonin, interleukin-6, vascular endothelial growth factor and oxidative metabolites in diagnosis of infection and staging in patients with gastric cancer

    PubMed Central

    Ilhan, Nevin; Ilhan, Necip; Ilhan, Yavuz; Akbulut, Handan; Küçüksu, Mehmet

    2004-01-01

    AIM: The current study was to determine the serum/plasma levels of VEGF, IL-6, malondialdehyde (MDA), nitric oxide (NO), PCT and CRP in gastric carcinoma and correlation with the stages of the disease and accompanying infection. METHODS: We examined the levels of serum VEGF, IL-6, PCT, CRP and plasma MDA, NO in 42 preoperative gastric cancer patients and 23 healthy subjects. There were infection anamneses that had no definite origin in 19 cancer patients. RESULTS: The VEGF levels (mean ± SD; pg/mL) were 478.05 ± 178.29 and 473.85 ± 131.24 in gastric cancer patients with and without infection, respectively, and these values were not significantly different (P>0.05). The levels of VEGF, CRP, PCT, IL-6, MDA and NO in cancer patients were significantly higher than those in healthy controls and the levels of CRP, PCT, IL-6, MDA and NO were statistically increased in infection group when compared with non-infection group (P<0.001). CONCLUSION: Although serum VEGF concentrations were increased in gastric cancer, this increase might not be related to infection. CRP, PCT, IL-6, MDA and NO have obvious drawbacks in the diagnosis of infections in cancer patients. These markers may not help to identify infections in the primary evaluation of cancer patients and hence to avoid unnecessary antibiotic treatments as well as hospitalization. According to the results of this study, IL-6, MDA, NO and especially VEGF can be used as useful parameters to diagnose and grade gastric cancer. PMID:15069709

  14. Inefficiency of C3H/HeN Mice to Control Chlamydial Lung Infection Correlates with Downregulation of Neutrophil Activation During the Late Stage of Infection

    PubMed Central

    Tang, Xiaofei; Bu, Xiaokun; Zhang, Naihong; Li, Xiaoxia; Huang, Huanjun; Bai, Hong; Yang, Xi

    2009-01-01

    We previously reported that massive infiltration of neutrophils in C3H/HeN (C3H) mice could not efficiently control Chlamydia muridarum (Cm) infection and might contribute to the high susceptibility of these mice to lung infection. To further define the nature of neutrophil responses in C3H mice during chlamydial infection, we examine the expression of adhesion molecules and CD11b related to neutrophils infiltration and activation, respectively, following intranasal Cm infection. The results showed that the expression of selectins (E-selectin, P-selectin and L-selectin), and intercellular cell adhesion molecule-1 (ICAM-1) in the lung of C3H mice increased more significantly than in C57BL/6 (B6) mice, the more resistant strain. These results correlated well with the massive neutrophils infiltration in C3H mice. In contrast, CD11b expression on peripheral blood and lung neutrophils in C3H mice exhibited a significant reduction compared with B6 mice during the late phage of infection (day 14). These findings suggest that the high-level expression of adhesion molecules in C3H mice may enhance neutrophils recruitment to the lung, but the decline of CD11b expression on neutrophils may attenuate neutrophil function. Therefore, CD11b down-regulation on neutrophils may contribute to the failure of C3H mice to control chlamydial lung infection. PMID:19728926

  15. Pineapple juice for digestion of swamp eel viscera for harvesting infective-stage larva of Gnathostoma spp.

    PubMed

    Soogarun, Suphan; Suwansaksri, Jamsai; Wiwanitkit, Viroj

    2004-06-01

    Third-stage larvae were used as antigen in the diagnosis of gnathostomiasis in Western blot analysis. Normally, the larvae were obtained from digestion of eel's liver (Fluta alba) by the enzyme pepsin. We used pineapple juice (Ananus comosus) instead of enzyme pepsin in harvesting Gnathostoma spinigerum third-stage larvae. The difference in recovered larvae numbers, between pineapple juice and pepsin, were not statistically significantly different (p>0.05). The larvae from pepsin and pineapple juice digestion were cultivated on BME for 7 days; the survival rates were not significantly different (p>0.05). Thus, pineapple juice is another enzyme of choice for recovering Gnathostoma spinigerum third-stage larvae.

  16. In Vivo Antiprotozoal Activity of the Chloroform Extract from Carica papaya Seeds against Amastigote Stage of Trypanosoma cruzi during Indeterminate and Chronic Phase of Infection

    PubMed Central

    Ortega-Pacheco, Antonio; Perez-Gutierrez, Salud; Guzman-Marin, Eugenia

    2014-01-01

    In order to evaluate the antiprotozoal activity of the chloroform extract of Carica papaya seeds during the subacute and chronic phase of infection of Trypanosoma cruzi, doses of 50 and 75 mg/kg were evaluated during the subacute phase, including a mixture of their main components (oleic, palmitic, and stearic acids). Subsequently, doses of 50 and 75 mg/kg in mice during the chronic phase of infection (100 dpi) were also evaluated. It was found that chloroform extract was able to reduce the amastigote nests numbers during the subacute phase in 55.5 and 69.7% (P > 0.05) as well as in 56.45% in animals treated with the mixture of fatty acids. Moreover, the experimental groups treated with 50 and 75 mg/kg during the chronic phase of the infection showed a significant reduction of 46.8 and 53.13% respectively (P < 0.05). It is recommended to carry out more studies to determine if higher doses of chloroformic extract or its administration in combination with other antichagasic drugs allows a better response over the intracellular stage of T. cruzi in infected animal models and determine if the chloroform extract of C. papaya could be considered as an alternative for treatment during the indeterminate and chronic phase of the infection. PMID:25276216

  17. Antibody against an Anaplasma marginale MSP5 epitope common to tick and erythrocyte stages identifies persistently infected cattle.

    PubMed Central

    Knowles, D; Torioni de Echaide, S; Palmer, G; McGuire, T; Stiller, D; McElwain, T

    1996-01-01

    A protein epitope of major surface protein 5 (MSP5), defined by monoclonal antibody (MAb) ANAF16C1, is conserved among Anaplasma species (E. S. Visser, T. C. McGuire, G. H. Palmer, W. C. Davis, V. Shkap, E. Pipano, and D. P. Knowles, Jr., Infect. Immun. 60:5139-5144, 1992) and is expressed in the salivary glands of infected ticks. A competitive inhibition ELISA (cELISA) for the detection of bovine anti-MSP5 antibodies was developed by using purified recombinant MSP5 fusion protein and MAb ANAF16C1. The specificity of the recombinant-MSP5 cELISA within North America was established by using 261 serum samples from cattle in the regions of Hawaii and Northern Ontario where anaplasmosis is not endemic and from cattle proven by splenectomy or subinoculation of whole blood into susceptible splenectomized recipients to be uninfected. The maximum percent inhibition by these sera was 18%. Sera known to be positive were obtained from 35 cattle either experimentally inoculated with infected erythrocytes or exposed to infected Dermacentor andersoni ticks. Thirty-four of the 35 serum samples inhibited MAb ANAF16C1 binding by > or = 25%. During acute infection, the MSP5 cELISA detected antibodies prior to or concomitantly with the appearance of rickettsiae in erythrocytes. Antibodies were detectable in sera from persistently infected cattle inoculated as long as 6 years previously. PMID:8862589

  18. Altered microRNA expression and pre-mRNA splicing events reveal new mechanisms associated with early stage Mycobacterium avium subspecies paratuberculosis infection

    PubMed Central

    Liang, Guanxiang; Malmuthuge, Nilusha; Guan, Yongjuan; Ren, Yuwei; Griebel, Philip J.; Guan, Le Luo

    2016-01-01

    The molecular regulatory mechanisms of host responses to Mycobacterium avium subsp. paratuberculosis (MAP) infection during the early subclinical stage are still not clear. In this study, surgically isolated ileal segments in newborn calves (n = 5) were used to establish in vivo MAP infection adjacent to an uninfected control intestinal compartment. RNA-Seq was used to profile the whole transcriptome (mRNAs) and the microRNAome (miRNAs) of ileal tissues collected at one-month post-infection. The most related function of the differentially expressed mRNAs between infected and uninfected tissues was “proliferation of endothelial cells”, indicating that MAP infection may lead to the over-proliferation of endothelial cells. In addition, 46.2% of detected mRNAs displayed alternative splicing events. The pre-mRNA of two genes related to macrophage maturation (monocyte to macrophage differentiation-associated) and lysosome function (adenosine deaminase) showed differential alternative splicing events, suggesting that specific changes in the pre-mRNA splicing sites may be a mechanism by which MAP escapes host immune responses. Moreover, 9 miRNAs were differentially expressed after MAP infection. The integrated analysis of microRNAome and transcriptome revealed that these miRNAs might regulate host responses to MAP infection, such as “proliferation of endothelial cells” (bta-miR-196 b), “bacteria recognition” (bta-miR-146 b), and “regulation of the inflammatory response” (bta-miR-146 b). PMID:27102525

  19. Induction of immunomodulatory miR-146a and miR-155 in small intestinal epithelium of Vibrio cholerae infected patients at acute stage of cholera

    PubMed Central

    Melgar, Silvia; Aung, Kyaw Min; Rahman, Arman; Qadri, Firdausi; Wai, Sun Nyunt; Shirin, Tahmina

    2017-01-01

    The potential immunomodulatory role of microRNAs in small intestine of patients with acute watery diarrhea caused by Vibrio cholerae O1 or enterotoxigenic Escherichia coli (ETEC) infection was investigated. Duodenal biopsies were obtained from study-participants at the acute (day 2) and convalescent (day 21) stages of disease, and from healthy individuals. Levels of miR-146a, miR-155 and miR-375 and target gene (IRAK1, TRAF6, CARD10) and 11 cytokine mRNAs were determined by qRT-PCR. The cellular source of microRNAs in biopsies was analyzed by in situ hybridization. The ability of V. cholerae bacteria and their secreted products to cause changes in microRNA- and mRNA levels in polarized tight monolayers of intestinal epithelial cells was investigated. miR-146a and miR-155 were expressed at significantly elevated levels at acute stage of V. cholerae infection and declined to normal at convalescent stage (P<0.009 versus controls; P = 0.03 versus convalescent stage, pairwise). Both microRNAs were mainly expressed in the epithelium. Only marginal down-regulation of target genes IRAK1 and CARD10 was seen and a weak cytokine-profile was identified in the acute infected mucosa. No elevation of microRNA levels was seen in ETEC infection. Challenge of tight monolayers with the wild type V. cholerae O1 strain C6706 and clinical isolates from two study-participants, caused significant increase in miR-155 and miR-146a by the strain C6706 (P<0.01). One clinical isolate caused reduction in IRAK1 levels (P<0.05) and none of the strains induced inflammatory cytokines. In contrast, secreted factors from these strains caused markedly increased levels of IL-8, IL-1β, and CARD10 (P<0.001), without inducing microRNA expression. Thus, miR-146a and miR-155 are expressed in the duodenal epithelium at the acute stage of cholera. The inducer is probably the V. cholerae bacterium. By inducing microRNAs the bacterium can limit the innate immune response of the host, including inflammation

  20. Infection

    MedlinePlus

    ... 23(4):251-69. Association for Professionals in Infection Control and Epidemiology (APIC) guideline. Back to Top Administration ... : Hospital Scope | Glossary | References | Site Map | Credits Freedom of ...

  1. Innate Nuclear Sensor IFI16 Translocates into the Cytoplasm during the Early Stage of In Vitro Human Cytomegalovirus Infection and Is Entrapped in the Egressing Virions during the Late Stage

    PubMed Central

    Dell'Oste, Valentina; Gatti, Deborah; Gugliesi, Francesca; De Andrea, Marco; Bawadekar, Mandar; Lo Cigno, Irene; Biolatti, Matteo; Vallino, Marta; Marschall, Manfred; Gariglio, Marisa

    2014-01-01

    defense mechanisms. Our findings describe that during early stages of infection, IFI16 successfully recognizes HCMV DNA. However, in late stages HCMV mislocalizes IFI16 into the cytoplasmic viral assembly complex and finally entraps the protein into mature virions. We clarify here the mechanisms HCMV relies to overcome intracellular viral restriction, which provides new insights about the relevance of DNA sensors during HCMV infection. PMID:24696486

  2. A Mechanistic Model of Botrytis cinerea on Grapevines That Includes Weather, Vine Growth Stage, and the Main Infection Pathways

    PubMed Central

    González-Domínguez, Elisa; Caffi, Tito; Ciliberti, Nicola; Rossi, Vittorio

    2015-01-01

    A mechanistic model for Botrytis cinerea on grapevine was developed. The model, which accounts for conidia production on various inoculum sources and for multiple infection pathways, considers two infection periods. During the first period (“inflorescences clearly visible” to “berries groat-sized”), the model calculates: i) infection severity on inflorescences and young clusters caused by conidia (SEV1). During the second period (“majority of berries touching” to “berries ripe for harvest”), the model calculates: ii) infection severity of ripening berries by conidia (SEV2); and iii) severity of berry-to-berry infection caused by mycelium (SEV3). The model was validated in 21 epidemics (vineyard × year combinations) between 2009 and 2014 in Italy and France. A discriminant function analysis (DFA) was used to: i) evaluate the ability of the model to predict mild, intermediate, and severe epidemics; and ii) assess how SEV1, SEV2, and SEV3 contribute to epidemics. The model correctly classified the severity of 17 of 21 epidemics. Results from DFA were also used to calculate the daily probabilities that an ongoing epidemic would be mild, intermediate, or severe. SEV1 was the most influential variable in discriminating between mild and intermediate epidemics, whereas SEV2 and SEV3 were relevant for discriminating between intermediate and severe epidemics. The model represents an improvement of previous B. cinerea models in viticulture and could be useful for making decisions about Botrytis bunch rot control. PMID:26457808

  3. Plasma Metabolomics Biosignature According to HIV Stage of Infection, Pace of Disease Progression, Viremia Level and Immunological Response to Treatment

    PubMed Central

    Scarpelini, Bruno; Zanoni, Michelle; Sucupira, Maria Cecilia Araripe; Truong, Hong-Ha M.; Janini, Luiz Mario Ramos; Segurado, Ismael Dale Cotrin; Diaz, Ricardo Sobhie

    2016-01-01

    Background We evaluated plasma samples HIV-infected individuals with different phenotypic profile among five HIV-infected elite controllers and five rapid progressors after recent HIV infection and one year later and from 10 individuals subjected to antiretroviral therapy, five of whom were immunological non-responders (INR), before and after one year of antiretroviral treatment compared to 175 samples from HIV-negative patients. A targeted quantitative tandem mass spectrometry metabolomics approach was used in order to determine plasma metabolomics biosignature that may relate to HIV infection, pace of HIV disease progression, and immunological response to treatment. Results Twenty-five unique metabolites were identified, including five metabolites that could distinguish rapid progressors and INRs at baseline. Severe deregulation in acylcarnitine and sphingomyelin metabolism compatible with mitochondrial deficiencies was observed. β-oxidation and sphingosine‐1‐phosphate-phosphatase-1 activity were down-regulated, whereas acyl-alkyl-containing phosphatidylcholines and alkylglyceronephosphate synthase levels were elevated in INRs. Evidence that elite controllers harbor an inborn error of metabolism (late-onset multiple acyl-coenzyme A dehydrogenase deficiency [MADD]) was detected. Conclusions Blood-based markers from metabolomics show a very high accuracy of discriminating HIV infection between varieties of controls and have the ability to predict rapid disease progression or poor antiretroviral immunological response. These metabolites can be used as biomarkers of HIV natural evolution or treatment response and provide insight into the mechanisms of the disease. PMID:27941971

  4. Clinical trial in healthy malaria-naïve adults to evaluate the safety, tolerability, immunogenicity and efficacy of MuStDO5, a five-gene, sporozoite/hepatic stage Plasmodium falciparum DNA vaccine combined with escalating dose human GM-CSF DNA

    PubMed Central

    Richie, Thomas L.; Charoenvit, Yupin; Wang, Ruobing; Epstein, Judith E.; Hedstrom, Richard C.; Kumar, Sanjai; Luke, Thomas C.; Freilich, Daniel A.; Aguiar, Joao C.; Sacci, Jr., John B.; Sedegah, Martha; Nosek, Jr., Ronald A.; De La Vega, Patricia; Berzins, Mara P.; Majam, Victoria F.; Abot, Esteban N.; Ganeshan, Harini; Richie, Nancy O.; Banania, Jo Glenna; Baraceros, Maria Fe B.; Geter, Tanya G.; Mere, Robin; Bebris, Lolita; Limbach, Keith; Hickey, Bradley W.; Lanar, David E.; Ng, Jennifer; Shi, Meng; Hobart, Peter M.; Norman, Jon A.; Soisson, Lorraine A.; Hollingdale, Michael R.; Rogers, William O.; Doolan, Denise L.; Hoffman, Stephen L.

    2012-01-01

    When introduced in the 1990s, immunization with DNA plasmids was considered potentially revolutionary for vaccine development, particularly for vaccines intended to induce protective CD8 T cell responses against multiple antigens. We conducted, in 1997−1998, the first clinical trial in healthy humans of a DNA vaccine, a single plasmid encoding Plasmodium falciparum circumsporozoite protein (PfCSP), as an initial step toward developing a multi-antigen malaria vaccine targeting the liver stages of the parasite. As the next step, we conducted in 2000–2001 a clinical trial of a five-plasmid mixture called MuStDO5 encoding pre-erythrocytic antigens PfCSP, PfSSP2/TRAP, PfEXP1, PfLSA1 and PfLSA3. Thirty-two, malaria-naïve, adult volunteers were enrolled sequentially into four cohorts receiving a mixture of 500 μg of each plasmid plus escalating doses (0, 20, 100 or 500 μg) of a sixth plasmid encoding human granulocyte macrophage-colony stimulating factor (hGM-CSF). Three doses of each formulation were administered intramuscularly by needle-less jet injection at 0, 4 and 8 weeks, and each cohort had controlled human malaria infection administered by five mosquito bites 18 d later. The vaccine was safe and well-tolerated, inducing moderate antigen-specific, MHC-restricted T cell interferon-γ responses but no antibodies. Although no volunteers were protected, T cell responses were boosted post malaria challenge. This trial demonstrated the MuStDO5 DNA and hGM-CSF plasmids to be safe and modestly immunogenic for T cell responses. It also laid the foundation for priming with DNA plasmids and boosting with recombinant viruses, an approach known for nearly 15 y to enhance the immunogenicity and protective efficacy of DNA vaccines. PMID:23151451

  5. 2-Octadecynoic acid as a dual life stage inhibitor of Plasmodium infections and plasmodial FAS-II enzymes.

    PubMed

    Carballeira, Néstor M; Bwalya, Angela Gono; Itoe, Maurice Ayamba; Andricopulo, Adriano D; Cordero-Maldonado, María Lorena; Kaiser, Marcel; Mota, Maria M; Crawford, Alexander D; Guido, Rafael V C; Tasdemir, Deniz

    2014-09-01

    The malaria parasite Plasmodium goes through two life stages in the human host, a non-symptomatic liver stage (LS) followed by a blood stage with all clinical manifestation of the disease. In this study, we investigated a series of 2-alkynoic fatty acids (2-AFAs) with chain lengths between 14 and 18 carbon atoms for dual in vitro activity against both life stages. 2-Octadecynoic acid (2-ODA) was identified as the best inhibitor of Plasmodium berghei parasites with ten times higher potency (IC50=0.34 μg/ml) than the control drug. In target determination studies, the same compound inhibited three Plasmodium falciparum FAS-II (PfFAS-II) elongation enzymes PfFabI, PfFabZ, and PfFabG with the lowest IC50 values (0.28-0.80 μg/ml, respectively). Molecular modeling studies provided insights into the molecular aspects underlying the inhibitory activity of this series of 2-AFAs and a likely explanation for the considerably different inhibition potentials. Blood stages of P. falciparum followed a similar trend where 2-ODA emerged as the most active compound, with 20 times less potency. The general toxicity and hepatotoxicity of 2-AFAs were evaluated by in vitro and in vivo methods in mammalian cell lines and zebrafish models, respectively. This study identifies 2-ODA as the most promising antiparasitic 2-AFA, particularly towards P. berghei parasites.

  6. Plasmodium vivax but Not Plasmodium falciparum Blood-Stage Infection in Humans Is Associated with the Expansion of a CD8+ T Cell Population with Cytotoxic Potential

    PubMed Central

    Burel, Julie G.; Apte, Simon H.; McCarthy, James S.; Doolan, Denise L.

    2016-01-01

    P. vivax and P. falciparum parasites display different tropism for host cells and induce very different clinical symptoms and pathology, suggesting that the immune responses required for protection may differ between these two species. However, no study has qualitatively compared the immune responses to P. falciparum or P. vivax in humans following primary exposure and infection. Here, we show that the two species differ in terms of the cellular immune responses elicited following primary infection. Specifically, P. vivax induced the expansion of a subset of CD8+ T cells expressing the activation marker CD38, whereas P. falciparum induced the expansion of CD38+ CD4+ T cells. The CD38+ CD8+ T cell population that expanded following P. vivax infection displayed greater cytotoxic potential compared to CD38- CD8+ T cells, and compared to CD38+ CD8+ T cells circulating during P. falciparum infection. We hypothesize that P. vivax infection leads to a stronger CD38+ CD8+ T cell activation because of its preferred tropism for MHC-I-expressing reticulocytes that, unlike mature red blood cells, can present antigen directly to CD8+ T cells. This study provides the first line of evidence to suggest an effector role for CD8+ T cells in P. vivax blood-stage immunity. It is also the first report of species-specific differences in the subset of T cells that are expanded following primary Plasmodium infection, suggesting that malaria vaccine development may require optimization according to the target parasite. Trial Registration anzctr.org.au ACTRN12612000814875; anzctr.org.au ACTRN12613000565741; anzctr.org.au ACTRN12613001040752; ClinicalTrials.gov NCT02281344; anzctr.org.au ACTRN12612001096842; anzctr.org.au ACTRN12613001008718 PMID:27930660

  7. Pasteurella multocida non-native joint infection after a dog lick: A case report describing a complicated two-stage revision and a comprehensive review of the literature.

    PubMed

    Lam, Philip W; Page, Andrea V

    2015-01-01

    Prosthetic joint infections (PJIs) are commonly caused by pathogens such as Staphylococcus aureus and coagulase-negative staphylococci; however, other microbial etiologies and specific risk factors are increasingly recognized. Pasteurella multocida is a Gram-negative coccobacillus that is part of the normal oral flora in many animals, and is particularly common in dogs and cats. PJIs caused by P multocida have been reported only rarely in the literature and typically occur in the context of an animal bite or scratch. The present article describes a P multocida joint infection that occurred after a dog lick and complicated a two-stage revision arthroplasty. A comprehensive review of the literature regarding P multocida PJIs follows.

  8. Pasteurella multocida non-native joint infection after a dog lick: A case report describing a complicated two-stage revision and a comprehensive review of the literature

    PubMed Central

    Philip W, Lam; Page, Andrea V

    2015-01-01

    Prosthetic joint infections (PJIs) are commonly caused by pathogens such as Staphylococcus aureus and coagulase-negative staphylococci; however, other microbial etiologies and specific risk factors are increasingly recognized. Pasteurella multocida is a Gram-negative coccobacillus that is part of the normal oral flora in many animals, and is particularly common in dogs and cats. PJIs caused by P multocida have been reported only rarely in the literature and typically occur in the context of an animal bite or scratch. The present article describes a P multocida joint infection that occurred after a dog lick and complicated a two-stage revision arthroplasty. A comprehensive review of the literature regarding P multocida PJIs follows. PMID:26361490

  9. Cytoskeleton remodling and alterations in smooth muscle contractility in the bovine jejunum during the early stage of Cooperia oncophora infection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Gastrointestinal nematodes of the genus Cooperia are arguably the most important parasites of cattle. We characterized the bovine jejunal transcriptome in response to C. oncophora infection using RNA-seq technology. Approximately 71% of the 25,670 bovine genes were detected in the jejunal transcript...

  10. Genome-wide prediction and functional validation of promoter motifs regulating gene expression in spore and infection stages of Phytophthora infestans.

    PubMed

    Roy, Sourav; Kagda, Meenakshi; Judelson, Howard S

    2013-03-01

    Most eukaryotic pathogens have complex life cycles in which gene expression networks orchestrate the formation of cells specialized for dissemination or host colonization. In the oomycete Phytophthora infestans, the potato late blight pathogen, major shifts in mRNA profiles during developmental transitions were identified using microarrays. We used those data with search algorithms to discover about 100 motifs that are over-represented in promoters of genes up-regulated in hyphae, sporangia, sporangia undergoing zoosporogenesis, swimming zoospores, or germinated cysts forming appressoria (infection structures). Most of the putative stage-specific transcription factor binding sites (TFBSs) thus identified had features typical of TFBSs such as position or orientation bias, palindromy, and conservation in related species. Each of six motifs tested in P. infestans transformants using the GUS reporter gene conferred the expected stage-specific expression pattern, and several were shown to bind nuclear proteins in gel-shift assays. Motifs linked to the appressoria-forming stage, including a functionally validated TFBS, were over-represented in promoters of genes encoding effectors and other pathogenesis-related proteins. To understand how promoter and genome architecture influence expression, we also mapped transcription patterns to the P. infestans genome assembly. Adjacent genes were not typically induced in the same stage, including genes transcribed in opposite directions from small intergenic regions, but co-regulated gene pairs occurred more than expected by random chance. These data help illuminate the processes regulating development and pathogenesis, and will enable future attempts to purify the cognate transcription factors.

  11. A Phosphorylcholine-Containing Glycolipid-like Antigen Present on the Surface of Infective Stage Larvae of Ascaris spp. Is a Major Antibody Target in Infected Pigs and Humans

    PubMed Central

    Masure, Dries; Wang, Tao; Nejsum, Peter; Hokke, Cornelis H.; Geldhof, Peter

    2016-01-01

    Background The pig parasite Ascaris suum plays and important role in veterinary medicine and represents a suitable model for A. lumbricoides, which infects over 800 million people. In pigs, continued exposure to Ascaris induces immunity at the level of the gut, protecting the host against migrating larvae. The objective of this study was to identify and characterize parasite antigens targeted by this local immune response that may be crucial for parasite invasion and establishment and to evaluate their protective and diagnostic potential. Methodology/Principal Findings Pigs were immunized by trickle infection for 30 weeks, challenged with 2,000 eggs at week 32 and euthanized two weeks after challenge. At necropsy, there was a 100% reduction in worms recovered from the intestine and a 97.2% reduction in liver white spots in comparison with challenged non-immune control animals. Antibodies purified from the intestinal mucus or from the supernatant of cultured antibody secreting cells from mesenteric lymph nodes of immune pigs were used to probe L3 extracts to identify antibody targets. This resulted in the recognition of a 12kDa antigen (As12) that is actively shed from infective Ascaris L3. As12 was characterized as a phosphorylcholine-containing glycolipid-like antigen that is highly resistant to different enzymatic and chemical treatments. Vaccinating pigs with an As12 fraction did not induce protective immunity to challenge infection. However, serological analysis using sera or plasma from experimentally infected pigs or naturally infected humans demonstrated that the As12 ELISA was able to detect long-term exposure to Ascaris with a high diagnostic sensitivity (98.4% and 92%, respectively) and specificity (95.5% and 90.0%) in pigs and humans, respectively. Conclusions/Significance These findings show the presence of a highly stage specific, glycolipid-like component (As12) that is actively secreted by infectious Ascaris larvae and which acts as a major antibody

  12. NOS2 variants reveal a dual genetic control of nitric oxide levels, susceptibility to Plasmodium infection, and cerebral malaria.

    PubMed

    Trovoada, Maria de Jesus; Martins, Madalena; Ben Mansour, Riadh; Sambo, Maria do Rosário; Fernandes, Ana B; Antunes Gonçalves, Lígia; Borja, Artur; Moya, Roni; Almeida, Paulo; Costa, João; Marques, Isabel; Macedo, M Paula; Coutinho, António; Narum, David L; Penha-Gonçalves, Carlos

    2014-03-01

    Nitric oxide (NO) is a proposed component of malaria pathogenesis, and the inducible nitric oxide synthase gene (NOS2) has been associated to malaria susceptibility. We analyzed the role of NOS2 polymorphisms on NO bioavailability and on susceptibility to infection, Plasmodium carrier status and clinical malaria. Two distinct West African sample collections were studied: a population-based collection of 1,168 apparently healthy individuals from the Príncipe Island and a hospital-based cohort of 269 Angolan children. We found that two NOS2 promoter single-nucleotide polymorphism (SNP) alleles associated to low NO plasma levels in noninfected individuals were also associated to reduced risk of pre-erythrocytic infection as measured anti-CSP antibody levels (6.25E-04 < P < 7.57E-04). In contrast, three SNP alleles within the NOS2 cistronic region conferring increased NO plasma levels in asymptomatic carriers were strongly associated to risk of parasite carriage (8.00E-05 < P < 7.90E-04). Notwithstanding, three SNP alleles in this region protected from cerebral malaria (7.90E-4 < P < 4.33E-02). Cohesively, the results revealed a dual regimen in the genetic control of NO bioavailability afforded by NOS2 depending on the infection status. NOS2 promoter variants operate in noninfected individuals to decrease both NO bioavailability and susceptibility to pre-erythrocytic infection. Conversely, NOS2 cistronic variants (namely, rs6505469) operate in infected individuals to increase NO bioavailability and confer increased susceptibility to unapparent infection but protect from cerebral malaria. These findings corroborate the hypothesis that NO anti-inflammatory properties impact on different steps of malaria pathogenesis, explicitly by favoring infection susceptibility and deterring severe malaria syndromes.

  13. Infection,

    DTIC Science & Technology

    1980-10-16

    inapparent infection. A refeeding program may thus become complicated by the sudden appearance of a life-threatening infectious illness (3). (3) The...Beisel, W. R. 23 Unusually low serum concentrations of inorganic phosphate have been reported in patients with gram-negative sepsis and in Reye’s syndrome ...infection should be corrected by a well-managed program of convalescent-period refeeding . This aspect of nutritional support is too often ignored. On the

  14. Host Cell Responses to Persistent Mycoplasmas - Different Stages in Infection of HeLa Cells with Mycoplasma hominis

    PubMed Central

    Hopfe, Miriam; Deenen, René; Degrandi, Daniel; Köhrer, Karl; Henrich, Birgit

    2013-01-01

    Mycoplasma hominis is a facultative human pathogen primarily associated with bacterial vaginosis and pelvic inflammatory disease, but it is also able to spread to other sites, leading to arthritis or, in neonates, meningitis. With a minimal set of 537 annotated genes, M. hominis is the second smallest self-replicating mycoplasma and thus an ideal model organism for studying the effects of an infectious agent on its host more closely. M. hominis adherence, colonisation and invasion of HeLa cells were characterised in a time-course study using scanning electron microscopy, confocal microscopy and microarray-based analysis of the HeLa cell transcriptome. At 4 h post infection, cytoadherence of M. hominis to the HeLa cell surface was accompanied by differential regulation of 723 host genes (>2 fold change in expression). Genes associated with immune responses and signal transduction pathways were mainly affected and components involved in cell-cycle regulation, growth and death were highly upregulated. At 48 h post infection, when mycoplasma invasion started, 1588 host genes were differentially expressed and expression of genes for lysosome-specific proteins associated with bacterial lysis was detected. In a chronically infected HeLa cell line (2 weeks), the proportion of intracellular mycoplasmas reached a maximum of 10% and M. hominis-filled protrusions of the host cell membrane were seen by confocal microscopy, suggesting exocytotic dissemination. Of the 1972 regulated host genes, components of the ECM-receptor interaction pathway and phagosome-related integrins were markedly increased. The immune response was quite different to that at the beginning of infection, with a prominent induction of IL1B gene expression, affecting pathways of MAPK signalling, and genes connected with cytokine-cytokine interactions and apoptosis. These data show for the first time the complex, time-dependent reaction of the host directed at mycoplasmal clearance and the counter measures of

  15. Extra-pulmonary tuberculosis infection in the dialysis patients with end stage renal diseases: case reports and literature review.

    PubMed

    Yang, Wen-fang; Han, Fei; Zhang, Xiao-hui; Zhang, Ping; Chen, Jiang-hua

    2013-01-01

    The diagnosis of extra-pulmonary tuberculosis (TB) seems relatively difficult due to the absence of specific symptoms and signs in patients on peritoneal dialysis or hemodialysis. We report four cases of extra-pulmonary tuberculosis on dialysis, with two cases on peritoneal dialysis and two cases on hemodialysis. The presentations, therapy, and outcomes of TB infection in these patients were reviewed. Otherwise, the English literature published in the PubMed database associating extra-pulmonary tuberculosis on dialysis over the last three decades is reviewed. A total of 61 studies containing 70 cases were included. The most common primary disease was diabetic nephropathy (22.86%, 16/70). The peritoneum (31.42%, 22/70), bone (21.42%, 15/70), and lymph node (20%, 14/70) were the most frequently infected. Single organ infection was common (90%, 63/70). Fever (58.57%, 41/70), pain (35.71%, 25/70), and enlarged lymph node (20%, 14/70) were the most common symptoms. Biopsy (67.14%, 47/70) and culture (40%, 28/70) provided most reliable methods for clear diagnosis of tuberculosis. The combined treatment of isoniazid, rifampicin, pyrazinamide, and ethambutol (44.29%, 31/70) was the most common therapy. The majority of patients improved (82.86%, 58/70); however, 12 cases got worse (17.14%), with 10 of them dying (14.29%). Physicians should be aware of the non-specific symptoms and location of infection, and consider tuberculosis in their differential diagnoses in dialysis patients presenting with symptoms such as fever, pain, and weight loss.

  16. [A very up-to-date stage in the fate of infectious diseases: parasitic and fungal opportunistic infections].

    PubMed

    Ambroise-Thomas, P; Grillot, R

    1995-04-01

    Opportunistic parasitosis and mycosis are becoming ever more widespread, mainly under the influence of major immunodeficiencies, either acquired (AIDS) or therapeutic. In this general overview, their main aspects, both clinical and epidemiological, are underlined. In terms of epidemiology, three types of phenomena have been observed: 1) emergence of human parasitosis unknown before (microsporidiosis due to Enterocytozoon bieneusi, Encephalitozoom hellem or Septata intestinalis); 2) among the human parasites already known, identification of very pathogenic strains (Toxoplasma gondii, Aspergillus fumigatus, Cryptococcus neoformans); 3) origin probably or certainly nosocomial of certain infections (pneumocystosis; toxoplasmosis and visceral leishmaniasis transmitted during bone-marrow or organ transplantations). The development of deep mycosis (invasive aspergillosis) is particularly promoted by granulopenia and alterations in the phagocytosis. On the other hand, opportunistic protozoosis (toxoplasmosis and leishmaniasis) and helminthiasis (strongyloidosis due to Strongyloides stercolaris) are related, above all, to disorders in cellular immunity (deficit of CD4+, mainly). Finally, several of these infections may be characterised by a variety of clinical pictures and outcome, depending on the contributory factors (immunodeficit or not) which led to the development of the infection.

  17. Species, developmental stage and infection with microbial pathogens of engorged ticks removed from dogs and questing ticks.

    PubMed

    Leschnik, M W; Khanakah, G; Duscher, G; Wille-Piazzai, W; Hörweg, C; Joachim, A; Stanek, G

    2012-12-01

    Research into tick-borne diseases implies vector sampling and the detection and identification of microbial pathogens. Ticks were collected simultaneously from dogs that had been exposed to tick bites and by flagging the ground in the area in which the dogs had been exposed. In total, 200 ticks were sampled, of which 104 came from dogs and 96 were collected by flagging. These ticks were subsequently examined for DNA of Borrelia burgdorferi sensu lato, Anaplasma phagocytophilum, Rickettsia spp. and Babesia canis. A mixed sample of adult ticks and nymphs of Ixodes ricinus (Ixodida: Ixodidae) and Haemaphysalis concinna (Ixodida: Ixodidae) was obtained by flagging. Female I. ricinus and adult Dermacentor reticulatus (Ixodida: Ixodidae) ticks dominated the engorged ticks removed from dogs. Rickettsia spp. were detected in 17.0% of the examined ticks, A. phagocytophilum in 3.5%, B. canis in 1.5%, and B. burgdorferi s.l. in 16.0%. Ticks with multiple infections were found only among the flagging sample. The ticks removed from the dogs included 22 infected ticks, whereas the flagging sample included 44 infected ticks. The results showed that the method for collecting ticks influences the species composition of the sample and enables the detection of a different pattern of pathogens. Sampling strategies should be taken into consideration when interpreting studies on tick-borne pathogens.

  18. The effect of previous cold storage on the subsequent recovery of infective third stage nematode larvae from sheep faeces.

    PubMed

    McKenna, P B

    1998-12-31

    An investigation undertaken to determine the effect of previous cold storage on the recovery of third stage larvae of gastrointestinal nematodes of sheep, showed that increasing periods of exposure of faeces to 4 degrees C resulted in decreasing numbers of larvae subsequently recovered from them. Differences in the abilities of the eggs of the various genera, to survive such treatment, were found to lead to significant changes in the percentage generic compositions of their third stage larvae--in some cases following the prior refrigeration of faecal samples for as little as 24 h. These results suggest that where larval cultures are intended to provide estimates of the proportions of the various worm eggs in the faeces of sheep harboring mixed gastrointestinal nematode burdens, they should be performed only on freshly collected samples.

  19. Value of the oral swab for the molecular diagnosis of dogs in different stages of infection with Leishmania infantum.

    PubMed

    Aschar, Mariana; de Oliveira, Eveline Tozzi Braga; Laurenti, Marcia Dalastra; Marcondes, Mary; Tolezano, Jose Eduardo; Hiramoto, Roberto Mitsuyoshi; Corbett, Carlos Eduardo P; da Matta, Vania Lucia Ribeiro

    2016-07-30

    This study was based on the need to employ a sensitive and specific method with samples that could be easily collected for diagnosing dogs infected with Leishmania infantum. To this end, we used real time-PCR (qPCR) to assess the value of the oral swab (OS) in detecting infected sick dogs (SD; n=62), including, for the first time, the analysis of apparently healthy infected dogs (AD; n=30), both from endemic areas for visceral leishmaniasis (VL). For comparison, we also evaluated the performance of the conjunctival swab (CS), blood (BL), lymph node (LN) and serology. We detected the presence of Leishmania DNA in the oral cavity in 62 out of the 92 dogs studied. The OS positivity (67.4%) was equivalent to the CS (68.5%) (p>0.05), higher than BL (52.2%) (p≤0.05), and lower than LN (84.8%) (p≤0.05). OS and CS performed well in SD dogs (82.3% and 83.9%, respectively) but not in AD dogs (36.7% for both samples). BL showed the lowest positivity (52.2%) and provided equivalent results between AD (60.0%) and SD (48.4%) dogs (p>0.05). LN yielded the highest positivity (84.8%), and it was also higher in the SD population (93.5%) compared to the AD population (66.7%) (p≤0.05). Parasite load was high in LN, moderate in OS and CS, and low in BL, showing the relationship between the levels of parasitism and the positivity rates found in these samples. Serology was positive in 82.2% of the SD group and in 70% of the AD dogs (p>0.05). Among the 20 seronegative dogs, seven (35%) were positive in either OS or CS, and 12 (60%) were positive when both noninvasive samples were jointly considered. The OS/CS combination resulted in a significant increase of positivity (p≤0.05) for the AD dogs (from 36.7% to 63.4%), as well as OS/serology (80%) and OS/CS/serology (83.4%). For the SD population, positivity reached up to 95.2% with the same combinations, showing that combination of samples and/or tests is required for the identification of dogs infected with L. infantum and that the

  20. Efficacy of a milbemycin oxime-praziquantel combination product against adult and immature stages of Toxocara cati in cats and kittens after induced infection.

    PubMed

    Schenker, R; Bowman, D; Epe, C; Cody, R; Seewald, W; Strehlau, G; Junquera, P

    2007-04-10

    Two studies were performed to examine the efficacy of milbemycin oxime against fourth-stage larvae or adults of Toxocara cati. In the study to determine efficacy against fourth-stage larvae, 20 domestic shorthair cats were inoculated with 500 embryonated eggs. Four weeks after inoculation, the animals were allocated to two groups, and cats in one group were treated with medicated tablets containing 4 mg milbemycin oxime and 10mg praziquantel (MILBEMAX) and cats in the other group with placebo tablets. Seven days after treatment the animals were euthanatized and necropsied for worm counting. The number of worms found was significantly (p=0.0002) lower in cats treated with medicated tablets than in cats treated with placebo tablets. The reduction in the number of worms was 96.53%. In the study to determine efficacy against mature adult worms, 13 kittens were inoculated with T. cati embryonated eggs. On day 45 after inoculation and after the infection had been confirmed through faecal examinations for 11 out of the 13 animals, the 11 infected animals were allocated to two groups and treated as in the first study. Seven days after treatment, all animals were euthanatized and necropsied for worm counting. The number of worms found was significantly (p=0.0043) lower in kittens treated with medicated tablets than in kittens treated with placebo tablets. The reduction in the number of worms was 95.90%. No adverse effects were recorded during either study. It is concluded that the milbemycin oxime-praziquantel tablets that were used are efficacious for the control of T. cati infections in cats.

  1. Soft X-ray microscopy analysis of cell volume and hemoglobin content in erythrocytes infected with asexual and sexual stages of Plasmodium falciparum.

    PubMed

    Hanssen, Eric; Knoechel, Christian; Dearnley, Megan; Dixon, Matthew W A; Le Gros, Mark; Larabell, Carolyn; Tilley, Leann

    2012-02-01

    Plasmodium falciparum, the most virulent agent of human malaria, undergoes both asexual cycling and sexual differentiation inside erythrocytes. As the intraerythrocytic parasite develops it increases in size and alters the permeability of the host cell plasma membrane. An intriguing question is: how is the integrity of the host erythrocyte maintained during the intraerythrocytic cycle? We have used water window cryo X-ray tomography to determine cell morphology and hemoglobin content at different stages of asexual and sexual differentiation. The cryo stabilization preserves native structure permitting accurate analyses of parasite and host cell volumes. Absorption of soft X-rays by protein adheres to Beer-Lambert's law permitting quantitation of the concentration of hemoglobin in the host cell compartment. During asexual development the volume of the parasite reaches about 50% of the uninfected erythrocyte volume but the infected erythrocyte volume remains relatively constant. The total hemoglobin content gradually decreases during the 48h cycle but its concentration remains constant until early trophozoite stage, decreases by 25%, then remains constant again until just prior to rupture. During early sexual development the gametocyte has a similar morphology to a trophozoite but then undergoes a dramatic shape change. Our cryo X-ray tomography analysis reveals that about 70% of the host cell hemoglobin is taken up and digested during gametocyte development and the parasite eventually occupies about 50% of the uninfected erythrocyte volume. The total volume of the infected erythrocyte remains constant, apart from some reversible shrinkage at stage IV, while the concentration of hemoglobin decreases to about 70% of that in an uninfected erythrocyte.

  2. APOBEC3G mRNA expression in exposed seronegative and early stage HIV infected individuals decreases with removal of exposure and with disease progression

    PubMed Central

    Vázquez-Pérez, Joel A; Ormsby, Christopher E; Hernández-Juan, Ramón; Torres, Klintsy J; Reyes-Terán, Gustavo

    2009-01-01

    Background APOBEC3G is an antiretroviral factor that acts by inducing G to A mutations. In this study, we examined the expression of APOBEC3G in uninfected HIV-1 exposed individuals at the time of their partner's diagnosis and one year later. We then compared this expression with that of infected individuals at different disease stages. APOBEC3G mRNA was measured in PBMCs from three groups: healthy controls with no known risk factor to HIV infection (n = 26), exposed uninfected individuals who had unprotected sex with their HIV+ partners for at least 3 months (n = 37), and HIV infected patients at various disease stages (n = 45), including 8 patients with low HIV viral loads < 10,000 copies/mL (LVL) for at least 3 years. Additionally, we obtained sequences from the env, gag, pol, nef, vif and the LTR of the patients' virus. Results Exposed uninfected individuals expressed higher APOBEC3G than healthy controls (3.86 vs. 1.69 relative expression units), and their expression significantly decreased after a year from the HIV diagnosis and subsequent treatment of their partners. Infected individuals showed a positive correlation (Rho = 0.57, p = 0.00006) of APOBEC3G expression with CD4+ T cell count, and a negative correlation with HIV viremia (Rho = -0.54, p = 0.00004). The percentage of G to A mutations had a positive correlation (Rho = 0.43, p = 0.0226) with APOBEC3G expression, and it was higher in LVL individuals than in the other patients (IQR 8.27 to 9.64 vs. 7.06 to 8.1, p = 0.0084). Out of 8 LVLs, 3 had hypermutations, and 4 had premature stop codons only in viral vif. Conclusion The results suggest that exposure to HIV may trigger APOBEC3G expression in PBMCs, in the absence of infection. Additionally, cessation of exposure or advanced disease is associated with decreased APOBEC3G expression. PMID:19254362

  3. Immunological signature of the different clinical stages of the HTLV-1 infection: establishing serum biomarkers for HTLV-1-associated disease morbidity.

    PubMed

    Starling, Ana Lúcia Borges; Coelho-Dos-Reis, Jordana Grazziela Alves; Peruhype-Magalhães, Vanessa; Pascoal-Xavier, Marcelo Antônio; Gonçalves, Denise Utsch; Béla, Samantha Ribeiro; Lambertucci, José Roberto; Labanca, Ludimila; Souza Pereira, Silvio Roberto; Teixeira-Carvalho, Andréa; Ribas, João Gabriel; Trindade, Bruno Caetano; Faccioli, Lucia Helena; Carneiro-Proietti, Anna Bárbara Freitas; Martins-Filho, Olindo Assis

    2015-01-01

    This study aimed at establishing the immunological signature and an algorithm for clinical management of the different clinical stages of the HTLV-1-infection based on serum biomarkers. A panel of serum biomarkers was evaluated by four sets of innovative/non-conventional data analysis approaches in samples from 87 HTLV-1 patients: asymptomatic carriers (AC), putative HTLV-1 associated myelopathy/tropical spastic paraparesis (pHAM/TSP) and HAM/TSP. The analysis of cumulative curves and molecular signatures pointed out that HAM/TSP presented a pro-inflammatory profile mediated by CXCL10/LTB-4/IL-6/TNF-α/IFN-γ, counterbalanced by IL-4/IL-10. The analysis of biomarker networks showed that AC presented a strongly intertwined pro-inflammatory/regulatory net with IL-4/IL-10 playing a central role, while HAM/TSP exhibited overall immune response toward a predominant pro-inflammatory profile. At last, the classification and regression trees proposed for clinical practice allowed for the construction of an algorithm to discriminate AC, pHAM and HAM/TSP patients with the elected biomarkers: IFN-γ, TNF-α, IL-10, IL-6, IL-4 and CysLT. These findings reveal a complex interaction among chemokine/leukotriene/cytokine in HTLV-1 infection and suggest the use of the selected but combined biomarkers for the follow-up/diagnosis of disease morbidity of HTLV-1-infected individuals.

  4. Efficient monitoring of the blood-stage infection in a malaria rodent model by the rotating-crystal magneto-optical method

    NASA Astrophysics Data System (ADS)

    Orbán, Ágnes; Rebelo, Maria; Molnár, Petra; Albuquerque, Inês S.; Butykai, Adam; Kézsmárki, István

    2016-03-01

    Intense research efforts have been focused on the improvement of the efficiency and sensitivity of malaria diagnostics, especially in resource-limited settings for the detection of asymptomatic infections. Our recently developed magneto-optical (MO) method allows the accurate quantification of malaria pigment crystals (hemozoin) in blood by their magnetically induced rotation. First evaluations of the method using β-hematin crystals and in vitro P. falciparum cultures implied its potential for high-sensitivity malaria diagnosis. To further investigate this potential, here we study the performance of the method in monitoring the in vivo onset and progression of the blood-stage infection in a rodent malaria model. Our results show that the MO method can detect the first generation of intraerythrocytic P. berghei parasites 66–76 hours after sporozoite injection, demonstrating similar sensitivity to Giesma-stained light microscopy and exceeding that of flow cytometric techniques. Magneto-optical measurements performed during and after the treatment of P. berghei infections revealed that both the follow up under treatment and the detection of later reinfections are feasible with this new technique. The present study demonstrates that the MO method – besides being label and reagent-free, automated and rapid – has a high in vivo sensitivity and is ready for in-field evaluation.

  5. Influence of stripe rust infection on the photosynthetic characteristics and antioxidant system of susceptible and resistant wheat cultivars at the adult plant stage

    PubMed Central

    Chen, Yang-Er; Cui, Jun-Mei; Su, Yan-Qiu; Yuan, Shu; Yuan, Ming; Zhang, Huai-Yu

    2015-01-01

    Wheat stripe rust (Puccinia striiformis f. sp. tritici, Pst), is one of the most serious diseases of wheat (Triticum aestivum L.) worldwide. To gain a better understanding of the protective mechanism against stripe rust at the adult plant stage, the differences in photosystem II and antioxidant enzymatic systems between susceptible and resistant wheat in response to stripe rust disease (P. striiformis) were investigated. We found that chlorophyll fluorescence and the activities of the antioxidant enzymes were higher in resistant wheat than in susceptible wheat after stripe rust infection. Compared with the susceptible wheat, the resistant wheat accumulated a higher level of D1 protein and a lower level of reactive oxygen species after infection. Furthermore, our results demonstrate that D1 and light-harvesting complex II (LHCII) phosphorylation are involved in the resistance to stripe rust in wheat. The CP29 protein was phosphorylated under stripe rust infection, like its phosphorylation in other monocots under environmental stresses. More extensive damages occur on the thylakoid membranes in the susceptible wheat compared with the resistant wheat. The findings provide evidence that thylakoid protein phosphorylation and antioxidant enzyme systems play important roles in plant responses and defense to biotic stress. PMID:26442087

  6. Efficient monitoring of the blood-stage infection in a malaria rodent model by the rotating-crystal magneto-optical method.

    PubMed

    Orbán, Ágnes; Rebelo, Maria; Molnár, Petra; Albuquerque, Inês S; Butykai, Adam; Kézsmárki, István

    2016-03-17

    Intense research efforts have been focused on the improvement of the efficiency and sensitivity of malaria diagnostics, especially in resource-limited settings for the detection of asymptomatic infections. Our recently developed magneto-optical (MO) method allows the accurate quantification of malaria pigment crystals (hemozoin) in blood by their magnetically induced rotation. First evaluations of the method using β-hematin crystals and in vitro P. falciparum cultures implied its potential for high-sensitivity malaria diagnosis. To further investigate this potential, here we study the performance of the method in monitoring the in vivo onset and progression of the blood-stage infection in a rodent malaria model. Our results show that the MO method can detect the first generation of intraerythrocytic P. berghei parasites 66-76 hours after sporozoite injection, demonstrating similar sensitivity to Giesma-stained light microscopy and exceeding that of flow cytometric techniques. Magneto-optical measurements performed during and after the treatment of P. berghei infections revealed that both the follow up under treatment and the detection of later reinfections are feasible with this new technique. The present study demonstrates that the MO method - besides being label and reagent-free, automated and rapid - has a high in vivo sensitivity and is ready for in-field evaluation.

  7. Surgical site infections in liver transplant recipients in the model for end-stage liver disease era: an analysis of the epidemiology, risk factors, and outcomes.

    PubMed

    Freire, Maristela Pinheiro; Soares Oshiro, Isabel C V; Bonazzi, Patricia Rodrigues; Guimarães, Thais; Ramos Figueira, Estela Regina; Bacchella, Telésforo; Costa, Silvia Figueiredo; Carneiro D'Albuquerque, Luiz Augusto; Abdala, Edson

    2013-09-01

    In recipients of liver transplantation (LT), surgical site infection (SSIs) are among the most common types of infection occurring in the first 60 days after LT. In 2007, the Model for End-Stage Liver Disease (MELD) scoring system was adopted as the basis for prioritizing organ allocation. Patients with higher MELD scores are at higher risk for developing SSIs as well as other health care-associated infections. However, there have been no studies comparing the incidence of SSIs in the pre-MELD era with the incidence in the period since its adoption. Therefore, the objectives of this study were to evaluate the incidence, etiology, epidemiology, and outcomes of post-LT SSIs in those 2 periods and to identify risk factors for SSIs. We evaluated all patients who underwent LT over a 10-year period (2002-2011). SSI cases were identified through active surveillance. The primary outcome measure was an SSI during the first 60 days after LT. Risk factors were analyzed via logistic regression, and 60-day survival rates were evaluated via Cox regression. We evaluated 543 patients who underwent LT 597 times. The SSI rates in the 2002-2006 and 2007-2011 periods were 30% and 24%, respectively (P = 0.21). We identified the following risk factors for SSIs: retransplantation, the transfusion of more than 2 U of blood during LT, dialysis, cold ischemia for >400 minutes, and a cytomegalovirus infection. The overall 60-day survival rate was 79%. Risk factors for 60-day mortality were retransplantation, dialysis, and a longer surgical time. The use of the MELD score modified the incidence and epidemiology of SSIs only during the first year after its adoption. Risks for SSIs were related more to intraoperative conditions and intercurrences after LT than to a patient's status before LT.

  8. Phagosomal Acidification Prevents Macrophage Inflammatory Cytokine Production to Malaria, and Dendritic Cells Are the Major Source at the Early Stages of Infection: IMPLICATION FOR MALARIA PROTECTIVE IMMUNITY DEVELOPMENT.

    PubMed

    Wu, Xianzhu; Gowda, Nagaraj M; Gowda, D Channe

    2015-09-18

    Inflammatory cytokines produced at the early stages of malaria infection contribute to shaping protective immunity and pathophysiology. To gain mechanistic insight into these processes, it is important to understand the cellular origin of cytokines because both cytokine input and cytokine-producing cells play key roles. Here, we determined cytokine responses by monocytes, macrophages, and dendritic cells (DCs) to purified Plasmodium falciparum and Plasmodium berghei ANKA, and by spleen macrophages and DCs from Plasmodium yoelii 17NXL-infected and P. berghei ANKA-infected mice. The results demonstrate that monocytes and macrophages do not produce inflammatory cytokines to malaria parasites and that DCs are the primary source early in infection, and DC subsets differentially produce cytokines. Importantly, blocking of phagosomal acidification by inhibiting vacuolar-type H(+)-ATPase enabled macrophages to elicit cytokine responses. Because cytokine responses to malaria parasites are mediated primarily through endosomal Toll-like receptors, our data indicate that the inability of macrophages to produce cytokines is due to the phagosomal acidification that disrupts endosomal ligand-receptor engagement. Macrophages efficiently produced cytokines to LPS upon simultaneously internalizing parasites and to heat-killed Escherichia coli, demonstrating that phagosomal acidification affects endosomal receptor-mediated, but not cell surface receptor-mediated, recognition of Toll-like receptor agonists. Enabling monocytes/macrophages to elicit immune responses to parasites by blocking endosomal acidification can be a novel strategy for the effective development of protective immunity to malaria. The results have important implications for enhancing the efficacy of a whole parasite-based malaria vaccine and for designing strategies for the development of protective immunity to pathogens that induce immune responses primarily through endosomal receptors.

  9. Identification of plant genes regulated in resistant potato Solanum sparsipilum during the early stages of infection by Globodera pallida.

    PubMed

    Jolivet, Katell; Grenier, Eric; Bouchet, Jean-Paul; Esquibet, Magali; Kerlan, Marie-Claire; Caromel, Bernard; Mugniéry, Didier; Lefebvre, Véronique

    2007-04-01

    Using a complementary (c)DNA-amplified fragment length polymorphism (AFLP) approach, we investigated differential gene expression linked to resistance mechanisms during the incompatible potato - Globodera pallida interaction. Expression was compared between a resistant and a susceptible potato clone, inoculated or not inoculated with G. pallida. These clones were issued from a cross between the resistant Solanum sparsipilum spl329.18 accession and the susceptible dihaploid S. tuberosum Caspar H3, and carried, respectively, resistant and susceptible alleles at the resistance quantitative trait loci (QTLs). Analysis was done on root fragments picked up at 4 time points, during a period of 6 days after infection, from penetration of the nematode in the root to degradation of the feeding site in resistant plants. A total of 2560 transcript-derived fragments (TDFs) were analyzed, resulting in the detection of 46 TDFs that were up- or downregulated. The number of TDFs that were up- or downregulated increased with time after inoculation. The majority of TDFs were upregulated at only 1 or 2 time points in response to infection. After isolation and sequencing of the TDFs of interest, a subset of 36 sequences were identified, among which 22 matched plant sequences and 2 matched nematode sequences. Some of the TDFs that matched plant genes showed clear homologies to genes involved in cell-cycle regulation, transcription regulation, resistance downstream signalling pathways, and defense mechanisms. Other sequences with homologies to plant genes of unknown function or without any significant similarity to known proteins were also found. Although not exhaustive, these results represent the most extensive list of genes with altered RNA levels after the incompatible G. pallida-potato interaction that has been published to date. The function of these genes could provide insight into resistance or plant defense mechanisms during incompatible potato-cyst nematode interactions.

  10. Economic Burden of Hepatitis C Virus Infection in Different Stages of Disease: A Report From Southern Iran

    PubMed Central

    Zare, Fatemeh; Fattahi, Mohammad Reza; Sepehrimanesh, Masood; Safarpour, Ali Reza

    2016-01-01

    Background Hepatitis C virus (HCV) infection is a major blood-borne infection which imposes high economic cost on the patients. Objectives The current study aimed to evaluate the total annual cost due to chronic HCV related diseases imposed on each patient and their family in Southern Iran. Patients and Methods Economic burden of chronic hepatitis C-related liver diseases (chronic hepatitis C, cirrhosis and hepatocellular carcinoma) were examined. The current retrospective study evaluated 200 Iranian patients for their socioeconomic status, utilization (direct and indirect costs) and treatment costs and work days lost due to illness by a structured questionnaire in 2015. Costs of hospital admissions were extracted from databases of Nemazee hospital, Shiraz, Iran. The outpatient expenditure per patient was measured through the rate of outpatient visits and average cost per visit reported by the patients; while the inpatient costs were calculated through annual rate of hospital admissions and average expenditure. Self-medication and direct non-medical costs were also reported. The human capital approach was used to measure the work loss cost. Results The total annual cost per patient for chronic hepatitis C, cirrhosis and hepatocellular carcinoma (HCC) based on purchasing power parity (PPP) were USD 1625.50, USD 6117.2, and USD 11047.2 in 2015, respectively. Conclusions Chronic hepatitis C-related liver diseases impose a substantial economic burden on patients, families and the society. The current study provides useful information on cost of treatment and work loss for different disease states, which can be further used in cost-effectiveness evaluations. PMID:27257424

  11. Opportunistic Infections

    MedlinePlus

    ... Infections Opportunistic Infections and Their Relationship to HIV/AIDS People with healthy immune systems can be exposed ... Disease Dementia Hospitalization & Palliative Care Related Topics on AIDS.gov Signs and Symptoms Immune System 101 Stages ...

  12. Plum Pox Virus 6K1 Protein Is Required for Viral Replication and Targets the Viral Replication Complex at the Early Stage of Infection

    PubMed Central

    Cui, Hongguang

    2016-01-01

    ABSTRACT The potyviral RNA genome encodes two polyproteins that are proteolytically processed by three viral protease domains into 11 mature proteins. Extensive molecular studies have identified functions for the majority of the viral proteins. For example, 6K2, one of the two smallest potyviral proteins, is an integral membrane protein and induces the endoplasmic reticulum (ER)-originated replication vesicles that target the chloroplast for robust viral replication. However, the functional role of 6K1, the other smallest protein, remains uncharacterized. In this study, we developed a series of recombinant full-length viral cDNA clones derived from a Canadian Plum pox virus (PPV) isolate. We found that deletion of any of the short motifs of 6K1 (each of which ranged from 5 to 13 amino acids), most of the 6K1 sequence (but with the conserved sequence of the cleavage sites being retained), or all of the 6K1 sequence in the PPV infectious clone abolished viral replication. The trans expression of 6K1 or the cis expression of a dislocated 6K1 failed to rescue the loss-of-replication phenotype, suggesting the temporal and spatial requirement of 6K1 for viral replication. Disruption of the N- or C-terminal cleavage site of 6K1, which prevented the release of 6K1 from the polyprotein, either partially or completely inhibited viral replication, suggesting the functional importance of the mature 6K1. We further found that green fluorescent protein-tagged 6K1 formed punctate inclusions at the viral early infection stage and colocalized with chloroplast-bound viral replicase elements 6K2 and NIb. Taken together, our results suggest that 6K1 is required for viral replication and is an important viral element of the viral replication complex at the early infection stage. IMPORTANCE Potyviruses account for more than 30% of known plant viruses and consist of many agriculturally important viruses. The genomes of potyviruses encode two polyproteins that are proteolytically

  13. Expression Analysis of Lily Type Lectin Isotypes in the Rock Bream, Oplegnathus fasciatus: in the Tissue, Developmental Stage and Viral Infection.

    PubMed

    Lee, Young Mee; Yang, In Jung; Noh, Jae Koo; Kim, Hyun Chul; Park, Choul-Ji; Park, Jong-Won; Noh, Gyeong Eon; Kim, Woo-Jin; Kim, Kyung-Kil

    2016-12-01

    Lectins belong to the pattern-recognition receptors (PRRs) class and play important roles in the recognition and elimination of pathogens via the innate immune system. Recently, it was reported that lily-type lectin-1 is involved when a pathogen attacks in the early immune response of fish. However, this study is limited to information that the lectin is involved in the innate immune response against viral infection. In the present study, the lily-type lectin-2 and -3 of Oplegnathus fasciatus (OfLTL-2 and 3) have been presented to be included B-lectin domain and two D-mannose binding sites in the amino acid sequence that an important feature for the fundamental structure. To investigate the functional properties of OfLTLs, the tissue distribution in the healthy rock bream and temporal expression during early developmental stage analysis are performed using quantitative real-time PCR. OfLTL-2 and 3 are predominantly expressed in the liver and skin, but rarely expressed in other organ. Also, the transcripts of OfLTLs are not expressed during the early developmental stage but its transcripts are increased after immune-related organs which are fully formed. In the challenge experiment with RBIV (rock bream iridovirus), the expression of OfLTLs was increased much more strongly in the late response than the early, unlike previously known. These results suggest that OfLTLs are specifically expressed in the immune-related tissues when those organs are fully formed and it can be inferred that the more intensively involved in the second half to the virus infection.

  14. Expression Analysis of Lily Type Lectin Isotypes in the Rock Bream, Oplegnathus fasciatus: in the Tissue, Developmental Stage and Viral Infection

    PubMed Central

    Lee, Young Mee; Yang, In Jung; Noh, Jae Koo; Kim, Hyun Chul; Park, Choul-Ji; Park, Jong-Won; Noh, Gyeong Eon; Kim, Woo-Jin; Kim, Kyung-Kil

    2016-01-01

    ABSTRACT Lectins belong to the pattern-recognition receptors (PRRs) class and play important roles in the recognition and elimination of pathogens via the innate immune system. Recently, it was reported that lily-type lectin-1 is involved when a pathogen attacks in the early immune response of fish. However, this study is limited to information that the lectin is involved in the innate immune response against viral infection. In the present study, the lily-type lectin-2 and -3 of Oplegnathus fasciatus (OfLTL-2 and 3) have been presented to be included B-lectin domain and two D-mannose binding sites in the amino acid sequence that an important feature for the fundamental structure. To investigate the functional properties of OfLTLs, the tissue distribution in the healthy rock bream and temporal expression during early developmental stage analysis are performed using quantitative real-time PCR. OfLTL-2 and 3 are predominantly expressed in the liver and skin, but rarely expressed in other organ. Also, the transcripts of OfLTLs are not expressed during the early developmental stage but its transcripts are increased after immune-related organs which are fully formed. In the challenge experiment with RBIV (rock bream iridovirus), the expression of OfLTLs was increased much more strongly in the late response than the early, unlike previously known. These results suggest that OfLTLs are specifically expressed in the immune-related tissues when those organs are fully formed and it can be inferred that the more intensively involved in the second half to the virus infection. PMID:28144635

  15. [Antiparasitic effects of peracetic acid (PAA) against infective stages (theronts) of white spot disease, Ichthyophthirius multifiliis in vitro].

    PubMed

    Meinelt, T; Staaks, J; Staaks, G; Stüber, A; Bräunig, I

    2007-10-01

    White spot disease, caused by the protozoan parasite Ichthyophthirius multifiliis (I. multifiliis), invades nearly all fresh water fish species and causes huge economic losses. In Germany no protocide substance is legal for the treatment of I. multifilis. As an alternative substance the peracetic acid (PAA) was tested to treat the free invasive stage (theront) of the parasite. PAA concentrations of 0.3 ppm were able to kill all theronts in 120 min in our investigations. As a result of these investigations we recommend an interval-application of 0.3 to 0.5 ppm PAA for 30 to 150 min. This application should be prolonged for two life cycles of the parasite. Biotic parameters as e. g. fish species, and age as well as abiotic parameters as e. g. temperature, pH and organic load of the water could possibly influence the efficiency of the PAA application and should therefore be taken into account while picking the dosage and length of the PAA exposure.

  16. [Infect of pingshen decoction on serum HGF, Cys C and TGF-beta1 diabetic nephropathy in early stage].

    PubMed

    Bao, Hui-Lan; Ye, Shang-He; Lou, Shi-Xian; Lu, Xiao-Wen; Zhou, Xiang-Feng

    2014-03-01

    Study the serum level of HGF, Cys C and TGF-beta1 in type 2 diabetic nephropathy (DN), the infect of Pingshen decoction on those index. Selected 69 cases of 2 type DN and randomly divided into therapy group (36 cases) and control group (33 cases). The therapy group were treated with Pingshen decoction 1 dose/d, bid po. The control group were treated with NephritisShu tablet, 6 tablet, tid po. 8 weeks was a course. Before and after treatment, we examine the serum level of HGF, Cys C and TGF-beta1 by ELISA and immunonephelometry, and compare with 30 cases of healthy control group. The study demonstrates that before treatment, the serum level of HGF in both groups were significantly lower than healthy control group (P < 0.01), but Cys C, TGF-beta1 were significantly higher (P < 0.01). After treatment, the serum level of HGF of both groups were increased. The serum level of HGF of therapy group were significantly higher than of control group (P < 0.01), but the serum level of Cys C and TGF-beta1 were significantly lower than control group (P < 0.01). The serum level of HGF was correlated negatively with Cys C,TGF-beta1. In control group, the UAER, urine beta2-MG and quantity of 24-hour urine protein were significantly decreased after treatment (P < 0.01). The index of urine of therapy group were significantly lower than control group (P < 0.01). Results indicate that test of serum level of HGF and Cys C,TGF-beta1 of diabetic nephropathy have important clinical significance. Pingshen decoction can effectively intervene in the serum level of HGF and Cys C, TGF-beta1 and index of urine.

  17. Drought increases cowpea (Vigna unguiculata [L.] Walp.) susceptibility to cowpea severe mosaic virus (CPSMV) at early stage of infection.

    PubMed

    Silva, Rodolpho G G; Vasconcelos, Ilka M; Martins, Thiago F; Varela, Anna L N; Souza, Pedro F N; Lobo, Ana K M; Silva, Fredy D A; Silveira, Joaquim A G; Oliveira, Jose T A

    2016-12-01

    The physiological and biochemical responses of a drought tolerant, virus-susceptible cowpea genotype exposed to drought stress (D), infected by Cowpea severe mosaic virus (CPSMV) (V), and to these two combined stresses (DV), at 2 and 6 days post viral inoculation (DPI), were evaluated. Gas exchange parameters (net photosynthesis, transpiration rate, stomatal conductance, and internal CO2 partial pressure) were reduced in D and DV at 2 and 6 DPI compared to control plants (C). Photosynthesis was reduced by stomatal and biochemical limitations. Water use efficiency increased at 2 DPI in D, DV, and V, but at 6 DPI only in D and DV compared to C. Photochemical parameters (effective quantum efficiency of photosystem II and electron transport rate) decreased in D and DV compared to C, especially at 6 DPI. The potential quantum efficiency of photosystem II did not change, indicating reversible photoinhibition of photosystem II. In DV, catalase decreased at 2 and 6 DPI, ascorbate peroxidase increased at 2 DPI, but decreased at 6 DPI. Hydrogen peroxide increased at 2 and 6 DPI. Peroxidase increased at 6 DPI and chitinase at 2 and 6 DPI. β-1,3-glucanase decreased in DV at 6 DPI compared to V. Drought increased cowpea susceptibility to CPSMV at 2 DPI, as verified by RT-PCR. However, at 6 DPI, the cowpea plants overcome this effect. Likewise, CPSMV increased the negative effects of drought at 2 DPI, but not at 6 DPI. It was concluded that the responses to combined stresses are not additive and cannot be extrapolated from the study of individual stresses.

  18. Human immunodeficiency virus type 1 long terminal repeat variants from 42 patients representing all stages of infection display a wide range of sequence polymorphism and transcription activity.

    PubMed Central

    Estable, M C; Bell, B; Merzouki, A; Montaner, J S; O'Shaughnessy, M V; Sadowski, I J

    1996-01-01

    Despite extensive in vitro studies identifying a myriad of cellular transcription factors that bind the human immunodeficiency virus type 1 5' long terminal repeat (LTR), the relative contribution of these factors to human immunodeficiency virus type 1 replication in infected individuals remains obscure. To address this question, we investigated 478 proviral quasispecies derived from uncultured peripheral blood mononuclear cells of 42 patients representing all stages of infection. In addition to highly conserved TATA box, SP-1, and NF-kappaB sites, the Ets core and an adjacent 5'-ACYGCTGA-3' motif were extremely conserved. Importantly, the most frequent naturally occurring length polymorphism (MFNLP) duplicated 5'-ACYGCTGA-3' motifs in LTRs in which this same motif was disrupted or in LTRs in which a single point mutation to the Ets core ablated binding of c-Ets 1 and another factor distinct from both c-Ets 1 and Elf 1. The MFNLP's location was precise (position -121) and surprisingly frequent (38% of patients) and demarcated LTR Nef-coding sequences from LTR noncoding sequences that appear to be evolving independently. Aside from these features, we found no definitive clinical or transcription phenotype common to all MFNLP LTRs. We also found previously described and novel point polymorphisms, including some conferring TAR-dependent and TAR- independent Tat unresponsiveness, and showed that differential binding of nuclear factor(s) to a TCTAA TATA box variant may be the mechanism for the latter. PMID:8648743

  19. Antibody responses and viral load in patients with Crimean-Congo hemorrhagic fever: a comprehensive analysis during the early stages of the infection.

    PubMed

    Ergunay, Koray; Kocak Tufan, Zeliha; Bulut, Cemal; Kinikli, Sami; Demiroz, Ali Pekcan; Ozkul, Aykut

    2014-05-01

    This study was performed to assess viral load, viral nucleocapsid (N), and glycoprotein precursor (GPC) antibodies in consecutive samples obtained from Crimean-Congo hemorrhagic fever patients to reveal viral replication kinetics and antiviral immune responses during the early stages of the infection. Among 116 samples from 20 individuals, 43.9% and 76.7% were positive for viral RNA and IgM/IgG antibodies, respectively, whereas both markers could be detected in 22.4%. Mean duration of viremia was 3 days (range: 1-6 days). N-IgM antibodies were identified as the initial serological marker during the infection, becoming detectable in a median of 2-3 days after disease onset, followed by GPC-IgM (4-6 days) and IgG antibodies (5-6 days). Clearance of viremia followed or coincided N-IgM response. Partial S gene sequences amplified in viremic patients were identical or closely related to previously characterized strains and grouped within European lineage I group II viruses via neighbor-joining analysis without significant amino acid substitutions.

  20. Staged treatment of pilon fractures

    PubMed Central

    Deivaraju, Chenthuran; Vlasak, Richard; Sadasivan, Kalia

    2015-01-01

    Aim To evaluate outcomes following staged anterolateral plating of pilon fractures. Methods Over a 5 year period, patients with pilon fractures received four treatment regimens (staged anterolateral plating, staged medial plating, definitive external fixation, early total care). We defined five outcomes (reduction, soft tissue complications, infection, non-union, malunion) and assessed the outcome of fractures treated by these interventions. Results Staged anterolateral plating or staged medial plating achieved comparable reduction and soft tissue complications. Staged medial plating had higher infection rates, malunion and non-union rates. Conclusions Staged anterolateral plating is superior to staged medial plating in the management of pilon fractures. PMID:26719618

  1. The Mannose Receptor (CD206) is an important pattern recognition receptor (PRR) in the detection of the infective stage of the helminth Schistosoma mansoni and modulates IFNγ production.

    PubMed

    Paveley, Ross A; Aynsley, Sarah A; Turner, Joseph D; Bourke, Claire D; Jenkins, Stephen J; Cook, Peter C; Martinez-Pomares, Luisa; Mountford, Adrian P

    2011-11-01

    In this study, infective larvae of the parasitic helminth Schistosoma mansoni were shown to contain a large number of glycosylated components specific for the Mannose Receptor (MR; CD206), which is an important pattern recognition receptor (PRR) of the innate immune system. MR ligands were particularly rich in excretory/secretory (E/S) material released during transformation of cercariae into schistosomula, a process critical for infection of the host. E/S material from carboxyfluorescein diacetate succinimidyl ester (CFDA-SE)-labelled cercariae showed enhanced binding by cells lines that over-express the MR. Conversely, uptake was significantly lower by bone marrow-derived macrophages (MΦ) from MR(-/-) mice, although they were more active as judged by enhanced pro-inflammatory cytokine production and CD40 expression. After natural percutaneous infection of MR(-/-) mice with CFDA-SE-labelled parasites, there were fewer cells in the skin and draining lymph nodes that were CFDA-SE(+) compared with wild-type mice, implying reduced uptake and presentation of larval parasite antigen. However, antigen-specific proliferation of skin draining lymph node cells was significantly enhanced and they secreted markedly elevated levels of IFNγ but decreased levels of IL-4. In conclusion, we show that the MR on mononuclear phagocytic cells, which are plentiful in the skin, plays a significant role in internalising E/S material released by the invasive stages of the parasite which in turn modulates their production of pro-inflammatory cytokines. In the absence of the MR, antigen-specific CD4(+) cells are Th1 biased, suggesting that ligation of the MR by glycosylated E/S material released by schistosome larvae modulates the production of CD4(+) cell specific IFNγ.

  2. Comparative Genome Analysis of Lactobacillus rhamnosus Clinical Isolates from Initial Stages of Dental Pulp Infection: Identification of a New Exopolysaccharide Cluster

    PubMed Central

    Nadkarni, Mangala A.; Chen, Zhiliang; Wilkins, Marc R.; Hunter, Neil

    2014-01-01

    The human oral microbiome has a major role in oral diseases including dental caries. Our studies on progression of caries infection through dentin and more recently, the invasion of vital dental pulp, detected Lactobacillus rhamnosus in the initial stages of infection of vital pulp tissue. In this study employing current high-throughput next generation sequencing technology we sought to obtain insight into genomic traits of tissue invasive L. rhamnosus, to recognise biomarkers that could provide an understanding of pathogenic potential of lactobacilli, generally regarded as safe. Roche GS FLX+ technology was used to generate whole genome sequences of two clinical isolates of L. rhamnosus infecting vital pulp. Detailed genome-wide comparison of the genetic profiles of tissue invasive L. rhamnosus with probiotic L. rhamnosus was performed to test the hypothesis that specific strains of L. rhamnosus possessing a unique gene complement are selected for the capacity to invade vital pulp tissue. Analysis identified 264 and 258 genes respectively, from dental pulp-invasive L. rhamnosus strains LRHMDP2 and LRHMDP3 isolated from two different subjects that were not present in the reference probiotic L. rhamnosus strain ATCC 53103 (GG). Distinct genome signatures identified included the presence of a modified exopolysaccharide cluster, a characteristic confirmed in a further six clinical isolates. Additional features of LRHMDP2 and LRHMDP3 were altered transcriptional regulators from RpoN, NtrC, MutR, ArsR and zinc-binding Cro/CI families, as well as changes in the two-component sensor kinase response regulator and ABC transporters for ferric iron. Both clinical isolates of L. rhamnosus contained a single SpaFED cluster, as in L. rhamnosus Lc705, instead of the two Spa clusters (SpaCBA and SpaFED) identified in L. rhamnosus ATCC 53103 (GG). Genomic distance analysis and SNP divergence confirmed a close relationship of the clinical isolates but segregation from the reference

  3. Impaired maraviroc and raltegravir clearance in a human immunodeficiency virus-infected patient with end-stage liver disease and renal impairment: a management dilemma.

    PubMed

    Pau, Alice K; Penzak, Scott R; Boyd, Sarita D; McLaughlin, Mary; Morse, Caryn G

    2012-01-01

    Current product labels for maraviroc and raltegravir provide no dosing guidance for patients with end-stage liver disease and worsening renal function. We describe a 41-year-old man with human immunodeficiency virus (HIV) infection and rapidly progressive liver failure and vanishing bile duct syndrome at presentation. Despite discontinuation of all potential offending drugs, the patient's liver function continued to deteriorate. To achieve and maintain HIV suppression while awaiting liver transplantation, a regimen consisting of maraviroc, raltegravir, and enfuvirtide was started. These agents were chosen because the patient was not exposed to them before the onset of liver failure. While receiving product label-recommended twice-daily dosing of these drugs, he achieved and maintained HIV suppression. During a complicated and prolonged hospitalization, the patient also developed renal dysfunction. As hepatic metabolism is the primary route of clearance of maraviroc and raltegravir, we predicted that using approved doses of these drugs could result in significant drug accumulation. Since the safety profiles of supratherapeutic concentrations of these agents are not well defined, we chose to use therapeutic drug monitoring to guide further dosing. The reported concentrations showed severely impaired metabolic clearance of both drugs, with markedly prolonged elimination half-lives of 189 hours for maraviroc and 61 hours for raltegravir. Previously reported half-lives for maraviroc and raltegravir in HIV-infected patients with normal hepatic and renal function are 14-18 hours and 9-12 hours, respectively. Based on these results, the dosing intervals were extended from twice/day to twice/week for maraviroc and every 48 hours for raltegravir. Unfortunately, the patient's clinical condition continued to deteriorate, and he eventually died of complications related to end-stage liver disease. This case illustrates the difficulties in managing antiretroviral therapy in

  4. Liver-inherent immune system: its role in blood-stage malaria.

    PubMed

    Wunderlich, Frank; Al-Quraishy, Saleh; Dkhil, Mohamed A

    2014-01-01

    The liver is well known as that organ which is obligately required for the intrahepatocyte development of the pre-erythrocytic stages of the malaria-causative agent Plasmodium. However, largely neglected is the fact that the liver is also a central player of the host defense against the morbidity- and mortality-causing blood stages of the malaria parasites. Indeed, the liver is equipped with a unique immune system that acts locally, however, with systemic impact. Its main "antipodal" functions are to recognize and to generate effective immunoreactivity against pathogens on the one hand, and to generate tolerance to avoid immunoreactivity with "self" and harmless substances as dietary compounds on the other hand. This review provides an introductory survey of the liver-inherent immune system: its pathogen recognition receptors including Toll-like receptors (TLRs) and its major cell constituents with their different facilities to fight and eliminate pathogens. Then, evidence is presented that the liver is also an essential organ to overcome blood-stage malaria. Finally, we discuss effector responses of the liver-inherent immune system directed against blood-stage malaria: activation of TLRs, acute phase response, phagocytic activity, cytokine-mediated pro- and anti-inflammatory responses, generation of "protective" autoimmunity by extrathymic T cells and B-1 cells, and T cell-mediated repair of liver injuries mainly produced by malaria-induced overreactions of the liver-inherent immune system.

  5. Modeling the impact of hepatitis C viral clearance on end-stage liver disease in an HIV co-infected cohort with Targeted Maximum Likelihood Estimation

    PubMed Central

    Schnitzer, Mireille E; Moodie, Erica EM; van der Laan, Mark J; Platt, Robert W; Klein, Marina B

    2013-01-01

    Summary Despite modern effective HIV treatment, hepatitis C virus (HCV) co-infection is associated with a high risk of progression to end-stage liver disease (ESLD) which has emerged as the primary cause of death in this population. Clinical interest lies in determining the impact of clearance of HCV on risk for ESLD. In this case study, we examine whether HCV clearance affects risk of ESLD using data from the multicenter Canadian Co-infection Cohort Study. Complications in this survival analysis arise from the time-dependent nature of the data, the presence of baseline confounders, loss to follow-up, and confounders that change over time, all of which can obscure the causal effect of interest. Additional challenges included non-censoring variable missingness and event sparsity. In order to efficiently estimate the ESLD-free survival probabilities under a specific history of HCV clearance, we demonstrate the doubly-robust and semiparametric efficient method of Targeted Maximum Likelihood Estimation (TMLE). Marginal structural models (MSM) can be used to model the effect of viral clearance (expressed as a hazard ratio) on ESLD-free survival and we demonstrate a way to estimate the parameters of a logistic model for the hazard function with TMLE. We show the theoretical derivation of the efficient influence curves for the parameters of two different MSMs and how they can be used to produce variance approximations for parameter estimates. Finally, the data analysis evaluating the impact of HCV on ESLD was undertaken using multiple imputations to account for the non-monotone missing data. PMID:24571372

  6. Protective immune responses elicited by immunization with a chimeric blood-stage malaria vaccine persist but are not boosted by Plasmodium yoelii challenge infection

    PubMed Central

    Alaro, James R.; Lynch, Michele M.; Burns, James M.

    2010-01-01

    An efficacious malaria vaccine remains elusive despite concerted efforts. Using the Plasmodium yoelii murine model, we previously reported that immunization with the C-terminal 19 kDa domain of merozoite surface protein 1 (MSP119) fused to full-length MSP8 protected against lethal P. yoelii 17XL, well beyond that achieved by single or combined immunizations with the component antigens. Here, we continue the evaluation of the chimeric PyMSP1/8 vaccine. We show that immunization with rPyMSP1/8 vaccine elicited an MSP8-restricted T cell response that was sufficient to provide help for both PyMSP119 and PyMSP8 specific B cells to produce high and sustained levels of protective antibodies. The enhanced efficacy of immunization with rPyMSP1/8, in comparison to a combined formulation of rPyMSP142 and rPyMSP8, was not due to improved conformation of protective B cell epitopes in the chimeric molecule. Unexpectedly, rPyMSP1/8 vaccine-induced antibody responses were not boosted by exposure to P. yoelii 17XL infected RBCs. However, rPyMSP1/8 immunized and infected mice mounted robust responses to a diverse set of blood-stage antigens. The data support the further development of an MSP1/8 chimeric vaccine but also suggest that vaccines that prime for responses to a diverse set of parasite proteins will be required to maximize vaccine efficacy. PMID:20709001

  7. A glass fiber-reinforced composite - bioactive glass cranioplasty implant: A case study of an early development stage implant removed due to a late infection.

    PubMed

    Posti, Jussi P; Piitulainen, Jaakko M; Hupa, Leena; Fagerlund, Susanne; Frantzén, Janek; Aitasalo, Kalle M J; Vuorinen, Ville; Serlo, Willy; Syrjänen, Stina; Vallittu, Pekka K

    2015-03-01

    This case study describes the properties of an early development stage bioactive glass containing fiber-reinforced composite calvarial implant with histology that has been in function for two years and three months. The patient is a 33-year old woman with a history of substance abuse, who sustained a severe traumatic brain injury later unsuccessfully treated with an autologous bone flap and a custom-made porous polyethylene implant. She was thereafter treated with developmental stage glass fiber-reinforced composite - bioactive glass implant. After two years and three months, the implant was removed due to an implant site infection. The implant was analyzed histologically, mechanically, and in terms of chemistry and dissolution of bioactive glass. Mechanical integrity of the load bearing fiber-reinforced composite part of the implant was not affected by the in vivo period. Bioactive glass particles demonstrated surface layers of hydroxyapatite like mineral and dissolution, and related increase of pH was considerably less after two and three months period than that for fresh bioactive glass. There was a difference in the histology of the tissues inside the implant areas near to the margin of the implant that absorbed blood during implant installation surgery, showed fibrous tissue with blood vessels, osteoblasts, collagenous fibers with osteoid formation, and tiny clusters of more mature hard tissue. In the center of the implant, where there was less absorbed blood, only fibrous tissue was observed. This finding is in line with the combined positron emission tomography - computed tomography examination with (18F)-fluoride marker, which demonstrated activity of the mineralizing bone by osteoblasts especially at the area near to the margin of the implant 10 months after implantation. Based on these promising reactions found in the bioactive glass containing fiber-reinforced composite implant that has been implanted for two years and three months, calvarial

  8. Single or dual experimental infections with Vibrio aestuarianus and OsHV-1 in diploid and triploid Crassostrea gigas at the spat, juvenile and adult stages.

    PubMed

    Azéma, Patrick; Travers, Marie-Agnès; Benabdelmouna, Abdellah; Dégremont, Lionel

    2016-09-01

    French production of the Pacific cupped oyster, Crassostrea gigas, is currently threatened by two pathogens, OsHV-1 and V. aestuarianus. While oysters selected for their higher resistance to OsHV-1 are now available for the industry, the impact of V. aestuarianus on such oysters is unknown, especially for triploids. In addition, experimental infection has used the virus or the bacteria alone, but there have been no investigations of dual exposure to these pathogens. This study is the first report of single or dual exposure in spat (Spat1 and Spat2), juvenile and adult naïve oysters. For each of the two stocks evaluated, unselected oysters and oysters selected for their higher resistance to OsHV-1 infection were tested, as well as their triploid siblings of the selected oysters produced using cytochalasin B. We confirmed that resistance to OsHV-1 infection and susceptibility to V. aestuarianus increased with age and size, although selected oysters were not significantly impacted by OsHV-1 whatever their ploidy, size or age. We found different mortality patterns depending on the pathogen tested. The mortality pattern was similar for oysters exposed to OsHV-1 or to both pathogens in the Spat1 trial (4months old and 1.9g). The mortality pattern was similar for oysters exposed to V. aestuarianus or to both pathogens in the Adult trial (25months old and 63.1g). Surprisingly, mortality was much higher (ranging from 75.9% to 100%), in particular for the selected oysters, for the Spat2 (8months old/3.9g) and Juvenile trials (16months old/18.4g) given a dual exposure, regardless of the level of selection for OsHV-1 and the ploidy state. Our findings highlight an important threat for oyster farmers: oysters exposed to both pathogens could experience dramatic mortality rates, even in oysters selected for their higher resistance to OsHV-1. Finally, our study demonstrated for the first time that triploid oysters were more susceptible to experimental challenges with V

  9. Safety and Reproducibility of a Clinical Trial System Using Induced Blood Stage Plasmodium vivax Infection and Its Potential as a Model to Evaluate Malaria Transmission

    PubMed Central

    Elliott, Suzanne; Sekuloski, Silvana; Sikulu, Maggy; Hugo, Leon; Khoury, David; Cromer, Deborah; Davenport, Miles; Sattabongkot, Jetsumon; Ivinson, Karen; Ockenhouse, Christian; McCarthy, James

    2016-01-01

    Background Interventions to interrupt transmission of malaria from humans to mosquitoes represent an appealing approach to assist malaria elimination. A limitation has been the lack of systems to test the efficacy of such interventions before proceeding to efficacy trials in the field. We have previously demonstrated the feasibility of induced blood stage malaria (IBSM) infection with Plasmodium vivax. In this study, we report further validation of the IBSM model, and its evaluation for assessment of transmission of P. vivax to Anopheles stephensi mosquitoes. Methods Six healthy subjects (three cohorts, n = 2 per cohort) were infected with P. vivax by inoculation with parasitized erythrocytes. Parasite growth was monitored by quantitative PCR, and gametocytemia by quantitative reverse transcriptase PCR (qRT-PCR) for the mRNA pvs25. Parasite multiplication rate (PMR) and size of inoculum were calculated by linear regression. Mosquito transmission studies were undertaken by direct and membrane feeding assays over 3 days prior to commencement of antimalarial treatment, and midguts of blood fed mosquitoes dissected and checked for presence of oocysts after 7–9 days. Results The clinical course and parasitemia were consistent across cohorts, with all subjects developing mild to moderate symptoms of malaria. No serious adverse events were reported. Asymptomatic elevated liver function tests were detected in four of six subjects; these resolved without treatment. Direct feeding of mosquitoes was well tolerated. The estimated PMR was 9.9 fold per cycle. Low prevalence of mosquito infection was observed (1.8%; n = 32/1801) from both direct (4.5%; n = 20/411) and membrane (0.9%; n = 12/1360) feeds. Conclusion The P. vivax IBSM model proved safe and reliable. The clinical course and PMR were reproducible when compared with the previous study using this model. The IBSM model presented in this report shows promise as a system to test transmission-blocking interventions

  10. A whole parasite vaccine to control the blood stages of Plasmodium: the case for lateral thinking.

    PubMed

    Good, Michael F

    2011-08-01

    Now, 27 years following the cloning of malaria antigens with the promise of the rapid development of a malaria vaccine, we face significant obstacles that are belatedly being addressed. Poor immunogenicity of subunit vaccine antigens and significant antigenic diversity of target epitopes represent major hurdles for which there are no clear strategies for a way forward within the current paradigm. Thus, a different paradigm - a vaccine that uses the whole organism - is now being examined. Although most advances in this approach relate to a vaccine for the pre-erythrocytic stages (sporozoites, liver stages), this opinion paper will outline the possibilities of developing a whole parasite vaccine for the blood stage and address some of the challenges for this strategy, which are entirely different to the challenges for a subunit vaccine. It is the view of the author that both vaccine paradigms should be pursued, but that success will come more quickly using the paranormal approach of exposing individuals to ultra-low doses of whole attenuated or killed parasites.

  11. Evaluation of viral load thresholds for predicting new WHO Stage 3 and 4 events in HIV-infected children receiving highly active antiretroviral therapy

    PubMed Central

    Siberry, George K; Harris, D. Robert; Oliveira, Ricardo Hugo; Krauss, Margot R.; Hofer, Cristina B.; Tiraboschi, Adriana Aparecida; Marques, Heloisa; Succi, Regina C.; Abreu, Thalita; Negra, Marinella Della; Mofenson, Lynne M.; Hazra, Rohan

    2012-01-01

    Background This study evaluated a wide range of viral load (VL) thresholds to identify a cut-point that best predicts new clinical events in children on stable highly-active antiretroviral therapy (HAART). Methods Cox proportional hazards modeling was used to assess the adjusted risk of World Health Organization stage 3 or 4 clinical events (WHO events) as a function of time-varying CD4, VL, and hemoglobin values in a cohort study of Latin American children on HAART ≥ 6 months. Models were fit using different VL cut-points between 400 and 50,000 copies/mL, with model fit evaluated on the basis of the minimum Akaike Information Criterion (AIC) value, a standard model fit statistic. Results Models were based on 67 subjects with WHO events out of 550 subjects on study. The VL cutpoints of > 2600 copies/mL and > 32,000 copies/mL corresponded to the lowest AIC values and were associated with the highest hazard ratios [2.0 (p = 0.015) and 2.1 (p = 0.0058), respectively] for WHO events. Conclusions In HIV-infected Latin American children on stable HAART, two distinct VL thresholds (> 2,600 copies/mL and > 32,000 copies/mL) were identified for predicting children at significantly increased risk of HIV-related clinical illness, after accounting for CD4 level, hemoglobin level, and other significant factors. PMID:22343177

  12. Infection control measures on ships and in ports during the early stage of pandemic influenza A (H1N1) 2009.

    PubMed

    Schlaich, Clara; Gau, Bettina; Cohen, Nicole J; Kojima, Kazunobu; Marano, Nina; Menucci, Daniel

    2012-01-01

    Shipping companies were surveyed to evaluate the effect of public health measures during the influenza A (H1N1) pandemic of 2009 on ship and port operations. Of 31 companies that operated 960 cruise, cargo, and other ships, 32% experienced health-screening measures by port health authorities. Approximately a quarter of ports (26%) performed screening at embarkation and 77% of shipping companies changed procedures during the early stage of the pandemic. Four companies reported outbreaks of pandemic influenza A (H1N1) 2009 on ships, which were ultimately stopped through infection control practices. Public health measures did not interfere substantially with port and ship operations with the exception of some port authorities that delayed embarking and disembarking procedures in a few ships. However, in the shipping companies' experience, measures were inconsistent between port health authorities. Access to antiviral drugs and pandemic vaccine was not provided in all ports. Current guidelines on medical care, hygiene, and emergency procedures on ships need to address pandemic influenza preparedness in future revisions.

  13. Breadth of humoral response and antigenic targets of sporozoite-inhibitory antibodies associated with sterile protection induced by controlled human malaria infection

    PubMed Central

    Peng, Kaitian; Goh, Yun Shan; Siau, Anthony; Franetich, Jean-François; Chia, Wan Ni; Ong, Alice Soh Meoy; Malleret, Benoit; Wu, Ying Ying; Snounou, Georges; Hermsen, Cornelus C.; Adams, John H.; Mazier, Dominique; Preiser, Peter R.; Sauerwein, Robert W.; Grüner, Anne-Charlotte; Rénia, Laurent

    2017-01-01

    The development of an effective malaria vaccine has remained elusive even until today. This is due to our incomplete understanding of the immune mechanisms that confer and/or correlate with protection. Human volunteers have been protected experimentally from a subsequent challenge by immunization with Plasmodium falciparum sporozoites under drug cover. Here, we demonstrate that sera from the protected individuals contain neutralizing antibodies against the pre erythrocytic stage. To identify the antigen(s) recognized by these antibodies, a newly developed library of P. falciparum antigens was screened with the neutralizing sera. Antibodies from protected individuals recognized a broad antigenic repertoire of which three antigens, PfMAEBL, PfTRAP and PfSEA1 were recognized by most protected individuals. As a proof of principle, we demonstrated that anti-PfMAEBL antibodies block liver stage development in human hepatocytes. Thus, these antigens identified are promising targets for vaccine development against malaria. PMID:27130708

  14. The Threshold of Protection from Liver-Stage Malaria Relies on a Fine Balance between the Number of Infected Hepatocytes and Effector CD8+ T Cells Present in the Liver

    PubMed Central

    Longley, Rhea J.; Gola, Anita; Ulaszewska, Marta; Lambe, Teresa; Hill, Adrian V. S.

    2017-01-01

    Since the demonstration of sterile protection afforded by injection of irradiated sporozoites, CD8+ T cells have been shown to play a significant role in protection from liver-stage malaria. This is, however, dependent on the presence of an extremely high number of circulating effector cells, thought to be necessary to scan, locate, and kill infected hepatocytes in the short time that parasites are present in the liver. We used an adoptive transfer model to elucidate the kinetics of the effector CD8+ T cell response in the liver following Plasmodium berghei sporozoite challenge. Although effector CD8+ T cells require <24 h to find, locate, and kill infected hepatocytes, active migration of Ag-specific CD8+ T cells into the liver was not observed during the 2-d liver stage of infection, as divided cells were only detected from day 3 postchallenge. However, the percentage of donor cells recruited into division was shown to indicate the level of Ag presentation from infected hepatocytes. By titrating the number of transferred Ag-specific effector CD8+ T cells and sporozoites, we demonstrate that achieving protection toward liver-stage malaria is reliant on CD8+ T cells being able to locate infected hepatocytes, resulting in a protection threshold dependent on a fine balance between the number of infected hepatocytes and CD8+ T cells present in the liver. With such a fine balance determining protection, achieving a high number of CD8+ T cells will be critical to the success of a cell-mediated vaccine against liver-stage malaria. PMID:28087668

  15. Hierarchical Cluster Analysis of Three-Dimensional Reconstructions of Unbiased Sampled Microglia Shows not Continuous Morphological Changes from Stage 1 to 2 after Multiple Dengue Infections in Callithrix penicillata

    PubMed Central

    Diniz, Daniel G.; Silva, Geane O.; Naves, Thaís B.; Fernandes, Taiany N.; Araújo, Sanderson C.; Diniz, José A. P.; de Farias, Luis H. S.; Sosthenes, Marcia C. K.; Diniz, Cristovam G.; Anthony, Daniel C.; da Costa Vasconcelos, Pedro F.; Picanço Diniz, Cristovam W.

    2016-01-01

    It is known that microglial morphology and function are related, but few studies have explored the subtleties of microglial morphological changes in response to specific pathogens. In the present report we quantitated microglia morphological changes in a monkey model of dengue disease with virus CNS invasion. To mimic multiple infections that usually occur in endemic areas, where higher dengue infection incidence and abundant mosquito vectors carrying different serotypes coexist, subjects received once a week subcutaneous injections of DENV3 (genotype III)-infected culture supernatant followed 24 h later by an injection of anti-DENV2 antibody. Control animals received either weekly anti-DENV2 antibodies, or no injections. Brain sections were immunolabeled for DENV3 antigens and IBA-1. Random and systematic microglial samples were taken from the polymorphic layer of dentate gyrus for 3-D reconstructions, where we found intense immunostaining for TNFα and DENV3 virus antigens. We submitted all bi- or multimodal morphological parameters of microglia to hierarchical cluster analysis and found two major morphological phenotypes designated types I and II. Compared to type I (stage 1), type II microglia were more complex; displaying higher number of nodes, processes and trees and larger surface area and volumes (stage 2). Type II microglia were found only in infected monkeys, whereas type I microglia was found in both control and infected subjects. Hierarchical cluster analysis of morphological parameters of 3-D reconstructions of random and systematic selected samples in control and ADE dengue infected monkeys suggests that microglia morphological changes from stage 1 to stage 2 may not be continuous. PMID:27047345

  16. Assessment of Humoral Immune Responses to Blood-Stage Malaria Antigens following ChAd63-MVA Immunization, Controlled Human Malaria Infection and Natural Exposure

    PubMed Central

    Elias, Sean C.; Miura, Kazutoyo; Milne, Kathryn H.; de Cassan, Simone C.; Collins, Katharine A.; Halstead, Fenella D.; Bliss, Carly M.; Ewer, Katie J.; Osier, Faith H.; Hodgson, Susanne H.; Duncan, Christopher J. A.; O’Hara, Geraldine A.; Long, Carole A.; Hill, Adrian V. S.; Draper, Simon J.

    2014-01-01

    The development of protective vaccines against many difficult infectious pathogens will necessitate the induction of effective antibody responses. Here we assess humoral immune responses against two antigens from the blood-stage merozoite of the Plasmodium falciparum human malaria parasite – MSP1 and AMA1. These antigens were delivered to healthy malaria-naïve adult volunteers in Phase Ia clinical trials using recombinant replication-deficient viral vectors – ChAd63 to prime the immune response and MVA to boost. In subsequent Phase IIa clinical trials, immunized volunteers underwent controlled human malaria infection (CHMI) with P. falciparum to assess vaccine efficacy, whereby all but one volunteer developed low-density blood-stage parasitemia. Here we assess serum antibody responses against both the MSP1 and AMA1 antigens following i) ChAd63-MVA immunization, ii) immunization and CHMI, and iii) primary malaria exposure in the context of CHMI in unimmunized control volunteers. Responses were also assessed in a cohort of naturally-immune Kenyan adults to provide comparison with those induced by a lifetime of natural malaria exposure. Serum antibody responses against MSP1 and AMA1 were characterized in terms of i) total IgG responses before and after CHMI, ii) responses to allelic variants of MSP1 and AMA1, iii) functional growth inhibitory activity (GIA), iv) IgG avidity, and v) isotype responses (IgG1-4, IgA and IgM). These data provide the first in-depth assessment of the quality of adenovirus-MVA vaccine-induced antibody responses in humans, along with assessment of how these responses are modulated by subsequent low-density parasite exposure. Notable differences were observed in qualitative aspects of the human antibody responses against these malaria antigens depending on the means of their induction and/or exposure of the host to the malaria parasite. Given the continued clinical development of viral vectored vaccines for malaria and a range of other

  17. Assessment of humoral immune responses to blood-stage malaria antigens following ChAd63-MVA immunization, controlled human malaria infection and natural exposure.

    PubMed

    Biswas, Sumi; Choudhary, Prateek; Elias, Sean C; Miura, Kazutoyo; Milne, Kathryn H; de Cassan, Simone C; Collins, Katharine A; Halstead, Fenella D; Bliss, Carly M; Ewer, Katie J; Osier, Faith H; Hodgson, Susanne H; Duncan, Christopher J A; O'Hara, Geraldine A; Long, Carole A; Hill, Adrian V S; Draper, Simon J

    2014-01-01

    The development of protective vaccines against many difficult infectious pathogens will necessitate the induction of effective antibody responses. Here we assess humoral immune responses against two antigens from the blood-stage merozoite of the Plasmodium falciparum human malaria parasite--MSP1 and AMA1. These antigens were delivered to healthy malaria-naïve adult volunteers in Phase Ia clinical trials using recombinant replication-deficient viral vectors--ChAd63 to prime the immune response and MVA to boost. In subsequent Phase IIa clinical trials, immunized volunteers underwent controlled human malaria infection (CHMI) with P. falciparum to assess vaccine efficacy, whereby all but one volunteer developed low-density blood-stage parasitemia. Here we assess serum antibody responses against both the MSP1 and AMA1 antigens following i) ChAd63-MVA immunization, ii) immunization and CHMI, and iii) primary malaria exposure in the context of CHMI in unimmunized control volunteers. Responses were also assessed in a cohort of naturally-immune Kenyan adults to provide comparison with those induced by a lifetime of natural malaria exposure. Serum antibody responses against MSP1 and AMA1 were characterized in terms of i) total IgG responses before and after CHMI, ii) responses to allelic variants of MSP1 and AMA1, iii) functional growth inhibitory activity (GIA), iv) IgG avidity, and v) isotype responses (IgG1-4, IgA and IgM). These data provide the first in-depth assessment of the quality of adenovirus-MVA vaccine-induced antibody responses in humans, along with assessment of how these responses are modulated by subsequent low-density parasite exposure. Notable differences were observed in qualitative aspects of the human antibody responses against these malaria antigens depending on the means of their induction and/or exposure of the host to the malaria parasite. Given the continued clinical development of viral vectored vaccines for malaria and a range of other diseases

  18. Assessment of immune interference, antagonism, and diversion following human immunization with biallelic blood-stage malaria viral-vectored vaccines and controlled malaria infection.

    PubMed

    Elias, Sean C; Collins, Katharine A; Halstead, Fenella D; Choudhary, Prateek; Bliss, Carly M; Ewer, Katie J; Sheehy, Susanne H; Duncan, Christopher J A; Biswas, Sumi; Hill, Adrian V S; Draper, Simon J

    2013-02-01

    Overcoming antigenic variation is one of the major challenges in the development of an effective vaccine against Plasmodium falciparum, a causative agent of human malaria. Inclusion of multiple Ag variants in subunit vaccine candidates is one strategy that has aimed to overcome this problem for the leading blood-stage malaria vaccine targets, that is, merozoite surface protein 1 (MSP1) and apical membrane Ag 1 (AMA1). However, previous studies, utilizing malaria Ags, have concluded that inclusion of multiple allelic variants, encoding altered peptide ligands, in such a vaccine may be detrimental to both the priming and in vivo restimulation of Ag-experienced T cells. In this study, we analyze the T cell responses to two alleles of MSP1 and AMA1 induced by vaccination of malaria-naive adult volunteers with bivalent viral-vectored vaccine candidates. We show a significant bias to the 3D7/MAD20 allele compared with the Wellcome allele for the 33 kDa region of MSP1, but not for the 19 kDa fragment or the AMA1 Ag. Although this bias could be caused by "immune interference" at priming, the data do not support a significant role for "immune antagonism" during memory T cell restimulation, despite observation of the latter at a minimal epitope level in vitro. A lack of class I HLA epitopes in the Wellcome allele that are recognized by vaccinated volunteers may in fact contribute to the observed bias. We also show that controlled infection with 3D7 strain P. falciparum parasites neither boosts existing 3D7-specific T cell responses nor appears to "immune divert" cellular responses toward the Wellcome allele.

  19. Infection and Other Complications

    MedlinePlus

    ... is Lymphedema? What Causes Lymphedema What is the Lymphatic System? Signs and Symptoms Stage 0 Stage 1 Stage ... is Lymphedema? What Causes Lymphedema What is the Lymphatic System? Signs and Symptoms Infection and Other Complications NLN ...

  20. Model for In Vivo Assessment of Humoral Protection against Malaria Sporozoite Challenge by Passive Transfer of Monoclonal Antibodies and Immune Serum

    PubMed Central

    Sack, Brandon K.; Miller, Jessica L.; Vaughan, Ashley M.; Douglass, Alyse; Kaushansky, Alexis; Mikolajczak, Sebastian; Coppi, Alida; Gonzalez-Aseguinolaza, Gloria; Tsuji, Moriya; Zavala, Fidel; Sinnis, Photini

    2014-01-01

    Evidence from clinical trials of malaria vaccine candidates suggests that both cell-mediated and humoral immunity to pre-erythrocytic parasite stages can provide protection against infection. Novel pre-erythrocytic antibody (Ab) targets could be key to improving vaccine formulations, which are currently based on targeting antigens such as the circumsporozoite protein (CSP). However, methods to assess the effects of sporozoite-specific Abs on pre-erythrocytic infection in vivo remain underdeveloped. Here, we combined passive transfer of monoclonal Abs (MAbs) or immune serum with a luciferase-expressing Plasmodium yoelii sporozoite challenge to assess Ab-mediated inhibition of liver infection in mice. Passive transfer of a P. yoelii CSP MAb showed inhibition of liver infection when mice were challenged with sporozoites either intravenously or by infectious mosquito bite. However, inhibition was most potent for the mosquito bite challenge, leading to a more significant reduction of liver-stage burden and even a lack of progression to blood-stage parasitemia. This suggests that Abs provide effective protection against a natural infection. Inhibition of liver infection was also achieved by passive transfer of immune serum from whole-parasite-immunized mice. Furthermore, we demonstrated that passive transfer of a MAb against P. falciparum CSP inhibited liver-stage infection in a humanized mouse/P. falciparum challenge model. Together, these models constitute unique and sensitive in vivo methods to assess serum-transferable protection against Plasmodium sporozoite challenge. PMID:24478094

  1. Parasite-Specific CD4+ IFN-γ+ IL-10+ T Cells Distribute within Both Lymphoid and Nonlymphoid Compartments and Are Controlled Systemically by Interleukin-27 and ICOS during Blood-Stage Malaria Infection

    PubMed Central

    Villegas-Mendez, Ana; Shaw, Tovah N.; Inkson, Colette A.; Strangward, Patrick; de Souza, J. Brian

    2015-01-01

    Immune-mediated pathology in interleukin-10 (IL-10)-deficient mice during blood-stage malaria infection typically manifests in nonlymphoid organs, such as the liver and lung. Thus, it is critical to define the cellular sources of IL-10 in these sensitive nonlymphoid compartments during infection. Moreover, it is important to determine if IL-10 production is controlled through conserved or disparate molecular programs in distinct anatomical locations during malaria infection, as this may enable spatiotemporal tuning of the regulatory immune response. In this study, using dual gamma interferon (IFN-γ)–yellow fluorescent protein (YFP) and IL-10–green fluorescent protein (GFP) reporter mice, we show that CD4+ YFP+ T cells are the major source of IL-10 in both lymphoid and nonlymphoid compartments throughout the course of blood-stage Plasmodium yoelii infection. Mature splenic CD4+ YFP+ GFP+ T cells, which preferentially expressed high levels of CCR5, were capable of migrating to and seeding the nonlymphoid tissues, indicating that the systemically distributed host-protective cells have a common developmental history. Despite exhibiting comparable phenotypes, CD4+ YFP+ GFP+ T cells from the liver and lung produced significantly larger quantities of IL-10 than their splenic counterparts, showing that the CD4+ YFP+ GFP+ T cells exert graded functions in distinct tissue locations during infection. Unexpectedly, given the unique environmental conditions within discrete nonlymphoid and lymphoid organs, we show that IL-10 production by CD4+ YFP+ T cells is controlled systemically during malaria infection through IL-27 receptor signaling that is supported after CD4+ T cell priming by ICOS signaling. The results in this study substantially improve our understanding of the systemic IL-10 response to malaria infection, particularly within sensitive nonlymphoid organs. PMID:26459508

  2. Dysregulated expression of IFN-γ and IL-10 and impaired IFN-γ-mediated responses at different disease stages in patients with genital herpes simplex virus-2 infection

    PubMed Central

    SINGH, R; KUMAR, A; CREERY, W D; RUBEN, M; GIULIVI, A; DIAZ-MITOMA, F

    2003-01-01

    Cell-mediated T-helper type-1 (Th1) responses play a vital role in the immunopathogenesis of genital infections caused by herpes simplex virus 2 (HSV-2). We investigated the role of Th responses in HSV-2 infection at different disease stages by analysing the production of Th cytokines in HSV-stimulated peripheral blood mononuclear cells (PBMCs). IFN-γ production decreased over time following a recurrence, whereas levels of IL-10, and to a lesser extent IL-2, remained elevated during this period. In addition, PBMCs from asymptomatic seropositive individuals produced high levels of IFN-γ and low levels of IL-10, in contrast to individuals with a history of genital ulcers. Following a recurrence, virus copy number in the genital lesions decreased progressively over time, in a manner similar to IFN-γ production by HSV-2-stimulated PBMCs. Enhanced production of IFN-γ may modulate HSV replication and B7 expression on monocytic cells of HSV-infected individuals. In contrast to seronegative controls, IFN-γ failed to enhance B7 expression on monocytic cells of HSV-infected individuals. In addition, monocytic cells from HSV-2-infected individuals with recurrent disease supported greater HSV replication than did those of HSV-infected asymptomatic individuals or seronegative controls. Furthermore, addition of IFN-γ resulted in enhanced HSV replication in monocytic cells of HSV-infected individuals with recurrent disease, in contrast to the inhibition observed in HSV-seropositive asymptomatic individuals and seronegative controls. Taken together, our results suggest that dysregulated production of IFN-γ at different disease stages and the impaired ability of monocytic cells to respond to IFN-γ may play a role in the pathogenesis of recurrent genital herpes disease. PMID:12823283

  3. IL-2 contributes to maintaining a balance between CD4+Foxp3+ regulatory T cells and effector CD4+ T cells required for immune control of blood-stage malaria infection.

    PubMed

    Berretta, Floriana; St-Pierre, Jessica; Piccirillo, Ciriaco A; Stevenson, Mary M

    2011-04-15

    To investigate the role of CD4(+)CD25(+)Foxp3(+) regulatory T (Treg) cells in blood-stage malaria, we compared Plasmodium chabaudi AS infection in wild-type (WT) C57BL/6 and transgenic mice overexpressing the transcription factor Foxp3 (Foxp3Tg) and observed that Foxp3Tg mice experienced lethal infection and deficient malaria-specific immune responses. Adoptive transfer of total CD4(+) T cells from Foxp3Tg mice or CD4(+)CD25(+) T cells from WT mice to naive WT recipients confirmed that high numbers of Treg cells compromised immune control of malaria. Transfer of GFP(+)CD4(+)CD25(+) T cells to naive WT recipients together with immunohistochemical staining of spleens from infected WT mice demonstrated that Foxp3(+) Treg cells localized in the T cell area of the spleen. Determination of CD4(+)Foxp3(+) Treg cell responses in the spleen of infected WT mice revealed a significant but transient increase in CD4(+)Foxp3(+) Treg cells early in infection. This was followed by a significant and sustained decrease due to reduced proliferation and apoptosis of CD4(+)Foxp3(+) Treg cells. Importantly, the kinetics of IL-2 secretion by effector CD4(+)Foxp3(-) T cells coincided with changes in CD4(+)Foxp3(+) cells and the differentiation of CD4(+)T-bet(+)IFN-γ(+) cells required for immune control of infection. Administration of the IL-2/anti-IL-2 mAb (clone JES6-1) complex to infected WT mice increased the severity of P. chabaudi AS infection and promoted expansion of Foxp3(+) Treg cells. Collectively, these data demonstrate that the ability to control and eliminate P. chabaudi AS infection is due to a tight balance between natural Treg cells and effector CD4(+) Th1 cells, a balance regulated in part by IL-2.

  4. Fatty acid composition of Echinostoma trivolvis (Trematoda) rediae and adults and of the digestive gland-gonad complex of Helisoma trivolvis (Gastropoda) infected with the intramolluscan stages of this echinostome.

    PubMed

    Fried, B; Rao, K S; Sherma, J; Huffman, J E

    1993-01-01

    Gas-liquid chromatographic studies were done to determine the fatty acid composition of the digestive gland-gonad (DGG) complex of Helisoma trivolvis snails infected with the intramolluscan stages of Echinostoma trivolvis, of rediae freed from the DGG, of uninfected DGG, and of 41-day-old adult worms grown in golden hamsters. The DGG of infected snails showed significantly higher levels of stearic acid (18:0), hexatrienoic acid (16:3n-4), and docosahexanoic acid (22:6n-3) than that of uninfected snails. However, the DGG of uninfected snails showed significantly higher levels of 20:2 non-methylene-interrupted diene (NMID) and adrenic acid (22:4n-6) than that of infected snails. The profiles of other fatty acids were remarkably similar in both infected and uninfected snails. Adult worms showed significantly higher amounts of numerous saturated fatty acids and dienes as compared with the rediae. However, the rediae showed significantly higher amounts of certain monoenes and trienes as compared with the adults. Fatty acid differences between rediae and adults probably reflect differences in either the available lipid pools in the immediate host sites or the metabolic activity of each stage of this echinostome.

  5. Report of a consultation on the optimization of clinical challenge trials for evaluation of candidate blood stage malaria vaccines, 18-19 March 2009, Bethesda, MD, USA.

    PubMed

    Moorthy, V S; Diggs, C; Ferro, S; Good, M F; Herrera, S; Hill, A V; Imoukhuede, E B; Kumar, S; Loucq, C; Marsh, K; Ockenhouse, C F; Richie, T L; Sauerwein, R W

    2009-09-25

    Development and optimization of first generation malaria vaccine candidates has been facilitated by the existence of a well-established Plasmodium falciparum clinical challenge model in which infectious sporozoites are administered to human subjects via mosquito bite. While ideal for testing pre-erythrocytic stage vaccines, some researchers believe that the sporozoite challenge model is less appropriate for testing blood stage vaccines. Here we report a consultation, co-sponsored by PATH MVI, USAID, EMVI and WHO, where scientists from all institutions globally that have conducted such clinical challenges in recent years and representatives from regulatory agencies and funding agencies met to discuss clinical malaria challenge models. Participants discussed strengthening and harmonizing the sporozoite challenge model and considered the pros and cons of further developing a blood stage challenge possibly better suited for evaluating the efficacy of blood stage vaccines. This report summarizes major findings and recommendations, including an update on the Plasmodium vivax clinical challenge model, the prospects for performing experimental challenge trials in malaria endemic countries and an update on clinical safety data. While the focus of the meeting was on the optimization of clinical challenge models for evaluation of blood stage candidate malaria vaccines, many of the considerations are relevant for the application of challenge trials to other purposes.

  6. A multi-stage compartmental model for HIV-infected individuals: II--application to insurance functions and health-care costs.

    PubMed

    Billard, L; Dayananda, P W A

    2014-03-01

    Stochastic population processes have received a lot of attention over the years. One approach focuses on compartmental modeling. Billard and Dayananda (2012) developed one such multi-stage model for epidemic processes in which the possibility that individuals can die at any stage from non-disease related causes was also included. This extra feature is of particular interest to the insurance and health-care industries among others especially when the epidemic is HIV/AIDS. Rather than working with numbers of individuals in each stage, they obtained distributional results dealing with the waiting time any one individual spent in each stage given the initial stage. In this work, the impact of the HIV/AIDS epidemic on several functions relevant to these industries (such as adjustments to premiums) is investigated. Theoretical results are derived, followed by a numerical study.

  7. Antigens for a Vaccine that Prevents Severe Malaria

    DTIC Science & Technology

    2007-03-01

    Hutagalung, R . et al. (1999) Influence of hemoglobin E trait on the severity of falciparum malaria. J. Infect. Dis. 179, 283–286 8 Ruwende, C. et al...erythrocytic stage in mam- malian malaria parasites. Nature 161: 126. 2. Shortt HE, Fairley NH, Covell G, Shute PG, Garnham PC, 1951. The pre-erythrocytic...stage of Plasmodium falciparum. Trans R Soc Trop Med Hyg 44: 405–419. 3. Schaudinn F, 1903. Studien ueber krankheitserregende Proto- zoen II

  8. Stage design

    DOEpatents

    Shacter, J.

    1975-12-01

    A method is described of cycling gases through a plurality of diffusion stages comprising the steps of admitting the diffused gases from a first diffusion stage into an axial compressor, simultaneously admitting the undiffused gases from a second diffusion stage into an intermediate pressure zone of said compressor corresponding in pressure to the pressure of said undiffused gases, and then admitting the resulting compressed mixture of diffused and undiffused gases into a third diffusion stage.

  9. Effects of intra-mammary bacterial infection with coagulase negative staphylococci and stage of lactation on shedding of epithelial cells and infiltration of leukocytes into milk: comparison among cows, goats and sheep.

    PubMed

    Leitner, Gabriel; Merin, Uzi; Krifucks, Oleg; Blum, Shlomo; Rivas, Ariel L; Silanikove, Nissim

    2012-06-30

    The effects of mammary gland bacterial infection and stage of lactation on leukocyte infiltration into the mammary gland were compared among cows, goats and sheep. Animals were at two stages of lactation: mid or late. In mid-lactation animals, bacterial-free glands and coagulase negative Staphylococcus (CNS)-infected glands were compared. In late lactation only uninfected glands were studied. Of mid-lactation bacteria-free animals, goats had the highest number of leukocytes and % polymorphonuclears (PMNs), whereas sheep had the lowest and leukocytes number in cows were intermediate between sheep and goats. Based on %PMN, two cell clusters were found in sheep, which overlapped with the parallel cell clusters of cows and goats, but with a slightly higher number of leukocytes in each cell cluster. At late lactation, goats had higher values for %PMN and leukocyte numbers in comparison to cows, which had a similar cellular profile to sheep. The cellular immune response to CNS infection was similar for the three animal species, although the number of cells was different, while the basal cell level at mid-lactation and especially at the end of lactation was species specific.

  10. [Direct cost related to management and care provision for HIV-infected children in the asymptomatic stage in Abidjan, Cote d'Ivoire].

    PubMed

    Djohan, G; Kouakoussui, A; Msellati, P

    2005-12-01

    The objective of this study was to estimate the direct cost of medical and psychological care provided to asymptomatic HIV-infected children in Abidjan, Cote d'Ivoire. For this purpose, a retrospective study was carried out among a group of asymptomatic HIV-infected children in Abidjan who were part of the "projet enfant Yopougon" (ANRS 1244/1278). The study reviewed these childrens' hospital records and files dating between October 2000 and March 2003. The follow up period for a total of 46 children represented a cumulative of 83.4 children years and showed that 8 potentially death-threatening medical events were recorded on average per child per year. The mean annual cost for the management and delivery of medical and psychological care per asymptomatic HIV-infected child was 132, 730 FCFA per year, or rather 11,000 FCFA (16.63 Euros) per month. This relatively low cost should be used to advocate for more financial support from governments and the international community to contribute to more effective management of care and services for HIV-infected children.

  11. Electrolyte level and blood pH in dogs infected by various 18S RNA strains of Babaesia canis canis on the early stage of babesiosis.

    PubMed

    Adaszek, Łukasz; Górna, Marta; Winiarczyk, Stanisław

    2012-01-01

    The purpose of the studies was to determine electrolyte disturbances and blood pH changes in dogs with babesiosis and possibly show a connection between the Babesia (B.) canis strain causing the infection and the intensity of these irregularities. 40 animals (group 1) with early babesiosis and 40 healthy dogs (group 2) were studied and their blood pH and blood levels of potassium, chlorides; calcium and sodium were determined. At the same time, molecular typing of parasites was carried out to detect which B.canis strain (18S RNA-A or 185 RNA-B) had caused the disease in dogs of group 1. In group 1, four dogs were acidaemic, twelve had normal blood pH, and 24 were alkalaemic. Potassium concentration was below normal in 16 out of 40 dogs (40%) and normal in 24 dogs. Hypochloremia was present in 36 out of 40 dogs; chloride was normal in the remaining four animals. Serum sodium concentration was low in 16 of 40 dogs, normal in 20 of 40 dogs and high in four dogs. Calcium concentration was normal in all 40 dogs. In dogs of group 2 no abnormalities of haematological or blood biochemical parameters were observed. 29 out of the 40 dogs of group 1 were infected with the 18S RNA-A strain and eleven with the 18S RNA-B strain of Babesia canis canis. We did not observe any correlation between the type of strain causing the infection and the electrolyte disturbances in the serum of sick dogs. Hypocalaemia was observed in ten specimen infected with 18S RNA-A and six infected with 18S RNA-B. Additionally, in dogs infected with 18S RNA-A, hypochloraemia (28), hyponatraemia (10), hypernatraemia (2) were observed, as well as blood pH drop (4) or increase (14). The 18S RNA-B-infected dogs suffered from hypochloraemia (8), hyponatraemia (6), hypernatraemia (2) and increase in blood pH (10).The studies conducted did not answer the question of whether the type of electrolyte disturbances in dogs with babesiosis can be connected with the strain of the parasite that induced the disease, as

  12. Life-history studies on two molecular strains of mesocestoides (Cestoda: Mesocestoididae): identification of sylvatic hosts and infectivity of immature life stages.

    PubMed

    Padgett, Kerry A; Boyce, Walter M

    2004-02-01

    Life-cycle studies were conducted on 2 molecular strains of Mesocestoides tapeworms that represent different evolutionary lineages (clades A and B). Wild carnivores, reptiles, and rodents were examined for tapeworm infections at 2 enzootic sites: (1) San Miguel Island (SMI), a small island off the coast of southern California and (2) Hopland Research and Extension Center (HREC), a field station in northern California. Results indicate that deer mice (Peromyscus maniculatus) and coyotes (Canis latrans) may play an important role in the life cycles of Mesocestoides (clades A and B) in California. Over half the coyotes at HREC and at least a third of the population of island fox (Urocyon littoralis) at SMI were found to harbor clade A adult Mesocestoides spp. One of every 4 Mesocestoides-infected coyotes had tapeworms representing both clades A and B. Experimental inoculations revealed that proglottids (clades A and B) were not directly infectious to rodents, reptiles, or dogs. On the other hand, mice, lizards, and hamsters fed tetrathyridia of Mesocestoides spp. (clades A or B) developed peritoneal tetrathyridial infections. A dog that was fed tetrathyridia (clade B) developed an adult tapeworm infection. Acephalic metacestodes given orally to western fence lizards, laboratory mice, or domestic dogs did not result in metacestode or adult tapeworm infections. Whereas most clade A acephalic metacestodes from dogs were asexually proliferative, clade A tetrathyridia isolated from wild deer mice did not show evidence of asexual replication. Our study supports the hypothesis that a second, as of yet unidentified, intermediate host is necessary to complete the life cycles of Mesocestoides spp., and that acephalic metacestodes represent an aberrant form, incapable of further development.

  13. IL28B polymorphisms influence stage of fibrosis and spontaneous or interferon-induced viral clearance in thalassemia patients with hepatitis C virus infection

    PubMed Central

    Di Marco, Vito; Bronte, Fabrizio; Calvaruso, Vincenza; Capra, Marcello; Borsellino, Zelia; Maggio, Aurelio; Renda, Maria Concetta; Pitrolo, Lorella; Lo Pinto, Maria Carmela; Rizzo, Michele; Fiorenza, Flavia; Gerardi, Calogera; Grimaudo, Stefania; Di Cristina, Antonietta; Levrero, Massimo; Craxì, Antonio

    2012-01-01

    Background Polymorphisms in the interleukin-28B are important determinants in the spontaneous and drug-induced control of hepatitis C virus infection. Design and Methods We assessed the association of rs8099917 and rs12979860 polymorphisms with spontaneous viral clearance, severity of liver fibrosis, and response to interferon-monotherapy in 245 thalassemia major patients with hepatitis C virus infection. Results Ninety-eight patients (40%) had a spontaneous viral clearance while 147 patients (60%) developed a chronic infection. Spontaneous viral clearance was more frequent among patients with the T/T genotype of rs8099917 polymorphism (OR 2.130; P=0.008) or C/C genotype of rs12979860 polymorphism (OR 2.425; P=0.001). During observation, 131 patients with chronic infection underwent a liver biopsy; age (OR 1.058; P=0.01) G/T or G/G genotypes of rs8099917 polymorphism (OR 3.962; P=0.001), and C/T or T/T genotypes of rs12979860 polymorphism (OR 3.494; P=0.005) were associated with severe liver fibrosis, independent of liver iron concentration. Finally, T/T genotype of rs8099917 polymorphism (OR 3.014; P=0.03) or C/C genotype of rs12979860 polymorphism (OR 3.285; P=0.01), age (OR 0.902; P=0.001), female gender (OR 3.418; P=0.01) and 2 or 3 virus C genotypes (OR 4.700; P=0.007) were independently associated with sustained virological response in 114 patients treated with alpha-interferon. Conclusions Polymorphisms in the interleukin-28B are associated with the control of hepatitis C virus infection in thalassemia major patients, and understanding allelic patterns has an important role in determining prognosis and therapeutic management. PMID:22180419

  14. Cardamom Bushy Dwarf Virus Infection in Large Cardamom Alters Plant Selection Preference, Life Stages, and Fecundity of Aphid Vector, Micromyzus kalimpongensis (Hemiptera: Aphididae).

    PubMed

    Ghosh, Amalendu; Das, Amrita; Vijayanandraj, S; Mandal, Bikash

    2016-02-01

    Cardamom bushy dwarf virus (CBDV) causes foorkey disease of large cardamom (Ammomum subulatum Roxburgh) in the eastern sub-Himalayan mountains. Although the aphid Micromyzus kalimpongensis Basu (Hemiptera: Aphididae) is known as a vector of CBDV, its behavior in dissemination of CBDV has not been investigated. In the present study, M. kalimpongensis was observed to colonize in higher number on CBDV-infected large cardamom plants compared with the healthy plants in the several plantations in Sikkim and Darjeeling hills. The affinity of M. kalimpongensis to the diseased large cardamom plants was further confirmed in a contained field experiment with intact plant as well as in a laboratory bioassay with the plant extract, where significantly higher number of aphids settled on the diseased plants or extracts compared with the healthy counterparts. Aphids grown on CBDV-infected large cardamom plants had shortened nymphal period and increased longevity and fecundity compared with those grown on the healthy plants. In the contained field experiment, M. kalimpongensis migrated to the CBDV-infected plants, colonized there, acquired CBDV, and once the diseased plants withered, migrated to healthy plants, which eventually became diseased. Our results suggest a general pattern of spread of CBDV by M. kalimpongensis where CBDV-infected plants attract or arrest and stimulate emergence and migration of viruliferous aphids that otherwise are sedentary in the underground plant parts of large cardamom. To our knowledge, this is the first study that shows the influence of a plant virus from the family Nanoviridae in altering behavior of its insect vector that favors its dissemination.

  15. Proteome profile of maize (Zea Mays L.) leaf tissue at the flowering stage after long-term adjustment to rice black-streaked dwarf virus infection.

    PubMed

    Li, Kunpeng; Xu, Changzheng; Zhang, Juren

    2011-10-10

    Maize rough dwarf disease (MRDD) is a viral disease and causes great yield loss. To better understand the effects of MRDD on plant growth and metabolism, comparative proteomic analysis of leaves from virus-infected and normal plants was performed. In order to eliminate the interference of Ribulose-1, 5-bisphosphate carboxylase with low-abundance proteins, total proteins were pre-fractionated by 15% PEG and the proteins from supernatant and precipitated fractions were analyzed by 2-DE, subsequently. Out of approximately 1200 protein spots detected, less than 2% of the spots on the gels were overlapping between the fractions of precipitation and supernatant. We identified 91 differentially accumulated proteins that belong to multiple metabolic/biochemical pathways in plants. Further analysis of these identified proteins indicated that MRDD resulted in dramatic changes in the fundamental metabolism, including glycolysis and starch metabolism, and eventually the significant differences in morphology and development between virus-infected and normal plants. Moreover, MRDD occurrence increased the demands for G-proteins, antioxidant enzymes, lipoxygenases and UDP-glucosyltransferase BX9, which may play important roles in response of plant against virus infection. The results also suggested that MRDD is a complicated disease controlled by multigene participating in different pathways.

  16. Stearylamine Liposomal Delivery of Monensin in Combination with Free Artemisinin Eliminates Blood Stages of Plasmodium falciparum in Culture and P. berghei Infection in Murine Malaria

    PubMed Central

    Rohra, Shilpa; Raza, Mohsin; Hasan, Gulam Mustafa; Dutt, Suparna

    2015-01-01

    The global emergence of drug resistance in malaria is impeding the therapeutic efficacy of existing antimalarial drugs. Therefore, there is a critical need to develop an efficient drug delivery system to circumvent drug resistance. The anticoccidial drug monensin, a carboxylic ionophore, has been shown to have antimalarial properties. Here, we developed a liposome-based drug delivery of monensin and evaluated its antimalarial activity in lipid formulations of soya phosphatidylcholine (SPC) cholesterol (Chol) containing either stearylamine (SA) or phosphatidic acid (PA) and different densities of distearoyl phosphatidylethanolamine-methoxy-polyethylene glycol 2000 (DSPE-mPEG-2000). These formulations were found to be more effective than a comparable dose of free monensin in Plasmodium falciparum (3D7) cultures and established mice models of Plasmodium berghei strains NK65 and ANKA. Parasite killing was determined by a radiolabeled [3H]hypoxanthine incorporation assay (in vitro) and microscopic counting of Giemsa-stained infected erythrocytes (in vivo). The enhancement of antimalarial activity was dependent on the liposomal lipid composition and preferential uptake by infected red blood cells (RBCs). The antiplasmodial activity of monensin in SA liposome (50% inhibitory concentration [IC50], 0.74 nM) and SPC:Chol-liposome with 5 mol% DSPE-mPEG 2000 (IC50, 0.39 nM) was superior to that of free monensin (IC50, 3.17 nM), without causing hemolysis of erythrocytes. Liposomes exhibited a spherical shape, with sizes ranging from 90 to 120 nm, as measured by dynamic light scattering and high-resolution electron microscopy. Monensin in long-circulating liposomes of stearylamine with 5 mol% DSPE-mPEG 2000 in combination with free artemisinin resulted in enhanced killing of parasites, prevented parasite recrudescence, and improved survival. This is the first report to demonstrate that monensin in PEGylated stearylamine (SA) liposome has therapeutic potential against malaria

  17. Ethical issues in a stage 1 cognitive-behavioral therapy feasibility study and trial to reduce alcohol use among HIV-infected outpatients in western Kenya.

    PubMed

    Papas, Rebecca K; Gakinya, Benson N; Baliddawa, Joyce B; Martino, Steve; Bryant, Kendall J; Meslin, Eric M; Sidle, John E

    2012-07-01

    Epidemics of both HIV/AIDS and alcohol abuse in sub-Saharan Africa have spurred the conduct of local behavioral therapy trials for these problems, but the ethical issues involved in these trials have not been fully examined. In this paper, we discuss ethical issues that emerged during the conduct of a behavioral intervention adaptation and trial using cognitive-behavioral therapy to reduce alcohol use among HIV-infected outpatients in Eldoret, Kenya. The study was performed within our multinational collaboration, the USAID-Academic Model Providing Access to Healthcare Partnership. We discuss relevant ethical considerations and how we addressed them.

  18. Ethical Issues in a Stage 1 Cognitive-Behavioral Therapy Feasibility Study and Trial to Reduce Alcohol Use Among HIV-Infected Outpatients in Western Kenya

    PubMed Central

    Papas, Rebecca K.; Gakinya, Benson N.; Baliddawa, Joyce B.; Martino, Steve; Bryant, Kendall J.; Meslin, Eric M.; Sidle, John E.

    2013-01-01

    Epidemics of both HIV/AIDS and alcohol abuse in sub-Saharan Africa have spurred the conduct of local behavioral therapy trials for these problems, but the ethical issues involved in these trials have not been fully examined. In this paper, we discuss ethical issues that emerged during the conduct of a behavioral intervention adaptation and trial using cognitive-behavioral therapy to reduce alcohol use among HIV-infected outpatients in Eldoret, Kenya. The study was performed within our multinational collaboration, the USAID-Academic Model Providing Access to Healthcare Partnership. We discuss relevant ethical considerations and how we addressed them. PMID:22850141

  19. Telbivudine treatment of hepatitis B virus-infected pregnant women at different gestational stages for the prevention of mother-to-child transmission

    PubMed Central

    Tan, Zhangmin; Yin, Yuzhu; Zhou, Jin; Wu, Lingling; Xu, Chengfang; Hou, Hongying

    2016-01-01

    Abstract This prospective study evaluated the viability of telbivudine for blocking mother-to-child transmission (MTCT) of hepatitis B virus (HBV) infection. Pregnant women positive for the hepatitis B surface antigen began telbivudine treatment before 14 weeks of gestation (i.e., early), between 14 and 28 weeks of gestation (late), or not at all (control). In the late-treatment group, 55 women terminated telbivudine therapy within puerperium. All neonates underwent routine hepatitis B immunoglobulin plus vaccination. Mothers and infants were followed for 7 months after birth. Pregnancy outcomes were similar among the 3 groups. HBV MTCT rates in the early and late treatment and control groups were 0, 0, and 4.69%, respectively. The rates of infant vaccination success among the 3 groups were similar, as were neonatal outcomes including birth weights, asphyxia, hyperbilirubinemia, Apgar score, birth defects, and weight and height at 7 months. Puerperal discontinuation of telbivudine did not increase the alanine transaminase value at 7 months after birth, but increased serum HBV DNA levels, and rates of positive hepatitis Be-antigen. Telbivudine treatment in HBV-infected pregnant women was associated with lower serum HBV DNA levels and reduced rates of HBV MTCT; there were no associated changes in pregnancy or neonatal outcomes at birth or 7 months after birth, or in the rate of infant vaccination success. Puerperal drug withdrawal after short-term antiviral therapy will not influence hepatic function, but may increase virus replication. PMID:27749537

  20. Malaria infection of the mosquito Anopheles gambiae activates immune-responsive genes during critical transition stages of the parasite life cycle.

    PubMed Central

    Dimopoulos, G; Seeley, D; Wolf, A; Kafatos, F C

    1998-01-01

    Six gene markers have been used to map the progress of the innate immune response of the mosquito vector, Anopheles gambiae, upon infection by the malaria parasite, Plasmodium berghei. In addition to four previously reported genes, the set of markers included NOS (a nitric oxide synthase gene fragment) and ICHIT (a gene encoding two putative chitin-binding domains separated by a polythreonine-rich mucin region). In the midgut, a robust response occurs at 24 h post-infection, at a time when malaria ookinetes traverse the midgut epithelium, but subsides at later phases of malaria development. In contrast, the salivary glands show no significant response at 24 h, but are activated in a prolonged late phase when sporozoites are released from the midgut into the haemolymph and invade the glands, between 10 and 25 days after blood feeding. Furthermore, the abdomen of the mosquito minus the midgut shows significant activation of immune markers, with complex kinetics that are distinct from those of both midgut and salivary glands. The parasite evidently elicits immune responses in multiple tissues of the mosquito, two of which are epithelia that the parasite must traverse to complete its development. The mechanisms of these responses and their significance for malaria transmission are discussed. PMID:9799221

  1. Third Stage

    NASA Video Gallery

    Once the third stage finishes its work, Kepler will have sufficient energy to leave the gravitational pull of Earth and go into orbit around the Sun, trailing behind Earth and slowly drifting away ...

  2. A New Nonpolar N-Hydroxy Imidazoline Lead Compound with Improved Activity in a Murine Model of Late-Stage Trypanosoma brucei brucei Infection Is Not Cross-Resistant with Diamidines

    PubMed Central

    Ríos Martínez, Carlos H.; Miller, Florence; Ganeshamoorthy, Kayathiri; Glacial, Fabienne; Kaiser, Marcel; de Koning, Harry P.; Eze, Anthonius A.; Lagartera, Laura; Herraiz, Tomás

    2014-01-01

    Treatment of late-stage sleeping sickness requires drugs that can cross the blood-brain barrier (BBB) to reach the parasites located in the brain. We report here the synthesis and evaluation of four new N-hydroxy and 12 new N-alkoxy derivatives of bisimidazoline leads as potential agents for the treatment of late-stage sleeping sickness. These compounds, which have reduced basicity compared to the parent leads (i.e., are less ionized at physiological pH), were evaluated in vitro against Trypanosoma brucei rhodesiense and in vivo in murine models of first- and second-stage sleeping sickness. Resistance profile, physicochemical parameters, in vitro BBB permeability, and microsomal stability also were determined. The N-hydroxy imidazoline analogues were the most effective in vivo, with 4-((1-hydroxy-4,5-dihydro-1H-imidazol-2-yl)amino)-N-(4-((1-hydroxy-4,5-dihydro-1H-imidazol-2-yl)amino)phenyl)benzamide (14d) showing 100% cures in the first-stage disease, while 15d, 16d, and 17d appeared to slightly improve survival. In addition, 14d showed weak activity in the chronic model of central nervous system infection in mice. No evidence of reduction of this compound with hepatic microsomes and mitochondria was found in vitro, suggesting that N-hydroxy imidazolines are metabolically stable and have intrinsic activity against T. brucei. In contrast to its unsubstituted parent compound, the uptake of 14d in T. brucei was independent of known drug transporters (i.e., T. brucei AT1/P2 and HAPT), indicating a lower predisposition to cross-resistance with other diamidines and arsenical drugs. Hence, the N-hydroxy bisimidazolines (14d in particular) represent a new class of promising antitrypanosomal agents. PMID:25421467

  3. A new nonpolar N-hydroxy imidazoline lead compound with improved activity in a murine model of late-stage Trypanosoma brucei brucei infection is not cross-resistant with diamidines.

    PubMed

    Ríos Martínez, Carlos H; Miller, Florence; Ganeshamoorthy, Kayathiri; Glacial, Fabienne; Kaiser, Marcel; de Koning, Harry P; Eze, Anthonius A; Lagartera, Laura; Herraiz, Tomás; Dardonville, Christophe

    2015-02-01

    Treatment of late-stage sleeping sickness requires drugs that can cross the blood-brain barrier (BBB) to reach the parasites located in the brain. We report here the synthesis and evaluation of four new N-hydroxy and 12 new N-alkoxy derivatives of bisimidazoline leads as potential agents for the treatment of late-stage sleeping sickness. These compounds, which have reduced basicity compared to the parent leads (i.e., are less ionized at physiological pH), were evaluated in vitro against Trypanosoma brucei rhodesiense and in vivo in murine models of first- and second-stage sleeping sickness. Resistance profile, physicochemical parameters, in vitro BBB permeability, and microsomal stability also were determined. The N-hydroxy imidazoline analogues were the most effective in vivo, with 4-((1-hydroxy-4,5-dihydro-1H-imidazol-2-yl)amino)-N-(4-((1-hydroxy-4,5-dihydro-1H-imidazol-2-yl)amino)phenyl)benzamide (14d) showing 100% cures in the first-stage disease, while 15d, 16d, and 17d appeared to slightly improve survival. In addition, 14d showed weak activity in the chronic model of central nervous system infection in mice. No evidence of reduction of this compound with hepatic microsomes and mitochondria was found in vitro, suggesting that N-hydroxy imidazolines are metabolically stable and have intrinsic activity against T. brucei. In contrast to its unsubstituted parent compound, the uptake of 14d in T. brucei was independent of known drug transporters (i.e., T. brucei AT1/P2 and HAPT), indicating a lower predisposition to cross-resistance with other diamidines and arsenical drugs. Hence, the N-hydroxy bisimidazolines (14d in particular) represent a new class of promising antitrypanosomal agents.

  4. A study of the level and dynamics of Eimeria populations in naturally infected, grazing beef cattle at various stages of production in the Mid-Atlantic USA.

    PubMed

    Lucas, Aaron S; Swecker, William S; Lindsay, David S; Scaglia, Guillermo; Neel, James P S; Elvinger, Francois C; Zajac, Anne M

    2014-05-28

    There is little information available on the species dynamics of eimerian parasites in grazing cattle in the central Appalachian region of the United States. Therefore, the objective of this study was to describe the level of infection and species dynamics of Eimeria spp. in grazing beef cattle of various age groups over the course of a year in the central Appalachian region. Rectal fecal samples were collected from male and female calves (n=72) monthly from May through October 2005, heifers only (n=36) monthly from November 2005 to April 2006, and cows (n=72) in May, July, and September, 2005. Eimeria spp. oocysts were seen in 399 of 414 (96%) fecal samples collected from the calves from May through October. Fecal oocysts counts (FOC) in the calves were lower (P<0.05) in May than all other months and no significant differences were detected from June through September. Eimeria spp. oocysts were detected in 198 of 213 (92%) of fecal samples collected from the 36 replacement heifers monthly from November to April and monthly mean FOC did not differ during this time period. The prevalence of oocyst shedding increased to 100% in calves in September and remained near 100% in the replacement heifers during the sampling period. Eimeria spp. oocysts were also detected in 150 of 200 (75%) samples collected in May, July, and September from the cows and mean FOC did not differ significantly over the sampling period. Eimeria spp. composition was dominated by Eimeria bovis in fecal samples collected from calves, replacement heifers and cows. Mixed Eimeria spp. infections were, however, common in all groups and 13 Eimeria spp. oocysts were identified throughout the sampling period.

  5. Alteration of antibodies against the fifth-stage larvae and changes in brain magnetic resonance images in experimentally infected rabbits with Angiostrongylus cantonensis.

    PubMed

    Wang, Lian-Chen; Wan, Yung-Liang

    2004-10-01

    Magnetic resonance (MR) imaging has been suggested to be helpful in delineating the lesions during the acute phase of angiostrongyliasis caused by Angiostrongylus cantonensis. In this study, antibody titers in serum samples of 3 rabbits were determined by enzyme-linked immunosorbent assay, and brain MR images were obtained from 6 rabbits. The antibody titer elevated rapidly in the first 4 wk postinfection (PI) before reaching a plateau. However, suspicious changes in brain MR images near the left lateral ventricle and hippocampus were found only in 1 rabbit on day 28 PI. These findings indicate that immunologic responses in the central nervous system at the early stage of angiostrongyliasis are not sufficient to be observed by image studies.

  6. Identification of Two New Protective Pre-erythrocytic Malaria Vaccine Antigen Candidates

    DTIC Science & Technology

    2011-01-01

    Kalpana Gowda1, Noelle Patterson1,2, Esteban Abot1,2, Martha Sedegah1, John Sacci3 and Thomas Richie1 Abstract Background: Despite years of effort, a...pur- chased from Charles River Laboratories (Wilmington, MA). P. yoelii (17XNL non-lethal strain) parasites were maintained by alternating passage in...National Research Council, National Academy Press, 1995. Thomas Richie is a military service member and Kalpana Gowda and Martha Sedegah are

  7. Effects of four tropical tanniniferous plant extracts on the inhibition of larval migration and the exsheathment process of Trichostrongylus colubriformis infective stage.

    PubMed

    Alonso-Díaz, M A; Torres-Acosta, J F J; Sandoval-Castro, C A; Capetillo-Leal, C; Brunet, S; Hoste, H

    2008-05-06

    The anthelmintic (AH) effect of Acacia pennatula, Leucaena leucocephala, Lisyloma latisiliquum and Piscidia piscipula was evaluated in the infective larvae (L(3)) of Trichostrongylus colubriformis. Different concentrations of lyophilized extracts were tested using the larval migration inhibition (LMI) test. An inhibitor of tannins (the polyvinyl polypyrrolidone [PVPP]) was used to verify whether these compounds were responsible for the AH effects. Then, the effect of extracts on larval exsheathment was examined by observing the exsheathment process at 10-min intervals for 70 min. The LMI test showed a dose-dependant AH effect for A. pennatula, L. leucocephala and L. latisiliquum (P<0.01), but not for P. piscipula. The restoration of L(3) migration to values similar to those of controls after the addition of PVPP, indicates that tannins are involved in AH effects. Trichostrongylus colubriformis exsheathment was partially or totally blocked by the four plants extracts. Tropical tanniniferous plants evaluated in the current study may have potential as AH for the control of T. colubriformis if in vivo investigations indicate useful effects.

  8. Stage Posts

    ERIC Educational Resources Information Center

    Soulsby, Jim

    2004-01-01

    Uncertainty about identity and the future is occurring at a stage of life when people do question what they have achieved and what they still want to achieve. The notion of midlife crisis has been in existence for some time but recently its occurrence has coincided with opportunities to take early retirement or redundancy. This has meant that the…

  9. Multiple circulating infections can mimic the early stages of viral hemorrhagic fevers and possible human exposure to filoviruses in Sierra Leone prior to the 2014 outbreak.

    PubMed

    Boisen, Matthew L; Schieffelin, John S; Goba, Augustine; Oottamasathien, Darin; Jones, Abigail B; Shaffer, Jeffrey G; Hastie, Kathryn M; Hartnett, Jessica N; Momoh, Mambu; Fullah, Mohammed; Gabiki, Michael; Safa, Sidiki; Zandonatti, Michelle; Fusco, Marnie; Bornholdt, Zach; Abelson, Dafna; Gire, Stephen K; Andersen, Kristian G; Tariyal, Ridhi; Stremlau, Mathew; Cross, Robert W; Geisbert, Joan B; Pitts, Kelly R; Geisbert, Thomas W; Kulakoski, Peter; Wilson, Russell B; Henderson, Lee; Sabeti, Pardis C; Grant, Donald S; Garry, Robert F; Saphire, Erica O; Branco, Luis M; Khan, Sheik Humarr

    2015-02-01

    Lassa fever (LF) is a severe viral hemorrhagic fever caused by Lassa virus (LASV). The LF program at the Kenema Government Hospital (KGH) in Eastern Sierra Leone currently provides diagnostic services and clinical care for more than 500 suspected LF cases per year. Nearly two-thirds of suspected LF patients presenting to the LF Ward test negative for either LASV antigen or anti-LASV immunoglobulin M (IgM), and therefore are considered to have a non-Lassa febrile illness (NLFI). The NLFI patients in this study were generally severely ill, which accounts for their high case fatality rate of 36%. The current studies were aimed at determining possible causes of severe febrile illnesses in non-LF cases presenting to the KGH, including possible involvement of filoviruses. A seroprevalence survey employing commercial enzyme-linked immunosorbent assay tests revealed significant IgM and IgG reactivity against dengue virus, chikungunya virus, West Nile virus (WNV), Leptospira, and typhus. A polymerase chain reaction-based survey using sera from subjects with acute LF, evidence of prior LASV exposure, or NLFI revealed widespread infection with Plasmodium falciparum malaria in febrile patients. WNV RNA was detected in a subset of patients, and a 419 nt amplicon specific to filoviral L segment RNA was detected at low levels in a single patient. However, 22% of the patients presenting at the KGH between 2011 and 2014 who were included in this survey registered anti-Ebola virus (EBOV) IgG or IgM, suggesting prior exposure to this agent. The 2014 Ebola virus disease (EVD) outbreak is already the deadliest and most widely dispersed outbreak of its kind on record. Serological evidence reported here for possible human exposure to filoviruses in Sierra Leone prior to the current EVD outbreak supports genetic analysis that EBOV may have been present in West Africa for some time prior to the 2014 outbreak.

  10. Honeybee (Apis mellifera) Venom Reinforces Viral Clearance during the Early Stage of Infection with Porcine Reproductive and Respiratory Syndrome Virus through the Up-Regulation of Th1-Specific Immune Responses.

    PubMed

    Lee, Jin-A; Kim, Yun-Mi; Hyun, Pung-Mi; Jeon, Jong-Woon; Park, Jin-Kyu; Suh, Guk-Hyun; Jung, Bock-Gie; Lee, Bong-Joo

    2015-05-22

    Porcine reproductive and respiratory syndrome (PRRS) is a chronic and immunosuppressive viral disease that is responsible for substantial economic losses for the swine industry. Honeybee venom (HBV) is known to possess several beneficial biological properties, particularly, immunomodulatory effects. Therefore, this study aimed at evaluating the effects of HBV on the immune response and viral clearance during the early stage of infection with porcine reproductive and respiratory syndrome virus (PRRSV) in pigs. HBV was administered via three routes of nasal, neck, and rectal and then the pigs were inoculated with PRRSV intranasally. The CD4+/CD8+ cell ratio and levels of interferon (IFN)-γ and interleukin (IL)-12 were significantly increased in the HBV-administered healthy pigs via nasal and rectal administration. In experimentally PRRSV-challenged pigs with virus, the viral genome load in the serum, lung, bronchial lymph nodes and tonsil was significantly decreased, as was the severity of interstitial pneumonia, in the nasal and rectal administration group. Furthermore, the levels of Th1 cytokines (IFN-γ and IL-12) were significantly increased, along with up-regulation of pro-inflammatory cytokines (TNF-α and IL-1β) with HBV administration. Thus, HBV administration-especially via the nasal or rectal route-could be a suitable strategy for immune enhancement and prevention of PRRSV infection in pigs.

  11. Incidence of WHO Stage 3 and 4 Events, Tuberculosis, and Mortality in Untreated, HIV-Infected Children Enrolling in Care Before 1 Year of Age: An Iedea (International Epidemiologic Databases To Evaluate AIDS) East Africa Regional Analysis

    PubMed Central

    Ciaranello, Andrea; Lu, Zhigang; Ayaya, Samuel; Losina, Elena; Musick, Beverly; Vreeman, Rachel; Freedberg, Kenneth A.; Abrams, Elaine J.; Dillabaugh, Lisa; Doherty, Katie; Ssali, John; Yiannoutsos, Constantin T.; Wools-Kaloustian, Kara

    2014-01-01

    Background Few studies have reported CD4%- and age-stratified rates of WHO Stage 3 (WHO3) events, WHO Stage 4 (WHO4) events, tuberculosis (TB), and mortality in HIV-infected infants before initiation of antiretroviral therapy (ART). Methods HIV-infected children enrolled before 1 year of age in the International Epidemiologic Databases to Evaluate AIDS (IeDEA) East Africa region (10/01/2002-11/30/2008) were included. We estimated incidence rates of earliest clinical event (WHO3, WHO4, and TB), prior to ART initiation per local guidelines, stratified by current age (< or ≥6 months) and current CD4% (<15%, 15–24%, ≥25%). CD4%-stratified mortality rates were estimated separately for children who did not experience a clinical event (“background” mortality) and for children who experienced an event, including “acute” mortality (≤30 days post-event) and “later” mortality (>30 days post-event). Results Among 847 children (median enrollment age: 4.8 months; median pre-ART follow-up: 10.8 months; 603 (71%) with ≥1 CD4% recorded), event rates were comparable for those aged <6 and ≥6 months. Current CD4% was associated with risk of WHO4 events for children <6 months old, and with all evaluated events for children ≥6 months old (p<0.05). “Background” mortality was 3.7–8.4/100py. “Acute” mortality (≤30 days post-event) was 33.8/100py (after TB) and 41.1/100py (after WHO3 or WHO4). “Later” mortality (>30 days post-event) ranged by CD4% from 4.7–29.1/100py. Conclusions In treatment-naïve, HIV-infected infants, WHO3, WHO4, and TB events were common before and after 6 months of age and led to substantial increases in mortality. Early infant HIV diagnosis and treatment are critically important, regardless of CD4%. PMID:24378935

  12. Safety, Immunogenicity and Efficacy of Prime-Boost Vaccination with ChAd63 and MVA Encoding ME-TRAP against Plasmodium falciparum Infection in Adults in Senegal

    PubMed Central

    Mensah, Victorine A.; Gueye, Aly; Ndiaye, Magatte; Edwards, Nick J.; Wright, Danny; Anagnostou, Nicholas A.; Syll, Massamba; Ndaw, Amy; Abiola, Annie; Bliss, Carly; Gomis, Jules-François; Petersen, Ines; Ogwang, Caroline; Dieye, Tandakha; Viebig, Nicola K.; Lawrie, Alison M.; Roberts, Rachel; Nicosia, Alfredo; Faye, Babacar; Gaye, Oumar; Leroy, Odile; Ewer, Katie J.; Bejon, Philip; Hill, Adrian V. S.; Cisse, Badara

    2016-01-01

    Malaria transmission is in decline in some parts of Africa, partly due to the scaling up of control measures. If the goal of elimination is to be achieved, additional control measures including an effective and durable vaccine will be required. Studies utilising the prime-boost approach to deliver viral vectors encoding the pre-erythrocytic antigen ME-TRAP (multiple epitope thrombospondin-related adhesion protein) have shown promising safety, immunogenicity and efficacy in sporozoite challenge studies. More recently, a study in Kenyan adults, similar to that reported here, showed substantial efficacy against P. falciparum infection. One hundred and twenty healthy male volunteers, living in a malaria endemic area of Senegal were randomised to receive either the Chimpanzee adenovirus (ChAd63) ME-TRAP as prime vaccination, followed eight weeks later by modified vaccinia Ankara (MVA) also encoding ME-TRAP as booster, or two doses of anti-rabies vaccine as a comparator. Prior to follow-up, antimalarials were administered to clear parasitaemia and then participants were monitored by PCR for malaria infection for eight weeks. The primary endpoint was time-to-infection with P. falciparum malaria, determined by two consecutive positive PCR results. Secondary endpoints included adverse event reporting, measures of cellular and humoral immunogenicity and a meta-analysis of combined vaccine efficacy with the parallel study in Kenyan adults.We show that this pre-erythrocytic malaria vaccine is safe and induces significant immunogenicity, with a peak T-cell response at seven days after boosting of 932 Spot Forming Cells (SFC)/106 Peripheral Blood Mononuclear Cells(PBMC) compared to 57 SFC/ 106 PBMCs in the control group. However, a vaccine efficacy was not observed: 12 of 57 ME-TRAP vaccinees became PCR positive during the intensive monitoring period as compared to 13 of the 58 controls (P = 0.80). This trial confirms that vaccine efficacy against malaria infection in adults may

  13. Brentuximab Vedotin and Combination Chemotherapy in Treating Patients With Stage II-IV HIV-Associated Hodgkin Lymphoma

    ClinicalTrials.gov

    2017-01-31

    AIDS-Related Hodgkin Lymphoma; CD30-Positive Neoplastic Cells Present; Classical Hodgkin Lymphoma; HIV Infection; Stage II Hodgkin Lymphoma; Stage IIA Hodgkin Lymphoma; Stage IIB Hodgkin Lymphoma; Stage III Hodgkin Lymphoma; Stage IIIA Hodgkin Lymphoma; Stage IIIB Hodgkin Lymphoma; Stage IV Hodgkin Lymphoma; Stage IVA Hodgkin Lymphoma; Stage IVB Hodgkin Lymphoma

  14. Early Results of Pilot Study Using Hepatitis C Virus (HCV) Positive Kidneys to Transplant HCV Infected Patients with End-Stage Renal Disease Allowing for Successful Interferon-Free Direct Acting Antiviral Therapy after Transplantation

    PubMed Central

    Gallegos-Orozco, Juan F; Kim, Robin; Thiesset, Heather F; Hatch, Jenny; Lynch, Keisa; Chaly, Jr, Thomas; Shihab, Fuad; Ahmed, Faris; Hall, Isaac

    2016-01-01

    Introduction: Hepatitis C virus (HCV) infection in kidney transplant (KTX) patients reduces long-term patient and graft survival. Direct-acting antivirals (DAA) are > 90% effective in achieving sustained viral response (SVR); however, DAAs are not routinely available to patients with end-stage renal disease (ESRD). The University of Utah Transplant Program developed a protocol to allow HCV-positive potential KTX recipients to accept HCV-positive donors' kidneys. Three months after successful KTX, they were eligible for DAA therapy. Methods: HCV-positive patients approved for KTX by the University of Utah Transplant Selection Committee were eligible to be enrolled in this study. Patients consented for the use of HCV-positive donor organs. Three to six months after successful KTX, these patients were treated for HCV with interferon-free direct-acting antiviral regimens according to viral genotype and prior treatment experience. Results: Between 2014-2015, 12 HCV-positive patients were listed for KTX. Eight patients were kidney only eligible, seven patients received HCV-positive deceased donor kidneys, and one received an HCV-negative organ. Currently, six patients have completed treatment, all have achieved sustained viral response (SVR), and one patient is currently awaiting treatment. All seven patients have functioning kidney grafts. Wait time for KTX was reduced amongst all blood groups from an average of 1,350 days to only 65 days. Conclusions: HCV-positive patients with ESRD can successfully receive an HCV-positive donor's kidney. Once transplanted, these patients can receive DAA therapy and achieve SVR. Use of HCV-positive organs reduced time on the waitlist by greater than three years and expanded the donor organ pool. PMID:28018760

  15. Stages and Behaviors

    MedlinePlus

    ... Stages Early-Stage Caregiving Middle-Stage Caregiving Late-Stage Caregiving Understand Behaviors Aggression | Agitation Confusion | Depression Hallucinations | Suspicion Sleep Issues and Sundowning Repetition | Wandering Get Help 24/ ...

  16. Ovarian Cancer Stage II

    MedlinePlus

    ... Download Title: Ovarian Cancer Stage II Description: Three-panel drawing of stage IIA, IIB, and stage II primary peritoneal cancer; the first panel (stage IIA) shows cancer inside both ovaries that ...

  17. Second Stage Separation

    NASA Video Gallery

    When the second stage burn is complete, the spacecraft and third stage are spun up to 55 rpm to stabilize the third stage during its short firing. The second stage is then jettisoned and the third ...

  18. Protective immunity to liver-stage malaria

    PubMed Central

    Holz, Lauren E; Fernandez-Ruiz, Daniel; Heath, William R

    2016-01-01

    Despite decades of research and recent clinical trials, an efficacious long-lasting preventative vaccine for malaria remains elusive. This parasite infects mammals via mosquito bites, progressing through several stages including the relatively short asymptomatic liver stage followed by the more persistent cyclic blood stage, the latter of which is responsible for all disease symptoms. As the liver acts as a bottleneck to blood-stage infection, it represents a potential site for parasite and disease control. In this review, we discuss immunity to liver-stage malaria. It is hoped that the knowledge gained from animal models of malaria immunity will translate into a more powerful and effective vaccine to reduce this global health problem. PMID:27867517

  19. Protective immunity to liver-stage malaria.

    PubMed

    Holz, Lauren E; Fernandez-Ruiz, Daniel; Heath, William R

    2016-10-01

    Despite decades of research and recent clinical trials, an efficacious long-lasting preventative vaccine for malaria remains elusive. This parasite infects mammals via mosquito bites, progressing through several stages including the relatively short asymptomatic liver stage followed by the more persistent cyclic blood stage, the latter of which is responsible for all disease symptoms. As the liver acts as a bottleneck to blood-stage infection, it represents a potential site for parasite and disease control. In this review, we discuss immunity to liver-stage malaria. It is hoped that the knowledge gained from animal models of malaria immunity will translate into a more powerful and effective vaccine to reduce this global health problem.

  20. Periprosthetic Joint Infections

    PubMed Central

    Lima, Ana Lucia L.; Oliveira, Priscila R.; Carvalho, Vladimir C.; Saconi, Eduardo S.; Cabrita, Henrique B.; Rodrigues, Marcelo B.

    2013-01-01

    Implantation of joint prostheses is becoming increasingly common, especially for the hip and knee. Infection is considered to be the most devastating of prosthesis-related complications, leading to prolonged hospitalization, repeated surgical intervention, and even definitive loss of the implant. The main risk factors to periprosthetic joint infections (PJIs) are advanced age, malnutrition, obesity, diabetes mellitus, HIV infection at an advanced stage, presence of distant infectious foci, and antecedents of arthroscopy or infection in previous arthroplasty. Joint prostheses can become infected through three different routes: direct implantation, hematogenic infection, and reactivation of latent infection. Gram-positive bacteria predominate in cases of PJI, mainly Staphylococcus aureus and Staphylococcus epidermidis. PJIs present characteristic signs that can be divided into acute and chronic manifestations. The main imaging method used in diagnosing joint prosthesis infections is X-ray. Computed tomography (CT) scan may assist in distinguishing between septic and aseptic loosening. Three-phase bone scintigraphy using technetium has high sensitivity, but low specificity. Positron emission tomography using fluorodeoxyglucose (FDG-PET) presents very divergent results in the literature. Definitive diagnosis of infection should be made by isolating the microorganism through cultures on material obtained from joint fluid puncturing, surgical wound secretions, surgical debridement procedures, or sonication fluid. Success in treating PJI depends on extensive surgical debridement and adequate and effective antibiotic therapy. Treatment in two stages using a spacer is recommended for most chronic infections in arthroplasty cases. Treatment in a single procedure is appropriate in carefully selected cases. PMID:24023542

  1. T-cell immunity to peptide epitopes of liver-stage antigen 1 in an area of Papua New Guinea in which malaria is holoendemic.

    PubMed Central

    Connelly, M; King, C L; Bucci, K; Walters, S; Genton, B; Alpers, M P; Hollingdale, M; Kazura, J W

    1997-01-01

    Liver-stage antigen 1 (LSA1) is one of several pre-erythrocytic antigens considered for inclusion in a multiantigen, multistage subunit vaccine against falciparum malaria. We examined T-cell proliferation and cytokine responses to peptides corresponding to amino acids 84 to 107, 1813 to 1835, and 1888 to 1909 of LSA1 in asymptomatic adults living in an area of Papua New Guinea where malaria is holoendemic. Whereas T cells from North Americans never exposed to malaria did not respond to any of the peptides, those from 52 of 55 adults from the area where malaria is endemic had vigorous proliferation responses to one or more of the LSA1 peptides (mean stimulation indices of 6.8 to 7.2). Gamma interferon (IFN-gamma) production driven by LSA1 peptides ranged from 34 to more than 3,500 pg/2 x 10(6) cells, was derived primarily from CD8+ cells, and was dissociated from T-cell proliferation. The frequencies of IFN-gamma response to the amino acid 1819 to 1835 and 1888 to 1909 peptides were significantly greater than that to the amino acid 84 to 107 peptide (87 and 88% versus 33% of subjects; P < 0.0001). In contrast to proliferation and IFN-gamma, interleukin 4 (IL-4) and/or IL-5 responses to LSA1 peptides were detected in only 18% of the subjects. These data show that T-cell immunity to epitopes in the N- and C-terminal regions of LSA1 are common in persons living in this area of Papua New Guinea where malaria is endemic. The dominance of type 1 CD8 cell IFN-gamma responses is consistent with a role for this T-cell population in immunity to liver-stage Plasmodium falciparum in humans. PMID:9393799

  2. Central line infections - hospitals

    MedlinePlus

    ... infection; CVC - infection; Central venous device - infection; Infection control - central line infection; Nosocomial infection - central line infection; Hospital acquired infection - central line infection; Patient safety - central ...

  3. Pneumococcal Infections

    MedlinePlus

    ... the bloodstream (bacteremia) Joint infection (arthritis) Ear infection (otitis media) Infection of the sinus membranes (sinusitis) Eye infection ( ... breathing; for bacteremia, fever and less energy; for ear infections, fever and ear pain; and for sinustitis, fever ...

  4. [ZIKA--VIRUS INFECTION].

    PubMed

    Velev, V

    2016-01-01

    This review summarizes the knowledge of the scientific community for Zika-virus infection. It became popular because of severe congenital damage causes of CNS in newborns whose mothers are infected during pregnancy, as well as the risk of pandemic distribution. Discusses the peculiarities of the biology and ecology of vectors--blood-sucking mosquitoes Aedes; stages in the spread of infection and practical problems which caused during pregnancy. Attention is paid to the recommendations that allow leading national and international medical organizations to deal with the threat Zika-virus infection.

  5. HIV infections in otolaryngology

    PubMed Central

    Rzewnicki, Ireneusz; Olszewska, Ewa; Rogowska-Szadkowska, Dorota

    2012-01-01

    Summary HIV (human immunodeficiency virus) infection may produce no clinical symptoms for 10 years on average. However, after many years of infection most people develop symptoms that indicate progression of the disease. There are no regular characteristic symptoms or early stage, and no logical sequence of AIDS indicator disorders has been observed. People who are not aware of the infection are referred to physicians of various specializations, including otolaryngologists. It is on their knowledge about HIV infections, among other factors, that early diagnosis of the disease depends. Appropriate and quick introduction of anti-retroviral drugs may let a person with HIV live decades longer. PMID:22367140

  6. Ovarian Cancer Stage I

    MedlinePlus

    ... Three-panel drawing of stage IA, IB, and IC; the first panel (stage IA) shows cancer inside ... cancer inside both ovaries. The third panel (stage IC) shows cancer inside both ovaries, and one ovary ...

  7. Cervical Cancer Stage IIIA

    MedlinePlus

    ... hyphen, e.g. -historical Searches are case-insensitive Cervical Cancer Stage IIIA Add to My Pictures View / ... 1275x1275 View Download Large: 2550x2550 View Download Title: Cervical Cancer Stage IIIA Description: Stage IIIA cervical cancer; ...

  8. Cervical Cancer Stage IIIB

    MedlinePlus

    ... hyphen, e.g. -historical Searches are case-insensitive Cervical Cancer Stage IIIB Add to My Pictures View / ... 1425x1326 View Download Large: 2850x2651 View Download Title: Cervical Cancer Stage IIIB Description: Stage IIIB cervical cancer; ...

  9. Cervical Cancer Stage IVB

    MedlinePlus

    ... hyphen, e.g. -historical Searches are case-insensitive Cervical Cancer Stage IVB Add to My Pictures View / ... 1200x1305 View Download Large: 2400x2610 View Download Title: Cervical Cancer Stage IVB Description: Stage IVB cervical cancer; ...

  10. Cervical Cancer Stage IVA

    MedlinePlus

    ... hyphen, e.g. -historical Searches are case-insensitive Cervical Cancer Stage IVA Add to My Pictures View / ... 1575x1200 View Download Large: 3150x2400 View Download Title: Cervical Cancer Stage IVA Description: Stage IVA cervical cancer; ...

  11. Periprosthetic Shoulder Infection

    PubMed Central

    Franceschini, Vincenzo; Chillemi, Claudio

    2013-01-01

    Shoulder arthroplasty is considered the most effective surgical procedure for endstage shoulder pain from different causes including osteoarthritis, cuff-tear arthropathy, trauma, and tumors. Although uncommon and less frequent than knee or hip periprosthetic infection, periprosthetic shoulder infection represents a devastating complication and, despite treatment, is associated with unsatisfactory results. The most commonly identified microorganisms in periprosthetic shoulder infections are Staphylococcus aureus, coagulase-negative Staphylococci and Propionibacterium acnes. Diagnosis is not always easy and mainly derives from the integration of clinical symptoms, laboratory exams, radiological studies and microbiological swabs. Different options are available for treatment, including antibiotic therapy, lavage and debridement with retention of the prosthesis, one-stage reimplantation, two-stage reimplantation with antibiotic-impregnated cement spacer and resection arthroplasty. The aim of this review is to describe the current knowledge regarding risk factors, etiology, diagnosis and treatment of periprosthetic shoulder infection. PMID:23919098

  12. Streptococcal Infections

    MedlinePlus

    ... disease) Group B strep can cause blood infections, pneumonia and meningitis in newborns. A screening test during ... urinary tract infections, blood infections, skin infections and pneumonia in adults. Antibiotics are used to treat strep ...

  13. Kidney Infection

    MedlinePlus

    ... X-ray called a voiding cystourethrogram. Antibiotics for kidney infections Antibiotics are the first line of treatment ... the infection is completely eliminated. Hospitalization for severe kidney infections For a severe kidney infection, your doctor ...

  14. A study of the level and dynamics of Eimeria populations in naturally infected, grazing beef cattle at various stages of production in the mid-Atlantic U.S.A.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    There is little information available on the species dynamics of eimerian parasites in grazing cattle in the central Appalachian region of the United States. Therefore, the objective of this study was to describe the level of infection and species dynamics of Eimeria spp. in grazing beef cattle of ...

  15. Plasmodium vivax liver stage development and hypnozoite persistence in human liver-chimeric mice.

    PubMed

    Mikolajczak, Sebastian A; Vaughan, Ashley M; Kangwanrangsan, Niwat; Roobsoong, Wanlapa; Fishbaugher, Matthew; Yimamnuaychok, Narathatai; Rezakhani, Nastaran; Lakshmanan, Viswanathan; Singh, Naresh; Kaushansky, Alexis; Camargo, Nelly; Baldwin, Michael; Lindner, Scott E; Adams, John H; Sattabongkot, Jetsumon; Prachumsri, Jetsumon; Kappe, Stefan H I

    2015-04-08

    Plasmodium vivax malaria is characterized by periodic relapses of symptomatic blood stage parasite infections likely initiated by activation of dormant liver stage parasites-hypnozoites. The lack of tractable P. vivax animal models constitutes an obstacle in examining P. vivax liver stage infection and drug efficacy. To overcome this obstacle, we have used human liver-chimeric (huHep) FRG KO mice as a model for P. vivax infection. FRG KO huHep mice support P. vivax sporozoite infection, liver stage development, and hypnozoite formation. We show complete P. vivax liver stage development, including maturation into infectious exo-erythrocytic merozoites as well as the formation and persistence of hypnozoites. Prophylaxis or treatment with the antimalarial primaquine can prevent and eliminate liver stage infection, respectively. Thus, P. vivax-infected FRG KO huHep mice are a model to investigate liver stage development and dormancy and may facilitate the discovery of drugs targeting relapsing malaria.

  16. Lunar Module Ascent Stage

    NASA Technical Reports Server (NTRS)

    1969-01-01

    The Lunar Module 'Spider' ascent stage is photographed from the Command/Service Module on the fifth day of the Apollo 9 earth-orbital mission. The Lunar Module's descent stage had already been jettisoned.

  17. Ages and Stages: Teen

    MedlinePlus

    ... Pediatrician Ages & Stages Prenatal Baby Toddler Preschool Gradeschool Teen Dating & Sex Fitness Nutrition Driving Safety School Substance Abuse Young Adult Healthy Children > Ages & Stages > Teen Teen Article Body Adolescence can be a rough ...

  18. Breast cancer staging

    MedlinePlus

    ... this page: //medlineplus.gov/ency/patientinstructions/000911.htm Breast cancer staging To use the sharing features on this ... Once your health care team knows you have breast cancer , they will do more tests to stage it. ...

  19. Stages of Adolescence

    MedlinePlus

    ... Español Text Size Email Print Share Stages of Adolescence Page Content Article Body Adolescence, these years from puberty to adulthood, may be roughly divided into three stages: early adolescence, generally ages eleven to fourteen; middle adolescence, ages ...

  20. Stages of Gallbladder Cancer

    MedlinePlus

    ... Serosal (outer) layer. Between these layers is supporting connective tissue . Primary gallbladder cancer starts in the inner layer ... has spread beyond the muscle layer to the connective tissue around the muscle. Stage IIIA In stage IIIA , ...

  1. Stages of Endometrial Cancer

    MedlinePlus

    ... Stage II endometrial cancer. Cancer has spread into connective tissue of the cervix, but has not spread outside ... uterus. In stage II , cancer has spread into connective tissue of the cervix , but has not spread outside ...

  2. Pancreatic Cancer Stage 3

    MedlinePlus

    ... 3 Description: Stage III pancreatic cancer; drawing shows cancer in the pancreas, common hepatic artery, and portal vein. Also shown ... and superior mesenteric artery. Stage III pancreatic cancer. Cancer ... near the pancreas. These include the superior mesenteric artery, celiac axis, ...

  3. Lung transplant infection.

    PubMed

    Burguete, Sergio R; Maselli, Diego J; Fernandez, Juan F; Levine, Stephanie M

    2013-01-01

    Lung transplantation has become an accepted therapeutic procedure for the treatment of end-stage pulmonary parenchymal and vascular disease. Despite improved survival rates over the decades, lung transplant recipients have lower survival rates than other solid organ transplant recipients. The morbidity and mortality following lung transplantation is largely due to infection- and rejection-related complications. This article will review the common infections that develop in the lung transplant recipient, including the general risk factors for infection in this population, and the most frequent bacterial, viral, fungal and other less frequent opportunistic infections. The epidemiology, diagnosis, prophylaxis, treatment and outcomes for the different microbial pathogens will be reviewed. The effects of infection on lung transplant rejection will also be discussed.

  4. Cervical Cancer Stage IB

    MedlinePlus

    ... hyphen, e.g. -historical Searches are case-insensitive Cervical Cancer Stage IB Add to My Pictures View / ... 1613x1200 View Download Large: 3225x2400 View Download Title: Cervical Cancer Stage IB Description: Stage IB1 and IB2 ...

  5. Cervical Cancer Stage IA

    MedlinePlus

    ... hyphen, e.g. -historical Searches are case-insensitive Cervical Cancer Stage IA Add to My Pictures View / ... 1500x1200 View Download Large: 3000x2400 View Download Title: Cervical Cancer Stage IA Description: Stage IA1 and IA2 ...

  6. Beyond Erikson's Eight Stages.

    ERIC Educational Resources Information Center

    Whitney, Ruth

    1979-01-01

    Erik Erikson has described eight stages of the healthy personality. This essay offers a revised version of the eight stages. Although most individuals develop through the eight stages, each is personally unique because patterns of fluctuation between safety and growth differ from one individual to another. (Author)

  7. Ovarian Cancer Stage IV

    MedlinePlus

    ... hyphen, e.g. -historical Searches are case-insensitive Ovarian Cancer Stage IV Add to My Pictures View /Download : ... 1200x1335 View Download Large: 2400x2670 View Download Title: Ovarian Cancer Stage IV Description: Drawing of stage IV shows ...

  8. Ovarian Cancer Stage IIIC

    MedlinePlus

    ... hyphen, e.g. -historical Searches are case-insensitive Ovarian Cancer Stage IIIC Add to My Pictures View /Download : ... 1530x1350 View Download Large: 3060x2700 View Download Title: Ovarian Cancer Stage IIIC Description: Drawing of stage IIIC shows ...

  9. Presence of Rheumatoid Factor during Chronic HCV Infection Is Associated with Expansion of Mature Activated Memory B-Cells that Are Hypo-Responsive to B-Cell Receptor Stimulation and Persist during the Early Stage of IFN Free Therapy.

    PubMed

    Reyes-Avilés, Elane; Kostadinova, Lenche; Rusterholtz, Anne; Cruz-Lebrón, Angelica; Falck-Ytter, Yngve; Anthony, Donald D

    2015-01-01

    Approximately half of those with chronic hepatitis C virus (HCV) infection have circulating rheumatoid factor (RF), and a portion of these individuals develop cryoglobulinemic vasculitis. B cell phenotype/function in relation to RF in serum has been unclear. We examined B cell subset distribution, activation state (CD86), cell cycle state (Ki67), and ex-vivo response to BCR, TLR9 and TLR7/8 stimulation, in chronic HCV-infected donors with or without RF, and uninfected donors. Mature-activated B-cells of HCV-infected donors had lower CD86 expression compared to uninfected donors, and in the presence of RF they also showed reduced CD86 expression in response to BCR and TLR9 stimulation. Additionally, mature activated memory B cells of HCV RF+ donors less commonly expressed Ki67+ than HCV RF- donors, and did not proliferate as well in response to BCR stimulation. Proportions of mature-activated B cells were enhanced, while naïve B-cells were lower in the peripheral blood of HCV-RF+ compared to RF- and uninfected donors. None of these parameters normalize by week 8 of IFN free direct acting antiviral (DAA) therapy in HCV RF+ donors, while in RF- donors, mature activated B cell proportions did normalize. These data indicate that while chronic HCV infection alone results in a lower state of activation in mature activated memory B cells, the presence of RF in serum is associated with a more pronounced state of unresponsiveness and an overrepresentation of these B cells in the blood. This phenotype persists at least during the early time window after removal of HCV from the host.

  10. Second stage of labor.

    PubMed

    Cheng, Yvonne W; Caughey, Aaron B

    2015-06-01

    Current American College of Obstetricians and Gynecologists' definition of prolonged second stage diagnoses 10% to 14% of nulliparous and 3% to 3.5% of multiparous women as having a prolonged second stage. The progression of labor in modern obstetrics may have deviated from the current labor norms established in the 1950s, likely due to differences in obstetric population characteristics and variation in clinical practice. Optimal management of the second stage in women with and without epidural remains debatable. Although prolonged second stage is associated with increased risk of maternal morbidity, conflicting data exist regarding the duration of second stage and associated neonatal morbidity and mortality.

  11. Cetuximab, Cisplatin, and Radiation Therapy in Treating Patients With Stage IB, Stage II, Stage III, or Stage IVA Cervical Cancer

    ClinicalTrials.gov

    2014-12-29

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Small Cell Carcinoma; Cervical Squamous Cell Carcinoma; Stage IB Cervical Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage IVA Cervical Cancer

  12. Three stage rocket vehicle with parallel staging

    NASA Technical Reports Server (NTRS)

    Marshall, W. R. (Inventor)

    1984-01-01

    A three stage rocket vehicle has a large forward propellant tank and a small aft propellant tank axially aligned. Secured to the rear end of the aft propellant tank is an engine mount structure carrying rocket engines. Offset and secured to the propellant tanks is a payload structure. The propellants from the large forward tank are fed into the aft propellant tank. This arrangement enables the vehicle to parallel stage its use of engines and components and results in significant payload capability. The design and components fully utilize existing space shuttle elements and tooling.

  13. Staged electrostatic precipitator

    DOEpatents

    Miller, Stanley J.; Almlie, Jay C.; Zhuang, Ye

    2016-03-01

    A device includes a chamber having an air inlet and an air outlet. The device includes a plurality of stages including at least a first stage adjacent a second stage. The plurality of stages are disposed in the chamber and each stage has a plurality of discharge electrodes disposed in an interior region and is bounded by an upstream baffle on an end proximate the air inlet and bounded by a downstream baffle on an end proximate the air outlet. Each stage has at least one sidewall between the upstream baffle and the downstream baffle. The sidewall is configured as a collection electrode and has a plurality of apertures disposed along a length between the upstream baffle and the downstream baffle. The upstream baffle of the first stage is positioned in staggered alignment relative to the upstream baffle of the second stage and the downstream baffle of the first stage are positioned in staggered alignment relative to the downstream baffle of the second stage.

  14. Two stage catalytic combustor

    NASA Technical Reports Server (NTRS)

    Alvin, Mary Anne (Inventor); Bachovchin, Dennis (Inventor); Smeltzer, Eugene E. (Inventor); Lippert, Thomas E. (Inventor); Bruck, Gerald J. (Inventor)

    2010-01-01

    A catalytic combustor (14) includes a first catalytic stage (30), a second catalytic stage (40), and an oxidation completion stage (49). The first catalytic stage receives an oxidizer (e.g., 20) and a fuel (26) and discharges a partially oxidized fuel/oxidizer mixture (36). The second catalytic stage receives the partially oxidized fuel/oxidizer mixture and further oxidizes the mixture. The second catalytic stage may include a passageway (47) for conducting a bypass portion (46) of the mixture past a catalyst (e.g., 41) disposed therein. The second catalytic stage may have an outlet temperature elevated sufficiently to complete oxidation of the mixture without using a separate ignition source. The oxidation completion stage is disposed downstream of the second catalytic stage and may recombine the bypass portion with a catalyst exposed portion (48) of the mixture and complete oxidation of the mixture. The second catalytic stage may also include a reticulated foam support (50), a honeycomb support, a tube support or a plate support.

  15. Hookworm infection

    MedlinePlus

    Hookworm disease; Ground itch; Ancylostoma duodenale infection; Necator americanus infection; Parasitic infection - hookworm ... The last 2 types also occur in animals. Hookworm disease is common in the moist tropics and ...

  16. Staph Infections

    MedlinePlus

    ... Staph Infection? Staph is the shortened name for Staphylococcus (pronounced: staf-uh-low-KAH-kus), a type ... most staph infections are caused by the species Staphylococcus aureus (S. aureus) . S. aureus most commonly causes skin infections ...

  17. Staphylococcal Infections

    MedlinePlus

    ... bacteria. There are over 30 types, but Staphylococcus aureus causes most staph infections (pronounced "staff infections"), including ... staph bacteria such as MRSA (methicillin-resistant Staphylococcus aureus) are resistant to certain antibiotics, making infections harder ...

  18. Telbivudine treatment of hepatitis B virus-infected pregnant women at different gestational stages for the prevention of mother-to-child transmission: Outcomes of telbivudine treatment during pregnancy.

    PubMed

    Tan, Zhangmin; Yin, Yuzhu; Zhou, Jin; Wu, Lingling; Xu, Chengfang; Hou, Hongying

    2016-10-01

    This prospective study evaluated the viability of telbivudine for blocking mother-to-child transmission (MTCT) of hepatitis B virus (HBV) infection.Pregnant women positive for the hepatitis B surface antigen began telbivudine treatment before 14 weeks of gestation (i.e., early), between 14 and 28 weeks of gestation (late), or not at all (control). In the late-treatment group, 55 women terminated telbivudine therapy within puerperium. All neonates underwent routine hepatitis B immunoglobulin plus vaccination. Mothers and infants were followed for 7 months after birth.Pregnancy outcomes were similar among the 3 groups. HBV MTCT rates in the early and late treatment and control groups were 0, 0, and 4.69%, respectively. The rates of infant vaccination success among the 3 groups were similar, as were neonatal outcomes including birth weights, asphyxia, hyperbilirubinemia, Apgar score, birth defects, and weight and height at 7 months. Puerperal discontinuation of telbivudine did not increase the alanine transaminase value at 7 months after birth, but increased serum HBV DNA levels, and rates of positive hepatitis Be-antigen.Telbivudine treatment in HBV-infected pregnant women was associated with lower serum HBV DNA levels and reduced rates of HBV MTCT; there were no associated changes in pregnancy or neonatal outcomes at birth or 7 months after birth, or in the rate of infant vaccination success. Puerperal drug withdrawal after short-term antiviral therapy will not influence hepatic function, but may increase virus replication.

  19. HIV-Resistant Gene Modified Stem Cells and Chemotherapy in Treating Patients With Lymphoma With HIV Infection

    ClinicalTrials.gov

    2017-01-19

    HIV Infection; Stage I Adult Hodgkin Lymphoma; Stage I Adult Non-Hodgkin Lymphoma; Stage II Adult Hodgkin Lymphoma; Stage II Adult Non-Hodgkin Lymphoma; Stage III Adult Hodgkin Lymphoma; Stage III Adult Non-Hodgkin Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Adult Non-Hodgkin Lymphoma

  20. Evaluation of a real-time two-step RT-PCR assay for quantitation of Chronic bee paralysis virus (CBPV) genome in experimentally-infected bee tissues and in life stages of a symptomatic colony.

    PubMed

    Blanchard, Philippe; Ribière, Magali; Celle, Olivier; Lallemand, Perrine; Schurr, Frank; Olivier, Violaine; Iscache, Anne Laure; Faucon, Jean Paul

    2007-04-01

    A two-step real-time RT-PCR assay, based on TaqMan technology using a fluorescent probe (FAM-TAMRA) was developed to quantify Chronic bee paralysis virus (CBPV) genome in bee samples. Standard curves obtained from a CBPV control RNA and from a plasmid containing a partial sequence of CBPV showed that this assay provided linear detection over a 7-log range (R(2)>0.99) with a limit of detection of 100 copies, and reliable inter-assay and intra-assay reproducibility. Standardisation including RNA purification and cDNAs synthesis was also validated. The CBPV TaqMan methodology was first evaluated by quantifying the CBPV genomic load in bee samples from an experimental infection obtained by topical application. Up to 1.9 x 10(10) CBPV copies per segment of insect body (head, thorax and abdomen) were revealed whereas a lower CBPV genomic load was detected in dissected organs such as mandibular and hypopharyngeal glands, brain and alimentary canal (up to 7.2 x 10(6) CBPV copies). The CBPV genomic loads in different categories of bees from a hive presenting the trembling symptoms typical of Chronic paralysis were then quantified. Significantly higher CBPV loads were found in guard, symptomatic and dead bees (up to 1.9 x 10(13) CBPV copies) than in forager, drones and house bees (up to 3.4 x 10(6) CBPV copies). The results obtained for symptomatic or dead bees support the correlation between high CBPV genomic load and pathology expression. Moreover, the high CBPV genomic load revealed in guard bees highlights the possible pivotal role played by this category of bees in CBPV infection.

  1. "High Stage" Organizing.

    ERIC Educational Resources Information Center

    Torbert, William R.

    Although a psychological theory of stages of transformation in human development currently exists, organizational researchers have yet to elaborate and test any theory of organizational transformation of comparable elegance. According to the organizational stage theory being developed since 1974 by William Torbert, bureaucratic organization, which…

  2. Skin Infections

    MedlinePlus

    ... it can get infected by them. Some common types of skin infections are Bacterial: Cellulitis and impetigo. Staphylococcal infections can also affect the skin. Viral: Shingles, warts, and herpes simplex Fungal: Athlete's foot and yeast infections Parasitic: Body lice, head lice, and scabies ...

  3. Early stage colon cancer.

    PubMed

    Freeman, Hugh James

    2013-12-14

    Evidence has now accumulated that colonoscopy and removal of polyps, especially during screening and surveillance programs, is effective in overall risk reduction for colon cancer. After resection of malignant pedunculated colon polyps or early stage colon cancers, long-term repeated surveillance programs can also lead to detection and removal of asymptomatic high risk advanced adenomas and new early stage metachronous cancers. Early stage colon cancer can be defined as disease that appears to have been completely resected with no subsequent evidence of involvement of adjacent organs, lymph nodes or distant sites. This differs from the clinical setting of an apparent "curative" resection later pathologically upstaged following detection of malignant cells extending into adjacent organs, peritoneum, lymph nodes or other distant sites, including liver. This highly selected early stage colon cancer group remains at high risk for subsequent colon polyps and metachronous colon cancer. Precise staging is important, not only for assessing the need for adjuvant chemotherapy, but also for patient selection for continued surveillance. With advanced stages of colon cancer and a more guarded outlook, repeated surveillance should be limited. In future, novel imaging technologies (e.g., confocal endomicroscopy), coupled with increased pathological recognition of high risk markers for lymph node involvement (e.g., "tumor budding") should lead to improved staging and clinical care.

  4. Staging for vulvar cancer.

    PubMed

    Hacker, Neville F; Barlow, Ellen L

    2015-08-01

    Vulvar cancer has been staged by the International Federation of Gynaecology and Obstetrics (FIGO) since 1969, and the original staging system was based on clinical findings only. This system provided a very good spread of prognostic groupings. Because vulvar cancer is virtually always treated surgically, the status of the lymph nodes is the most important prognostic factor and this can only be determined with certainty by histological examination of resected lymph nodes, FIGO introduced a surgical staging system in 1988. This was modified in 1994 to include a category of microinvasive vulvar cancer (stage IA), because such patients have virtually no risk of lymph node metastases. This system did not give a reasonably even spread of prognostic groupings. In addition, patients with stage III disease were shown to be a heterogeneous group prognostically, and the number of positive nodes and the morphology of those nodes were not taken into account. A new surgical staging system for vulvar cancer was introduced by FIGO in 2009. Initial retrospective analyses have suggested that this new staging system has overcome the major deficiencies in the 1994 system.

  5. A Key Role for Plasmodium Subtilisin-like SUB1 Protease in Egress of Malaria Parasites from Host Hepatocytes*

    PubMed Central

    Tawk, Lina; Lacroix, Céline; Gueirard, Pascale; Kent, Robyn; Gorgette, Olivier; Thiberge, Sabine; Mercereau-Puijalon, Odile; Ménard, Robert; Barale, Jean-Christophe

    2013-01-01

    In their mammalian host, Plasmodium parasites have two obligatory intracellular development phases, first in hepatocytes and subsequently in erythrocytes. Both involve an orchestrated process of invasion into and egress from host cells. The Plasmodium SUB1 protease plays a dual role at the blood stage by enabling egress of the progeny merozoites from the infected erythrocyte and priming merozoites for subsequent erythrocyte invasion. Here, using conditional mutagenesis in P. berghei, we show that SUB1 plays an essential role at the hepatic stage. Stage-specific sub1 invalidation during prehepatocytic development showed that SUB1-deficient parasites failed to rupture the parasitophorous vacuole membrane and to egress from hepatocytes. Furthermore, mechanically released parasites were not adequately primed and failed to establish a blood stage infection in vivo. The critical involvement of SUB1 in both pre-erythrocytic and erythrocytic developmental phases qualifies SUB1 as an attractive multistage target for prophylactic and therapeutic anti-Plasmodium intervention strategies. PMID:24089525

  6. Fixed-Dose Artesunate–Amodiaquine Combination vs Chloroquine for Treatment of Uncomplicated Blood Stage P. vivax Infection in the Brazilian Amazon: An Open-Label Randomized, Controlled Trial

    PubMed Central

    Alencar, Aline C.; Melo, Gisely C.; Magalhaes, Belisa L.; Machado, Kim; Alencar Filho, Aristóteles C.; Kuehn, Andrea; Marques, Marly M.; Manso, Monica Costa; Felger, Ingrid; Vieira, José L. F.; Lameyre, Valerie; Daniel-Ribeiro, Claudio T.; Lacerda, Marcus V. G.

    2017-01-01

    Background. Despite increasing evidence of the development of Plasmodium vivax chloroquine (CQ) resistance, there have been no trials comparing its efficacy with that of artemisinin-based combination therapies (ACTs) in Latin America. Methods. This randomized controlled trial compared the antischizontocidal efficacy and safety of a 3-day supervised treatment of the fixed-dose combination artesunate-amodiaquine Winthrop® (ASAQ) versus CQ for treatment of uncomplicated P. vivax infection in Manaus, Brazil. Patients were followed for 42 days. Primary endpoints were adequate clinical and parasitological responses (ACPR) rates at day 28. Genotype-adjustment was performed. Results. From 2012 to 2013, 380 patients were enrolled. In the per-protocol (PP) analysis, adjusted-ACPR was achieved in 100% (165/165) and 93.6% (161/172) of patients in the ASAQ and CQ arm (difference 6.4%, 95% CI 2.7%; 10.1%) at day 28 and in 97.4% (151/155) and 77.7% (129/166), respectively (difference 19.7%, 95% CI 12.9%; 26.5%), at day 42. Apart from ITT D28 assessment, superiority of ASAQ on ACPR was demonstrated. ASAQ presented faster clearance of parasitaemia and fever. Based on CQ blood level measurements, CQ resistance prevalence was estimated at 11.5% (95% CI: 7.5-17.3) up to day 42. At least one emergent adverse event (AE) was recorded for 79/190 (41x6%) in the ASAQ group and for 85/190 (44x7%) in the CQ group. Both treatments had similar safety profiles. Conclusions. ASAQ exhibited high efficacy against CQ resistant P. vivax and is an adequate alternative in the study area. Studies with an efficacious comparator, longer follow-up and genotype-adjustment can improve CQR characterization. Clinical Trials Registration. NCT01378286. PMID:27988484

  7. Plasmodium vivax liver stage development and hypnozoite persistence in human liver-chimeric mice

    PubMed Central

    Mikolajczak, Sebastian A.; Vaughan, Ashley M.; Kangwanrangsan, Niwat; Roobsoong, Wanlapa; Fishbaugher, Matthew; Yimamnuaychok, Narathatai; Rezakhani, Nastaran; Lakshmanan, Viswanathan; Singh, Naresh; Kaushansky, Alexis; Camargo, Nelly; Baldwin, Michael; Lindner, Scott E.; Adams, John H.; Prachumsri, Jetsumon; Kappe, Stefan H.I.

    2017-01-01

    Plasmodium vivax malaria is characterized by periodic relapses of symptomatic blood stage parasite infections likely initiated by activation of dormant liver stage parasites -hypnozoites. The lack of tractable animal models for P. vivax constitutes a severe obstacle to investigate this unique aspect of its biology and to test drug efficacy against liver stages. We show that the FRG KO huHep liver-humanized mice support P. vivax sporozoite infection, development of liver stages, and the formation of small non-replicating hypnozoites. Cellular characterization of P. vivax liver stage development in vivo demonstrates complete maturation into infectious exo-erythrocytic merozoites and continuing persistence of hypnozoites. Primaquine prophylaxis or treatment prevents and eliminates liver stage infection. Thus, the P. vivax/FRG KO huHep mouse infection model constitutes an important new tool to investigate the biology of liver stage development and dormancy and might aid in the discovery of new drugs for the prevention of relapsing malaria. PMID:25800544

  8. Staging Airliner Service

    NASA Technical Reports Server (NTRS)

    Hahn, Andrew S.

    2007-01-01

    There is a general consensus building that historically high fuel prices and greater public awareness of the emissions that result from burning fuel are going to be long-term concerns for those who design, build, and operate airliners. The possibility of saving both fuel and reducing emissions has rekindled interest in breaking very long-range airline flights into multiple stages or even adopting in-flight refueling. It is likely that staging will result in lower fuel burn, and recent published reports have suggested that the savings are substantial, particularly if the airliner is designed from the outset for this kind of operation. Given that staging runs against the design and operation historical trend, this result begs for further attention. This paper will examine the staging question, examining both analytic and numeric performance estimation methodologies to quantify the likely amount of fuel savings that can be expected and the resulting design impacts on the airliner.

  9. Radar stage uncertainty

    USGS Publications Warehouse

    Fulford, J.M.; Davies, W.J.

    2005-01-01

    The U.S. Geological Survey is investigating the performance of radars used for stage (or water-level) measurement. This paper presents a comparison of estimated uncertainties and data for radar water-level measurements with float, bubbler, and wire weight water-level measurements. The radar sensor was also temperature-tested in a laboratory. The uncertainty estimates indicate that radar measurements are more accurate than uncorrected pressure sensors at higher water stages, but are less accurate than pressure sensors at low stages. Field data at two sites indicate that radar sensors may have a small negative bias. Comparison of field radar measurements with wire weight measurements found that the radar tends to measure slightly lower values as stage increases. Copyright ASCE 2005.

  10. Stages of Pancreatic Cancer

    MedlinePlus

    ... cancer) cells form in the tissues of the pancreas. The pancreas is a gland about 6 inches ... spleen , and bile ducts . Tests that examine the pancreas are used to detect (find), diagnose, and stage ...

  11. Cryogenic Propulsion Stage

    NASA Technical Reports Server (NTRS)

    Jones, David

    2011-01-01

    The CPS is an in-space cryogenic propulsive stage based largely on state of the practice design for launch vehicle upper stages. However, unlike conventional propulsive stages, it also contains power generation and thermal control systems to limit the loss of liquid hydrogen and oxygen due to boil-off during extended in-space storage. The CPS provides the necessary (Delta)V for rapid transfer of in-space elements to their destinations or staging points (i.e., E-M L1). The CPS is designed around a block upgrade strategy to provide maximum mission/architecture flexibility. Block 1 CPS: Short duration flight times (hours), passive cryo fluid management. Block 2 CPS: Long duration flight times (days/weeks/months), active and passive cryo fluid management.

  12. Stages of Pregnancy

    MedlinePlus

    ... three stages. Expand all | Collapse all First trimester (week 1–week 12) During the first trimester your body undergoes ... is different, so is each pregnancy. Second trimester (week 13–week 28) Most women find the second ...

  13. Precision adjustable stage

    DOEpatents

    Cutburth, Ronald W.; Silva, Leonard L.

    1988-01-01

    An improved mounting stage of the type used for the detection of laser beams is disclosed. A stage center block is mounted on each of two opposite sides by a pair of spaced ball bearing tracks which provide stability as well as simplicity. The use of the spaced ball bearing pairs in conjunction with an adjustment screw which also provides support eliminates extraneous stabilization components and permits maximization of the area of the center block laser transmission hole.

  14. Infection and Cardiovascular Disease

    ClinicalTrials.gov

    2016-02-17

    Cardiovascular Diseases; Coronary Disease; Cerebrovascular Accident; Heart Diseases; Myocardial Infarction; Infection; Chlamydia Infections; Cytomegalovirus Infections; Helicobacter Infections; Atherosclerosis

  15. Bioimpedance Spectroscopy in Detecting Lower-Extremity Lymphedema in Patients With Stage I, Stage II, Stage III, or Stage IV Vulvar Cancer Undergoing Surgery and Lymphadenectomy

    ClinicalTrials.gov

    2016-02-09

    Lymphedema; Perioperative/Postoperative Complications; Stage IA Vulvar Cancer; Stage IB Vulvar Cancer; Stage II Vulvar Cancer; Stage IIIA Vulvar Cancer; Stage IIIB Vulvar Cancer; Stage IIIC Vulvar Cancer; Stage IVA Vulvar Cancer; Stage IVB Vulvar Cancer

  16. Multiple stage railgun

    DOEpatents

    Hawke, Ronald S.; Scudder, Jonathan K.; Aaland, Kristian

    1982-01-01

    A multiple stage magnetic railgun accelerator (10) for accelerating a projectile (15) by movement of a plasma arc (13) along the rails (11,12). The railgun (10) is divided into a plurality of successive rail stages (10a-n) which are sequentially energized by separate energy sources (14a-n) as the projectile (15) moves through the bore (17) of the railgun (10). Propagation of energy from an energized rail stage back towards the breech end (29) of the railgun (10) can be prevented by connection of the energy sources (14a-n) to the rails (11,12) through isolation diodes (34a-n). Propagation of energy from an energized rail stage back towards the breech end of the railgun can also be prevented by dividing the rails (11,12) into electrically isolated rail sections (11a-n, 12a-n). In such case means (55a-n) are used to extinguish the arc at the end of each energized stage and a fuse (31) or laser device (61) is used to initiate a new plasma arc in the next energized rail stage.

  17. Chemotherapy Toxicity On Quality of Life in Older Patients With Stage I, Stage II, Stage III, or Stage IV Ovarian Epithelial, Primary Peritoneal Cavity, or Fallopian Tube Cancer

    ClinicalTrials.gov

    2016-02-09

    Stage I Ovarian Cancer; Stage IA Fallopian Tube Cancer; Stage IB Fallopian Tube Cancer; Stage IC Fallopian Tube Cancer; Stage II Ovarian Cancer; Stage IIA Fallopian Tube Cancer; Stage IIB Fallopian Tube Cancer; Stage IIC Fallopian Tube Cancer; Stage III Ovarian Cancer; Stage III Primary Peritoneal Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIC Fallopian Tube Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer

  18. Reading Aloud: Discrete Stage(s) Redux

    PubMed Central

    Robidoux, Serje; Besner, Derek

    2017-01-01

    Interactive activation accounts of processing have had a broad and deep influence on cognitive psychology, particularly so in the context of computational accounts of reading aloud at the single word level. Here we address the issue of whether such a framework can simulate the joint effects of stimulus quality and word frequency (which have been shown to produce both additive and interactive effects depending on the context). We extend previous work on this question by considering an alternative implementation of a stimulus quality manipulation, and the role of interactive activation. Simulations with a version of the Dual Route Cascaded model (a model with interactive activation dynamics along the lexical route) demonstrate that the model is unable to simulate the entire pattern seen in human performance. We discuss how a hybrid interactive activation model that includes some context dependent staged processing could accommodate these data. PMID:28289395

  19. Rotavirus Infections

    MedlinePlus

    Rotavirus is a virus that causes gastroenteritis. Symptoms include severe diarrhea, vomiting, fever, and dehydration. Almost all ... the U.S. are likely to be infected with rotavirus before their 5th birthday. Infections happen most often ...

  20. Postpartum Infections

    MedlinePlus

    ... Fundamentals Heart and Blood Vessel Disorders Hormonal and Metabolic Disorders Immune Disorders Infections Injuries and Poisoning Kidney and ... Fundamentals Heart and Blood Vessel Disorders Hormonal and Metabolic Disorders Immune Disorders Infections Injuries and Poisoning Kidney and ...

  1. Staph Infections

    MedlinePlus

    ... About Staph Infections Staph infections are caused by Staphylococcus aureus bacteria. Many healthy people carry these bacteria ... MRSA You may have heard about methicillin-resistant Staphylococcus aureus (MRSA), a type of staph bacteria with ...

  2. Hantavirus Infections

    MedlinePlus

    ... but deadly viral infection. It is spread by mice and rats. They shed the virus in their ... breathe infected air or come into contact with rodents or their urine or droppings. You cannot catch ...

  3. Spinal infections.

    PubMed

    Tay, Bobby K-B; Deckey, Jeffrey; Hu, Serena S

    2002-01-01

    Spinal infections can occur in a variety of clinical situations. Their presentation ranges from the infant with diskitis who is unwilling to crawl or walk to the adult who develops an infection after a spinal procedure. The most common types of spinal infections are hematogenous bacterial or fungal infections, pediatric diskitis, epidural abscess, and postoperative infections. Prompt and accurate diagnosis of spinal infections, the cornerstone of treatment, requires a high index of suspicion in at-risk patients and the appropriate evaluation to identify the organism and determine the extent of infection. Neurologic function and spinal stability also should be carefully evaluated. The goals of therapy should include eradicating the infection, relieving pain, preserving or restoring neurologic function, improving nutrition, and maintaining spinal stability.

  4. MRSA Infection

    MedlinePlus

    ... MRSA infection By Mayo Clinic Staff Methicillin-resistant Staphylococcus aureus (MRSA) infection is caused by a type ... a fever, see your doctor. Different varieties of Staphylococcus aureus bacteria, commonly called "staph," exist. Staph bacteria ...

  5. Salmonella Infection

    MedlinePlus

    Salmonella infection Overview By Mayo Clinic Staff Salmonella infection (salmonellosis) is a common bacterial disease that affects the intestinal tract. Salmonella bacteria typically live in animal and human intestines and are ...

  6. Neonatal Infections

    MedlinePlus

    ... previous continue E. Coli Infection What is it? Escherichia coli (E. coli) is another bacterial culprit behind some ... at home. Most newborns who become ill from E. coli infection have particularly fragile immune systems that make them ...

  7. Coronavirus Infections

    MedlinePlus

    Coronaviruses are common viruses that most people get some time in their life. They are common throughout the world, and they can infect people and animals. Several different coronaviruses can infect people ...

  8. Vaginal Infections

    PubMed Central

    Nicolle, Lindsay E.

    1989-01-01

    Vaginal infections are among the most common complaints for which women see their physicians. The patient complains primarily of vaginal discharge or pruritus. Optimal management of these infections requires a careful history, physical examination, and laboratory assessment to determine the pathogen. Specific therapy is available for the three important causes of vaginal infection: yeast vulvovaginitis, trichomoniasis, and bacterial vaginosis. Concomitant sexually transmitted diseases should be excluded in women with complaints suggestive of vaginal infection. PMID:21248968

  9. Bone Infections

    MedlinePlus

    ... bloodstream. People who are at risk for bone infections include those with diabetes, poor circulation, or recent injury to the bone. You may also be at risk if you are having hemodialysis. Symptoms of bone infections include Pain in the infected area Chills and ...

  10. Staging of intrahepatic cholangiocarcinoma

    PubMed Central

    Ronnekleiv-Kelly, Sean M.

    2017-01-01

    Intrahepatic cholangiocarcinoma (ICC) comprises approximately 5−30% of primary liver tumors, however it has been increasing over the last several decades. Up to and including the 6th edition of the American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) edition staging system, ICC was staged the same as hepatocellular carcinoma. In the 7th edition AJCC/UICC manual, the staging system of ICC was revised such that a distinct classification was proposed. Pathologic features for prognosis included vascular invasion, tumor multiplicity, local extension, periductal infiltration and lymph nodal metastasis. Over the last decade, as the incidence of ICC has increased and surgery for this indication has become more common, more data has been published on the prognostic factors associated with long-term survival. PMID:28261593

  11. Staged fluidized bed

    DOEpatents

    Mallon, R.G.

    1983-05-13

    The invention relates to oil shale retorting and more particularly to staged fluidized bed oil shale retorting. Method and apparatus are disclosed for narrowing the distribution of residence times of any size particle and equalizing the residence times of large and small particles in fluidized beds. Particles are moved up one fluidized column and down a second fluidized column with the relative heights selected to equalize residence times of large and small particles. Additional pairs of columns are staged to narrow the distribution of residence times and provide complete processing of the material.

  12. Crescentic ramp turbine stage

    NASA Technical Reports Server (NTRS)

    Lee, Ching-Pang (Inventor); Tam, Anna (Inventor); Kirtley, Kevin Richard (Inventor); Lamson, Scott Henry (Inventor)

    2007-01-01

    A turbine stage includes a row of airfoils joined to corresponding platforms to define flow passages therebetween. Each airfoil includes opposite pressure and suction sides and extends in chord between opposite leading and trailing edges. Each platform includes a crescentic ramp increasing in height from the leading and trailing edges toward the midchord of the airfoil along the pressure side thereof.

  13. End-Stage.

    ERIC Educational Resources Information Center

    Moua, Mai Neng

    2001-01-01

    Through her reflections on dealing with dialysis for end-stage renal disease and awaiting a kidney transplant, the author presents insights into how her experience was shaped by the physical, emotional, and multicultural forces she faced. Among the issues discussed are her ambivalent feelings between pursuing a regular lifestyle and receiving…

  14. STS upper stage operations

    NASA Technical Reports Server (NTRS)

    Kitchens, M. D.; Schnyer, A. D.

    1977-01-01

    Several design/development and operational approaches for STS upper stages are being pursued to realize maximum operational and economic benefits upon the introduction of the STS in the 1980s. The paper focuses special attention on safety operations, launch site operations and on-orbit operations.

  15. Pancreatic Cancer Stage 4

    MedlinePlus

    ... lung, liver, and peritoneal cavity. An inset shows cancer cells spreading from the pancreas, through the blood and lymph system, to another ... abdomen that contains the intestines, stomach, and liver). Cancer may also have spread to ... pancreas or to lymph nodes. Stage IV pancreatic cancer. ...

  16. Stage a Water Show

    ERIC Educational Resources Information Center

    Frasier, Debra

    2008-01-01

    In the author's book titled "The Incredible Water Show," the characters from "Miss Alaineus: A Vocabulary Disaster" used an ocean of information to stage an inventive performance about the water cycle. In this article, the author relates how she turned the story into hands-on science teaching for real-life fifth-grade students. The author also…

  17. Arbovirus Infections

    PubMed Central

    Beckham, J. David; Tyler, Kenneth L.

    2016-01-01

    Purpose of Review Arbovirus (arthropod-borne virus) infections are increasingly important causes of neurologic disease in the United States through both endemic transmission and travel-associated infections. This article reviews the major arbovirus infections that can cause neurologic disease likely to be encountered in the United States. Recent Findings West Nile virus continues to be an important cause of epidemic encephalitis, while emerging arbovirus infections such as dengue and chikungunya have rapidly expanded their geographic distribution. As emerging arboviruses expand in new geographic regions, neurologic abnormalities are reported in new patient populations. Summary Emerging arbovirus infections are increasingly important causes of neurologic disease throughout the world and in the United States. While no US Food and Drug Administration (FDA)–approved therapy is yet available for these infections, prompt recognition and diagnosis from the consulting neurologist will ensure appropriate supportive care for the patient. PMID:26633778

  18. Relationship of tadpole stage to location of echinostome cercaria encystment and the consequences for tadpole survival

    USGS Publications Warehouse

    Schotthoefer, A.M.; Cole, R.A.; Beasley, V.R.

    2003-01-01

    The effect of echinostome infections on the survival of Rana pipiens tadpoles was examined in relation to developmental stage of tadpoles. Individual tadpoles of Gosner stages 25, 27, 32a??33, and 37a??39 were exposed to 1 of 4 levels of cercariae (0, 20, 50, or 100). Only tadpoles at stage 25, the earliest stage infected, died within a 5-day experimental period. This stage-specific mortality rate could be explained, in part, by the stage-specific location of encystment of cercariae, which was documented in a separate experiment. In accordance with kidney development, cercariae predominately encysted in the pronephroi during early stages of tadpole development (stages 25 through 31a??32) and only in the mesonephroi and associated ducts at later stages (stages 37 through 46). As the mesonephros develops, renal capacity presumably increases. Thus, tadpoles died only when metacercariae concentrated in the functional portion of the kidney with the most limited renal capacity. As tadpoles aged, they also became less susceptible to infections. On average, 69.5% of cercariae that were exposed to stage 25a??26 tadpoles successfully encysted, compared with only 8.4% of cercariae exposed to stage 37a??38 tadpoles. Exposures of metamorphic frogs (poststage 46) to cercariae revealed that these individuals can become infected with echinostomes. Collectively, our data highlight the host stagea??dependent dynamics of tadpolea??echinostome interactions.

  19. Saturn IB Second Stage (S-IVB Stage)

    NASA Technical Reports Server (NTRS)

    1968-01-01

    This cutaway drawing shows the S-IVB stage in its Saturn IB configuration. As a part of the Marshall Space Flight Center's (MSFC) 'building block' approach to the Saturn development, the S-IVB stage was utilized in the Saturn IB launch vehicle as a second stage and, later, the Saturn V launch vehicle as a third stage. The stage was powered by a single J-2 engine, initially capable of 200,000 pounds of thrust.

  20. [Hand infections].

    PubMed

    Schiele, Philippe; Le Nen, Dominique

    2013-11-01

    Superficial and deep hand infections are frequent in general medical practice. Clinical examination is a crucial step for an adapted provided care. Most of the time, surgery is the only way to heal infections. However, in some cases (like bites), empiric antibiotherapy is first indicated to limit infection. Staphyloccocus aureus as well as Group Beta Streptococcus are the most frequently pathogenes associated with hand infections. Methicillin resistant S. Aureus must always be considered in the diagnoses. Whatever treatment is provided, clinical assessement must be repeated within two days. An early adaquated treatment prevent functional complications and in some cases death of the patients.

  1. Staged cascade fluidized bed combustor

    DOEpatents

    Cannon, Joseph N.; De Lucia, David E.; Jackson, William M.; Porter, James H.

    1984-01-01

    A fluid bed combustor comprising a plurality of fluidized bed stages interconnected by downcomers providing controlled solids transfer from stage to stage. Each stage is formed from a number of heat transfer tubes carried by a multiapertured web which passes fluidizing air to upper stages. The combustor cross section is tapered inwardly from the middle towards the top and bottom ends. Sorbent materials, as well as non-volatile solid fuels, are added to the top stages of the combustor, and volatile solid fuels are added at an intermediate stage.

  2. Rituximab and Oblimersen in Treating Patients With Stage II, Stage III, or Stage IV Follicular Non-Hodgkin's Lymphoma

    ClinicalTrials.gov

    2013-01-04

    Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma

  3. Anthrax: Gene Expression Analysis of the Early Stages of Infection

    DTIC Science & Technology

    2007-11-02

    atxA and acpA , located on virulence plasmids pXO I and pXO2, respectively. We used DNA microarrays to determine which genes in the B. anthracis...genome are controlled by atxA and/or acpA . The regulation of numerous genes present on the virulence plasmids was documented and both positive and negative...effects were observed. Certain atxA-regulated genes were affected synergistically in an atxA, acpA double mutants. AcpA appears to be a minor

  4. Salmonella Infections

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Infections with bacteria of the genus Salmonella are responsible for both acute and chronic poultry diseases. These diseases cause economically significant losses for poultry producers in many nations and absorb large investments of public and private resources in testing and control efforts. Infect...

  5. Staph Infections

    MedlinePlus

    ... doctor. previous continue Can I Prevent a Staph Skin Infection? Staphylococcus aureus bacteria are everywhere. Many healthy people carry staph bacteria without getting sick. Cleanliness and good hygiene are ... You can help prevent staph skin infections by washing your hands often and by ...

  6. Eye Infections

    MedlinePlus

    ... Issues Listen Español Text Size Email Print Share Eye Infections in Infants & Children Page Content ​​​If the ... must be treated early to prevent serious complications. Eye infections that occur after the newborn period: These ...

  7. Skin Infections

    MedlinePlus

    ... feels sick or has fever or chills has red streaks near the infected area Think Prevention! Wash hands well and often, especially after touching infected areas. Clean cuts and scrapes with soap and water, apply an antibiotic ointment, and cover with a ...

  8. Campylobacter Infections

    MedlinePlus

    ... feces (poop), which can lead to infection in humans via contaminated food, meats (especially chicken), water taken from contaminated sources (streams or rivers near where animals graze), and milk products that haven't been ... the human digestive system, Campylobacter infects and attacks the lining ...

  9. Photoacoustic spectroscopy of man infecting protozoans

    SciTech Connect

    Acosta-Avalos, D.; Alvarado-Gil, J. J.; Vargas, H.

    1998-08-28

    In this paper the fundamentals of photothermal spectroscopy are presented, special emphasis is done in the obtention of the optical absorption spectra. It is shown that this spectroscopy can be used successfully for the monitoring of protozoans that could infect the human. The usefulness of the technique is illustrated in the special case of Leishmania, where it is possible to find that the stage when the protozoan infect vertebrate cells show important differences in relation to the protozoans infecting insects.

  10. Complete attenuation of genetically engineered Plasmodium falciparum sporozoites in human subjects.

    PubMed

    Kublin, James G; Mikolajczak, Sebastian A; Sack, Brandon K; Fishbaugher, Matt E; Seilie, Annette; Shelton, Lisa; VonGoedert, Tracie; Firat, Melike; Magee, Sara; Fritzen, Emma; Betz, Will; Kain, Heather S; Dankwa, Dorender A; Steel, Ryan W J; Vaughan, Ashley M; Noah Sather, D; Murphy, Sean C; Kappe, Stefan H I

    2017-01-04

    Immunization of humans with whole sporozoites confers complete, sterilizing immunity against malaria infection. However, achieving consistent safety while maintaining immunogenicity of whole parasite vaccines remains a formidable challenge. We generated a genetically attenuated Plasmodium falciparum (Pf) malaria parasite by deleting three genes expressed in the pre-erythrocytic stage (Pf p52(-)/p36(-)/sap1(-)). We then tested the safety and immunogenicity of the genetically engineered (Pf GAP3KO) sporozoites in human volunteers. Pf GAP3KO sporozoites were delivered to 10 volunteers using infected mosquito bites with a single exposure consisting of 150 to 200 bites per subject. All subjects remained blood stage-negative and developed inhibitory antibodies to sporozoites. GAP3KO rodent malaria parasites engendered complete, protracted immunity against infectious sporozoite challenge in mice. The results warrant further clinical testing of Pf GAP3KO and its potential development into a vaccine strain.

  11. Nuclear Cryogenic Propulsion Stage

    NASA Technical Reports Server (NTRS)

    Houts, Michael G.; Borowski, S. K.; George, J. A.; Kim, T.; Emrich, W. J.; Hickman, R. R.; Broadway, J. W.; Gerrish, H. P.; Adams, R. B.

    2012-01-01

    The fundamental capability of Nuclear Thermal Propulsion (NTP) is game changing for space exploration. A first generation Nuclear Cryogenic Propulsion Stage (NCPS) based on NTP could provide high thrust at a specific impulse above 900 s, roughly double that of state of the art chemical engines. Characteristics of fission and NTP indicate that useful first generation systems will provide a foundation for future systems with extremely high performance. The role of the NCPS in the development of advanced nuclear propulsion systems could be analogous to the role of the DC-3 in the development of advanced aviation. Progress made under the NCPS project could help enable both advanced NTP and advanced NEP.

  12. Dual stage check valve

    NASA Technical Reports Server (NTRS)

    Whitten, D. E. (Inventor)

    1973-01-01

    A dual stage seat valve head arrangement is described which consists of a primary sealing point located between a fixed orifice seat and a valve poppet, and a secondary sealing point between an orifice poppet and a valve poppet. Upstream of the valve orifice is a flexible, convoluted metal diaphragm attached to the orifice poppet. Downstream of the valve orifice, a finger spring exerts a force against the valve poppet, tending to keep the valve in a closed position. The series arrangement of a double seat and poppet is able to tolerate small particle contamination while minimizing chatter by controlling throttling or metering across the secondary seat, thus preserving the primary sealing surface.

  13. Chimpanzee sleep stages.

    NASA Technical Reports Server (NTRS)

    Freemon, F. R.; Mcnew, J. J.; Adey, W. R.

    1971-01-01

    The electroencephalogram and electro-oculogram of two unrestrained juvenile chimpanzees was monitored for 7 consecutive nights using telemetry methods. Of the sleeping time, 23% was spent in the rapid eye movement of REM type of sleep, whereas 8, 4, 15, and 10% were spent in non-REM stages 1 through 4, respectively. Seven to nine periods of REM sleep occurred per night. The average time from the beginning of one REM period to the beginning of the next was approximately 85 min.

  14. The March Toward Malaria Vaccines

    PubMed Central

    Hoffman, Stephen L.; Vekemans, Johan; Richie, Thomas L.; Duffy, Patrick E.

    2016-01-01

    In 2013 there were an estimated 584,000 deaths and 198 million clinical illnesses due to malaria, the majority in sub-Saharan Africa. Vaccines would be the ideal addition to the existing armamentarium of anti-malaria tools. However, malaria is caused by parasites, and parasites are much more complex in terms of their biology than the viruses and bacteria for which we have vaccines, passing through multiple stages of development in the human host, each stage expressing hundreds of unique antigens. This complexity makes it more difficult to develop a vaccine for parasites than for viruses and bacteria, since an immune response targeting one stage may not offer protection against a later stage, because different antigens are the targets of protective immunity at different stages. Furthermore, depending on the life cycle stage and whether the parasite is extra- or intra-cellular, antibody and/or cellular immune responses provide protection. It is thus not surprising that there is no vaccine on the market for prevention of malaria, or any human parasitic infection. In fact, no vaccine for any disease with this breadth of targets and immune responses exists. In this limited review, we focus on four approaches to malaria vaccines, (1) a recombinant protein with adjuvant vaccine aimed at Plasmodium falciparum (Pf) pre-erythrocytic stages of the parasite cycle (RTS,S/AS01), (2) whole sporozoite vaccines aimed at Pf pre-erythrocytic stages (PfSPZ Vaccine and PfSPZ-CVac), (3) prime boost vaccines that include recombinant DNA, viruses and bacteria, and protein with adjuvant aimed primarily at Pf pre-erythrocytic, but also asexual erythrocytic stages, and (4) recombinant protein with adjuvant vaccines aimed at Pf and Plasmodium vivax sexual erythrocytic and mosquito stages. We recognize that we are not covering all approaches to malaria vaccine development, or most of the critically important work on development of vaccines against P. vivax, the second most important cause of

  15. The March Toward Malaria Vaccines.

    PubMed

    Hoffman, Stephen L; Vekemans, Johan; Richie, Thomas L; Duffy, Patrick E

    2015-12-01

    In 2013 there were an estimated 584,000 deaths and 198 million clinical illnesses due to malaria, the majority in sub-Saharan Africa. Vaccines would be the ideal addition to the existing armamentarium of anti-malaria tools. However, malaria is caused by parasites, and parasites are much more complex in terms of their biology than the viruses and bacteria for which we have vaccines, passing through multiple stages of development in the human host, each stage expressing hundreds of unique antigens. This complexity makes it more difficult to develop a vaccine for parasites than for viruses and bacteria, since an immune response targeting one stage may not offer protection against a later stage, because different antigens are the targets of protective immunity at different stages. Furthermore, depending on the life cycle stage and whether the parasite is extra- or intra-cellular, antibody and/or cellular immune responses provide protection. It is thus not surprising that there is no vaccine on the market for prevention of malaria, or any human parasitic infection. In fact, no vaccine for any disease with this breadth of targets and immune responses exists. In this limited review, we focus on four approaches to malaria vaccines, (1) a recombinant protein with adjuvant vaccine aimed at Plasmodium falciparum (Pf) pre-erythrocytic stages of the parasite cycle (RTS,S/AS01), (2) whole sporozoite vaccines aimed at Pf pre-erythrocytic stages (PfSPZ Vaccine and PfSPZ-CVac), (3) prime boost vaccines that include recombinant DNA, viruses and bacteria, and protein with adjuvant aimed primarily at Pf pre-erythrocytic, but also asexual erythrocytic stages, and (4) recombinant protein with adjuvant vaccines aimed at Pf and Plasmodium vivax sexual erythrocytic and mosquito stages. We recognize that we are not covering all approaches to malaria vaccine development, or most of the critically important work on development of vaccines against P. vivax, the second most important cause of

  16. The march toward malaria vaccines.

    PubMed

    Hoffman, Stephen L; Vekemans, Johan; Richie, Thomas L; Duffy, Patrick E

    2015-11-27

    In 2013 there were an estimated 584,000 deaths and 198 million clinical illnesses due to malaria, the majority in sub-Saharan Africa. Vaccines would be the ideal addition to the existing armamentarium of anti-malaria tools. However, malaria is caused by parasites, and parasites are much more complex in terms of their biology than the viruses and bacteria for which we have vaccines, passing through multiple stages of development in the human host, each stage expressing hundreds of unique antigens. This complexity makes it more difficult to develop a vaccine for parasites than for viruses and bacteria, since an immune response targeting one stage may not offer protection against a later stage, because different antigens are the targets of protective immunity at different stages. Furthermore, depending on the life cycle stage and whether the parasite is extra- or intra-cellular, antibody and/or cellular immune responses provide protection. It is thus not surprising that there is no vaccine on the market for prevention of malaria, or any human parasitic infection. In fact, no vaccine for any disease with this breadth of targets and immune responses exists. In this limited review, we focus on four approaches to malaria vaccines, (1) a recombinant protein with adjuvant vaccine aimed at Plasmodium falciparum (Pf) pre-erythrocytic stages of the parasite cycle (RTS,S/AS01), (2) whole sporozoite vaccines aimed at Pf pre-erythrocytic stages (PfSPZ Vaccine and PfSPZ-CVac), (3) prime boost vaccines that include recombinant DNA, viruses and bacteria, and protein with adjuvant aimed primarily at Pf pre-erythrocytic, but also asexual erythrocytic stages, and (4) recombinant protein with adjuvant vaccines aimed at Pf and Plasmodium vivax sexual erythrocytic and mosquito stages. We recognize that we are not covering all approaches to malaria vaccine development, or most of the critically important work on development of vaccines against P. vivax, the second most important cause of

  17. Changes in Brain Function in Patients With Stage I, Stage II, Stage III, or Stage IV Ovarian, Primary Peritoneal, or Fallopian Tube Cancer Who Are Receiving Chemotherapy

    ClinicalTrials.gov

    2016-10-26

    Cognitive Side Effects of Cancer Therapy; Malignant Ovarian Epithelial Tumor; Ovarian Brenner Tumor; Ovarian Carcinosarcoma; Ovarian Choriocarcinoma; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Dysgerminoma; Ovarian Embryonal Carcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mixed Germ Cell Tumor; Ovarian Mucinous Cystadenocarcinoma; Ovarian Polyembryoma; Ovarian Sarcoma; Ovarian Seromucinous Carcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Teratoma; Ovarian Yolk Sac Tumor; Stage I Ovarian Cancer; Stage IA Fallopian Tube Cancer; Stage IA Ovarian Cancer; Stage IA Ovarian Germ Cell Tumor; Stage IB Fallopian Tube Cancer; Stage IB Ovarian Cancer; Stage IB Ovarian Germ Cell Tumor; Stage IC Fallopian Tube Cancer; Stage IC Ovarian Cancer; Stage IC Ovarian Germ Cell Tumor; Stage II Ovarian Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIA Ovarian Germ Cell Tumor; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIB Ovarian Germ Cell Tumor; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; Stage IIC Ovarian Germ Cell Tumor; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Ovarian Germ Cell Tumor; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Ovarian Germ Cell Tumor; Stage IV Primary Peritoneal Cancer; Undifferentiated Ovarian Carcinoma

  18. Upper stage technology evaluation studies

    NASA Technical Reports Server (NTRS)

    1972-01-01

    Studies to evaluate advanced technology relative to chemical upper stages and orbit-to-orbit stages are reported. The work described includes: development of LH2/LOX stage data, development of data to indicate stage sensitivity to engine tolerance, modified thermal routines to accommodate storable propellants, added stage geometries to computer program for monopropellant configurations, determination of the relative gain obtainable through improvement of stage mass fraction, future propulsion concepts, effect of ultrahigh chamber-pressure increases, and relative gains obtainable through improved mass fraction.

  19. Human Influenza Virus Infections.

    PubMed

    Peteranderl, Christin; Herold, Susanne; Schmoldt, Carole

    2016-08-01

    Seasonal and pandemic influenza are the two faces of respiratory infections caused by influenza viruses in humans. As seasonal influenza occurs on an annual basis, the circulating virus strains are closely monitored and a yearly updated vaccination is provided, especially to identified risk populations. Nonetheless, influenza virus infection may result in pneumonia and acute respiratory failure, frequently complicated by bacterial coinfection. Pandemics are, in contrary, unexpected rare events related to the emergence of a reassorted human-pathogenic influenza A virus (IAV) strains that often causes increased morbidity and spreads extremely rapidly in the immunologically naive human population, with huge clinical and economic impact. Accordingly, particular efforts are made to advance our knowledge on the disease biology and pathology and recent studies have brought new insights into IAV adaptation mechanisms to the human host, as well as into the key players in disease pathogenesis on the host side. Current antiviral strategies are only efficient at the early stages of the disease and are challenged by the genomic instability of the virus, highlighting the need for novel antiviral therapies targeting the pulmonary host response to improve viral clearance, reduce the risk of bacterial coinfection, and prevent or attenuate acute lung injury. This review article summarizes our current knowledge on the molecular basis of influenza infection and disease progression, the key players in pathogenesis driving severe disease and progression to lung failure, as well as available and envisioned prevention and treatment strategies against influenza virus infection.

  20. Metabolomics Identifies Multiple Candidate Biomarkers to Diagnose and Stage Human African Trypanosomiasis

    PubMed Central

    Vincent, Isabel M.; Daly, Rónán; Courtioux, Bertrand; Cattanach, Amy M.; Biéler, Sylvain; Ndung’u, Joseph M.; Bisser, Sylvie; Barrett, Michael P.

    2016-01-01

    Treatment for human African trypanosomiasis is dependent on the species of trypanosome causing the disease and the stage of the disease (stage 1 defined by parasites being present in blood and lymphatics whilst for stage 2, parasites are found beyond the blood-brain barrier in the cerebrospinal fluid (CSF)). Currently, staging relies upon detecting the very low number of parasites or elevated white blood cell numbers in CSF. Improved staging is desirable, as is the elimination of the need for lumbar puncture. Here we use metabolomics to probe samples of CSF, plasma and urine from 40 Angolan patients infected with Trypanosoma brucei gambiense, at different disease stages. Urine samples provided no robust markers indicative of infection or stage of infection due to inherent variability in urine concentrations. Biomarkers in CSF were able to distinguish patients at stage 1 or advanced stage 2 with absolute specificity. Eleven metabolites clearly distinguished the stage in most patients and two of these (neopterin and 5-hydroxytryptophan) showed 100% specificity and sensitivity between our stage 1 and advanced stage 2 samples. Neopterin is an inflammatory biomarker previously shown in CSF of stage 2 but not stage 1 patients. 5-hydroxytryptophan is an important metabolite in the serotonin synthetic pathway, the key pathway in determining somnolence, thus offering a possible link to the eponymous symptoms of “sleeping sickness”. Plasma also yielded several biomarkers clearly indicative of the presence (87% sensitivity and 95% specificity) and stage of disease (92% sensitivity and 81% specificity). A logistic regression model including these metabolites showed clear separation of patients being either at stage 1 or advanced stage 2 or indeed diseased (both stages) versus control. PMID:27941966

  1. Waste glass melting stages

    SciTech Connect

    Anderson, L.D.; Dennis, T.; Elliott, M.L.; Hrma, P.

    1993-04-01

    Three different simulated nuclear waste glass feeds, consisting of dried waste and glass frit, were heat treated for 1 hour in a gradient furnace at temperatures ranging from approximately 600[degrees]C--1000[degrees]C. Simulated melter feeds from the Hanford Waste Vitrification Plant (HWVP), the Defense Waste Processing Facility (DWPF), and Kernforschungszentrum Karlsruhe (KfK) in Germany were used. The samples were thin-sectioned and examined by optical microscopy to investigate the stages of the conversion from feed to glass. Various phenomena were seen, such as frit softening, bubble formation, foaming, bubble motion and removal, convective mixing, and homogenization. Behavior of different feeds was similar, although the degree of gas generation and melt homogenization varied.

  2. Waste glass melting stages

    SciTech Connect

    Anderson, L.D.; Dennis, T.; Elliott, M.L.; Hrma, P.

    1993-04-01

    Three different simulated nuclear waste glass feeds, consisting of dried waste and glass frit, were heat treated for 1 hour in a gradient furnace at temperatures ranging from approximately 600{degrees}C--1000{degrees}C. Simulated melter feeds from the Hanford Waste Vitrification Plant (HWVP), the Defense Waste Processing Facility (DWPF), and Kernforschungszentrum Karlsruhe (KfK) in Germany were used. The samples were thin-sectioned and examined by optical microscopy to investigate the stages of the conversion from feed to glass. Various phenomena were seen, such as frit softening, bubble formation, foaming, bubble motion and removal, convective mixing, and homogenization. Behavior of different feeds was similar, although the degree of gas generation and melt homogenization varied.

  3. Breast infection

    MedlinePlus

    ... female breast anatomy Breast infection Female breast References Hunt KK, Mittendorf EA. Diseases of the breast. In: ... Jacobson, MD, Professor of Obstetrics and Gynecology, Loma Linda University School of Medicine, Loma Linda Center for ...

  4. Tapeworm Infection

    MedlinePlus

    ... a laboratory for testing. A laboratory uses microscopic identification techniques to check for eggs or tapeworm segments ... to the anus to collect eggs for microscopic identification. Blood test. For tissue-invasive infections, your doctor ...

  5. Pinworm Infection

    MedlinePlus

    ... length. While the infected person sleeps, female pinworms lay thousands of eggs in the folds of skin ... Female pinworms move to the anal area to lay their eggs, which often results in anal itching. ...

  6. Campylobacter Infections

    MedlinePlus

    ... infections are connected with touching or eating undercooked poultry. Therefore, proper food handling and preparation are important. ... family: Wash your hands thoroughly after handling raw poultry. Also, wash cutting boards and utensils with soap ...

  7. Viral Infections

    MedlinePlus

    ... from medicines, which usually move through your bloodstream. Antibiotics do not work for viral infections. There are a few antiviral medicines available. Vaccines can help prevent you from getting many viral diseases. NIH: National Institute of Allergy and Infectious Diseases

  8. Staph Infections

    MedlinePlus

    ... of today's staph infections can be cured with penicillin. The emergence of antibiotic-resistant strains of staph ... Resistant Staphylococcus aureus (MRSA) — Prevention. National Institute of Allergy and Infectious Diseases. http://www.niaid.nih.gov/ ...

  9. Bacterial Infections

    MedlinePlus

    ... body will learn to resist them causing antibiotic resistance. Later, you could get or spread an infection that those antibiotics cannot cure. NIH: National Institute of Allergy and Infectious Diseases

  10. Mycobacterial Infections

    MedlinePlus

    ... many different kinds. The most common one causes tuberculosis. Another one causes leprosy. Still others cause infections ... aren't "typical" because they don't cause tuberculosis. But they can still harm people, especially people ...

  11. Staphylococcal Infections

    MedlinePlus

    ... Page Content Article Body Infections caused by staphylococcal organisms can lead to a variety of diseases, including ... blood tests may be ordered to identify the organism involved. Antibiotics taken by mouth are usually prescribed ...

  12. Hand Infections

    MedlinePlus

    ... spread to others. Necrotizing Fasciitis, or “Flesh-Eating Bacteria” Necrotizing fasciitis is a very rare but severe infection. Streptococcus pyogenes or other “flesh-eating bacteria” enter the body through a cut. Bacteria toxins ...

  13. Shigella Infections

    MedlinePlus

    ... Adenovirus Amebiasis E. Coli Stool Test: Bacteria Culture Cholera Giardiasis Rotavirus What Are Germs? Why Is Hand ... to Wash My Hands? Food Poisoning Salmonellosis Shigellosis Cholera E. Coli Gastrointestinal Infections and Diarrhea Salmonellosis Contact ...

  14. Spinal Infections

    MedlinePlus

    ... spinal infection include fever, chills, headache, neck stiffness, pain, wound redness and tenderness, and wound drainage. In some cases, patients may notice new weakness, numbness or tingling sensations in the arms and/or legs. The symptoms ...

  15. How Are Myelodysplastic Syndromes Staged?

    MedlinePlus

    ... Syndromes Early Detection, Diagnosis, and Staging How Are Myelodysplastic Syndromes Scored? Doctors often group cancers into different stages ... Ask Your Doctor About Myelodysplastic Syndromes? More In Myelodysplastic Syndromes About Myelodysplastic Syndromes Causes, Risk Factors, and Prevention ...

  16. Pancreatic Cancer Stage 2A

    MedlinePlus

    ... 2A Description: Stage IIA pancreatic cancer; drawing shows cancer in the pancreas and duodenum. The bile duct and pancreatic duct are also shown. Stage IIA pancreatic cancer. Cancer has spread to nearby tissue and organs ...

  17. Pancreatic Cancer Stage 2B

    MedlinePlus

    ... 2B Description: Stage IIB pancreatic cancer; drawing shows cancer in the pancreas and in nearby lymph nodes. Also shown are the bile duct, pancreatic duct, and duodenum. Stage IIB pancreatic cancer. Cancer has spread to nearby lymph nodes and ...

  18. How Is Ovarian Cancer Staged?

    MedlinePlus

    ... recent FIGO staging. Stages of ovarian and fallopian tube cancer Once a patient's T, N, and M ... only within the ovary (or ovaries) or fallopian tube(s). It has not spread to organs and tissues ...

  19. Stage III xanthogranulomatous pyelonephritis treated with antibiotherapy and percutaneous drainage.

    PubMed

    Ergun, T; Akin, A; Lakadamyali, H

    2011-01-01

    Xanthogranulomatous pyelonephritis (XPN) is a rare inflammatory condition usually secondary to chronic obstruction caused by nephrolithiasis and resulting in infection and irreversible destruction of the renal parenchyma. Its standard therapy consists of total or partial nephrectomy. A case of stage III xanthogranulomatous pyelonephritis treated with antibiotherapy and percutaneous drainage is presented in this paper.

  20. Hepatitis C: What Happens in End-Stage Liver Disease?

    MedlinePlus

    ... diseases or liver diseases (hepatologist). Newer, more-effective hepatitis C treatments can eliminate the virus in many people, reducing the risk of end-stage liver disease. With Michael F. Picco, ... and natural history of hepatitis C virus infection. http://www.uptodate.com/home. ...

  1. The principles of cancer staging

    PubMed Central

    Brierley, James; Gospodarowicz, Mary; O’Sullivan, Brian

    2016-01-01

    The anatomic disease extent or tumour stage of a cancer at diagnosis as a determinant of prognosis is discussed. The importance of cancer stage in individual patient prognosis and determination of treatment is reviewed as well as its value in research and cancer control activities. The conflict between the need for stability of cancer stage definitions over time and the need to evolve with advances in medicine are examined. The ecancer elearning modules on Cancer Stage are introduced. PMID:28101141

  2. Stage measurement at gaging stations

    USGS Publications Warehouse

    Buchanan, Thomas J.; Somers, William P.

    1968-01-01

    Continuous measurements of stream stage are used in determining records of stream discharge. In addition a record of stream stage is useful in itself, as in designing structures affected by stream elevation or in planning the use of flood plains. This report describes instruments and structures commonly used in obtaining a record of stream stage.

  3. Vaginal Yeast Infections

    MedlinePlus

    ... Surgery? A Week of Healthy Breakfasts Shyness Vaginal Yeast Infections KidsHealth > For Teens > Vaginal Yeast Infections Print ... side effect of taking antibiotics. What Is a Yeast Infection? A yeast infection is a common infection ...

  4. Vaccination in HIV-Infected Adults

    PubMed Central

    Wallace, Mark R.

    2014-01-01

    Abstract Vaccines are critical components for protecting HIV-infected adults from an increasing number of preventable diseases. However, missed opportunities for vaccination among HIV-infected persons persist, likely due to concerns regarding the safety and efficacy of vaccines, as well as the changing nature of vaccine guidelines. In addition, the optimal timing of vaccination among HIV-infected adults in regards to HIV stage and receipt of antiretroviral therapy remain important questions. This article provides a review of the current recommendations regarding vaccines among HIV-infected adults and a comprehensive summary of the evidence-based literature of the benefits and risks of vaccines among this vulnerable population. PMID:25029589

  5. The infected total knee: management options.

    PubMed

    Cuckler, John M

    2005-06-01

    The management of infection after total knee arthroplasty depends on the chronicity of the infection, host factors, and sensitivity of the infecting bacteria. Two-stage salvage consisting of removal of implants and cement, placement of an antibiotic spacer, and appropriate intravenous antibiotic therapy followed by reimplantation with an antibiotic-impregnated cement appears to be the predominant approach to managing this complication. The use of articulated spacers consisting of the sterilized femoral and polyethylene components with antibiotic cement allows maintenance of motion and bone stock. This report details the author's experience with 44 infected knee arthroplasties.

  6. Bevacizumab, Cisplatin, Radiation Therapy, and Fluorouracil in Treating Patients With Stage IIB, Stage III, Stage IVA, or Stage IVB Nasopharyngeal Cancer

    ClinicalTrials.gov

    2014-04-21

    Stage II Squamous Cell Carcinoma of the Nasopharynx; Stage III Lymphoepithelioma of the Nasopharynx; Stage III Squamous Cell Carcinoma of the Nasopharynx; Stage IV Lymphoepithelioma of the Nasopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx

  7. Oblimersen Sodium and Combination Chemotherapy in Treating Patients With Newly Diagnosed Stage I, Stage II, Stage III, or Stage IV Diffuse Large B-Cell Lymphoma

    ClinicalTrials.gov

    2012-10-11

    Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Stage I Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma

  8. Plasmodium yoelii macrophage migration inhibitory factor is necessary for efficient liver-stage development.

    PubMed

    Miller, Jessica L; Harupa, Anke; Kappe, Stefan H I; Mikolajczak, Sebastian A

    2012-04-01

    Mammalian macrophage migration inhibitory factor (MIF) is a multifaceted cytokine involved in both extracellular and intracellular functions. Malaria parasites express a MIF homologue that might modulate host immune responses against blood-stage parasites, but the potential importance of MIF against other life cycle stages remains unstudied. In this study, we characterized the MIF homologue of Plasmodium yoelii throughout the life cycle, with emphasis on preerythrocytic stages. P. yoelii MIF (Py-MIF) was expressed in blood-stage parasites and detected at low levels in mosquito salivary gland sporozoites. MIF expression was strong throughout liver-stage development and localized to the cytoplasm of the parasite, with no evidence of release into the host hepatocyte. To examine the importance of Py-MIF for liver-stage development, we generated a Py-mif knockout parasite (P. yoelii Δmif). P. yoelii Δmif parasites grew normally as asexual erythrocytic-stage parasites and showed normal infection of mosquitoes. In contrast, the P. yoelii Δmif strain was attenuated during the liver stage. Mice infected with P. yoelii Δmif sporozoites either did not develop blood-stage parasitemia or exhibited a delay in the onset of blood-stage patency. Furthermore, P. yoelii Δmif parasites exhibited growth retardation in vivo. Combined, the data indicate that Plasmodium MIF is important for liver-stage development of P. yoelii, during which it is likely to play an intrinsic role in parasite development rather than modulating host immune responses to infection.

  9. Short-interval two-stage approach to primary total knee arthroplasty for acutely septic osteoarthritic knees.

    PubMed

    Hochreiter, Bettina; Strahm, Carol; Behrend, Henrik

    2016-10-01

    Treatment strategies for advanced knee osteoarthritis with coexistent joint infection are not well established. While in periprosthetic joint infection the two-stage approach has been studied extensively, only few case reports on two-stage total knee arthroplasty (TKA) for knee osteoarthritis with coexistent joint infection have been published. The purpose of this paper was to report on our method of implementing a two-stage TKA with intervening antibiotic-loaded articulating cement spacers and a short interval between first- and second-stage procedures to treat two patients with Staphylococcus aureus-infected end-stage knee osteoarthritis. Consistent infection eradication was found at a 1-year follow-up with postoperative range of motion and knee scores comparing favourably with those of other case series. Level of evidence V.

  10. Infection: musculoskeletal.

    PubMed

    Jaramillo, Diego

    2011-05-01

    The imaging approach to osteomyelitis has evolved in the past two decades. Advances in MRI allow for whole body imaging, decreasing the need for scintigraphy when symptoms are not localized or the disease may be multifocal. There is an increasing clinical need for depiction of abscesses in the soft tissues and subperiosteal space, particularly because methicillin-resistant Staphylococcus aureus infections constitute more than one-third of all the infections. The increasing emphasis on radiation dose reduction has also led away from scintigraphy and computed tomography. MR imaging has become the advanced imaging modality of choice in osteomyelitis. There is an increasing understanding of the appropriate role for gadolinium enhancement, which is not indicated when the pre-gadolinium images are normal. Other related infections, including pyomyositis, are best imaged with MRI.

  11. Endemic infection reduces transmission potential of an epidemic parasite during co-infection

    PubMed Central

    Randall, J.; Cable, J.; Guschina, I. A.; Harwood, J. L.; Lello, J.

    2013-01-01

    Endemic, low-virulence parasitic infections are common in nature. Such infections may deplete host resources, which in turn could affect the reproduction of other parasites during co-infection. We aimed to determine whether the reproduction, and therefore transmission potential, of an epidemic parasite was limited by energy costs imposed on the host by an endemic infection. Total lipids, triacylglycerols (TAG) and polar lipids were measured in cockroaches (Blattella germanica) that were fed ad libitum, starved or infected with an endemic parasite, Gregarina blattarum. Reproductive output of an epidemic parasite, Steinernema carpocapsae, was then assessed by counting the number of infective stages emerging from these three host groups. We found both starvation and gregarine infection reduced cockroach lipids, mainly through depletion of TAG. Further, both starvation and G. blattarum infection resulted in reduced emergence of nematode transmission stages. This is, to our knowledge, the first study to demonstrate directly that host resource depletion caused by endemic infection could affect epidemic disease transmission. In view of the ubiquity of endemic infections in nature, future studies of epidemic transmission should take greater account of endemic co-infections. PMID:23966641

  12. Advanced two-stage compressor program design of inlet stage

    NASA Technical Reports Server (NTRS)

    Bryce, C. A.; Paine, C. J.; Mccutcheon, A. R. S.; Tu, R. K.; Perrone, G. L.

    1973-01-01

    The aerodynamic design of an inlet stage for a two-stage, 10/1 pressure ratio, 2 lb/sec flow rate compressor is discussed. Initially a performance comparison was conducted for an axial, mixed flow and centrifugal second stage. A modified mixed flow configuration with tandem rotors and tandem stators was selected for the inlet stage. The term conical flow compressor was coined to describe a particular type of mixed flow compressor configuration which utilizes axial flow type blading and an increase in radius to increase the work input potential. Design details of the conical flow compressor are described.

  13. Differential Expression of Hox and Notch Genes in Larval and Adult Stages of Echinococcus granulosus

    PubMed Central

    Dezaki, Ebrahim Saedi; Yaghoobi, Mohammad Mehdi; Taheri, Elham; Almani, Pooya Ghaseminejad; Tohidi, Farideh; Gottstein, Bruno; Harandi, Majid Fasihi

    2016-01-01

    This investigation aimed to evaluate the differential expression of HoxB7 and notch genes in different developmental stages of Echinococcus granulosus sensu stricto. The expression of HoxB7 gene was observed at all developmental stages. Nevertheless, significant fold differences in the expression level was documented in the juvenile worm with 3 or more proglottids, the germinal layer from infected sheep, and the adult worm from an experimentally infected dog. The notch gene was expressed at all developmental stages of E. granulosus; however, the fold difference was significantly increased at the microcysts in monophasic culture medium and the germinal layer of infected sheep in comparison with other stages. The findings demonstrated that the 2 aforementioned genes evaluated in the present study were differentially expressed at different developmental stages of the parasite and may contribute to some important biological processes of E. granulosus. PMID:27853123

  14. Approach to urinary tract infections

    PubMed Central

    Najar, M. S.; Saldanha, C. L.; Banday, K. A.

    2009-01-01

    Urinary tract infection (UTI) is the most common infection experienced by humans after respiratory and gastro-intestinal infections, and also the most common cause of both community-acquired and nosocomial infections for patients admitted to hospitals. For better management and prognosis, it is mandatory to know the possible site of infection, whether the infection is uncomplicated or complicated, re-infection or relapse, or treatment failure and its pathogenesis and risk factors. Asymptomatic bacteriuria is common in certain age groups and has different connotations. It needs to be treated and completely cured in pregnant women and preschool children. Reflux nephropathy in children could result in chronic kidney disease; otherwise, urinary tract infections do not play a major role in the pathogenesis of end-stage renal disease. Symptomatic urinary tract infections occur most commonly in women of child-bearing age. Cystitis predominates, but needs to be distinguished from acute urethral syndrome that affects both sexes and has a different management plan than UTIs. The prostatitis symptoms are much more common than bacterial prostatic infections. The treatment needs to be prolonged in bacterial prostatitis and as cure rates are not very high and relapses are common, the classification of prostatitis needs to be understood. The consensus conference convened by National Institute of Health added two more groups of patients, namely, chronic prostatitis/chronic pelvic pain syndrome and asymptomatic inflammatory prostatitis, in addition to acute and chronic bacterial prostatitis. Although white blood cells in urine signify inflammation, they do not always signify UTI. Quantitative cultures of urine provide definitive evidence of UTI. Imaging studies should be done 3-6 weeks after cure of acute infection to identify abnormalities predisposing to infection or renal damage or which may affect management. Treatment of cystitis in women should be a three-day course and if

  15. Approach to urinary tract infections.

    PubMed

    Najar, M S; Saldanha, C L; Banday, K A

    2009-10-01

    Urinary tract infection (UTI) is the most common infection experienced by humans after respiratory and gastro-intestinal infections, and also the most common cause of both community-acquired and nosocomial infections for patients admitted to hospitals. For better management and prognosis, it is mandatory to know the possible site of infection, whether the infection is uncomplicated or complicated, re-infection or relapse, or treatment failure and its pathogenesis and risk factors. Asymptomatic bacteriuria is common in certain age groups and has different connotations. It needs to be treated and completely cured in pregnant women and preschool children. Reflux nephropathy in children could result in chronic kidney disease; otherwise, urinary tract infections do not play a major role in the pathogenesis of end-stage renal disease. Symptomatic urinary tract infections occur most commonly in women of child-bearing age. Cystitis predominates, but needs to be distinguished from acute urethral syndrome that affects both sexes and has a different management plan than UTIs. The prostatitis symptoms are much more common than bacterial prostatic infections. The treatment needs to be prolonged in bacterial prostatitis and as cure rates are not very high and relapses are common, the classification of prostatitis needs to be understood. The consensus conference convened by National Institute of Health added two more groups of patients, namely, chronic prostatitis/chronic pelvic pain syndrome and asymptomatic inflammatory prostatitis, in addition to acute and chronic bacterial prostatitis. Although white blood cells in urine signify inflammation, they do not always signify UTI. Quantitative cultures of urine provide definitive evidence of UTI. Imaging studies should be done 3-6 weeks after cure of acute infection to identify abnormalities predisposing to infection or renal damage or which may affect management. Treatment of cystitis in women should be a three-day course and if

  16. Multi-stage complex contagions.

    PubMed

    Melnik, Sergey; Ward, Jonathan A; Gleeson, James P; Porter, Mason A

    2013-03-01

    The spread of ideas across a social network can be studied using complex contagion models, in which agents are activated by contact with multiple activated neighbors. The investigation of complex contagions can provide crucial insights into social influence and behavior-adoption cascades on networks. In this paper, we introduce a model of a multi-stage complex contagion on networks. Agents at different stages-which could, for example, represent differing levels of support for a social movement or differing levels of commitment to a certain product or idea-exert different amounts of influence on their neighbors. We demonstrate that the presence of even one additional stage introduces novel dynamical behavior, including interplay between multiple cascades, which cannot occur in single-stage contagion models. We find that cascades-and hence collective action-can be driven not only by high-stage influencers but also by low-stage influencers.

  17. Staged membrane oxidation reactor system

    DOEpatents

    Repasky, John Michael; Carolan, Michael Francis; Stein, VanEric Edward; Chen, Christopher Ming-Poh

    2014-05-20

    Ion transport membrane oxidation system comprising (a) two or more membrane oxidation stages, each stage comprising a reactant zone, an oxidant zone, one or more ion transport membranes separating the reactant zone from the oxidant zone, a reactant gas inlet region, a reactant gas outlet region, an oxidant gas inlet region, and an oxidant gas outlet region; (b) an interstage reactant gas flow path disposed between each pair of membrane oxidation stages and adapted to place the reactant gas outlet region of a first stage of the pair in flow communication with the reactant gas inlet region of a second stage of the pair; and (c) one or more reactant interstage feed gas lines, each line being in flow communication with any interstage reactant gas flow path or with the reactant zone of any membrane oxidation stage receiving interstage reactant gas.

  18. Staged membrane oxidation reactor system

    DOEpatents

    Repasky, John Michael; Carolan, Michael Francis; Stein, VanEric Edward; Chen, Christopher Ming-Poh

    2013-04-16

    Ion transport membrane oxidation system comprising (a) two or more membrane oxidation stages, each stage comprising a reactant zone, an oxidant zone, one or more ion transport membranes separating the reactant zone from the oxidant zone, a reactant gas inlet region, a reactant gas outlet region, an oxidant gas inlet region, and an oxidant gas outlet region; (b) an interstage reactant gas flow path disposed between each pair of membrane oxidation stages and adapted to place the reactant gas outlet region of a first stage of the pair in flow communication with the reactant gas inlet region of a second stage of the pair; and (c) one or more reactant interstage feed gas lines, each line being in flow communication with any interstage reactant gas flow path or with the reactant zone of any membrane oxidation stage receiving interstage reactant gas.

  19. Staged membrane oxidation reactor system

    DOEpatents

    Repasky, John Michael; Carolan, Michael Francis; Stein, VanEric Edward; Chen, Christopher Ming-Poh

    2012-09-11

    Ion transport membrane oxidation system comprising (a) two or more membrane oxidation stages, each stage comprising a reactant zone, an oxidant zone, one or more ion transport membranes separating the reactant zone from the oxidant zone, a reactant gas inlet region, a reactant gas outlet region, an oxidant gas inlet region, and an oxidant gas outlet region; (b) an interstage reactant gas flow path disposed between each pair of membrane oxidation stages and adapted to place the reactant gas outlet region of a first stage of the pair in flow communication with the reactant gas inlet region of a second stage of the pair; and (c) one or more reactant interstage feed gas lines, each line being in flow communication with any interstage reactant gas flow path or with the reactant zone of any membrane oxidation stage receiving interstage reactant gas.

  20. Staged Repository Development Programmes

    SciTech Connect

    Isaacs, T

    2003-10-01

    Programs to manage and ultimately dispose of high-level radioactive wastes are unique from scientific and technological as well as socio-political aspects. From a scientific and technological perspective, high-level radioactive wastes remain potentially hazardous for geological time periods-many millennia-and scientific and technological programs must be put in place that result in a system that provides high confidence that the wastes will be isolated from the accessible environment for these many thousands of years. Of course, ''proof'' in the classical sense is not possible at the outset, since the performance of the system can only be known with assurance, if ever, after the waste has been emplaced for those geological time periods. Adding to this challenge, many uncertainties exist in both the natural and engineered systems that are intended to isolate the wastes, and some of the uncertainties will remain regardless of the time and expense in attempting to characterize the system and assess its performance. What was perhaps underappreciated in the early days of waste management and repository program development were the unique and intense reactions that the institutional, political, and public bodies would have to repository program development, particularly in programs attempting to identify and then select sites for characterization, design, licensing, and ultimate development. Reactions in most nations were strong, focused, unrelenting, and often successful in hindering, derailing, and even stopping national repository programs. The reasons for such reactions and the measures to successfully respond to them are still evolving and continue to be the focus of many national program and political leaders. Adaptive Staging suggests an approach to repository program development that reflects the unique challenges associated with the disposal of high-level radioactive waste. The step-wise, incremental, learn-as-you-go approach is intended to maximize the

  1. Tinea Infections

    MedlinePlus

    Tinea is the name of a group of diseases caused by a fungus. Types of tinea include ringworm, athlete's foot and jock itch. These infections are ... depend on the affected area of the body: Ringworm is a red skin rash that forms a ...

  2. Paratyphoid Infections

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The numerous motile members of the bacterial genus Salmonella are collectively referred to as paratyphoid (PT) salmonellae. Found throughout the world, these organisms infect a wide variety of hosts (including invertebrate and vertebrate wildlife, domestic animals, and humans) to yield either asympt...

  3. [Infected pseudarthrosis].

    PubMed

    Kinzl, L; Suger, G

    1996-09-01

    In open fractures the rate of infected non-union defects has in recent years decreased due to the increased primary application of external fixation. In spite of this positive state of affairs the condition is still encountered often enough to warrant specific treatment strategies and techniques. In the treatment of infected pseudarthroses the general principles of osteitis treatment are applied. This includes radical excision of infected pseudarthrotic bone and of the diseased surrounding soft tissue, provides mechanical stability in the non-union area and requires effective local treatment of the infection in combination with systemic, target-specific and temporary well-defined antibiotic therapy as well as procedures to improve local circulation. The incorporation of autogenous bone transplants in defects appears to depend on close contact between the transplant and the vascularized receiving site and on the quantity of the transplanted osseous material. A promising alternative method of dealing with extensive bone defects is osteogenesis produced by callus distraction; therefore special attention is given to Ilizarov's ring fixation system. Unstable scar formation demands local muscular flaps or microvascularized free flap transfer, which seems to be superior to other methods.

  4. Fungal Infections

    MedlinePlus

    ... it, you'll be saying bye-bye to fungi (say: FUN-guy). What Is a Fungal Infection? Fungi , the word for more than one fungus, can ... but of course, they're not!). Because the fungi that cause tinea (ringworm) live on different parts ...

  5. Chlamydia Infections

    MedlinePlus

    ... PID). PID can cause permanent damage to your reproductive system. This can lead to long-term pelvic pain, infertility, and ectopic pregnancy. Women who have had chlamydia infections more than once are at higher risk of serious reproductive health complications. Men often don't have health ...

  6. Ares I Upper Stage Element

    NASA Technical Reports Server (NTRS)

    Chojnacki, Kent

    2009-01-01

    This slide presentation reviews the elements that make up the Ares I launch vehicle, with particular attention devoted to the upper stage of the vehicle. The upper stage elememnts, a lunar mission profile, and the upper stage objectives are reviewed. The work that Marshall Space Flight Center is doing is highlighted: work on the full scale welding process, the vertical milling machining, and the thermal protection system.

  7. Paclitaxel and Carboplatin Before Radiation Therapy With Paclitaxel in Treating HPV-Positive Patients With Stage III-IV Oropharynx, Hypopharynx, or Larynx Cancer

    ClinicalTrials.gov

    2016-09-07

    Human Papilloma Virus Infection; Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage III Verrucous Carcinoma of the Larynx; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Verrucous Carcinoma of the Larynx; Stage IVA Squamous Cell Carcinoma of the Larynx; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Verrucous Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVB Verrucous Carcinoma of the Larynx; Stage IVC Squamous Cell Carcinoma of the Larynx; Stage IVC Squamous Cell Carcinoma of the Oropharynx; Stage IVC Verrucous Carcinoma of the Larynx

  8. Interferon-mediated innate immune responses against malaria parasite liver stages.

    PubMed

    Miller, Jessica L; Sack, Brandon K; Baldwin, Michael; Vaughan, Ashley M; Kappe, Stefan H I

    2014-04-24

    Mosquito-transmitted malaria parasites infect hepatocytes and asymptomatically replicate as liver stages. Using RNA sequencing, we show that a rodent malaria liver-stage infection stimulates a robust innate immune response including type I interferon (IFN) and IFNγ pathways. Liver-stage infection is suppressed by these infection-engendered innate responses. This suppression was abrogated in mice deficient in IFNγ, the type I IFN α/β receptor (IFNAR), and interferon regulatory factor 3. Natural killer and CD49b(+)CD3(+) natural killer T (NKT) cells increased in the liver after a primary infection, and CD1d-restricted NKT cells, which secrete IFNγ, were critical in reducing liver-stage burden of a secondary infection. Lack of IFNAR signaling abrogated the increase in NKT cell numbers in the liver, showing a link between type I IFN signaling, cell recruitment, and subsequent parasite elimination. Our findings demonstrate innate immune sensing of malaria parasite liver-stage infection and that the ensuing innate responses can eliminate the parasite.

  9. Staging of neoplasms. Volume 7

    SciTech Connect

    Glazer, G.M.

    1986-01-01

    This book is divided into ten chapters. The first, an overview of the importance of staging, is followed by separate chapters on computed tomographic (CT) evaluation of lymph node metastases; metastatic disease to the thorax; staging of laryngeal, hypopharyngeal, esophageal, non-small cell lung, and renal carcinoma; and pediatric abdominal malignancies. CT staging of lymphomas is dealt with in a separate chapter. The final chapter summarizes initial experiences with staging of neoplasms by magnetic resonance (MR) imaging. Other neoplasms, such as pelvic, pancreatic, and gastrointestinal, are not discussed in depth. The book concludes with ten case studies, most of which deal with pelvic and gastrointestinal malignancies.

  10. Carboplatin and Paclitaxel With or Without Cisplatin and Radiation Therapy in Treating Patients With Stage I, Stage II, Stage III, or Stage IVA Endometrial Cancer

    ClinicalTrials.gov

    2016-02-09

    Endometrial Clear Cell Adenocarcinoma; Endometrial Serous Adenocarcinoma; Stage IA Uterine Corpus Cancer; Stage IB Uterine Corpus Cancer; Stage II Uterine Corpus Cancer; Stage IIIA Uterine Corpus Cancer; Stage IIIB Uterine Corpus Cancer; Stage IIIC Uterine Corpus Cancer; Stage IVA Uterine Corpus Cancer

  11. Second stage gasifier in staged gasification and integrated process

    DOEpatents

    Liu, Guohai; Vimalchand, Pannalal; Peng, Wan Wang

    2015-10-06

    A second stage gasification unit in a staged gasification integrated process flow scheme and operating methods are disclosed to gasify a wide range of low reactivity fuels. The inclusion of second stage gasification unit operating at high temperatures closer to ash fusion temperatures in the bed provides sufficient flexibility in unit configurations, operating conditions and methods to achieve an overall carbon conversion of over 95% for low reactivity materials such as bituminous and anthracite coals, petroleum residues and coke. The second stage gasification unit includes a stationary fluidized bed gasifier operating with a sufficiently turbulent bed of predefined inert bed material with lean char carbon content. The second stage gasifier fluidized bed is operated at relatively high temperatures up to 1400.degree. C. Steam and oxidant mixture can be injected to further increase the freeboard region operating temperature in the range of approximately from 50 to 100.degree. C. above the bed temperature.

  12. Schistosoma Mansoni Infection: Intestinal Schistosomiasis

    DTIC Science & Technology

    1992-01-01

    patients should be :reated. The two mnain Diagnosis oral drugs available for the treatment of all stages of S. mansoni infection are praziquantel and...rep~eatedlly for laterally spilled eggs. Eosino- * praziquantel is administered either as a single dose, philia is usual in acute, but not chronic...with praziquantel , 75 mg/kg in three divided doses 4-hourly. Cortico- steroidls (prednisone, 5 mig t.d.s.) are used for 2-3 days to control the fever and

  13. Inhibition of Plasmodium Liver Infection by Ivermectin

    PubMed Central

    Mendes, António M.; Albuquerque, Inês S.; Machado, Marta; Pissarra, Joana; Meireles, Patrícia

    2016-01-01

    ABSTRACT Avermectins are powerful endectocides with an established potential to reduce the incidence of vector-borne diseases. Here, we show that several avermectins inhibit the hepatic stage of Plasmodium infection in vitro. Notably, ivermectin potently inhibits liver infection in vivo by impairing parasite development inside hepatocytes. This impairment has a clear impact on the ensuing blood stage parasitemia, reducing disease severity and enhancing host survival. Ivermectin has been proposed as a tool to control malaria transmission because of its effects on the mosquito vector. Our study extends the effect of ivermectin to the early stages of mammalian host infection and supports the inclusion of this multipurpose drug in malaria control strategies. PMID:27895022

  14. HIV co-infection accelerates decay of humoral responses in spontaneous resolvers of HCV infection.

    PubMed

    Liu, Y; Shen, T; Zhang, C; Long, L; Duan, Z; Lu, F

    2014-10-01

    Acute hepatitis C virus (HCV) infection is primarily followed by chronic infection, while spontaneous recovery of HCV infection (SR-HCV) occurs in a minority of those infected. Identification of SR-HCV clinically depends on two combined indicators, persistently undetectable peripheral HCV RNA and positivity for anti-HCV. However, the characteristics of dynamic variation in anti-HCV antibodies in SR-HCV, especially in those patients co-infected with HIV, are still undefined. In this study, a cohort of patients infected with HCV through commercial blood collection practices was studied. We found that the annual decreasing rate of anti-HCV presented a gradually accelerated process in HCV resolvers. However, the variation in the decline of anti-HCV presented a slowly accelerated process within the early decrease stage and a gradually decelerated process within the latter decrease stage. In addition, we deduced that it expended approximately 16 years from natural HCV recovery to undetectable peripheral anti-HCV in HCV resolvers co-infected with HIV, while this time was estimated to be 20 years in SR-HCV without HIV co-infection. Our data indicated that the decay of anti-HCV was accelerated by HIV-related impairment of immune function. The prevalence of HCV infection may be severely underestimated in this large-scale retrospective epidemiologic investigation in an HIV-infected population.

  15. A Model of Moral Stages

    ERIC Educational Resources Information Center

    Reed, Don Collins

    2008-01-01

    The argument of this paper focuses on the relationship between cognitive structures and structures of interaction. It contends that there is still a place in moral development theory and research for a concept of moral stages. The thesis, in short, is that moral stages are not structures of thought. They are structures of action encoded in…

  16. The Theatre Student: Stage Violence.

    ERIC Educational Resources Information Center

    Katz, Albert M.

    Stage violence is a complex art which, when conceived inventively, approached with professional care and respect, and practiced with patience and energy, can be the highlight of a scene or of an entire play. This book is designed for amateurs who have not had the benefit of formal training in stage violence. Chapters discuss falling (the…

  17. Multiple stage miniature stepping motor

    DOEpatents

    Niven, William A.; Shikany, S. David; Shira, Michael L.

    1981-01-01

    A stepping motor comprising a plurality of stages which may be selectively activated to effect stepping movement of the motor, and which are mounted along a common rotor shaft to achieve considerable reduction in motor size and minimum diameter, whereby sequential activation of the stages results in successive rotor steps with direction being determined by the particular activating sequence followed.

  18. Lernpunkt Deutsch--Stage 1.

    ERIC Educational Resources Information Center

    Theil, Elvira

    1997-01-01

    Evaluates the first stage of "Lernpunkt Deutsch," a new three-stage German course designed for upper elementary and early secondary school. Describes the publisher's package of materials and the appropriateness of the course, utility of the different package elements, format of the materials, and assesses whether the course provides pedagogically…

  19. Multi-stage complex contagions

    NASA Astrophysics Data System (ADS)

    Melnik, Sergey; Ward, Jonathan A.; Gleeson, James P.; Porter, Mason A.

    2013-03-01

    The spread of ideas across a social network can be studied using complex contagion models, in which agents are activated by contact with multiple activated neighbors. The investigation of complex contagions can provide crucial insights into social influence and behavior-adoption cascades on networks. In this paper, we introduce a model of a multi-stage complex contagion on networks. Agents at different stages—which could, for example, represent differing levels of support for a social movement or differing levels of commitment to a certain product or idea—exert different amounts of influence on their neighbors. We demonstrate that the presence of even one additional stage introduces novel dynamical behavior, including interplay between multiple cascades, which cannot occur in single-stage contagion models. We find that cascades—and hence collective action—can be driven not only by high-stage influencers but also by low-stage influencers.

  20. Ares I Upper Stage Overview

    NASA Technical Reports Server (NTRS)

    Verhage, Marc

    2007-01-01

    The Upper Stage Element of NASA's Ares I Crew Launch Vehicle (CLV) is a "clean-sheet" approach that is being designed and developed in-house, with Element management at MSFC. The Upper Stage Element concept is a self-supporting cylindrical structure, approximately 84' long and 18' in diameter. While the First Stage Solid Rocket Booster (SRB) design has changed since the CLV inception, the Upper Stage Element design has remained essentially a clean-sheet design approach. A clean-sheet upper stage design does offer many advantages: a design for increased reliability; built-in evolvability to allow for commonality/growth without major redesign; incorporation of state-of-the-art materials and hardware; and incorporation of design, fabrication, and test techniques and processes to facilitate a more operable system.

  1. Subminiature infrared detector translation stage

    NASA Technical Reports Server (NTRS)

    Bell, Alan D.

    1989-01-01

    This paper describes a precision subminiature three-axis translation stage used in the GOES Sounder to provide positional adjustment of 12 cooled infrared detectors. Four separate translation stages and detectors are packaged into a detector mechanism which has an overall size of 0.850 x 1.230 x 0.600 inches. Each translation stage is capable of + or - 0.015 inch motion in the X and Y axes and +0.050/-0.025 inch motion in the Z axis with a sensitivity of 0.0002 inches. The function of the detector translation stage allows real time detector signal peaking during Sounder alignment. The translation stage operates in a cryogenic environment under a 10 to the -6th torr vacuum.

  2. Suramin inhibits EV71 infection.

    PubMed

    Wang, Yaxin; Qing, Jie; Sun, Yuna; Rao, Zihe

    2014-03-01

    Enterovirus-71 (EV71) is one of the major causative reagents for hand-foot-and-mouth disease. In particular, EV71 causes severe central nervous system infections and leads to numerous dead cases. Although several inactivated whole-virus vaccines have entered in clinical trials, no antiviral agent has been provided for clinical therapy. In the present work, we screened our compound library and identified that suramin, which has been clinically used to treat variable diseases, could inhibit EV71 proliferation with an IC50 value of 40 μM. We further revealed that suramin could block the attachment of EV71 to host cells to regulate the early stage of EV71 infection, as well as affected other steps of EV71 life cycle. Our results are helpful to understand the mechanism for EV71 life cycle and provide a potential for the usage of an approved drug, suramin, as the antiviral against EV71 infection.

  3. Infective endocarditis.

    PubMed

    Cahill, Thomas J; Prendergast, Bernard D

    2016-02-27

    Infective endocarditis occurs worldwide, and is defined by infection of a native or prosthetic heart valve, the endocardial surface, or an indwelling cardiac device. The causes and epidemiology of the disease have evolved in recent decades with a doubling of the average patient age and an increased prevalence in patients with indwelling cardiac devices. The microbiology of the disease has also changed, and staphylococci, most often associated with health-care contact and invasive procedures, have overtaken streptococci as the most common cause of the disease. Although novel diagnostic and therapeutic strategies have emerged, 1 year mortality has not improved and remains at 30%, which is worse than for many cancers. Logistical barriers and an absence of randomised trials hinder clinical management, and longstanding controversies such as use of antibiotic prophylaxis remain unresolved. In this Seminar, we discuss clinical practice, controversies, and strategies needed to target this potentially devastating disease.

  4. Protozoan Infections

    DTIC Science & Technology

    1989-01-01

    Infectious Disease Service, Walter Reed Army Medical Center,N Washington, DC, USA MONTE S. MELTZER 0 CAROL A. NACY ( Department of Immunology/Walter Reed...patient’s demise. Toxoplasma gondii infects a wide range of animals, including humans. The parasite undergoes sexual reproduction only in felines , the...definitive hosts. Felines are required to maintain the life cycle in nature, since incidental hosts do not excrete the parasite in their faeces. Humans

  5. Stage measurement at gaging stations

    USGS Publications Warehouse

    Sauer, Vernon B.; Turnipseed, D. Phil

    2010-01-01

    Stream and reservoir stage are critical parameters in the computation of stream discharge and reservoir volume, respectively. In addition, a record of stream stage is useful in the design of structures that may be affected by stream elevation, as well as for the planning for various uses of flood plains. This report describes equipment and methodology for the observation, sensing, and recording of stage in streams and reservoirs. Although the U.S. Geological Survey (USGS) still uses the traditional, basic stilling-well float system as a predominant gaging station, modern electronic stage sensors and water-level recorders are now commonly used. Bubble gages coupled with nonsubmersible pressure transducers eliminate the need for stilling wells. Submersible pressure transducers have become common in use for the measurement of stage in both rivers and lakes. Furthermore, noncontact methods, such as radar, acoustic, and laser methods of sensing water levels, are being developed and tested, and in the case of radar, are commonly used for the measurement of stage. This report describes commonly used gaging-station structures, as well as the design and operation of gaging stations. Almost all of the equipment and instruments described in this report will meet the accuracy standard set by the USGS Office of Surface Water (OSW) for the measurement of stage for most applications, which is ?0.01 foot (ft) or 0.2 percent of the effective stage. Several telemetry systems are used to transmit stage data from the gaging station to the office, although satellite telemetry has become the standard. These telemetry systems provide near real-time stage data, as well as other information that alerts the hydrographer to extreme or abnormal events, and instrument malfunctions.

  6. Infective endocarditis.

    PubMed

    Ferro, José M; Fonseca, Ana Catarina

    2014-01-01

    Infective endocarditis is a serious disease of the endocardium of the heart and cardiac valves, caused by a variety of infectious agents, ranging from streptococci to rickettsia. The proportion of cases associated with rheumatic valvulopathy and dental surgery has decreased in recent years, while endocarditis associated with intravenous drug abuse, prosthetic valves, degenerative valve disease, implanted cardiac devices, and iatrogenic or nosocomial infections has emerged. Endocarditis causes constitutional, cardiac and multiorgan symptoms and signs. The central nervous system can be affected in the form of meningitis, cerebritis, encephalopathy, seizures, brain abscess, ischemic embolic stroke, mycotic aneurysm, and subarachnoid or intracerebral hemorrhage. Stroke in endocarditis is an ominous prognostic sign. Treatment of endocarditis includes prolonged appropriate antimicrobial therapy and in selected cases, cardiac surgery. In ischemic stroke associated with infective endocarditis there is no indication to start antithrombotic drugs. In previously anticoagulated patients with an ischemic stroke, oral anticoagulants should be replaced by unfractionated heparin, while in intracranial hemorrhage, all anticoagulation should be interrupted. The majority of unruptured mycotic aneurysms can be treated by antibiotics, but for ruptured aneurysms, endovascular or neurosurgical therapy is indicated.

  7. Malaria Parasite Liver Infection and Exoerythrocytic Biology.

    PubMed

    Vaughan, Ashley M; Kappe, Stefan H I

    2017-02-27

    In their infection cycle, malaria parasites undergo replication and population expansions within the vertebrate host and the mosquito vector. Host infection initiates with sporozoite invasion of hepatocytes, followed by a dramatic parasite amplification event during liver stage parasite growth and replication within hepatocytes. Each liver stage forms up to 90,000 exoerythrocytic merozoites, which are in turn capable of initiating a blood stage infection. Liver stages not only exploit host hepatocyte resources for nutritional needs but also endeavor to prevent hepatocyte cell death and detection by the host's immune system. Research over the past decade has identified numerous parasite factors that play a critical role during liver infection and has started to delineate a complex web of parasite-host interactions that sustain successful parasite colonization of the mammalian host. Targeting the parasites' obligatory infection of the liver as a gateway to the blood, with drugs and vaccines, constitutes the most effective strategy for malaria eradication, as it would prevent clinical disease and onward transmission of the parasite.

  8. Eradication of infection, survival, and radiological results of uncemented revision stems in infected total hip arthroplasties

    PubMed Central

    Born, Philipp; Ilchmann, Thomas; Zimmerli, Werner; Zwicky, Lukas; Graber, Peter; Ochsner, Peter E; Clauss, Martin

    2016-01-01

    Background and purpose — The use of uncemented revision stems is an established option in 2-stage procedures in patients with periprosthetic joint infection (PJI) after total hip arthroplasty (THA). However, in 1-stage procedures, they are still rarely used. There are still no detailed data on radiological outcome after uncemented 1-stage revisions. We assessed (1) the clinical outcome, including reoperation due to persistent infection and any other reoperation, and (2) the radiological outcome after 1- and 2-stage revision, using an uncemented stem. Patients and methods — Between January 1993 and December 2012, an uncemented revision stem was used in 81 THAs revised for PJI. Patients were treated with 1- or 2-stage procedures according to a well-defined algorithm (1-stage: n = 28; 2-stage: n = 53). All hips had a clinical and radiological follow-up. Outcome parameters were eradication of infection, re-revision of the stem, and radiological changes. Survival was calculated using Kaplan-Meier analysis. Radiographs were analyzed for bone restoration and signs of loosening. The mean clinical follow-up time was 7 (2–15) years. Results — The 7-year infection-free survival was 96% (95% CI: 92–100), 100% for 1-stage revision and 94% for 2-stage revision (95% CI: 87–100) (p = 0.2). The 7-year survival for aseptic loosening of the stem was 97% (95% CI: 93–100), 97% for 1-stage revision (95% CI: 90–100) and 97% for 2-stage revision (95% CI: 92–100) (p = 0.3). No further infection or aseptic loosening occurred later than 7 years postoperatively. The radiographic results were similar for 1- and 2-stage procedures. Interpretation — Surgical management of PJI with stratification to 1- or 2-stage exchange according to a well-defined algorithm combined with antibiotic treatment allows the safe use of uncemented revision stems. Eradication of infection can be achieved in most cases, and medium- and long-term results appear to be comparable to those for revisions

  9. Eradication of infection, survival, and radiological results of uncemented revision stems in infected total hip arthroplasties.

    PubMed

    Born, Philipp; Ilchmann, Thomas; Zimmerli, Werner; Zwicky, Lukas; Graber, Peter; Ochsner, Peter E; Clauss, Martin

    2016-12-01

    Background and purpose - The use of uncemented revision stems is an established option in 2-stage procedures in patients with periprosthetic joint infection (PJI) after total hip arthroplasty (THA). However, in 1-stage procedures, they are still rarely used. There are still no detailed data on radiological outcome after uncemented 1-stage revisions. We assessed (1) the clinical outcome, including reoperation due to persistent infection and any other reoperation, and (2) the radiological outcome after 1- and 2-stage revision, using an uncemented stem. Patients and methods - Between January 1993 and December 2012, an uncemented revision stem was used in 81 THAs revised for PJI. Patients were treated with 1- or 2-stage procedures according to a well-defined algorithm (1-stage: n = 28; 2-stage: n = 53). All hips had a clinical and radiological follow-up. Outcome parameters were eradication of infection, re-revision of the stem, and radiological changes. Survival was calculated using Kaplan-Meier analysis. Radiographs were analyzed for bone restoration and signs of loosening. The mean clinical follow-up time was 7 (2-15) years. Results - The 7-year infection-free survival was 96% (95% CI: 92-100), 100% for 1-stage revision and 94% for 2-stage revision (95% CI: 87-100) (p = 0.2). The 7-year survival for aseptic loosening of the stem was 97% (95% CI: 93-100), 97% for 1-stage revision (95% CI: 90-100) and 97% for 2-stage revision (95% CI: 92-100) (p = 0.3). No further infection or aseptic loosening occurred later than 7 years postoperatively. The radiographic results were similar for 1- and 2-stage procedures. Interpretation - Surgical management of PJI with stratification to 1- or 2-stage exchange according to a well-defined algorithm combined with antibiotic treatment allows the safe use of uncemented revision stems. Eradication of infection can be achieved in most cases, and medium- and long-term results appear to be comparable to those for revisions for aseptic

  10. Oral antibiotics are effective for highly resistant hip arthroplasty infections.

    PubMed

    Cordero-Ampuero, José; Esteban, Jaime; García-Cimbrelo, Eduardo

    2009-09-01

    Infected arthroplasties reportedly have a lower eradication rate when caused by highly resistant and/or polymicrobial isolates and in these patients most authors recommend intravenous antibiotics. We asked whether two-stage revision with interim oral antibiotics could eradicate these infections. We prospectively followed 36 patients (mean age, 71.8 years) with late hip arthroplasty infections. Combinations of oral antibiotics were prescribed according to cultures, biofilm, and intracellular effectiveness. The minimum followup was 1 year (mean, 4.4 years; range, 1-12 years). We presumed eradication in the absence of clinical, serologic, and radiographic signs of infection. Infection was eradicated in all 13 patients with highly resistant bacteria who completed a two-stage protocol (10 with methicillin-resistant Staphylococci) and in eight of 11 patients treated with only the first stage (and six of nine with methicillin-resistant Staphylococci). Infection was eradicated in six of six patients with polymicrobial isolates (of sensitive and/or resistant bacteria) who completed a two-stage protocol and in five of seven with polymicrobial isolates treated with only the first surgery. The Harris hip score averaged 88.1 (range, 70-98) in patients who underwent reimplantation and 56.8 (range, 32-76) in patients who underwent resection arthroplasty. Long cycles of combined oral antibiotics plus a two-stage surgical exchange appear a promising alternative for infections by highly resistant bacteria, methicillin-resistant Staphylococci, and polymicrobial infections.

  11. Fungal nail infection

    MedlinePlus

    ... Common fungal infections include: Athlete's foot Jock itch Ringworm on the skin of the body or head ... fungal infection. Alternative Names Nails - fungal infection; Onychomycosis; Tinea unguium Images Nail infection, candidal Yeast and mold ...

  12. Fish tapeworm infection

    MedlinePlus

    Fish tapeworm infection is an intestinal infection with the tapeworm parasite found in fish. ... The fish tapeworm ( Diphyllobothrium latum ) is the largest parasite that infects humans. Humans become infected when they eat raw or undercooked ...

  13. Managing urinary tract infections.

    PubMed

    Saadeh, Sermin A; Mattoo, Tej K

    2011-11-01

    Urinary tract infections (UTI) are common in childhood. Presence of pyuria and bacteriuria in an appropriately collected urine sample are diagnostic of UTI. The risk of UTI is increased with an underlying urological abnormality such as vesicoureteral reflux, constipation, and voiding dysfunction. Patients with acute pyelonephritis are at risk of renal scarring and subsequent complications such as hypertension, proteinuria with and without FSGS, pregnancy-related complications and even end-stage renal failure. The relevance and the sequence of the renal imaging following initial UTI, and the role of antimicrobial prophylaxis and surgical intervention are currently undergoing an intense debate. Prompt treatment of UTI and appropriate follow-up of those at increased risk of recurrence and/or renal scarring are important.

  14. How Is Kaposi Sarcoma Staged?

    MedlinePlus

    ... the lungs is a particularly bad sign. I (immune system) status The immune status is assessed using a ... in healthy people but affect people with suppressed immune systems) or thrush (a fungal infection in the mouth). ...

  15. Liver-Stage Specific Response among Endemic Populations: Diet and Immunity

    PubMed Central

    Dalai, Sarat Kumar; Yadav, Naveen; Patidar, Manoj; Patel, Hardik; Singh, Agam Prasad

    2015-01-01

    Developing effective anti-malarial vaccine has been a challenge for long. Various factors including complex life cycle of parasite and lack of knowledge of stage specific critical antigens are some of the reasons. Moreover, inadequate understanding of the immune responses vis-à-vis sterile protection induced naturally by Plasmodia infection has further compounded the problem. It has been shown that people living in endemic areas take years to develop protective immunity to blood stage infection. But hardly anyone believes that immunity to liver-stage infection could be developed. Various experimental model studies using attenuated parasite suggest that liver-stage immunity might exist among endemic populations. This could be induced because of the attenuation of parasite in liver by various compounds present in the diet of endemic populations. PMID:25852693

  16. Cognitive Development and Group Stages.

    ERIC Educational Resources Information Center

    Saidla, Debie D.

    1990-01-01

    Attempts to integrate Perry's (1970) scheme of the cognitive development of college students with a model of group development adapted by Waldo (1985) based on Tuckman's (1965) formulation of developmental group stages. (Author)

  17. Neuroblastoma: diagnostic imaging and staging

    SciTech Connect

    Stark, D.D.; Moss, A.A.; Brasch, R.C.; deLorimier, A.A.; Albin, A.R.; London, D.A.; Gooding, C.A.

    1983-07-01

    Results of computed tomography (CT), scintigraphy, excretory urography, and other imaging tests used to diagnose and stage 38 cases of neuroblastoma prior to treatment were reviewed. Findings of these examinations were correlated with clinical data, laboratory data, results of biopsy, and surgical findings. CT was the most sensitive single test (100%) for the detection and delineation of the primary tumor. Calcifications that suggested the histologic diagnosis of neuroblastoma were present in 79% of the cases. Rim calcifications, the most specific pattern for neuroblastoma, were identified in 29% of all cases. CT alone accurately staged 82% of cases; when complemented by bone marrow biopsy, staging accuracy was 97%. CT alone was more accurate than any combination of imaging tests that excluded CT. An algorithm using CT is presented for the diagnosis and staging of neuroblastoma at reduced cost and with increased efficiency.

  18. Five Developmental Stages of Spelling.

    ERIC Educational Resources Information Center

    Gentry, J. Richard

    1984-01-01

    Precommunicative, semiphonetic, phonetic, transitional, and correct spelling are the developmental stages in the acquisition of spelling competency. Samples of children's early spelling patterns are presented. A system for classifying early spelling strategy is outlined. (DF)

  19. Two stage to orbit design

    NASA Technical Reports Server (NTRS)

    1991-01-01

    A preliminary design of a two-stage to orbit vehicle was conducted with the requirements to carry a 10,000 pound payload into a 300 mile low-earth orbit using an airbreathing first stage, and to take off and land unassisted on a 15,000 foot runway. The goal of the design analysis was to produce the most efficient vehicle in size and weight which could accomplish the mission requirements. Initial parametric analysis indicated that the weight of the orbiter and the transonic performance of the system were the two parameters that had the largest impact on the design. The resulting system uses a turbofan ramjet powered first stage to propel a scramjet and rocket powered orbiter to the stage point of Mach 6 to 6.5 at an altitude of 90,000 ft.

  20. Two stage liquefaction of coal

    DOEpatents

    Neuworth, Martin B.

    1981-01-01

    A two stage coal liquefaction process and apparatus comprising hydrogen donor solvent extracting, solvent deashing, and catalytic hydrocracking. Preferrably, the catalytic hydrocracking is performed in an ebullating bed hydrocracker.

  1. Minuteman 3, stage 3 surveillance

    NASA Astrophysics Data System (ADS)

    Davis, R.; Porter, L. C., Jr.

    1986-01-01

    The program effort during this reporting period consisted of laboratory testing of both the Morton Thiokol, Inc./ASPC Minuteman 3 Third Stage Surveillance components and material samples. In addition, bondline aging testing and analysis using samples from previously dissected motors were accomplished. In support of the program, all flight and static tests, for both First and Third Stage Minuteman motors, were reviewed and tabulated for incorporation into reliability and motor historical records.

  2. Crew Launch Vehicle Upper Stage

    NASA Technical Reports Server (NTRS)

    Davis, D. J.; Cook, J. R.

    2006-01-01

    The Agency s Crew Launch Vehicle (CLV) will be the first human rated space transportation system developed in the United States since the Space Shuttle. The CLV will utilize existing Shuttle heritage hardware and systems combined with a "clean sheet design" for the Upper Stage. The Upper Stage element will be designed and developed by a team of NASA engineers managed by the Marshall Space Flight Center (MSFC) in Huntsville, Alabama. The team will design the Upper Stage based on the Exploration Systems Architecture Study (ESAS) Team s point of departure conceptual design as illustrated in the figure below. This concept is a self-supporting cylindrical structure, approximately 1 15 feet long and 216 inches in diameter. While this "clean-sheet" upper stage design inherently carries more risk than utilizing a modified design, the approach also has many advantages. This paper will discuss the advantages and disadvantages of pursuing a "clean-sheet" design for the new CLV Upper Stage as well as describe in detail the overall design of the Upper Stage and its integration into NASA s CLV.

  3. Antemortem Prediction of Braak Stage

    PubMed Central

    Carlson, Jesper O. E.; Gatz, Margaret; Pedersen, Nancy L.; Graff, Caroline; Nennesmo, Inger; Lindström, Anna-Karin; Gerritsen, Lotte

    2015-01-01

    We examined the extent to which tauopathy distribution, as determined by Braak staging, might be predicted by various risk factors in older individuals. The Swedish Twin Registry provided extensive information on neuropsychological function, lifestyle and cardiovascular risk factors of 128 patients for whom autopsy data including Braak staging were available. Logistic regression was used to develop a prognostic model that targeted discrimination between Braak stages 0-II vs. III-VI. The analysis showed that Braak stage III-VI was significantly predicted by having one or more APOE ε4 alleles, older age, high total cholesterol, absence of diabetes and cardiovascular disease, and poorer scores on the Wechsler Adult Intelligence Score Information test, verbal fluency, and recognition memory but better verbal recall. The algorithm predicted Braak stage III-VI well (receiver-operating characteristic area under curve: 0.897; 95% CI: 0.842-0.951). Using a cut-off of 50% risk or more, the sensitivity was 85%, the specificity was 70%, and the negative predictive value was 69%. This study demonstrates that tauopathy distribution can be accurately predicted using a combination of antemortem patient data. These results provide further insight into tauopathy development and AD-related disease mechanisms and suggest a prognostic model that predicts the spread of neurofibrillary tangles above the transentorhinal stage. PMID:26469248

  4. Staged regenerative sorption heat pump

    NASA Technical Reports Server (NTRS)

    Jones, Jack A. (Inventor)

    1995-01-01

    A regenerative adsorbent heat pump process and system for cooling and heating a space. A sorbent is confined in a plurality of compressors of which at least four are first stage and at least four are second stage. The first stage operates over a first pressure region and the second stage over a second pressure region which is higher than the first. Sorbate from the first stage enters the second stage. The sorbate loop includes a condenser, expansion valve, evaporator and the compressors. A single sorbate loop can be employed for single-temperature-control such as air conditioning and heating. Two sorbate loops can be used for two-temperature-control as in a refrigerator and freezer. The evaporator temperatures control the freezer and refrigerator temperatures. Alternatively the refrigerator temperature can be cooled by the freezer with one sorbate loop. A heat transfer fluid is circulated in a closed loop which includes a radiator and the compressors. Low temperature heat is exhausted by the radiator. High temperature heat is added to the heat transfer fluid entering the compressors which are desorbing vapor. Heat is transferred from compressors which are sorbing vapor to the heat transfer fluid, and from the heat transfer fluid to the compressors which are desorbing vapor. Each compressor is subjected to the following phases, heating to its highest temperature, cooling down from its highest temperature, cooling to its lowest temperature, and warming up from its lowest temperature. The phases are repeated to complete a cycle and regenerate heat.

  5. Infections in liver transplant recipients

    PubMed Central

    Romero, Fabian A; Razonable, Raymund R

    2011-01-01

    Liver transplantation is a standard life-saving procedure for the treatment of many end-stage liver diseases. The success of this procedure may be limited by infectious complications. In this article, we review the contemporary state of infectious complications during the post-operative period, with particular emphasis on those that occur most commonly during the first 6 mo after liver transplantation. Bacteria, and less commonly Candida infections, remain the predominant pathogens during the immediate post-operative period, especially during the first month, and infections caused by drug-resistant strains are emerging. Infections caused by cytomegalovirus and Aspergillus sp. present clinically during the “opportunistic” period characterized by intense immunosuppression. As newer potent immunosuppressive therapies with the major aim of reducing allograft rejection are developed, one potential adverse effect is an increase in certain infections. Hence, it is essential for liver transplant centers to have an effective approach to prevention that is based on predicted infection risk, local antimicrobial resistance patterns, and surveillance. A better understanding of the common and most important infectious complications is anticipated to lead to improvements in quality of life and survival of liver transplant recipients. PMID:21603030

  6. Ecopathology of ranaviruses infecting amphibians.

    PubMed

    Miller, Debra; Gray, Matthew; Storfer, Andrew

    2011-11-01

    Ranaviruses are capable of infecting amphibians from at least 14 families and over 70 individual species. Ranaviruses infect multiple cell types, often culminating in organ necrosis and massive hemorrhaging. Subclinical infections have been documented, although their role in ranavirus persistence and emergence remains unclear. Water is an effective transmission medium for ranaviruses, and survival outside the host may be for significant duration. In aquatic communities, amphibians, reptiles and fish may serve as reservoirs. Controlled studies have shown that susceptibility to ranavirus infection and disease varies among amphibian species and developmental stages, and likely is impacted by host-pathogen coevolution, as well as, exogenous environmental factors. Field studies have demonstrated that the likelihood of epizootics is increased in areas of cattle grazing, where aquatic vegetation is sparse and water quality is poor. Translocation of infected amphibians through commercial trade (e.g., food, fish bait, pet industry) contributes to the spread of ranaviruses. Such introductions may be of particular concern, as several studies report that ranaviruses isolated from ranaculture, aquaculture, and bait facilities have greater virulence (i.e., ability to cause disease) than wild-type isolates. Future investigations should focus on the genetic basis for pathogen virulence and host susceptibility, ecological and anthropogenic mechanisms contributing to emergence, and vaccine development for use in captive populations and species reintroduction programs.

  7. Ecopathology of Ranaviruses Infecting Amphibians

    PubMed Central

    Miller, Debra; Gray, Matthew; Storfer, Andrew

    2011-01-01

    Ranaviruses are capable of infecting amphibians from at least 14 families and over 70 individual species. Ranaviruses infect multiple cell types, often culminating in organ necrosis and massive hemorrhaging. Subclinical infections have been documented, although their role in ranavirus persistence and emergence remains unclear. Water is an effective transmission medium for ranaviruses, and survival outside the host may be for significant duration. In aquatic communities, amphibians, reptiles and fish may serve as reservoirs. Controlled studies have shown that susceptibility to ranavirus infection and disease varies among amphibian species and developmental stages, and likely is impacted by host-pathogen coevolution, as well as, exogenous environmental factors. Field studies have demonstrated that the likelihood of epizootics is increased in areas of cattle grazing, where aquatic vegetation is sparse and water quality is poor. Translocation of infected amphibians through commercial trade (e.g., food, fish bait, pet industry) contributes to the spread of ranaviruses. Such introductions may be of particular concern, as several studies report that ranaviruses isolated from ranaculture, aquaculture, and bait facilities have greater virulence (i.e., ability to cause disease) than wild-type isolates. Future investigations should focus on the genetic basis for pathogen virulence and host susceptibility, ecological and anthropogenic mechanisms contributing to emergence, and vaccine development for use in captive populations and species reintroduction programs. PMID:22163349

  8. [Norovirus infections].

    PubMed

    Stock, Ingo

    2007-10-01

    During the last winter season, there was the hitherto largest norovirus gastroenteritis epidemic in Germany. Noroviruses are genetically highly variable, non-enveloped viruses with a single-stranded, positive sense RNA genome. They are the major cause of epidemic non-bacterial gastroenteritis worldwide, and have been identified as the cause of more than 70% of outbreaks and approximately half of all gastroenteritis outbreaks. Noroviruses also are frequently involved in sporadic cases of gastroenteritis. Typically, norovirus-associated enteritis is characterized by the sudden onset of vomiting and watery diarrhoea, frequently accompanied by several unspecific symptoms, e. g. abdominal pain, anorexia, malaise, headache, and low-grade fever. Diarrhoea without emesis as well as asymptomatic infections is also common. With few exceptions, diseases due to noroviruses are self-limited and the illness duration is restricted to a few days. Noroviruses are transmitted primarily from person-to-person by the faecal-oral route, but airborne transmission also occurs. Contamination of food and water represent important sources for human infection. Treatment ofnorovirus gastroenteritis is usually symptomatic and comprises a sufficient fluid and electrolyte substitution. There is no specific antiviral therapy. For prophylaxis, obeying of common hygienic rules in canteen kitchens and community institutions is regarded to be sufficient. Food with high risk of contamination should be cooked thoroughly. Because of the high stability of noroviruses to several environmental conditions, disinfection should be performed applying disinfectants with proven activity against noroviruses.

  9. Periprosthetic Knee Infection: Ten Strategies That Work

    PubMed Central

    Cavanaugh, Priscilla Ku; Diaz-Ledezma, Claudio

    2013-01-01

    Periprosthetic joint infection (PJI) is one of the most serious complications following total knee arthroplasty (TKA). The demand for TKA is rapidly increasing, resulting in a subsequent increase in infections involving knee prosthesis. Despite the existence of common management practices, the best approach for several aspects in the management of periprosthetic knee infection remains controversial. This review examines the current understanding in the management of the following aspects of PJI: preoperative risk stratification, preoperative antibiotics, preoperative skin preparation, outpatient diagnosis, assessing for infection in revision cases, improving culture utility, irrigation and debridement, one and two-stage revision, and patient prognostic information. Moreover, ten strategies for the management of periprosthetic knee infection based on available literature, and experience of the authors were reviewed. PMID:24368992

  10. Alteration of cell cycle progression by Sindbis virus infection

    SciTech Connect

    Yi, Ruirong; Saito, Kengo; Isegawa, Naohisa; Shirasawa, Hiroshi

    2015-07-10

    We examined the impact of Sindbis virus (SINV) infection on cell cycle progression in a cancer cell line, HeLa, and a non-cancerous cell line, Vero. Cell cycle analyses showed that SINV infection is able to alter the cell cycle progression in both HeLa and Vero cells, but differently, especially during the early stage of infection. SINV infection affected the expression of several cell cycle regulators (CDK4, CDK6, cyclin E, p21, cyclin A and cyclin B) in HeLa cells and caused HeLa cells to accumulate in S phase during the early stage of infection. Monitoring SINV replication in HeLa and Vero cells expressing cell cycle indicators revealed that SINV which infected HeLa cells during G{sub 1} phase preferred to proliferate during S/G{sub 2} phase, and the average time interval for viral replication was significantly shorter in both HeLa and Vero cells infected during G{sub 1} phase than in cells infected during S/G{sub 2} phase. - Highlights: • SINV infection was able to alter the cell cycle progression of infected cancer cells. • SINV infection can affect the expression of cell cycle regulators. • SINV infection exhibited a preference for the timing of viral replication among the cell cycle phases.

  11. Chikungunya virus infection: an overview.

    PubMed

    Caglioti, Claudia; Lalle, Eleonora; Castilletti, Concetta; Carletti, Fabrizio; Capobianchi, Maria Rosaria; Bordi, Licia

    2013-07-01

    Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus belonging to the Togaviridae family, first isolated in Tanzania in 1952. The main vectors are mosquitoes from the Aedes species. Recently, the establishment of an envelope mutation increased infectivity for A. albopictus. CHIKV has recently re-emerged causing millions of infections in countries around the Indian Ocean characterized by climate conditions favourable to high vector density. Importation of human cases to European regions with high density of suitable arthropod vectors (such as A. albopictus) may trigger autochthonous outbreaks. The clinical signs of CHIKV infection include non-specific flu-like symptoms, and a characteristic rash accompanied by joint pain that may last for a long time after the resolution of the infection. The death rate is not particularly high, but excess mortality has been observed in concomitance with large CHIKV outbreaks. Deregulation of innate defense mechanisms, such as cytokine inflammatory response, may participate in the main clinical signs of CHIKV infection, and the establishment of persistent (chronic) disease. There is no specific therapy, and prevention is the main countermeasure. Prevention is based on insect control and in avoiding mosquito bites in endemic countries. Diagnosis is based on the detection of virus by molecular methods or by virus culture on the first days of infection, and by detection of an immune response in later stages. CHIKV infection must be suspected in patients with compatible clinical symptoms returning from epidemic/endemic areas. Differential diagnosis should take into account the cross-reactivity with other viruses from the same antigenic complex (i.e. O'nyong-nyong virus).

  12. Emergence of Persistent Infection due to Heterogeneity

    NASA Astrophysics Data System (ADS)

    Agrawal, Vidit; Moitra, Promit; Sinha, Sudeshna

    2017-02-01

    We explore the emergence of persistent infection in a closed region where the disease progression of the individuals is given by the SIRS model, with an individual becoming infected on contact with another infected individual. We investigate the persistence of contagion qualitatively and quantitatively, under increasing heterogeneity in the partitioning of the population into different disease compartments, as well as increasing heterogeneity in the phases of the disease among individuals within a compartment. We observe that when the initial population is uniform, consisting of individuals at the same stage of disease progression, infection arising from a contagious seed does not persist. However when the initial population consists of randomly distributed refractory and susceptible individuals, a single source of infection can lead to sustained infection in the population, as heterogeneity facilitates the de-synchronization of the phases in the disease cycle of the individuals. We also show how the average size of the window of persistence of infection depends on the degree of heterogeneity in the initial composition of the population. In particular, we show that the infection eventually dies out when the entire initial population is susceptible, while even a few susceptibles among an heterogeneous refractory population gives rise to a large persistent infected set.

  13. Emergence of Persistent Infection due to Heterogeneity

    PubMed Central

    Agrawal, Vidit; Moitra, Promit; Sinha, Sudeshna

    2017-01-01

    We explore the emergence of persistent infection in a closed region where the disease progression of the individuals is given by the SIRS model, with an individual becoming infected on contact with another infected individual. We investigate the persistence of contagion qualitatively and quantitatively, under increasing heterogeneity in the partitioning of the population into different disease compartments, as well as increasing heterogeneity in the phases of the disease among individuals within a compartment. We observe that when the initial population is uniform, consisting of individuals at the same stage of disease progression, infection arising from a contagious seed does not persist. However when the initial population consists of randomly distributed refractory and susceptible individuals, a single source of infection can lead to sustained infection in the population, as heterogeneity facilitates the de-synchronization of the phases in the disease cycle of the individuals. We also show how the average size of the window of persistence of infection depends on the degree of heterogeneity in the initial composition of the population. In particular, we show that the infection eventually dies out when the entire initial population is susceptible, while even a few susceptibles among an heterogeneous refractory population gives rise to a large persistent infected set. PMID:28145522

  14. [Pulmonary fungal infection in patients with AIDS].

    PubMed

    Denis, B; Lortholary, O

    2013-10-01

    Fungal infections are the most common opportunistic infections (OI) occurring during the course of HIV infection, though their incidence has decreased dramatically with the introduction of highly active antiretroviral therapy (cART). Most cases occur in untreated patients, noncompliant patients or patients whose multiple antiretroviral regimens have failed and they are a good marker of the severity of cellular immunodepression. Pneumocystis jiroveci pneumonia is the second most frequent OI in France and cryptococcosis remains a major problem in the Southern Hemisphere. With the increase in travel, imported endemic fungal infection can occur and may mimic other infections, notably tuberculosis. Fungal infections often have a pulmonary presentation but an exhaustive search for dissemination should be made in patients infected with HIV, at least those at an advanced stage of immune deficiency. Introduction of cART in combination with anti-fungal treatment depends on the risk of AIDS progression and on the risk of cumulative toxicity and the immune reconstitution inflammatory syndrome (IRIS) if introduced too early. Fungal infections in HIV infected patients remain a problem in the cART era. IRIS can complicate the management and requires an optimised treatment regime.

  15. Saturn IB First Stage (S-IB Stage) at MSFC

    NASA Technical Reports Server (NTRS)

    1965-01-01

    Workers at the Marshall Space Flight Center (MSFC) begin hoisting S-IB-200D, a dynamic test version of the Saturn IB launch vehicle's first stage (S-IB stage), into the Center's Dynamic Test Stand on January 11, 1965. Test Laboratory persornel assembled a complete Saturn IB to test the structural soundness of the launch vehicle. Developed by the MSFC as an interim vehicle in MSFC's 'building block' approach to Saturn rocket development, the Saturn IB utilized Saturn I technology to further develop and refine large boosters and the Apollo spacecraft capabilities required for the manned lunar missions.

  16. HIV transmission rates from persons living with HIV who are aware and unaware of their infection.

    PubMed

    Hall, H Irene; Holtgrave, David R; Maulsby, Catherine

    2012-04-24

    Transmission rate modeling estimated secondary infections from those aware and unaware of their HIV infection. An estimated 49% of transmissions were from the 20% of persons living with HIV unaware of their infection. About eight transmissions would be averted per 100 persons newly aware of their infection; with more infections averted the higher the percentage of persons with viral suppression who can be linked to care. Improving all stages of HIV care would substantially reduce transmission rates.

  17. Stage Separation Performance Analysis Project

    NASA Technical Reports Server (NTRS)

    Chen, Yen-Sen; Zhang, Sijun; Liu, Jiwen; Wang, Ten-See

    2001-01-01

    Stage separation process is an important phenomenon in multi-stage launch vehicle operation. The transient flowfield coupled with the multi-body systems is a challenging problem in design analysis. The thermodynamics environment with burning propellants during the upper-stage engine start in the separation processes adds to the complexity of the-entire system. Understanding the underlying flow physics and vehicle dynamics during stage separation is required in designing a multi-stage launch vehicle with good flight performance. A computational fluid dynamics model with the capability to coupling transient multi-body dynamics systems will be a useful tool for simulating the effects of transient flowfield, plume/jet heating and vehicle dynamics. A computational model using generalize mesh system will be used as the basis of this development. The multi-body dynamics system will be solved, by integrating a system of six-degree-of-freedom equations of motion with high accuracy. Multi-body mesh system and their interactions will be modeled using parallel computing algorithms. Adaptive mesh refinement method will also be employed to enhance solution accuracy in the transient process.

  18. Two-Stage Centrifugal Fan

    NASA Technical Reports Server (NTRS)

    Converse, David

    2011-01-01

    Fan designs are often constrained by envelope, rotational speed, weight, and power. Aerodynamic performance and motor electrical performance are heavily influenced by rotational speed. The fan used in this work is at a practical limit for rotational speed due to motor performance characteristics, and there is no more space available in the packaging for a larger fan. The pressure rise requirements keep growing. The way to ordinarily accommodate a higher DP is to spin faster or grow the fan rotor diameter. The invention is to put two radially oriented stages on a single disk. Flow enters the first stage from the center; energy is imparted to the flow in the first stage blades, the flow is redirected some amount opposite to the direction of rotation in the fixed stators, and more energy is imparted to the flow in the second- stage blades. Without increasing either rotational speed or disk diameter, it is believed that as much as 50 percent more DP can be achieved with this design than with an ordinary, single-stage centrifugal design. This invention is useful primarily for fans having relatively low flow rates with relatively high pressure rise requirements.

  19. Virology, Immunology, and Clinical Course of HIV Infection.

    ERIC Educational Resources Information Center

    McCutchan, J. Allen

    1990-01-01

    Presents overview of medical aspects of human immunodeficiency virus Type 1 (HIV-1) disease. Addresses structure and replication of virus, current methods for detecting HIV-1 in infected persons, effects of the virus on immune system, and clinical course of HIV-1 disease. Emphasizes variable causes of progression through HIV-1 infection stages;…

  20. Adenovirus infection reverses the antiviral state induced by human interferon.

    PubMed

    Feduchi, E; Carrasco, L

    1987-04-06

    HeLa cells treated with human lymphoblastoid interferon do not synthesize poliovirus proteins. The antiviral state against poliovirus is reversed if cells are previously infected with adenovirus type 5. A late gene product seems to be involved in this reversion, since no effect is observed at early stages of infection or in the presence of aphidicolin.

  1. Spatiotemporal dynamics of HIV infection

    NASA Astrophysics Data System (ADS)

    Strain, Matthew Carl

    during the primary or chronic stages of HIV infection. The nonlinear clearance of HIV DNA therefore predicts lifelong virus production, even in treated patients. Collectively, these results demonstrate that important features of the spatiotemporal dynamics of HIV infection both in vitro and in vivo are best explained with explicit spatial models.

  2. Mars Science Laboratory's Descent Stage

    NASA Technical Reports Server (NTRS)

    2008-01-01

    This portion of NASA's Mars Science Laboratory, called the descent stage, does its main work during the final few minutes before touchdown on Mars.

    The descent stage will provide rocket-powered deceleration for a phase of the arrival at Mars after the phases using the heat shield and parachute. When it nears the surface, the descent stage will lower the rover on a bridle the rest of the way to the ground.

    The Mars Science Laboratory spacecraft is being assembled and tested for launch in 2011.

    This image was taken at NASA's Jet Propulsion Laboratory, Pasadena, Calif., which manages the Mars Science Laboratory Mission for NASA's Science Mission Directorate, Washington. JPL is a division of the California Institute of Technology.

  3. 40 CFR 264.554 - Staging piles.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... existing permit (for example, RAP), closure plan, or order be modified to allow me to use a staging pile? (1) To modify a permit, other than a RAP, to incorporate a staging pile or staging pile operating... under § 270.42 of this chapter. (2) To modify a RAP to incorporate a staging pile or staging...

  4. 40 CFR 264.554 - Staging piles.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... existing permit (for example, RAP), closure plan, or order be modified to allow me to use a staging pile? (1) To modify a permit, other than a RAP, to incorporate a staging pile or staging pile operating... under § 270.42 of this chapter. (2) To modify a RAP to incorporate a staging pile or staging...

  5. 40 CFR 264.554 - Staging piles.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... existing permit (for example, RAP), closure plan, or order be modified to allow me to use a staging pile? (1) To modify a permit, other than a RAP, to incorporate a staging pile or staging pile operating... under § 270.42 of this chapter. (2) To modify a RAP to incorporate a staging pile or staging...

  6. Size Does Matter: Staging of Silene latifolia Floral Buds for Transcriptome Studies

    PubMed Central

    Toh, Su San; Perlin, Michael H.

    2015-01-01

    Dioecious plants in the Caryophyllaceae family are susceptible to infection by members of the anthericolous smut fungi. In our studies of the Silene latifolia/Microbotryum lychnidis-dioicae pathosystem, we were interested in characterizing the plant-pathogen interaction at the molecular level before and during teliosporogenesis. This takes place during floral bud development, and we hoped to capture the interaction by Illumina Next-Gen RNA-Sequencing. Using previous literature that documented the stages of the floral buds for S. latifolia, we examined the floral buds from plants grown and infected under growth chamber conditions, using the disserting microscope to determine the stage of floral buds based on the morphology. We compiled the information and determined the size of floral buds that correspond to the desired stages of development for tissue collection, for the purpose of RNA-sequencing. This offers a practical approach for researchers who require a large number of floral buds/tissue categorized by stages of development, ascertaining whether infected/uninfected buds are at comparable stages of development and whether this also holds true for male vs. female buds. We also document our experience in infecting the plants and some of the unusual morphologies we observed after infection. PMID:26378529

  7. Circulating immune cell subpopulations in pestivirus persistently infected calves and non-infected calves varying in immune status [Abstract

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The circulating immune cell subpopulations in cattle representing varying stages of immune status categorized as; colostrum deprived (CD), receiving colostrum (COL), colostrum plus vaccination (VAC) and persistently infected with a pestivirus (PI) were compared. The PI calves were infected with a H...

  8. Circulating immune cell subpopulations in pestivirus persistently infected calves and non-infected calves varying in immune status.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Circulating immune cell subpopulations in cattle representing varying stages of immune status categorized as; colostrum deprived (CD), receiving colostrum (COL), colostrum plus vaccination (VAC) and persistently infected with a pestivirus (PI) were compared. The PI calves were infected with a HoBi-...

  9. A Sporozoite- and Liver Stage-expressed Tryptophan-rich Protein Plays an Auxiliary Role in Plasmodium Liver Stage Development and Is a Potential Vaccine Candidate.

    PubMed

    Jaijyan, Dabbu Kumar; Singh, Himanshu; Singh, Agam Prasad

    2015-08-07

    The liver stages of the malaria parasite are clinically silent and constitute ideal targets for causal prophylactic drugs and vaccines. Cellular and molecular events responsible for liver stage development are poorly characterized. Here, we show that sporozoite, liver stage tryptophan-rich protein (SLTRiP) forms large multimers. Mice immunized with a purified recombinant SLTRiP protein gave high antibody titers in both inbred and outbred mice. Immunized mice showed highly significant levels of protection upon challenge with sporozoites and exhibited 10,000-fold fewer parasite 18S-rRNA copy numbers in their livers. The protection offered by immunization with SLTRiP came mainly from T-cells, and antibodies had little role to play despite their high titers. Immunofluorescence assays showed that SLTRiP is expressed in the sporozoite and early to late liver stages of malaria parasites. SLTRiP protein is exported to the cytosol of infected host cells during the early hours of parasite infection. Parasites deficient in SLTRiP were moderately defective in liver stage parasite development. A transcriptome profile of SLTRiP-deficient parasite-infected hepatocytes highlighted that SLTRiP interferes with multiple pathways in the host cell. We have demonstrated a role for SLTRiP in sporozoites and the liver stage of malaria parasites.

  10. Congenital Toxoplasmosis in Chronically Infected and Subsequently Challenged Ewes.

    PubMed

    Dos Santos, Thaís Rabelo; Faria, Gabriela da Silva Magalhães; Guerreiro, Bruna Martins; Dal Pietro, Nathalia Helena Pereira da Silva; Lopes, Welber Daniel Zanetti; da Silva, Helenara Machado; Garcia, João Luis; Luvizotto, Maria Cecília Rui; Bresciani, Katia Denise Saraiva; da Costa, Alvimar José

    2016-01-01

    This experiment studied congenital transmission in sheep experimentally infected with oocysts of Toxoplasma gondii and reinfected at one of three stages of pregnancy. Twenty ewes were experimentally infected with T. gondii strain ME49 (day 0). After the T. gondii infection became chronic (IFAT≤512), the ewes were allocated with rams for coverage. After the diagnosis of pregnancy, these ewes were allocated into four experimental groups (n = 5): I-reinfected with T. gondii on the 40th day of gestation (DG); II-reinfected on DG 80; III-reinfected on DG 120; and IV-saline solution on DG 120 (not reinfected). Five ewes (IFAT<64) were kept as negative controls (uninfected, group V), therefore in groups I-III were infected prior to pregnancy and re-infected during pregnancy, group IV was only infected prior to pregnancy, and group V was not infected. Parasitism by T. gondii was investigated (histopathology, immunohistochemistry, mouse bioassay and PCR) in mothers and lambs tissue. All ewes produced lambs serologically positive for T. gondii. The results of the mouse bioassay, immunohistochemistry and PCR assays revealed the presence of T. gondii in all 20 sheep and their lambs. The congenital transmission of T. gondii was associated with fetal loss and abnormalities in persistently infected sheep and in ewes infected and subsequently reinfected by this protozoan. Therefore, congenital T. gondii infection was common when ewes were chronically infected prior to pregnancy, with or without reinfection during at various stages of gestation.

  11. Congenital Toxoplasmosis in Chronically Infected and Subsequently Challenged Ewes

    PubMed Central

    dos Santos, Thaís Rabelo; Faria, Gabriela da Silva Magalhães; Guerreiro, Bruna Martins; dal Pietro, Nathalia Helena Pereira da Silva; Lopes, Welber Daniel Zanetti; da Silva, Helenara Machado; Garcia, João Luis; Luvizotto, Maria Cecília Rui; Bresciani, Katia Denise Saraiva; da Costa, Alvimar José

    2016-01-01

    This experiment studied congenital transmission in sheep experimentally infected with oocysts of Toxoplasma gondii and reinfected at one of three stages of pregnancy. Twenty ewes were experimentally infected with T. gondii strain ME49 (day 0). After the T. gondii infection became chronic (IFAT≤512), the ewes were allocated with rams for coverage. After the diagnosis of pregnancy, these ewes were allocated into four experimental groups (n = 5): I-reinfected with T. gondii on the 40th day of gestation (DG); II-reinfected on DG 80; III-reinfected on DG 120; and IV-saline solution on DG 120 (not reinfected). Five ewes (IFAT<64) were kept as negative controls (uninfected, group V), therefore in groups I-III were infected prior to pregnancy and re-infected during pregnancy, group IV was only infected prior to pregnancy, and group V was not infected. Parasitism by T. gondii was investigated (histopathology, immunohistochemistry, mouse bioassay and PCR) in mothers and lambs tissue. All ewes produced lambs serologically positive for T. gondii. The results of the mouse bioassay, immunohistochemistry and PCR assays revealed the presence of T. gondii in all 20 sheep and their lambs. The congenital transmission of T. gondii was associated with fetal loss and abnormalities in persistently infected sheep and in ewes infected and subsequently reinfected by this protozoan. Therefore, congenital T. gondii infection was common when ewes were chronically infected prior to pregnancy, with or without reinfection during at various stages of gestation. PMID:27788185

  12. Synchronous attack is advantageous: mixed genotype infections lead to higher infection success in trematode parasites

    PubMed Central

    Karvonen, Anssi; Rellstab, Christian; Louhi, Katja-Riikka; Jokela, Jukka

    2012-01-01

    Co-infecting parasite genotypes typically compete for host resources limiting their fitness. The intensity of such competition depends on whether parasites are reproducing in a host, or using it primarily as a transmission vehicle while not multiplying in host tissues (referred to as ‘competition hypothesis’). Alternatively, simultaneous attack and co-infection by several parasite genotypes might facilitate parasite infection because such a diverse attack could present an additional challenge to host immune defence (referred to as ‘facilitation hypothesis’). We tested the competition hypothesis by comparing the production of transmission stages (cercariae) from snails infected with one or two genotypes of the trematode Diplostomum pseudospathaceum. We found that cercarial production did not differ between the two groups of snails, suggesting lower per genotype production in double infections, and competition for host resources. Second, we tested the facilitation hypothesis by comparing parasite infection success on fishes (proportion of parasites establishing in the host) using cercariae originating from single-infected snails, double-infected snails and artificial mixtures of the single genotypes. In both cases, we found higher infection success when fishes were challenged with two parasite genotypes instead of one, supporting the facilitation hypothesis. Our results suggest that constraints defining the success of multiple genotype infections in parasites with multiple host life cycles include both between-genotype resource competition in the host and performance of host immune defences against a diverse parasite challenge. PMID:21632629

  13. Screening for Breast Cancer: Staging and Treatment

    MedlinePlus

    ... page please turn JavaScript on. Feature: Screening For Breast Cancer Staging and Treatment Past Issues / Summer 2014 Table of Contents Staging The extent (stage) of breast cancer needs to be determined to help choose the ...

  14. Listeria Infections (For Parents)

    MedlinePlus

    ... Old Feeding Your 1- to 2-Year-Old Listeria Infections KidsHealth > For Parents > Listeria Infections A A ... to Call the Doctor en español Listeriosis About Listeria Listeria infections (known as listeriosis ) are rare. When ...

  15. Listeria Infection (Listeriosis)

    MedlinePlus

    Listeria infection Overview By Mayo Clinic Staff Listeria infection is a foodborne bacterial illness that can be very serious for pregnant women and people with impaired immune systems. Listeria infection is ...

  16. Ear Infection (Middle Ear)

    MedlinePlus

    Ear infection (middle ear) Overview By Mayo Clinic Staff An ear infection (acute otitis media) is most often a bacterial or viral infection that affects the middle ear, the air-filled space behind the eardrum that ...

  17. Drama for Classroom and Stage.

    ERIC Educational Resources Information Center

    Johnson, Albert and Bertha

    This book with a three-part format contains information which the would-be thespian needs to know for maximum enjoyment and success in stage activities. The first part, "Heritage," traces the history and development of the theater from primitive ritual through the drama of classical Greece and Rome, the Renaissance, and modern Europe and America,…

  18. Multi-stage flash degaser

    DOEpatents

    Rapier, P.M.

    1980-06-26

    A multi-stage flash degaser is incorporated in an energy conversion system having a direct-contact, binary-fluid heat exchanger to remove essentially all of the noncondensable gases from geothermal brine ahead of the direct-contact binary-fluid heat exchanger in order that the heat exchanger and a turbine and condenser of the system can operate at optimal efficiency.

  19. All the World's a Stage

    ERIC Educational Resources Information Center

    Stanistreet, Paul

    2011-01-01

    Open Stages is Britain's biggest amateur theatre project, a hugely ambitious scheme to bring the professional and amateur theatre worlds together. It is a learning project but, as the Royal Shakespeare Company's Ian Wainwright tells this author, it is not only the amateurs who are learning. Wainwright states that the amateur and professional…

  20. Stages of neuronal network formation

    NASA Astrophysics Data System (ADS)

    Woiterski, Lydia; Claudepierre, Thomas; Luxenhofer, Robert; Jordan, Rainer; Käs, Josef A.

    2013-02-01

    Graph theoretical approaches have become a powerful tool for investigating the architecture and dynamics of complex networks. The topology of network graphs revealed small-world properties for very different real systems among these neuronal networks. In this study, we observed the early development of mouse retinal ganglion cell (RGC) networks in vitro using time-lapse video microscopy. By means of a time-resolved graph theoretical analysis of the connectivity, shortest path length and the edge length, we were able to discover the different stages during the network formation. Starting from single cells, at the first stage neurons connected to each other ending up in a network with maximum complexity. In the further course, we observed a simplification of the network which manifested in a change of relevant network parameters such as the minimization of the path length. Moreover, we found that RGC networks self-organized as small-world networks at both stages; however, the optimization occurred only in the second stage.